Pituitary, Thyroid & Adrenal Disorders

This transcript has been edited for clarity.

Hi. I’m Art Caplan. I’m at the division of medical ethics at New York University’s Grossman School of Medicine in New York City.

We’ve had an organ shortage for many decades now. We can do more transplants than we have organs made available. We try very hard to get organ donation from those who die. That’s a commendable thing to do. I think doctors should always be discussing the opportunity to donate organs upon death, even in primary care settings.

It’s good to find out what people’s attitudes are. Let them learn about organ donation as something they can think about. Let them talk about it with family and friends and partners so that they know their wishes.

However, despite these efforts to encourage organ donation, we still have far fewer organs than we could use to transplant people, many people die on waiting lists because there are no organs to give them, and we’re in a situation where demand for organ transplant is actually increasing.

There is more capacity to do transplants both in the United States and elsewhere, and more people are living longer, so organ failure starts to become more common before, let’s say, terminal illness is really there. Now, we have more people who might benefit from organ transplant in an aging population.

One place to turn to help reduce the shortage of organs is to living donation. At least insofar as kidneys go, kidney donation from living persons has become a prominent source of organs for those who need kidneys – most of whom are surviving on dialysis, by the way, at a very high cost and often with a quality of life that they don’t find particularly easy to accept.

Transplant is far preferred, even though they have to take immunosuppression to keep those organ transplants going, and that has its own risks and side effects. They still get more mobility. They still are able to have a broader diet. They enjoy life far more than they do having to show up for dialysis three times a week for a couple of hours, every week, for every week that they live.

There is an interest in living kidney donation. One battle has been that, well, maybe we could get more kidneys if we just paid people to sell us their kidneys. That has been resisted, and I’ve been resistant to that idea, too, because I worry that it leads to exploitation.

The people who sell their kidneys are poor. They’re often in debt. They feel coerced by their circumstances, so they make a kidney sale. This happens in countries like India, where there are markets underground, and you see that it’s the poorest of the poor who do this, and they don’t really work their way out of debt. They just wind up without a kidney, help relieve their debt a little bit, and pretty soon, because they don’t have a job or an income except that sale of a kidney, they’re not much better off than they were before they started.

Also, people who sell kidneys for money are more likely not to admit to their own health problems, raising risks about the quality of organs. Then, of course, it puts doctors in a position to take out an organ for pay, even though it doesn’t benefit you, so that you can sell it. This raises some questions about whether that’s consistent with medical ethics.

A different idea has emerged. New York State Governor Kathy Hochul just signed legislation that allows living donors to be compensated for legitimate costs. That’s a little different matter. You’re not buying the organ, but you’re saying that if you experience health care problems due to complications from a donation, if you need money for transportation, if you lost money because you did this altruistically and you had to take time off from work and had expenses for a babysitter, restaurants, or other things, the state is going to try to create funds that will compensate you.

That, I think we should agree, is not a bad idea. You’re in a situation there where you don’t want to make people who are heroic, altruistic, and trying to help others by donating a kidney end up financially worse off.

I think there’s a difference between making someone financially whole after the decision to make a kidney available and creating a market where the poorest of the poor come forward to just sell because they see no other choice in terms of how to get rid of debts. I see these situations as not ethically equivalent, so I support efforts to try to compensate people who are our heroes. I don’t think we should ask them to financially suffer.

We’ll watch to see what happens as the New York state law comes into effect. By the way, New York is one of the states that really lags in the supply of organs for transplant, so this measure is particularly important for that state. Many other states should be considering this legislation as well.

It’s one thing to reward, if you will, donors by making sure they don’t suffer financial loss. It’s a very different thing to say, let’s have a free market and we’ll pay whoever it is that’s willing to sell us a kidney to do so. The former seems to me to be humane and just, whereas the latter risks exploitation.
 

A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity.

Hi. I’m Art Caplan. I’m at the division of medical ethics at New York University’s Grossman School of Medicine in New York City.

We’ve had an organ shortage for many decades now. We can do more transplants than we have organs made available. We try very hard to get organ donation from those who die. That’s a commendable thing to do. I think doctors should always be discussing the opportunity to donate organs upon death, even in primary care settings.

It’s good to find out what people’s attitudes are. Let them learn about organ donation as something they can think about. Let them talk about it with family and friends and partners so that they know their wishes.

However, despite these efforts to encourage organ donation, we still have far fewer organs than we could use to transplant people, many people die on waiting lists because there are no organs to give them, and we’re in a situation where demand for organ transplant is actually increasing.

There is more capacity to do transplants both in the United States and elsewhere, and more people are living longer, so organ failure starts to become more common before, let’s say, terminal illness is really there. Now, we have more people who might benefit from organ transplant in an aging population.

One place to turn to help reduce the shortage of organs is to living donation. At least insofar as kidneys go, kidney donation from living persons has become a prominent source of organs for those who need kidneys – most of whom are surviving on dialysis, by the way, at a very high cost and often with a quality of life that they don’t find particularly easy to accept.

Transplant is far preferred, even though they have to take immunosuppression to keep those organ transplants going, and that has its own risks and side effects. They still get more mobility. They still are able to have a broader diet. They enjoy life far more than they do having to show up for dialysis three times a week for a couple of hours, every week, for every week that they live.

There is an interest in living kidney donation. One battle has been that, well, maybe we could get more kidneys if we just paid people to sell us their kidneys. That has been resisted, and I’ve been resistant to that idea, too, because I worry that it leads to exploitation.

The people who sell their kidneys are poor. They’re often in debt. They feel coerced by their circumstances, so they make a kidney sale. This happens in countries like India, where there are markets underground, and you see that it’s the poorest of the poor who do this, and they don’t really work their way out of debt. They just wind up without a kidney, help relieve their debt a little bit, and pretty soon, because they don’t have a job or an income except that sale of a kidney, they’re not much better off than they were before they started.

Also, people who sell kidneys for money are more likely not to admit to their own health problems, raising risks about the quality of organs. Then, of course, it puts doctors in a position to take out an organ for pay, even though it doesn’t benefit you, so that you can sell it. This raises some questions about whether that’s consistent with medical ethics.

A different idea has emerged. New York State Governor Kathy Hochul just signed legislation that allows living donors to be compensated for legitimate costs. That’s a little different matter. You’re not buying the organ, but you’re saying that if you experience health care problems due to complications from a donation, if you need money for transportation, if you lost money because you did this altruistically and you had to take time off from work and had expenses for a babysitter, restaurants, or other things, the state is going to try to create funds that will compensate you.

That, I think we should agree, is not a bad idea. You’re in a situation there where you don’t want to make people who are heroic, altruistic, and trying to help others by donating a kidney end up financially worse off.

I think there’s a difference between making someone financially whole after the decision to make a kidney available and creating a market where the poorest of the poor come forward to just sell because they see no other choice in terms of how to get rid of debts. I see these situations as not ethically equivalent, so I support efforts to try to compensate people who are our heroes. I don’t think we should ask them to financially suffer.

We’ll watch to see what happens as the New York state law comes into effect. By the way, New York is one of the states that really lags in the supply of organs for transplant, so this measure is particularly important for that state. Many other states should be considering this legislation as well.

It’s one thing to reward, if you will, donors by making sure they don’t suffer financial loss. It’s a very different thing to say, let’s have a free market and we’ll pay whoever it is that’s willing to sell us a kidney to do so. The former seems to me to be humane and just, whereas the latter risks exploitation.
 

A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity.

Hi. I’m Art Caplan. I’m at the division of medical ethics at New York University’s Grossman School of Medicine in New York City.

We’ve had an organ shortage for many decades now. We can do more transplants than we have organs made available. We try very hard to get organ donation from those who die. That’s a commendable thing to do. I think doctors should always be discussing the opportunity to donate organs upon death, even in primary care settings.

It’s good to find out what people’s attitudes are. Let them learn about organ donation as something they can think about. Let them talk about it with family and friends and partners so that they know their wishes.

However, despite these efforts to encourage organ donation, we still have far fewer organs than we could use to transplant people, many people die on waiting lists because there are no organs to give them, and we’re in a situation where demand for organ transplant is actually increasing.

There is more capacity to do transplants both in the United States and elsewhere, and more people are living longer, so organ failure starts to become more common before, let’s say, terminal illness is really there. Now, we have more people who might benefit from organ transplant in an aging population.

One place to turn to help reduce the shortage of organs is to living donation. At least insofar as kidneys go, kidney donation from living persons has become a prominent source of organs for those who need kidneys – most of whom are surviving on dialysis, by the way, at a very high cost and often with a quality of life that they don’t find particularly easy to accept.

Transplant is far preferred, even though they have to take immunosuppression to keep those organ transplants going, and that has its own risks and side effects. They still get more mobility. They still are able to have a broader diet. They enjoy life far more than they do having to show up for dialysis three times a week for a couple of hours, every week, for every week that they live.

There is an interest in living kidney donation. One battle has been that, well, maybe we could get more kidneys if we just paid people to sell us their kidneys. That has been resisted, and I’ve been resistant to that idea, too, because I worry that it leads to exploitation.

The people who sell their kidneys are poor. They’re often in debt. They feel coerced by their circumstances, so they make a kidney sale. This happens in countries like India, where there are markets underground, and you see that it’s the poorest of the poor who do this, and they don’t really work their way out of debt. They just wind up without a kidney, help relieve their debt a little bit, and pretty soon, because they don’t have a job or an income except that sale of a kidney, they’re not much better off than they were before they started.

Also, people who sell kidneys for money are more likely not to admit to their own health problems, raising risks about the quality of organs. Then, of course, it puts doctors in a position to take out an organ for pay, even though it doesn’t benefit you, so that you can sell it. This raises some questions about whether that’s consistent with medical ethics.

A different idea has emerged. New York State Governor Kathy Hochul just signed legislation that allows living donors to be compensated for legitimate costs. That’s a little different matter. You’re not buying the organ, but you’re saying that if you experience health care problems due to complications from a donation, if you need money for transportation, if you lost money because you did this altruistically and you had to take time off from work and had expenses for a babysitter, restaurants, or other things, the state is going to try to create funds that will compensate you.

That, I think we should agree, is not a bad idea. You’re in a situation there where you don’t want to make people who are heroic, altruistic, and trying to help others by donating a kidney end up financially worse off.

I think there’s a difference between making someone financially whole after the decision to make a kidney available and creating a market where the poorest of the poor come forward to just sell because they see no other choice in terms of how to get rid of debts. I see these situations as not ethically equivalent, so I support efforts to try to compensate people who are our heroes. I don’t think we should ask them to financially suffer.

We’ll watch to see what happens as the New York state law comes into effect. By the way, New York is one of the states that really lags in the supply of organs for transplant, so this measure is particularly important for that state. Many other states should be considering this legislation as well.

It’s one thing to reward, if you will, donors by making sure they don’t suffer financial loss. It’s a very different thing to say, let’s have a free market and we’ll pay whoever it is that’s willing to sell us a kidney to do so. The former seems to me to be humane and just, whereas the latter risks exploitation.
 

A version of this article first appeared on Medscape.com.

New data released by the U.S. Department of Defense show that the incidence of many types of cancer is higher among military pilots and aviation support personnel in comparison with the general population.

“Military aircrew and ground crew were overall more likely to be diagnosed with cancer, but less likely to die from cancer compared to the U.S. population,” the report concludes.

The study involved 156,050 aircrew and 737,891 ground crew. Participants were followed between 1992 and 2017. Both groups were predominantly male and non-Hispanic.

Data on cancer incidence and mortality for these two groups were compared with data from groups of similar age in the general population through use of the Surveillance, Epidemiology, and End Results (SEER) Database of the National Cancer Institute.

For aircrew, the study found an 87% higher rate of melanoma, a 39% higher rate of thyroid cancer, a 16% higher rate of prostate cancer, and a 24% higher rate of cancer for all sites combined.

A higher rate of melanoma and prostate cancer among aircrew has been reported previously, but the increased rate of thyroid cancer is a new finding, the authors note.

The uptick in melanoma has also been reported in studies of civilian pilots and cabin crew. It has been attributed to exposure to hazardous ultraviolet and cosmic radiation.

For ground crew members, the analysis found a 19% higher rate of cancers of the brain and nervous system, a 15% higher rate of thyroid cancer, a 9% higher rate of melanoma and of kidney and renal pelvis cancers, and a 3% higher rate of cancer for all sites combined.

There is little to compare these findings with: This is the first time that cancer risk has been evaluated in such a large population of military ground crew.
 

Lower rates of cancer mortality

In contrast to the increase in cancer incidence, the report found a decrease in cancer mortality.

When compared with a demographically similar U.S. population, the mortality rate among aircrew was 56% lower for all cancer sites; for ground crew, the mortality rate was 35% lower.

However, the report authors emphasize that “it is important to note that the military study population was relatively young.”

The median age at the end of follow-up for the cancer incidence analysis was 41 years for aircrew and 26 years for ground crew. The median age at the end of follow-up for the cancer mortality analysis was 48 years for aircrew and 41 years for ground crew.

“Results may have differed if additional older former Service members had been included in the study, since cancer risk and mortality rates increase with age,” the authors comment.

Other studies have found an increase in deaths from melanoma as well as an increase in the incidence of melanoma. A meta-analysis published in 2019 in the British Journal of Dermatology found that airline pilots and cabin crew have about twice the risk of melanoma and other skin cancers than the general population. Pilots are also more likely to die from melanoma.
 

Further study underway

The findings on military air and ground crew come from phase 1 of a study that was required by Congress in the 2021 defense bill. Because the investigators found an increase in the incidence of cancer, phase 2 of the study is now necessary.

The report authors explain that phase 2 will consist of identifying the carcinogenic toxicants or hazardous materials associated with military flight operations; identifying operating environments that could be associated with increased amounts of ionizing and nonionizing radiation; identifying specific duties, dates of service, and types of aircraft flown that could have increased the risk for cancer; identifying duty locations associated with a higher incidence of cancers; identifying potential exposures through military service that are not related to aviation; and determining the appropriate age to begin screening military aircrew and ground crew for cancers.

A version of this article first appeared on Medscape.com.

New data released by the U.S. Department of Defense show that the incidence of many types of cancer is higher among military pilots and aviation support personnel in comparison with the general population.

“Military aircrew and ground crew were overall more likely to be diagnosed with cancer, but less likely to die from cancer compared to the U.S. population,” the report concludes.

The study involved 156,050 aircrew and 737,891 ground crew. Participants were followed between 1992 and 2017. Both groups were predominantly male and non-Hispanic.

Data on cancer incidence and mortality for these two groups were compared with data from groups of similar age in the general population through use of the Surveillance, Epidemiology, and End Results (SEER) Database of the National Cancer Institute.

For aircrew, the study found an 87% higher rate of melanoma, a 39% higher rate of thyroid cancer, a 16% higher rate of prostate cancer, and a 24% higher rate of cancer for all sites combined.

A higher rate of melanoma and prostate cancer among aircrew has been reported previously, but the increased rate of thyroid cancer is a new finding, the authors note.

The uptick in melanoma has also been reported in studies of civilian pilots and cabin crew. It has been attributed to exposure to hazardous ultraviolet and cosmic radiation.

For ground crew members, the analysis found a 19% higher rate of cancers of the brain and nervous system, a 15% higher rate of thyroid cancer, a 9% higher rate of melanoma and of kidney and renal pelvis cancers, and a 3% higher rate of cancer for all sites combined.

There is little to compare these findings with: This is the first time that cancer risk has been evaluated in such a large population of military ground crew.
 

Lower rates of cancer mortality

In contrast to the increase in cancer incidence, the report found a decrease in cancer mortality.

When compared with a demographically similar U.S. population, the mortality rate among aircrew was 56% lower for all cancer sites; for ground crew, the mortality rate was 35% lower.

However, the report authors emphasize that “it is important to note that the military study population was relatively young.”

The median age at the end of follow-up for the cancer incidence analysis was 41 years for aircrew and 26 years for ground crew. The median age at the end of follow-up for the cancer mortality analysis was 48 years for aircrew and 41 years for ground crew.

“Results may have differed if additional older former Service members had been included in the study, since cancer risk and mortality rates increase with age,” the authors comment.

Other studies have found an increase in deaths from melanoma as well as an increase in the incidence of melanoma. A meta-analysis published in 2019 in the British Journal of Dermatology found that airline pilots and cabin crew have about twice the risk of melanoma and other skin cancers than the general population. Pilots are also more likely to die from melanoma.
 

Further study underway

The findings on military air and ground crew come from phase 1 of a study that was required by Congress in the 2021 defense bill. Because the investigators found an increase in the incidence of cancer, phase 2 of the study is now necessary.

The report authors explain that phase 2 will consist of identifying the carcinogenic toxicants or hazardous materials associated with military flight operations; identifying operating environments that could be associated with increased amounts of ionizing and nonionizing radiation; identifying specific duties, dates of service, and types of aircraft flown that could have increased the risk for cancer; identifying duty locations associated with a higher incidence of cancers; identifying potential exposures through military service that are not related to aviation; and determining the appropriate age to begin screening military aircrew and ground crew for cancers.

A version of this article first appeared on Medscape.com.

New data released by the U.S. Department of Defense show that the incidence of many types of cancer is higher among military pilots and aviation support personnel in comparison with the general population.

“Military aircrew and ground crew were overall more likely to be diagnosed with cancer, but less likely to die from cancer compared to the U.S. population,” the report concludes.

The study involved 156,050 aircrew and 737,891 ground crew. Participants were followed between 1992 and 2017. Both groups were predominantly male and non-Hispanic.

Data on cancer incidence and mortality for these two groups were compared with data from groups of similar age in the general population through use of the Surveillance, Epidemiology, and End Results (SEER) Database of the National Cancer Institute.

For aircrew, the study found an 87% higher rate of melanoma, a 39% higher rate of thyroid cancer, a 16% higher rate of prostate cancer, and a 24% higher rate of cancer for all sites combined.

A higher rate of melanoma and prostate cancer among aircrew has been reported previously, but the increased rate of thyroid cancer is a new finding, the authors note.

The uptick in melanoma has also been reported in studies of civilian pilots and cabin crew. It has been attributed to exposure to hazardous ultraviolet and cosmic radiation.

For ground crew members, the analysis found a 19% higher rate of cancers of the brain and nervous system, a 15% higher rate of thyroid cancer, a 9% higher rate of melanoma and of kidney and renal pelvis cancers, and a 3% higher rate of cancer for all sites combined.

There is little to compare these findings with: This is the first time that cancer risk has been evaluated in such a large population of military ground crew.
 

Lower rates of cancer mortality

In contrast to the increase in cancer incidence, the report found a decrease in cancer mortality.

When compared with a demographically similar U.S. population, the mortality rate among aircrew was 56% lower for all cancer sites; for ground crew, the mortality rate was 35% lower.

However, the report authors emphasize that “it is important to note that the military study population was relatively young.”

The median age at the end of follow-up for the cancer incidence analysis was 41 years for aircrew and 26 years for ground crew. The median age at the end of follow-up for the cancer mortality analysis was 48 years for aircrew and 41 years for ground crew.

“Results may have differed if additional older former Service members had been included in the study, since cancer risk and mortality rates increase with age,” the authors comment.

Other studies have found an increase in deaths from melanoma as well as an increase in the incidence of melanoma. A meta-analysis published in 2019 in the British Journal of Dermatology found that airline pilots and cabin crew have about twice the risk of melanoma and other skin cancers than the general population. Pilots are also more likely to die from melanoma.
 

Further study underway

The findings on military air and ground crew come from phase 1 of a study that was required by Congress in the 2021 defense bill. Because the investigators found an increase in the incidence of cancer, phase 2 of the study is now necessary.

The report authors explain that phase 2 will consist of identifying the carcinogenic toxicants or hazardous materials associated with military flight operations; identifying operating environments that could be associated with increased amounts of ionizing and nonionizing radiation; identifying specific duties, dates of service, and types of aircraft flown that could have increased the risk for cancer; identifying duty locations associated with a higher incidence of cancers; identifying potential exposures through military service that are not related to aviation; and determining the appropriate age to begin screening military aircrew and ground crew for cancers.

A version of this article first appeared on Medscape.com.

The Environmental Protection Agency is proposing a new rule that would greatly limit the concentration of endocrine-disrupting “forever” chemicals in drinking water. 

The EPA on Tuesday announced the proposed National Primary Drinking Water Regulation (NPDWR) for six polyfluoroalkyl substances, more commonly known as PFAS, which are human-made chemicals used as oil and water repellents and coatings for common products including cookware, carpets, and textiles. Such substances are also widely used in cosmetics and food packaging.

curtoicurto/Getty Images

The Endocrine Society, which represents more than 18,000 doctors who treat hormone disorders, says it fully supports the new EPA proposal. It explains that these substances, also known as endocrine-disrupting chemicals, “do not break down when they are released into the environment, and they continue to accumulate over time. They pose health dangers at incredibly low levels and have been linked to endocrine disorders such as cancer, thyroid disruption, and reproductive difficulties.”

“This is the first time the government has regulated a new chemical in drinking water in more than 30 years,” the society notes, adding, this “will require major water treatment upgrades at utilities across the country.”

Robert F. Powelson, president and CEO of the National Association of Water Companies, says addressing the PFAS in the nation’s water supply will cost “billions of dollars.”

“It’s a burden that under the current structure will disproportionately fall on water and wastewater customers in small communities and low-income families,” Mr. Powelson says in a statement. He says the onus should instead fall on “the polluters” – those who manufacture and use PFAS chemicals, who “should be held directly responsible for the clean-up costs.” 

Although the EPA is proposing a health-based maximum contaminant level goal of zero for these chemicals in drinking water, it acknowledges that this is unenforceable and so has set what it considers an enforceable level, or maximum contaminant level (MCL), of 4 parts per trillion for two of the PFAS, perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS). 

A different standard has been proposed for the remaining four chemicals: perfluorononanoic acid (PFNA) and hexafluoropropylene oxide dimer acid (HFPO-DA) – known together as GenX chemicals – perfluorohexane sulfonic acid (PFHxS), and perfluorobutane sulfonic acid (PFBS).

Officials from the EPA told The Washington Post that these proposed limits would be as strong or stronger than limits from about a dozen states that have set their own drinking water standards in recent years. 

“The experts here felt this was the level of stringency required to protect public health, and that the law would allow for us,” EPA Administrator Michael Regan told the newspaper. “This is a transformative action that we’re taking.”

The EPA is requesting public comment on the proposed regulation and will hold a public hearing on May 4, which members of the public can register to attend and comment on the rule proposal. The last day to register is April 28. 

The EPA wants to finalize regulation by the end of 2023, although delays are common on new rules. 

If it is fully implemented, “the rule will prevent thousands of deaths and reduce tens of thousands of serious PFAS-attributable illnesses,” the EPA statement says.

A version of this article first appeared on Medscape.com.

The Environmental Protection Agency is proposing a new rule that would greatly limit the concentration of endocrine-disrupting “forever” chemicals in drinking water. 

The EPA on Tuesday announced the proposed National Primary Drinking Water Regulation (NPDWR) for six polyfluoroalkyl substances, more commonly known as PFAS, which are human-made chemicals used as oil and water repellents and coatings for common products including cookware, carpets, and textiles. Such substances are also widely used in cosmetics and food packaging.

curtoicurto/Getty Images

The Endocrine Society, which represents more than 18,000 doctors who treat hormone disorders, says it fully supports the new EPA proposal. It explains that these substances, also known as endocrine-disrupting chemicals, “do not break down when they are released into the environment, and they continue to accumulate over time. They pose health dangers at incredibly low levels and have been linked to endocrine disorders such as cancer, thyroid disruption, and reproductive difficulties.”

“This is the first time the government has regulated a new chemical in drinking water in more than 30 years,” the society notes, adding, this “will require major water treatment upgrades at utilities across the country.”

Robert F. Powelson, president and CEO of the National Association of Water Companies, says addressing the PFAS in the nation’s water supply will cost “billions of dollars.”

“It’s a burden that under the current structure will disproportionately fall on water and wastewater customers in small communities and low-income families,” Mr. Powelson says in a statement. He says the onus should instead fall on “the polluters” – those who manufacture and use PFAS chemicals, who “should be held directly responsible for the clean-up costs.” 

Although the EPA is proposing a health-based maximum contaminant level goal of zero for these chemicals in drinking water, it acknowledges that this is unenforceable and so has set what it considers an enforceable level, or maximum contaminant level (MCL), of 4 parts per trillion for two of the PFAS, perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS). 

A different standard has been proposed for the remaining four chemicals: perfluorononanoic acid (PFNA) and hexafluoropropylene oxide dimer acid (HFPO-DA) – known together as GenX chemicals – perfluorohexane sulfonic acid (PFHxS), and perfluorobutane sulfonic acid (PFBS).

Officials from the EPA told The Washington Post that these proposed limits would be as strong or stronger than limits from about a dozen states that have set their own drinking water standards in recent years. 

“The experts here felt this was the level of stringency required to protect public health, and that the law would allow for us,” EPA Administrator Michael Regan told the newspaper. “This is a transformative action that we’re taking.”

The EPA is requesting public comment on the proposed regulation and will hold a public hearing on May 4, which members of the public can register to attend and comment on the rule proposal. The last day to register is April 28. 

The EPA wants to finalize regulation by the end of 2023, although delays are common on new rules. 

If it is fully implemented, “the rule will prevent thousands of deaths and reduce tens of thousands of serious PFAS-attributable illnesses,” the EPA statement says.

A version of this article first appeared on Medscape.com.

The Environmental Protection Agency is proposing a new rule that would greatly limit the concentration of endocrine-disrupting “forever” chemicals in drinking water. 

The EPA on Tuesday announced the proposed National Primary Drinking Water Regulation (NPDWR) for six polyfluoroalkyl substances, more commonly known as PFAS, which are human-made chemicals used as oil and water repellents and coatings for common products including cookware, carpets, and textiles. Such substances are also widely used in cosmetics and food packaging.

curtoicurto/Getty Images

The Endocrine Society, which represents more than 18,000 doctors who treat hormone disorders, says it fully supports the new EPA proposal. It explains that these substances, also known as endocrine-disrupting chemicals, “do not break down when they are released into the environment, and they continue to accumulate over time. They pose health dangers at incredibly low levels and have been linked to endocrine disorders such as cancer, thyroid disruption, and reproductive difficulties.”

“This is the first time the government has regulated a new chemical in drinking water in more than 30 years,” the society notes, adding, this “will require major water treatment upgrades at utilities across the country.”

Robert F. Powelson, president and CEO of the National Association of Water Companies, says addressing the PFAS in the nation’s water supply will cost “billions of dollars.”

“It’s a burden that under the current structure will disproportionately fall on water and wastewater customers in small communities and low-income families,” Mr. Powelson says in a statement. He says the onus should instead fall on “the polluters” – those who manufacture and use PFAS chemicals, who “should be held directly responsible for the clean-up costs.” 

Although the EPA is proposing a health-based maximum contaminant level goal of zero for these chemicals in drinking water, it acknowledges that this is unenforceable and so has set what it considers an enforceable level, or maximum contaminant level (MCL), of 4 parts per trillion for two of the PFAS, perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS). 

A different standard has been proposed for the remaining four chemicals: perfluorononanoic acid (PFNA) and hexafluoropropylene oxide dimer acid (HFPO-DA) – known together as GenX chemicals – perfluorohexane sulfonic acid (PFHxS), and perfluorobutane sulfonic acid (PFBS).

Officials from the EPA told The Washington Post that these proposed limits would be as strong or stronger than limits from about a dozen states that have set their own drinking water standards in recent years. 

“The experts here felt this was the level of stringency required to protect public health, and that the law would allow for us,” EPA Administrator Michael Regan told the newspaper. “This is a transformative action that we’re taking.”

The EPA is requesting public comment on the proposed regulation and will hold a public hearing on May 4, which members of the public can register to attend and comment on the rule proposal. The last day to register is April 28. 

The EPA wants to finalize regulation by the end of 2023, although delays are common on new rules. 

If it is fully implemented, “the rule will prevent thousands of deaths and reduce tens of thousands of serious PFAS-attributable illnesses,” the EPA statement says.

A version of this article first appeared on Medscape.com.

With #Ozempic and #ozempicweightloss continuing to trend on social media, along with the mainstream media focusing on celebrities who rely on Ozempic (semaglutide) for weight loss, the daily requests for this new medication have been increasing.

Accompanying these requests are concerns and questions about potential risks, including this most recent message from one of my patients: “Dr. P – I saw the warnings. Is this medication going to make me get thyroid cancer? Please let me know!”

Let’s look at what we know to date, including recent studies, and how to advise our patients on this very hot topic.
 

Using GLP-1 receptor agonists for obesity

We have extensive prior experience with glucagon-like peptide 1 (GLP-1) receptor agonists, such as semaglutide, for treating type 2 diabetes and now recently as agents for weight loss.

Large clinical trials have documented the benefits of this medication class not only for weight reduction but also for cardiovascular and renal benefits in patients with diabetes. The subcutaneously injectable medications work by promoting insulin secretion, slowing gastric emptying, and suppressing glucagon secretion, with a low risk for hypoglycemia.

The Food and Drug Administration approved daily-injection GLP-1 agonist liraglutide for weight loss in 2014, and weekly-injection semaglutide for chronic weight management in 2021, in patients with a body mass index ≥ 27 with at least one weight-related condition or a BMI ≥ 30.

The brand name for semaglutide approved for weight loss is Wegovy, and the dose is slightly higher (maximum 2.4 mg/wk) than that of Ozempic (maximum 2.0 mg/wk), which is semaglutide approved for type 2 diabetes.

In trials for weight loss, data showed a mean change in body weight of almost 15% in the semaglutide group at week 68 compared with placebo, which is very impressive, particularly compared with other FDA-approved oral long-term weight loss medications.

The newest synthetic dual-acting agent is tirzepatide, which targets GLP-1 but is also a glucose-dependent insulinotropic polypeptide (GIP) agonist. The weekly subcutaneous injection was approved in May 2022 as Mounjaro for treating type 2 diabetes and produced even greater weight loss than semaglutide in clinical trials. Tirzepatide is now in trials for obesity and is under expedited review by the FDA for weight loss.
 

Why the concern about thyroid cancer?

Early on with the FDA approvals of GLP-1 agonists, a warning accompanied the products’ labels to not use this class of medications in patients with medullary thyroid cancer, a family history of medullary thyroid cancer, or multiple endocrine neoplasia syndrome type 2. This warning was based on data from animal studies.

Human pancreatic cells aren’t the only cells that express GLP-1 receptors. These receptors are also expressed by parafollicular cells (C cells) of the thyroid, which secrete calcitonin and are the cells involved in medullary thyroid cancer. A dose-related and duration-dependent increase in thyroid C-cell tumor incidence was noted in rodents. The same relationship was not demonstrated in monkeys. Humans have far fewer C cells than rats, and human C cells have very low expression of the GLP-1 receptor.

Over a decade ago, a study examining the FDA’s database of reported adverse events found an increased risk for thyroid cancer in patients treated with exenatide, another GLP-1 agonist. The reporting system wasn’t designed to distinguish thyroid cancer subtypes.

Numerous subsequent studies didn’t confirm this relationship. The LEADER trial looked at liraglutide in patients with type 2 diabetes and showed no effect of GLP-1 receptor activation on human serum calcitonin levels, C-cell proliferation, or C-cell malignancy. Similarly, a large meta-analysis in patients with type 2 diabetes didn’t find a statistically increased risk for thyroid cancer with liraglutide, and no thyroid malignancies were reported with exenatide.

Two U.S. administrative databases from commercial health plans (a retrospective cohort study and a nested case-control study) compared type 2 diabetes patients who were taking exenatide vs. other antidiabetic drugs and found that exenatide was not significantly associated with an increased risk for thyroid cancer.

And a recent meta-analysis of 45 trials showed no significant effects on the occurrence of thyroid cancer with GLP-1 receptor agonists. Of note, it did find an increased risk for overall thyroid disorders, although there was no clear statistically significant finding pointing to a specific thyroid disorder.

Differing from prior studies, a recent nationwide French health care system study provided newer data suggesting a moderate increased risk for thyroid cancer in a cohort of patients with type 2 diabetes who were taking GLP-1 agonists. The increase in relative risk was noted for all types of thyroid cancer in patients using GLP-1 receptor agonists for 1-3 years.

An accompanying commentary by Caroline A. Thompson, PhD, and Til Stürmer, MD, provides perspective on this study’s potential limitations. These include detection bias, as the study results focused only on the statistically significant data. Also discussed were limitations to the case-control design, issues with claims-based tumor type classification (unavailability of surgical pathology), and an inability to adjust for family history and obesity, which is a risk factor alone for thyroid cancer. There was also no adjustment for exposure to head/neck radiation.

While this study has important findings to consider, it deserves further investigation, with future studies linking data to tumor registry data before a change is made in clinical practice.

No clear relationship has been drawn between GLP-1 receptor agonists and thyroid cancer in humans. Numerous confounding factors limit the data. Studies generally don’t specify the type of thyroid cancer, and they lump medullary thyroid cancer, the rarest form, with papillary thyroid cancer.

Is a detection bias present where weight loss makes nodules more visible on the neck among those treated with GLP-1 agonists? And/or are patients treated with GLP-1 agonists being screened more stringently for thyroid nodules and/or cancer?
 

How to advise our patients and respond to the EMR messages

The TikTok videos may continue, the celebrity chatter may increase, and we, as physicians, will continue to look to real-world data with randomized controlled trials to tailor our decision-making and guide our patients.

It’s prudent to advise patients that if they have a personal or family history of medullary thyroid cancer or multiple endocrine neoplasia syndrome type 2, in particular, they should avoid using this class of medication. Thyroid cancer remains a rare outcome, and GLP-1 receptor agonists remain a very important and beneficial treatment option for the right patient.

A version of this article first appeared on Medscape.com.

With #Ozempic and #ozempicweightloss continuing to trend on social media, along with the mainstream media focusing on celebrities who rely on Ozempic (semaglutide) for weight loss, the daily requests for this new medication have been increasing.

Accompanying these requests are concerns and questions about potential risks, including this most recent message from one of my patients: “Dr. P – I saw the warnings. Is this medication going to make me get thyroid cancer? Please let me know!”

Let’s look at what we know to date, including recent studies, and how to advise our patients on this very hot topic.
 

Using GLP-1 receptor agonists for obesity

We have extensive prior experience with glucagon-like peptide 1 (GLP-1) receptor agonists, such as semaglutide, for treating type 2 diabetes and now recently as agents for weight loss.

Large clinical trials have documented the benefits of this medication class not only for weight reduction but also for cardiovascular and renal benefits in patients with diabetes. The subcutaneously injectable medications work by promoting insulin secretion, slowing gastric emptying, and suppressing glucagon secretion, with a low risk for hypoglycemia.

The Food and Drug Administration approved daily-injection GLP-1 agonist liraglutide for weight loss in 2014, and weekly-injection semaglutide for chronic weight management in 2021, in patients with a body mass index ≥ 27 with at least one weight-related condition or a BMI ≥ 30.

The brand name for semaglutide approved for weight loss is Wegovy, and the dose is slightly higher (maximum 2.4 mg/wk) than that of Ozempic (maximum 2.0 mg/wk), which is semaglutide approved for type 2 diabetes.

In trials for weight loss, data showed a mean change in body weight of almost 15% in the semaglutide group at week 68 compared with placebo, which is very impressive, particularly compared with other FDA-approved oral long-term weight loss medications.

The newest synthetic dual-acting agent is tirzepatide, which targets GLP-1 but is also a glucose-dependent insulinotropic polypeptide (GIP) agonist. The weekly subcutaneous injection was approved in May 2022 as Mounjaro for treating type 2 diabetes and produced even greater weight loss than semaglutide in clinical trials. Tirzepatide is now in trials for obesity and is under expedited review by the FDA for weight loss.
 

Why the concern about thyroid cancer?

Early on with the FDA approvals of GLP-1 agonists, a warning accompanied the products’ labels to not use this class of medications in patients with medullary thyroid cancer, a family history of medullary thyroid cancer, or multiple endocrine neoplasia syndrome type 2. This warning was based on data from animal studies.

Human pancreatic cells aren’t the only cells that express GLP-1 receptors. These receptors are also expressed by parafollicular cells (C cells) of the thyroid, which secrete calcitonin and are the cells involved in medullary thyroid cancer. A dose-related and duration-dependent increase in thyroid C-cell tumor incidence was noted in rodents. The same relationship was not demonstrated in monkeys. Humans have far fewer C cells than rats, and human C cells have very low expression of the GLP-1 receptor.

Over a decade ago, a study examining the FDA’s database of reported adverse events found an increased risk for thyroid cancer in patients treated with exenatide, another GLP-1 agonist. The reporting system wasn’t designed to distinguish thyroid cancer subtypes.

Numerous subsequent studies didn’t confirm this relationship. The LEADER trial looked at liraglutide in patients with type 2 diabetes and showed no effect of GLP-1 receptor activation on human serum calcitonin levels, C-cell proliferation, or C-cell malignancy. Similarly, a large meta-analysis in patients with type 2 diabetes didn’t find a statistically increased risk for thyroid cancer with liraglutide, and no thyroid malignancies were reported with exenatide.

Two U.S. administrative databases from commercial health plans (a retrospective cohort study and a nested case-control study) compared type 2 diabetes patients who were taking exenatide vs. other antidiabetic drugs and found that exenatide was not significantly associated with an increased risk for thyroid cancer.

And a recent meta-analysis of 45 trials showed no significant effects on the occurrence of thyroid cancer with GLP-1 receptor agonists. Of note, it did find an increased risk for overall thyroid disorders, although there was no clear statistically significant finding pointing to a specific thyroid disorder.

Differing from prior studies, a recent nationwide French health care system study provided newer data suggesting a moderate increased risk for thyroid cancer in a cohort of patients with type 2 diabetes who were taking GLP-1 agonists. The increase in relative risk was noted for all types of thyroid cancer in patients using GLP-1 receptor agonists for 1-3 years.

An accompanying commentary by Caroline A. Thompson, PhD, and Til Stürmer, MD, provides perspective on this study’s potential limitations. These include detection bias, as the study results focused only on the statistically significant data. Also discussed were limitations to the case-control design, issues with claims-based tumor type classification (unavailability of surgical pathology), and an inability to adjust for family history and obesity, which is a risk factor alone for thyroid cancer. There was also no adjustment for exposure to head/neck radiation.

While this study has important findings to consider, it deserves further investigation, with future studies linking data to tumor registry data before a change is made in clinical practice.

No clear relationship has been drawn between GLP-1 receptor agonists and thyroid cancer in humans. Numerous confounding factors limit the data. Studies generally don’t specify the type of thyroid cancer, and they lump medullary thyroid cancer, the rarest form, with papillary thyroid cancer.

Is a detection bias present where weight loss makes nodules more visible on the neck among those treated with GLP-1 agonists? And/or are patients treated with GLP-1 agonists being screened more stringently for thyroid nodules and/or cancer?
 

How to advise our patients and respond to the EMR messages

The TikTok videos may continue, the celebrity chatter may increase, and we, as physicians, will continue to look to real-world data with randomized controlled trials to tailor our decision-making and guide our patients.

It’s prudent to advise patients that if they have a personal or family history of medullary thyroid cancer or multiple endocrine neoplasia syndrome type 2, in particular, they should avoid using this class of medication. Thyroid cancer remains a rare outcome, and GLP-1 receptor agonists remain a very important and beneficial treatment option for the right patient.

A version of this article first appeared on Medscape.com.

With #Ozempic and #ozempicweightloss continuing to trend on social media, along with the mainstream media focusing on celebrities who rely on Ozempic (semaglutide) for weight loss, the daily requests for this new medication have been increasing.

Accompanying these requests are concerns and questions about potential risks, including this most recent message from one of my patients: “Dr. P – I saw the warnings. Is this medication going to make me get thyroid cancer? Please let me know!”

Let’s look at what we know to date, including recent studies, and how to advise our patients on this very hot topic.
 

Using GLP-1 receptor agonists for obesity

We have extensive prior experience with glucagon-like peptide 1 (GLP-1) receptor agonists, such as semaglutide, for treating type 2 diabetes and now recently as agents for weight loss.

Large clinical trials have documented the benefits of this medication class not only for weight reduction but also for cardiovascular and renal benefits in patients with diabetes. The subcutaneously injectable medications work by promoting insulin secretion, slowing gastric emptying, and suppressing glucagon secretion, with a low risk for hypoglycemia.

The Food and Drug Administration approved daily-injection GLP-1 agonist liraglutide for weight loss in 2014, and weekly-injection semaglutide for chronic weight management in 2021, in patients with a body mass index ≥ 27 with at least one weight-related condition or a BMI ≥ 30.

The brand name for semaglutide approved for weight loss is Wegovy, and the dose is slightly higher (maximum 2.4 mg/wk) than that of Ozempic (maximum 2.0 mg/wk), which is semaglutide approved for type 2 diabetes.

In trials for weight loss, data showed a mean change in body weight of almost 15% in the semaglutide group at week 68 compared with placebo, which is very impressive, particularly compared with other FDA-approved oral long-term weight loss medications.

The newest synthetic dual-acting agent is tirzepatide, which targets GLP-1 but is also a glucose-dependent insulinotropic polypeptide (GIP) agonist. The weekly subcutaneous injection was approved in May 2022 as Mounjaro for treating type 2 diabetes and produced even greater weight loss than semaglutide in clinical trials. Tirzepatide is now in trials for obesity and is under expedited review by the FDA for weight loss.
 

Why the concern about thyroid cancer?

Early on with the FDA approvals of GLP-1 agonists, a warning accompanied the products’ labels to not use this class of medications in patients with medullary thyroid cancer, a family history of medullary thyroid cancer, or multiple endocrine neoplasia syndrome type 2. This warning was based on data from animal studies.

Human pancreatic cells aren’t the only cells that express GLP-1 receptors. These receptors are also expressed by parafollicular cells (C cells) of the thyroid, which secrete calcitonin and are the cells involved in medullary thyroid cancer. A dose-related and duration-dependent increase in thyroid C-cell tumor incidence was noted in rodents. The same relationship was not demonstrated in monkeys. Humans have far fewer C cells than rats, and human C cells have very low expression of the GLP-1 receptor.

Over a decade ago, a study examining the FDA’s database of reported adverse events found an increased risk for thyroid cancer in patients treated with exenatide, another GLP-1 agonist. The reporting system wasn’t designed to distinguish thyroid cancer subtypes.

Numerous subsequent studies didn’t confirm this relationship. The LEADER trial looked at liraglutide in patients with type 2 diabetes and showed no effect of GLP-1 receptor activation on human serum calcitonin levels, C-cell proliferation, or C-cell malignancy. Similarly, a large meta-analysis in patients with type 2 diabetes didn’t find a statistically increased risk for thyroid cancer with liraglutide, and no thyroid malignancies were reported with exenatide.

Two U.S. administrative databases from commercial health plans (a retrospective cohort study and a nested case-control study) compared type 2 diabetes patients who were taking exenatide vs. other antidiabetic drugs and found that exenatide was not significantly associated with an increased risk for thyroid cancer.

And a recent meta-analysis of 45 trials showed no significant effects on the occurrence of thyroid cancer with GLP-1 receptor agonists. Of note, it did find an increased risk for overall thyroid disorders, although there was no clear statistically significant finding pointing to a specific thyroid disorder.

Differing from prior studies, a recent nationwide French health care system study provided newer data suggesting a moderate increased risk for thyroid cancer in a cohort of patients with type 2 diabetes who were taking GLP-1 agonists. The increase in relative risk was noted for all types of thyroid cancer in patients using GLP-1 receptor agonists for 1-3 years.

An accompanying commentary by Caroline A. Thompson, PhD, and Til Stürmer, MD, provides perspective on this study’s potential limitations. These include detection bias, as the study results focused only on the statistically significant data. Also discussed were limitations to the case-control design, issues with claims-based tumor type classification (unavailability of surgical pathology), and an inability to adjust for family history and obesity, which is a risk factor alone for thyroid cancer. There was also no adjustment for exposure to head/neck radiation.

While this study has important findings to consider, it deserves further investigation, with future studies linking data to tumor registry data before a change is made in clinical practice.

No clear relationship has been drawn between GLP-1 receptor agonists and thyroid cancer in humans. Numerous confounding factors limit the data. Studies generally don’t specify the type of thyroid cancer, and they lump medullary thyroid cancer, the rarest form, with papillary thyroid cancer.

Is a detection bias present where weight loss makes nodules more visible on the neck among those treated with GLP-1 agonists? And/or are patients treated with GLP-1 agonists being screened more stringently for thyroid nodules and/or cancer?
 

How to advise our patients and respond to the EMR messages

The TikTok videos may continue, the celebrity chatter may increase, and we, as physicians, will continue to look to real-world data with randomized controlled trials to tailor our decision-making and guide our patients.

It’s prudent to advise patients that if they have a personal or family history of medullary thyroid cancer or multiple endocrine neoplasia syndrome type 2, in particular, they should avoid using this class of medication. Thyroid cancer remains a rare outcome, and GLP-1 receptor agonists remain a very important and beneficial treatment option for the right patient.

A version of this article first appeared on Medscape.com.

With the rising popularity of weight-loss drug injections, I’ve received many questions from patients about the pros, cons, and costs. While Ozempic (semaglutide) is perhaps the best known, it’s technically an agent approved only for type 2 diabetes that has been used off label for obesity. The same substance, semaglutide, is approved for use in obesity, but at a higher dose, under the brand name Wegovy. Alternatives are available, and results will vary depending on the specific agent used and the individual.

Ultimately, I decided to try these new injections for myself. I am not a paid representative for, nor an advocate of, any of these medications; I’m here only to share my personal experience.

In my discussions with patients about weight, I sometimes felt like an imposter. While I was overweight by medical standards, I fortunately had none of the underlying health problems. I wasn’t on medications for blood pressure nor did I have diabetes, but I was counseling people to lose weight and eat better while not always following my own advice.

Since having children and turning 40, my metabolism, like many other women’s, seems to have plummeted. I tried a number of older weight-loss medications, like phentermine and phendimetrazine, under the supervision of medical professionals.

Each time, the efforts worked for a short while, particularly when I followed good portion control and practiced moderate exercise. Once the side effects (that is, tachycardia, palpitations, mood changes, constipation) became intolerable, or I became tired or fearful of being on the medications too long, I’d stop and I would regain some of the weight.

When the newer subcutaneous injectable medications arrived on the scene and I started to talk to my patients about them, I was intrigued by their novel mode of action and seeming benefits.

These medications, glucagonlike peptide–1 (GLP-1) receptor agonists, were first approved for type 2 diabetes, and it soon became apparent that patients were losing significant amounts of weight taking them, so manufacturers conducted further trials in obesity patients without type 2 diabetes.

The first of these, liraglutide, is injected daily and was first approved as Victoza for type 2 diabetes; it later received an additional approval for obesity, in December 2014, as Saxenda.

Semaglutide, another of the new GLP-1 agonists, was first approved for type 2 diabetes as Ozempic but again was found to lead to substantial weight loss, so a subsequent approval of the drug for obesity, as Wegovy, came in June 2021. Semaglutide is injected once a week.

Semaglutide was branded a “game changer” when it was licensed for obesity because the mean weight loss seen in trials was around 15%, more than for any other drug and approaching what could be achieved with bariatric surgery, some doctors said.

These medications work in a different way from the older weight loss drugs, which had focused on the use of amphetamines. The newer medications became very popular because treating obesity helps lower blood glucose, blood pressure, cholesterol, kidney disease risk, and other comorbidities that occur with diabetes. Plus, for most people, there were fewer side effects.

I first tried Saxenda when it arrived on the market, via some samples that our pharmaceutical representative brought, both out of curiosity and to see if it would help me lose the stubborn baby weight. I ended up stopping the daily injections after my second or third week because of nausea and vomiting. I took a break, got a prescription for antinausea medicine, and tried again because it did indeed decrease my appetite. However, when I took my prescription to the pharmacy, my insurance wouldn’t cover it. It happens to doctors, too.

Fast-forward to 2017-2018. The baby weight was still holding on despite lifestyle changes, diet, and exercising. The newer drug classes hit the market, and again we had samples from our reps. When our rep explained the potential for weight loss in patients without diabetes, I tried Ozempic off label. Within the first 2 weeks, I noticed a 3- to- 5-lb weight loss.

When Ozempic was on backorder, I switched to a low dose of Mounjaro (tirzepatide), a new dual GLP-1 and glucose-dependent insulinotropic polypeptide agonist, approved for type 2 diabetes in May 2022, again using it off label as a weekly injection, as it isn’t currently approved for weight loss. However, it does produce significant weight loss and is awaiting approval for obesity.

With these new medications, I noticed that both my patients and I didn’t complain as much about nausea and vomiting, but I did experience stomach upset, constipation, and acid reflux.

The appetite suppression is effective. It slows down the emptying of the gut so I feel full longer. I’ve lost 30 lb with these weekly injections and would like to lose another 20 lb. I follow a routine of reasonable, portion-controlled eating and moderate exercise (30 minutes of cardiovascular activity at least two to three times a week).

Discontinuing the medications may cause rebound weight gain, especially if I’m no longer following a routine of healthy eating and/or moderate exercise. I deal with minimal constipation by taking stool softeners, and I take antacids for acid reflux.

Here’s what I recommend applying when working with patients who have obesity: First, explain how these medications work. Then conduct a health history to make sure these injections are right for them. Patients with a family history of pancreatic cancer can’t take these medications. You also want to monitor use in patients with a history of hypoglycemia so their blood sugar doesn’t drop too low. It’s also important to make sure your patients are able to afford the medication. My husband takes Ozempic for diabetes, and recently we were told that a refill would cost about $1,500 a month, even with insurance. “Covered” doesn’t necessarily mean affordable.

Take a baseline hemoglobin A1c and repeat it after the patient has been on the medication for 2-3 weeks. Also remind them that they can’t rely solely on the medication but need to practice portion control and healthier eating and to exercise more.

For myself, I want to lose those remaining 20 lb or so by eating healthy and being physically active without having to rely on medication for the rest of my life. Research on these medications is still early so we don’t know the long-term effects yet.

As clinicians, I feel it’s okay to be honest with our patients about our own personal struggles to help them understand that they are not alone and that losing weight is a challenge for everyone.

Dr. Swiner is a family physician in Durham, N.C. She reported no conflicts of interest.

A version of this article first appeared on Medscape.com.

With the rising popularity of weight-loss drug injections, I’ve received many questions from patients about the pros, cons, and costs. While Ozempic (semaglutide) is perhaps the best known, it’s technically an agent approved only for type 2 diabetes that has been used off label for obesity. The same substance, semaglutide, is approved for use in obesity, but at a higher dose, under the brand name Wegovy. Alternatives are available, and results will vary depending on the specific agent used and the individual.

Ultimately, I decided to try these new injections for myself. I am not a paid representative for, nor an advocate of, any of these medications; I’m here only to share my personal experience.

In my discussions with patients about weight, I sometimes felt like an imposter. While I was overweight by medical standards, I fortunately had none of the underlying health problems. I wasn’t on medications for blood pressure nor did I have diabetes, but I was counseling people to lose weight and eat better while not always following my own advice.

Since having children and turning 40, my metabolism, like many other women’s, seems to have plummeted. I tried a number of older weight-loss medications, like phentermine and phendimetrazine, under the supervision of medical professionals.

Each time, the efforts worked for a short while, particularly when I followed good portion control and practiced moderate exercise. Once the side effects (that is, tachycardia, palpitations, mood changes, constipation) became intolerable, or I became tired or fearful of being on the medications too long, I’d stop and I would regain some of the weight.

When the newer subcutaneous injectable medications arrived on the scene and I started to talk to my patients about them, I was intrigued by their novel mode of action and seeming benefits.

These medications, glucagonlike peptide–1 (GLP-1) receptor agonists, were first approved for type 2 diabetes, and it soon became apparent that patients were losing significant amounts of weight taking them, so manufacturers conducted further trials in obesity patients without type 2 diabetes.

The first of these, liraglutide, is injected daily and was first approved as Victoza for type 2 diabetes; it later received an additional approval for obesity, in December 2014, as Saxenda.

Semaglutide, another of the new GLP-1 agonists, was first approved for type 2 diabetes as Ozempic but again was found to lead to substantial weight loss, so a subsequent approval of the drug for obesity, as Wegovy, came in June 2021. Semaglutide is injected once a week.

Semaglutide was branded a “game changer” when it was licensed for obesity because the mean weight loss seen in trials was around 15%, more than for any other drug and approaching what could be achieved with bariatric surgery, some doctors said.

These medications work in a different way from the older weight loss drugs, which had focused on the use of amphetamines. The newer medications became very popular because treating obesity helps lower blood glucose, blood pressure, cholesterol, kidney disease risk, and other comorbidities that occur with diabetes. Plus, for most people, there were fewer side effects.

I first tried Saxenda when it arrived on the market, via some samples that our pharmaceutical representative brought, both out of curiosity and to see if it would help me lose the stubborn baby weight. I ended up stopping the daily injections after my second or third week because of nausea and vomiting. I took a break, got a prescription for antinausea medicine, and tried again because it did indeed decrease my appetite. However, when I took my prescription to the pharmacy, my insurance wouldn’t cover it. It happens to doctors, too.

Fast-forward to 2017-2018. The baby weight was still holding on despite lifestyle changes, diet, and exercising. The newer drug classes hit the market, and again we had samples from our reps. When our rep explained the potential for weight loss in patients without diabetes, I tried Ozempic off label. Within the first 2 weeks, I noticed a 3- to- 5-lb weight loss.

When Ozempic was on backorder, I switched to a low dose of Mounjaro (tirzepatide), a new dual GLP-1 and glucose-dependent insulinotropic polypeptide agonist, approved for type 2 diabetes in May 2022, again using it off label as a weekly injection, as it isn’t currently approved for weight loss. However, it does produce significant weight loss and is awaiting approval for obesity.

With these new medications, I noticed that both my patients and I didn’t complain as much about nausea and vomiting, but I did experience stomach upset, constipation, and acid reflux.

The appetite suppression is effective. It slows down the emptying of the gut so I feel full longer. I’ve lost 30 lb with these weekly injections and would like to lose another 20 lb. I follow a routine of reasonable, portion-controlled eating and moderate exercise (30 minutes of cardiovascular activity at least two to three times a week).

Discontinuing the medications may cause rebound weight gain, especially if I’m no longer following a routine of healthy eating and/or moderate exercise. I deal with minimal constipation by taking stool softeners, and I take antacids for acid reflux.

Here’s what I recommend applying when working with patients who have obesity: First, explain how these medications work. Then conduct a health history to make sure these injections are right for them. Patients with a family history of pancreatic cancer can’t take these medications. You also want to monitor use in patients with a history of hypoglycemia so their blood sugar doesn’t drop too low. It’s also important to make sure your patients are able to afford the medication. My husband takes Ozempic for diabetes, and recently we were told that a refill would cost about $1,500 a month, even with insurance. “Covered” doesn’t necessarily mean affordable.

Take a baseline hemoglobin A1c and repeat it after the patient has been on the medication for 2-3 weeks. Also remind them that they can’t rely solely on the medication but need to practice portion control and healthier eating and to exercise more.

For myself, I want to lose those remaining 20 lb or so by eating healthy and being physically active without having to rely on medication for the rest of my life. Research on these medications is still early so we don’t know the long-term effects yet.

As clinicians, I feel it’s okay to be honest with our patients about our own personal struggles to help them understand that they are not alone and that losing weight is a challenge for everyone.

Dr. Swiner is a family physician in Durham, N.C. She reported no conflicts of interest.

A version of this article first appeared on Medscape.com.

With the rising popularity of weight-loss drug injections, I’ve received many questions from patients about the pros, cons, and costs. While Ozempic (semaglutide) is perhaps the best known, it’s technically an agent approved only for type 2 diabetes that has been used off label for obesity. The same substance, semaglutide, is approved for use in obesity, but at a higher dose, under the brand name Wegovy. Alternatives are available, and results will vary depending on the specific agent used and the individual.

Ultimately, I decided to try these new injections for myself. I am not a paid representative for, nor an advocate of, any of these medications; I’m here only to share my personal experience.

In my discussions with patients about weight, I sometimes felt like an imposter. While I was overweight by medical standards, I fortunately had none of the underlying health problems. I wasn’t on medications for blood pressure nor did I have diabetes, but I was counseling people to lose weight and eat better while not always following my own advice.

Since having children and turning 40, my metabolism, like many other women’s, seems to have plummeted. I tried a number of older weight-loss medications, like phentermine and phendimetrazine, under the supervision of medical professionals.

Each time, the efforts worked for a short while, particularly when I followed good portion control and practiced moderate exercise. Once the side effects (that is, tachycardia, palpitations, mood changes, constipation) became intolerable, or I became tired or fearful of being on the medications too long, I’d stop and I would regain some of the weight.

When the newer subcutaneous injectable medications arrived on the scene and I started to talk to my patients about them, I was intrigued by their novel mode of action and seeming benefits.

These medications, glucagonlike peptide–1 (GLP-1) receptor agonists, were first approved for type 2 diabetes, and it soon became apparent that patients were losing significant amounts of weight taking them, so manufacturers conducted further trials in obesity patients without type 2 diabetes.

The first of these, liraglutide, is injected daily and was first approved as Victoza for type 2 diabetes; it later received an additional approval for obesity, in December 2014, as Saxenda.

Semaglutide, another of the new GLP-1 agonists, was first approved for type 2 diabetes as Ozempic but again was found to lead to substantial weight loss, so a subsequent approval of the drug for obesity, as Wegovy, came in June 2021. Semaglutide is injected once a week.

Semaglutide was branded a “game changer” when it was licensed for obesity because the mean weight loss seen in trials was around 15%, more than for any other drug and approaching what could be achieved with bariatric surgery, some doctors said.

These medications work in a different way from the older weight loss drugs, which had focused on the use of amphetamines. The newer medications became very popular because treating obesity helps lower blood glucose, blood pressure, cholesterol, kidney disease risk, and other comorbidities that occur with diabetes. Plus, for most people, there were fewer side effects.

I first tried Saxenda when it arrived on the market, via some samples that our pharmaceutical representative brought, both out of curiosity and to see if it would help me lose the stubborn baby weight. I ended up stopping the daily injections after my second or third week because of nausea and vomiting. I took a break, got a prescription for antinausea medicine, and tried again because it did indeed decrease my appetite. However, when I took my prescription to the pharmacy, my insurance wouldn’t cover it. It happens to doctors, too.

Fast-forward to 2017-2018. The baby weight was still holding on despite lifestyle changes, diet, and exercising. The newer drug classes hit the market, and again we had samples from our reps. When our rep explained the potential for weight loss in patients without diabetes, I tried Ozempic off label. Within the first 2 weeks, I noticed a 3- to- 5-lb weight loss.

When Ozempic was on backorder, I switched to a low dose of Mounjaro (tirzepatide), a new dual GLP-1 and glucose-dependent insulinotropic polypeptide agonist, approved for type 2 diabetes in May 2022, again using it off label as a weekly injection, as it isn’t currently approved for weight loss. However, it does produce significant weight loss and is awaiting approval for obesity.

With these new medications, I noticed that both my patients and I didn’t complain as much about nausea and vomiting, but I did experience stomach upset, constipation, and acid reflux.

The appetite suppression is effective. It slows down the emptying of the gut so I feel full longer. I’ve lost 30 lb with these weekly injections and would like to lose another 20 lb. I follow a routine of reasonable, portion-controlled eating and moderate exercise (30 minutes of cardiovascular activity at least two to three times a week).

Discontinuing the medications may cause rebound weight gain, especially if I’m no longer following a routine of healthy eating and/or moderate exercise. I deal with minimal constipation by taking stool softeners, and I take antacids for acid reflux.

Here’s what I recommend applying when working with patients who have obesity: First, explain how these medications work. Then conduct a health history to make sure these injections are right for them. Patients with a family history of pancreatic cancer can’t take these medications. You also want to monitor use in patients with a history of hypoglycemia so their blood sugar doesn’t drop too low. It’s also important to make sure your patients are able to afford the medication. My husband takes Ozempic for diabetes, and recently we were told that a refill would cost about $1,500 a month, even with insurance. “Covered” doesn’t necessarily mean affordable.

Take a baseline hemoglobin A1c and repeat it after the patient has been on the medication for 2-3 weeks. Also remind them that they can’t rely solely on the medication but need to practice portion control and healthier eating and to exercise more.

For myself, I want to lose those remaining 20 lb or so by eating healthy and being physically active without having to rely on medication for the rest of my life. Research on these medications is still early so we don’t know the long-term effects yet.

As clinicians, I feel it’s okay to be honest with our patients about our own personal struggles to help them understand that they are not alone and that losing weight is a challenge for everyone.

Dr. Swiner is a family physician in Durham, N.C. She reported no conflicts of interest.

A version of this article first appeared on Medscape.com.

A 43-year-old man presents to the emergency department with dizziness and a 6-hour history of passing maroon stool. He has been in good health with the only medical problem in his history being depression.

He is taking sertraline. On exam, his blood pressure is 100/60, and his pulse is 100, both while lying down. His blood pressure while standing is 90/60 and his pulse while standing is 130. The rest of his exam is normal. His lab values include hemoglobin of 10, hematocrit of 30, white blood cell of 4.6, platelet count of 175,000, sodium of 142, chloride of 100, bicarbonate of 24, potassium of 3.8, blood urea nitrogen (BUN) of 38, and creatinine clearance (Cr) of 1.1.

What is the most likely source of his bleeding?

A. Gastric ulcer

B. Meckel’s diverticulum

C. Arteriovenous malformation

D. Diverticulosis

E. Hemorrhoids

What makes the most sense

The most likely cause of this patient’s maroon stool is an upper gastrointestinal bleed, so it would make the most sense for a gastric ulcer to be the source of his bleeding. The clue here is the very high BUN/Cr ratio.

We were all taught early in our training that a high BUN/Cr ratio represented volume depletion. This is certainly the most common cause, but very high BUN/Cr ratios (over 30) can represent causes beyond volume depletion.

Witting and colleagues studied factors that predicted upper GI bleeding in patients presenting without hematemesis. They found that the three strongest predictors were black stool (odds ratio, 16.6), BUN/Cr ratio greater than 30 (OR, 10), and age greater than 50 (OR, 8.4).¹

Srygley and colleagues reviewed high-quality studies of factors associated with upper GI bleeding.² Factors that were found to increase the likelihood of an upper gastrointestinal bleed were Melenic stool on exam (likelihood ratio, 25), blood or coffee grounds on nasogastric aspiration (LR, 9.6), and BUN/Cr ratio greater than 30 (LR, 7.5).

Very high BUN/Cr ratios can indicate problems other than UGI bleeding and volume depletion. High BUN/Cr ratios are seen in patients with heart failure.

Zhang and colleagues studied if a high BUN/Cr ratio helped distinguish heart failure from asthma and chronic obstructive pulmonary disease (COPD).³ They found that, compared with those in the asthma group, the BUN/Cr ratios were significantly increased in the heart failure group (P < .05), whereas no significant differences in BUN/Cr ratios were found between the asthma and COPD groups.

Cheang and colleagues conducted their own study, as well as a meta-analysis, looking to see if high BUN/Cr ratios predicted increased mortality in patients with acute heart failure.⁴ In the meta-analysis of 8 studies (including their own), they found that the highest BUN/Cr ratio category was associated with an 77% higher all-cause mortality than the lowest category (hazard ratio, 1.77; 95% confidence interval, 1.52-2.07).

High dose corticosteroids can raise BUN levels, especially in patients with chronic kidney disease, and cause unexpectedly high BUN/Cr ratios.
 

Pearl

Very high BUN/Cr ratios (greater than 30) can signify upper GI bleeding, heart failure, or high-dose corticosteroid use.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at dpaauw@uw.edu.

References

1. Am J Emerg Med. 2006 May;24(3):280-5.

2. JAMA. 2012;307(10):1072-9.

3. Comput Math Methods Med. 2022 Jul 21. doi: 10.1155/2022/4586458.

4. Cardiorenal Med. 2020;10:415-28.

A 43-year-old man presents to the emergency department with dizziness and a 6-hour history of passing maroon stool. He has been in good health with the only medical problem in his history being depression.

He is taking sertraline. On exam, his blood pressure is 100/60, and his pulse is 100, both while lying down. His blood pressure while standing is 90/60 and his pulse while standing is 130. The rest of his exam is normal. His lab values include hemoglobin of 10, hematocrit of 30, white blood cell of 4.6, platelet count of 175,000, sodium of 142, chloride of 100, bicarbonate of 24, potassium of 3.8, blood urea nitrogen (BUN) of 38, and creatinine clearance (Cr) of 1.1.

What is the most likely source of his bleeding?

A. Gastric ulcer

B. Meckel’s diverticulum

C. Arteriovenous malformation

D. Diverticulosis

E. Hemorrhoids

What makes the most sense

The most likely cause of this patient’s maroon stool is an upper gastrointestinal bleed, so it would make the most sense for a gastric ulcer to be the source of his bleeding. The clue here is the very high BUN/Cr ratio.

We were all taught early in our training that a high BUN/Cr ratio represented volume depletion. This is certainly the most common cause, but very high BUN/Cr ratios (over 30) can represent causes beyond volume depletion.

Witting and colleagues studied factors that predicted upper GI bleeding in patients presenting without hematemesis. They found that the three strongest predictors were black stool (odds ratio, 16.6), BUN/Cr ratio greater than 30 (OR, 10), and age greater than 50 (OR, 8.4).¹

Srygley and colleagues reviewed high-quality studies of factors associated with upper GI bleeding.² Factors that were found to increase the likelihood of an upper gastrointestinal bleed were Melenic stool on exam (likelihood ratio, 25), blood or coffee grounds on nasogastric aspiration (LR, 9.6), and BUN/Cr ratio greater than 30 (LR, 7.5).

Very high BUN/Cr ratios can indicate problems other than UGI bleeding and volume depletion. High BUN/Cr ratios are seen in patients with heart failure.

Zhang and colleagues studied if a high BUN/Cr ratio helped distinguish heart failure from asthma and chronic obstructive pulmonary disease (COPD).³ They found that, compared with those in the asthma group, the BUN/Cr ratios were significantly increased in the heart failure group (P < .05), whereas no significant differences in BUN/Cr ratios were found between the asthma and COPD groups.

Cheang and colleagues conducted their own study, as well as a meta-analysis, looking to see if high BUN/Cr ratios predicted increased mortality in patients with acute heart failure.⁴ In the meta-analysis of 8 studies (including their own), they found that the highest BUN/Cr ratio category was associated with an 77% higher all-cause mortality than the lowest category (hazard ratio, 1.77; 95% confidence interval, 1.52-2.07).

High dose corticosteroids can raise BUN levels, especially in patients with chronic kidney disease, and cause unexpectedly high BUN/Cr ratios.
 

Pearl

Very high BUN/Cr ratios (greater than 30) can signify upper GI bleeding, heart failure, or high-dose corticosteroid use.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at dpaauw@uw.edu.

References

1. Am J Emerg Med. 2006 May;24(3):280-5.

2. JAMA. 2012;307(10):1072-9.

3. Comput Math Methods Med. 2022 Jul 21. doi: 10.1155/2022/4586458.

4. Cardiorenal Med. 2020;10:415-28.

A 43-year-old man presents to the emergency department with dizziness and a 6-hour history of passing maroon stool. He has been in good health with the only medical problem in his history being depression.

He is taking sertraline. On exam, his blood pressure is 100/60, and his pulse is 100, both while lying down. His blood pressure while standing is 90/60 and his pulse while standing is 130. The rest of his exam is normal. His lab values include hemoglobin of 10, hematocrit of 30, white blood cell of 4.6, platelet count of 175,000, sodium of 142, chloride of 100, bicarbonate of 24, potassium of 3.8, blood urea nitrogen (BUN) of 38, and creatinine clearance (Cr) of 1.1.

What is the most likely source of his bleeding?

A. Gastric ulcer

B. Meckel’s diverticulum

C. Arteriovenous malformation

D. Diverticulosis

E. Hemorrhoids

What makes the most sense

The most likely cause of this patient’s maroon stool is an upper gastrointestinal bleed, so it would make the most sense for a gastric ulcer to be the source of his bleeding. The clue here is the very high BUN/Cr ratio.

We were all taught early in our training that a high BUN/Cr ratio represented volume depletion. This is certainly the most common cause, but very high BUN/Cr ratios (over 30) can represent causes beyond volume depletion.

Witting and colleagues studied factors that predicted upper GI bleeding in patients presenting without hematemesis. They found that the three strongest predictors were black stool (odds ratio, 16.6), BUN/Cr ratio greater than 30 (OR, 10), and age greater than 50 (OR, 8.4).¹

Srygley and colleagues reviewed high-quality studies of factors associated with upper GI bleeding.² Factors that were found to increase the likelihood of an upper gastrointestinal bleed were Melenic stool on exam (likelihood ratio, 25), blood or coffee grounds on nasogastric aspiration (LR, 9.6), and BUN/Cr ratio greater than 30 (LR, 7.5).

Very high BUN/Cr ratios can indicate problems other than UGI bleeding and volume depletion. High BUN/Cr ratios are seen in patients with heart failure.

Zhang and colleagues studied if a high BUN/Cr ratio helped distinguish heart failure from asthma and chronic obstructive pulmonary disease (COPD).³ They found that, compared with those in the asthma group, the BUN/Cr ratios were significantly increased in the heart failure group (P < .05), whereas no significant differences in BUN/Cr ratios were found between the asthma and COPD groups.

Cheang and colleagues conducted their own study, as well as a meta-analysis, looking to see if high BUN/Cr ratios predicted increased mortality in patients with acute heart failure.⁴ In the meta-analysis of 8 studies (including their own), they found that the highest BUN/Cr ratio category was associated with an 77% higher all-cause mortality than the lowest category (hazard ratio, 1.77; 95% confidence interval, 1.52-2.07).

High dose corticosteroids can raise BUN levels, especially in patients with chronic kidney disease, and cause unexpectedly high BUN/Cr ratios.
 

Pearl

Very high BUN/Cr ratios (greater than 30) can signify upper GI bleeding, heart failure, or high-dose corticosteroid use.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at dpaauw@uw.edu.

References

1. Am J Emerg Med. 2006 May;24(3):280-5.

2. JAMA. 2012;307(10):1072-9.

3. Comput Math Methods Med. 2022 Jul 21. doi: 10.1155/2022/4586458.

4. Cardiorenal Med. 2020;10:415-28.

Patients with advanced renal cell carcinoma who are taking a tyrosine kinase inhibitor (TKI) to prolong their lives will typically keep going without a break until the disease progresses or toxicities such as severe fatigue and diarrhea become intolerable.

That might soon change with the publication of a unique study. Lasting 10 years, the phase 3 STAR trial involved 920 patients across 60 cancer centers. These patients had advanced kidney cancer and were taking either sunitinib (Sutent) or pazopanib (Votrient).

The results showed that taking an occasional respite from TKI therapy had little impact on the patient’s survival.

The study was published online in The Lancet Oncology.

The study was funded by the United Kingdom’s National Institute for Health and Care Research because drug companies never run studies on how to reduce the use of their drug, commented lead author Janet Brown, MD, of the University of Sheffield (England).

“We rely on the NIHR to do these important trials that … companies wouldn’t do,” she commented to this news organization.

Commenting on the rationale for STAR, coauthor Jenny Hewison, PhD, of Leeds (England) University School of Medicine, explained that patients often find it difficult to tolerate TKIs. “Although these patients are getting the best treatment that we can offer them, it’s very demanding. … It could make them feel tired, quite unwell. And there can be a range of other effects including sickness and diarrhea.”

As an example, 77% of patients in the pivotal trial of sunitinib in kidney cancer experienced grade 3 or 4 adverse events such as hypertension (13%), fatigue (15%), diarrhea (10%) and hand-foot syndrome (8%).

Both sunitinib and pazopanib carry label warnings of severe and fatal hepatotoxicity.

Also, in contrast to conventional chemotherapy, which is usually given in a finite number of courses, treatment with TKIs carries on indefinitely.

“It feels like you’re taking [TKIs] for the whole of the rest of your life,” said Dr. Brown.
 

Study details

The STAR trial, an open-label, noninferiority, randomized controlled study, is the first phase 3 study of treatment breaks in renal cell carcinoma. The participants had inoperable locoregional or metastatic clear cell renal cell carcinoma (ccRCC) and had received no systemic therapy for advanced disease.

They were randomly assigned before TKI treatment to a conventional continuation strategy or a drug-free interval approach. The treating physician decided whether a patient would take sunitinib or pazopanib.

All participants took their drugs for four cycles (6 weeks each cycle). At the 24-week point, those with a complete response, partial response, or stable disease began their randomized assignment.

Individuals who took a break continued until their disease progressed, at which point therapy was resumed. They could take further treatment breaks once their disease was back under control. The group on continuous treatment kept going until disease progression or intolerable toxicities. Median follow up was 58 months.

In both the per-protocol and intent-to-treat (ITT) populations, overall survival was 28 months for the people who received continuous treatment vs. 27 months for those who took a break. Statistical noninferiority was established in the ITT population but not in the per-protocol population.

The median length of all treatment breaks was 87 days. Many people took two or more breaks; one patient took nine breaks overall. The breaks were popular: only 3% of participants who were meant to stop therapy withdrew from the study in order to continue their treatment.

Said Dr. Hewison: “In the very early days of planning the study there were some doubts as to whether it would succeed because of potential unwillingness of people to stop treatment for a while.”

Dr. Brown agreed: “People did worry about that initially, but it actually seemed to be more the other way around. By that time – 6 months – people were relieved to be there. …We actually had some people from the other arm asking, could they also have a break?”

To understand better the benefits of treatment breaks to patients, Janine Bestall, PhD, a senior research fellow in applied health research at the University of Leeds, conducted a qualitative study in parallel with the main trial.

Summing up the patients’ experiences, Dr. Bestall said the drug-free periods “gave them more time.”

Dr. Bestall quoted one patient who said: “I know that things can happen and it grows back, but you’ve always got the buffer there knowing that you can go back and get help. But you actually lead a normal life and the advantage is, yeah, you can go on holiday, you can actually do more things in the garden, cleaning up, painting, whatever needs doing, you do it.”

Dr. Brown said, “I had a lady who, when she was on the trial, had four breaks in total, one when her daughter got married, and [she said] that was really nice for her to do all the shopping and all the normal things that you do, and not be on something that was making her tired and causing sore hands and diarrhea.” 

The drug-free interval strategy provided annual cost savings of 3,235 pounds sterling ($3,850) and a noninferior quality-adjusted life-year (QALY) benefit in both the ITT and per-protocol populations.

Serious adverse reactions occurred in 9% of patients in the treatment-break group versus 12% of the continuous-treatment group.

The authors of the study concluded, “Treatment breaks might be a feasible and cost-effective option with lifestyle benefits for patients during tyrosine kinase inhibitor therapy in patients with renal cell carcinoma.”
 

Changes in treatment strategies

The STAR trial started recruiting in January 2012.

Since that time, immunotherapy has taken over as first-line treatment for many patients with advanced ccRCC in both the United Kingdom and the United States.

However, TKIs still have a place. The NCCN Kidney Cancer 2022 Guidelines recommend both sunitinib and pazopanib as options for first-line therapy in advanced disease. The 2022 ASCO Metastatic ccRCC guidelines recommend either drug as first-line treatment in combination with an immune checkpoint inhibitor or in monotherapy if there are “coexisting medical problems.”

In the United States, intermittent sunitinib in metastatic RCC was tested in a small study in 2017 with little activity in the literature since then. The authors, led by Moshe Ornstein, MD, from the Cleveland Clinic, concluded at the time that sunitinib treatment breaks were feasible and “clinical efficacy does not seem to be compromised.” Dr. Ornstein was approached for comment on this latest U.K. study but declined.

Back in the United Kingdom, the results of STAR arrived just in time.

Said Dr. Brown: “This has … been really helpful in the U.K. in the pandemic when people said, can these patients have extra breaks? At the worst of the pandemic we were able to say, sure, if it’s stable, we can keep them off for 3-6 months. …And so that’s already had a powerful impact.”

Dr. Brown concluded, “I think what the trial does allow us to do, as individual oncologists, is to look at the patients that this might be suitable for – it won’t be everybody – and to say yes, it’s okay to personalize things.”

The study was funded by the U.K.’s National Institute for Health and Care Research. Dr. Bestall reported no relevant financial relationships. Dr. Hewison reported funding to her institution from the NIHR Health Technology Assessment. Dr. Brown reports having served as a consultant or adviser for Novartis, Ipsen, Amgen, Merck Sharp & Dohme, Bristol-Myers Squibb, and Bayer; honoraria from Novartis, Ipsen, Amgen, Merck Sharp & Dohme, Bristol-Myers Squibb, and Bayer; research funding paid to their institution from the National Institute for Health and Care Research; and travel expenses from Ipsen. Other coauthors reported numerous relationships with industry.

A version of this article first appeared on Medscape.com.

Patients with advanced renal cell carcinoma who are taking a tyrosine kinase inhibitor (TKI) to prolong their lives will typically keep going without a break until the disease progresses or toxicities such as severe fatigue and diarrhea become intolerable.

That might soon change with the publication of a unique study. Lasting 10 years, the phase 3 STAR trial involved 920 patients across 60 cancer centers. These patients had advanced kidney cancer and were taking either sunitinib (Sutent) or pazopanib (Votrient).

The results showed that taking an occasional respite from TKI therapy had little impact on the patient’s survival.

The study was published online in The Lancet Oncology.

The study was funded by the United Kingdom’s National Institute for Health and Care Research because drug companies never run studies on how to reduce the use of their drug, commented lead author Janet Brown, MD, of the University of Sheffield (England).

“We rely on the NIHR to do these important trials that … companies wouldn’t do,” she commented to this news organization.

Commenting on the rationale for STAR, coauthor Jenny Hewison, PhD, of Leeds (England) University School of Medicine, explained that patients often find it difficult to tolerate TKIs. “Although these patients are getting the best treatment that we can offer them, it’s very demanding. … It could make them feel tired, quite unwell. And there can be a range of other effects including sickness and diarrhea.”

As an example, 77% of patients in the pivotal trial of sunitinib in kidney cancer experienced grade 3 or 4 adverse events such as hypertension (13%), fatigue (15%), diarrhea (10%) and hand-foot syndrome (8%).

Both sunitinib and pazopanib carry label warnings of severe and fatal hepatotoxicity.

Also, in contrast to conventional chemotherapy, which is usually given in a finite number of courses, treatment with TKIs carries on indefinitely.

“It feels like you’re taking [TKIs] for the whole of the rest of your life,” said Dr. Brown.
 

Study details

The STAR trial, an open-label, noninferiority, randomized controlled study, is the first phase 3 study of treatment breaks in renal cell carcinoma. The participants had inoperable locoregional or metastatic clear cell renal cell carcinoma (ccRCC) and had received no systemic therapy for advanced disease.

They were randomly assigned before TKI treatment to a conventional continuation strategy or a drug-free interval approach. The treating physician decided whether a patient would take sunitinib or pazopanib.

All participants took their drugs for four cycles (6 weeks each cycle). At the 24-week point, those with a complete response, partial response, or stable disease began their randomized assignment.

Individuals who took a break continued until their disease progressed, at which point therapy was resumed. They could take further treatment breaks once their disease was back under control. The group on continuous treatment kept going until disease progression or intolerable toxicities. Median follow up was 58 months.

In both the per-protocol and intent-to-treat (ITT) populations, overall survival was 28 months for the people who received continuous treatment vs. 27 months for those who took a break. Statistical noninferiority was established in the ITT population but not in the per-protocol population.

The median length of all treatment breaks was 87 days. Many people took two or more breaks; one patient took nine breaks overall. The breaks were popular: only 3% of participants who were meant to stop therapy withdrew from the study in order to continue their treatment.

Said Dr. Hewison: “In the very early days of planning the study there were some doubts as to whether it would succeed because of potential unwillingness of people to stop treatment for a while.”

Dr. Brown agreed: “People did worry about that initially, but it actually seemed to be more the other way around. By that time – 6 months – people were relieved to be there. …We actually had some people from the other arm asking, could they also have a break?”

To understand better the benefits of treatment breaks to patients, Janine Bestall, PhD, a senior research fellow in applied health research at the University of Leeds, conducted a qualitative study in parallel with the main trial.

Summing up the patients’ experiences, Dr. Bestall said the drug-free periods “gave them more time.”

Dr. Bestall quoted one patient who said: “I know that things can happen and it grows back, but you’ve always got the buffer there knowing that you can go back and get help. But you actually lead a normal life and the advantage is, yeah, you can go on holiday, you can actually do more things in the garden, cleaning up, painting, whatever needs doing, you do it.”

Dr. Brown said, “I had a lady who, when she was on the trial, had four breaks in total, one when her daughter got married, and [she said] that was really nice for her to do all the shopping and all the normal things that you do, and not be on something that was making her tired and causing sore hands and diarrhea.” 

The drug-free interval strategy provided annual cost savings of 3,235 pounds sterling ($3,850) and a noninferior quality-adjusted life-year (QALY) benefit in both the ITT and per-protocol populations.

Serious adverse reactions occurred in 9% of patients in the treatment-break group versus 12% of the continuous-treatment group.

The authors of the study concluded, “Treatment breaks might be a feasible and cost-effective option with lifestyle benefits for patients during tyrosine kinase inhibitor therapy in patients with renal cell carcinoma.”
 

Changes in treatment strategies

The STAR trial started recruiting in January 2012.

Since that time, immunotherapy has taken over as first-line treatment for many patients with advanced ccRCC in both the United Kingdom and the United States.

However, TKIs still have a place. The NCCN Kidney Cancer 2022 Guidelines recommend both sunitinib and pazopanib as options for first-line therapy in advanced disease. The 2022 ASCO Metastatic ccRCC guidelines recommend either drug as first-line treatment in combination with an immune checkpoint inhibitor or in monotherapy if there are “coexisting medical problems.”

In the United States, intermittent sunitinib in metastatic RCC was tested in a small study in 2017 with little activity in the literature since then. The authors, led by Moshe Ornstein, MD, from the Cleveland Clinic, concluded at the time that sunitinib treatment breaks were feasible and “clinical efficacy does not seem to be compromised.” Dr. Ornstein was approached for comment on this latest U.K. study but declined.

Back in the United Kingdom, the results of STAR arrived just in time.

Said Dr. Brown: “This has … been really helpful in the U.K. in the pandemic when people said, can these patients have extra breaks? At the worst of the pandemic we were able to say, sure, if it’s stable, we can keep them off for 3-6 months. …And so that’s already had a powerful impact.”

Dr. Brown concluded, “I think what the trial does allow us to do, as individual oncologists, is to look at the patients that this might be suitable for – it won’t be everybody – and to say yes, it’s okay to personalize things.”

The study was funded by the U.K.’s National Institute for Health and Care Research. Dr. Bestall reported no relevant financial relationships. Dr. Hewison reported funding to her institution from the NIHR Health Technology Assessment. Dr. Brown reports having served as a consultant or adviser for Novartis, Ipsen, Amgen, Merck Sharp & Dohme, Bristol-Myers Squibb, and Bayer; honoraria from Novartis, Ipsen, Amgen, Merck Sharp & Dohme, Bristol-Myers Squibb, and Bayer; research funding paid to their institution from the National Institute for Health and Care Research; and travel expenses from Ipsen. Other coauthors reported numerous relationships with industry.

A version of this article first appeared on Medscape.com.

Patients with advanced renal cell carcinoma who are taking a tyrosine kinase inhibitor (TKI) to prolong their lives will typically keep going without a break until the disease progresses or toxicities such as severe fatigue and diarrhea become intolerable.

That might soon change with the publication of a unique study. Lasting 10 years, the phase 3 STAR trial involved 920 patients across 60 cancer centers. These patients had advanced kidney cancer and were taking either sunitinib (Sutent) or pazopanib (Votrient).

The results showed that taking an occasional respite from TKI therapy had little impact on the patient’s survival.

The study was published online in The Lancet Oncology.

The study was funded by the United Kingdom’s National Institute for Health and Care Research because drug companies never run studies on how to reduce the use of their drug, commented lead author Janet Brown, MD, of the University of Sheffield (England).

“We rely on the NIHR to do these important trials that … companies wouldn’t do,” she commented to this news organization.

Commenting on the rationale for STAR, coauthor Jenny Hewison, PhD, of Leeds (England) University School of Medicine, explained that patients often find it difficult to tolerate TKIs. “Although these patients are getting the best treatment that we can offer them, it’s very demanding. … It could make them feel tired, quite unwell. And there can be a range of other effects including sickness and diarrhea.”

As an example, 77% of patients in the pivotal trial of sunitinib in kidney cancer experienced grade 3 or 4 adverse events such as hypertension (13%), fatigue (15%), diarrhea (10%) and hand-foot syndrome (8%).

Both sunitinib and pazopanib carry label warnings of severe and fatal hepatotoxicity.

Also, in contrast to conventional chemotherapy, which is usually given in a finite number of courses, treatment with TKIs carries on indefinitely.

“It feels like you’re taking [TKIs] for the whole of the rest of your life,” said Dr. Brown.
 

Study details

The STAR trial, an open-label, noninferiority, randomized controlled study, is the first phase 3 study of treatment breaks in renal cell carcinoma. The participants had inoperable locoregional or metastatic clear cell renal cell carcinoma (ccRCC) and had received no systemic therapy for advanced disease.

They were randomly assigned before TKI treatment to a conventional continuation strategy or a drug-free interval approach. The treating physician decided whether a patient would take sunitinib or pazopanib.

All participants took their drugs for four cycles (6 weeks each cycle). At the 24-week point, those with a complete response, partial response, or stable disease began their randomized assignment.

Individuals who took a break continued until their disease progressed, at which point therapy was resumed. They could take further treatment breaks once their disease was back under control. The group on continuous treatment kept going until disease progression or intolerable toxicities. Median follow up was 58 months.

In both the per-protocol and intent-to-treat (ITT) populations, overall survival was 28 months for the people who received continuous treatment vs. 27 months for those who took a break. Statistical noninferiority was established in the ITT population but not in the per-protocol population.

The median length of all treatment breaks was 87 days. Many people took two or more breaks; one patient took nine breaks overall. The breaks were popular: only 3% of participants who were meant to stop therapy withdrew from the study in order to continue their treatment.

Said Dr. Hewison: “In the very early days of planning the study there were some doubts as to whether it would succeed because of potential unwillingness of people to stop treatment for a while.”

Dr. Brown agreed: “People did worry about that initially, but it actually seemed to be more the other way around. By that time – 6 months – people were relieved to be there. …We actually had some people from the other arm asking, could they also have a break?”

To understand better the benefits of treatment breaks to patients, Janine Bestall, PhD, a senior research fellow in applied health research at the University of Leeds, conducted a qualitative study in parallel with the main trial.

Summing up the patients’ experiences, Dr. Bestall said the drug-free periods “gave them more time.”

Dr. Bestall quoted one patient who said: “I know that things can happen and it grows back, but you’ve always got the buffer there knowing that you can go back and get help. But you actually lead a normal life and the advantage is, yeah, you can go on holiday, you can actually do more things in the garden, cleaning up, painting, whatever needs doing, you do it.”

Dr. Brown said, “I had a lady who, when she was on the trial, had four breaks in total, one when her daughter got married, and [she said] that was really nice for her to do all the shopping and all the normal things that you do, and not be on something that was making her tired and causing sore hands and diarrhea.” 

The drug-free interval strategy provided annual cost savings of 3,235 pounds sterling ($3,850) and a noninferior quality-adjusted life-year (QALY) benefit in both the ITT and per-protocol populations.

Serious adverse reactions occurred in 9% of patients in the treatment-break group versus 12% of the continuous-treatment group.

The authors of the study concluded, “Treatment breaks might be a feasible and cost-effective option with lifestyle benefits for patients during tyrosine kinase inhibitor therapy in patients with renal cell carcinoma.”
 

Changes in treatment strategies

The STAR trial started recruiting in January 2012.

Since that time, immunotherapy has taken over as first-line treatment for many patients with advanced ccRCC in both the United Kingdom and the United States.

However, TKIs still have a place. The NCCN Kidney Cancer 2022 Guidelines recommend both sunitinib and pazopanib as options for first-line therapy in advanced disease. The 2022 ASCO Metastatic ccRCC guidelines recommend either drug as first-line treatment in combination with an immune checkpoint inhibitor or in monotherapy if there are “coexisting medical problems.”

In the United States, intermittent sunitinib in metastatic RCC was tested in a small study in 2017 with little activity in the literature since then. The authors, led by Moshe Ornstein, MD, from the Cleveland Clinic, concluded at the time that sunitinib treatment breaks were feasible and “clinical efficacy does not seem to be compromised.” Dr. Ornstein was approached for comment on this latest U.K. study but declined.

Back in the United Kingdom, the results of STAR arrived just in time.

Said Dr. Brown: “This has … been really helpful in the U.K. in the pandemic when people said, can these patients have extra breaks? At the worst of the pandemic we were able to say, sure, if it’s stable, we can keep them off for 3-6 months. …And so that’s already had a powerful impact.”

Dr. Brown concluded, “I think what the trial does allow us to do, as individual oncologists, is to look at the patients that this might be suitable for – it won’t be everybody – and to say yes, it’s okay to personalize things.”

The study was funded by the U.K.’s National Institute for Health and Care Research. Dr. Bestall reported no relevant financial relationships. Dr. Hewison reported funding to her institution from the NIHR Health Technology Assessment. Dr. Brown reports having served as a consultant or adviser for Novartis, Ipsen, Amgen, Merck Sharp & Dohme, Bristol-Myers Squibb, and Bayer; honoraria from Novartis, Ipsen, Amgen, Merck Sharp & Dohme, Bristol-Myers Squibb, and Bayer; research funding paid to their institution from the National Institute for Health and Care Research; and travel expenses from Ipsen. Other coauthors reported numerous relationships with industry.

A version of this article first appeared on Medscape.com.

“Congratulations on the baby. You look great!” I enthusiastically proclaimed to my classmate. It was the start of the fall semester of my sophomore year of college.

At my small women’s college, the previous semester’s gossip had been about our classmate, S*. She had gone from being very thin to noticeably gaining a lot of weight in a few months. The rumors were that S was pregnant and gave birth over summer break. As a busy biology premed major, this was my first time hearing the news. So when I saw her standing in the hallway, back to her previous weight, I was excited for her.

In true extravert fashion, I commented on the baby and her new size. But no sooner had the words left my mouth than I regretted them.

The hall grew awkwardly silent as S’s face flushed and she asked, “Excuse me?!” Instantly I knew that the rumors weren’t true.

Thankfully, at that moment, the classroom opened and we walked in. Whew! After class, S asked if we could talk. She explained that she had a thyroid tumor and struggled to adjust to the treatments, which caused her weight fluctuations. She had never been pregnant.

My awkward statement had been the first time anyone on campus had directly mentioned her weight, though she suspected that people were talking about her. We became fast friends after this rocky beginning. Although we lost touch after college, S taught me an invaluable lesson about making assumptions about people’s weight: Ask before you assume.

Now, years later, as an internist and obesity specialist, this lesson continues to be reinforced daily.

In daily life, comments about weight can be perceived as rude. In the clinical setting, however, assumptions about weight are a form of weight bias. Weight bias can lead to weight stigma and even be dangerous to health care.

Let’s discuss the insidious influence of weight bias in health care through two commonly used phrases and then look at a few solutions to address weight bias in health care individually and systematically.
 

Common weight bias assumptions

“Great job, you lost weight!” In checking your patient’s vital signs, you notice that this patient with obesity has a significant weight change. You congratulate them upon entering the room. Unfortunately, their weight loss was a result of minimal eating after losing a loved one. This isn’t healthy weight loss. One of the adverse effects of weight bias is that it infers that weight loss is always a good thing, especially in people with larger bodies. This is a dangerous presumption. Let’s remember that the body favors fat storage, hence why “unintentional weight loss” is a recognized medical condition prompting evaluation. We have to be careful not to celebrate weight loss “at all costs,” such as fad diets that haven’t been shown to improve health outcomes.

Furthermore, patients who lose weight quickly (more than 4-8 lb/month) require closer follow-up and evaluation for secondary causes of weight loss. Patients may lose weight at a faster rate with the new antiobesity medications, but clinicians still should ensure that age-appropriate health maintenance screening is done and be vigilant for secondary causes of weight changes.

“Have you tried losing weight yet?” Three times. That’s how many times Chanté Burkett went to her doctor about her painful, enlarging firm stomach. She was advised to continue working on weight loss, which she did diligently. But Ms. Burkett’s abdomen kept growing and her concerns were dismissed. A visit to urgent care and a CT scan revealed that Ms. Burkett’s excess abdominal “fat” was a 13-lb mucinous cystadenoma. Sadly, cases like hers aren’t rare, isolated events. Weight bias can cause anchoring on one diagnosis, preventing consideration of other diagnostic possibilities. Even worse, anchoring will lead to the wrong intervention, such as prescribing weight loss for presumed increased adiposity instead of ordering the appropriate testing.

It’s also essential to recognize that, even if someone does have the disease of obesity, weight loss isn’t the solution to every medical concern. Even if weight loss is helpful, other, more pressing treatments may still be necessary. Telling a person with obesity who has an acute complaint to “just lose weight” is comparable to telling a patient with coronary artery disease who presents with an 80% vessel occlusion and chest pain to follow a low-fat diet. In both cases, you need to address the acute concern appropriately, then focus on the chronic treatment.
 

Ways to reduce clinical weight bias

How do you reduce clinical weight bias?

Ask, don’t assume. The information from the scale is simply data. Instead of judging it positively or negatively and creating a story, ask the patient. An unbiased way to approach the conversation is to say, “Great to see you. You seem [positive adjective of choice]. How have you been?” Wait until the vitals section to objectively discuss weight unless the patient offers the discussion earlier or their chief complaint lists a weight-related concern.

Order necessary tests to evaluate weight. Weight is the vital sign that people wear externally, so we feel that we can readily interpret it without any further assessment. However, resist the urge to interpret scale data without context. Keeping an open mind helps prevent anchoring and missing critical clues in the clinical history.

Address weight changes effectively. Sometimes there is an indication to prescribe weight loss as part of the treatment plan. However, remember that weight loss isn’t simply “calories in vs. calories out.” Obesity is a complex medical disease that requires a multimodal treatment approach. As clinicians, we have access to the most powerful tools for weight loss. Unfortunately, weight bias contributes to limited prescribing of metabolic medications (“antiobesity medications” or AOMs). In addition, systemic weight bias prevents insurance coverage of AOMs. The Treat and Reduce Obesity Act has been introduced into Congress to help improve life-transforming access to AOMs.

Acknowledge your bias. Our experiences make us all susceptible to bias. The Harvard Weight Implicit Association Test is free and a helpful way to assess your level of weight bias. I take it annually to ensure that I remain objective in my practice.

Addressing weight bias needs to extend beyond the individual level.

Systemically, health care needs to address the following:

Language. Use people-centered language. For example, “People aren’t obese. They have obesity.”

Accessibility. Health care settings must be comfortable and accessible for people of all sizes. Furthermore, improvements to access the services that comprehensive obesity care requires, such as AOMs, bariatric procedures and bariatric surgery, mental health care, nutrition, fitness specialists, health coaches, and more, are needed.

Education. Medical students and trainees have to learn the newest obesity science and know how to treat obesity effectively. Acknowledge and address biased tools. Recent data have shown that some of our screening tools, such as body mass index, have inherent bias. It’s time to focus on using improved diagnostic tools and personalized treatments.

We are at a pivotal time in our scientific understanding of body weight regulation and the disease of obesity. Clinical weight bias is primarily rooted in flawed science influenced by biased cultural norms and other forms of discrimination, such as racial and gender bias. We must move past assumptions to give our patients the optimal individualized care they need. So next time you observe a weight change, instead of commenting on their weight, say, “Great to see you! How have you been?”

S*: Initial has been changed to protect privacy.

Dr. Gonsahn-Bollie is an integrative obesity specialist focused on individualized solutions for emotional and biological overeating. Connect with her at www.embraceyouweightloss.com or on Instagram @embraceyoumd. Her bestselling book, “Embrace You: Your Guide to Transforming Weight Loss Misconceptions Into Lifelong Wellness”, was Healthline.com’s Best Overall Weight Loss Book of 2022 and one of Livestrong.com’s 8 Best Weight-Loss Books to Read in 2022. She has disclosed no relevant financial relationships. A version of this article originally appeared on Medscape.com.

“Congratulations on the baby. You look great!” I enthusiastically proclaimed to my classmate. It was the start of the fall semester of my sophomore year of college.

At my small women’s college, the previous semester’s gossip had been about our classmate, S*. She had gone from being very thin to noticeably gaining a lot of weight in a few months. The rumors were that S was pregnant and gave birth over summer break. As a busy biology premed major, this was my first time hearing the news. So when I saw her standing in the hallway, back to her previous weight, I was excited for her.

In true extravert fashion, I commented on the baby and her new size. But no sooner had the words left my mouth than I regretted them.

The hall grew awkwardly silent as S’s face flushed and she asked, “Excuse me?!” Instantly I knew that the rumors weren’t true.

Thankfully, at that moment, the classroom opened and we walked in. Whew! After class, S asked if we could talk. She explained that she had a thyroid tumor and struggled to adjust to the treatments, which caused her weight fluctuations. She had never been pregnant.

My awkward statement had been the first time anyone on campus had directly mentioned her weight, though she suspected that people were talking about her. We became fast friends after this rocky beginning. Although we lost touch after college, S taught me an invaluable lesson about making assumptions about people’s weight: Ask before you assume.

Now, years later, as an internist and obesity specialist, this lesson continues to be reinforced daily.

In daily life, comments about weight can be perceived as rude. In the clinical setting, however, assumptions about weight are a form of weight bias. Weight bias can lead to weight stigma and even be dangerous to health care.

Let’s discuss the insidious influence of weight bias in health care through two commonly used phrases and then look at a few solutions to address weight bias in health care individually and systematically.
 

Common weight bias assumptions

“Great job, you lost weight!” In checking your patient’s vital signs, you notice that this patient with obesity has a significant weight change. You congratulate them upon entering the room. Unfortunately, their weight loss was a result of minimal eating after losing a loved one. This isn’t healthy weight loss. One of the adverse effects of weight bias is that it infers that weight loss is always a good thing, especially in people with larger bodies. This is a dangerous presumption. Let’s remember that the body favors fat storage, hence why “unintentional weight loss” is a recognized medical condition prompting evaluation. We have to be careful not to celebrate weight loss “at all costs,” such as fad diets that haven’t been shown to improve health outcomes.

Furthermore, patients who lose weight quickly (more than 4-8 lb/month) require closer follow-up and evaluation for secondary causes of weight loss. Patients may lose weight at a faster rate with the new antiobesity medications, but clinicians still should ensure that age-appropriate health maintenance screening is done and be vigilant for secondary causes of weight changes.

“Have you tried losing weight yet?” Three times. That’s how many times Chanté Burkett went to her doctor about her painful, enlarging firm stomach. She was advised to continue working on weight loss, which she did diligently. But Ms. Burkett’s abdomen kept growing and her concerns were dismissed. A visit to urgent care and a CT scan revealed that Ms. Burkett’s excess abdominal “fat” was a 13-lb mucinous cystadenoma. Sadly, cases like hers aren’t rare, isolated events. Weight bias can cause anchoring on one diagnosis, preventing consideration of other diagnostic possibilities. Even worse, anchoring will lead to the wrong intervention, such as prescribing weight loss for presumed increased adiposity instead of ordering the appropriate testing.

It’s also essential to recognize that, even if someone does have the disease of obesity, weight loss isn’t the solution to every medical concern. Even if weight loss is helpful, other, more pressing treatments may still be necessary. Telling a person with obesity who has an acute complaint to “just lose weight” is comparable to telling a patient with coronary artery disease who presents with an 80% vessel occlusion and chest pain to follow a low-fat diet. In both cases, you need to address the acute concern appropriately, then focus on the chronic treatment.
 

Ways to reduce clinical weight bias

How do you reduce clinical weight bias?

Ask, don’t assume. The information from the scale is simply data. Instead of judging it positively or negatively and creating a story, ask the patient. An unbiased way to approach the conversation is to say, “Great to see you. You seem [positive adjective of choice]. How have you been?” Wait until the vitals section to objectively discuss weight unless the patient offers the discussion earlier or their chief complaint lists a weight-related concern.

Order necessary tests to evaluate weight. Weight is the vital sign that people wear externally, so we feel that we can readily interpret it without any further assessment. However, resist the urge to interpret scale data without context. Keeping an open mind helps prevent anchoring and missing critical clues in the clinical history.

Address weight changes effectively. Sometimes there is an indication to prescribe weight loss as part of the treatment plan. However, remember that weight loss isn’t simply “calories in vs. calories out.” Obesity is a complex medical disease that requires a multimodal treatment approach. As clinicians, we have access to the most powerful tools for weight loss. Unfortunately, weight bias contributes to limited prescribing of metabolic medications (“antiobesity medications” or AOMs). In addition, systemic weight bias prevents insurance coverage of AOMs. The Treat and Reduce Obesity Act has been introduced into Congress to help improve life-transforming access to AOMs.

Acknowledge your bias. Our experiences make us all susceptible to bias. The Harvard Weight Implicit Association Test is free and a helpful way to assess your level of weight bias. I take it annually to ensure that I remain objective in my practice.

Addressing weight bias needs to extend beyond the individual level.

Systemically, health care needs to address the following:

Language. Use people-centered language. For example, “People aren’t obese. They have obesity.”

Accessibility. Health care settings must be comfortable and accessible for people of all sizes. Furthermore, improvements to access the services that comprehensive obesity care requires, such as AOMs, bariatric procedures and bariatric surgery, mental health care, nutrition, fitness specialists, health coaches, and more, are needed.

Education. Medical students and trainees have to learn the newest obesity science and know how to treat obesity effectively. Acknowledge and address biased tools. Recent data have shown that some of our screening tools, such as body mass index, have inherent bias. It’s time to focus on using improved diagnostic tools and personalized treatments.

We are at a pivotal time in our scientific understanding of body weight regulation and the disease of obesity. Clinical weight bias is primarily rooted in flawed science influenced by biased cultural norms and other forms of discrimination, such as racial and gender bias. We must move past assumptions to give our patients the optimal individualized care they need. So next time you observe a weight change, instead of commenting on their weight, say, “Great to see you! How have you been?”

S*: Initial has been changed to protect privacy.

Dr. Gonsahn-Bollie is an integrative obesity specialist focused on individualized solutions for emotional and biological overeating. Connect with her at www.embraceyouweightloss.com or on Instagram @embraceyoumd. Her bestselling book, “Embrace You: Your Guide to Transforming Weight Loss Misconceptions Into Lifelong Wellness”, was Healthline.com’s Best Overall Weight Loss Book of 2022 and one of Livestrong.com’s 8 Best Weight-Loss Books to Read in 2022. She has disclosed no relevant financial relationships. A version of this article originally appeared on Medscape.com.

“Congratulations on the baby. You look great!” I enthusiastically proclaimed to my classmate. It was the start of the fall semester of my sophomore year of college.

At my small women’s college, the previous semester’s gossip had been about our classmate, S*. She had gone from being very thin to noticeably gaining a lot of weight in a few months. The rumors were that S was pregnant and gave birth over summer break. As a busy biology premed major, this was my first time hearing the news. So when I saw her standing in the hallway, back to her previous weight, I was excited for her.

In true extravert fashion, I commented on the baby and her new size. But no sooner had the words left my mouth than I regretted them.

The hall grew awkwardly silent as S’s face flushed and she asked, “Excuse me?!” Instantly I knew that the rumors weren’t true.

Thankfully, at that moment, the classroom opened and we walked in. Whew! After class, S asked if we could talk. She explained that she had a thyroid tumor and struggled to adjust to the treatments, which caused her weight fluctuations. She had never been pregnant.

My awkward statement had been the first time anyone on campus had directly mentioned her weight, though she suspected that people were talking about her. We became fast friends after this rocky beginning. Although we lost touch after college, S taught me an invaluable lesson about making assumptions about people’s weight: Ask before you assume.

Now, years later, as an internist and obesity specialist, this lesson continues to be reinforced daily.

In daily life, comments about weight can be perceived as rude. In the clinical setting, however, assumptions about weight are a form of weight bias. Weight bias can lead to weight stigma and even be dangerous to health care.

Let’s discuss the insidious influence of weight bias in health care through two commonly used phrases and then look at a few solutions to address weight bias in health care individually and systematically.
 

Common weight bias assumptions

“Great job, you lost weight!” In checking your patient’s vital signs, you notice that this patient with obesity has a significant weight change. You congratulate them upon entering the room. Unfortunately, their weight loss was a result of minimal eating after losing a loved one. This isn’t healthy weight loss. One of the adverse effects of weight bias is that it infers that weight loss is always a good thing, especially in people with larger bodies. This is a dangerous presumption. Let’s remember that the body favors fat storage, hence why “unintentional weight loss” is a recognized medical condition prompting evaluation. We have to be careful not to celebrate weight loss “at all costs,” such as fad diets that haven’t been shown to improve health outcomes.

Furthermore, patients who lose weight quickly (more than 4-8 lb/month) require closer follow-up and evaluation for secondary causes of weight loss. Patients may lose weight at a faster rate with the new antiobesity medications, but clinicians still should ensure that age-appropriate health maintenance screening is done and be vigilant for secondary causes of weight changes.

“Have you tried losing weight yet?” Three times. That’s how many times Chanté Burkett went to her doctor about her painful, enlarging firm stomach. She was advised to continue working on weight loss, which she did diligently. But Ms. Burkett’s abdomen kept growing and her concerns were dismissed. A visit to urgent care and a CT scan revealed that Ms. Burkett’s excess abdominal “fat” was a 13-lb mucinous cystadenoma. Sadly, cases like hers aren’t rare, isolated events. Weight bias can cause anchoring on one diagnosis, preventing consideration of other diagnostic possibilities. Even worse, anchoring will lead to the wrong intervention, such as prescribing weight loss for presumed increased adiposity instead of ordering the appropriate testing.

It’s also essential to recognize that, even if someone does have the disease of obesity, weight loss isn’t the solution to every medical concern. Even if weight loss is helpful, other, more pressing treatments may still be necessary. Telling a person with obesity who has an acute complaint to “just lose weight” is comparable to telling a patient with coronary artery disease who presents with an 80% vessel occlusion and chest pain to follow a low-fat diet. In both cases, you need to address the acute concern appropriately, then focus on the chronic treatment.
 

Ways to reduce clinical weight bias

How do you reduce clinical weight bias?

Ask, don’t assume. The information from the scale is simply data. Instead of judging it positively or negatively and creating a story, ask the patient. An unbiased way to approach the conversation is to say, “Great to see you. You seem [positive adjective of choice]. How have you been?” Wait until the vitals section to objectively discuss weight unless the patient offers the discussion earlier or their chief complaint lists a weight-related concern.

Order necessary tests to evaluate weight. Weight is the vital sign that people wear externally, so we feel that we can readily interpret it without any further assessment. However, resist the urge to interpret scale data without context. Keeping an open mind helps prevent anchoring and missing critical clues in the clinical history.

Address weight changes effectively. Sometimes there is an indication to prescribe weight loss as part of the treatment plan. However, remember that weight loss isn’t simply “calories in vs. calories out.” Obesity is a complex medical disease that requires a multimodal treatment approach. As clinicians, we have access to the most powerful tools for weight loss. Unfortunately, weight bias contributes to limited prescribing of metabolic medications (“antiobesity medications” or AOMs). In addition, systemic weight bias prevents insurance coverage of AOMs. The Treat and Reduce Obesity Act has been introduced into Congress to help improve life-transforming access to AOMs.

Acknowledge your bias. Our experiences make us all susceptible to bias. The Harvard Weight Implicit Association Test is free and a helpful way to assess your level of weight bias. I take it annually to ensure that I remain objective in my practice.

Addressing weight bias needs to extend beyond the individual level.

Systemically, health care needs to address the following:

Language. Use people-centered language. For example, “People aren’t obese. They have obesity.”

Accessibility. Health care settings must be comfortable and accessible for people of all sizes. Furthermore, improvements to access the services that comprehensive obesity care requires, such as AOMs, bariatric procedures and bariatric surgery, mental health care, nutrition, fitness specialists, health coaches, and more, are needed.

Education. Medical students and trainees have to learn the newest obesity science and know how to treat obesity effectively. Acknowledge and address biased tools. Recent data have shown that some of our screening tools, such as body mass index, have inherent bias. It’s time to focus on using improved diagnostic tools and personalized treatments.

We are at a pivotal time in our scientific understanding of body weight regulation and the disease of obesity. Clinical weight bias is primarily rooted in flawed science influenced by biased cultural norms and other forms of discrimination, such as racial and gender bias. We must move past assumptions to give our patients the optimal individualized care they need. So next time you observe a weight change, instead of commenting on their weight, say, “Great to see you! How have you been?”

S*: Initial has been changed to protect privacy.

Dr. Gonsahn-Bollie is an integrative obesity specialist focused on individualized solutions for emotional and biological overeating. Connect with her at www.embraceyouweightloss.com or on Instagram @embraceyoumd. Her bestselling book, “Embrace You: Your Guide to Transforming Weight Loss Misconceptions Into Lifelong Wellness”, was Healthline.com’s Best Overall Weight Loss Book of 2022 and one of Livestrong.com’s 8 Best Weight-Loss Books to Read in 2022. She has disclosed no relevant financial relationships. A version of this article originally appeared on Medscape.com.

A new consensus statement from the American Thyroid Association (ATA) and European Thyroid Association (ETA) offers recommendations for endocrinologists on the management of thyroid eye disease (TED), addressing key questions, including about important novel treatments, that transcend international borders.

The consensus statement is important as new therapies transform the treatment of TED that, notably, have even played a key role in simplifying the name of the disease, which has had numerous other, often confusing names over the years, ranging from thyrotropic exophthalmos to Graves ophthalmopathy, Terry F. Davies, MD, of the thyroid research unit, department of medicine, Icahn School of Medicine at Mount Sinai, New York, said in an editorial published along with the statement in Thyroid.

“The emergence of novel therapies has changed the entire discussion concerning TED and not just its name,” he wrote. “These are early and exciting days in the treatment of TED, which is likely to be a much more manageable disease in the years to come.”

However, Dr. Davies stressed to this news organization that there are still a lot of unanswered questions, particularly when it comes to newer therapies. For example, teprotumumab can cost up to $300,000 for one course of treatment for one patient, the consensus statement notes.
 

When to consult an ophthalmologist

Graves disease is the most common cause of hyperthyroidism and affects > 1% of the U.S. population. TED is the most common complication of Graves disease that occurs outside of the thyroid gland. TED causes a variety of eye-related signs and symptoms, which can be disfiguring and negatively affect quality of life, and in rare cases, threaten vision.

Key issues covered in the consensus statement include timely diagnosis of TED, assessment of disease activity and severity, initial care and referral for specialty care, and treatment recommendations for moderate to severe TED.

In terms of disease assessment, for instance, the statement authors noted the important distinction in TED “between the two interdependent components of inflammatory activity, manifested by pain, redness, and edema, and disease severity, including proptosis, lid malposition, exposure keratopathy, impaired ocular motility, and optic neuropathy.”

“The presence of multiple features of inflammation usually signifies active disease,” they explained.

For initial care, input from endocrinologists as well as ophthalmologists with experience in TED management is urged, and “an ophthalmologist should be consulted when the diagnosis of TED is uncertain, in cases of moderate to severe TED, and when surgical intervention needs to be considered.”

Furthermore, “urgent referral is required when sight-threatening TED is suspected or confirmed,” the authors noted.
 

Debate over some treatment recommendations

In terms of therapy, for initial care, “a single course of selenium selenite 100 mcg twice daily for 6 months may be considered for patients with mild, active TED, particularly in regions of selenium insufficiency,” the consensus statement recommends.

Intravenous glucocorticoid (IVGC) therapy is meanwhile recommended as a preferred treatment for active moderate to severe TED specifically when disease activity is the prominent feature in the absence of significant proptosis or diplopia.

For patients with active moderate to severe TED who are glucocorticoid-resistant, the authors noted that rituximab and tocilizumab may be considered and that teprotumumab has not been evaluated in this setting.

Teprotumumab, if available, is a preferred therapy for patients with active moderate to severe TED who have significant proptosis.

There is, however, some debate over the issue, editorial author Dr. Davies told this news organization.

“It is still argued over how bad the eyes need to be before recommending this new treatment,” he said. “I think the answer is in the proptosis – the amount of bulging present rather than just inflammation,” Dr. Davies said.

“There is also a real clinical problem in that we have no specific biomarker for the disease, however, high levels of TSH receptor antibody are often a good indicator of eye disease.”

The authors cautioned, however, that clinical trials with medical therapies have been limited by inclusion criteria and other factors, and biologics have meanwhile increased the cost of treatment “many-fold” compared with conventional agents.

Therefore, “clinicians should balance the demonstrated efficacy of recently introduced therapies [such as teprotumumab] against the absence of experience on sustained long-term efficacy, safety, and cost-effectiveness,” they noted.

Importantly, “one course consisting of eight infusions of teprotumumab has a retail cost of approximately $300,000, depending on patient weight, [which is] approximately 2,000 times that of IVGC,” they noted.

“The process involved in selecting therapy with these drugs and other drugs includes a consideration of both short- and long-term efficacy, adverse effects that are both known and unknown, the likelihood of disease aggravation or relapse after a previously beneficial response, and the relative cost and availability,” said Henry B. Burch, MD, who is at the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, in Bethesda, Md., and is on the consensus statement task force.

To help with those decisions, the consensus statement provides comprehensive tables that compare drug efficacy for key outcomes including inflammation, proptosis, diplopia, and quality of life, and importantly, comparisons also of drug costs and potential adverse effects for each of the current TED therapies.
 

Consensus statement not a guideline

The groups noted that the consensus statement is not meant to be a clinical practice guideline and was not written to “establish a standard of care, replace sound clinical judgment, or capture all nuances likely to be present in any particular patient,” and “specific outcomes are not guaranteed.”

What the statement is intended for is to “provide a concise and timely appraisal of a rapidly changing therapeutic arena” for practicing endocrinologists, they explained.

Overall, the authors recommend an individualized management approach, based on factors ranging from disease severity, duration, its impact on daily living, patient age, comorbidities, and importantly, the costs of therapies.

Ultimately, patient satisfaction is essential in TED management, Dr. Burch added.

“Consideration of the impact of TED on patient’s satisfaction with their appearance and visual functioning is a key component in management decisions concerning TED.”A version of this article first appeared on Medscape.com.

A new consensus statement from the American Thyroid Association (ATA) and European Thyroid Association (ETA) offers recommendations for endocrinologists on the management of thyroid eye disease (TED), addressing key questions, including about important novel treatments, that transcend international borders.

The consensus statement is important as new therapies transform the treatment of TED that, notably, have even played a key role in simplifying the name of the disease, which has had numerous other, often confusing names over the years, ranging from thyrotropic exophthalmos to Graves ophthalmopathy, Terry F. Davies, MD, of the thyroid research unit, department of medicine, Icahn School of Medicine at Mount Sinai, New York, said in an editorial published along with the statement in Thyroid.

“The emergence of novel therapies has changed the entire discussion concerning TED and not just its name,” he wrote. “These are early and exciting days in the treatment of TED, which is likely to be a much more manageable disease in the years to come.”

However, Dr. Davies stressed to this news organization that there are still a lot of unanswered questions, particularly when it comes to newer therapies. For example, teprotumumab can cost up to $300,000 for one course of treatment for one patient, the consensus statement notes.
 

When to consult an ophthalmologist

Graves disease is the most common cause of hyperthyroidism and affects > 1% of the U.S. population. TED is the most common complication of Graves disease that occurs outside of the thyroid gland. TED causes a variety of eye-related signs and symptoms, which can be disfiguring and negatively affect quality of life, and in rare cases, threaten vision.

Key issues covered in the consensus statement include timely diagnosis of TED, assessment of disease activity and severity, initial care and referral for specialty care, and treatment recommendations for moderate to severe TED.

In terms of disease assessment, for instance, the statement authors noted the important distinction in TED “between the two interdependent components of inflammatory activity, manifested by pain, redness, and edema, and disease severity, including proptosis, lid malposition, exposure keratopathy, impaired ocular motility, and optic neuropathy.”

“The presence of multiple features of inflammation usually signifies active disease,” they explained.

For initial care, input from endocrinologists as well as ophthalmologists with experience in TED management is urged, and “an ophthalmologist should be consulted when the diagnosis of TED is uncertain, in cases of moderate to severe TED, and when surgical intervention needs to be considered.”

Furthermore, “urgent referral is required when sight-threatening TED is suspected or confirmed,” the authors noted.
 

Debate over some treatment recommendations

In terms of therapy, for initial care, “a single course of selenium selenite 100 mcg twice daily for 6 months may be considered for patients with mild, active TED, particularly in regions of selenium insufficiency,” the consensus statement recommends.

Intravenous glucocorticoid (IVGC) therapy is meanwhile recommended as a preferred treatment for active moderate to severe TED specifically when disease activity is the prominent feature in the absence of significant proptosis or diplopia.

For patients with active moderate to severe TED who are glucocorticoid-resistant, the authors noted that rituximab and tocilizumab may be considered and that teprotumumab has not been evaluated in this setting.

Teprotumumab, if available, is a preferred therapy for patients with active moderate to severe TED who have significant proptosis.

There is, however, some debate over the issue, editorial author Dr. Davies told this news organization.

“It is still argued over how bad the eyes need to be before recommending this new treatment,” he said. “I think the answer is in the proptosis – the amount of bulging present rather than just inflammation,” Dr. Davies said.

“There is also a real clinical problem in that we have no specific biomarker for the disease, however, high levels of TSH receptor antibody are often a good indicator of eye disease.”

The authors cautioned, however, that clinical trials with medical therapies have been limited by inclusion criteria and other factors, and biologics have meanwhile increased the cost of treatment “many-fold” compared with conventional agents.

Therefore, “clinicians should balance the demonstrated efficacy of recently introduced therapies [such as teprotumumab] against the absence of experience on sustained long-term efficacy, safety, and cost-effectiveness,” they noted.

Importantly, “one course consisting of eight infusions of teprotumumab has a retail cost of approximately $300,000, depending on patient weight, [which is] approximately 2,000 times that of IVGC,” they noted.

“The process involved in selecting therapy with these drugs and other drugs includes a consideration of both short- and long-term efficacy, adverse effects that are both known and unknown, the likelihood of disease aggravation or relapse after a previously beneficial response, and the relative cost and availability,” said Henry B. Burch, MD, who is at the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, in Bethesda, Md., and is on the consensus statement task force.

To help with those decisions, the consensus statement provides comprehensive tables that compare drug efficacy for key outcomes including inflammation, proptosis, diplopia, and quality of life, and importantly, comparisons also of drug costs and potential adverse effects for each of the current TED therapies.
 

Consensus statement not a guideline

The groups noted that the consensus statement is not meant to be a clinical practice guideline and was not written to “establish a standard of care, replace sound clinical judgment, or capture all nuances likely to be present in any particular patient,” and “specific outcomes are not guaranteed.”

What the statement is intended for is to “provide a concise and timely appraisal of a rapidly changing therapeutic arena” for practicing endocrinologists, they explained.

Overall, the authors recommend an individualized management approach, based on factors ranging from disease severity, duration, its impact on daily living, patient age, comorbidities, and importantly, the costs of therapies.

Ultimately, patient satisfaction is essential in TED management, Dr. Burch added.

“Consideration of the impact of TED on patient’s satisfaction with their appearance and visual functioning is a key component in management decisions concerning TED.”A version of this article first appeared on Medscape.com.

A new consensus statement from the American Thyroid Association (ATA) and European Thyroid Association (ETA) offers recommendations for endocrinologists on the management of thyroid eye disease (TED), addressing key questions, including about important novel treatments, that transcend international borders.

The consensus statement is important as new therapies transform the treatment of TED that, notably, have even played a key role in simplifying the name of the disease, which has had numerous other, often confusing names over the years, ranging from thyrotropic exophthalmos to Graves ophthalmopathy, Terry F. Davies, MD, of the thyroid research unit, department of medicine, Icahn School of Medicine at Mount Sinai, New York, said in an editorial published along with the statement in Thyroid.

“The emergence of novel therapies has changed the entire discussion concerning TED and not just its name,” he wrote. “These are early and exciting days in the treatment of TED, which is likely to be a much more manageable disease in the years to come.”

However, Dr. Davies stressed to this news organization that there are still a lot of unanswered questions, particularly when it comes to newer therapies. For example, teprotumumab can cost up to $300,000 for one course of treatment for one patient, the consensus statement notes.
 

When to consult an ophthalmologist

Graves disease is the most common cause of hyperthyroidism and affects > 1% of the U.S. population. TED is the most common complication of Graves disease that occurs outside of the thyroid gland. TED causes a variety of eye-related signs and symptoms, which can be disfiguring and negatively affect quality of life, and in rare cases, threaten vision.

Key issues covered in the consensus statement include timely diagnosis of TED, assessment of disease activity and severity, initial care and referral for specialty care, and treatment recommendations for moderate to severe TED.

In terms of disease assessment, for instance, the statement authors noted the important distinction in TED “between the two interdependent components of inflammatory activity, manifested by pain, redness, and edema, and disease severity, including proptosis, lid malposition, exposure keratopathy, impaired ocular motility, and optic neuropathy.”

“The presence of multiple features of inflammation usually signifies active disease,” they explained.

For initial care, input from endocrinologists as well as ophthalmologists with experience in TED management is urged, and “an ophthalmologist should be consulted when the diagnosis of TED is uncertain, in cases of moderate to severe TED, and when surgical intervention needs to be considered.”

Furthermore, “urgent referral is required when sight-threatening TED is suspected or confirmed,” the authors noted.
 

Debate over some treatment recommendations

In terms of therapy, for initial care, “a single course of selenium selenite 100 mcg twice daily for 6 months may be considered for patients with mild, active TED, particularly in regions of selenium insufficiency,” the consensus statement recommends.

Intravenous glucocorticoid (IVGC) therapy is meanwhile recommended as a preferred treatment for active moderate to severe TED specifically when disease activity is the prominent feature in the absence of significant proptosis or diplopia.

For patients with active moderate to severe TED who are glucocorticoid-resistant, the authors noted that rituximab and tocilizumab may be considered and that teprotumumab has not been evaluated in this setting.

Teprotumumab, if available, is a preferred therapy for patients with active moderate to severe TED who have significant proptosis.

There is, however, some debate over the issue, editorial author Dr. Davies told this news organization.

“It is still argued over how bad the eyes need to be before recommending this new treatment,” he said. “I think the answer is in the proptosis – the amount of bulging present rather than just inflammation,” Dr. Davies said.

“There is also a real clinical problem in that we have no specific biomarker for the disease, however, high levels of TSH receptor antibody are often a good indicator of eye disease.”

The authors cautioned, however, that clinical trials with medical therapies have been limited by inclusion criteria and other factors, and biologics have meanwhile increased the cost of treatment “many-fold” compared with conventional agents.

Therefore, “clinicians should balance the demonstrated efficacy of recently introduced therapies [such as teprotumumab] against the absence of experience on sustained long-term efficacy, safety, and cost-effectiveness,” they noted.

Importantly, “one course consisting of eight infusions of teprotumumab has a retail cost of approximately $300,000, depending on patient weight, [which is] approximately 2,000 times that of IVGC,” they noted.

“The process involved in selecting therapy with these drugs and other drugs includes a consideration of both short- and long-term efficacy, adverse effects that are both known and unknown, the likelihood of disease aggravation or relapse after a previously beneficial response, and the relative cost and availability,” said Henry B. Burch, MD, who is at the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, in Bethesda, Md., and is on the consensus statement task force.

To help with those decisions, the consensus statement provides comprehensive tables that compare drug efficacy for key outcomes including inflammation, proptosis, diplopia, and quality of life, and importantly, comparisons also of drug costs and potential adverse effects for each of the current TED therapies.
 

Consensus statement not a guideline

The groups noted that the consensus statement is not meant to be a clinical practice guideline and was not written to “establish a standard of care, replace sound clinical judgment, or capture all nuances likely to be present in any particular patient,” and “specific outcomes are not guaranteed.”

What the statement is intended for is to “provide a concise and timely appraisal of a rapidly changing therapeutic arena” for practicing endocrinologists, they explained.

Overall, the authors recommend an individualized management approach, based on factors ranging from disease severity, duration, its impact on daily living, patient age, comorbidities, and importantly, the costs of therapies.

Ultimately, patient satisfaction is essential in TED management, Dr. Burch added.

“Consideration of the impact of TED on patient’s satisfaction with their appearance and visual functioning is a key component in management decisions concerning TED.”A version of this article first appeared on Medscape.com.

Congenital hypothyroidism is one of the most common preventable causes of intellectual disabilities worldwide, but newborn screening has not been established in all countries.

Additionally, screening alone is not enough to prevent adverse outcomes in children, write authors of a technical report published online in Pediatrics (Jan. 2023;151[1]:e2022060420).

Susan R. Rose, MD, with the division of endocrinology at Cincinnati Children’s Hospital Medical Center in Ohio, led the work group that updated guidance for screening and management of congenital hypothyroidism. The group worked in conjunction with the American Academy of Pediatrics Section on Endocrinology, the AAP Council on Genetics, the Pediatric Endocrine Society, and the American Thyroid Association.

In addition to screening, timely diagnosis, effective treatment, and follow-up are important.

Tests don’t always tell the full story with congenital hypothyroidism.

“Physicians need to consider hypothyroidism in the face of clinical symptoms, even if newborn screening thyroid test results are normal,” the authors write.

They add that newborn screening for congenital hypothyroidism followed by prompt levothyroxine therapy can prevent severe intellectual disability, psychomotor dysfunction, and impaired growth.

Incidence of congenital hypothyroidism ranges from approximately 1 in 2,000 to 1 in 4,000 newborn infants in countries that have newborn screening data, according to the report.

Following are highlights of the guidance:
 

Clinical signs

Symptoms and signs include large posterior fontanelle, lethargy, large tongue, prolonged jaundice, umbilical hernia, constipation, and/or hypothermia. With these signs, measuring serum thyroid-stimulating hormone (TSH) and free thyroxine (FT4) is indicated, regardless of screening results.

Newborn screening in first days

Population screening is cost effective when performed by state or other public health laboratories working with hospitals or birthing centers in their area, the authors write.

Multidisciplinary teams are best able to conduct comprehensive care when cases are detected.

The screening includes a dried blood spot from a heel stick on an approved paper card using appropriate collection methods. The blood spots are then sent to the laboratory. The preferred age for collecting the specimen is 48-72 hours of age.

That timing may be difficult, the authors note, as 90% of infants in the United States and Europe are discharged before 48 hours, but taking the specimen before discharge is important to avoid missing the early diagnosis.

“However, collection of the NBS [newborn screening] specimen before 48 hours of age, and particularly before 24 hours of age, necessitates the use of age-specific TSH reference ranges or repeat screening, particularly to avoid false-positive results,” the authors note.

If a newborn infant is transferred to another hospital, communication about the screening is critical.
 

Testing strategies

Three test strategies are used for screening: a primary TSH – reflex T4 measurement; primary T4 – reflex TSH measurement; and combined T4 and TSH measurement.

“All three test strategies detect moderate to severe primary congenital hypothyroidism with similar accuracy,” the authors write.

Most newborn screening programs in the United States and worldwide use a primary TSH test strategy.
 

Multiple births, same-sex twins

The incidence of congenital hypothyroidism appears to be higher with multiple births (1:876 in twin births and 1:575 in higher-order multiple births in one study). Another study showed the incidence of congenital hypothyroidism in same-sex twins to be 1 in 593, compared with 1 in 3,060 in different-sex twins.

“Most twin pairs (> 95%) are discordant for congenital hypothyroidism,” the authors write. “However, in monozygotic twins who share placental circulation, blood from a euthyroid fetal twin with normal thyroid hormone levels may cross to a fetal twin with congenital hypothyroidism, temporarily correcting the hypothyroidism and preventing its detection by newborn screening at 24-72 hours of life. Thus, all monozygotic twins, or same-sex twins for whom zygosity is unknown, should undergo repeat newborn screening around 2 weeks of age.”
 

Down syndrome

Congenital hypothyroidism incidence in infants with trisomy 21 (Down syndrome) is high and ranges from 1% to 12% in various reports. The infants tend to have lower T4 concentrations and higher TSH concentrations than do infants without trisomy. Down syndrome is associated with other comorbidities, including congenital heart disease, “that may further increase the risk of abnormal newborn screening results because of acute illness or excess iodine exposure,” the authors write.

Even infants with Down syndrome who don’t have congenital hypothyroidism are still at significant risk of developing primary hypothyroidism in their first year (approximately 7% in one prospective study).

“Therefore, in these infants, a second newborn screening should be performed at 2-4 weeks of life and serum TSH should be measured at 6 and 12 months of life,” the authors say.
 

Communication with primary care provider

Direct communication between the newborn screening program and the primary care physician is important for appropriate follow-up. Consulting a pediatric endocrinologist can speed diagnosis and management.

Serum confirmation after abnormal screening

The next step if any child’s screening results suggest congenital hypothyroidism is to perform a physical exam (for goiter, lingual thyroid gland, and/or physical signs of hypothyroidism) and to measure the concentrations of TSH and FT4 (or total T4) in the blood.

For confirmation of abnormal screening results, the authors say, measurement of FT4 is preferred over measuring total T4.
 

Interpreting serum confirmation

Some interpretations are clear cut: “Elevated TSH with low FT4 on the confirmatory serum testing indicates overt primary hypothyroidism,” the authors write.

But there are various other outcomes with more controversy.

Elevated TSH and normal FT4, for instance, is known as hyperthyrotropinemia or subclinical hypothyroidism and represents a mild primary thyroid abnormality.

In this scenario, there is controversy regarding the need for L-T4 therapy because there are few and conflicting studies regarding how mild congenital hypothyroidism affects cognitive development.

“[E]xpert opinion suggests that persistent TSH elevation > 10 mIU/L is an indication to initiate L-T4 treatment,” the authors write.

Normal TSH and low T4 is seen in patients with central hypothyroidism, prematurity, low birth weight, acute illness, or thyroxine-binding globulin deficiency.

“The concept that central hypothyroidism is usually mild appears unfounded: A study from the Netherlands found that mean pretreatment serum FT4 levels in central congenital hypothyroidism were similar to those of patients with moderately severe primary congenital hypothyroidism. Therefore, L-T4 treatment of central congenital hypothyroidism is indicated.”
 

Imaging

Routine thyroid imaging is controversial for patients with congenital hypothyroidism. In most cases, it won’t alter clinical management before age 3 years.

Thyroid ultrasonography can find thyroid tissue without radiation exposure and can be performed at any time after a congenital hypothyroidism diagnosis.

“Ultrasonography has lower sensitivity than scintigraphy for detecting ectopic thyroid tissue, the most common cause of congenital hypothyroidism, although its sensitivity is improved by the use of color Doppler,” the authors write.

Infants with normal thyroid imaging at birth may have transient hypothyroidism. In these patients, reevaluation of thyroid hormone therapy after 3 years of age to assess for persistent hypothyroidism may be beneficial.
 

Treatment

Congenital hypothyroidism is treated with enteral L-T4 at a starting dose of 10-15 mcg/kg per day, given once a day.

L-T4 tablets are the treatment of choice and generic tablets are fine for most children, the authors write, adding that a brand name formulation may be more consistent and better for children with severe congenital hypothyroidism.

An oral solution of L-T4 has been approved by the U.S. Food and Drug Administration for use in children.

“[H]owever, limited experience with its use showed that dosing may not be equivalent to dosing with tablet formulations,” the guidance states.

The goal of initial L-T4 therapy is to normalize serum FT4 and TSH levels as quickly as possible. The outlook is poorer for infants whose hypothyroidism is detected later in life, who receive inadequate doses of L-T4, or who have more severe forms.

Age-specific TSH reference ranges vary by laboratory, but recent studies indicate the top limit of normal TSH in infants in the first 3 months of life is 4.1-4.8 mIU/L.

“[T]herefore, TSH values above 5 mIU/L generally are abnormal if observed after 3 months of age. Whether overtreatment (defined by elevated serum FT4) is harmful remains unclear and evidence is conflicting,” the authors write.
 

Monitoring

In the near-term follow-up, close laboratory monitoring is necessary during L-T4 treatment to maintain blood TSH and FT4 in the target ranges. Studies support measuring those levels every 1-2 months in the first 6 months of life for children with congenital hypothyroidism, every 2-3 months in the second 6 months, and then every 3-4 months between 1 and 3 years of age.

In long-term follow-up, attention to behavioral and cognitive development is important, because children with congenital hypothyroidism may be at higher risk for neurocognitive and socioemotional dysfunction compared with their peers, even with adequate treatment of congenital hypothyroidism. Hearing deficits are reported in about 10% of children with congenital hypothyroidism.
 

Developmental outcomes

When L-T4 therapy is maintained and TSH and FT4 are within target range, growth and adult height are generally normal in children with congenital hypothyroidism.

In contrast, the neurodevelopmental prognosis is less certain when treatment starts late.

“[I]nfants with severe congenital hypothyroidism and intrauterine hypothyroidism (as indicated by retarded skeletal maturation at birth) may have low-to-normal intelligence,” the report states. “Similarly, although more than 80% of infants given L-T4 replacement therapy before 3 months of age have an intelligence [quotient] greater than 85, 77% of these infants show signs of cognitive impairment in arithmetic ability, speech, or fine motor coordination later in life.”

If a child is properly treated for congenital hypothyroidism but growth or development is abnormal, testing for other illness, hearing deficit, or other hormone deficiency is needed, the report states.

The authors report no relevant financial relationships.

Congenital hypothyroidism is one of the most common preventable causes of intellectual disabilities worldwide, but newborn screening has not been established in all countries.

Additionally, screening alone is not enough to prevent adverse outcomes in children, write authors of a technical report published online in Pediatrics (Jan. 2023;151[1]:e2022060420).

Susan R. Rose, MD, with the division of endocrinology at Cincinnati Children’s Hospital Medical Center in Ohio, led the work group that updated guidance for screening and management of congenital hypothyroidism. The group worked in conjunction with the American Academy of Pediatrics Section on Endocrinology, the AAP Council on Genetics, the Pediatric Endocrine Society, and the American Thyroid Association.

In addition to screening, timely diagnosis, effective treatment, and follow-up are important.

Tests don’t always tell the full story with congenital hypothyroidism.

“Physicians need to consider hypothyroidism in the face of clinical symptoms, even if newborn screening thyroid test results are normal,” the authors write.

They add that newborn screening for congenital hypothyroidism followed by prompt levothyroxine therapy can prevent severe intellectual disability, psychomotor dysfunction, and impaired growth.

Incidence of congenital hypothyroidism ranges from approximately 1 in 2,000 to 1 in 4,000 newborn infants in countries that have newborn screening data, according to the report.

Following are highlights of the guidance:
 

Clinical signs

Symptoms and signs include large posterior fontanelle, lethargy, large tongue, prolonged jaundice, umbilical hernia, constipation, and/or hypothermia. With these signs, measuring serum thyroid-stimulating hormone (TSH) and free thyroxine (FT4) is indicated, regardless of screening results.

Newborn screening in first days

Population screening is cost effective when performed by state or other public health laboratories working with hospitals or birthing centers in their area, the authors write.

Multidisciplinary teams are best able to conduct comprehensive care when cases are detected.

The screening includes a dried blood spot from a heel stick on an approved paper card using appropriate collection methods. The blood spots are then sent to the laboratory. The preferred age for collecting the specimen is 48-72 hours of age.

That timing may be difficult, the authors note, as 90% of infants in the United States and Europe are discharged before 48 hours, but taking the specimen before discharge is important to avoid missing the early diagnosis.

“However, collection of the NBS [newborn screening] specimen before 48 hours of age, and particularly before 24 hours of age, necessitates the use of age-specific TSH reference ranges or repeat screening, particularly to avoid false-positive results,” the authors note.

If a newborn infant is transferred to another hospital, communication about the screening is critical.
 

Testing strategies

Three test strategies are used for screening: a primary TSH – reflex T4 measurement; primary T4 – reflex TSH measurement; and combined T4 and TSH measurement.

“All three test strategies detect moderate to severe primary congenital hypothyroidism with similar accuracy,” the authors write.

Most newborn screening programs in the United States and worldwide use a primary TSH test strategy.
 

Multiple births, same-sex twins

The incidence of congenital hypothyroidism appears to be higher with multiple births (1:876 in twin births and 1:575 in higher-order multiple births in one study). Another study showed the incidence of congenital hypothyroidism in same-sex twins to be 1 in 593, compared with 1 in 3,060 in different-sex twins.

“Most twin pairs (> 95%) are discordant for congenital hypothyroidism,” the authors write. “However, in monozygotic twins who share placental circulation, blood from a euthyroid fetal twin with normal thyroid hormone levels may cross to a fetal twin with congenital hypothyroidism, temporarily correcting the hypothyroidism and preventing its detection by newborn screening at 24-72 hours of life. Thus, all monozygotic twins, or same-sex twins for whom zygosity is unknown, should undergo repeat newborn screening around 2 weeks of age.”
 

Down syndrome

Congenital hypothyroidism incidence in infants with trisomy 21 (Down syndrome) is high and ranges from 1% to 12% in various reports. The infants tend to have lower T4 concentrations and higher TSH concentrations than do infants without trisomy. Down syndrome is associated with other comorbidities, including congenital heart disease, “that may further increase the risk of abnormal newborn screening results because of acute illness or excess iodine exposure,” the authors write.

Even infants with Down syndrome who don’t have congenital hypothyroidism are still at significant risk of developing primary hypothyroidism in their first year (approximately 7% in one prospective study).

“Therefore, in these infants, a second newborn screening should be performed at 2-4 weeks of life and serum TSH should be measured at 6 and 12 months of life,” the authors say.
 

Communication with primary care provider

Direct communication between the newborn screening program and the primary care physician is important for appropriate follow-up. Consulting a pediatric endocrinologist can speed diagnosis and management.

Serum confirmation after abnormal screening

The next step if any child’s screening results suggest congenital hypothyroidism is to perform a physical exam (for goiter, lingual thyroid gland, and/or physical signs of hypothyroidism) and to measure the concentrations of TSH and FT4 (or total T4) in the blood.

For confirmation of abnormal screening results, the authors say, measurement of FT4 is preferred over measuring total T4.
 

Interpreting serum confirmation

Some interpretations are clear cut: “Elevated TSH with low FT4 on the confirmatory serum testing indicates overt primary hypothyroidism,” the authors write.

But there are various other outcomes with more controversy.

Elevated TSH and normal FT4, for instance, is known as hyperthyrotropinemia or subclinical hypothyroidism and represents a mild primary thyroid abnormality.

In this scenario, there is controversy regarding the need for L-T4 therapy because there are few and conflicting studies regarding how mild congenital hypothyroidism affects cognitive development.

“[E]xpert opinion suggests that persistent TSH elevation > 10 mIU/L is an indication to initiate L-T4 treatment,” the authors write.

Normal TSH and low T4 is seen in patients with central hypothyroidism, prematurity, low birth weight, acute illness, or thyroxine-binding globulin deficiency.

“The concept that central hypothyroidism is usually mild appears unfounded: A study from the Netherlands found that mean pretreatment serum FT4 levels in central congenital hypothyroidism were similar to those of patients with moderately severe primary congenital hypothyroidism. Therefore, L-T4 treatment of central congenital hypothyroidism is indicated.”
 

Imaging

Routine thyroid imaging is controversial for patients with congenital hypothyroidism. In most cases, it won’t alter clinical management before age 3 years.

Thyroid ultrasonography can find thyroid tissue without radiation exposure and can be performed at any time after a congenital hypothyroidism diagnosis.

“Ultrasonography has lower sensitivity than scintigraphy for detecting ectopic thyroid tissue, the most common cause of congenital hypothyroidism, although its sensitivity is improved by the use of color Doppler,” the authors write.

Infants with normal thyroid imaging at birth may have transient hypothyroidism. In these patients, reevaluation of thyroid hormone therapy after 3 years of age to assess for persistent hypothyroidism may be beneficial.
 

Treatment

Congenital hypothyroidism is treated with enteral L-T4 at a starting dose of 10-15 mcg/kg per day, given once a day.

L-T4 tablets are the treatment of choice and generic tablets are fine for most children, the authors write, adding that a brand name formulation may be more consistent and better for children with severe congenital hypothyroidism.

An oral solution of L-T4 has been approved by the U.S. Food and Drug Administration for use in children.

“[H]owever, limited experience with its use showed that dosing may not be equivalent to dosing with tablet formulations,” the guidance states.

The goal of initial L-T4 therapy is to normalize serum FT4 and TSH levels as quickly as possible. The outlook is poorer for infants whose hypothyroidism is detected later in life, who receive inadequate doses of L-T4, or who have more severe forms.

Age-specific TSH reference ranges vary by laboratory, but recent studies indicate the top limit of normal TSH in infants in the first 3 months of life is 4.1-4.8 mIU/L.

“[T]herefore, TSH values above 5 mIU/L generally are abnormal if observed after 3 months of age. Whether overtreatment (defined by elevated serum FT4) is harmful remains unclear and evidence is conflicting,” the authors write.
 

Monitoring

In the near-term follow-up, close laboratory monitoring is necessary during L-T4 treatment to maintain blood TSH and FT4 in the target ranges. Studies support measuring those levels every 1-2 months in the first 6 months of life for children with congenital hypothyroidism, every 2-3 months in the second 6 months, and then every 3-4 months between 1 and 3 years of age.

In long-term follow-up, attention to behavioral and cognitive development is important, because children with congenital hypothyroidism may be at higher risk for neurocognitive and socioemotional dysfunction compared with their peers, even with adequate treatment of congenital hypothyroidism. Hearing deficits are reported in about 10% of children with congenital hypothyroidism.
 

Developmental outcomes

When L-T4 therapy is maintained and TSH and FT4 are within target range, growth and adult height are generally normal in children with congenital hypothyroidism.

In contrast, the neurodevelopmental prognosis is less certain when treatment starts late.

“[I]nfants with severe congenital hypothyroidism and intrauterine hypothyroidism (as indicated by retarded skeletal maturation at birth) may have low-to-normal intelligence,” the report states. “Similarly, although more than 80% of infants given L-T4 replacement therapy before 3 months of age have an intelligence [quotient] greater than 85, 77% of these infants show signs of cognitive impairment in arithmetic ability, speech, or fine motor coordination later in life.”

If a child is properly treated for congenital hypothyroidism but growth or development is abnormal, testing for other illness, hearing deficit, or other hormone deficiency is needed, the report states.

The authors report no relevant financial relationships.

Congenital hypothyroidism is one of the most common preventable causes of intellectual disabilities worldwide, but newborn screening has not been established in all countries.

Additionally, screening alone is not enough to prevent adverse outcomes in children, write authors of a technical report published online in Pediatrics (Jan. 2023;151[1]:e2022060420).

Susan R. Rose, MD, with the division of endocrinology at Cincinnati Children’s Hospital Medical Center in Ohio, led the work group that updated guidance for screening and management of congenital hypothyroidism. The group worked in conjunction with the American Academy of Pediatrics Section on Endocrinology, the AAP Council on Genetics, the Pediatric Endocrine Society, and the American Thyroid Association.

In addition to screening, timely diagnosis, effective treatment, and follow-up are important.

Tests don’t always tell the full story with congenital hypothyroidism.

“Physicians need to consider hypothyroidism in the face of clinical symptoms, even if newborn screening thyroid test results are normal,” the authors write.

They add that newborn screening for congenital hypothyroidism followed by prompt levothyroxine therapy can prevent severe intellectual disability, psychomotor dysfunction, and impaired growth.

Incidence of congenital hypothyroidism ranges from approximately 1 in 2,000 to 1 in 4,000 newborn infants in countries that have newborn screening data, according to the report.

Following are highlights of the guidance:
 

Clinical signs

Symptoms and signs include large posterior fontanelle, lethargy, large tongue, prolonged jaundice, umbilical hernia, constipation, and/or hypothermia. With these signs, measuring serum thyroid-stimulating hormone (TSH) and free thyroxine (FT4) is indicated, regardless of screening results.

Newborn screening in first days

Population screening is cost effective when performed by state or other public health laboratories working with hospitals or birthing centers in their area, the authors write.

Multidisciplinary teams are best able to conduct comprehensive care when cases are detected.

The screening includes a dried blood spot from a heel stick on an approved paper card using appropriate collection methods. The blood spots are then sent to the laboratory. The preferred age for collecting the specimen is 48-72 hours of age.

That timing may be difficult, the authors note, as 90% of infants in the United States and Europe are discharged before 48 hours, but taking the specimen before discharge is important to avoid missing the early diagnosis.

“However, collection of the NBS [newborn screening] specimen before 48 hours of age, and particularly before 24 hours of age, necessitates the use of age-specific TSH reference ranges or repeat screening, particularly to avoid false-positive results,” the authors note.

If a newborn infant is transferred to another hospital, communication about the screening is critical.
 

Testing strategies

Three test strategies are used for screening: a primary TSH – reflex T4 measurement; primary T4 – reflex TSH measurement; and combined T4 and TSH measurement.

“All three test strategies detect moderate to severe primary congenital hypothyroidism with similar accuracy,” the authors write.

Most newborn screening programs in the United States and worldwide use a primary TSH test strategy.
 

Multiple births, same-sex twins

The incidence of congenital hypothyroidism appears to be higher with multiple births (1:876 in twin births and 1:575 in higher-order multiple births in one study). Another study showed the incidence of congenital hypothyroidism in same-sex twins to be 1 in 593, compared with 1 in 3,060 in different-sex twins.

“Most twin pairs (> 95%) are discordant for congenital hypothyroidism,” the authors write. “However, in monozygotic twins who share placental circulation, blood from a euthyroid fetal twin with normal thyroid hormone levels may cross to a fetal twin with congenital hypothyroidism, temporarily correcting the hypothyroidism and preventing its detection by newborn screening at 24-72 hours of life. Thus, all monozygotic twins, or same-sex twins for whom zygosity is unknown, should undergo repeat newborn screening around 2 weeks of age.”
 

Down syndrome

Congenital hypothyroidism incidence in infants with trisomy 21 (Down syndrome) is high and ranges from 1% to 12% in various reports. The infants tend to have lower T4 concentrations and higher TSH concentrations than do infants without trisomy. Down syndrome is associated with other comorbidities, including congenital heart disease, “that may further increase the risk of abnormal newborn screening results because of acute illness or excess iodine exposure,” the authors write.

Even infants with Down syndrome who don’t have congenital hypothyroidism are still at significant risk of developing primary hypothyroidism in their first year (approximately 7% in one prospective study).

“Therefore, in these infants, a second newborn screening should be performed at 2-4 weeks of life and serum TSH should be measured at 6 and 12 months of life,” the authors say.
 

Communication with primary care provider

Direct communication between the newborn screening program and the primary care physician is important for appropriate follow-up. Consulting a pediatric endocrinologist can speed diagnosis and management.

Serum confirmation after abnormal screening

The next step if any child’s screening results suggest congenital hypothyroidism is to perform a physical exam (for goiter, lingual thyroid gland, and/or physical signs of hypothyroidism) and to measure the concentrations of TSH and FT4 (or total T4) in the blood.

For confirmation of abnormal screening results, the authors say, measurement of FT4 is preferred over measuring total T4.
 

Interpreting serum confirmation

Some interpretations are clear cut: “Elevated TSH with low FT4 on the confirmatory serum testing indicates overt primary hypothyroidism,” the authors write.

But there are various other outcomes with more controversy.

Elevated TSH and normal FT4, for instance, is known as hyperthyrotropinemia or subclinical hypothyroidism and represents a mild primary thyroid abnormality.

In this scenario, there is controversy regarding the need for L-T4 therapy because there are few and conflicting studies regarding how mild congenital hypothyroidism affects cognitive development.

“[E]xpert opinion suggests that persistent TSH elevation > 10 mIU/L is an indication to initiate L-T4 treatment,” the authors write.

Normal TSH and low T4 is seen in patients with central hypothyroidism, prematurity, low birth weight, acute illness, or thyroxine-binding globulin deficiency.

“The concept that central hypothyroidism is usually mild appears unfounded: A study from the Netherlands found that mean pretreatment serum FT4 levels in central congenital hypothyroidism were similar to those of patients with moderately severe primary congenital hypothyroidism. Therefore, L-T4 treatment of central congenital hypothyroidism is indicated.”
 

Imaging

Routine thyroid imaging is controversial for patients with congenital hypothyroidism. In most cases, it won’t alter clinical management before age 3 years.

Thyroid ultrasonography can find thyroid tissue without radiation exposure and can be performed at any time after a congenital hypothyroidism diagnosis.

“Ultrasonography has lower sensitivity than scintigraphy for detecting ectopic thyroid tissue, the most common cause of congenital hypothyroidism, although its sensitivity is improved by the use of color Doppler,” the authors write.

Infants with normal thyroid imaging at birth may have transient hypothyroidism. In these patients, reevaluation of thyroid hormone therapy after 3 years of age to assess for persistent hypothyroidism may be beneficial.
 

Treatment

Congenital hypothyroidism is treated with enteral L-T4 at a starting dose of 10-15 mcg/kg per day, given once a day.

L-T4 tablets are the treatment of choice and generic tablets are fine for most children, the authors write, adding that a brand name formulation may be more consistent and better for children with severe congenital hypothyroidism.

An oral solution of L-T4 has been approved by the U.S. Food and Drug Administration for use in children.

“[H]owever, limited experience with its use showed that dosing may not be equivalent to dosing with tablet formulations,” the guidance states.

The goal of initial L-T4 therapy is to normalize serum FT4 and TSH levels as quickly as possible. The outlook is poorer for infants whose hypothyroidism is detected later in life, who receive inadequate doses of L-T4, or who have more severe forms.

Age-specific TSH reference ranges vary by laboratory, but recent studies indicate the top limit of normal TSH in infants in the first 3 months of life is 4.1-4.8 mIU/L.

“[T]herefore, TSH values above 5 mIU/L generally are abnormal if observed after 3 months of age. Whether overtreatment (defined by elevated serum FT4) is harmful remains unclear and evidence is conflicting,” the authors write.
 

Monitoring

In the near-term follow-up, close laboratory monitoring is necessary during L-T4 treatment to maintain blood TSH and FT4 in the target ranges. Studies support measuring those levels every 1-2 months in the first 6 months of life for children with congenital hypothyroidism, every 2-3 months in the second 6 months, and then every 3-4 months between 1 and 3 years of age.

In long-term follow-up, attention to behavioral and cognitive development is important, because children with congenital hypothyroidism may be at higher risk for neurocognitive and socioemotional dysfunction compared with their peers, even with adequate treatment of congenital hypothyroidism. Hearing deficits are reported in about 10% of children with congenital hypothyroidism.
 

Developmental outcomes

When L-T4 therapy is maintained and TSH and FT4 are within target range, growth and adult height are generally normal in children with congenital hypothyroidism.

In contrast, the neurodevelopmental prognosis is less certain when treatment starts late.

“[I]nfants with severe congenital hypothyroidism and intrauterine hypothyroidism (as indicated by retarded skeletal maturation at birth) may have low-to-normal intelligence,” the report states. “Similarly, although more than 80% of infants given L-T4 replacement therapy before 3 months of age have an intelligence [quotient] greater than 85, 77% of these infants show signs of cognitive impairment in arithmetic ability, speech, or fine motor coordination later in life.”

If a child is properly treated for congenital hypothyroidism but growth or development is abnormal, testing for other illness, hearing deficit, or other hormone deficiency is needed, the report states.

The authors report no relevant financial relationships.