Pituitary, Thyroid & Adrenal Disorders

WASHINGTON – False negative rates from fine needle aspiration (FNA) biopsies of large thyroid nodules are lower than commonly reported when studies are expanded to include all nodules (including those that were not operated on), compared with only those that were.

While more research is needed, “the risk of false negative FNA results for large nodules may not be as high as reported in previous studies if you include patients who do not have indication for surgery, such as compressive symptoms, suspicious ultrasound features, etc.,” senior author Tracy Tylee, MD, an associate professor of endocrinology at the University of Washington, Seattle, said in an interview.

The implication is that nonsurgical options such as radiofrequency ablation may be appropriate for more patients than realized, she added.

“Clinicians should consider following these patients more conservatively, either with a second FNA to confirm [the] nodule is benign or with ultrasound follow-up for 5 years with intervention only if [there are] significant changes on imaging,” she said.

The findings were presented at the annual meeting of the American Thyroid Association.
 

Concerns about nodules over 4 cm having high false negative rates

Management of large thyroid nodules over 4 cm that are classified as Bethesda II, indicative of being benign, is complicated by concerns of false negatives in such cases. While the false negative rate for thyroid nodules in general is approximately 3%, the rate for large nodules over 4 cm has been reported as high as 35%.

Importantly, however, most studies evaluating the issue only involve patients who have received thyroid surgery, whereas most benign nodules are not referred for surgery.

“This may overestimate the false negative FNA biopsy risk for this group,” first author Melbin Thomas, MD, also of the University of Washington, said in her talk.

To better assess the false negative rate in the broader context of large nodules that did and did not undergo surgery, Dr. Thomas and her colleagues conducted a retrospective chart review of all patients undergoing FNA biopsy at her center between 2008 and 2014 for thyroid nodules larger than 4 cm and initially classified as Bethesda II, or benign.

With a follow-up of up to 10 years, nodules were considered accurately benign if they showed benign pathology on surgical resection, if they remained benign based on repeat FNA biopsy with Bethesda II results, or if there were no changes on imaging characteristics on ultrasound after at least 2 years.

Overall, 47 nodules over 4 cm and Bethesda II cytology were included, with an average follow-up of 5 years (range 2.2-9.7 years).

Of the nodules, 23 were treated with surgery, two of which were determined to have been malignant (8.7%) and, hence, false negatives. Nine of the nodules had repeat FNA, with none found to be malignant, and 15 received repeat ultrasound, also with no malignancies.

Overall, the false negative rate including all patients was 4.3%.

“False negative FNA biopsy results were not markedly elevated if nodules greater than 4 cm are evaluated, but rates were considerably higher if limited to surgical patients,” Dr. Thomas said.

Clinicians may be compelled to perform more aggressive surgery on large but benign thyroid nodules for a number of reasons, Dr. Tylee noted.

“A concern is that we may discontinue follow-up on these larger nodules and fail to diagnose a cancer early on, before there has been extrathyroidal extension or lymph node metastases,” she said.

In such cases, patients could wind up presenting at a higher stage of disease and require more intensive therapy.

However, with a low false negative rate overall, “all of this can increase the long-term health care costs and anxiety for patients, so having a better understanding of the true benign rate for large nodules is important,” she concluded.

Commenting on the research, Rodis D. Paparodis, MD, chief of Endocrinology, Diabetes, and Metabolism Clinics, in Patras, Greece, said the findings underscore that, as a surgical procedure, “thyroidectomy should be used cautiously, only when the benefit outweighs the risk.”

In his own previous multicenter study, Dr. Paparodis conducted a review of nearly 2,500 thyroidectomies that were performed based on size or longterm slow growth despite preoperative benign FNA findings. The results showed that only 1.9% of patients had any form of thyroid cancer in the nodule that had led to surgery; however, multiple other significant cancers were often present in other locations in the gland.

“Therefore, we suggest that careful sonographic evaluation of all thyroid nodules is warranted prior to deciding and planning the extent of surgical management for multinodular goiter,” he told this news organization.

“In addition, FNA of all suspicious nodules is required as well, to avoid unnecessary surprises in surgical pathology.”

Dr. Tylee, Dr. Thomas, and Dr. Paparodis report no relevant financial relationships.

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

WASHINGTON – False negative rates from fine needle aspiration (FNA) biopsies of large thyroid nodules are lower than commonly reported when studies are expanded to include all nodules (including those that were not operated on), compared with only those that were.

While more research is needed, “the risk of false negative FNA results for large nodules may not be as high as reported in previous studies if you include patients who do not have indication for surgery, such as compressive symptoms, suspicious ultrasound features, etc.,” senior author Tracy Tylee, MD, an associate professor of endocrinology at the University of Washington, Seattle, said in an interview.

The implication is that nonsurgical options such as radiofrequency ablation may be appropriate for more patients than realized, she added.

“Clinicians should consider following these patients more conservatively, either with a second FNA to confirm [the] nodule is benign or with ultrasound follow-up for 5 years with intervention only if [there are] significant changes on imaging,” she said.

The findings were presented at the annual meeting of the American Thyroid Association.
 

Concerns about nodules over 4 cm having high false negative rates

Management of large thyroid nodules over 4 cm that are classified as Bethesda II, indicative of being benign, is complicated by concerns of false negatives in such cases. While the false negative rate for thyroid nodules in general is approximately 3%, the rate for large nodules over 4 cm has been reported as high as 35%.

Importantly, however, most studies evaluating the issue only involve patients who have received thyroid surgery, whereas most benign nodules are not referred for surgery.

“This may overestimate the false negative FNA biopsy risk for this group,” first author Melbin Thomas, MD, also of the University of Washington, said in her talk.

To better assess the false negative rate in the broader context of large nodules that did and did not undergo surgery, Dr. Thomas and her colleagues conducted a retrospective chart review of all patients undergoing FNA biopsy at her center between 2008 and 2014 for thyroid nodules larger than 4 cm and initially classified as Bethesda II, or benign.

With a follow-up of up to 10 years, nodules were considered accurately benign if they showed benign pathology on surgical resection, if they remained benign based on repeat FNA biopsy with Bethesda II results, or if there were no changes on imaging characteristics on ultrasound after at least 2 years.

Overall, 47 nodules over 4 cm and Bethesda II cytology were included, with an average follow-up of 5 years (range 2.2-9.7 years).

Of the nodules, 23 were treated with surgery, two of which were determined to have been malignant (8.7%) and, hence, false negatives. Nine of the nodules had repeat FNA, with none found to be malignant, and 15 received repeat ultrasound, also with no malignancies.

Overall, the false negative rate including all patients was 4.3%.

“False negative FNA biopsy results were not markedly elevated if nodules greater than 4 cm are evaluated, but rates were considerably higher if limited to surgical patients,” Dr. Thomas said.

Clinicians may be compelled to perform more aggressive surgery on large but benign thyroid nodules for a number of reasons, Dr. Tylee noted.

“A concern is that we may discontinue follow-up on these larger nodules and fail to diagnose a cancer early on, before there has been extrathyroidal extension or lymph node metastases,” she said.

In such cases, patients could wind up presenting at a higher stage of disease and require more intensive therapy.

However, with a low false negative rate overall, “all of this can increase the long-term health care costs and anxiety for patients, so having a better understanding of the true benign rate for large nodules is important,” she concluded.

Commenting on the research, Rodis D. Paparodis, MD, chief of Endocrinology, Diabetes, and Metabolism Clinics, in Patras, Greece, said the findings underscore that, as a surgical procedure, “thyroidectomy should be used cautiously, only when the benefit outweighs the risk.”

In his own previous multicenter study, Dr. Paparodis conducted a review of nearly 2,500 thyroidectomies that were performed based on size or longterm slow growth despite preoperative benign FNA findings. The results showed that only 1.9% of patients had any form of thyroid cancer in the nodule that had led to surgery; however, multiple other significant cancers were often present in other locations in the gland.

“Therefore, we suggest that careful sonographic evaluation of all thyroid nodules is warranted prior to deciding and planning the extent of surgical management for multinodular goiter,” he told this news organization.

“In addition, FNA of all suspicious nodules is required as well, to avoid unnecessary surprises in surgical pathology.”

Dr. Tylee, Dr. Thomas, and Dr. Paparodis report no relevant financial relationships.

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

WASHINGTON – False negative rates from fine needle aspiration (FNA) biopsies of large thyroid nodules are lower than commonly reported when studies are expanded to include all nodules (including those that were not operated on), compared with only those that were.

While more research is needed, “the risk of false negative FNA results for large nodules may not be as high as reported in previous studies if you include patients who do not have indication for surgery, such as compressive symptoms, suspicious ultrasound features, etc.,” senior author Tracy Tylee, MD, an associate professor of endocrinology at the University of Washington, Seattle, said in an interview.

The implication is that nonsurgical options such as radiofrequency ablation may be appropriate for more patients than realized, she added.

“Clinicians should consider following these patients more conservatively, either with a second FNA to confirm [the] nodule is benign or with ultrasound follow-up for 5 years with intervention only if [there are] significant changes on imaging,” she said.

The findings were presented at the annual meeting of the American Thyroid Association.
 

Concerns about nodules over 4 cm having high false negative rates

Management of large thyroid nodules over 4 cm that are classified as Bethesda II, indicative of being benign, is complicated by concerns of false negatives in such cases. While the false negative rate for thyroid nodules in general is approximately 3%, the rate for large nodules over 4 cm has been reported as high as 35%.

Importantly, however, most studies evaluating the issue only involve patients who have received thyroid surgery, whereas most benign nodules are not referred for surgery.

“This may overestimate the false negative FNA biopsy risk for this group,” first author Melbin Thomas, MD, also of the University of Washington, said in her talk.

To better assess the false negative rate in the broader context of large nodules that did and did not undergo surgery, Dr. Thomas and her colleagues conducted a retrospective chart review of all patients undergoing FNA biopsy at her center between 2008 and 2014 for thyroid nodules larger than 4 cm and initially classified as Bethesda II, or benign.

With a follow-up of up to 10 years, nodules were considered accurately benign if they showed benign pathology on surgical resection, if they remained benign based on repeat FNA biopsy with Bethesda II results, or if there were no changes on imaging characteristics on ultrasound after at least 2 years.

Overall, 47 nodules over 4 cm and Bethesda II cytology were included, with an average follow-up of 5 years (range 2.2-9.7 years).

Of the nodules, 23 were treated with surgery, two of which were determined to have been malignant (8.7%) and, hence, false negatives. Nine of the nodules had repeat FNA, with none found to be malignant, and 15 received repeat ultrasound, also with no malignancies.

Overall, the false negative rate including all patients was 4.3%.

“False negative FNA biopsy results were not markedly elevated if nodules greater than 4 cm are evaluated, but rates were considerably higher if limited to surgical patients,” Dr. Thomas said.

Clinicians may be compelled to perform more aggressive surgery on large but benign thyroid nodules for a number of reasons, Dr. Tylee noted.

“A concern is that we may discontinue follow-up on these larger nodules and fail to diagnose a cancer early on, before there has been extrathyroidal extension or lymph node metastases,” she said.

In such cases, patients could wind up presenting at a higher stage of disease and require more intensive therapy.

However, with a low false negative rate overall, “all of this can increase the long-term health care costs and anxiety for patients, so having a better understanding of the true benign rate for large nodules is important,” she concluded.

Commenting on the research, Rodis D. Paparodis, MD, chief of Endocrinology, Diabetes, and Metabolism Clinics, in Patras, Greece, said the findings underscore that, as a surgical procedure, “thyroidectomy should be used cautiously, only when the benefit outweighs the risk.”

In his own previous multicenter study, Dr. Paparodis conducted a review of nearly 2,500 thyroidectomies that were performed based on size or longterm slow growth despite preoperative benign FNA findings. The results showed that only 1.9% of patients had any form of thyroid cancer in the nodule that had led to surgery; however, multiple other significant cancers were often present in other locations in the gland.

“Therefore, we suggest that careful sonographic evaluation of all thyroid nodules is warranted prior to deciding and planning the extent of surgical management for multinodular goiter,” he told this news organization.

“In addition, FNA of all suspicious nodules is required as well, to avoid unnecessary surprises in surgical pathology.”

Dr. Tylee, Dr. Thomas, and Dr. Paparodis report no relevant financial relationships.

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

Thyroxine and L-thyroxine are two of the 10 most frequently prescribed medicinal products. “One large health insurance company ranks thyroid hormone at fourth place in the list of most-sold medications in the United States. It is possibly the second most commonly prescribed preparation,” said Joachim Feldkamp, MD, PhD, director of the University Clinic for General Internal Medicine, Endocrinology, Diabetology, and Infectious Diseases at Central Hospital, Bielefeld, Germany, at the online press conference for the German Society of Endocrinology’s hormone week.

The preparation is prescribed when the thyroid gland produces too little thyroid hormone. The messenger substance thyroid-stimulating hormone (TSH) is used as a screening value to assess thyroid function. An increase in TSH can indicate that too little thyroid hormone is being produced.

“But this does not mean that an underactive thyroid gland is hiding behind every elevated TSH value,” said Dr. Feldkamp. Normally, the TSH value lies between 0.3 and 4.2 mU/L. “Hypothyroidism, as it’s known, is formally present if the TSH value lies above the upper limit of 4.2 mU/L,” said Dr. Feldkamp.
 

Check again

However, not every elevated TSH value needs to be treated immediately. “From large-scale investigations, we know that TSH values are subject to fluctuations,” said Dr. Feldkamp. Individual measurements must therefore be taken with a grain of salt and almost never justify a therapeutic decision. Therefore, a slightly elevated TSH value should be checked again 2-6 months later, and the patient should be asked if they are experiencing any symptoms. “In 50%-60% of cases, the TSH value normalized at the second checkup without requiring any treatment,” Dr. Feldkamp explained.

The TSH value could be elevated for several reasons:

• Fluctuations depending on the time of day. At night and early in the morning, the TSH value is much higher than in the afternoon. An acute lack of sleep can lead to higher TSH values in the morning.
• Fluctuations depending on the time of year. In winter, TSH values are slightly higher than in the summer owing to adaptation to cooler temperatures. Researchers in the Arctic, for example, have significantly higher TSH values than people who live in warmer regions.
• Age-dependent differences. Children and adolescents have higher TSH values than adults do. The TSH values of adolescents cannot be based on those of adults because this would lead to incorrect treatment. In addition, TSH values increase with age, and slightly elevated values are initially no cause for treatment in people aged 70-80 years. Caution is advised during treatment, because overtreatment can lead to cardiac arrhythmias and a decrease in bone density.
• Sex-specific differences. The TSH values of women are generally a little higher than those in men.
• Obesity. In obesity, TSH increases and often exceeds the normal values usually recorded in persons of normal weight. The elevated values do not reflect a state of hypofunction but rather the body’s adjustment mechanism. If these patients lose weight, the TSH values will drop spontaneously. Slightly elevated TSH values in obese people should not be treated with thyroid hormones.

The nutritional supplement biotin (vitamin H or vitamin B7), which is often taken for skin, hair, and nail growth disorders, can distort measured values. In many of the laboratory methods used, the biotin competes with the test substances used. As a result, it can lead to falsely high and falsely low TSH values. At high doses of biotin (for example, 10 mg), there should be at least a 3-day pause (and ideally a pause of 1 week) before measuring TSH.
 

Hasty prescriptions

“Sometimes, because of the assumption that every high TSH value is due to sickness-related hypothyroidism, thyroid hormones can be prescribed too quickly,” said Dr. Feldkamp. This is also true for patients with thyroid nodules due to iodine deficiency, who are often still treated with thyroid hormones.

“These days, because we are generally an iodine-deficient nation, iodine would potentially be given in combination with thyroid hormones but not with thyroid hormones alone. There are lots of patients who have been taking thyroid hormones for 30 or 40 years due to thyroid nodules. That should definitely be reviewed,” said Dr. Feldkamp.
 

When to treat?

Dr. Feldkamp does not believe that standard determination of the TSH value is sensible and advises that clinicians examine patients with newly occurring symptoms, such as excess weight, impaired weight regulation despite reduced appetite, depression, or a high need for sleep.

If there are symptoms, the thyroid function must be clarified further. “This includes determination of free thyroid hormones T3 and T4; detection of antibodies against autologous thyroid tissue such as TPO-Ab [antibody against thyroid peroxidase], TG-Ab [antibody against thyroglobulin], and TRAb [antibody against TSH receptor]; and ultrasound examination of the metabolic organ,” said Dr. Feldkamp. Autoimmune-related hypothyroidism (Hashimoto’s thyroiditis) is the most common cause of an overly high TSH level.

Treatment should take place in the following situations:

• In young patients with TSH values greater than 10 mU/L;
• In young (< 65 years) symptomatic patients with TSH values of 4 to less than 10 mU/L;
• With elevated TSH values that result from thyroid surgery or radioactive iodine therapy;
• In patients with a diffuse enlarged or severely nodular thyroid gland
• In pregnant women with elevated TSH values.

This article was translated from Medscape’s German Edition and a version appeared on Medscape.com.

Thyroxine and L-thyroxine are two of the 10 most frequently prescribed medicinal products. “One large health insurance company ranks thyroid hormone at fourth place in the list of most-sold medications in the United States. It is possibly the second most commonly prescribed preparation,” said Joachim Feldkamp, MD, PhD, director of the University Clinic for General Internal Medicine, Endocrinology, Diabetology, and Infectious Diseases at Central Hospital, Bielefeld, Germany, at the online press conference for the German Society of Endocrinology’s hormone week.

The preparation is prescribed when the thyroid gland produces too little thyroid hormone. The messenger substance thyroid-stimulating hormone (TSH) is used as a screening value to assess thyroid function. An increase in TSH can indicate that too little thyroid hormone is being produced.

“But this does not mean that an underactive thyroid gland is hiding behind every elevated TSH value,” said Dr. Feldkamp. Normally, the TSH value lies between 0.3 and 4.2 mU/L. “Hypothyroidism, as it’s known, is formally present if the TSH value lies above the upper limit of 4.2 mU/L,” said Dr. Feldkamp.
 

Check again

However, not every elevated TSH value needs to be treated immediately. “From large-scale investigations, we know that TSH values are subject to fluctuations,” said Dr. Feldkamp. Individual measurements must therefore be taken with a grain of salt and almost never justify a therapeutic decision. Therefore, a slightly elevated TSH value should be checked again 2-6 months later, and the patient should be asked if they are experiencing any symptoms. “In 50%-60% of cases, the TSH value normalized at the second checkup without requiring any treatment,” Dr. Feldkamp explained.

The TSH value could be elevated for several reasons:

• Fluctuations depending on the time of day. At night and early in the morning, the TSH value is much higher than in the afternoon. An acute lack of sleep can lead to higher TSH values in the morning.
• Fluctuations depending on the time of year. In winter, TSH values are slightly higher than in the summer owing to adaptation to cooler temperatures. Researchers in the Arctic, for example, have significantly higher TSH values than people who live in warmer regions.
• Age-dependent differences. Children and adolescents have higher TSH values than adults do. The TSH values of adolescents cannot be based on those of adults because this would lead to incorrect treatment. In addition, TSH values increase with age, and slightly elevated values are initially no cause for treatment in people aged 70-80 years. Caution is advised during treatment, because overtreatment can lead to cardiac arrhythmias and a decrease in bone density.
• Sex-specific differences. The TSH values of women are generally a little higher than those in men.
• Obesity. In obesity, TSH increases and often exceeds the normal values usually recorded in persons of normal weight. The elevated values do not reflect a state of hypofunction but rather the body’s adjustment mechanism. If these patients lose weight, the TSH values will drop spontaneously. Slightly elevated TSH values in obese people should not be treated with thyroid hormones.

The nutritional supplement biotin (vitamin H or vitamin B7), which is often taken for skin, hair, and nail growth disorders, can distort measured values. In many of the laboratory methods used, the biotin competes with the test substances used. As a result, it can lead to falsely high and falsely low TSH values. At high doses of biotin (for example, 10 mg), there should be at least a 3-day pause (and ideally a pause of 1 week) before measuring TSH.
 

Hasty prescriptions

“Sometimes, because of the assumption that every high TSH value is due to sickness-related hypothyroidism, thyroid hormones can be prescribed too quickly,” said Dr. Feldkamp. This is also true for patients with thyroid nodules due to iodine deficiency, who are often still treated with thyroid hormones.

“These days, because we are generally an iodine-deficient nation, iodine would potentially be given in combination with thyroid hormones but not with thyroid hormones alone. There are lots of patients who have been taking thyroid hormones for 30 or 40 years due to thyroid nodules. That should definitely be reviewed,” said Dr. Feldkamp.
 

When to treat?

Dr. Feldkamp does not believe that standard determination of the TSH value is sensible and advises that clinicians examine patients with newly occurring symptoms, such as excess weight, impaired weight regulation despite reduced appetite, depression, or a high need for sleep.

If there are symptoms, the thyroid function must be clarified further. “This includes determination of free thyroid hormones T3 and T4; detection of antibodies against autologous thyroid tissue such as TPO-Ab [antibody against thyroid peroxidase], TG-Ab [antibody against thyroglobulin], and TRAb [antibody against TSH receptor]; and ultrasound examination of the metabolic organ,” said Dr. Feldkamp. Autoimmune-related hypothyroidism (Hashimoto’s thyroiditis) is the most common cause of an overly high TSH level.

Treatment should take place in the following situations:

• In young patients with TSH values greater than 10 mU/L;
• In young (< 65 years) symptomatic patients with TSH values of 4 to less than 10 mU/L;
• With elevated TSH values that result from thyroid surgery or radioactive iodine therapy;
• In patients with a diffuse enlarged or severely nodular thyroid gland
• In pregnant women with elevated TSH values.

This article was translated from Medscape’s German Edition and a version appeared on Medscape.com.

Thyroxine and L-thyroxine are two of the 10 most frequently prescribed medicinal products. “One large health insurance company ranks thyroid hormone at fourth place in the list of most-sold medications in the United States. It is possibly the second most commonly prescribed preparation,” said Joachim Feldkamp, MD, PhD, director of the University Clinic for General Internal Medicine, Endocrinology, Diabetology, and Infectious Diseases at Central Hospital, Bielefeld, Germany, at the online press conference for the German Society of Endocrinology’s hormone week.

The preparation is prescribed when the thyroid gland produces too little thyroid hormone. The messenger substance thyroid-stimulating hormone (TSH) is used as a screening value to assess thyroid function. An increase in TSH can indicate that too little thyroid hormone is being produced.

“But this does not mean that an underactive thyroid gland is hiding behind every elevated TSH value,” said Dr. Feldkamp. Normally, the TSH value lies between 0.3 and 4.2 mU/L. “Hypothyroidism, as it’s known, is formally present if the TSH value lies above the upper limit of 4.2 mU/L,” said Dr. Feldkamp.
 

Check again

However, not every elevated TSH value needs to be treated immediately. “From large-scale investigations, we know that TSH values are subject to fluctuations,” said Dr. Feldkamp. Individual measurements must therefore be taken with a grain of salt and almost never justify a therapeutic decision. Therefore, a slightly elevated TSH value should be checked again 2-6 months later, and the patient should be asked if they are experiencing any symptoms. “In 50%-60% of cases, the TSH value normalized at the second checkup without requiring any treatment,” Dr. Feldkamp explained.

The TSH value could be elevated for several reasons:

• Fluctuations depending on the time of day. At night and early in the morning, the TSH value is much higher than in the afternoon. An acute lack of sleep can lead to higher TSH values in the morning.
• Fluctuations depending on the time of year. In winter, TSH values are slightly higher than in the summer owing to adaptation to cooler temperatures. Researchers in the Arctic, for example, have significantly higher TSH values than people who live in warmer regions.
• Age-dependent differences. Children and adolescents have higher TSH values than adults do. The TSH values of adolescents cannot be based on those of adults because this would lead to incorrect treatment. In addition, TSH values increase with age, and slightly elevated values are initially no cause for treatment in people aged 70-80 years. Caution is advised during treatment, because overtreatment can lead to cardiac arrhythmias and a decrease in bone density.
• Sex-specific differences. The TSH values of women are generally a little higher than those in men.
• Obesity. In obesity, TSH increases and often exceeds the normal values usually recorded in persons of normal weight. The elevated values do not reflect a state of hypofunction but rather the body’s adjustment mechanism. If these patients lose weight, the TSH values will drop spontaneously. Slightly elevated TSH values in obese people should not be treated with thyroid hormones.

The nutritional supplement biotin (vitamin H or vitamin B7), which is often taken for skin, hair, and nail growth disorders, can distort measured values. In many of the laboratory methods used, the biotin competes with the test substances used. As a result, it can lead to falsely high and falsely low TSH values. At high doses of biotin (for example, 10 mg), there should be at least a 3-day pause (and ideally a pause of 1 week) before measuring TSH.
 

Hasty prescriptions

“Sometimes, because of the assumption that every high TSH value is due to sickness-related hypothyroidism, thyroid hormones can be prescribed too quickly,” said Dr. Feldkamp. This is also true for patients with thyroid nodules due to iodine deficiency, who are often still treated with thyroid hormones.

“These days, because we are generally an iodine-deficient nation, iodine would potentially be given in combination with thyroid hormones but not with thyroid hormones alone. There are lots of patients who have been taking thyroid hormones for 30 or 40 years due to thyroid nodules. That should definitely be reviewed,” said Dr. Feldkamp.
 

When to treat?

Dr. Feldkamp does not believe that standard determination of the TSH value is sensible and advises that clinicians examine patients with newly occurring symptoms, such as excess weight, impaired weight regulation despite reduced appetite, depression, or a high need for sleep.

If there are symptoms, the thyroid function must be clarified further. “This includes determination of free thyroid hormones T3 and T4; detection of antibodies against autologous thyroid tissue such as TPO-Ab [antibody against thyroid peroxidase], TG-Ab [antibody against thyroglobulin], and TRAb [antibody against TSH receptor]; and ultrasound examination of the metabolic organ,” said Dr. Feldkamp. Autoimmune-related hypothyroidism (Hashimoto’s thyroiditis) is the most common cause of an overly high TSH level.

Treatment should take place in the following situations:

• In young patients with TSH values greater than 10 mU/L;
• In young (< 65 years) symptomatic patients with TSH values of 4 to less than 10 mU/L;
• With elevated TSH values that result from thyroid surgery or radioactive iodine therapy;
• In patients with a diffuse enlarged or severely nodular thyroid gland
• In pregnant women with elevated TSH values.

This article was translated from Medscape’s German Edition and a version appeared on Medscape.com.

WASHINGTON – Transgender female veterans are more likely to have thyroid cancer at rates comparable with cisgender women rather than cisgender men. Experts urge a cautious interpretation of these recent study results.

“In our clinic of about 50 transgender women, we noticed that we had two diagnosed cases of thyroid cancer in a year,” first author John Christensen, MD, of UC Davis Health, division of endocrinology, diabetes & metabolism, Sacramento, said in an interivew. He presented their findings at the annual meeting of the American Thyroid Association.

Comparatively, the thyroid cancer prevalence among cisgender male veterans is estimated at about 0.19%; the rate among all those assigned male at birth in the general population is 0.13%, whereas the rate among those assigned female at birth, which has historically been higher for all thyroid cancer subtypes, is 0.44%, according to U.S. cancer statistics for 2020 from the National Cancer Institute.

“About one-third of our [veteran] patients had been receiving estrogen for an average of over 3 years before diagnosis, which could suggest estrogen gender‐affirming hormone therapy [GAHT] may be a potentially important risk factor,” Dr. Christensen said.

Sustained use of external estrogen, especially in cisgender women undergoing fertility treatments, has been linked to an increased risk for thyroid cancer. This is because it can lead to an increase in estrogen receptors in cancerous cells. But experts caution that many other factors also come into play.

“There is definitely an implication that if you give extra estrogen to someone assigned female at birth, you may have an increased risk of thyroid cancer,” Dr. Christensen said. “So, it would stand to reason that even in those who are not assigned female at birth, there may be a risk from exogenous estrogen that may lead to an increased risk of thyroid cancer down the line.”

To investigate the issue in a larger population, Dr. Christensen and colleagues evaluated data from the comprehensive, nationwide Veterans Affairs Informatics and Computing Infrastructure database, including approximately 9 million veterans who had outpatient visits between December 2017 and January 2022.

Of the veterans, 9,988 were determined to likely be transgender women, based on either having an ICD-10 diagnosis code for gender dysphoria or being assigned male at birth and having received an estrogen or estradiol prescription.

Of those patients, 76 had an ICD-10 code indicating thyroid cancer and 34 had verification of the thyroid cancer on chart review, representing a prevalence of 0.34% among transgender female veterans.

The average age at thyroid cancer diagnosis among the veterans was 53.8 years, and 29.4% (10 of 34) of those patients had extrathyroidal disease at the time of their thyroid cancer diagnosis. The median body mass index, available for 26 patients, was 32, which is indicative of obesity.

In terms of the patients’ thyroid cancer subtypes, 22 were papillary cancer, 5 were a follicular variant of papillary cancer, 5 were both papillary and follicular cancer, 4 were follicular cancer, 3 were a Hürthle cell variant of follicular cancer, and one was unknown.

Among 11 (32.3%) of the 34 veterans receiving estrogen GAHT at diagnosis, treatment began an average of 3.38 years prior to diagnosis at variable doses and using various routes of administration.

About half of the patients had a history of smoking; however, Dr. Christensen noted that the role of smoking as being a risk factor in estrogenic cancers has been debated. Though most patients were obese, obesity is both very common and not well established in terms of its quantitative impact on the risk for cancer development.

With the small size of the thyroid cancer cohort and omissions in the medical record among the study’s important limitations, Dr. Christensen urged a cautious interpretation of the findings.

“We are certainly suspicious that GAHT may be associated with an increased risk of thyroid cancer, but I would characterize the trends in our data as being potentially suggestive or hypothesis generating – not conclusive,” he added. “I would hate for any transgender women reading this to stop taking GAHT without talking to their doctors first.”

Commenting on the issue, Maurice Garcia, MD, a clinical associate professor of urology and director of the transgender surgery and health program at Cedars-Sinai Medical Center, Los Angeles, said that any definitive evidence of an increase in cancer risk among transgender people is lacking.

“With an estimated 1.5 [million] to 1.6 million people in the U.S. who are transgender, with many of them receiving GAHT, we haven’t observed a bump or high incidence of any kind of cancer among these people so far,” he said.

“There’s certainly a high potential that hormone therapy, whether it’s feminizing or masculinizing hormone therapy, can affect an individual’s cancer risk,” he added. “But we don’t know of any [definitive evidence] yet of an increase, and, there’s also even the question of whether there could be an opposite effect.”

Regarding the thyroid cancer data, Dr. Garcia agreed that the preliminary nature of the study is a key limitation. “It’s hard to tell if these were comparable groups, or whether those in the transgender group came in with higher risk factors for thyroid cancer.

“Until more statistical analysis is done, I think all that can be said is that it’s speculative.”

Dr. Garcia, who coauthored a review on cancer screening for transgender individuals, underscored that, despite a lack of data suggesting that transgender patients need cancer screening any more than their matched cisgender counterparts, “the point is that we cannot forget to screen them at all.”

Dr. Christensen and Dr. Garcia had no disclosures to report.

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

WASHINGTON – Transgender female veterans are more likely to have thyroid cancer at rates comparable with cisgender women rather than cisgender men. Experts urge a cautious interpretation of these recent study results.

“In our clinic of about 50 transgender women, we noticed that we had two diagnosed cases of thyroid cancer in a year,” first author John Christensen, MD, of UC Davis Health, division of endocrinology, diabetes & metabolism, Sacramento, said in an interivew. He presented their findings at the annual meeting of the American Thyroid Association.

Comparatively, the thyroid cancer prevalence among cisgender male veterans is estimated at about 0.19%; the rate among all those assigned male at birth in the general population is 0.13%, whereas the rate among those assigned female at birth, which has historically been higher for all thyroid cancer subtypes, is 0.44%, according to U.S. cancer statistics for 2020 from the National Cancer Institute.

“About one-third of our [veteran] patients had been receiving estrogen for an average of over 3 years before diagnosis, which could suggest estrogen gender‐affirming hormone therapy [GAHT] may be a potentially important risk factor,” Dr. Christensen said.

Sustained use of external estrogen, especially in cisgender women undergoing fertility treatments, has been linked to an increased risk for thyroid cancer. This is because it can lead to an increase in estrogen receptors in cancerous cells. But experts caution that many other factors also come into play.

“There is definitely an implication that if you give extra estrogen to someone assigned female at birth, you may have an increased risk of thyroid cancer,” Dr. Christensen said. “So, it would stand to reason that even in those who are not assigned female at birth, there may be a risk from exogenous estrogen that may lead to an increased risk of thyroid cancer down the line.”

To investigate the issue in a larger population, Dr. Christensen and colleagues evaluated data from the comprehensive, nationwide Veterans Affairs Informatics and Computing Infrastructure database, including approximately 9 million veterans who had outpatient visits between December 2017 and January 2022.

Of the veterans, 9,988 were determined to likely be transgender women, based on either having an ICD-10 diagnosis code for gender dysphoria or being assigned male at birth and having received an estrogen or estradiol prescription.

Of those patients, 76 had an ICD-10 code indicating thyroid cancer and 34 had verification of the thyroid cancer on chart review, representing a prevalence of 0.34% among transgender female veterans.

The average age at thyroid cancer diagnosis among the veterans was 53.8 years, and 29.4% (10 of 34) of those patients had extrathyroidal disease at the time of their thyroid cancer diagnosis. The median body mass index, available for 26 patients, was 32, which is indicative of obesity.

In terms of the patients’ thyroid cancer subtypes, 22 were papillary cancer, 5 were a follicular variant of papillary cancer, 5 were both papillary and follicular cancer, 4 were follicular cancer, 3 were a Hürthle cell variant of follicular cancer, and one was unknown.

Among 11 (32.3%) of the 34 veterans receiving estrogen GAHT at diagnosis, treatment began an average of 3.38 years prior to diagnosis at variable doses and using various routes of administration.

About half of the patients had a history of smoking; however, Dr. Christensen noted that the role of smoking as being a risk factor in estrogenic cancers has been debated. Though most patients were obese, obesity is both very common and not well established in terms of its quantitative impact on the risk for cancer development.

With the small size of the thyroid cancer cohort and omissions in the medical record among the study’s important limitations, Dr. Christensen urged a cautious interpretation of the findings.

“We are certainly suspicious that GAHT may be associated with an increased risk of thyroid cancer, but I would characterize the trends in our data as being potentially suggestive or hypothesis generating – not conclusive,” he added. “I would hate for any transgender women reading this to stop taking GAHT without talking to their doctors first.”

Commenting on the issue, Maurice Garcia, MD, a clinical associate professor of urology and director of the transgender surgery and health program at Cedars-Sinai Medical Center, Los Angeles, said that any definitive evidence of an increase in cancer risk among transgender people is lacking.

“With an estimated 1.5 [million] to 1.6 million people in the U.S. who are transgender, with many of them receiving GAHT, we haven’t observed a bump or high incidence of any kind of cancer among these people so far,” he said.

“There’s certainly a high potential that hormone therapy, whether it’s feminizing or masculinizing hormone therapy, can affect an individual’s cancer risk,” he added. “But we don’t know of any [definitive evidence] yet of an increase, and, there’s also even the question of whether there could be an opposite effect.”

Regarding the thyroid cancer data, Dr. Garcia agreed that the preliminary nature of the study is a key limitation. “It’s hard to tell if these were comparable groups, or whether those in the transgender group came in with higher risk factors for thyroid cancer.

“Until more statistical analysis is done, I think all that can be said is that it’s speculative.”

Dr. Garcia, who coauthored a review on cancer screening for transgender individuals, underscored that, despite a lack of data suggesting that transgender patients need cancer screening any more than their matched cisgender counterparts, “the point is that we cannot forget to screen them at all.”

Dr. Christensen and Dr. Garcia had no disclosures to report.

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

WASHINGTON – Transgender female veterans are more likely to have thyroid cancer at rates comparable with cisgender women rather than cisgender men. Experts urge a cautious interpretation of these recent study results.

“In our clinic of about 50 transgender women, we noticed that we had two diagnosed cases of thyroid cancer in a year,” first author John Christensen, MD, of UC Davis Health, division of endocrinology, diabetes & metabolism, Sacramento, said in an interivew. He presented their findings at the annual meeting of the American Thyroid Association.

Comparatively, the thyroid cancer prevalence among cisgender male veterans is estimated at about 0.19%; the rate among all those assigned male at birth in the general population is 0.13%, whereas the rate among those assigned female at birth, which has historically been higher for all thyroid cancer subtypes, is 0.44%, according to U.S. cancer statistics for 2020 from the National Cancer Institute.

“About one-third of our [veteran] patients had been receiving estrogen for an average of over 3 years before diagnosis, which could suggest estrogen gender‐affirming hormone therapy [GAHT] may be a potentially important risk factor,” Dr. Christensen said.

Sustained use of external estrogen, especially in cisgender women undergoing fertility treatments, has been linked to an increased risk for thyroid cancer. This is because it can lead to an increase in estrogen receptors in cancerous cells. But experts caution that many other factors also come into play.

“There is definitely an implication that if you give extra estrogen to someone assigned female at birth, you may have an increased risk of thyroid cancer,” Dr. Christensen said. “So, it would stand to reason that even in those who are not assigned female at birth, there may be a risk from exogenous estrogen that may lead to an increased risk of thyroid cancer down the line.”

To investigate the issue in a larger population, Dr. Christensen and colleagues evaluated data from the comprehensive, nationwide Veterans Affairs Informatics and Computing Infrastructure database, including approximately 9 million veterans who had outpatient visits between December 2017 and January 2022.

Of the veterans, 9,988 were determined to likely be transgender women, based on either having an ICD-10 diagnosis code for gender dysphoria or being assigned male at birth and having received an estrogen or estradiol prescription.

Of those patients, 76 had an ICD-10 code indicating thyroid cancer and 34 had verification of the thyroid cancer on chart review, representing a prevalence of 0.34% among transgender female veterans.

The average age at thyroid cancer diagnosis among the veterans was 53.8 years, and 29.4% (10 of 34) of those patients had extrathyroidal disease at the time of their thyroid cancer diagnosis. The median body mass index, available for 26 patients, was 32, which is indicative of obesity.

In terms of the patients’ thyroid cancer subtypes, 22 were papillary cancer, 5 were a follicular variant of papillary cancer, 5 were both papillary and follicular cancer, 4 were follicular cancer, 3 were a Hürthle cell variant of follicular cancer, and one was unknown.

Among 11 (32.3%) of the 34 veterans receiving estrogen GAHT at diagnosis, treatment began an average of 3.38 years prior to diagnosis at variable doses and using various routes of administration.

About half of the patients had a history of smoking; however, Dr. Christensen noted that the role of smoking as being a risk factor in estrogenic cancers has been debated. Though most patients were obese, obesity is both very common and not well established in terms of its quantitative impact on the risk for cancer development.

With the small size of the thyroid cancer cohort and omissions in the medical record among the study’s important limitations, Dr. Christensen urged a cautious interpretation of the findings.

“We are certainly suspicious that GAHT may be associated with an increased risk of thyroid cancer, but I would characterize the trends in our data as being potentially suggestive or hypothesis generating – not conclusive,” he added. “I would hate for any transgender women reading this to stop taking GAHT without talking to their doctors first.”

Commenting on the issue, Maurice Garcia, MD, a clinical associate professor of urology and director of the transgender surgery and health program at Cedars-Sinai Medical Center, Los Angeles, said that any definitive evidence of an increase in cancer risk among transgender people is lacking.

“With an estimated 1.5 [million] to 1.6 million people in the U.S. who are transgender, with many of them receiving GAHT, we haven’t observed a bump or high incidence of any kind of cancer among these people so far,” he said.

“There’s certainly a high potential that hormone therapy, whether it’s feminizing or masculinizing hormone therapy, can affect an individual’s cancer risk,” he added. “But we don’t know of any [definitive evidence] yet of an increase, and, there’s also even the question of whether there could be an opposite effect.”

Regarding the thyroid cancer data, Dr. Garcia agreed that the preliminary nature of the study is a key limitation. “It’s hard to tell if these were comparable groups, or whether those in the transgender group came in with higher risk factors for thyroid cancer.

“Until more statistical analysis is done, I think all that can be said is that it’s speculative.”

Dr. Garcia, who coauthored a review on cancer screening for transgender individuals, underscored that, despite a lack of data suggesting that transgender patients need cancer screening any more than their matched cisgender counterparts, “the point is that we cannot forget to screen them at all.”

Dr. Christensen and Dr. Garcia had no disclosures to report.

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

WASHINGTON – The routine practice of holding use of blood-thinning medications at the time of an ultrasound-guided thyroid nodule fine needle aspiration (FNA) biopsy shows no significant safety benefit in preventing the risk of complications such as hematomas or nondiagnostic results; however, experts suggest using individualized decision-making with the practice.

“Our data indicates that there is no need to routinely hold anticoagulation or antiplatelet therapy prior to thyroid nodule FNA biopsy,” first author Michelle Lundholm, MD, of the Cleveland Clinic said in an interview.

“[The practice] impacts neither the safety of the FNA procedure nor the adequacy of the sample,” she said.

The late-breaking research was presented at the annual meeting of the American Thyroid Association.

Key concerns in the use of anticoagulants and/or antiplatelet medications during thyroid nodule FNA biopsy include the increased risk of postprocedural hematoma or nondiagnostic results, with, for instance, one study showing higher rates of nondiagnostic results among patients remaining on aspirin therapy during the FNA biopsy.

However, holding the medically indicated therapies can have risks of its own, including concerns of thrombotic events such as deep vein thrombosis or stroke. However, evidence comparing the risks with each strategy in thyroid nodule FNA is lacking.

To investigate, Dr. Lundholm and colleagues conducted a review of data on 2,945 patients who had undergone a total of 4,741 thyroid nodule FNAs in the Cleveland Clinic’s diverse network of centers between 2010 and 2023. The patients had a mean age of 66.2; 69.6% were female and 75.7% were White.

All patients had an active prescription for an anticoagulant or antiplatelet medication up to 10 days prior to their thyroid nodule FNA biopsy. Specifically, 73.7% were on 81 mg aspirin, 8.5% were on 325 mg aspirin, 7.4% were taking other antiplatelet medication such as clopidogrel or ticagrelor; 7.0% were on warfarin, 8.2% were on a direct oral anticoagulant (DOAC); 6.3% were on heparin products; and 10.3% of patients were on two or more blood-thinning medications.

The results show that, overall, 13.0% (n =  614) of the thyroid nodule FNA biopsies had nondiagnostic results, which is within the average rates in the literature ranging from 6% to 36%, Dr. Lundholm noted.

Blood-thinning medications were held in 20.8% of the FNA biopsies, however, there were no differences in nondiagnostic results between those who had drugs held (12.2%) or who continued on the medications (13.2%; P  = .41).

After multivariate adjustment for age and sex, the lack of significant differences in receiving nondiagnostic results among those who did or did not continue blood thinners was consistent overall (odds ratio, 1.10; P = .38), and in the specific groups of 81 mg aspirin (OR, 1.00; P = .99); 325 mg aspirin or clopidogrel/ticagrelor (OR, 1.50; P = .15); or warfarin, DOAC, or heparin/enoxaparin (OR, 1.27; P = .27).

In terms of hematoma risk, ED records within 48 hours of the FNA showed that such events were rare, with only one hematoma occurring overall, involving a patient who was on 81 mg of aspirin for secondary stroke prevention that was not interrupted for FNA biopsy. The patient was discharged and did not require medical intervention.  

Four other hematomas occurred among patients who were not being treated with blood thinners, with none requiring intervention.

The findings indicate that “hematoma can happen in any patient, but rarely requires intervention,” Dr. Lundholm said.

However, while thrombotic events were also rare, serious events occurred in three patients within 48 hours of the thyroid nodule FNA biopsy when a blood thinner was withheld, including ischemic strokes among two patients who were on a DOAC and 81 mg of aspirin that were withheld, and one MI occurring in a patient on a DOAC that was held for the FNA.

Unlike hematomas, the thrombotic events each had significant long‐term sequelae, Dr. Lundholm noted.

“Having these ischemic strokes and heart attack really led to a change in these patients’ lives,” she said. “While we can never assume that [the events occurred] because the blood-thinner therapy was held, the timing within 48 hours is certainly very suspicious.”

There were no deep vein thrombosis or pulmonary embolism events.
 

Withholding practices vary

In a previous survey of 60 clinicians conducted by Dr. Lundholm and colleagues, wide variation was reported in the rates of withholding antiplatelet or anticoagulant medications prior to thyroid nodule FNA biopsy.

The survey of endocrinologists, interventional radiologists, and ear, nose, and throat providers showed rates of withholding 81 mg of aspirin prior to FNA biopsy of just 13.3%, withholding 325 mg of aspirin, 15%, other antiplatelets, 41.7%, warfarin, 73.3%, DOACs, 43.3%, and heparin, 43.3%.

“We found heterogeneity in withholding patterns even within the same department,” she said. “This is reflective of the fact that evidence is mixed.”

Guidelines on the issue from the Society of Interventional Radiology and the International Society on Thrombosis and Hemostasis recommend that providers consider the balance of the procedure and patient bleeding risk versus the clotting risk, Dr. Lundholm noted.

However, a caveat is that those recommendations are based on pooled data from similar minimal risk procedures, she explained.

“There is a lack of data on bleeding risks for individual interventions like thyroid biopsy, and, as such, there is no specific procedure-related risk determination.”

Meanwhile, Dr. Lundholm said that notable limitations regarding the current research include that the study may not have caught all patient cases that presented with complications to an outside ED.

Furthermore, the study results pertain to the safety of blood thinners in routine use, with key aspects that can influence complication rates, such as provider experience, needle size, and nodule features unavailable for analysis.
 

At MD Anderson, case-by-case

Commenting on the research, Anastasios Maniakas, MD, PhD, of the department of head and neck surgery, division of surgery, University of Texas MD Anderson Cancer Center, Houston, said the study is important, noting that, at his institution, the approach regarding holding blood-thinning medications is generally determined on an individual basis.

“I think this was a good study, but I don’t think it’s practice changing because these decisions may differ on a case-by-case basis,” Dr. Maniakas, who comoderated the session, said in an interview.

“At MD Anderson, we probably have one of the highest volumes in the country for thyroid nodule FNAs, and we do hold blood thinners because we often have to do more significant biopsies, with multiple passages and larger needles to be used,” Dr. Maniakas said.

“If you’re going to use perhaps the smallest possible gauge needle, then I think it is reasonable to not hold blood thinners, but if you’re going to be doing multiple passages and you need to do a core biopsy and use a large needle, then it is wiser to try to hold the medications for a day or 2.

“We haven’t had any complications, but I think there’s still a lot of apprehension to not hold blood thinners,” Dr. Maniakas said. “So, overall, I think the message is that it has to be on a case-by-case basis.”

Dr. Lundholm and Dr. Maniakas reported no relevant financial relationships.

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

WASHINGTON – The routine practice of holding use of blood-thinning medications at the time of an ultrasound-guided thyroid nodule fine needle aspiration (FNA) biopsy shows no significant safety benefit in preventing the risk of complications such as hematomas or nondiagnostic results; however, experts suggest using individualized decision-making with the practice.

“Our data indicates that there is no need to routinely hold anticoagulation or antiplatelet therapy prior to thyroid nodule FNA biopsy,” first author Michelle Lundholm, MD, of the Cleveland Clinic said in an interview.

“[The practice] impacts neither the safety of the FNA procedure nor the adequacy of the sample,” she said.

The late-breaking research was presented at the annual meeting of the American Thyroid Association.

Key concerns in the use of anticoagulants and/or antiplatelet medications during thyroid nodule FNA biopsy include the increased risk of postprocedural hematoma or nondiagnostic results, with, for instance, one study showing higher rates of nondiagnostic results among patients remaining on aspirin therapy during the FNA biopsy.

However, holding the medically indicated therapies can have risks of its own, including concerns of thrombotic events such as deep vein thrombosis or stroke. However, evidence comparing the risks with each strategy in thyroid nodule FNA is lacking.

To investigate, Dr. Lundholm and colleagues conducted a review of data on 2,945 patients who had undergone a total of 4,741 thyroid nodule FNAs in the Cleveland Clinic’s diverse network of centers between 2010 and 2023. The patients had a mean age of 66.2; 69.6% were female and 75.7% were White.

All patients had an active prescription for an anticoagulant or antiplatelet medication up to 10 days prior to their thyroid nodule FNA biopsy. Specifically, 73.7% were on 81 mg aspirin, 8.5% were on 325 mg aspirin, 7.4% were taking other antiplatelet medication such as clopidogrel or ticagrelor; 7.0% were on warfarin, 8.2% were on a direct oral anticoagulant (DOAC); 6.3% were on heparin products; and 10.3% of patients were on two or more blood-thinning medications.

The results show that, overall, 13.0% (n =  614) of the thyroid nodule FNA biopsies had nondiagnostic results, which is within the average rates in the literature ranging from 6% to 36%, Dr. Lundholm noted.

Blood-thinning medications were held in 20.8% of the FNA biopsies, however, there were no differences in nondiagnostic results between those who had drugs held (12.2%) or who continued on the medications (13.2%; P  = .41).

After multivariate adjustment for age and sex, the lack of significant differences in receiving nondiagnostic results among those who did or did not continue blood thinners was consistent overall (odds ratio, 1.10; P = .38), and in the specific groups of 81 mg aspirin (OR, 1.00; P = .99); 325 mg aspirin or clopidogrel/ticagrelor (OR, 1.50; P = .15); or warfarin, DOAC, or heparin/enoxaparin (OR, 1.27; P = .27).

In terms of hematoma risk, ED records within 48 hours of the FNA showed that such events were rare, with only one hematoma occurring overall, involving a patient who was on 81 mg of aspirin for secondary stroke prevention that was not interrupted for FNA biopsy. The patient was discharged and did not require medical intervention.  

Four other hematomas occurred among patients who were not being treated with blood thinners, with none requiring intervention.

The findings indicate that “hematoma can happen in any patient, but rarely requires intervention,” Dr. Lundholm said.

However, while thrombotic events were also rare, serious events occurred in three patients within 48 hours of the thyroid nodule FNA biopsy when a blood thinner was withheld, including ischemic strokes among two patients who were on a DOAC and 81 mg of aspirin that were withheld, and one MI occurring in a patient on a DOAC that was held for the FNA.

Unlike hematomas, the thrombotic events each had significant long‐term sequelae, Dr. Lundholm noted.

“Having these ischemic strokes and heart attack really led to a change in these patients’ lives,” she said. “While we can never assume that [the events occurred] because the blood-thinner therapy was held, the timing within 48 hours is certainly very suspicious.”

There were no deep vein thrombosis or pulmonary embolism events.
 

Withholding practices vary

In a previous survey of 60 clinicians conducted by Dr. Lundholm and colleagues, wide variation was reported in the rates of withholding antiplatelet or anticoagulant medications prior to thyroid nodule FNA biopsy.

The survey of endocrinologists, interventional radiologists, and ear, nose, and throat providers showed rates of withholding 81 mg of aspirin prior to FNA biopsy of just 13.3%, withholding 325 mg of aspirin, 15%, other antiplatelets, 41.7%, warfarin, 73.3%, DOACs, 43.3%, and heparin, 43.3%.

“We found heterogeneity in withholding patterns even within the same department,” she said. “This is reflective of the fact that evidence is mixed.”

Guidelines on the issue from the Society of Interventional Radiology and the International Society on Thrombosis and Hemostasis recommend that providers consider the balance of the procedure and patient bleeding risk versus the clotting risk, Dr. Lundholm noted.

However, a caveat is that those recommendations are based on pooled data from similar minimal risk procedures, she explained.

“There is a lack of data on bleeding risks for individual interventions like thyroid biopsy, and, as such, there is no specific procedure-related risk determination.”

Meanwhile, Dr. Lundholm said that notable limitations regarding the current research include that the study may not have caught all patient cases that presented with complications to an outside ED.

Furthermore, the study results pertain to the safety of blood thinners in routine use, with key aspects that can influence complication rates, such as provider experience, needle size, and nodule features unavailable for analysis.
 

At MD Anderson, case-by-case

Commenting on the research, Anastasios Maniakas, MD, PhD, of the department of head and neck surgery, division of surgery, University of Texas MD Anderson Cancer Center, Houston, said the study is important, noting that, at his institution, the approach regarding holding blood-thinning medications is generally determined on an individual basis.

“I think this was a good study, but I don’t think it’s practice changing because these decisions may differ on a case-by-case basis,” Dr. Maniakas, who comoderated the session, said in an interview.

“At MD Anderson, we probably have one of the highest volumes in the country for thyroid nodule FNAs, and we do hold blood thinners because we often have to do more significant biopsies, with multiple passages and larger needles to be used,” Dr. Maniakas said.

“If you’re going to use perhaps the smallest possible gauge needle, then I think it is reasonable to not hold blood thinners, but if you’re going to be doing multiple passages and you need to do a core biopsy and use a large needle, then it is wiser to try to hold the medications for a day or 2.

“We haven’t had any complications, but I think there’s still a lot of apprehension to not hold blood thinners,” Dr. Maniakas said. “So, overall, I think the message is that it has to be on a case-by-case basis.”

Dr. Lundholm and Dr. Maniakas reported no relevant financial relationships.

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

WASHINGTON – The routine practice of holding use of blood-thinning medications at the time of an ultrasound-guided thyroid nodule fine needle aspiration (FNA) biopsy shows no significant safety benefit in preventing the risk of complications such as hematomas or nondiagnostic results; however, experts suggest using individualized decision-making with the practice.

“Our data indicates that there is no need to routinely hold anticoagulation or antiplatelet therapy prior to thyroid nodule FNA biopsy,” first author Michelle Lundholm, MD, of the Cleveland Clinic said in an interview.

“[The practice] impacts neither the safety of the FNA procedure nor the adequacy of the sample,” she said.

The late-breaking research was presented at the annual meeting of the American Thyroid Association.

Key concerns in the use of anticoagulants and/or antiplatelet medications during thyroid nodule FNA biopsy include the increased risk of postprocedural hematoma or nondiagnostic results, with, for instance, one study showing higher rates of nondiagnostic results among patients remaining on aspirin therapy during the FNA biopsy.

However, holding the medically indicated therapies can have risks of its own, including concerns of thrombotic events such as deep vein thrombosis or stroke. However, evidence comparing the risks with each strategy in thyroid nodule FNA is lacking.

To investigate, Dr. Lundholm and colleagues conducted a review of data on 2,945 patients who had undergone a total of 4,741 thyroid nodule FNAs in the Cleveland Clinic’s diverse network of centers between 2010 and 2023. The patients had a mean age of 66.2; 69.6% were female and 75.7% were White.

All patients had an active prescription for an anticoagulant or antiplatelet medication up to 10 days prior to their thyroid nodule FNA biopsy. Specifically, 73.7% were on 81 mg aspirin, 8.5% were on 325 mg aspirin, 7.4% were taking other antiplatelet medication such as clopidogrel or ticagrelor; 7.0% were on warfarin, 8.2% were on a direct oral anticoagulant (DOAC); 6.3% were on heparin products; and 10.3% of patients were on two or more blood-thinning medications.

The results show that, overall, 13.0% (n =  614) of the thyroid nodule FNA biopsies had nondiagnostic results, which is within the average rates in the literature ranging from 6% to 36%, Dr. Lundholm noted.

Blood-thinning medications were held in 20.8% of the FNA biopsies, however, there were no differences in nondiagnostic results between those who had drugs held (12.2%) or who continued on the medications (13.2%; P  = .41).

After multivariate adjustment for age and sex, the lack of significant differences in receiving nondiagnostic results among those who did or did not continue blood thinners was consistent overall (odds ratio, 1.10; P = .38), and in the specific groups of 81 mg aspirin (OR, 1.00; P = .99); 325 mg aspirin or clopidogrel/ticagrelor (OR, 1.50; P = .15); or warfarin, DOAC, or heparin/enoxaparin (OR, 1.27; P = .27).

In terms of hematoma risk, ED records within 48 hours of the FNA showed that such events were rare, with only one hematoma occurring overall, involving a patient who was on 81 mg of aspirin for secondary stroke prevention that was not interrupted for FNA biopsy. The patient was discharged and did not require medical intervention.  

Four other hematomas occurred among patients who were not being treated with blood thinners, with none requiring intervention.

The findings indicate that “hematoma can happen in any patient, but rarely requires intervention,” Dr. Lundholm said.

However, while thrombotic events were also rare, serious events occurred in three patients within 48 hours of the thyroid nodule FNA biopsy when a blood thinner was withheld, including ischemic strokes among two patients who were on a DOAC and 81 mg of aspirin that were withheld, and one MI occurring in a patient on a DOAC that was held for the FNA.

Unlike hematomas, the thrombotic events each had significant long‐term sequelae, Dr. Lundholm noted.

“Having these ischemic strokes and heart attack really led to a change in these patients’ lives,” she said. “While we can never assume that [the events occurred] because the blood-thinner therapy was held, the timing within 48 hours is certainly very suspicious.”

There were no deep vein thrombosis or pulmonary embolism events.
 

Withholding practices vary

In a previous survey of 60 clinicians conducted by Dr. Lundholm and colleagues, wide variation was reported in the rates of withholding antiplatelet or anticoagulant medications prior to thyroid nodule FNA biopsy.

The survey of endocrinologists, interventional radiologists, and ear, nose, and throat providers showed rates of withholding 81 mg of aspirin prior to FNA biopsy of just 13.3%, withholding 325 mg of aspirin, 15%, other antiplatelets, 41.7%, warfarin, 73.3%, DOACs, 43.3%, and heparin, 43.3%.

“We found heterogeneity in withholding patterns even within the same department,” she said. “This is reflective of the fact that evidence is mixed.”

Guidelines on the issue from the Society of Interventional Radiology and the International Society on Thrombosis and Hemostasis recommend that providers consider the balance of the procedure and patient bleeding risk versus the clotting risk, Dr. Lundholm noted.

However, a caveat is that those recommendations are based on pooled data from similar minimal risk procedures, she explained.

“There is a lack of data on bleeding risks for individual interventions like thyroid biopsy, and, as such, there is no specific procedure-related risk determination.”

Meanwhile, Dr. Lundholm said that notable limitations regarding the current research include that the study may not have caught all patient cases that presented with complications to an outside ED.

Furthermore, the study results pertain to the safety of blood thinners in routine use, with key aspects that can influence complication rates, such as provider experience, needle size, and nodule features unavailable for analysis.
 

At MD Anderson, case-by-case

Commenting on the research, Anastasios Maniakas, MD, PhD, of the department of head and neck surgery, division of surgery, University of Texas MD Anderson Cancer Center, Houston, said the study is important, noting that, at his institution, the approach regarding holding blood-thinning medications is generally determined on an individual basis.

“I think this was a good study, but I don’t think it’s practice changing because these decisions may differ on a case-by-case basis,” Dr. Maniakas, who comoderated the session, said in an interview.

“At MD Anderson, we probably have one of the highest volumes in the country for thyroid nodule FNAs, and we do hold blood thinners because we often have to do more significant biopsies, with multiple passages and larger needles to be used,” Dr. Maniakas said.

“If you’re going to use perhaps the smallest possible gauge needle, then I think it is reasonable to not hold blood thinners, but if you’re going to be doing multiple passages and you need to do a core biopsy and use a large needle, then it is wiser to try to hold the medications for a day or 2.

“We haven’t had any complications, but I think there’s still a lot of apprehension to not hold blood thinners,” Dr. Maniakas said. “So, overall, I think the message is that it has to be on a case-by-case basis.”

Dr. Lundholm and Dr. Maniakas reported no relevant financial relationships.

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

Postoperative parathyroid hormone (PTH) showed 100% sensitivity in predicting postthyroidectomy hypocalcemia, according to the results of a prospective study of 60 patients.

Postthyroidectomy hypocalcemia remains a major complication in patients who have undergone total thyroidectomy, and early identification can reduce disease burden and improve outcomes, according to Ahmed Sobhy Youssef, MD, of the University of Oklahoma Health Sciences Center, Oklahoma City, and colleagues.

In a presentation at the annual meeting of the American Academy of Otolaryngology-Head and Neck Surgery, Dr. Youssef presented results of the study, which looked at early postoperative parathyroid hormone as a predictor of postthyroidectomy hypocalcemia.

During his fellowship in Oklahoma in the wake of the COVID-19 pandemic, Dr. Youssef observed a wide variation in follow-up for calcium levels after thyroidectomy. “Some surgeons will order PTH and ionized calcium 4 hours after surgery, others would order later, at 6-8 hours,” he said in an interview. However, “all patients would be admitted for 1-2 nights [before being] discharged home, which meant more restrictions on the number of beds allowed for our head and neck cancer service.”

Discussion with his department chair led to a literature review seeking strategies to discharge patients earlier, and Dr. Youssef developed the idea for early PTH testing.

The study population included 60 adults who underwent thyroidectomy for benign or malignant disease at a single center between January 2022 and January 2023. The researchers measured PTH at 1 hour after surgery and compared it to results of a standard postoperative measure at 4 hours after surgery.

The researchers found a significant positive correlation between PTH measured 1 hour after surgery and ionized calcium (Ca) at 4 hours. The sensitivity of the early PTH assay, defined as “measured below 14 pg/ml,” was 100% to detect hypocalcemia, with an area under the curve of 0.797.

“The results were amazing,” said Dr. Youssef. “We found that when we measure PTH as early as 1 hour after total thyroidectomy, while patients are still in recovery, PTH was very sensitive to predict hypocalcemia.” The correlation was strong with measures at 4 hours.

“Our takeaway message is the 1-hour level PTH is very reliable in predicting hypocalcemia,” he added. This measure can serve as a guide for discharging patients the same day, with instructions to return if they develop any symptoms of hypocalcemia.

The use of early PTH also helped to reduce hospital admissions and identified patients who were eligible for same-day discharge with no need for additional replacement medications, Dr. Youssef said.

So far, “we have had no readmissions for thyroidectomy patients since we started to follow this protocol at our institution,” he noted.

The findings were limited by the relatively small sample size, and more research is needed. However, the results suggest that early measurement of PTH at 1 hour after surgery is an accurate predictor of hypocalcemia in total thyroidectomy patients.

“I strongly recommend high thyroidectomy volume institutions apply the same protocol and publish their data about that so we can come up with a consensus/guideline for management of calcium following thyroidectomy,” Dr. Youssef said.
 

More proof of PTH’s predictive power

“The utility of postoperative PTH for predicting symptomatic hypocalcemia is beneficial for guiding postoperative management of patients following total thyroidectomy,” said Larissa Sweeny, MD, of the University of Miami, who served as a moderator for the session in which the study was presented.

“Proper identification of patients that require supplemental medications following surgery reduces administration of medications to patients that do not require supplemental medications,” Dr. Sweeny said in an interview.

In addition, better identification not only ensures that the patients who do require supplemental medications receive them but also reduces postoperative complications and readmissions, she said.

For clinical practice, the current study “reinforces the utility of postoperative PTH lab values for guiding medication administration following total thyroidectomy,” said Dr. Sweeny. “I have been using postoperative PTH lab values following total thyroidectomy to guide my postoperative management of these patients for over 6 years.” 

However, looking ahead to additional research, “Correlation with dosage of supplemental calcium and duration to return of normal PTH would be helpful information,” Dr. Sweeny said.

The study received no outside funding. The researchers and Dr. Sweeny report no relevant financial relationships. 

A version of this article appeared on Medscape.com.

Postoperative parathyroid hormone (PTH) showed 100% sensitivity in predicting postthyroidectomy hypocalcemia, according to the results of a prospective study of 60 patients.

Postthyroidectomy hypocalcemia remains a major complication in patients who have undergone total thyroidectomy, and early identification can reduce disease burden and improve outcomes, according to Ahmed Sobhy Youssef, MD, of the University of Oklahoma Health Sciences Center, Oklahoma City, and colleagues.

In a presentation at the annual meeting of the American Academy of Otolaryngology-Head and Neck Surgery, Dr. Youssef presented results of the study, which looked at early postoperative parathyroid hormone as a predictor of postthyroidectomy hypocalcemia.

During his fellowship in Oklahoma in the wake of the COVID-19 pandemic, Dr. Youssef observed a wide variation in follow-up for calcium levels after thyroidectomy. “Some surgeons will order PTH and ionized calcium 4 hours after surgery, others would order later, at 6-8 hours,” he said in an interview. However, “all patients would be admitted for 1-2 nights [before being] discharged home, which meant more restrictions on the number of beds allowed for our head and neck cancer service.”

Discussion with his department chair led to a literature review seeking strategies to discharge patients earlier, and Dr. Youssef developed the idea for early PTH testing.

The study population included 60 adults who underwent thyroidectomy for benign or malignant disease at a single center between January 2022 and January 2023. The researchers measured PTH at 1 hour after surgery and compared it to results of a standard postoperative measure at 4 hours after surgery.

The researchers found a significant positive correlation between PTH measured 1 hour after surgery and ionized calcium (Ca) at 4 hours. The sensitivity of the early PTH assay, defined as “measured below 14 pg/ml,” was 100% to detect hypocalcemia, with an area under the curve of 0.797.

“The results were amazing,” said Dr. Youssef. “We found that when we measure PTH as early as 1 hour after total thyroidectomy, while patients are still in recovery, PTH was very sensitive to predict hypocalcemia.” The correlation was strong with measures at 4 hours.

“Our takeaway message is the 1-hour level PTH is very reliable in predicting hypocalcemia,” he added. This measure can serve as a guide for discharging patients the same day, with instructions to return if they develop any symptoms of hypocalcemia.

The use of early PTH also helped to reduce hospital admissions and identified patients who were eligible for same-day discharge with no need for additional replacement medications, Dr. Youssef said.

So far, “we have had no readmissions for thyroidectomy patients since we started to follow this protocol at our institution,” he noted.

The findings were limited by the relatively small sample size, and more research is needed. However, the results suggest that early measurement of PTH at 1 hour after surgery is an accurate predictor of hypocalcemia in total thyroidectomy patients.

“I strongly recommend high thyroidectomy volume institutions apply the same protocol and publish their data about that so we can come up with a consensus/guideline for management of calcium following thyroidectomy,” Dr. Youssef said.
 

More proof of PTH’s predictive power

“The utility of postoperative PTH for predicting symptomatic hypocalcemia is beneficial for guiding postoperative management of patients following total thyroidectomy,” said Larissa Sweeny, MD, of the University of Miami, who served as a moderator for the session in which the study was presented.

“Proper identification of patients that require supplemental medications following surgery reduces administration of medications to patients that do not require supplemental medications,” Dr. Sweeny said in an interview.

In addition, better identification not only ensures that the patients who do require supplemental medications receive them but also reduces postoperative complications and readmissions, she said.

For clinical practice, the current study “reinforces the utility of postoperative PTH lab values for guiding medication administration following total thyroidectomy,” said Dr. Sweeny. “I have been using postoperative PTH lab values following total thyroidectomy to guide my postoperative management of these patients for over 6 years.” 

However, looking ahead to additional research, “Correlation with dosage of supplemental calcium and duration to return of normal PTH would be helpful information,” Dr. Sweeny said.

The study received no outside funding. The researchers and Dr. Sweeny report no relevant financial relationships. 

A version of this article appeared on Medscape.com.

Postoperative parathyroid hormone (PTH) showed 100% sensitivity in predicting postthyroidectomy hypocalcemia, according to the results of a prospective study of 60 patients.

Postthyroidectomy hypocalcemia remains a major complication in patients who have undergone total thyroidectomy, and early identification can reduce disease burden and improve outcomes, according to Ahmed Sobhy Youssef, MD, of the University of Oklahoma Health Sciences Center, Oklahoma City, and colleagues.

In a presentation at the annual meeting of the American Academy of Otolaryngology-Head and Neck Surgery, Dr. Youssef presented results of the study, which looked at early postoperative parathyroid hormone as a predictor of postthyroidectomy hypocalcemia.

During his fellowship in Oklahoma in the wake of the COVID-19 pandemic, Dr. Youssef observed a wide variation in follow-up for calcium levels after thyroidectomy. “Some surgeons will order PTH and ionized calcium 4 hours after surgery, others would order later, at 6-8 hours,” he said in an interview. However, “all patients would be admitted for 1-2 nights [before being] discharged home, which meant more restrictions on the number of beds allowed for our head and neck cancer service.”

Discussion with his department chair led to a literature review seeking strategies to discharge patients earlier, and Dr. Youssef developed the idea for early PTH testing.

The study population included 60 adults who underwent thyroidectomy for benign or malignant disease at a single center between January 2022 and January 2023. The researchers measured PTH at 1 hour after surgery and compared it to results of a standard postoperative measure at 4 hours after surgery.

The researchers found a significant positive correlation between PTH measured 1 hour after surgery and ionized calcium (Ca) at 4 hours. The sensitivity of the early PTH assay, defined as “measured below 14 pg/ml,” was 100% to detect hypocalcemia, with an area under the curve of 0.797.

“The results were amazing,” said Dr. Youssef. “We found that when we measure PTH as early as 1 hour after total thyroidectomy, while patients are still in recovery, PTH was very sensitive to predict hypocalcemia.” The correlation was strong with measures at 4 hours.

“Our takeaway message is the 1-hour level PTH is very reliable in predicting hypocalcemia,” he added. This measure can serve as a guide for discharging patients the same day, with instructions to return if they develop any symptoms of hypocalcemia.

The use of early PTH also helped to reduce hospital admissions and identified patients who were eligible for same-day discharge with no need for additional replacement medications, Dr. Youssef said.

So far, “we have had no readmissions for thyroidectomy patients since we started to follow this protocol at our institution,” he noted.

The findings were limited by the relatively small sample size, and more research is needed. However, the results suggest that early measurement of PTH at 1 hour after surgery is an accurate predictor of hypocalcemia in total thyroidectomy patients.

“I strongly recommend high thyroidectomy volume institutions apply the same protocol and publish their data about that so we can come up with a consensus/guideline for management of calcium following thyroidectomy,” Dr. Youssef said.
 

More proof of PTH’s predictive power

“The utility of postoperative PTH for predicting symptomatic hypocalcemia is beneficial for guiding postoperative management of patients following total thyroidectomy,” said Larissa Sweeny, MD, of the University of Miami, who served as a moderator for the session in which the study was presented.

“Proper identification of patients that require supplemental medications following surgery reduces administration of medications to patients that do not require supplemental medications,” Dr. Sweeny said in an interview.

In addition, better identification not only ensures that the patients who do require supplemental medications receive them but also reduces postoperative complications and readmissions, she said.

For clinical practice, the current study “reinforces the utility of postoperative PTH lab values for guiding medication administration following total thyroidectomy,” said Dr. Sweeny. “I have been using postoperative PTH lab values following total thyroidectomy to guide my postoperative management of these patients for over 6 years.” 

However, looking ahead to additional research, “Correlation with dosage of supplemental calcium and duration to return of normal PTH would be helpful information,” Dr. Sweeny said.

The study received no outside funding. The researchers and Dr. Sweeny report no relevant financial relationships. 

A version of this article appeared on Medscape.com.

WASHINGTON – Adding the PD-1 inhibitor pembrolizumab to the established combination of dabrafenib and trametinib (DT) significantly improves survival outcomes in BRAF V600E-mutated anaplastic thyroid cancer - particularly when administered in a neoadjuvant fashion, prior to surgery. Overall survival rates in the study exceeded 5 years.

“The very long median overall survival in the study’s neoadjuvant group is quite remarkable for a group of patients who used to have a very poor prognosis,” senior author Maria E. Cabanillas, MD, associate professor in the department of endocrine neoplasia and hormonal disorders at the University of Texas MD Anderson Cancer Center in Houston, said in an interview.

“This median overall survival definitely exceeds any other treatments thus far in BRAF-mutated anaplastic thyroid cancer.”

The research was presented at the annual meeting of the American Thyroid Association.

Anaplastic thyroid cancer, though rare, is the most aggressive form of thyroid cancer. It accounts for just 1% of the cancers but causes about 50% of thyroid cancer mortality.

The historical median overall survival is 5-6 months.

With research in recent years showing that as many as 40% of anaplastic thyroid cancers harbor BRAF V600E mutations, the door has opened for potential benefits with the combination of the BRAF inhibitor dabrafenib with the MEK-inhibitor drug trametinib.

The treatment combination was shown in research that included the phase 2 ROAR trial to yield important responses. It was approved by the Food and Drug Administration in 2018 for locally advanced or metastatic BRAF V600E-mutant anaplastic thyroid cancer, as well as other cancers.

However, a key caveat of DT is that patients eventually develop resistance mutations, leading to disease progression.

To overcome the problem, Dr. Cabanillas and her team found two key strategies that show promise – the addition of immunotherapy, such as pembrolizumab to DT, and the use of a neoadjuvant approach, with surgery performed after an initial response to the triplet therapy.
 

Triple therapy showed highly favorable results

In a study presented at the 2022 ATA annual meeting, researchers reported on the triple therapy of BRAF/MEK inhibitors vemurafenib and cobimetinib plus immunotherapy with atezolizumab. Results were highly favorable, with an overall response rate of 72% and an impressive 2-year survival of 67%.

However, a major limitation was that the study lacked a control arm. In the current study, the addition of pembrolizumab to DT was compared with DT alone. The investigators also sought to determine the survival benefits of a neoadjuvant strategy.

For the study, first author Sarah Hamidi, MD, also of the MD Anderson Cancer Center, and her colleagues identified 94 patients with BRAF-mutated anaplastic thyroid cancer who were treated either with first‐line DT or DT plus pembrolizumab between 2014 and 2023, either outside of a trial or in a reported clinical trial.

The study compared three treatment regimens – DT alone (n = 23), DT with pembrolizumab added before or after disease progression (n = 48), and DT with neoadjuvant pembrolizumab added prior to or after surgery (n = 23).

There were no significant differences in baseline characteristics between the groups. Metastatic disease was present at the start of treatment among 87.0% of the DT group, 79.2% of the pembrolizumab group prior to or after disease progression, and 65.2% of the neoadjuvant pembrolizumab group.

The median follow-up of the three groups was 102 months, 28 months, and 42 months, respectively. The median overall survival was 9 months with DT alone, vs. 17 months with DT plus pembrolizumab before or after progression and 63 months with neoadjuvant pembrolizumab plus DT (P < .001).

The 12- and 24-month survival rates with DT alone were 33.7% and 28.9%, respectively; for DT plus pembrolizumab before or after progression, the rates were 60.2% and 36.5%; and for neoadjuvant pembrolizumab plus DT, the rates were 80.7% and 74.5%.

In an analysis that did not include the neoadjuvant group, median progression-free survival was significantly longer with DT plus pembrolizumab as an initial treatment (11.0 months) compared with DT alone (4.0 months; P  =  .049).

A subanalysis that evaluated the timing of the addition of pembrolizumab to DT before or after disease progression showed no significant differences between the two in median overall survival (17 months vs. 16 months; P = .554).

“This is valuable information, especially for centers where pembrolizumab cannot be easily obtained as a first-line therapy for anaplastic thyroid cancer,” Dr. Hamidi said in presenting the findings.

She noted, however, that the results should be interpreted with caution, given the small number of patients who received pembrolizumab before progression (n = 34) and especially after progression (n = 14).

In terms of safety, there were no grade 5 adverse events (AEs); 32.4% of patients experienced immune‐related AEs, most frequently, colitis and hepatitis.
 

Therapies “improve survival”

Overall, the results are important, Dr. Cabanillas said.

The results are “very exciting when you think about the fact that 10 years ago, patients with anaplastic thyroid cancer had a median overall survival measured in months, and now we see that those with a BRAF mutation have a real chance at survival when managed appropriately from the start,” she told this news organization.

She noted that a key caveat is the study’s retrospective nature. Other important considerations are that pembrolizumab adds toxicity as well as cost, and it is largely used off label in anaplastic thyroid cancer.

Nevertheless, “it does feel like there needs to be a call to action in the guidelines for this disease so that it includes neoadjuvant DT or DT plus pembrolizumab as the primary treatment of patients with BRAF-mutated anaplastic thyroid cancer because the initial treatment is critical here,” Dr. Cabanillas said.

She added that a phase 2 trial with neoadjuvant DT plus pembrolizumab is ongoing. Enrollment is expected to be completed soon.

Commenting on the findings, Sarimar Agosto Salgado, MD, of the department of head and neck – endocrine oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Fla., who was a comoderator of the session, said the results are encouraging.

“These findings are promising because they open the landscape of options of therapies that we can provide these patients,” she said in an interview.

“Anaplastic thyroid cancer has been a disease with a very short survival despite aggressive therapies, but we are seeing that not only have these therapies been able to improve survival but also patients’ quality of life.”

Particularly encouraging is how quickly the therapies can work, Dr. Salgado added.

“Many times when patients present to the clinic, the rapid response to these systemic therapies can even [allow them to avoid] having a tracheostomy, and we’re also seeing that some of these patients are able to go from unresectable disease to resectable disease, and then by having the main tumor out, their survival improves.

“So, this is definitely a big ray of hope for these patients.”

Dr. Cabanillas has received research funding from Merck. Dr. Hamidi has disclosed no relevant financial relationships. Dr. Salgado has relationships with Lilly and Exelixis.
 

A version of this article appeared on Medscape.com.

WASHINGTON – Adding the PD-1 inhibitor pembrolizumab to the established combination of dabrafenib and trametinib (DT) significantly improves survival outcomes in BRAF V600E-mutated anaplastic thyroid cancer - particularly when administered in a neoadjuvant fashion, prior to surgery. Overall survival rates in the study exceeded 5 years.

“The very long median overall survival in the study’s neoadjuvant group is quite remarkable for a group of patients who used to have a very poor prognosis,” senior author Maria E. Cabanillas, MD, associate professor in the department of endocrine neoplasia and hormonal disorders at the University of Texas MD Anderson Cancer Center in Houston, said in an interview.

“This median overall survival definitely exceeds any other treatments thus far in BRAF-mutated anaplastic thyroid cancer.”

The research was presented at the annual meeting of the American Thyroid Association.

Anaplastic thyroid cancer, though rare, is the most aggressive form of thyroid cancer. It accounts for just 1% of the cancers but causes about 50% of thyroid cancer mortality.

The historical median overall survival is 5-6 months.

With research in recent years showing that as many as 40% of anaplastic thyroid cancers harbor BRAF V600E mutations, the door has opened for potential benefits with the combination of the BRAF inhibitor dabrafenib with the MEK-inhibitor drug trametinib.

The treatment combination was shown in research that included the phase 2 ROAR trial to yield important responses. It was approved by the Food and Drug Administration in 2018 for locally advanced or metastatic BRAF V600E-mutant anaplastic thyroid cancer, as well as other cancers.

However, a key caveat of DT is that patients eventually develop resistance mutations, leading to disease progression.

To overcome the problem, Dr. Cabanillas and her team found two key strategies that show promise – the addition of immunotherapy, such as pembrolizumab to DT, and the use of a neoadjuvant approach, with surgery performed after an initial response to the triplet therapy.
 

Triple therapy showed highly favorable results

In a study presented at the 2022 ATA annual meeting, researchers reported on the triple therapy of BRAF/MEK inhibitors vemurafenib and cobimetinib plus immunotherapy with atezolizumab. Results were highly favorable, with an overall response rate of 72% and an impressive 2-year survival of 67%.

However, a major limitation was that the study lacked a control arm. In the current study, the addition of pembrolizumab to DT was compared with DT alone. The investigators also sought to determine the survival benefits of a neoadjuvant strategy.

For the study, first author Sarah Hamidi, MD, also of the MD Anderson Cancer Center, and her colleagues identified 94 patients with BRAF-mutated anaplastic thyroid cancer who were treated either with first‐line DT or DT plus pembrolizumab between 2014 and 2023, either outside of a trial or in a reported clinical trial.

The study compared three treatment regimens – DT alone (n = 23), DT with pembrolizumab added before or after disease progression (n = 48), and DT with neoadjuvant pembrolizumab added prior to or after surgery (n = 23).

There were no significant differences in baseline characteristics between the groups. Metastatic disease was present at the start of treatment among 87.0% of the DT group, 79.2% of the pembrolizumab group prior to or after disease progression, and 65.2% of the neoadjuvant pembrolizumab group.

The median follow-up of the three groups was 102 months, 28 months, and 42 months, respectively. The median overall survival was 9 months with DT alone, vs. 17 months with DT plus pembrolizumab before or after progression and 63 months with neoadjuvant pembrolizumab plus DT (P < .001).

The 12- and 24-month survival rates with DT alone were 33.7% and 28.9%, respectively; for DT plus pembrolizumab before or after progression, the rates were 60.2% and 36.5%; and for neoadjuvant pembrolizumab plus DT, the rates were 80.7% and 74.5%.

In an analysis that did not include the neoadjuvant group, median progression-free survival was significantly longer with DT plus pembrolizumab as an initial treatment (11.0 months) compared with DT alone (4.0 months; P  =  .049).

A subanalysis that evaluated the timing of the addition of pembrolizumab to DT before or after disease progression showed no significant differences between the two in median overall survival (17 months vs. 16 months; P = .554).

“This is valuable information, especially for centers where pembrolizumab cannot be easily obtained as a first-line therapy for anaplastic thyroid cancer,” Dr. Hamidi said in presenting the findings.

She noted, however, that the results should be interpreted with caution, given the small number of patients who received pembrolizumab before progression (n = 34) and especially after progression (n = 14).

In terms of safety, there were no grade 5 adverse events (AEs); 32.4% of patients experienced immune‐related AEs, most frequently, colitis and hepatitis.
 

Therapies “improve survival”

Overall, the results are important, Dr. Cabanillas said.

The results are “very exciting when you think about the fact that 10 years ago, patients with anaplastic thyroid cancer had a median overall survival measured in months, and now we see that those with a BRAF mutation have a real chance at survival when managed appropriately from the start,” she told this news organization.

She noted that a key caveat is the study’s retrospective nature. Other important considerations are that pembrolizumab adds toxicity as well as cost, and it is largely used off label in anaplastic thyroid cancer.

Nevertheless, “it does feel like there needs to be a call to action in the guidelines for this disease so that it includes neoadjuvant DT or DT plus pembrolizumab as the primary treatment of patients with BRAF-mutated anaplastic thyroid cancer because the initial treatment is critical here,” Dr. Cabanillas said.

She added that a phase 2 trial with neoadjuvant DT plus pembrolizumab is ongoing. Enrollment is expected to be completed soon.

Commenting on the findings, Sarimar Agosto Salgado, MD, of the department of head and neck – endocrine oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Fla., who was a comoderator of the session, said the results are encouraging.

“These findings are promising because they open the landscape of options of therapies that we can provide these patients,” she said in an interview.

“Anaplastic thyroid cancer has been a disease with a very short survival despite aggressive therapies, but we are seeing that not only have these therapies been able to improve survival but also patients’ quality of life.”

Particularly encouraging is how quickly the therapies can work, Dr. Salgado added.

“Many times when patients present to the clinic, the rapid response to these systemic therapies can even [allow them to avoid] having a tracheostomy, and we’re also seeing that some of these patients are able to go from unresectable disease to resectable disease, and then by having the main tumor out, their survival improves.

“So, this is definitely a big ray of hope for these patients.”

Dr. Cabanillas has received research funding from Merck. Dr. Hamidi has disclosed no relevant financial relationships. Dr. Salgado has relationships with Lilly and Exelixis.
 

A version of this article appeared on Medscape.com.

WASHINGTON – Adding the PD-1 inhibitor pembrolizumab to the established combination of dabrafenib and trametinib (DT) significantly improves survival outcomes in BRAF V600E-mutated anaplastic thyroid cancer - particularly when administered in a neoadjuvant fashion, prior to surgery. Overall survival rates in the study exceeded 5 years.

“The very long median overall survival in the study’s neoadjuvant group is quite remarkable for a group of patients who used to have a very poor prognosis,” senior author Maria E. Cabanillas, MD, associate professor in the department of endocrine neoplasia and hormonal disorders at the University of Texas MD Anderson Cancer Center in Houston, said in an interview.

“This median overall survival definitely exceeds any other treatments thus far in BRAF-mutated anaplastic thyroid cancer.”

The research was presented at the annual meeting of the American Thyroid Association.

Anaplastic thyroid cancer, though rare, is the most aggressive form of thyroid cancer. It accounts for just 1% of the cancers but causes about 50% of thyroid cancer mortality.

The historical median overall survival is 5-6 months.

With research in recent years showing that as many as 40% of anaplastic thyroid cancers harbor BRAF V600E mutations, the door has opened for potential benefits with the combination of the BRAF inhibitor dabrafenib with the MEK-inhibitor drug trametinib.

The treatment combination was shown in research that included the phase 2 ROAR trial to yield important responses. It was approved by the Food and Drug Administration in 2018 for locally advanced or metastatic BRAF V600E-mutant anaplastic thyroid cancer, as well as other cancers.

However, a key caveat of DT is that patients eventually develop resistance mutations, leading to disease progression.

To overcome the problem, Dr. Cabanillas and her team found two key strategies that show promise – the addition of immunotherapy, such as pembrolizumab to DT, and the use of a neoadjuvant approach, with surgery performed after an initial response to the triplet therapy.
 

Triple therapy showed highly favorable results

In a study presented at the 2022 ATA annual meeting, researchers reported on the triple therapy of BRAF/MEK inhibitors vemurafenib and cobimetinib plus immunotherapy with atezolizumab. Results were highly favorable, with an overall response rate of 72% and an impressive 2-year survival of 67%.

However, a major limitation was that the study lacked a control arm. In the current study, the addition of pembrolizumab to DT was compared with DT alone. The investigators also sought to determine the survival benefits of a neoadjuvant strategy.

For the study, first author Sarah Hamidi, MD, also of the MD Anderson Cancer Center, and her colleagues identified 94 patients with BRAF-mutated anaplastic thyroid cancer who were treated either with first‐line DT or DT plus pembrolizumab between 2014 and 2023, either outside of a trial or in a reported clinical trial.

The study compared three treatment regimens – DT alone (n = 23), DT with pembrolizumab added before or after disease progression (n = 48), and DT with neoadjuvant pembrolizumab added prior to or after surgery (n = 23).

There were no significant differences in baseline characteristics between the groups. Metastatic disease was present at the start of treatment among 87.0% of the DT group, 79.2% of the pembrolizumab group prior to or after disease progression, and 65.2% of the neoadjuvant pembrolizumab group.

The median follow-up of the three groups was 102 months, 28 months, and 42 months, respectively. The median overall survival was 9 months with DT alone, vs. 17 months with DT plus pembrolizumab before or after progression and 63 months with neoadjuvant pembrolizumab plus DT (P < .001).

The 12- and 24-month survival rates with DT alone were 33.7% and 28.9%, respectively; for DT plus pembrolizumab before or after progression, the rates were 60.2% and 36.5%; and for neoadjuvant pembrolizumab plus DT, the rates were 80.7% and 74.5%.

In an analysis that did not include the neoadjuvant group, median progression-free survival was significantly longer with DT plus pembrolizumab as an initial treatment (11.0 months) compared with DT alone (4.0 months; P  =  .049).

A subanalysis that evaluated the timing of the addition of pembrolizumab to DT before or after disease progression showed no significant differences between the two in median overall survival (17 months vs. 16 months; P = .554).

“This is valuable information, especially for centers where pembrolizumab cannot be easily obtained as a first-line therapy for anaplastic thyroid cancer,” Dr. Hamidi said in presenting the findings.

She noted, however, that the results should be interpreted with caution, given the small number of patients who received pembrolizumab before progression (n = 34) and especially after progression (n = 14).

In terms of safety, there were no grade 5 adverse events (AEs); 32.4% of patients experienced immune‐related AEs, most frequently, colitis and hepatitis.
 

Therapies “improve survival”

Overall, the results are important, Dr. Cabanillas said.

The results are “very exciting when you think about the fact that 10 years ago, patients with anaplastic thyroid cancer had a median overall survival measured in months, and now we see that those with a BRAF mutation have a real chance at survival when managed appropriately from the start,” she told this news organization.

She noted that a key caveat is the study’s retrospective nature. Other important considerations are that pembrolizumab adds toxicity as well as cost, and it is largely used off label in anaplastic thyroid cancer.

Nevertheless, “it does feel like there needs to be a call to action in the guidelines for this disease so that it includes neoadjuvant DT or DT plus pembrolizumab as the primary treatment of patients with BRAF-mutated anaplastic thyroid cancer because the initial treatment is critical here,” Dr. Cabanillas said.

She added that a phase 2 trial with neoadjuvant DT plus pembrolizumab is ongoing. Enrollment is expected to be completed soon.

Commenting on the findings, Sarimar Agosto Salgado, MD, of the department of head and neck – endocrine oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Fla., who was a comoderator of the session, said the results are encouraging.

“These findings are promising because they open the landscape of options of therapies that we can provide these patients,” she said in an interview.

“Anaplastic thyroid cancer has been a disease with a very short survival despite aggressive therapies, but we are seeing that not only have these therapies been able to improve survival but also patients’ quality of life.”

Particularly encouraging is how quickly the therapies can work, Dr. Salgado added.

“Many times when patients present to the clinic, the rapid response to these systemic therapies can even [allow them to avoid] having a tracheostomy, and we’re also seeing that some of these patients are able to go from unresectable disease to resectable disease, and then by having the main tumor out, their survival improves.

“So, this is definitely a big ray of hope for these patients.”

Dr. Cabanillas has received research funding from Merck. Dr. Hamidi has disclosed no relevant financial relationships. Dr. Salgado has relationships with Lilly and Exelixis.
 

A version of this article appeared on Medscape.com.

While artificial intelligence (AI) appears to be on its way to transforming all fields of medicine, its potential benefits in endocrinology, with its substantial complexity, may be uniquely important. However, hurdles encountered with the latest AI iterations of chatbots underscore the need to proceed with caution.

“In contrast to other medical fields, endocrinology is not connected to a single organ structure; rather, it is a complicated biological system of hormones and metabolites, [intertwined with] various receptors, signaling pathways and intricate feedback mechanisms,” explained the authors of a recent article on the issue in Nature Reviews Endocrinology.

With interconnections that are “often beyond the comprehension and reasoning capabilities of the human brain, AI [is anticipated] to be exceptionally well-suited to tackle this remarkable heterogeneity and complexity,” they wrote.

Since the first regulatory approvals for AI-based technology were granted back in 2015, endocrinology has already been revolutionized by AI-based tools, most notably with AI biosensors for continuous glucose monitoring systems alerting patients of glucose levels, and automated insulin-delivery systems.

AI-based machine learning has also ushered in improved detection and analysis of thyroid nodules and potential malignancies, with algorithms in the analysis of radiological test images enabling detection through a deeper analysis than can be applied with individual specialists.

Likewise, the benefits of AI in imaging extend to osteoporosis.

“Imaging certainly is one of the most promising fields, including (but not limited to) conventional radiography, computed tomography, and magnetic resonance tomography,” explained Hans Peter Dimai, MD, a professor of medicine and endocrinology at the Medical University of Graz (Austria), and the past president of the Austrian Bone and Mineral Society.

“A typical indication is fracture detection, not in terms of replacing expert radiologists or orthopedists but rather in terms of supporting those who are in specialist training,” he said in an interview.

“Particularly the underdiagnosis of vertebral fractures has been an issue in past decades, with dramatic implications for the individual, since the first vertebral fracture would multiply the risk for any future fracture, and therefore requires immediate action from a physician’s side.”

The areas expected to further benefit from AI continue to grow as systems evolve, with advances being reported across a variety of endocrinologic conditions.

Papillary thyroid cancer (PTC): Central lymph node metastasis of papillary thyroid cancer is predictive of tumor recurrence and overall survival in PTC. However, few tests are able to diagnose the metastasis in the cancer with high accuracy. Using a convolutional neural network prediction model built with a deep-learning algorithm, researchers described high diagnostic sensitivity and specificity of a model, as reported in a study published in Feburary. The prediction model, developed using genetic mutations and clinicopathologic factors, showed high prediction efficacy, with validation in subclinical as well as clinical metastasis groups, suggesting broad applicability.

Adrenal tumors: Adrenal incidentalomas, or masses that are incidentally discovered when performing abdominal imaging for other reasons, can be a perplexing clinical challenge. Discovery of these is increasing as imaging technology advances. However, an AI-based machine learning approach utilizing CT is being developed to differentiate between subclinical pheochromocytoma and lipid-poor adenomas. As reported in a 2022 study, the prediction model scoring system used traditional radiological features on CT images to provide for a noninvasive method in assisting in the diagnosis and providing personalized care for people with adrenal tumors.

Osteoporosis – bone mineral density (BMD): In the diagnosis of osteoporosis, the measurement of BMD using dual-energy x-ray absorptiometry (DXA) is the gold standard. However, the availability of DXA devices in many countries is inadequate, leaving an unmet need for alternative approaches. But one AI-based algorithm shows promising diagnostic accuracy, compared with DXA, potentially providing a low-cost screening alternative for the early diagnosis of osteoporosis.  

Osteoporosis – Fracture Risk Assessment Tool (FRAX): In fracture risk and prevention, the free FRAX tool, available online, is the gold standard and recommended in nearly all osteoporosis guidelines. However, several studies on AI-based tools show some benefit over FRAX, including one approach using longitudinal data with conventional spine radiographs, showing predictive accuracy that exceeds FRAX.  

Osteoporosis – treatment: And for the often challenging process of treatment decision-making in osteoporosis, AI-based software, developed from more than 15,000 osteoporosis patients followed over 10 years, shows high accuracy in the prediction of response to treatment in terms of BMD increase, as described in another study. “Our results show that it is feasible to use a combination of electronic medical records–derived information to develop a machine-learning algorithm to predict a BMD response following osteoporosis treatment,” the authors reported. “This alternative approach can aid physicians to select an optimal therapeutic regimen in order to maximize a patient-specific treatment outcome.”
 

Chatbot wrinkles

The prospects of large language models (LLMs) and ChatGPT unleash the potential to understand and generate text in a similar capacity as humans. Although controversial, they could likewise be compelling.

However, such systems can be vastly more complex than earlier AI-based tools, and some studies are illustrating the kinds of stumbling blocks that need to be overcome.

For instance, in a study published in May, researchers explored the potential of ChatGPT 4.0 to synthesize clinical guidelines for diabetic ketoacidosis from three different sources to reflect the latest evidence and local context.

Such efforts are important but can be very resource-intensive when conducted without the use of AI assistance.

The study’s results showed that, although ChatGPT was able to generate a comprehensive table comparing the guidelines, there were multiple recurrent errors in misreporting and nonreporting, as well as inconsistencies, “rendering the results unreliable,” the authors wrote.

“Although ChatGPT demonstrates the potential for the synthesis of clinical guidelines, the presence of multiple recurrent errors and inconsistencies underscores the need for expert human intervention and validation,” the authors concluded.

Likewise, other research using ChatGPT for use in vitreoretinal diseases, including diabetic retinopathy, further demonstrated disappointing results, with the technology showing the chatbot provided completely accurate responses to only 8 (15.4%) of 52 questions, with some responses containing inappropriate or potentially harmful medical advice.

“For example, in response to ‘How do you get rid of epiretinal membrane?’, the platform described vitrectomy but also included incorrect options of injection therapy and laser therapy,” the authors wrote.

“The study highlights the limitations of using ChatGPT for the adaptation of clinical guidelines without expert human intervention,” they concluded.

And in research published in August that looked at the ability of ChatGPT to interpret guidelines – in this case 26 diagnosis descriptions from the National Comprehensive Cancer Network – results showed that as many as one-third of treatments recommended by the chatbot were at least partially not concordant with information stated in the NCCN guidelines, with recommendations varying based on how the question about treatment was presented.

“Clinicians should advise patients that LLM chatbots are not a reliable source of treatment information,” the authors wrote.
 

Diversity concerns

Among the most prominent concerns about chatbot inaccuracy has been the known lack of racial and ethnic diversity in large databases utilized in developing AI systems, potentially resulting in critical flaws in the information the systems produce.

In an editorial published with the NCCN guideline study, Atul Butte, MD, PhD, from the University of California, San Francisco, noted that the shortcomings should be weighed with the potential benefits.

“There is no doubt that AI and LLMs are not yet perfect, and they carry biases that will need to be addressed,” Dr. Butte wrote. “These algorithms will need to be carefully monitored as they are brought into health systems, [but] this does not alter the potential of how they can improve care for both the haves and have-nots of health care.”

In a comment, Dr. Butte elaborated that, once the system flaws are refined, a key benefit will be the broader application of top standards of care to more patients who may have limited resources.

“It is a privilege to get the very best level of care from the very best centers, but that privilege is not distributable to all right now,” Dr. Butte said.

“The real potential of LLMs and AI will be their ability to be trained from the patient, clinical, and outcomes data from the very best centers, and then used to deliver the best care through digital tools to all patients, especially to those without access to the best care or [those with] limited resources,” he said.

Further commenting on the issue of potential bias with chatbots, Matthew Li, MD, from the University of Alberta, Edmonton, said that awareness of the nature of the problem and need for diversity in data for training and testing AI-systems issues appears to be improving.

“Thanks to much research on this topic in recent years, I think most AI researchers in medicine are at least aware of these challenges now, which was not the case only a few years ago,” he said in an interview.

Across specialties, “the careful deployment of AI tools accounting for issues regarding AI model generalization, biases, and performance drift will be critical for ensuring safe and fair patient care,” Dr. Li noted.

On a broader level is the ongoing general concern of the potential for over-reliance on the technology by clinicians. For example, a recent study showing radiologists across all experience levels reading mammograms were prone to automation bias when being supported by an AI-based system.

“Concerns regarding over-reliance on AI remain,” said Dr. Li, who coauthored a study published in June on the issue.

“Ongoing research into and monitoring of the impact of AI systems as they are developed and deployed will be important to ensure safe patient care moving forward,” he said.

Ultimately, the clinical benefit of AI systems to patients should be the bottom line, Dr. Dimai added.

“In my opinion, the clinical relevance, i.e., the benefit for patients and/or physicians of a to-be-developed AI tool, must be clearly proven before its development starts and first clinical studies are carried out,” he said.

“This is not always the case,” Dr. Dimai said. “In other words, innovation per se should not be the only rationale and driving force for the development of such tools.”

Dr. Li, an associate editor for the journal Radiology: Artificial Intelligence, reports no relevant financial relationships. Dr. Dimai is a member of the key medical advisor team of Image Biopsy Lab.

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

While artificial intelligence (AI) appears to be on its way to transforming all fields of medicine, its potential benefits in endocrinology, with its substantial complexity, may be uniquely important. However, hurdles encountered with the latest AI iterations of chatbots underscore the need to proceed with caution.

“In contrast to other medical fields, endocrinology is not connected to a single organ structure; rather, it is a complicated biological system of hormones and metabolites, [intertwined with] various receptors, signaling pathways and intricate feedback mechanisms,” explained the authors of a recent article on the issue in Nature Reviews Endocrinology.

With interconnections that are “often beyond the comprehension and reasoning capabilities of the human brain, AI [is anticipated] to be exceptionally well-suited to tackle this remarkable heterogeneity and complexity,” they wrote.

Since the first regulatory approvals for AI-based technology were granted back in 2015, endocrinology has already been revolutionized by AI-based tools, most notably with AI biosensors for continuous glucose monitoring systems alerting patients of glucose levels, and automated insulin-delivery systems.

AI-based machine learning has also ushered in improved detection and analysis of thyroid nodules and potential malignancies, with algorithms in the analysis of radiological test images enabling detection through a deeper analysis than can be applied with individual specialists.

Likewise, the benefits of AI in imaging extend to osteoporosis.

“Imaging certainly is one of the most promising fields, including (but not limited to) conventional radiography, computed tomography, and magnetic resonance tomography,” explained Hans Peter Dimai, MD, a professor of medicine and endocrinology at the Medical University of Graz (Austria), and the past president of the Austrian Bone and Mineral Society.

“A typical indication is fracture detection, not in terms of replacing expert radiologists or orthopedists but rather in terms of supporting those who are in specialist training,” he said in an interview.

“Particularly the underdiagnosis of vertebral fractures has been an issue in past decades, with dramatic implications for the individual, since the first vertebral fracture would multiply the risk for any future fracture, and therefore requires immediate action from a physician’s side.”

The areas expected to further benefit from AI continue to grow as systems evolve, with advances being reported across a variety of endocrinologic conditions.

Papillary thyroid cancer (PTC): Central lymph node metastasis of papillary thyroid cancer is predictive of tumor recurrence and overall survival in PTC. However, few tests are able to diagnose the metastasis in the cancer with high accuracy. Using a convolutional neural network prediction model built with a deep-learning algorithm, researchers described high diagnostic sensitivity and specificity of a model, as reported in a study published in Feburary. The prediction model, developed using genetic mutations and clinicopathologic factors, showed high prediction efficacy, with validation in subclinical as well as clinical metastasis groups, suggesting broad applicability.

Adrenal tumors: Adrenal incidentalomas, or masses that are incidentally discovered when performing abdominal imaging for other reasons, can be a perplexing clinical challenge. Discovery of these is increasing as imaging technology advances. However, an AI-based machine learning approach utilizing CT is being developed to differentiate between subclinical pheochromocytoma and lipid-poor adenomas. As reported in a 2022 study, the prediction model scoring system used traditional radiological features on CT images to provide for a noninvasive method in assisting in the diagnosis and providing personalized care for people with adrenal tumors.

Osteoporosis – bone mineral density (BMD): In the diagnosis of osteoporosis, the measurement of BMD using dual-energy x-ray absorptiometry (DXA) is the gold standard. However, the availability of DXA devices in many countries is inadequate, leaving an unmet need for alternative approaches. But one AI-based algorithm shows promising diagnostic accuracy, compared with DXA, potentially providing a low-cost screening alternative for the early diagnosis of osteoporosis.  

Osteoporosis – Fracture Risk Assessment Tool (FRAX): In fracture risk and prevention, the free FRAX tool, available online, is the gold standard and recommended in nearly all osteoporosis guidelines. However, several studies on AI-based tools show some benefit over FRAX, including one approach using longitudinal data with conventional spine radiographs, showing predictive accuracy that exceeds FRAX.  

Osteoporosis – treatment: And for the often challenging process of treatment decision-making in osteoporosis, AI-based software, developed from more than 15,000 osteoporosis patients followed over 10 years, shows high accuracy in the prediction of response to treatment in terms of BMD increase, as described in another study. “Our results show that it is feasible to use a combination of electronic medical records–derived information to develop a machine-learning algorithm to predict a BMD response following osteoporosis treatment,” the authors reported. “This alternative approach can aid physicians to select an optimal therapeutic regimen in order to maximize a patient-specific treatment outcome.”
 

Chatbot wrinkles

The prospects of large language models (LLMs) and ChatGPT unleash the potential to understand and generate text in a similar capacity as humans. Although controversial, they could likewise be compelling.

However, such systems can be vastly more complex than earlier AI-based tools, and some studies are illustrating the kinds of stumbling blocks that need to be overcome.

For instance, in a study published in May, researchers explored the potential of ChatGPT 4.0 to synthesize clinical guidelines for diabetic ketoacidosis from three different sources to reflect the latest evidence and local context.

Such efforts are important but can be very resource-intensive when conducted without the use of AI assistance.

The study’s results showed that, although ChatGPT was able to generate a comprehensive table comparing the guidelines, there were multiple recurrent errors in misreporting and nonreporting, as well as inconsistencies, “rendering the results unreliable,” the authors wrote.

“Although ChatGPT demonstrates the potential for the synthesis of clinical guidelines, the presence of multiple recurrent errors and inconsistencies underscores the need for expert human intervention and validation,” the authors concluded.

Likewise, other research using ChatGPT for use in vitreoretinal diseases, including diabetic retinopathy, further demonstrated disappointing results, with the technology showing the chatbot provided completely accurate responses to only 8 (15.4%) of 52 questions, with some responses containing inappropriate or potentially harmful medical advice.

“For example, in response to ‘How do you get rid of epiretinal membrane?’, the platform described vitrectomy but also included incorrect options of injection therapy and laser therapy,” the authors wrote.

“The study highlights the limitations of using ChatGPT for the adaptation of clinical guidelines without expert human intervention,” they concluded.

And in research published in August that looked at the ability of ChatGPT to interpret guidelines – in this case 26 diagnosis descriptions from the National Comprehensive Cancer Network – results showed that as many as one-third of treatments recommended by the chatbot were at least partially not concordant with information stated in the NCCN guidelines, with recommendations varying based on how the question about treatment was presented.

“Clinicians should advise patients that LLM chatbots are not a reliable source of treatment information,” the authors wrote.
 

Diversity concerns

Among the most prominent concerns about chatbot inaccuracy has been the known lack of racial and ethnic diversity in large databases utilized in developing AI systems, potentially resulting in critical flaws in the information the systems produce.

In an editorial published with the NCCN guideline study, Atul Butte, MD, PhD, from the University of California, San Francisco, noted that the shortcomings should be weighed with the potential benefits.

“There is no doubt that AI and LLMs are not yet perfect, and they carry biases that will need to be addressed,” Dr. Butte wrote. “These algorithms will need to be carefully monitored as they are brought into health systems, [but] this does not alter the potential of how they can improve care for both the haves and have-nots of health care.”

In a comment, Dr. Butte elaborated that, once the system flaws are refined, a key benefit will be the broader application of top standards of care to more patients who may have limited resources.

“It is a privilege to get the very best level of care from the very best centers, but that privilege is not distributable to all right now,” Dr. Butte said.

“The real potential of LLMs and AI will be their ability to be trained from the patient, clinical, and outcomes data from the very best centers, and then used to deliver the best care through digital tools to all patients, especially to those without access to the best care or [those with] limited resources,” he said.

Further commenting on the issue of potential bias with chatbots, Matthew Li, MD, from the University of Alberta, Edmonton, said that awareness of the nature of the problem and need for diversity in data for training and testing AI-systems issues appears to be improving.

“Thanks to much research on this topic in recent years, I think most AI researchers in medicine are at least aware of these challenges now, which was not the case only a few years ago,” he said in an interview.

Across specialties, “the careful deployment of AI tools accounting for issues regarding AI model generalization, biases, and performance drift will be critical for ensuring safe and fair patient care,” Dr. Li noted.

On a broader level is the ongoing general concern of the potential for over-reliance on the technology by clinicians. For example, a recent study showing radiologists across all experience levels reading mammograms were prone to automation bias when being supported by an AI-based system.

“Concerns regarding over-reliance on AI remain,” said Dr. Li, who coauthored a study published in June on the issue.

“Ongoing research into and monitoring of the impact of AI systems as they are developed and deployed will be important to ensure safe patient care moving forward,” he said.

Ultimately, the clinical benefit of AI systems to patients should be the bottom line, Dr. Dimai added.

“In my opinion, the clinical relevance, i.e., the benefit for patients and/or physicians of a to-be-developed AI tool, must be clearly proven before its development starts and first clinical studies are carried out,” he said.

“This is not always the case,” Dr. Dimai said. “In other words, innovation per se should not be the only rationale and driving force for the development of such tools.”

Dr. Li, an associate editor for the journal Radiology: Artificial Intelligence, reports no relevant financial relationships. Dr. Dimai is a member of the key medical advisor team of Image Biopsy Lab.

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

While artificial intelligence (AI) appears to be on its way to transforming all fields of medicine, its potential benefits in endocrinology, with its substantial complexity, may be uniquely important. However, hurdles encountered with the latest AI iterations of chatbots underscore the need to proceed with caution.

“In contrast to other medical fields, endocrinology is not connected to a single organ structure; rather, it is a complicated biological system of hormones and metabolites, [intertwined with] various receptors, signaling pathways and intricate feedback mechanisms,” explained the authors of a recent article on the issue in Nature Reviews Endocrinology.

With interconnections that are “often beyond the comprehension and reasoning capabilities of the human brain, AI [is anticipated] to be exceptionally well-suited to tackle this remarkable heterogeneity and complexity,” they wrote.

Since the first regulatory approvals for AI-based technology were granted back in 2015, endocrinology has already been revolutionized by AI-based tools, most notably with AI biosensors for continuous glucose monitoring systems alerting patients of glucose levels, and automated insulin-delivery systems.

AI-based machine learning has also ushered in improved detection and analysis of thyroid nodules and potential malignancies, with algorithms in the analysis of radiological test images enabling detection through a deeper analysis than can be applied with individual specialists.

Likewise, the benefits of AI in imaging extend to osteoporosis.

“Imaging certainly is one of the most promising fields, including (but not limited to) conventional radiography, computed tomography, and magnetic resonance tomography,” explained Hans Peter Dimai, MD, a professor of medicine and endocrinology at the Medical University of Graz (Austria), and the past president of the Austrian Bone and Mineral Society.

“A typical indication is fracture detection, not in terms of replacing expert radiologists or orthopedists but rather in terms of supporting those who are in specialist training,” he said in an interview.

“Particularly the underdiagnosis of vertebral fractures has been an issue in past decades, with dramatic implications for the individual, since the first vertebral fracture would multiply the risk for any future fracture, and therefore requires immediate action from a physician’s side.”

The areas expected to further benefit from AI continue to grow as systems evolve, with advances being reported across a variety of endocrinologic conditions.

Papillary thyroid cancer (PTC): Central lymph node metastasis of papillary thyroid cancer is predictive of tumor recurrence and overall survival in PTC. However, few tests are able to diagnose the metastasis in the cancer with high accuracy. Using a convolutional neural network prediction model built with a deep-learning algorithm, researchers described high diagnostic sensitivity and specificity of a model, as reported in a study published in Feburary. The prediction model, developed using genetic mutations and clinicopathologic factors, showed high prediction efficacy, with validation in subclinical as well as clinical metastasis groups, suggesting broad applicability.

Adrenal tumors: Adrenal incidentalomas, or masses that are incidentally discovered when performing abdominal imaging for other reasons, can be a perplexing clinical challenge. Discovery of these is increasing as imaging technology advances. However, an AI-based machine learning approach utilizing CT is being developed to differentiate between subclinical pheochromocytoma and lipid-poor adenomas. As reported in a 2022 study, the prediction model scoring system used traditional radiological features on CT images to provide for a noninvasive method in assisting in the diagnosis and providing personalized care for people with adrenal tumors.

Osteoporosis – bone mineral density (BMD): In the diagnosis of osteoporosis, the measurement of BMD using dual-energy x-ray absorptiometry (DXA) is the gold standard. However, the availability of DXA devices in many countries is inadequate, leaving an unmet need for alternative approaches. But one AI-based algorithm shows promising diagnostic accuracy, compared with DXA, potentially providing a low-cost screening alternative for the early diagnosis of osteoporosis.  

Osteoporosis – Fracture Risk Assessment Tool (FRAX): In fracture risk and prevention, the free FRAX tool, available online, is the gold standard and recommended in nearly all osteoporosis guidelines. However, several studies on AI-based tools show some benefit over FRAX, including one approach using longitudinal data with conventional spine radiographs, showing predictive accuracy that exceeds FRAX.  

Osteoporosis – treatment: And for the often challenging process of treatment decision-making in osteoporosis, AI-based software, developed from more than 15,000 osteoporosis patients followed over 10 years, shows high accuracy in the prediction of response to treatment in terms of BMD increase, as described in another study. “Our results show that it is feasible to use a combination of electronic medical records–derived information to develop a machine-learning algorithm to predict a BMD response following osteoporosis treatment,” the authors reported. “This alternative approach can aid physicians to select an optimal therapeutic regimen in order to maximize a patient-specific treatment outcome.”
 

Chatbot wrinkles

The prospects of large language models (LLMs) and ChatGPT unleash the potential to understand and generate text in a similar capacity as humans. Although controversial, they could likewise be compelling.

However, such systems can be vastly more complex than earlier AI-based tools, and some studies are illustrating the kinds of stumbling blocks that need to be overcome.

For instance, in a study published in May, researchers explored the potential of ChatGPT 4.0 to synthesize clinical guidelines for diabetic ketoacidosis from three different sources to reflect the latest evidence and local context.

Such efforts are important but can be very resource-intensive when conducted without the use of AI assistance.

The study’s results showed that, although ChatGPT was able to generate a comprehensive table comparing the guidelines, there were multiple recurrent errors in misreporting and nonreporting, as well as inconsistencies, “rendering the results unreliable,” the authors wrote.

“Although ChatGPT demonstrates the potential for the synthesis of clinical guidelines, the presence of multiple recurrent errors and inconsistencies underscores the need for expert human intervention and validation,” the authors concluded.

Likewise, other research using ChatGPT for use in vitreoretinal diseases, including diabetic retinopathy, further demonstrated disappointing results, with the technology showing the chatbot provided completely accurate responses to only 8 (15.4%) of 52 questions, with some responses containing inappropriate or potentially harmful medical advice.

“For example, in response to ‘How do you get rid of epiretinal membrane?’, the platform described vitrectomy but also included incorrect options of injection therapy and laser therapy,” the authors wrote.

“The study highlights the limitations of using ChatGPT for the adaptation of clinical guidelines without expert human intervention,” they concluded.

And in research published in August that looked at the ability of ChatGPT to interpret guidelines – in this case 26 diagnosis descriptions from the National Comprehensive Cancer Network – results showed that as many as one-third of treatments recommended by the chatbot were at least partially not concordant with information stated in the NCCN guidelines, with recommendations varying based on how the question about treatment was presented.

“Clinicians should advise patients that LLM chatbots are not a reliable source of treatment information,” the authors wrote.
 

Diversity concerns

Among the most prominent concerns about chatbot inaccuracy has been the known lack of racial and ethnic diversity in large databases utilized in developing AI systems, potentially resulting in critical flaws in the information the systems produce.

In an editorial published with the NCCN guideline study, Atul Butte, MD, PhD, from the University of California, San Francisco, noted that the shortcomings should be weighed with the potential benefits.

“There is no doubt that AI and LLMs are not yet perfect, and they carry biases that will need to be addressed,” Dr. Butte wrote. “These algorithms will need to be carefully monitored as they are brought into health systems, [but] this does not alter the potential of how they can improve care for both the haves and have-nots of health care.”

In a comment, Dr. Butte elaborated that, once the system flaws are refined, a key benefit will be the broader application of top standards of care to more patients who may have limited resources.

“It is a privilege to get the very best level of care from the very best centers, but that privilege is not distributable to all right now,” Dr. Butte said.

“The real potential of LLMs and AI will be their ability to be trained from the patient, clinical, and outcomes data from the very best centers, and then used to deliver the best care through digital tools to all patients, especially to those without access to the best care or [those with] limited resources,” he said.

Further commenting on the issue of potential bias with chatbots, Matthew Li, MD, from the University of Alberta, Edmonton, said that awareness of the nature of the problem and need for diversity in data for training and testing AI-systems issues appears to be improving.

“Thanks to much research on this topic in recent years, I think most AI researchers in medicine are at least aware of these challenges now, which was not the case only a few years ago,” he said in an interview.

Across specialties, “the careful deployment of AI tools accounting for issues regarding AI model generalization, biases, and performance drift will be critical for ensuring safe and fair patient care,” Dr. Li noted.

On a broader level is the ongoing general concern of the potential for over-reliance on the technology by clinicians. For example, a recent study showing radiologists across all experience levels reading mammograms were prone to automation bias when being supported by an AI-based system.

“Concerns regarding over-reliance on AI remain,” said Dr. Li, who coauthored a study published in June on the issue.

“Ongoing research into and monitoring of the impact of AI systems as they are developed and deployed will be important to ensure safe patient care moving forward,” he said.

Ultimately, the clinical benefit of AI systems to patients should be the bottom line, Dr. Dimai added.

“In my opinion, the clinical relevance, i.e., the benefit for patients and/or physicians of a to-be-developed AI tool, must be clearly proven before its development starts and first clinical studies are carried out,” he said.

“This is not always the case,” Dr. Dimai said. “In other words, innovation per se should not be the only rationale and driving force for the development of such tools.”

Dr. Li, an associate editor for the journal Radiology: Artificial Intelligence, reports no relevant financial relationships. Dr. Dimai is a member of the key medical advisor team of Image Biopsy Lab.

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

People with long COVID have specific biomarkers in their blood, according to results of a study published in Nature. 

The findings may be a step toward creating blood tests to positively identify people with long COVID so specialized treatments can be employed, researchers said.

 “This is a decisive step forward in the development of valid and reliable blood testing protocols for long COVID,” said David Putrino, PhD., lead author and professor of rehabilitation and human performance and director of the Abilities Research Center at Icahn Mount Sinai Health System, New York.

Researchers from the Icahn School of Medicine at Mount Sinai and Yale School of Medicine looked at blood samples from about 270 people between January 2021 and June 2022. The people had never been infected with COVID, had fully recovered from an infection, or still showed symptoms at least four months after infection.

Using machine learning, the research teams were able to differentiate between people with and without long COVID with 96% accuracy based on distinctive features in the blood samples, according to a news release from Mount Sinai.

People with long COVID had abnormal T-cell activity and low levels of the hormone cortisol. Cortisol helps people feel alert and awake, which would explain why people with long COVID often report fatigue, NBC News said in a report on the study.

“It was one of the findings that most definitively separated the folks with long Covid from the people without long Covid,” Dr. Putrino told NBC News.

The study also found that long COVID appears to reactivate latent viruses including Epstein-Barr and mononucleosis, the study said.

The blood tests could allow doctors to come up with specialized treatments in people who report a wide variety of long COVID symptoms, Dr. Putrino said. 

“There is no ‘silver bullet’ for treating long COVID, because it is an illness that infiltrates complex systems such as the immune and hormonal regulation,” he said.

The Centers for Disease Control and Prevention says about one in five Americans who had COVID still have long COVID. Symptoms include fatigue, brain fog, dizziness, digestive problems, and loss of smell and taste.

A version of this article appeared on WebMD.com.

People with long COVID have specific biomarkers in their blood, according to results of a study published in Nature. 

The findings may be a step toward creating blood tests to positively identify people with long COVID so specialized treatments can be employed, researchers said.

 “This is a decisive step forward in the development of valid and reliable blood testing protocols for long COVID,” said David Putrino, PhD., lead author and professor of rehabilitation and human performance and director of the Abilities Research Center at Icahn Mount Sinai Health System, New York.

Researchers from the Icahn School of Medicine at Mount Sinai and Yale School of Medicine looked at blood samples from about 270 people between January 2021 and June 2022. The people had never been infected with COVID, had fully recovered from an infection, or still showed symptoms at least four months after infection.

Using machine learning, the research teams were able to differentiate between people with and without long COVID with 96% accuracy based on distinctive features in the blood samples, according to a news release from Mount Sinai.

People with long COVID had abnormal T-cell activity and low levels of the hormone cortisol. Cortisol helps people feel alert and awake, which would explain why people with long COVID often report fatigue, NBC News said in a report on the study.

“It was one of the findings that most definitively separated the folks with long Covid from the people without long Covid,” Dr. Putrino told NBC News.

The study also found that long COVID appears to reactivate latent viruses including Epstein-Barr and mononucleosis, the study said.

The blood tests could allow doctors to come up with specialized treatments in people who report a wide variety of long COVID symptoms, Dr. Putrino said. 

“There is no ‘silver bullet’ for treating long COVID, because it is an illness that infiltrates complex systems such as the immune and hormonal regulation,” he said.

The Centers for Disease Control and Prevention says about one in five Americans who had COVID still have long COVID. Symptoms include fatigue, brain fog, dizziness, digestive problems, and loss of smell and taste.

A version of this article appeared on WebMD.com.

People with long COVID have specific biomarkers in their blood, according to results of a study published in Nature. 

The findings may be a step toward creating blood tests to positively identify people with long COVID so specialized treatments can be employed, researchers said.

 “This is a decisive step forward in the development of valid and reliable blood testing protocols for long COVID,” said David Putrino, PhD., lead author and professor of rehabilitation and human performance and director of the Abilities Research Center at Icahn Mount Sinai Health System, New York.

Researchers from the Icahn School of Medicine at Mount Sinai and Yale School of Medicine looked at blood samples from about 270 people between January 2021 and June 2022. The people had never been infected with COVID, had fully recovered from an infection, or still showed symptoms at least four months after infection.

Using machine learning, the research teams were able to differentiate between people with and without long COVID with 96% accuracy based on distinctive features in the blood samples, according to a news release from Mount Sinai.

People with long COVID had abnormal T-cell activity and low levels of the hormone cortisol. Cortisol helps people feel alert and awake, which would explain why people with long COVID often report fatigue, NBC News said in a report on the study.

“It was one of the findings that most definitively separated the folks with long Covid from the people without long Covid,” Dr. Putrino told NBC News.

The study also found that long COVID appears to reactivate latent viruses including Epstein-Barr and mononucleosis, the study said.

The blood tests could allow doctors to come up with specialized treatments in people who report a wide variety of long COVID symptoms, Dr. Putrino said. 

“There is no ‘silver bullet’ for treating long COVID, because it is an illness that infiltrates complex systems such as the immune and hormonal regulation,” he said.

The Centers for Disease Control and Prevention says about one in five Americans who had COVID still have long COVID. Symptoms include fatigue, brain fog, dizziness, digestive problems, and loss of smell and taste.

A version of this article appeared on WebMD.com.

With ever-expanding treatment options for the ablation of benign thyroid nodules, the American Thyroid Association has issued an expert consensus statement that addresses the safe implementation and utilization of the techniques.

“There are no documents to date in the United States focusing primarily on the safe adoption and implementation of ablation techniques, including learning curve considerations and necessary pre-procedural skillsets,” reports the ATA task force in the consensus statement, which was published in Thyroid.

“Although these emerging technologies hold great promise, they are not without risk and require development of a unique skill set and environment for optimal, safe performance and consistent outcomes,” task force co-author Catherine F. Sinclair, MD, an associate professor at the Icahn School of Medicine at Mount Sinai, New York, said in an interview.

Chemical ablation has long been utilized as a nonsurgical option for benign thyroid nodule ablation. However, the current array of treatment options has expanded with thermal ablation. Techniques such as radiofrequency ablation (RFA), laser ablation, microwave ablation, and high-intensity focused ultrasound have gained favor as minimally invasive alternatives to surgery.

Much has been published on indications and outcomes with the use of the techniques. The multidisciplinary global task force was convened to address key issues regarding safety and utilization. The report is directed toward specialists, including surgeons, endocrinologists, and interventional radiologists.

The recommendations cover three broad categories: safety considerations spanning preprocedural to postprocedural periods; necessary skill sets for optimal, safe performance with the approaches; and the expectations for success in the context of risks and benefits.
 

Ablation methods can depend on nodule type

Among key issues addressed are which ablation methods are most appropriate for which types of nodules. Recommendations include chemical ablation, typically involving the injection of dehydrated ethanol in a target nodule. In solid nodules, diffusion with chemical ablation can be unpredictable, which makes it more appropriate for cystic nodules.

Thermal ablation is considered best suited for patients with compressive and/or cosmetic complaints that clearly involve a single or dominant nodule, as well as for autonomously functioning thyroid nodules that cause subclinical or overt hyperthyroidism.

While ethanol ablation is recommended as a first-line treatment for benign cystic thyroid nodules, its efficacy decreases when there is an increase of more than 20% of the solid component. In such cases, RFA or a combination of ethanol ablation and RFA may be considered, the task force recommends.
 

Patient counseling – managing expectations

Another key consideration in treatment with thyroid nodule ablation is managing patients’ expectations.

Patients should be advised of benefits, such as the avoidance of surgery and general anesthesia and less recovery time. Risks can include thermal or chemical injury to the recurrent laryngeal nerve and other vital structures. The task force underscores discussion of alternative options with patients.

Alternative management options to ablation, including observation, radioactive iodine for functioning nodules, and surgery should also be discussed, and “their relative advantages and disadvantages should be presented without bias such that the patient can make an informed, individual treatment decision,” the task force recommends.

Patients should be informed that, in contrast to surgical management, the benefits of ablation are not immediate; rather, they accrue over the course of months. Reduction in nodule size within the first month is often limited.

Pain, soreness, and some swelling of the nodule and surrounding tissues are common in the first week. These symptoms usually peak in the first 3-5 days after the procedure. Importantly, patients rarely require opioid medications, and their use should be avoided, the task force recommends.

Patients should also be informed about the possibilities of nodule regrowth following ablation and the possible need for more than one ablation procedure.

“Although regrowth definitions in the literature vary, risk of regrowth after thermal ablation is 5%-40% and increases the larger the baseline nodule volume,” the task force notes.

Of note, most studies on ablation to date have shown that thermal ablation complication rates are low. Twelve months post procedure, volume reductions are typically greater than 50%.
 

Follow-up

For long-term monitoring following ablation, follow-up neck ultrasound is typically recommended at 1-3 months and at 6 and 12 months post ablation to assess volume reduction, nodule appearance, nodule vascularity, and areas at risk for regrowth, the authors note.

Prolonged serial biochemical evaluation of thyroid function is only recommended in cases of hyperfunctioning thyroid nodules.

Key considerations for additional ablative sessions for nodules greater than 20-30 mL in volume should include a failure to achieve adequate reduction in volume, nodule regrowth in previously untreated peripheral areas, and/or persistent or new compressive symptoms.
 

Learning curve

Dr. Sinclair underscored that successful thyroid nodule ablation requires skill – and experience.

“Probably the greatest concern shared by the writing group on this statement was the potential for clinicians to start ablation practices without having an appropriate prior skill set,” she said.

“Ablation is an advanced, ultrasound-guided procedure, and clinicians need to be experienced in performing neck ultrasounds and biopsies,” she added. “To consider performing ablations without this skill set is both unrealistic and dangerous.”

RFA, currently the most commonly used thermal ablation method for benign thyroid nodule ablation in the U.S., “has a good safety profile but can have a steep learning curve initially,” she said.

Among the most important recommendations is that for their first 20-60 ablation procedures, clinicians should consider limiting treatment to small- to medium-sized benign nodules rather than large-volume disease, Dr. Sinclair added.

“In addition, prior to starting thyroid ablation practices, clinicians should be proficient in ultrasound imaging and fine-needle biopsies and can gain valuable experience by practicing on phantoms and having expert proctoring for the first few cases,” she said.

For initial ablative cases, the task force recommends that clinicians select moderate-size (< 20-30 mL), nonvascular nodules with favorable characteristics and location. The final volume reduction should be based not only on baseline nodule characteristics, such as volume and vascularity, but also on the practitioner’s skill.

Clinicians furthermore should be board certified or eligible in an appropriate medical specialty, have extensive background knowledge, and “should have clinical experience in the clinical diagnosis and treatment of thyroid nodules; neck imaging anatomy; thyroid ultrasound imaging and fine needle aspiration biopsy procedures; and ultrasound risk stratification for benign and malignant thyroid tumors,” the group recommends.

Importantly, the statement is designed to reflect a consensus opinion of the panel of experts but is not meant to serve as a formal guideline or a standard of care for the clinical practice of thermal ablation, Dr. Sinclair added.

“It is not the intent of the statement to replace individual decision-making, the wishes of the patient or family, or clinical judgment.”

The authors’ disclosures are detailed in the published report.

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

With ever-expanding treatment options for the ablation of benign thyroid nodules, the American Thyroid Association has issued an expert consensus statement that addresses the safe implementation and utilization of the techniques.

“There are no documents to date in the United States focusing primarily on the safe adoption and implementation of ablation techniques, including learning curve considerations and necessary pre-procedural skillsets,” reports the ATA task force in the consensus statement, which was published in Thyroid.

“Although these emerging technologies hold great promise, they are not without risk and require development of a unique skill set and environment for optimal, safe performance and consistent outcomes,” task force co-author Catherine F. Sinclair, MD, an associate professor at the Icahn School of Medicine at Mount Sinai, New York, said in an interview.

Chemical ablation has long been utilized as a nonsurgical option for benign thyroid nodule ablation. However, the current array of treatment options has expanded with thermal ablation. Techniques such as radiofrequency ablation (RFA), laser ablation, microwave ablation, and high-intensity focused ultrasound have gained favor as minimally invasive alternatives to surgery.

Much has been published on indications and outcomes with the use of the techniques. The multidisciplinary global task force was convened to address key issues regarding safety and utilization. The report is directed toward specialists, including surgeons, endocrinologists, and interventional radiologists.

The recommendations cover three broad categories: safety considerations spanning preprocedural to postprocedural periods; necessary skill sets for optimal, safe performance with the approaches; and the expectations for success in the context of risks and benefits.
 

Ablation methods can depend on nodule type

Among key issues addressed are which ablation methods are most appropriate for which types of nodules. Recommendations include chemical ablation, typically involving the injection of dehydrated ethanol in a target nodule. In solid nodules, diffusion with chemical ablation can be unpredictable, which makes it more appropriate for cystic nodules.

Thermal ablation is considered best suited for patients with compressive and/or cosmetic complaints that clearly involve a single or dominant nodule, as well as for autonomously functioning thyroid nodules that cause subclinical or overt hyperthyroidism.

While ethanol ablation is recommended as a first-line treatment for benign cystic thyroid nodules, its efficacy decreases when there is an increase of more than 20% of the solid component. In such cases, RFA or a combination of ethanol ablation and RFA may be considered, the task force recommends.
 

Patient counseling – managing expectations

Another key consideration in treatment with thyroid nodule ablation is managing patients’ expectations.

Patients should be advised of benefits, such as the avoidance of surgery and general anesthesia and less recovery time. Risks can include thermal or chemical injury to the recurrent laryngeal nerve and other vital structures. The task force underscores discussion of alternative options with patients.

Alternative management options to ablation, including observation, radioactive iodine for functioning nodules, and surgery should also be discussed, and “their relative advantages and disadvantages should be presented without bias such that the patient can make an informed, individual treatment decision,” the task force recommends.

Patients should be informed that, in contrast to surgical management, the benefits of ablation are not immediate; rather, they accrue over the course of months. Reduction in nodule size within the first month is often limited.

Pain, soreness, and some swelling of the nodule and surrounding tissues are common in the first week. These symptoms usually peak in the first 3-5 days after the procedure. Importantly, patients rarely require opioid medications, and their use should be avoided, the task force recommends.

Patients should also be informed about the possibilities of nodule regrowth following ablation and the possible need for more than one ablation procedure.

“Although regrowth definitions in the literature vary, risk of regrowth after thermal ablation is 5%-40% and increases the larger the baseline nodule volume,” the task force notes.

Of note, most studies on ablation to date have shown that thermal ablation complication rates are low. Twelve months post procedure, volume reductions are typically greater than 50%.
 

Follow-up

For long-term monitoring following ablation, follow-up neck ultrasound is typically recommended at 1-3 months and at 6 and 12 months post ablation to assess volume reduction, nodule appearance, nodule vascularity, and areas at risk for regrowth, the authors note.

Prolonged serial biochemical evaluation of thyroid function is only recommended in cases of hyperfunctioning thyroid nodules.

Key considerations for additional ablative sessions for nodules greater than 20-30 mL in volume should include a failure to achieve adequate reduction in volume, nodule regrowth in previously untreated peripheral areas, and/or persistent or new compressive symptoms.
 

Learning curve

Dr. Sinclair underscored that successful thyroid nodule ablation requires skill – and experience.

“Probably the greatest concern shared by the writing group on this statement was the potential for clinicians to start ablation practices without having an appropriate prior skill set,” she said.

“Ablation is an advanced, ultrasound-guided procedure, and clinicians need to be experienced in performing neck ultrasounds and biopsies,” she added. “To consider performing ablations without this skill set is both unrealistic and dangerous.”

RFA, currently the most commonly used thermal ablation method for benign thyroid nodule ablation in the U.S., “has a good safety profile but can have a steep learning curve initially,” she said.

Among the most important recommendations is that for their first 20-60 ablation procedures, clinicians should consider limiting treatment to small- to medium-sized benign nodules rather than large-volume disease, Dr. Sinclair added.

“In addition, prior to starting thyroid ablation practices, clinicians should be proficient in ultrasound imaging and fine-needle biopsies and can gain valuable experience by practicing on phantoms and having expert proctoring for the first few cases,” she said.

For initial ablative cases, the task force recommends that clinicians select moderate-size (< 20-30 mL), nonvascular nodules with favorable characteristics and location. The final volume reduction should be based not only on baseline nodule characteristics, such as volume and vascularity, but also on the practitioner’s skill.

Clinicians furthermore should be board certified or eligible in an appropriate medical specialty, have extensive background knowledge, and “should have clinical experience in the clinical diagnosis and treatment of thyroid nodules; neck imaging anatomy; thyroid ultrasound imaging and fine needle aspiration biopsy procedures; and ultrasound risk stratification for benign and malignant thyroid tumors,” the group recommends.

Importantly, the statement is designed to reflect a consensus opinion of the panel of experts but is not meant to serve as a formal guideline or a standard of care for the clinical practice of thermal ablation, Dr. Sinclair added.

“It is not the intent of the statement to replace individual decision-making, the wishes of the patient or family, or clinical judgment.”

The authors’ disclosures are detailed in the published report.

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

With ever-expanding treatment options for the ablation of benign thyroid nodules, the American Thyroid Association has issued an expert consensus statement that addresses the safe implementation and utilization of the techniques.

“There are no documents to date in the United States focusing primarily on the safe adoption and implementation of ablation techniques, including learning curve considerations and necessary pre-procedural skillsets,” reports the ATA task force in the consensus statement, which was published in Thyroid.

“Although these emerging technologies hold great promise, they are not without risk and require development of a unique skill set and environment for optimal, safe performance and consistent outcomes,” task force co-author Catherine F. Sinclair, MD, an associate professor at the Icahn School of Medicine at Mount Sinai, New York, said in an interview.

Chemical ablation has long been utilized as a nonsurgical option for benign thyroid nodule ablation. However, the current array of treatment options has expanded with thermal ablation. Techniques such as radiofrequency ablation (RFA), laser ablation, microwave ablation, and high-intensity focused ultrasound have gained favor as minimally invasive alternatives to surgery.

Much has been published on indications and outcomes with the use of the techniques. The multidisciplinary global task force was convened to address key issues regarding safety and utilization. The report is directed toward specialists, including surgeons, endocrinologists, and interventional radiologists.

The recommendations cover three broad categories: safety considerations spanning preprocedural to postprocedural periods; necessary skill sets for optimal, safe performance with the approaches; and the expectations for success in the context of risks and benefits.
 

Ablation methods can depend on nodule type

Among key issues addressed are which ablation methods are most appropriate for which types of nodules. Recommendations include chemical ablation, typically involving the injection of dehydrated ethanol in a target nodule. In solid nodules, diffusion with chemical ablation can be unpredictable, which makes it more appropriate for cystic nodules.

Thermal ablation is considered best suited for patients with compressive and/or cosmetic complaints that clearly involve a single or dominant nodule, as well as for autonomously functioning thyroid nodules that cause subclinical or overt hyperthyroidism.

While ethanol ablation is recommended as a first-line treatment for benign cystic thyroid nodules, its efficacy decreases when there is an increase of more than 20% of the solid component. In such cases, RFA or a combination of ethanol ablation and RFA may be considered, the task force recommends.
 

Patient counseling – managing expectations

Another key consideration in treatment with thyroid nodule ablation is managing patients’ expectations.

Patients should be advised of benefits, such as the avoidance of surgery and general anesthesia and less recovery time. Risks can include thermal or chemical injury to the recurrent laryngeal nerve and other vital structures. The task force underscores discussion of alternative options with patients.

Alternative management options to ablation, including observation, radioactive iodine for functioning nodules, and surgery should also be discussed, and “their relative advantages and disadvantages should be presented without bias such that the patient can make an informed, individual treatment decision,” the task force recommends.

Patients should be informed that, in contrast to surgical management, the benefits of ablation are not immediate; rather, they accrue over the course of months. Reduction in nodule size within the first month is often limited.

Pain, soreness, and some swelling of the nodule and surrounding tissues are common in the first week. These symptoms usually peak in the first 3-5 days after the procedure. Importantly, patients rarely require opioid medications, and their use should be avoided, the task force recommends.

Patients should also be informed about the possibilities of nodule regrowth following ablation and the possible need for more than one ablation procedure.

“Although regrowth definitions in the literature vary, risk of regrowth after thermal ablation is 5%-40% and increases the larger the baseline nodule volume,” the task force notes.

Of note, most studies on ablation to date have shown that thermal ablation complication rates are low. Twelve months post procedure, volume reductions are typically greater than 50%.
 

Follow-up

For long-term monitoring following ablation, follow-up neck ultrasound is typically recommended at 1-3 months and at 6 and 12 months post ablation to assess volume reduction, nodule appearance, nodule vascularity, and areas at risk for regrowth, the authors note.

Prolonged serial biochemical evaluation of thyroid function is only recommended in cases of hyperfunctioning thyroid nodules.

Key considerations for additional ablative sessions for nodules greater than 20-30 mL in volume should include a failure to achieve adequate reduction in volume, nodule regrowth in previously untreated peripheral areas, and/or persistent or new compressive symptoms.
 

Learning curve

Dr. Sinclair underscored that successful thyroid nodule ablation requires skill – and experience.

“Probably the greatest concern shared by the writing group on this statement was the potential for clinicians to start ablation practices without having an appropriate prior skill set,” she said.

“Ablation is an advanced, ultrasound-guided procedure, and clinicians need to be experienced in performing neck ultrasounds and biopsies,” she added. “To consider performing ablations without this skill set is both unrealistic and dangerous.”

RFA, currently the most commonly used thermal ablation method for benign thyroid nodule ablation in the U.S., “has a good safety profile but can have a steep learning curve initially,” she said.

Among the most important recommendations is that for their first 20-60 ablation procedures, clinicians should consider limiting treatment to small- to medium-sized benign nodules rather than large-volume disease, Dr. Sinclair added.

“In addition, prior to starting thyroid ablation practices, clinicians should be proficient in ultrasound imaging and fine-needle biopsies and can gain valuable experience by practicing on phantoms and having expert proctoring for the first few cases,” she said.

For initial ablative cases, the task force recommends that clinicians select moderate-size (< 20-30 mL), nonvascular nodules with favorable characteristics and location. The final volume reduction should be based not only on baseline nodule characteristics, such as volume and vascularity, but also on the practitioner’s skill.

Clinicians furthermore should be board certified or eligible in an appropriate medical specialty, have extensive background knowledge, and “should have clinical experience in the clinical diagnosis and treatment of thyroid nodules; neck imaging anatomy; thyroid ultrasound imaging and fine needle aspiration biopsy procedures; and ultrasound risk stratification for benign and malignant thyroid tumors,” the group recommends.

Importantly, the statement is designed to reflect a consensus opinion of the panel of experts but is not meant to serve as a formal guideline or a standard of care for the clinical practice of thermal ablation, Dr. Sinclair added.

“It is not the intent of the statement to replace individual decision-making, the wishes of the patient or family, or clinical judgment.”

The authors’ disclosures are detailed in the published report.

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

Weight loss of at least 5% over a 3-year period was associated with significantly increased mortality in women at age 90, 95, and 100 years compared with those whose weight remained stable, based on data from more than 50,000 individuals.

Previous studies of later-life weight changes and mortality have yielded inconsistent results driven by considerations of weight loss intentionality, and data on older adults in particular are limited, wrote Aladdin H. Shadyab, PhD, of the University of California, San Diego, and colleagues.

In a study published in the Journals of Gerontology: Medical Sciences, the researchers reviewed data from the Women’s Health Initiative, a prospective study of factors affecting chronic disease development in postmenopausal women. The study population included 54,437 women who entered the WHI between 1993 and 1998 at ages 50-79 years. The mean baseline age was 69.8 years; 89.5% of the participants were White, 5.7% were Black, 2.7% were Asian, 2.5% were Hispanic/Latino, and the remaining 1.0% were multiracial, American Indian/Alaskan Native, Native Hawaiian/Other Pacific Islander, or unknown.

The primary outcomes were the associations of short-term (3-year) and long-term (10-year) weight changes with survival to ages 90, 95, and 100 years.

A total of 30,647 women survived to at least 90 years (56.3%).

Overall, women with a short-term weight loss of 5% or more of body weight were 33% less likely to survive to age 90 years, 35% less likely to survive to age 95 years, and 38% less likely to survive to age 100 years than were those whose weight remained stable (odds ratios, 0.67, 0.65, and 0.62, respectively).

The associations were stronger in cases of unintentional short-term weight loss. Intentional weight loss from baseline to year 3 was associated with 17% lower odds of survival to age 90 compared to stable weight (OR, 0.83), but unintentional weight loss was associated with 51% lower odds of survival to age 90 (OR, 0.49).

Similarly, women with 10-year weight loss of at least 5% were 40% less likely to survive to 90 years and 49% less likely to survive to 95 years (OR, 0.60 and OR, 0.51, respectively). The sample size was too small to assess the relation of 10-year weight loss with survival to 100 years, and intentionality was not assessed for 10-year weight changes.

By contrast, weight gain of at least 5% had no significant effect on survival to ages 90, 95, or 100 years, but stable weight over time increased the odds of living to ages 90 to 100 years by 1.2-fold to 2-fold compared to either intentional or unintentional weight loss of at least 5%.

The trends in results were similar across body weight categories (normal weight, overweight, and obese as defined by body mass index). Baseline age and smoking status had no significant effect on the results.

Some of the proportion of self-reported intentional weight loss in the study population may have been unintentional, the researchers wrote in their discussion.

“It is important to note that perceived intentionality of weight loss may be influenced by the many societal pressures to lose weight, especially among women, and therefore overestimate the behavioral changes underlying experienced weight loss in older adults,” they said.

The findings were limited by several factors including the potential for inaccurate self-reported weight loss intention, and the likelihood that the mean older age of the population at baseline (older than 60 years) meant that they were more likely to live longer regardless of weight changes, the researchers noted. Other limitations included the primarily White study population, and other residual confounding factors such as ill health that might drive weight loss, the researchers noted.

However, the results were strengthened by the large sample size and long follow-up period, and suggest that “blanket recommendations for weight loss in older women are unlikely to lead to better survival at advanced ages,” they concluded.
 

Data support weight monitoring

The investigators acknowledged that their data do not affect clinical recommendations for moderate weight loss in older women to improve health outcomes, especially in those with overweight or obesity, but instead “support close monitoring of the amount and speed of weight loss, particularly when unintentional, as an indicator of underlying poor health and predictor of decreased lifespan in older women.”

Neil Skolnik, MD, professor of family and community medicine at the Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, agreed with this conclusion. The current study suggests that when older women lose a significant amount of weight unintentionally, it could be a sign of failing health, he said.

Weight gain or loss in old age is very different from weight issues in younger people, where clinicians may be encouraging weight loss to improve health outcomes, Dr. Skolnik said in an interview.

A key take-home message for clinicians, in addition to monitoring weight in older patients, is to emphasize nutrition for individuals in their 80s, 90s, and beyond, he said.

The study was supported by the National Heart, Lung, and Blood Institute. Dr. Shadyab had no financial conflicts to disclose. Dr. Skolnik had no financial conflicts to disclose and serves on the editorial advisory board of Family Practice News.

Weight loss of at least 5% over a 3-year period was associated with significantly increased mortality in women at age 90, 95, and 100 years compared with those whose weight remained stable, based on data from more than 50,000 individuals.

Previous studies of later-life weight changes and mortality have yielded inconsistent results driven by considerations of weight loss intentionality, and data on older adults in particular are limited, wrote Aladdin H. Shadyab, PhD, of the University of California, San Diego, and colleagues.

In a study published in the Journals of Gerontology: Medical Sciences, the researchers reviewed data from the Women’s Health Initiative, a prospective study of factors affecting chronic disease development in postmenopausal women. The study population included 54,437 women who entered the WHI between 1993 and 1998 at ages 50-79 years. The mean baseline age was 69.8 years; 89.5% of the participants were White, 5.7% were Black, 2.7% were Asian, 2.5% were Hispanic/Latino, and the remaining 1.0% were multiracial, American Indian/Alaskan Native, Native Hawaiian/Other Pacific Islander, or unknown.

The primary outcomes were the associations of short-term (3-year) and long-term (10-year) weight changes with survival to ages 90, 95, and 100 years.

A total of 30,647 women survived to at least 90 years (56.3%).

Overall, women with a short-term weight loss of 5% or more of body weight were 33% less likely to survive to age 90 years, 35% less likely to survive to age 95 years, and 38% less likely to survive to age 100 years than were those whose weight remained stable (odds ratios, 0.67, 0.65, and 0.62, respectively).

The associations were stronger in cases of unintentional short-term weight loss. Intentional weight loss from baseline to year 3 was associated with 17% lower odds of survival to age 90 compared to stable weight (OR, 0.83), but unintentional weight loss was associated with 51% lower odds of survival to age 90 (OR, 0.49).

Similarly, women with 10-year weight loss of at least 5% were 40% less likely to survive to 90 years and 49% less likely to survive to 95 years (OR, 0.60 and OR, 0.51, respectively). The sample size was too small to assess the relation of 10-year weight loss with survival to 100 years, and intentionality was not assessed for 10-year weight changes.

By contrast, weight gain of at least 5% had no significant effect on survival to ages 90, 95, or 100 years, but stable weight over time increased the odds of living to ages 90 to 100 years by 1.2-fold to 2-fold compared to either intentional or unintentional weight loss of at least 5%.

The trends in results were similar across body weight categories (normal weight, overweight, and obese as defined by body mass index). Baseline age and smoking status had no significant effect on the results.

Some of the proportion of self-reported intentional weight loss in the study population may have been unintentional, the researchers wrote in their discussion.

“It is important to note that perceived intentionality of weight loss may be influenced by the many societal pressures to lose weight, especially among women, and therefore overestimate the behavioral changes underlying experienced weight loss in older adults,” they said.

The findings were limited by several factors including the potential for inaccurate self-reported weight loss intention, and the likelihood that the mean older age of the population at baseline (older than 60 years) meant that they were more likely to live longer regardless of weight changes, the researchers noted. Other limitations included the primarily White study population, and other residual confounding factors such as ill health that might drive weight loss, the researchers noted.

However, the results were strengthened by the large sample size and long follow-up period, and suggest that “blanket recommendations for weight loss in older women are unlikely to lead to better survival at advanced ages,” they concluded.
 

Data support weight monitoring

The investigators acknowledged that their data do not affect clinical recommendations for moderate weight loss in older women to improve health outcomes, especially in those with overweight or obesity, but instead “support close monitoring of the amount and speed of weight loss, particularly when unintentional, as an indicator of underlying poor health and predictor of decreased lifespan in older women.”

Neil Skolnik, MD, professor of family and community medicine at the Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, agreed with this conclusion. The current study suggests that when older women lose a significant amount of weight unintentionally, it could be a sign of failing health, he said.

Weight gain or loss in old age is very different from weight issues in younger people, where clinicians may be encouraging weight loss to improve health outcomes, Dr. Skolnik said in an interview.

A key take-home message for clinicians, in addition to monitoring weight in older patients, is to emphasize nutrition for individuals in their 80s, 90s, and beyond, he said.

The study was supported by the National Heart, Lung, and Blood Institute. Dr. Shadyab had no financial conflicts to disclose. Dr. Skolnik had no financial conflicts to disclose and serves on the editorial advisory board of Family Practice News.

Weight loss of at least 5% over a 3-year period was associated with significantly increased mortality in women at age 90, 95, and 100 years compared with those whose weight remained stable, based on data from more than 50,000 individuals.

Previous studies of later-life weight changes and mortality have yielded inconsistent results driven by considerations of weight loss intentionality, and data on older adults in particular are limited, wrote Aladdin H. Shadyab, PhD, of the University of California, San Diego, and colleagues.

In a study published in the Journals of Gerontology: Medical Sciences, the researchers reviewed data from the Women’s Health Initiative, a prospective study of factors affecting chronic disease development in postmenopausal women. The study population included 54,437 women who entered the WHI between 1993 and 1998 at ages 50-79 years. The mean baseline age was 69.8 years; 89.5% of the participants were White, 5.7% were Black, 2.7% were Asian, 2.5% were Hispanic/Latino, and the remaining 1.0% were multiracial, American Indian/Alaskan Native, Native Hawaiian/Other Pacific Islander, or unknown.

The primary outcomes were the associations of short-term (3-year) and long-term (10-year) weight changes with survival to ages 90, 95, and 100 years.

A total of 30,647 women survived to at least 90 years (56.3%).

Overall, women with a short-term weight loss of 5% or more of body weight were 33% less likely to survive to age 90 years, 35% less likely to survive to age 95 years, and 38% less likely to survive to age 100 years than were those whose weight remained stable (odds ratios, 0.67, 0.65, and 0.62, respectively).

The associations were stronger in cases of unintentional short-term weight loss. Intentional weight loss from baseline to year 3 was associated with 17% lower odds of survival to age 90 compared to stable weight (OR, 0.83), but unintentional weight loss was associated with 51% lower odds of survival to age 90 (OR, 0.49).

Similarly, women with 10-year weight loss of at least 5% were 40% less likely to survive to 90 years and 49% less likely to survive to 95 years (OR, 0.60 and OR, 0.51, respectively). The sample size was too small to assess the relation of 10-year weight loss with survival to 100 years, and intentionality was not assessed for 10-year weight changes.

By contrast, weight gain of at least 5% had no significant effect on survival to ages 90, 95, or 100 years, but stable weight over time increased the odds of living to ages 90 to 100 years by 1.2-fold to 2-fold compared to either intentional or unintentional weight loss of at least 5%.

The trends in results were similar across body weight categories (normal weight, overweight, and obese as defined by body mass index). Baseline age and smoking status had no significant effect on the results.

Some of the proportion of self-reported intentional weight loss in the study population may have been unintentional, the researchers wrote in their discussion.

“It is important to note that perceived intentionality of weight loss may be influenced by the many societal pressures to lose weight, especially among women, and therefore overestimate the behavioral changes underlying experienced weight loss in older adults,” they said.

The findings were limited by several factors including the potential for inaccurate self-reported weight loss intention, and the likelihood that the mean older age of the population at baseline (older than 60 years) meant that they were more likely to live longer regardless of weight changes, the researchers noted. Other limitations included the primarily White study population, and other residual confounding factors such as ill health that might drive weight loss, the researchers noted.

However, the results were strengthened by the large sample size and long follow-up period, and suggest that “blanket recommendations for weight loss in older women are unlikely to lead to better survival at advanced ages,” they concluded.
 

Data support weight monitoring

The investigators acknowledged that their data do not affect clinical recommendations for moderate weight loss in older women to improve health outcomes, especially in those with overweight or obesity, but instead “support close monitoring of the amount and speed of weight loss, particularly when unintentional, as an indicator of underlying poor health and predictor of decreased lifespan in older women.”

Neil Skolnik, MD, professor of family and community medicine at the Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, agreed with this conclusion. The current study suggests that when older women lose a significant amount of weight unintentionally, it could be a sign of failing health, he said.

Weight gain or loss in old age is very different from weight issues in younger people, where clinicians may be encouraging weight loss to improve health outcomes, Dr. Skolnik said in an interview.

A key take-home message for clinicians, in addition to monitoring weight in older patients, is to emphasize nutrition for individuals in their 80s, 90s, and beyond, he said.

The study was supported by the National Heart, Lung, and Blood Institute. Dr. Shadyab had no financial conflicts to disclose. Dr. Skolnik had no financial conflicts to disclose and serves on the editorial advisory board of Family Practice News.