Pituitary, Thyroid & Adrenal Disorders

Coronavirus disease of 2019 (COVID-19) may lead to subacute thyroiditis in some patients, which is suspected to have viral or postviral origin, especially with upper respiratory tract infections, according to a case study in the Journal of Clinical Endocrinology & Metabolism.

Alessandro Brancatella, a PhD student at the University Hospital Pisa (Italy), and colleagues described the case of an 18-year-old woman who was tested Feb. 21 for SARS-CoV-2 infection after her father was hospitalized because of COVID-19. Her results were positive for the virus, and not long after, she developed mild symptoms. By March 13 and again on March 14, test swabs for SARS-CoV-2 were both negative.

On March 17, she presented with fever, fatigue, palpitations, and neck pain that radiated to her jaw. Testing and physical examination pointed to subacute thyroiditis, and she was soon diagnosed and treated with prednisone. Her neck pain and fever disappeared within 2 days, and the remaining symptoms went away within a week.

The authors noted that the woman’s thyroid had been evaluated before she tested positive for SARS-CoV-2, and at that time, thyroid disease was ruled out. They also pointed out that, although the exact etiology for subacute thyroiditis is unknown, “it is common opinion that the disease is due to a viral infection or to a post-viral inflammatory reaction in genetically predisposed subjects.” They cited examples of viruses with suspected causal associations, including mumps, Epstein-Barr virus, and HIV, and they suggested that, based on the timing of the woman’s subacute thyroiditis and the normal results of her thyroid evaluation before developing COVID-19, SARS-CoV-2 be added to that list.

“To our knowledge, this is the first case of [subacute thyroiditis] related to SARS-CoV-2,” they concluded. “We therefore believe that physicians should be alerted about the possibility of this additional clinical manifestation related to SARS-CoV-2 infection.”

One author reported funding from the University of Pisa.

cpalmer@mdedge.com

SOURCE: Brancatella A et al. J Clin Endocrinol Metab. 2020 May 21. doi: 10.1210/clinem/dgaa276.

Coronavirus disease of 2019 (COVID-19) may lead to subacute thyroiditis in some patients, which is suspected to have viral or postviral origin, especially with upper respiratory tract infections, according to a case study in the Journal of Clinical Endocrinology & Metabolism.

Alessandro Brancatella, a PhD student at the University Hospital Pisa (Italy), and colleagues described the case of an 18-year-old woman who was tested Feb. 21 for SARS-CoV-2 infection after her father was hospitalized because of COVID-19. Her results were positive for the virus, and not long after, she developed mild symptoms. By March 13 and again on March 14, test swabs for SARS-CoV-2 were both negative.

On March 17, she presented with fever, fatigue, palpitations, and neck pain that radiated to her jaw. Testing and physical examination pointed to subacute thyroiditis, and she was soon diagnosed and treated with prednisone. Her neck pain and fever disappeared within 2 days, and the remaining symptoms went away within a week.

The authors noted that the woman’s thyroid had been evaluated before she tested positive for SARS-CoV-2, and at that time, thyroid disease was ruled out. They also pointed out that, although the exact etiology for subacute thyroiditis is unknown, “it is common opinion that the disease is due to a viral infection or to a post-viral inflammatory reaction in genetically predisposed subjects.” They cited examples of viruses with suspected causal associations, including mumps, Epstein-Barr virus, and HIV, and they suggested that, based on the timing of the woman’s subacute thyroiditis and the normal results of her thyroid evaluation before developing COVID-19, SARS-CoV-2 be added to that list.

“To our knowledge, this is the first case of [subacute thyroiditis] related to SARS-CoV-2,” they concluded. “We therefore believe that physicians should be alerted about the possibility of this additional clinical manifestation related to SARS-CoV-2 infection.”

One author reported funding from the University of Pisa.

cpalmer@mdedge.com

SOURCE: Brancatella A et al. J Clin Endocrinol Metab. 2020 May 21. doi: 10.1210/clinem/dgaa276.

Coronavirus disease of 2019 (COVID-19) may lead to subacute thyroiditis in some patients, which is suspected to have viral or postviral origin, especially with upper respiratory tract infections, according to a case study in the Journal of Clinical Endocrinology & Metabolism.

Alessandro Brancatella, a PhD student at the University Hospital Pisa (Italy), and colleagues described the case of an 18-year-old woman who was tested Feb. 21 for SARS-CoV-2 infection after her father was hospitalized because of COVID-19. Her results were positive for the virus, and not long after, she developed mild symptoms. By March 13 and again on March 14, test swabs for SARS-CoV-2 were both negative.

On March 17, she presented with fever, fatigue, palpitations, and neck pain that radiated to her jaw. Testing and physical examination pointed to subacute thyroiditis, and she was soon diagnosed and treated with prednisone. Her neck pain and fever disappeared within 2 days, and the remaining symptoms went away within a week.

The authors noted that the woman’s thyroid had been evaluated before she tested positive for SARS-CoV-2, and at that time, thyroid disease was ruled out. They also pointed out that, although the exact etiology for subacute thyroiditis is unknown, “it is common opinion that the disease is due to a viral infection or to a post-viral inflammatory reaction in genetically predisposed subjects.” They cited examples of viruses with suspected causal associations, including mumps, Epstein-Barr virus, and HIV, and they suggested that, based on the timing of the woman’s subacute thyroiditis and the normal results of her thyroid evaluation before developing COVID-19, SARS-CoV-2 be added to that list.

“To our knowledge, this is the first case of [subacute thyroiditis] related to SARS-CoV-2,” they concluded. “We therefore believe that physicians should be alerted about the possibility of this additional clinical manifestation related to SARS-CoV-2 infection.”

One author reported funding from the University of Pisa.

cpalmer@mdedge.com

SOURCE: Brancatella A et al. J Clin Endocrinol Metab. 2020 May 21. doi: 10.1210/clinem/dgaa276.

A new analysis of the large, randomized TRUST trial shows that L-thyroxine does not improve pronounced symptoms in older people with subclinical hypothyroidism.

The original trial established that the synthetic hormone did not improve symptoms in the overall trial population, a finding that called into question the routine prescribing of thyroid medication for this patient group.

But questions lingered as to whether patients with a higher burden of symptoms might still benefit from treatment with L-thyroxine.

For their research, published in Annals of Internal Medicine, Maria de Montmollin, MD, of the University of Bern (Switzerland), looked at results for 638 subjects randomized to L-thyroxine treatment (50 mcg daily for most patients) or placebo and followed for at least 1 year in the Thyroid Hormone Therapy for Older Adults With Subclinical Hypothyroidism (TRUST) trial (N Engl J Med. 2017;376:2534-2544). All were 65 years or older and met the criteria for subclinical hypothyroidism, defined as persistent elevated TSH levels (4.60-19.99 mIU/L) in combination with a normal free-thyroxine level.

Dr. de Montmollin and her colleagues identified 132 participants with high hypothyroid symptom burden at baseline and 133 patients with high scores for tiredness, using the Thyroid-Related Quality-of-Life Patient-Reported Outcome Questionnaire. Cutoffs were a baseline symptoms score of higher than 30 (on a 1-100 scale), or a tiredness score of over 40.

At 1 year, researchers saw no statistically significant improvements in either measure for the L-thyroxine treated patients, compared with placebo.

Among the patients with high symptom burden, those on L-thyroxine saw a score improvement of –12.3 points, compared with –10.4 for those on placebo, for an adjusted between-group difference of –2.0 (95% confidence interval, –5.5 to 1.5; P = 0.27). Tiredness scores also improved similarly, dropping 8.9 points for L-thyroxine–treated patients, compared with –10.9 for those receiving placebo, for an adjusted between-group difference of 0.0 (95% CI, –4.1 to 4.0; P = 0.99).

Dr. de Montmollin and colleagues also noted no significant between-group differences in two secondary measures they looked at in the study: patient self-reported quality of life and handgrip strength, an objective measure of weakness.

The results “do not support the hypothesis that the subgroup of adults with SCH [subclinical hypothyroidism] and high symptom burden before treatment benefit from L-thyroxine therapy,” the investigators wrote in their analysis. “This may be because of regression to the mean, the natural history of SCH, or the placebo effect and may explain why many persons with symptomatic SCH and their treating physicians are convinced that L-thyroxine is beneficial,” they added.

In an interview, Dr. de Montmollin commented that treating physicians “should reconsider prescribing or offering L-thyroxine to older adults with SCH, even those with consistent symptoms, because there is no clear evidence for its benefit in treating SCH to date and a risk of harm related to overtreatment is still possible. In addition, it is associated with unnecessary costs for the patient and for the health system.”

The investigators mentioned several limitations to their study, including its post hoc design and a small sample size. Additionally, they wrote, the findings “cannot exclude the possibility that a rare subgroup with greater symptom burden would benefit from L-thyroxine therapy” or that more aggressive treatment leading to lower TSH levels would confer benefit.

The study was sponsored by the National Health Service Greater Glasgow and Clyde Health Board, while the TRUST trial was sponsored by the European Union and with medication donated by Merck. Dr. de Montmollin and her coauthors disclosed no financial ties to industry.

SOURCE: De Montmollin et al. Ann Intern Med 2020 May 5. doi: 10.7326/M19-3193.

A new analysis of the large, randomized TRUST trial shows that L-thyroxine does not improve pronounced symptoms in older people with subclinical hypothyroidism.

The original trial established that the synthetic hormone did not improve symptoms in the overall trial population, a finding that called into question the routine prescribing of thyroid medication for this patient group.

But questions lingered as to whether patients with a higher burden of symptoms might still benefit from treatment with L-thyroxine.

For their research, published in Annals of Internal Medicine, Maria de Montmollin, MD, of the University of Bern (Switzerland), looked at results for 638 subjects randomized to L-thyroxine treatment (50 mcg daily for most patients) or placebo and followed for at least 1 year in the Thyroid Hormone Therapy for Older Adults With Subclinical Hypothyroidism (TRUST) trial (N Engl J Med. 2017;376:2534-2544). All were 65 years or older and met the criteria for subclinical hypothyroidism, defined as persistent elevated TSH levels (4.60-19.99 mIU/L) in combination with a normal free-thyroxine level.

Dr. de Montmollin and her colleagues identified 132 participants with high hypothyroid symptom burden at baseline and 133 patients with high scores for tiredness, using the Thyroid-Related Quality-of-Life Patient-Reported Outcome Questionnaire. Cutoffs were a baseline symptoms score of higher than 30 (on a 1-100 scale), or a tiredness score of over 40.

At 1 year, researchers saw no statistically significant improvements in either measure for the L-thyroxine treated patients, compared with placebo.

Among the patients with high symptom burden, those on L-thyroxine saw a score improvement of –12.3 points, compared with –10.4 for those on placebo, for an adjusted between-group difference of –2.0 (95% confidence interval, –5.5 to 1.5; P = 0.27). Tiredness scores also improved similarly, dropping 8.9 points for L-thyroxine–treated patients, compared with –10.9 for those receiving placebo, for an adjusted between-group difference of 0.0 (95% CI, –4.1 to 4.0; P = 0.99).

Dr. de Montmollin and colleagues also noted no significant between-group differences in two secondary measures they looked at in the study: patient self-reported quality of life and handgrip strength, an objective measure of weakness.

The results “do not support the hypothesis that the subgroup of adults with SCH [subclinical hypothyroidism] and high symptom burden before treatment benefit from L-thyroxine therapy,” the investigators wrote in their analysis. “This may be because of regression to the mean, the natural history of SCH, or the placebo effect and may explain why many persons with symptomatic SCH and their treating physicians are convinced that L-thyroxine is beneficial,” they added.

In an interview, Dr. de Montmollin commented that treating physicians “should reconsider prescribing or offering L-thyroxine to older adults with SCH, even those with consistent symptoms, because there is no clear evidence for its benefit in treating SCH to date and a risk of harm related to overtreatment is still possible. In addition, it is associated with unnecessary costs for the patient and for the health system.”

The investigators mentioned several limitations to their study, including its post hoc design and a small sample size. Additionally, they wrote, the findings “cannot exclude the possibility that a rare subgroup with greater symptom burden would benefit from L-thyroxine therapy” or that more aggressive treatment leading to lower TSH levels would confer benefit.

The study was sponsored by the National Health Service Greater Glasgow and Clyde Health Board, while the TRUST trial was sponsored by the European Union and with medication donated by Merck. Dr. de Montmollin and her coauthors disclosed no financial ties to industry.

SOURCE: De Montmollin et al. Ann Intern Med 2020 May 5. doi: 10.7326/M19-3193.

A new analysis of the large, randomized TRUST trial shows that L-thyroxine does not improve pronounced symptoms in older people with subclinical hypothyroidism.

The original trial established that the synthetic hormone did not improve symptoms in the overall trial population, a finding that called into question the routine prescribing of thyroid medication for this patient group.

But questions lingered as to whether patients with a higher burden of symptoms might still benefit from treatment with L-thyroxine.

For their research, published in Annals of Internal Medicine, Maria de Montmollin, MD, of the University of Bern (Switzerland), looked at results for 638 subjects randomized to L-thyroxine treatment (50 mcg daily for most patients) or placebo and followed for at least 1 year in the Thyroid Hormone Therapy for Older Adults With Subclinical Hypothyroidism (TRUST) trial (N Engl J Med. 2017;376:2534-2544). All were 65 years or older and met the criteria for subclinical hypothyroidism, defined as persistent elevated TSH levels (4.60-19.99 mIU/L) in combination with a normal free-thyroxine level.

Dr. de Montmollin and her colleagues identified 132 participants with high hypothyroid symptom burden at baseline and 133 patients with high scores for tiredness, using the Thyroid-Related Quality-of-Life Patient-Reported Outcome Questionnaire. Cutoffs were a baseline symptoms score of higher than 30 (on a 1-100 scale), or a tiredness score of over 40.

At 1 year, researchers saw no statistically significant improvements in either measure for the L-thyroxine treated patients, compared with placebo.

Among the patients with high symptom burden, those on L-thyroxine saw a score improvement of –12.3 points, compared with –10.4 for those on placebo, for an adjusted between-group difference of –2.0 (95% confidence interval, –5.5 to 1.5; P = 0.27). Tiredness scores also improved similarly, dropping 8.9 points for L-thyroxine–treated patients, compared with –10.9 for those receiving placebo, for an adjusted between-group difference of 0.0 (95% CI, –4.1 to 4.0; P = 0.99).

Dr. de Montmollin and colleagues also noted no significant between-group differences in two secondary measures they looked at in the study: patient self-reported quality of life and handgrip strength, an objective measure of weakness.

The results “do not support the hypothesis that the subgroup of adults with SCH [subclinical hypothyroidism] and high symptom burden before treatment benefit from L-thyroxine therapy,” the investigators wrote in their analysis. “This may be because of regression to the mean, the natural history of SCH, or the placebo effect and may explain why many persons with symptomatic SCH and their treating physicians are convinced that L-thyroxine is beneficial,” they added.

In an interview, Dr. de Montmollin commented that treating physicians “should reconsider prescribing or offering L-thyroxine to older adults with SCH, even those with consistent symptoms, because there is no clear evidence for its benefit in treating SCH to date and a risk of harm related to overtreatment is still possible. In addition, it is associated with unnecessary costs for the patient and for the health system.”

The investigators mentioned several limitations to their study, including its post hoc design and a small sample size. Additionally, they wrote, the findings “cannot exclude the possibility that a rare subgroup with greater symptom burden would benefit from L-thyroxine therapy” or that more aggressive treatment leading to lower TSH levels would confer benefit.

The study was sponsored by the National Health Service Greater Glasgow and Clyde Health Board, while the TRUST trial was sponsored by the European Union and with medication donated by Merck. Dr. de Montmollin and her coauthors disclosed no financial ties to industry.

SOURCE: De Montmollin et al. Ann Intern Med 2020 May 5. doi: 10.7326/M19-3193.

With a few notable exceptions, the majority of fine needle aspiration (FNA) biopsies of thyroid nodules should be delayed until the risk of COVID-19, and the burden on resources, has lessened, according to expert consensus.

copyright/Sebastian Kaulitzki/Fotolia

“Our group recommends that FNA biopsy of most asymptomatic thyroid nodules – taking into account the sonographic characteristics and patients’ clinical picture – be deferred to a later time, when risk of exposure to COVID-19 is more manageable and resource restriction is no longer a concern,” said the endocrinologists, writing in a guest editorial in Clinical Thyroidology.

All elective procedures have been canceled under guidance of the Centers for Disease Control and Prevention, in conjunction with the U.S. surgeon general, in response to the COVID-19 pandemic. However, thyroid nodule FNAs, though elective, fall into the category of being considered medically necessary and potentially prolonging life expectancy

Yet, with approximately 90% of asymptomatic thyroid nodules turning out to be benign and little evidence that early detection and treatment affects disease outcomes, there is a strong argument for deferral in most cases, stressed Ming Lee, MD, and colleagues, of the endocrinology division at Phoenix (Ariz.) Veterans Affairs Health Care System (PVAHCS), who convened a multidisciplinary meeting to address the urgent issue.

Patients should instead be interviewed by an endocrinologist (preferably via telehealth) to collect their clinical history as well as assess their perception of the disease and risk of malignancy, senior author S. Mitchell Harman, MD, chief of PVAHCS, said in an interview.

“The principal guiding factor should be the objectively assessed likelihood of malignancy of the individual patient’s nodule(s),” he said.

“In my opinion, we should also factor in the patient’s level of anxiety, since some patients are more sanguine about risk than others and our goal is to provide relief of anxiety as well as to determine need for, and course of, subsequent treatment,” Dr. Harman added. 

Vast majority of malignant thyroid nodules are DTC, which is ‘indolent’

Dr. Lee and colleagues noted that, even of the 10% of thyroid nodules that do prove to be malignant, the vast majority of these (90%) are differentiated thyroid cancers (DTC). In general, patients with DTC “follow an indolent course and have excellent outcomes.”

“There is little evidence that early detection and treatment of DTC significantly alters disease outcomes as the overall mortality rate for DTC has remained low, at around 0.5%,” they wrote.

They also noted that ultrasound features of thyroid nodules can help guide priority for the future timing of an FNA procedure, but should not be the sole basis for deciding on immediate thyroid FNA or surgery.

Exceptions to the rule

Exceptions for considering FNA include more urgent thyroid disease diagnoses, including those that are symptomatic:

Suspected medullary thyroid cancer

“Regarding medullary thyroid cancer (MTC), early diagnosis and surgery do significantly improve outcomes, therefore, delaying FNA of nodules harboring MTC could be potentially injurious,” the authors said.

They suggested, however, measuring calcitonin levels instead, which they noted “is still controversial” in the United States, but “we feel it would be justified in patients with thyroid nodules that would usually be indicated for FNA.”

Those with a family history of MTC, or nodules located in the posterior upper third of lateral lobes (the usual location of MTC), should have calcitonin levels measured.

If calcitonin levels are above 10 pg/mL, “FNA should be offered as early as possible.”

“Significantly elevated serum calcitonin levels (e.g., > 100 pg/mL) should be considered an indication for surgery without cytologic confirmation by FNA,” they added.

Anaplastic thyroid cancer

Anaplastic thyroid cancer, though rare, “is one of the few occasions when thyroid surgery should be performed on an urgent basis, as this condition can worsen very rapidly.

“Patients typically present with a rapidly enlarging thyroid mass that is associated with compressive symptoms, such as dysphagia and dyspnea,” they observed.

In this instance, although FNA is part of the preoperative work-up, it is often nondiagnostic and could require additional sampling.

“At the time of this pandemic, it is reasonable that after a multidisciplinary discussion, such patients with the appropriate clinical scenario be referred for thyroid surgery, with or without prior FNA, based on the team’s judgment,” the authors recommended.

Long-standing thyroid masses

These are usually large and/or closely associated with vital structures, such as the trachea and esophagus, and when such masses cause compressive symptoms, thyroid surgery typically is warranted.

And although prior FNA is helpful to obtain a cytologic diagnosis, as this may change the extent of surgery, it may not always be essential.

Broadly, symptomatic patients with compressive symptoms threatening vital structures can be directly referred to a surgeon, with the timing for surgery jointly decided based on the severity of symptoms, rapidity of disease progression, local COVID-19 status, and available resources.

“During the pandemic, we believe that the vast majority of thyroid FNAs should be considered optional, and extent of surgery can be determined by pathological analysis of frozen sections intraoperatively,” they wrote.

“The value of FNA in these situations is less compelling in the current COVID-19 setting, as the basis of decision for surgery has been already determined,” the authors explained.

If urgent FNA needed, screen patient for COVID-19 and use PPE

Should the need for an urgent thyroid FNA occur, patients should be screened and tested for COVID-19 by a clinician wearing personal protective equipment (PPE), said Dr. Lee and colleagues.

“It is crucial to carefully weigh the risks of COVID-19 exposure, availability of resources, and urgency of these procedures for each patient in our individual practice settings,” they noted.

As restrictions eventually loosen, precautions will still be necessary to some degree, Dr. Harman said.

“I do not consider FNA a ‘high-risk’ procedure in the era of COVID-19, since it does not routinely result in profuse aerosolization of respiratory fluids,” he said in an interview.

“However, patients do sometimes cough or choke due to pressure on the neck and the operator is, of necessity, very close to the patient’s face. Therefore, when we resume FNA, patients will be screened for symptoms of COVID-19 infection and both the operator and the patient will be masked,” Dr. Harman continued.

“We routinely wear gloves, [and] whether the operator will wear a surgical or an N95 mask, disposable gown, etc, will depend on CDC guidance and guidance received from our VA infectious disease experts as it is applied specifically to each patient evaluation.”

The authors have reported no relevant financial relationships.
 

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

With a few notable exceptions, the majority of fine needle aspiration (FNA) biopsies of thyroid nodules should be delayed until the risk of COVID-19, and the burden on resources, has lessened, according to expert consensus.

copyright/Sebastian Kaulitzki/Fotolia

“Our group recommends that FNA biopsy of most asymptomatic thyroid nodules – taking into account the sonographic characteristics and patients’ clinical picture – be deferred to a later time, when risk of exposure to COVID-19 is more manageable and resource restriction is no longer a concern,” said the endocrinologists, writing in a guest editorial in Clinical Thyroidology.

All elective procedures have been canceled under guidance of the Centers for Disease Control and Prevention, in conjunction with the U.S. surgeon general, in response to the COVID-19 pandemic. However, thyroid nodule FNAs, though elective, fall into the category of being considered medically necessary and potentially prolonging life expectancy

Yet, with approximately 90% of asymptomatic thyroid nodules turning out to be benign and little evidence that early detection and treatment affects disease outcomes, there is a strong argument for deferral in most cases, stressed Ming Lee, MD, and colleagues, of the endocrinology division at Phoenix (Ariz.) Veterans Affairs Health Care System (PVAHCS), who convened a multidisciplinary meeting to address the urgent issue.

Patients should instead be interviewed by an endocrinologist (preferably via telehealth) to collect their clinical history as well as assess their perception of the disease and risk of malignancy, senior author S. Mitchell Harman, MD, chief of PVAHCS, said in an interview.

“The principal guiding factor should be the objectively assessed likelihood of malignancy of the individual patient’s nodule(s),” he said.

“In my opinion, we should also factor in the patient’s level of anxiety, since some patients are more sanguine about risk than others and our goal is to provide relief of anxiety as well as to determine need for, and course of, subsequent treatment,” Dr. Harman added. 

Vast majority of malignant thyroid nodules are DTC, which is ‘indolent’

Dr. Lee and colleagues noted that, even of the 10% of thyroid nodules that do prove to be malignant, the vast majority of these (90%) are differentiated thyroid cancers (DTC). In general, patients with DTC “follow an indolent course and have excellent outcomes.”

“There is little evidence that early detection and treatment of DTC significantly alters disease outcomes as the overall mortality rate for DTC has remained low, at around 0.5%,” they wrote.

They also noted that ultrasound features of thyroid nodules can help guide priority for the future timing of an FNA procedure, but should not be the sole basis for deciding on immediate thyroid FNA or surgery.

Exceptions to the rule

Exceptions for considering FNA include more urgent thyroid disease diagnoses, including those that are symptomatic:

Suspected medullary thyroid cancer

“Regarding medullary thyroid cancer (MTC), early diagnosis and surgery do significantly improve outcomes, therefore, delaying FNA of nodules harboring MTC could be potentially injurious,” the authors said.

They suggested, however, measuring calcitonin levels instead, which they noted “is still controversial” in the United States, but “we feel it would be justified in patients with thyroid nodules that would usually be indicated for FNA.”

Those with a family history of MTC, or nodules located in the posterior upper third of lateral lobes (the usual location of MTC), should have calcitonin levels measured.

If calcitonin levels are above 10 pg/mL, “FNA should be offered as early as possible.”

“Significantly elevated serum calcitonin levels (e.g., > 100 pg/mL) should be considered an indication for surgery without cytologic confirmation by FNA,” they added.

Anaplastic thyroid cancer

Anaplastic thyroid cancer, though rare, “is one of the few occasions when thyroid surgery should be performed on an urgent basis, as this condition can worsen very rapidly.

“Patients typically present with a rapidly enlarging thyroid mass that is associated with compressive symptoms, such as dysphagia and dyspnea,” they observed.

In this instance, although FNA is part of the preoperative work-up, it is often nondiagnostic and could require additional sampling.

“At the time of this pandemic, it is reasonable that after a multidisciplinary discussion, such patients with the appropriate clinical scenario be referred for thyroid surgery, with or without prior FNA, based on the team’s judgment,” the authors recommended.

Long-standing thyroid masses

These are usually large and/or closely associated with vital structures, such as the trachea and esophagus, and when such masses cause compressive symptoms, thyroid surgery typically is warranted.

And although prior FNA is helpful to obtain a cytologic diagnosis, as this may change the extent of surgery, it may not always be essential.

Broadly, symptomatic patients with compressive symptoms threatening vital structures can be directly referred to a surgeon, with the timing for surgery jointly decided based on the severity of symptoms, rapidity of disease progression, local COVID-19 status, and available resources.

“During the pandemic, we believe that the vast majority of thyroid FNAs should be considered optional, and extent of surgery can be determined by pathological analysis of frozen sections intraoperatively,” they wrote.

“The value of FNA in these situations is less compelling in the current COVID-19 setting, as the basis of decision for surgery has been already determined,” the authors explained.

If urgent FNA needed, screen patient for COVID-19 and use PPE

Should the need for an urgent thyroid FNA occur, patients should be screened and tested for COVID-19 by a clinician wearing personal protective equipment (PPE), said Dr. Lee and colleagues.

“It is crucial to carefully weigh the risks of COVID-19 exposure, availability of resources, and urgency of these procedures for each patient in our individual practice settings,” they noted.

As restrictions eventually loosen, precautions will still be necessary to some degree, Dr. Harman said.

“I do not consider FNA a ‘high-risk’ procedure in the era of COVID-19, since it does not routinely result in profuse aerosolization of respiratory fluids,” he said in an interview.

“However, patients do sometimes cough or choke due to pressure on the neck and the operator is, of necessity, very close to the patient’s face. Therefore, when we resume FNA, patients will be screened for symptoms of COVID-19 infection and both the operator and the patient will be masked,” Dr. Harman continued.

“We routinely wear gloves, [and] whether the operator will wear a surgical or an N95 mask, disposable gown, etc, will depend on CDC guidance and guidance received from our VA infectious disease experts as it is applied specifically to each patient evaluation.”

The authors have reported no relevant financial relationships.
 

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

With a few notable exceptions, the majority of fine needle aspiration (FNA) biopsies of thyroid nodules should be delayed until the risk of COVID-19, and the burden on resources, has lessened, according to expert consensus.

copyright/Sebastian Kaulitzki/Fotolia

“Our group recommends that FNA biopsy of most asymptomatic thyroid nodules – taking into account the sonographic characteristics and patients’ clinical picture – be deferred to a later time, when risk of exposure to COVID-19 is more manageable and resource restriction is no longer a concern,” said the endocrinologists, writing in a guest editorial in Clinical Thyroidology.

All elective procedures have been canceled under guidance of the Centers for Disease Control and Prevention, in conjunction with the U.S. surgeon general, in response to the COVID-19 pandemic. However, thyroid nodule FNAs, though elective, fall into the category of being considered medically necessary and potentially prolonging life expectancy

Yet, with approximately 90% of asymptomatic thyroid nodules turning out to be benign and little evidence that early detection and treatment affects disease outcomes, there is a strong argument for deferral in most cases, stressed Ming Lee, MD, and colleagues, of the endocrinology division at Phoenix (Ariz.) Veterans Affairs Health Care System (PVAHCS), who convened a multidisciplinary meeting to address the urgent issue.

Patients should instead be interviewed by an endocrinologist (preferably via telehealth) to collect their clinical history as well as assess their perception of the disease and risk of malignancy, senior author S. Mitchell Harman, MD, chief of PVAHCS, said in an interview.

“The principal guiding factor should be the objectively assessed likelihood of malignancy of the individual patient’s nodule(s),” he said.

“In my opinion, we should also factor in the patient’s level of anxiety, since some patients are more sanguine about risk than others and our goal is to provide relief of anxiety as well as to determine need for, and course of, subsequent treatment,” Dr. Harman added. 

Vast majority of malignant thyroid nodules are DTC, which is ‘indolent’

Dr. Lee and colleagues noted that, even of the 10% of thyroid nodules that do prove to be malignant, the vast majority of these (90%) are differentiated thyroid cancers (DTC). In general, patients with DTC “follow an indolent course and have excellent outcomes.”

“There is little evidence that early detection and treatment of DTC significantly alters disease outcomes as the overall mortality rate for DTC has remained low, at around 0.5%,” they wrote.

They also noted that ultrasound features of thyroid nodules can help guide priority for the future timing of an FNA procedure, but should not be the sole basis for deciding on immediate thyroid FNA or surgery.

Exceptions to the rule

Exceptions for considering FNA include more urgent thyroid disease diagnoses, including those that are symptomatic:

Suspected medullary thyroid cancer

“Regarding medullary thyroid cancer (MTC), early diagnosis and surgery do significantly improve outcomes, therefore, delaying FNA of nodules harboring MTC could be potentially injurious,” the authors said.

They suggested, however, measuring calcitonin levels instead, which they noted “is still controversial” in the United States, but “we feel it would be justified in patients with thyroid nodules that would usually be indicated for FNA.”

Those with a family history of MTC, or nodules located in the posterior upper third of lateral lobes (the usual location of MTC), should have calcitonin levels measured.

If calcitonin levels are above 10 pg/mL, “FNA should be offered as early as possible.”

“Significantly elevated serum calcitonin levels (e.g., > 100 pg/mL) should be considered an indication for surgery without cytologic confirmation by FNA,” they added.

Anaplastic thyroid cancer

Anaplastic thyroid cancer, though rare, “is one of the few occasions when thyroid surgery should be performed on an urgent basis, as this condition can worsen very rapidly.

“Patients typically present with a rapidly enlarging thyroid mass that is associated with compressive symptoms, such as dysphagia and dyspnea,” they observed.

In this instance, although FNA is part of the preoperative work-up, it is often nondiagnostic and could require additional sampling.

“At the time of this pandemic, it is reasonable that after a multidisciplinary discussion, such patients with the appropriate clinical scenario be referred for thyroid surgery, with or without prior FNA, based on the team’s judgment,” the authors recommended.

Long-standing thyroid masses

These are usually large and/or closely associated with vital structures, such as the trachea and esophagus, and when such masses cause compressive symptoms, thyroid surgery typically is warranted.

And although prior FNA is helpful to obtain a cytologic diagnosis, as this may change the extent of surgery, it may not always be essential.

Broadly, symptomatic patients with compressive symptoms threatening vital structures can be directly referred to a surgeon, with the timing for surgery jointly decided based on the severity of symptoms, rapidity of disease progression, local COVID-19 status, and available resources.

“During the pandemic, we believe that the vast majority of thyroid FNAs should be considered optional, and extent of surgery can be determined by pathological analysis of frozen sections intraoperatively,” they wrote.

“The value of FNA in these situations is less compelling in the current COVID-19 setting, as the basis of decision for surgery has been already determined,” the authors explained.

If urgent FNA needed, screen patient for COVID-19 and use PPE

Should the need for an urgent thyroid FNA occur, patients should be screened and tested for COVID-19 by a clinician wearing personal protective equipment (PPE), said Dr. Lee and colleagues.

“It is crucial to carefully weigh the risks of COVID-19 exposure, availability of resources, and urgency of these procedures for each patient in our individual practice settings,” they noted.

As restrictions eventually loosen, precautions will still be necessary to some degree, Dr. Harman said.

“I do not consider FNA a ‘high-risk’ procedure in the era of COVID-19, since it does not routinely result in profuse aerosolization of respiratory fluids,” he said in an interview.

“However, patients do sometimes cough or choke due to pressure on the neck and the operator is, of necessity, very close to the patient’s face. Therefore, when we resume FNA, patients will be screened for symptoms of COVID-19 infection and both the operator and the patient will be masked,” Dr. Harman continued.

“We routinely wear gloves, [and] whether the operator will wear a surgical or an N95 mask, disposable gown, etc, will depend on CDC guidance and guidance received from our VA infectious disease experts as it is applied specifically to each patient evaluation.”

The authors have reported no relevant financial relationships.
 

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

Teprotumumab (Tepezza, Horizon Therapeutics), the first-ever medication approved specifically to treat thyroid eye disease, works in patients regardless of age, gender, and smoking status, new research finds.

The data were presented on March 31 by Raymond S. Douglas, MD, director of the thyroid eye disease program at Cedars-Sinai Medical Center, Los Angeles, during a virtual news conference held by the Endocrine Society. The study had been slated for presentation during ENDO 2020, the society’s annual meeting, which was canceled because of the COVID-19 pandemic.

Thyroid eye disease occurs in up to 50% of people with Graves disease, causing a variety of symptoms, such as eye pain, double vision, light sensitivity or difficulty closing the eye, as well as proptosis, or bulging of the eye, and vision-threatening complications. It affects more women than men, and the symptoms can lead to the progressive inability to perform important daily activities, such as driving or working.

Teprotumumab is a fully human monoclonal antibody inhibitor of the insulin-like growth factor-1 (IGF-1) receptor and was approved by the US Food and Drug Administration in January 2020. Prior to that, therapy typically involved steroids or, in severe cases, surgery.

Blocking the IGF-1 receptor leads to reduced inflammation and reversal of retro-orbital tissue expansion and hyaluronan production in the eye orbit. Teprotumumab is given as an infusion once every 3 weeks for a total of eight infusions.
 

“Exciting to have an agent” that reduces proptosis to this degree

Previously reported pooled phase 2 and phase 3 data from the randomized, placebo-controlled OPTIC trial involving 171 patients showed significantly greater reductions in proptosis, as well as diplopia, and clinical symptoms of inflammation with teprotumumab versus placebo.

“This has really been unheralded in comparison to other medical therapies previously offered,” Dr. Douglas said during the briefing.

Now, the new analysis shows that the drug works across patient subgroups, he added, highlighting in particular the fact that the agent seems to work equally well in smokers and nonsmokers. Smoking leads to a worse prognosis in thyroid eye disease.

Asked to comment, endocrinologist David C. Lieb, MD, of Eastern Virginia Medical School, Norfolk, said in an interview, “It’s reassuring that this drug appears to have benefits in reducing proptosis across multiple age groups, in both genders, and that there are also benefits seen in patients who smoke and who don’t.”

So far Dr. Lieb has two patients who have been prescribed teprotumumab by their ophthalmologists, but it’s too soon to know how they’ll respond.

“I have no first-hand experience yet, but it’s very exciting to have something to offer patients with active Graves eye disease, which causes a lot of disability for people. It makes work difficult and driving difficult. It’s exciting to have an agent that reduces proptosis to the degree that this one does because we haven’t had anything like this before,” he said.

All patient subgroups benefited in combined analysis

A total of 79 patients completed phase 2 and 76 patients completed phase 3 of the OPTIC trial.

Overall, the proportions achieving proptosis reductions of at least 2 mm without deterioration in the fellow eye at week 24 were 77.4% with teprotumumab versus 14.9% with placebo in the intention-to-treat analysis (P < .001), respectively, and 84.8% versus 17.1% in the per-protocol analysis (P < .001). The number needed to treat was 1.6.

Similar results were achieved across all subgroups of patients: those aged 65 and older versus younger than aged 65 years; male versus female; tobacco user versus nonuser; and U.S. versus E.U. study centers (all P < .001).

Overall, the average decrease in proptosis was 3.1 mm, compared to just 0.4 mm with placebo (P < .001). By subgroup, those reductions ranged from 3.55 mm for those aged 65 and older to 2.93 mm for the U.S. group.

The average proptosis reductions with teprotumumab were 2.99 mm among smokers versus 3.20 mm in nonsmokers, but responses in both groups were significant when compared with placebo.

Smoking contributes to the severity of thyroid eye disease and is associated with more optic neuropathy, poorer response to anti-inflammatory treatment, and worse outcomes, Dr. Douglas said. “Smoking appears to preferentially cause fibroblasts in the orbit to increase proinflammatory cytokines. ... It’s reassuring that this medicine does work in smokers since most other medications are much less effective in reducing inflammatory signs in smoking versus nonsmoking patients.”
 

Most adverse reactions disappeared after infusion stopped

In the pooled studies overall there were no deaths, but there were seven severe adverse events in the teprotumumab group versus one in the placebo group. Two adverse events in the teprotumumab group – diarrhea and infusion-related reaction – were considered treatment-related and led to drug discontinuation. Another adverse event, Hashimoto’s encephalopathy, was deemed possibly related to the drug and also led to discontinuation.

Treatment-emergent adverse events occurred in 79.8% of patients treated with teprotumumab versus 69.8% with placebo. Those occurring in 5% or more of patients included muscle spasms (25% vs. 7%), nausea (17% vs. 9%), alopecia (13% vs. 8%), and diarrhea (12% vs. 8%). Most were well tolerated and tended to resolve after the infusions ended, Dr. Douglas noted, adding muscle spasms tended to occur at night, improved with massage, and were not accompanied by electrolyte abnormalities.

Antidrug antibodies were detected in two teprotumumab-treated patients, one at study day 1 and another at week 3 during the 24-week treatment period. The patient with antibodies at day 1 also tested positive at week 72. “[Antidrug] antibodies appeared to be very uncommon,” Dr. Douglas noted.

The trial was sponsored by Horizon Therapeutics. Dr. Douglas is a consultant for Horizon Therapeutics and Immunovant. Dr. Lieb has reported no relevant financial relationships. The research will be published in a special supplemental issue of the Journal of the Endocrine Society. In addition to a series of news conferences on March 30-31, the society will host ENDO Online 2020 during June 8-22, which will present programming for clinicians and researchers.

This article first appeared on Medscape.com.

Teprotumumab (Tepezza, Horizon Therapeutics), the first-ever medication approved specifically to treat thyroid eye disease, works in patients regardless of age, gender, and smoking status, new research finds.

The data were presented on March 31 by Raymond S. Douglas, MD, director of the thyroid eye disease program at Cedars-Sinai Medical Center, Los Angeles, during a virtual news conference held by the Endocrine Society. The study had been slated for presentation during ENDO 2020, the society’s annual meeting, which was canceled because of the COVID-19 pandemic.

Thyroid eye disease occurs in up to 50% of people with Graves disease, causing a variety of symptoms, such as eye pain, double vision, light sensitivity or difficulty closing the eye, as well as proptosis, or bulging of the eye, and vision-threatening complications. It affects more women than men, and the symptoms can lead to the progressive inability to perform important daily activities, such as driving or working.

Teprotumumab is a fully human monoclonal antibody inhibitor of the insulin-like growth factor-1 (IGF-1) receptor and was approved by the US Food and Drug Administration in January 2020. Prior to that, therapy typically involved steroids or, in severe cases, surgery.

Blocking the IGF-1 receptor leads to reduced inflammation and reversal of retro-orbital tissue expansion and hyaluronan production in the eye orbit. Teprotumumab is given as an infusion once every 3 weeks for a total of eight infusions.
 

“Exciting to have an agent” that reduces proptosis to this degree

Previously reported pooled phase 2 and phase 3 data from the randomized, placebo-controlled OPTIC trial involving 171 patients showed significantly greater reductions in proptosis, as well as diplopia, and clinical symptoms of inflammation with teprotumumab versus placebo.

“This has really been unheralded in comparison to other medical therapies previously offered,” Dr. Douglas said during the briefing.

Now, the new analysis shows that the drug works across patient subgroups, he added, highlighting in particular the fact that the agent seems to work equally well in smokers and nonsmokers. Smoking leads to a worse prognosis in thyroid eye disease.

Asked to comment, endocrinologist David C. Lieb, MD, of Eastern Virginia Medical School, Norfolk, said in an interview, “It’s reassuring that this drug appears to have benefits in reducing proptosis across multiple age groups, in both genders, and that there are also benefits seen in patients who smoke and who don’t.”

So far Dr. Lieb has two patients who have been prescribed teprotumumab by their ophthalmologists, but it’s too soon to know how they’ll respond.

“I have no first-hand experience yet, but it’s very exciting to have something to offer patients with active Graves eye disease, which causes a lot of disability for people. It makes work difficult and driving difficult. It’s exciting to have an agent that reduces proptosis to the degree that this one does because we haven’t had anything like this before,” he said.

All patient subgroups benefited in combined analysis

A total of 79 patients completed phase 2 and 76 patients completed phase 3 of the OPTIC trial.

Overall, the proportions achieving proptosis reductions of at least 2 mm without deterioration in the fellow eye at week 24 were 77.4% with teprotumumab versus 14.9% with placebo in the intention-to-treat analysis (P < .001), respectively, and 84.8% versus 17.1% in the per-protocol analysis (P < .001). The number needed to treat was 1.6.

Similar results were achieved across all subgroups of patients: those aged 65 and older versus younger than aged 65 years; male versus female; tobacco user versus nonuser; and U.S. versus E.U. study centers (all P < .001).

Overall, the average decrease in proptosis was 3.1 mm, compared to just 0.4 mm with placebo (P < .001). By subgroup, those reductions ranged from 3.55 mm for those aged 65 and older to 2.93 mm for the U.S. group.

The average proptosis reductions with teprotumumab were 2.99 mm among smokers versus 3.20 mm in nonsmokers, but responses in both groups were significant when compared with placebo.

Smoking contributes to the severity of thyroid eye disease and is associated with more optic neuropathy, poorer response to anti-inflammatory treatment, and worse outcomes, Dr. Douglas said. “Smoking appears to preferentially cause fibroblasts in the orbit to increase proinflammatory cytokines. ... It’s reassuring that this medicine does work in smokers since most other medications are much less effective in reducing inflammatory signs in smoking versus nonsmoking patients.”
 

Most adverse reactions disappeared after infusion stopped

In the pooled studies overall there were no deaths, but there were seven severe adverse events in the teprotumumab group versus one in the placebo group. Two adverse events in the teprotumumab group – diarrhea and infusion-related reaction – were considered treatment-related and led to drug discontinuation. Another adverse event, Hashimoto’s encephalopathy, was deemed possibly related to the drug and also led to discontinuation.

Treatment-emergent adverse events occurred in 79.8% of patients treated with teprotumumab versus 69.8% with placebo. Those occurring in 5% or more of patients included muscle spasms (25% vs. 7%), nausea (17% vs. 9%), alopecia (13% vs. 8%), and diarrhea (12% vs. 8%). Most were well tolerated and tended to resolve after the infusions ended, Dr. Douglas noted, adding muscle spasms tended to occur at night, improved with massage, and were not accompanied by electrolyte abnormalities.

Antidrug antibodies were detected in two teprotumumab-treated patients, one at study day 1 and another at week 3 during the 24-week treatment period. The patient with antibodies at day 1 also tested positive at week 72. “[Antidrug] antibodies appeared to be very uncommon,” Dr. Douglas noted.

The trial was sponsored by Horizon Therapeutics. Dr. Douglas is a consultant for Horizon Therapeutics and Immunovant. Dr. Lieb has reported no relevant financial relationships. The research will be published in a special supplemental issue of the Journal of the Endocrine Society. In addition to a series of news conferences on March 30-31, the society will host ENDO Online 2020 during June 8-22, which will present programming for clinicians and researchers.

This article first appeared on Medscape.com.

Teprotumumab (Tepezza, Horizon Therapeutics), the first-ever medication approved specifically to treat thyroid eye disease, works in patients regardless of age, gender, and smoking status, new research finds.

The data were presented on March 31 by Raymond S. Douglas, MD, director of the thyroid eye disease program at Cedars-Sinai Medical Center, Los Angeles, during a virtual news conference held by the Endocrine Society. The study had been slated for presentation during ENDO 2020, the society’s annual meeting, which was canceled because of the COVID-19 pandemic.

Thyroid eye disease occurs in up to 50% of people with Graves disease, causing a variety of symptoms, such as eye pain, double vision, light sensitivity or difficulty closing the eye, as well as proptosis, or bulging of the eye, and vision-threatening complications. It affects more women than men, and the symptoms can lead to the progressive inability to perform important daily activities, such as driving or working.

Teprotumumab is a fully human monoclonal antibody inhibitor of the insulin-like growth factor-1 (IGF-1) receptor and was approved by the US Food and Drug Administration in January 2020. Prior to that, therapy typically involved steroids or, in severe cases, surgery.

Blocking the IGF-1 receptor leads to reduced inflammation and reversal of retro-orbital tissue expansion and hyaluronan production in the eye orbit. Teprotumumab is given as an infusion once every 3 weeks for a total of eight infusions.
 

“Exciting to have an agent” that reduces proptosis to this degree

Previously reported pooled phase 2 and phase 3 data from the randomized, placebo-controlled OPTIC trial involving 171 patients showed significantly greater reductions in proptosis, as well as diplopia, and clinical symptoms of inflammation with teprotumumab versus placebo.

“This has really been unheralded in comparison to other medical therapies previously offered,” Dr. Douglas said during the briefing.

Now, the new analysis shows that the drug works across patient subgroups, he added, highlighting in particular the fact that the agent seems to work equally well in smokers and nonsmokers. Smoking leads to a worse prognosis in thyroid eye disease.

Asked to comment, endocrinologist David C. Lieb, MD, of Eastern Virginia Medical School, Norfolk, said in an interview, “It’s reassuring that this drug appears to have benefits in reducing proptosis across multiple age groups, in both genders, and that there are also benefits seen in patients who smoke and who don’t.”

So far Dr. Lieb has two patients who have been prescribed teprotumumab by their ophthalmologists, but it’s too soon to know how they’ll respond.

“I have no first-hand experience yet, but it’s very exciting to have something to offer patients with active Graves eye disease, which causes a lot of disability for people. It makes work difficult and driving difficult. It’s exciting to have an agent that reduces proptosis to the degree that this one does because we haven’t had anything like this before,” he said.

All patient subgroups benefited in combined analysis

A total of 79 patients completed phase 2 and 76 patients completed phase 3 of the OPTIC trial.

Overall, the proportions achieving proptosis reductions of at least 2 mm without deterioration in the fellow eye at week 24 were 77.4% with teprotumumab versus 14.9% with placebo in the intention-to-treat analysis (P < .001), respectively, and 84.8% versus 17.1% in the per-protocol analysis (P < .001). The number needed to treat was 1.6.

Similar results were achieved across all subgroups of patients: those aged 65 and older versus younger than aged 65 years; male versus female; tobacco user versus nonuser; and U.S. versus E.U. study centers (all P < .001).

Overall, the average decrease in proptosis was 3.1 mm, compared to just 0.4 mm with placebo (P < .001). By subgroup, those reductions ranged from 3.55 mm for those aged 65 and older to 2.93 mm for the U.S. group.

The average proptosis reductions with teprotumumab were 2.99 mm among smokers versus 3.20 mm in nonsmokers, but responses in both groups were significant when compared with placebo.

Smoking contributes to the severity of thyroid eye disease and is associated with more optic neuropathy, poorer response to anti-inflammatory treatment, and worse outcomes, Dr. Douglas said. “Smoking appears to preferentially cause fibroblasts in the orbit to increase proinflammatory cytokines. ... It’s reassuring that this medicine does work in smokers since most other medications are much less effective in reducing inflammatory signs in smoking versus nonsmoking patients.”
 

Most adverse reactions disappeared after infusion stopped

In the pooled studies overall there were no deaths, but there were seven severe adverse events in the teprotumumab group versus one in the placebo group. Two adverse events in the teprotumumab group – diarrhea and infusion-related reaction – were considered treatment-related and led to drug discontinuation. Another adverse event, Hashimoto’s encephalopathy, was deemed possibly related to the drug and also led to discontinuation.

Treatment-emergent adverse events occurred in 79.8% of patients treated with teprotumumab versus 69.8% with placebo. Those occurring in 5% or more of patients included muscle spasms (25% vs. 7%), nausea (17% vs. 9%), alopecia (13% vs. 8%), and diarrhea (12% vs. 8%). Most were well tolerated and tended to resolve after the infusions ended, Dr. Douglas noted, adding muscle spasms tended to occur at night, improved with massage, and were not accompanied by electrolyte abnormalities.

Antidrug antibodies were detected in two teprotumumab-treated patients, one at study day 1 and another at week 3 during the 24-week treatment period. The patient with antibodies at day 1 also tested positive at week 72. “[Antidrug] antibodies appeared to be very uncommon,” Dr. Douglas noted.

The trial was sponsored by Horizon Therapeutics. Dr. Douglas is a consultant for Horizon Therapeutics and Immunovant. Dr. Lieb has reported no relevant financial relationships. The research will be published in a special supplemental issue of the Journal of the Endocrine Society. In addition to a series of news conferences on March 30-31, the society will host ENDO Online 2020 during June 8-22, which will present programming for clinicians and researchers.

This article first appeared on Medscape.com.

People with hypothyroidism who choose desiccated thyroid extract (DTE) over levothyroxine alone perceive that it works better, but patients may not be aware of the risks, new research suggests.

Those were among the findings from qualitative analyses of nearly 700 online posts from three popular online hypothyroidism forums that found that 75% of patients felt they fared better on DTE than the standard therapy of levothyroxine (LT4).

A select group of patients do better on combined T4/T3

Asked to comment, endocrinologist Rachel Pessah-Pollack, MD, of New York University Langone Health, said in an interview, “Animal-derived desiccated thyroid hormone contains both T4 and T3. We typically do not recommend using this because it can vary in concentration, meaning that the actual preparation is not physiologic.”

Dr. Pessah-Pollack, a coauthor of the 2012 joint clinical practice guidelines on hypothyroidism by the American Thyroid Association and American Association of Clinical Endocrinologists, added that one of the major concerns about using DTE is the risk for iatrogenic hyperthyroidism, which could potentially lead to atrial fibrillation and fractures.

“That is one of the main factors that drive many professional societies to really use caution regarding DTE. That’s also why major societies recommend against using DTE ... based on the evidence to date,” she said.

The whole issue of “combination therapy” in hypothyroidism is contentious, however. Physicians can also prescribe a “combination” of synthetic levothyroxine (LT4) and triiodothyronine (LT3) treatment; this, along with use of DTE products, has been a subject of debate for many years.

The current (2014) American Thyroid Association guidelines do not specifically rule out use of synthetic LT4/LT3 therapy, rather they “recommend only against the routine use of combination therapy.” And although they don’t expressly endorse use of DTE, they removed a statement saying it “should not be used.”

“There is definitely a select group of patients who do better on combined T4/T3 treatment, and we’re still trying to delineate who that population is,”Dr. Pessah-Pollack said.

“As long as these patients are closely monitored and aware of the risk of hyperthyroidism and have their levels followed to ensure that they’re not hyperthyroid, in select cases this is appropriate.”

“But, first-line is ensuring that a good evaluation occurs. ... Clearly this helps us understand that we do need more studies in this area – well-designed, blinded studies to really help us get to the bottom of this controversy.”
 

Those taking DTE cite improved symptoms, well-being

Dr. Toloza and colleagues analyzed 673 posts from three online forums, WebMD (Medscape’s parent company), PatientsLikeMe, and Drugs.com, selected from an initial 1,235 posts because they included more complete information.

About half (51%, n = 257) of patients had primary hypothyroidism/Hashimoto’s thyroiditis, 25% (n = 126) had postsurgical hypothyroidism, and 16% (n = 81) had postablation hypothyroidism. Among the 172 posts in which DTE dose information was available, the mean dose was 84.1 mg/day. Treatment duration ranged widely, from 2 weeks to 45 years.

Among the posts describing the source of the DTE prescription, the initial interest was driven mainly by the patient in 54% (n = 88), while 46% (n = 74) said that a clinician drove their interest in trying DTE. (The type of clinician was not reported.)

Among posts mentioning the source of DTE, local pharmacies were the most common (63%, n = 75), followed by pharmacies outside the United States (31%, n = 37), and online (6%, n = 7).

Previous thyroid treatments were mentioned in 300 posts, of which 93% mentioned LT4 monotherapy.

Among the reasons for changing to DTE were no improvement in clinical symptoms (47%, n = 75), development of side effects (24%, n = 38), no change in overall well-being (22%, n = 36), and no changes in laboratory work-up (7%, n = 12).

Perceived benefits of DTE included improvement in clinical symptoms (56%, n = 155), change in overall well-being (34%, n = 94), possibility of reaching previous health status (7%, n = 19), and low cost, compared with previous treatment (3%, n = 8).

Specific symptoms reported to have improved included fatigue (28%, n = 43), weight gain (17%, n = 26), and neurocognitive symptoms (5%, n = 8). The average time to notice benefits with DTE was about 30 days but ranged widely from 2 days to 4 months.

The majority of posts (77%, n = 99) stated that DTE was more effective than their previous therapy, while 13% (n = 17) described it as equally effective, and 10% (n = 13) said it was less effective.

Side effects of DTE were described by 20% (n = 136), including weight loss (15%), fatigue (11%), palpitations (11%), heat intolerance (11%), sleep disturbances (10%), high blood pressure (7%), and hair loss (5%).
 

“Doctors think they know how u feel”

A qualitative analysis of the posts yielded five major themes: experience with previous therapies before starting DTE, perceived effectiveness and benefits of DTE, DTE side effects, need for individualized therapy for hypothyroidism, and barriers to obtaining DTE.

One patient posted: “Synthroid [levothyroxine] did not help ... and gives me bad side effects. ... My endocrinologist blamed all side effects on everything except the Synthroid.”

Another wrote, “It [Armour] changed my life. ...I’m glad I found a medication that makes me feel normal again. ... All have improved; moods, skin (no itching), no headaches, goiter is down.”

Others cited the lower cost of Armour compared with Synthroid.

However, some expressed negative experiences with DTE, such as, “My doctor expected that this medication would help me with brain fog, energy, and tiredness. I experienced the opposite.”

And some couldn’t obtain it. One wrote, “Doctors think they know how u feel and do not even tell you about Armour. I asked my doctor and was told there was not enough studies on it to show its effectiveness.”
 

Better evaluation, more data needed

Dr. Pessah-Pollack pointed out that the study data don’t address whether patients’ initially prescribed levothyroxine doses were optimal, and noted that sometimes changes are needed, such as during pregnancy, following weight gain, or if the patient is taking other certain medications.

“It’s unclear from patient-reported symptoms whether or not they actually had an evaluation of their thyroid levels to ensure that their dose of thyroid hormone was correct before switching over to T4/T3 replacement. ... There are many factors that need to be taken into account before we decide that the medication itself isn’t working.”

What’s sorely needed, she said, are “well-designed, blinded studies that look at this controversy.”

“Here, we don’t know why patients are feeling better. ... We need to do additional work including validated symptom questionnaires and comparing thyroid levels of patients who are on Armour thyroid with those on levothyroxine monotherapy.”

Dr. Toloza agrees: “It is not possible to say that DTE is working better for the user due to the limitations and the nature of the data used in our study.”

“However, our findings are in-line with previously published research, which has shown that a subset of patients may prefer DTE to levothyroxine and have higher satisfaction with this treatment. Nevertheless, the reason behind this is still not well understood,” and it should be further investigated.

Dr. Toloza and colleagues reported that they had no conflicts of interests. Dr. Pessah-Pollack has reported being an adviser for Boehringer Ingelheim-Eli Lilly and Radius Health, and a moderator for Sanofi.

This article first appeared on Medscape.com.

People with hypothyroidism who choose desiccated thyroid extract (DTE) over levothyroxine alone perceive that it works better, but patients may not be aware of the risks, new research suggests.

Those were among the findings from qualitative analyses of nearly 700 online posts from three popular online hypothyroidism forums that found that 75% of patients felt they fared better on DTE than the standard therapy of levothyroxine (LT4).

A select group of patients do better on combined T4/T3

Asked to comment, endocrinologist Rachel Pessah-Pollack, MD, of New York University Langone Health, said in an interview, “Animal-derived desiccated thyroid hormone contains both T4 and T3. We typically do not recommend using this because it can vary in concentration, meaning that the actual preparation is not physiologic.”

Dr. Pessah-Pollack, a coauthor of the 2012 joint clinical practice guidelines on hypothyroidism by the American Thyroid Association and American Association of Clinical Endocrinologists, added that one of the major concerns about using DTE is the risk for iatrogenic hyperthyroidism, which could potentially lead to atrial fibrillation and fractures.

“That is one of the main factors that drive many professional societies to really use caution regarding DTE. That’s also why major societies recommend against using DTE ... based on the evidence to date,” she said.

The whole issue of “combination therapy” in hypothyroidism is contentious, however. Physicians can also prescribe a “combination” of synthetic levothyroxine (LT4) and triiodothyronine (LT3) treatment; this, along with use of DTE products, has been a subject of debate for many years.

The current (2014) American Thyroid Association guidelines do not specifically rule out use of synthetic LT4/LT3 therapy, rather they “recommend only against the routine use of combination therapy.” And although they don’t expressly endorse use of DTE, they removed a statement saying it “should not be used.”

“There is definitely a select group of patients who do better on combined T4/T3 treatment, and we’re still trying to delineate who that population is,”Dr. Pessah-Pollack said.

“As long as these patients are closely monitored and aware of the risk of hyperthyroidism and have their levels followed to ensure that they’re not hyperthyroid, in select cases this is appropriate.”

“But, first-line is ensuring that a good evaluation occurs. ... Clearly this helps us understand that we do need more studies in this area – well-designed, blinded studies to really help us get to the bottom of this controversy.”
 

Those taking DTE cite improved symptoms, well-being

Dr. Toloza and colleagues analyzed 673 posts from three online forums, WebMD (Medscape’s parent company), PatientsLikeMe, and Drugs.com, selected from an initial 1,235 posts because they included more complete information.

About half (51%, n = 257) of patients had primary hypothyroidism/Hashimoto’s thyroiditis, 25% (n = 126) had postsurgical hypothyroidism, and 16% (n = 81) had postablation hypothyroidism. Among the 172 posts in which DTE dose information was available, the mean dose was 84.1 mg/day. Treatment duration ranged widely, from 2 weeks to 45 years.

Among the posts describing the source of the DTE prescription, the initial interest was driven mainly by the patient in 54% (n = 88), while 46% (n = 74) said that a clinician drove their interest in trying DTE. (The type of clinician was not reported.)

Among posts mentioning the source of DTE, local pharmacies were the most common (63%, n = 75), followed by pharmacies outside the United States (31%, n = 37), and online (6%, n = 7).

Previous thyroid treatments were mentioned in 300 posts, of which 93% mentioned LT4 monotherapy.

Among the reasons for changing to DTE were no improvement in clinical symptoms (47%, n = 75), development of side effects (24%, n = 38), no change in overall well-being (22%, n = 36), and no changes in laboratory work-up (7%, n = 12).

Perceived benefits of DTE included improvement in clinical symptoms (56%, n = 155), change in overall well-being (34%, n = 94), possibility of reaching previous health status (7%, n = 19), and low cost, compared with previous treatment (3%, n = 8).

Specific symptoms reported to have improved included fatigue (28%, n = 43), weight gain (17%, n = 26), and neurocognitive symptoms (5%, n = 8). The average time to notice benefits with DTE was about 30 days but ranged widely from 2 days to 4 months.

The majority of posts (77%, n = 99) stated that DTE was more effective than their previous therapy, while 13% (n = 17) described it as equally effective, and 10% (n = 13) said it was less effective.

Side effects of DTE were described by 20% (n = 136), including weight loss (15%), fatigue (11%), palpitations (11%), heat intolerance (11%), sleep disturbances (10%), high blood pressure (7%), and hair loss (5%).
 

“Doctors think they know how u feel”

A qualitative analysis of the posts yielded five major themes: experience with previous therapies before starting DTE, perceived effectiveness and benefits of DTE, DTE side effects, need for individualized therapy for hypothyroidism, and barriers to obtaining DTE.

One patient posted: “Synthroid [levothyroxine] did not help ... and gives me bad side effects. ... My endocrinologist blamed all side effects on everything except the Synthroid.”

Another wrote, “It [Armour] changed my life. ...I’m glad I found a medication that makes me feel normal again. ... All have improved; moods, skin (no itching), no headaches, goiter is down.”

Others cited the lower cost of Armour compared with Synthroid.

However, some expressed negative experiences with DTE, such as, “My doctor expected that this medication would help me with brain fog, energy, and tiredness. I experienced the opposite.”

And some couldn’t obtain it. One wrote, “Doctors think they know how u feel and do not even tell you about Armour. I asked my doctor and was told there was not enough studies on it to show its effectiveness.”
 

Better evaluation, more data needed

Dr. Pessah-Pollack pointed out that the study data don’t address whether patients’ initially prescribed levothyroxine doses were optimal, and noted that sometimes changes are needed, such as during pregnancy, following weight gain, or if the patient is taking other certain medications.

“It’s unclear from patient-reported symptoms whether or not they actually had an evaluation of their thyroid levels to ensure that their dose of thyroid hormone was correct before switching over to T4/T3 replacement. ... There are many factors that need to be taken into account before we decide that the medication itself isn’t working.”

What’s sorely needed, she said, are “well-designed, blinded studies that look at this controversy.”

“Here, we don’t know why patients are feeling better. ... We need to do additional work including validated symptom questionnaires and comparing thyroid levels of patients who are on Armour thyroid with those on levothyroxine monotherapy.”

Dr. Toloza agrees: “It is not possible to say that DTE is working better for the user due to the limitations and the nature of the data used in our study.”

“However, our findings are in-line with previously published research, which has shown that a subset of patients may prefer DTE to levothyroxine and have higher satisfaction with this treatment. Nevertheless, the reason behind this is still not well understood,” and it should be further investigated.

Dr. Toloza and colleagues reported that they had no conflicts of interests. Dr. Pessah-Pollack has reported being an adviser for Boehringer Ingelheim-Eli Lilly and Radius Health, and a moderator for Sanofi.

This article first appeared on Medscape.com.

People with hypothyroidism who choose desiccated thyroid extract (DTE) over levothyroxine alone perceive that it works better, but patients may not be aware of the risks, new research suggests.

Those were among the findings from qualitative analyses of nearly 700 online posts from three popular online hypothyroidism forums that found that 75% of patients felt they fared better on DTE than the standard therapy of levothyroxine (LT4).

A select group of patients do better on combined T4/T3

Asked to comment, endocrinologist Rachel Pessah-Pollack, MD, of New York University Langone Health, said in an interview, “Animal-derived desiccated thyroid hormone contains both T4 and T3. We typically do not recommend using this because it can vary in concentration, meaning that the actual preparation is not physiologic.”

Dr. Pessah-Pollack, a coauthor of the 2012 joint clinical practice guidelines on hypothyroidism by the American Thyroid Association and American Association of Clinical Endocrinologists, added that one of the major concerns about using DTE is the risk for iatrogenic hyperthyroidism, which could potentially lead to atrial fibrillation and fractures.

“That is one of the main factors that drive many professional societies to really use caution regarding DTE. That’s also why major societies recommend against using DTE ... based on the evidence to date,” she said.

The whole issue of “combination therapy” in hypothyroidism is contentious, however. Physicians can also prescribe a “combination” of synthetic levothyroxine (LT4) and triiodothyronine (LT3) treatment; this, along with use of DTE products, has been a subject of debate for many years.

The current (2014) American Thyroid Association guidelines do not specifically rule out use of synthetic LT4/LT3 therapy, rather they “recommend only against the routine use of combination therapy.” And although they don’t expressly endorse use of DTE, they removed a statement saying it “should not be used.”

“There is definitely a select group of patients who do better on combined T4/T3 treatment, and we’re still trying to delineate who that population is,”Dr. Pessah-Pollack said.

“As long as these patients are closely monitored and aware of the risk of hyperthyroidism and have their levels followed to ensure that they’re not hyperthyroid, in select cases this is appropriate.”

“But, first-line is ensuring that a good evaluation occurs. ... Clearly this helps us understand that we do need more studies in this area – well-designed, blinded studies to really help us get to the bottom of this controversy.”
 

Those taking DTE cite improved symptoms, well-being

Dr. Toloza and colleagues analyzed 673 posts from three online forums, WebMD (Medscape’s parent company), PatientsLikeMe, and Drugs.com, selected from an initial 1,235 posts because they included more complete information.

About half (51%, n = 257) of patients had primary hypothyroidism/Hashimoto’s thyroiditis, 25% (n = 126) had postsurgical hypothyroidism, and 16% (n = 81) had postablation hypothyroidism. Among the 172 posts in which DTE dose information was available, the mean dose was 84.1 mg/day. Treatment duration ranged widely, from 2 weeks to 45 years.

Among the posts describing the source of the DTE prescription, the initial interest was driven mainly by the patient in 54% (n = 88), while 46% (n = 74) said that a clinician drove their interest in trying DTE. (The type of clinician was not reported.)

Among posts mentioning the source of DTE, local pharmacies were the most common (63%, n = 75), followed by pharmacies outside the United States (31%, n = 37), and online (6%, n = 7).

Previous thyroid treatments were mentioned in 300 posts, of which 93% mentioned LT4 monotherapy.

Among the reasons for changing to DTE were no improvement in clinical symptoms (47%, n = 75), development of side effects (24%, n = 38), no change in overall well-being (22%, n = 36), and no changes in laboratory work-up (7%, n = 12).

Perceived benefits of DTE included improvement in clinical symptoms (56%, n = 155), change in overall well-being (34%, n = 94), possibility of reaching previous health status (7%, n = 19), and low cost, compared with previous treatment (3%, n = 8).

Specific symptoms reported to have improved included fatigue (28%, n = 43), weight gain (17%, n = 26), and neurocognitive symptoms (5%, n = 8). The average time to notice benefits with DTE was about 30 days but ranged widely from 2 days to 4 months.

The majority of posts (77%, n = 99) stated that DTE was more effective than their previous therapy, while 13% (n = 17) described it as equally effective, and 10% (n = 13) said it was less effective.

Side effects of DTE were described by 20% (n = 136), including weight loss (15%), fatigue (11%), palpitations (11%), heat intolerance (11%), sleep disturbances (10%), high blood pressure (7%), and hair loss (5%).
 

“Doctors think they know how u feel”

A qualitative analysis of the posts yielded five major themes: experience with previous therapies before starting DTE, perceived effectiveness and benefits of DTE, DTE side effects, need for individualized therapy for hypothyroidism, and barriers to obtaining DTE.

One patient posted: “Synthroid [levothyroxine] did not help ... and gives me bad side effects. ... My endocrinologist blamed all side effects on everything except the Synthroid.”

Another wrote, “It [Armour] changed my life. ...I’m glad I found a medication that makes me feel normal again. ... All have improved; moods, skin (no itching), no headaches, goiter is down.”

Others cited the lower cost of Armour compared with Synthroid.

However, some expressed negative experiences with DTE, such as, “My doctor expected that this medication would help me with brain fog, energy, and tiredness. I experienced the opposite.”

And some couldn’t obtain it. One wrote, “Doctors think they know how u feel and do not even tell you about Armour. I asked my doctor and was told there was not enough studies on it to show its effectiveness.”
 

Better evaluation, more data needed

Dr. Pessah-Pollack pointed out that the study data don’t address whether patients’ initially prescribed levothyroxine doses were optimal, and noted that sometimes changes are needed, such as during pregnancy, following weight gain, or if the patient is taking other certain medications.

“It’s unclear from patient-reported symptoms whether or not they actually had an evaluation of their thyroid levels to ensure that their dose of thyroid hormone was correct before switching over to T4/T3 replacement. ... There are many factors that need to be taken into account before we decide that the medication itself isn’t working.”

What’s sorely needed, she said, are “well-designed, blinded studies that look at this controversy.”

“Here, we don’t know why patients are feeling better. ... We need to do additional work including validated symptom questionnaires and comparing thyroid levels of patients who are on Armour thyroid with those on levothyroxine monotherapy.”

Dr. Toloza agrees: “It is not possible to say that DTE is working better for the user due to the limitations and the nature of the data used in our study.”

“However, our findings are in-line with previously published research, which has shown that a subset of patients may prefer DTE to levothyroxine and have higher satisfaction with this treatment. Nevertheless, the reason behind this is still not well understood,” and it should be further investigated.

Dr. Toloza and colleagues reported that they had no conflicts of interests. Dr. Pessah-Pollack has reported being an adviser for Boehringer Ingelheim-Eli Lilly and Radius Health, and a moderator for Sanofi.

This article first appeared on Medscape.com.

Nearly one in five individuals with cancer who are treated with immune checkpoint inhibitors develop thyroid dysfunction, new research suggests.

Sebastian Kaulitzki/Fotolia

Immune checkpoint inhibitors have revolutionized the treatment of many different types of cancers, but can also trigger a variety of immune-related adverse effects. As these drugs become more widely used, rates of these events appear to be more common in the real-world compared with clinical trial settings.

In their new study, Zoe Quandt, MD, of the University of California, San Francisco (UCSF), and colleagues specifically looked at thyroid dysfunction in their own institution’s EHR data and found more than double the rate of hypothyroidism and more than triple the rate of hyperthyroidism, compared with rates in published trials.

Moreover, in contrast to previous studies that have found differences in thyroid dysfunction by checkpoint inhibitor type, Dr. Quandt and colleagues instead found significant differences by cancer type.

Dr. Quandt presented the findings during a virtual press briefing held March 31originally scheduled for ENDO 2020.

“Thyroid dysfunction following checkpoint inhibitor therapy appears to be much more common than was previously reported in clinical trials, and this is one of the first studies to show differences by cancer type rather than by checkpoint inhibitor type,” Dr. Quandt said during the presentation.

However, she also cautioned that there’s “a lot more research to be done to validate case definitions and validate these findings.”

Asked to comment, endocrinologist David C. Lieb, MD, associate professor of medicine at Eastern Virginia Medical School in Norfolk, said in an interview, “These drugs are becoming so much more commonly used, so it’s not surprising that we’re seeing more endocrine complications, especially thyroid disease.”

“Endocrinologists need to work closely with oncologists to make sure patients are being screened and followed appropriately.”

‘A much higher percentage than we were expecting’

Dr. Quandt’s study included 1,146 individuals treated with checkpoint inhibitors at UCSF during 2012-2018 who did not have thyroid cancer or preexisting thyroid dysfunction.

Pembrolizumab (Keytruda) was the most common treatment (45%), followed by nivolumab (Opdivo) (20%). Less than 10% of patients received atezolizumab (Tecentriq), durvalumab (Imfizi), ipilimumab (Yervoy) monotherapy, combined ipilimumab/nivolumab, or other combinations of checkpoint inhibitors.

A total of 19.1% developed thyroid disease, with 13.4% having hypothyroidism and 9.5% hyperthyroidism. These figures far exceed those found in a recent meta-analysis of 38 randomized clinical trials of checkpoint inhibitors that included 7551 patients.

“Using this approach, we found a much higher percentage of patients who developed thyroid dysfunction than we were expecting,” Dr. Quandt said.

In both cases, the two categories – hypothyroidism and hyperthyroidism – aren’t mutually exclusive as hypothyroidism can arise de novo or subsequent to hyperthyroidism.

Dr Lieb commented, “It would be interesting to see what the causes of hyperthyroidism are – thyroiditis or Graves disease.”

Dr. Quandt mentioned a possible reason for the large difference between clinical trial and real-world data.

“Once we’re actually using these drugs outside of clinical trials, some of the restrictions about using them in people with other autoimmune diseases have been lifted, so my guess is that as we give them to a broader population we’re seeing more of these [adverse effects],” she suggested.

Also, “In the initial trials, people weren’t quite as aware of the possibilities of these side effects, so now we’re doing many more labs. Patients get thyroid function tests with every infusion, so I think we’re probably catching more patients who develop disease.”
 

Differences by cancer type, not checkpoint inhibitor type

And in a new twist, Dr. Quandt found that, in contrast to the differences seen by checkpoint inhibitor type in randomized trials, “surprisingly, we found that this difference did not reach statistical significance.”

“Instead, we saw that cancer type was associated with development of thyroid dysfunction, even after taking checkpoint inhibitor type into account.”

The percentages of patients who developed thyroid dysfunction ranged from 9.7% of those with glioblastoma to 40.0% of those with renal cell carcinoma.

The reason for this is not clear, said Dr. Quandt in an interview.

One possibility relates to other treatments patients with cancer also receive. In renal cell carcinoma, for example, patients also are treated with tyrosine kinase inhibitors, which can also cause thyroid dysfunction, so they may be more susceptible. Or there may be shared antigens activating the immune system.

“That’s definitely one of the questions we’re looking at,” she said.

Dr. Quandt and Dr. Lieb have reported no relevant financial relationships.

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

Nearly one in five individuals with cancer who are treated with immune checkpoint inhibitors develop thyroid dysfunction, new research suggests.

Sebastian Kaulitzki/Fotolia

Immune checkpoint inhibitors have revolutionized the treatment of many different types of cancers, but can also trigger a variety of immune-related adverse effects. As these drugs become more widely used, rates of these events appear to be more common in the real-world compared with clinical trial settings.

In their new study, Zoe Quandt, MD, of the University of California, San Francisco (UCSF), and colleagues specifically looked at thyroid dysfunction in their own institution’s EHR data and found more than double the rate of hypothyroidism and more than triple the rate of hyperthyroidism, compared with rates in published trials.

Moreover, in contrast to previous studies that have found differences in thyroid dysfunction by checkpoint inhibitor type, Dr. Quandt and colleagues instead found significant differences by cancer type.

Dr. Quandt presented the findings during a virtual press briefing held March 31originally scheduled for ENDO 2020.

“Thyroid dysfunction following checkpoint inhibitor therapy appears to be much more common than was previously reported in clinical trials, and this is one of the first studies to show differences by cancer type rather than by checkpoint inhibitor type,” Dr. Quandt said during the presentation.

However, she also cautioned that there’s “a lot more research to be done to validate case definitions and validate these findings.”

Asked to comment, endocrinologist David C. Lieb, MD, associate professor of medicine at Eastern Virginia Medical School in Norfolk, said in an interview, “These drugs are becoming so much more commonly used, so it’s not surprising that we’re seeing more endocrine complications, especially thyroid disease.”

“Endocrinologists need to work closely with oncologists to make sure patients are being screened and followed appropriately.”

‘A much higher percentage than we were expecting’

Dr. Quandt’s study included 1,146 individuals treated with checkpoint inhibitors at UCSF during 2012-2018 who did not have thyroid cancer or preexisting thyroid dysfunction.

Pembrolizumab (Keytruda) was the most common treatment (45%), followed by nivolumab (Opdivo) (20%). Less than 10% of patients received atezolizumab (Tecentriq), durvalumab (Imfizi), ipilimumab (Yervoy) monotherapy, combined ipilimumab/nivolumab, or other combinations of checkpoint inhibitors.

A total of 19.1% developed thyroid disease, with 13.4% having hypothyroidism and 9.5% hyperthyroidism. These figures far exceed those found in a recent meta-analysis of 38 randomized clinical trials of checkpoint inhibitors that included 7551 patients.

“Using this approach, we found a much higher percentage of patients who developed thyroid dysfunction than we were expecting,” Dr. Quandt said.

In both cases, the two categories – hypothyroidism and hyperthyroidism – aren’t mutually exclusive as hypothyroidism can arise de novo or subsequent to hyperthyroidism.

Dr Lieb commented, “It would be interesting to see what the causes of hyperthyroidism are – thyroiditis or Graves disease.”

Dr. Quandt mentioned a possible reason for the large difference between clinical trial and real-world data.

“Once we’re actually using these drugs outside of clinical trials, some of the restrictions about using them in people with other autoimmune diseases have been lifted, so my guess is that as we give them to a broader population we’re seeing more of these [adverse effects],” she suggested.

Also, “In the initial trials, people weren’t quite as aware of the possibilities of these side effects, so now we’re doing many more labs. Patients get thyroid function tests with every infusion, so I think we’re probably catching more patients who develop disease.”
 

Differences by cancer type, not checkpoint inhibitor type

And in a new twist, Dr. Quandt found that, in contrast to the differences seen by checkpoint inhibitor type in randomized trials, “surprisingly, we found that this difference did not reach statistical significance.”

“Instead, we saw that cancer type was associated with development of thyroid dysfunction, even after taking checkpoint inhibitor type into account.”

The percentages of patients who developed thyroid dysfunction ranged from 9.7% of those with glioblastoma to 40.0% of those with renal cell carcinoma.

The reason for this is not clear, said Dr. Quandt in an interview.

One possibility relates to other treatments patients with cancer also receive. In renal cell carcinoma, for example, patients also are treated with tyrosine kinase inhibitors, which can also cause thyroid dysfunction, so they may be more susceptible. Or there may be shared antigens activating the immune system.

“That’s definitely one of the questions we’re looking at,” she said.

Dr. Quandt and Dr. Lieb have reported no relevant financial relationships.

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

Nearly one in five individuals with cancer who are treated with immune checkpoint inhibitors develop thyroid dysfunction, new research suggests.

Sebastian Kaulitzki/Fotolia

Immune checkpoint inhibitors have revolutionized the treatment of many different types of cancers, but can also trigger a variety of immune-related adverse effects. As these drugs become more widely used, rates of these events appear to be more common in the real-world compared with clinical trial settings.

In their new study, Zoe Quandt, MD, of the University of California, San Francisco (UCSF), and colleagues specifically looked at thyroid dysfunction in their own institution’s EHR data and found more than double the rate of hypothyroidism and more than triple the rate of hyperthyroidism, compared with rates in published trials.

Moreover, in contrast to previous studies that have found differences in thyroid dysfunction by checkpoint inhibitor type, Dr. Quandt and colleagues instead found significant differences by cancer type.

Dr. Quandt presented the findings during a virtual press briefing held March 31originally scheduled for ENDO 2020.

“Thyroid dysfunction following checkpoint inhibitor therapy appears to be much more common than was previously reported in clinical trials, and this is one of the first studies to show differences by cancer type rather than by checkpoint inhibitor type,” Dr. Quandt said during the presentation.

However, she also cautioned that there’s “a lot more research to be done to validate case definitions and validate these findings.”

Asked to comment, endocrinologist David C. Lieb, MD, associate professor of medicine at Eastern Virginia Medical School in Norfolk, said in an interview, “These drugs are becoming so much more commonly used, so it’s not surprising that we’re seeing more endocrine complications, especially thyroid disease.”

“Endocrinologists need to work closely with oncologists to make sure patients are being screened and followed appropriately.”

‘A much higher percentage than we were expecting’

Dr. Quandt’s study included 1,146 individuals treated with checkpoint inhibitors at UCSF during 2012-2018 who did not have thyroid cancer or preexisting thyroid dysfunction.

Pembrolizumab (Keytruda) was the most common treatment (45%), followed by nivolumab (Opdivo) (20%). Less than 10% of patients received atezolizumab (Tecentriq), durvalumab (Imfizi), ipilimumab (Yervoy) monotherapy, combined ipilimumab/nivolumab, or other combinations of checkpoint inhibitors.

A total of 19.1% developed thyroid disease, with 13.4% having hypothyroidism and 9.5% hyperthyroidism. These figures far exceed those found in a recent meta-analysis of 38 randomized clinical trials of checkpoint inhibitors that included 7551 patients.

“Using this approach, we found a much higher percentage of patients who developed thyroid dysfunction than we were expecting,” Dr. Quandt said.

In both cases, the two categories – hypothyroidism and hyperthyroidism – aren’t mutually exclusive as hypothyroidism can arise de novo or subsequent to hyperthyroidism.

Dr Lieb commented, “It would be interesting to see what the causes of hyperthyroidism are – thyroiditis or Graves disease.”

Dr. Quandt mentioned a possible reason for the large difference between clinical trial and real-world data.

“Once we’re actually using these drugs outside of clinical trials, some of the restrictions about using them in people with other autoimmune diseases have been lifted, so my guess is that as we give them to a broader population we’re seeing more of these [adverse effects],” she suggested.

Also, “In the initial trials, people weren’t quite as aware of the possibilities of these side effects, so now we’re doing many more labs. Patients get thyroid function tests with every infusion, so I think we’re probably catching more patients who develop disease.”
 

Differences by cancer type, not checkpoint inhibitor type

And in a new twist, Dr. Quandt found that, in contrast to the differences seen by checkpoint inhibitor type in randomized trials, “surprisingly, we found that this difference did not reach statistical significance.”

“Instead, we saw that cancer type was associated with development of thyroid dysfunction, even after taking checkpoint inhibitor type into account.”

The percentages of patients who developed thyroid dysfunction ranged from 9.7% of those with glioblastoma to 40.0% of those with renal cell carcinoma.

The reason for this is not clear, said Dr. Quandt in an interview.

One possibility relates to other treatments patients with cancer also receive. In renal cell carcinoma, for example, patients also are treated with tyrosine kinase inhibitors, which can also cause thyroid dysfunction, so they may be more susceptible. Or there may be shared antigens activating the immune system.

“That’s definitely one of the questions we’re looking at,” she said.

Dr. Quandt and Dr. Lieb have reported no relevant financial relationships.

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

The American Association of Endocrine Surgeons has issued a first-of-its-kind set of clinical guidelines for the surgical treatment of thyroid disease, offering evidence-based recommendations on the wide-ranging aspects of thyroidectomy and the management of benign, as well as malignant, thyroid nodules and cancer.

Whereas various endocrine and thyroid societies issue guidelines on many aspects of the management of thyroid disease, the new AAES guidelines are the first specifically to address surgical management of thyroid disease in adults.

“These guidelines truly focus on the surgical decision-making and management of thyroid disease. However, there is something for all clinicians who take care of patients with thyroid disease,” lead author Kepal N. Patel, MD, of NYU Langone Health in New York City, said in an interview.

The guidelines, published in the Annals of Surgery, include a total of 66 recommendations from a multidisciplinary panel of 19 experts who reviewed medical literature spanning 1985-2018.

More than 100,000 thyroidectomies are performed each year in the United States alone, and as surgical indications and treatment paradigms evolve, the need for surgical guidance is more important than ever, Dr. Patel said.

“Such transformations have propagated differences in clinical interpretation and management, and as a result, clinical uncertainty, and even controversy, have emerged,” he said. “Recognizing the importance of these changes, the AAES determined that evidence-based clinical guidelines were necessary to enhance the safe and effective surgical treatment of benign and malignant thyroid disease.”

Key areas addressed in the guidelines include the addition of new cytologic and pathologic diagnostic criteria, molecular profiling tests, operative techniques, and adjuncts, as well as the nuances surrounding the sometimes challenging newer concept of “borderline” thyroid tumors, Dr. Patel noted.

In terms of imaging recommendations, for instance, the guidelines recommend the preoperative use of computed tomography or magnetic resonance imaging, as stated in Recommendation 6: “CT or MRI with intravenous contrast should be used preoperatively as an adjunct to ultrasound in selected patients with clinical suspicion for advanced locoregional thyroid cancer.” The recommendation is cited as being “strong,” with a “low quality of evidence.”

Further diagnostic recommendations cover issues that include voice assessment, the risk for vocal fold dysfunction related to thyroid disease and surgery, and the use of fine-needle aspiration biopsy in evaluating suspicious thyroid nodules and lymph nodes.

The guidelines also address the indications for thyroidectomy, with recommendations regarding the extent and outcomes of surgery spanning different categories of thyroid disease. A key recommendation along those lines, for instance, indicates that, when possible, thyroidectomy should be performed by surgeons who perform a high volume of such procedures.

Approaches for safe and effective perioperative management are also covered, and include measures to prevent complications and the use of thyroid tissue diagnosis during surgery, such as core-needle biopsy of the thyroid and cervical lymph nodes, and incisional biopsy of the thyroid, nodal dissection, and concurrent parathyroidectomy.

Other recommendations address the optimal management of thyroid cancer, with an emphasis on a personalized, evidence-based approach tailored to the patient’s situation and preferences.

The authors underscored that, as technology rapidly evolves, “in the future, this work will certainly and rightly need to be done again.” In the meantime, they wrote, recommendations should be relevant to “the target audience [of] the practicing surgeon in a community hospital, academic center, or training program.”

An AAES press release noted that “the members of the expert panel hope their efforts will meet the need for evidence-based recommendations to ‘define practice, personalize care, stratify risk, reduce health care costs, improve outcomes, and identify rational challenges for future efforts.’ ”

The authors of the guidelines reported no conflicts of interest in regard to the guidelines, although the article lists disclosures for six authors.

This article first appeared on Medscape.com.
 

The American Association of Endocrine Surgeons has issued a first-of-its-kind set of clinical guidelines for the surgical treatment of thyroid disease, offering evidence-based recommendations on the wide-ranging aspects of thyroidectomy and the management of benign, as well as malignant, thyroid nodules and cancer.

Whereas various endocrine and thyroid societies issue guidelines on many aspects of the management of thyroid disease, the new AAES guidelines are the first specifically to address surgical management of thyroid disease in adults.

“These guidelines truly focus on the surgical decision-making and management of thyroid disease. However, there is something for all clinicians who take care of patients with thyroid disease,” lead author Kepal N. Patel, MD, of NYU Langone Health in New York City, said in an interview.

The guidelines, published in the Annals of Surgery, include a total of 66 recommendations from a multidisciplinary panel of 19 experts who reviewed medical literature spanning 1985-2018.

More than 100,000 thyroidectomies are performed each year in the United States alone, and as surgical indications and treatment paradigms evolve, the need for surgical guidance is more important than ever, Dr. Patel said.

“Such transformations have propagated differences in clinical interpretation and management, and as a result, clinical uncertainty, and even controversy, have emerged,” he said. “Recognizing the importance of these changes, the AAES determined that evidence-based clinical guidelines were necessary to enhance the safe and effective surgical treatment of benign and malignant thyroid disease.”

Key areas addressed in the guidelines include the addition of new cytologic and pathologic diagnostic criteria, molecular profiling tests, operative techniques, and adjuncts, as well as the nuances surrounding the sometimes challenging newer concept of “borderline” thyroid tumors, Dr. Patel noted.

In terms of imaging recommendations, for instance, the guidelines recommend the preoperative use of computed tomography or magnetic resonance imaging, as stated in Recommendation 6: “CT or MRI with intravenous contrast should be used preoperatively as an adjunct to ultrasound in selected patients with clinical suspicion for advanced locoregional thyroid cancer.” The recommendation is cited as being “strong,” with a “low quality of evidence.”

Further diagnostic recommendations cover issues that include voice assessment, the risk for vocal fold dysfunction related to thyroid disease and surgery, and the use of fine-needle aspiration biopsy in evaluating suspicious thyroid nodules and lymph nodes.

The guidelines also address the indications for thyroidectomy, with recommendations regarding the extent and outcomes of surgery spanning different categories of thyroid disease. A key recommendation along those lines, for instance, indicates that, when possible, thyroidectomy should be performed by surgeons who perform a high volume of such procedures.

Approaches for safe and effective perioperative management are also covered, and include measures to prevent complications and the use of thyroid tissue diagnosis during surgery, such as core-needle biopsy of the thyroid and cervical lymph nodes, and incisional biopsy of the thyroid, nodal dissection, and concurrent parathyroidectomy.

Other recommendations address the optimal management of thyroid cancer, with an emphasis on a personalized, evidence-based approach tailored to the patient’s situation and preferences.

The authors underscored that, as technology rapidly evolves, “in the future, this work will certainly and rightly need to be done again.” In the meantime, they wrote, recommendations should be relevant to “the target audience [of] the practicing surgeon in a community hospital, academic center, or training program.”

An AAES press release noted that “the members of the expert panel hope their efforts will meet the need for evidence-based recommendations to ‘define practice, personalize care, stratify risk, reduce health care costs, improve outcomes, and identify rational challenges for future efforts.’ ”

The authors of the guidelines reported no conflicts of interest in regard to the guidelines, although the article lists disclosures for six authors.

This article first appeared on Medscape.com.
 

The American Association of Endocrine Surgeons has issued a first-of-its-kind set of clinical guidelines for the surgical treatment of thyroid disease, offering evidence-based recommendations on the wide-ranging aspects of thyroidectomy and the management of benign, as well as malignant, thyroid nodules and cancer.

Whereas various endocrine and thyroid societies issue guidelines on many aspects of the management of thyroid disease, the new AAES guidelines are the first specifically to address surgical management of thyroid disease in adults.

“These guidelines truly focus on the surgical decision-making and management of thyroid disease. However, there is something for all clinicians who take care of patients with thyroid disease,” lead author Kepal N. Patel, MD, of NYU Langone Health in New York City, said in an interview.

The guidelines, published in the Annals of Surgery, include a total of 66 recommendations from a multidisciplinary panel of 19 experts who reviewed medical literature spanning 1985-2018.

More than 100,000 thyroidectomies are performed each year in the United States alone, and as surgical indications and treatment paradigms evolve, the need for surgical guidance is more important than ever, Dr. Patel said.

“Such transformations have propagated differences in clinical interpretation and management, and as a result, clinical uncertainty, and even controversy, have emerged,” he said. “Recognizing the importance of these changes, the AAES determined that evidence-based clinical guidelines were necessary to enhance the safe and effective surgical treatment of benign and malignant thyroid disease.”

Key areas addressed in the guidelines include the addition of new cytologic and pathologic diagnostic criteria, molecular profiling tests, operative techniques, and adjuncts, as well as the nuances surrounding the sometimes challenging newer concept of “borderline” thyroid tumors, Dr. Patel noted.

In terms of imaging recommendations, for instance, the guidelines recommend the preoperative use of computed tomography or magnetic resonance imaging, as stated in Recommendation 6: “CT or MRI with intravenous contrast should be used preoperatively as an adjunct to ultrasound in selected patients with clinical suspicion for advanced locoregional thyroid cancer.” The recommendation is cited as being “strong,” with a “low quality of evidence.”

Further diagnostic recommendations cover issues that include voice assessment, the risk for vocal fold dysfunction related to thyroid disease and surgery, and the use of fine-needle aspiration biopsy in evaluating suspicious thyroid nodules and lymph nodes.

The guidelines also address the indications for thyroidectomy, with recommendations regarding the extent and outcomes of surgery spanning different categories of thyroid disease. A key recommendation along those lines, for instance, indicates that, when possible, thyroidectomy should be performed by surgeons who perform a high volume of such procedures.

Approaches for safe and effective perioperative management are also covered, and include measures to prevent complications and the use of thyroid tissue diagnosis during surgery, such as core-needle biopsy of the thyroid and cervical lymph nodes, and incisional biopsy of the thyroid, nodal dissection, and concurrent parathyroidectomy.

Other recommendations address the optimal management of thyroid cancer, with an emphasis on a personalized, evidence-based approach tailored to the patient’s situation and preferences.

The authors underscored that, as technology rapidly evolves, “in the future, this work will certainly and rightly need to be done again.” In the meantime, they wrote, recommendations should be relevant to “the target audience [of] the practicing surgeon in a community hospital, academic center, or training program.”

An AAES press release noted that “the members of the expert panel hope their efforts will meet the need for evidence-based recommendations to ‘define practice, personalize care, stratify risk, reduce health care costs, improve outcomes, and identify rational challenges for future efforts.’ ”

The authors of the guidelines reported no conflicts of interest in regard to the guidelines, although the article lists disclosures for six authors.

This article first appeared on Medscape.com.
 

The Food and Drug Administration has approved the oral cortisol synthesis inhibitor osilodrostat (Isturisa) for the nonsurgical treatment of adults with Cushing’s disease who either are not good candidates for pituitary gland surgery – the recommended first-line therapy – or in whom the disease persists after surgery.

Cushing’s disease is a rare condition caused when a pituitary tumor releases too much of the hormone adrenocorticotropin, which in turn, triggers the adrenal gland to overproduce cortisol. The condition is associated with serious health complications, including high blood pressure, obesity, type 2 diabetes, and compromised immunity.

Osilodrostat is the first therapy approved by the FDA to tackle the overproduction of cortisol, which it does by blocking the 11-beta-hydroxylase enzyme and thus preventing cortisol synthesis, the agency said in a press release.

In November 2019, the European Medicines Agency recommended the granting of a marketing authorization for osilodrostat, also for treating adults with Cushing’s disease.

The U.S. approval was based on outcomes from a study that evaluated the drug’s safety and efficacy in 137 adults with Cushing’s disease who had undergone pituitary surgery but were not cured, or who were not surgical candidates, according the release. About three-quarters of the patients were women, and the mean age was 41 years.

All of the patients started a 24-week, single-arm, open-label period at a dose of 2 mg of osilodrostat twice daily that could be increased every 2 weeks to 30 mg twice daily.

By week 24, cortisol levels in roughly half the patients were within the normal range, and 71 patients who did not need any more dose increases and who tolerated the drug were randomized to either osilodrostat or placebo for an 8-week withdrawal study. At the end of that time, 86% of the osilodrostat patients maintained their normal-range cortisol levels, compared with 30% of those taking placebo.

Osilodrostat is taken as an oral tablet twice a day, in the morning and evening. Among the common side effects reported in the study were adrenal insufficiency, headache, vomiting, nausea, fatigue, and edema, although hypocortisolism, QTc prolongation, and elevations in adrenal hormone precursors, and androgens may also occur, according to the release.

The drug had been given an Orphan Drug Designation in recognition of its intended use in the treatment of a rare disease. The approval was granted to Novartis.

The Food and Drug Administration has approved the oral cortisol synthesis inhibitor osilodrostat (Isturisa) for the nonsurgical treatment of adults with Cushing’s disease who either are not good candidates for pituitary gland surgery – the recommended first-line therapy – or in whom the disease persists after surgery.

Cushing’s disease is a rare condition caused when a pituitary tumor releases too much of the hormone adrenocorticotropin, which in turn, triggers the adrenal gland to overproduce cortisol. The condition is associated with serious health complications, including high blood pressure, obesity, type 2 diabetes, and compromised immunity.

Osilodrostat is the first therapy approved by the FDA to tackle the overproduction of cortisol, which it does by blocking the 11-beta-hydroxylase enzyme and thus preventing cortisol synthesis, the agency said in a press release.

In November 2019, the European Medicines Agency recommended the granting of a marketing authorization for osilodrostat, also for treating adults with Cushing’s disease.

The U.S. approval was based on outcomes from a study that evaluated the drug’s safety and efficacy in 137 adults with Cushing’s disease who had undergone pituitary surgery but were not cured, or who were not surgical candidates, according the release. About three-quarters of the patients were women, and the mean age was 41 years.

All of the patients started a 24-week, single-arm, open-label period at a dose of 2 mg of osilodrostat twice daily that could be increased every 2 weeks to 30 mg twice daily.

By week 24, cortisol levels in roughly half the patients were within the normal range, and 71 patients who did not need any more dose increases and who tolerated the drug were randomized to either osilodrostat or placebo for an 8-week withdrawal study. At the end of that time, 86% of the osilodrostat patients maintained their normal-range cortisol levels, compared with 30% of those taking placebo.

Osilodrostat is taken as an oral tablet twice a day, in the morning and evening. Among the common side effects reported in the study were adrenal insufficiency, headache, vomiting, nausea, fatigue, and edema, although hypocortisolism, QTc prolongation, and elevations in adrenal hormone precursors, and androgens may also occur, according to the release.

The drug had been given an Orphan Drug Designation in recognition of its intended use in the treatment of a rare disease. The approval was granted to Novartis.

The Food and Drug Administration has approved the oral cortisol synthesis inhibitor osilodrostat (Isturisa) for the nonsurgical treatment of adults with Cushing’s disease who either are not good candidates for pituitary gland surgery – the recommended first-line therapy – or in whom the disease persists after surgery.

Cushing’s disease is a rare condition caused when a pituitary tumor releases too much of the hormone adrenocorticotropin, which in turn, triggers the adrenal gland to overproduce cortisol. The condition is associated with serious health complications, including high blood pressure, obesity, type 2 diabetes, and compromised immunity.

Osilodrostat is the first therapy approved by the FDA to tackle the overproduction of cortisol, which it does by blocking the 11-beta-hydroxylase enzyme and thus preventing cortisol synthesis, the agency said in a press release.

In November 2019, the European Medicines Agency recommended the granting of a marketing authorization for osilodrostat, also for treating adults with Cushing’s disease.

The U.S. approval was based on outcomes from a study that evaluated the drug’s safety and efficacy in 137 adults with Cushing’s disease who had undergone pituitary surgery but were not cured, or who were not surgical candidates, according the release. About three-quarters of the patients were women, and the mean age was 41 years.

All of the patients started a 24-week, single-arm, open-label period at a dose of 2 mg of osilodrostat twice daily that could be increased every 2 weeks to 30 mg twice daily.

By week 24, cortisol levels in roughly half the patients were within the normal range, and 71 patients who did not need any more dose increases and who tolerated the drug were randomized to either osilodrostat or placebo for an 8-week withdrawal study. At the end of that time, 86% of the osilodrostat patients maintained their normal-range cortisol levels, compared with 30% of those taking placebo.

Osilodrostat is taken as an oral tablet twice a day, in the morning and evening. Among the common side effects reported in the study were adrenal insufficiency, headache, vomiting, nausea, fatigue, and edema, although hypocortisolism, QTc prolongation, and elevations in adrenal hormone precursors, and androgens may also occur, according to the release.

The drug had been given an Orphan Drug Designation in recognition of its intended use in the treatment of a rare disease. The approval was granted to Novartis.

Thyroid dysfunction is common in patients with diabetes, with a prevalence of around 17%, according to a new analysis of an Australian population.

The results add to the debate over whether patients with diabetes should undergo clinical or biochemical screening for thyroid dysfunction. The American Diabetes Association and U.K. National Institute for Health and Care Excellence guidelines do not recommend general thyroid function monitoring in type 2 diabetes, but the authors of the new study noted concerns that thyroid dysfunction could have metabolic consequences in type 2 disease.

Although the prevalence of undiagnosed thyroid disease in participants with type 2 diabetes was similar to that found in the general Australian population, the researchers, led by Kristen E. Peters, PhD, MedSc, and Timothy M.E. Davis, BMedSc MB, DPhil, of the University of Western Australia, Perth, noted in an article in Clinical Endocrinology that thyroid disease may worsen cardiometabolic risk factors, potentially giving it more significance in this population.

For their study, the researchers analyzed longitudinal data from 1,617 participants in the Fremantle Diabetes Study Phase II, of whom 8.0% had type 1 diabetes, 87.1% had type 2 diabetes, and 4.9% had latent autoimmune diabetes of adults (LADA).

All of the participants filled out questionnaires and underwent baseline fasting biochemical tests and were invited to return for biennial clinical and biochemical measures and to complete biennial questionnaires that were mailed to them. The participants were followed from 2008-2011 (baseline/recruitment period) to 2016. At baseline, 11.7% of the sample (189 of 1,617) had known thyroid disease, based on previous hospitalization of self-reported thyroid medication. Thyroid disease was more prevalent in women than in men (20.4% vs. 3.8%; P less than .001), and there was a nonsignificant trend for a higher prevalence of thyroid disease in participants with type 1 disease, compared with LADA and type 2 (16.9%, 11.4%, and 11.2%, respectively).

Among the 1,428 participants with no documented thyroid disease, 93 (6.5%) were found to have an abnormal thyroid-stimulating hormone (TSH) at baseline testing. Of those 93 participants, 79 had type 2 diabetes, 9 had type 1, and 5 had LADA; across all diabetes types, 5.1% of the participants had subclinical hypothyroidism, 1.1% had overt hypothyroidism, 0.1% had subclinical hyperthyroidism, and 0.2% had overt hyperthyroidism.

Overall, the baseline prevalence of any thyroid disease, known or previously undiagnosed, was 17.4% – 282 of 1,617 participants, of whom 23.8% had type 1 diabetes, 17.7% had LADA, and 16.8% had type 2.

At the end of year 4, serum concentrations were available for 844 participants who had no history of thyroid disease and normal baseline TSH. Over the course of the follow-up period (5,694 patient-years), 25 participants (3%) with normal baseline TSH levels had a first hospitalization for thyroid disease or started thyroid medication, including 2.8% of those with type 1 diabetes and 3.1% of those with type 2. Of the remaining 819 participants who did not have baseline thyroid disease, 3.4% developed subclinical hypothyroidism, 0.2% developed overt hypothyroidism, and 0.5% developed subclinical hyperthyroidism. In each case, there was no statistically significant difference in risk of developing thyroid dysfunction by diabetes type.

“The incidence of any new thyroid disease, including those [participants] with an abnormal follow-up TSH and those with known incident thyroid disease, was 59/844 (7.0%) during [4 years] of follow-up,” the authors noted. “The total incidence of new overt disease was 3.2% (27/844), with 7.4% (2/27) of these patients unaware of the condition. All of the patients with LADA remained euthyroid during follow-up.”

Among the limitations of the study, the authors noted, were that the identification of participants with thyroid disease depended on the available documentation in the databases the researchers used, they were not able to establish pretreatment of thyroid function in most participants with incident thyroid dysfunction, and they did not record free T3.

“Thyroid dysfunction, whether diagnosed or detected on biochemical screening, is common in diabetes regardless of type,” the authors wrote. “Subclinical hypothyroidism is the commonest form [of thyroid dysfunction], and it has a variable course. This latter observation alone makes an argument for periodic biochemical screening in all people with diabetes (not just type 1) as part of routine management.”

However, in an interview, Robert Eckel, MD, professor of medicine at University of Colorado at Denver, Aurora, said that the authors’ suggestion for routine thyroid function testing of patients with any type of diabetes may be premature. He noted that the study lacked a control group, making it difficult to justify a change in practice.

“My take-home message is that the current guidelines are probably not modified by [these findings], but the idea that 17% [of individuals with diabetes] have thyroid disease is worth noting. However, the absence of a control group limits changing recommendations based on this particular study,” said Dr. Eckel, who is also current president, medicine and science, of the ADA.

The study was supported by the National Health and Medical Research Council of Australia and the Spinnaker Health Research Foundation. The study authors did not disclose an financial conflicts.

SOURCE: Peters KE et al. Clin Endocrinol. 2020 Jan 27. doi: 10.1111/cen.14164.

Thyroid dysfunction is common in patients with diabetes, with a prevalence of around 17%, according to a new analysis of an Australian population.

The results add to the debate over whether patients with diabetes should undergo clinical or biochemical screening for thyroid dysfunction. The American Diabetes Association and U.K. National Institute for Health and Care Excellence guidelines do not recommend general thyroid function monitoring in type 2 diabetes, but the authors of the new study noted concerns that thyroid dysfunction could have metabolic consequences in type 2 disease.

Although the prevalence of undiagnosed thyroid disease in participants with type 2 diabetes was similar to that found in the general Australian population, the researchers, led by Kristen E. Peters, PhD, MedSc, and Timothy M.E. Davis, BMedSc MB, DPhil, of the University of Western Australia, Perth, noted in an article in Clinical Endocrinology that thyroid disease may worsen cardiometabolic risk factors, potentially giving it more significance in this population.

For their study, the researchers analyzed longitudinal data from 1,617 participants in the Fremantle Diabetes Study Phase II, of whom 8.0% had type 1 diabetes, 87.1% had type 2 diabetes, and 4.9% had latent autoimmune diabetes of adults (LADA).

All of the participants filled out questionnaires and underwent baseline fasting biochemical tests and were invited to return for biennial clinical and biochemical measures and to complete biennial questionnaires that were mailed to them. The participants were followed from 2008-2011 (baseline/recruitment period) to 2016. At baseline, 11.7% of the sample (189 of 1,617) had known thyroid disease, based on previous hospitalization of self-reported thyroid medication. Thyroid disease was more prevalent in women than in men (20.4% vs. 3.8%; P less than .001), and there was a nonsignificant trend for a higher prevalence of thyroid disease in participants with type 1 disease, compared with LADA and type 2 (16.9%, 11.4%, and 11.2%, respectively).

Among the 1,428 participants with no documented thyroid disease, 93 (6.5%) were found to have an abnormal thyroid-stimulating hormone (TSH) at baseline testing. Of those 93 participants, 79 had type 2 diabetes, 9 had type 1, and 5 had LADA; across all diabetes types, 5.1% of the participants had subclinical hypothyroidism, 1.1% had overt hypothyroidism, 0.1% had subclinical hyperthyroidism, and 0.2% had overt hyperthyroidism.

Overall, the baseline prevalence of any thyroid disease, known or previously undiagnosed, was 17.4% – 282 of 1,617 participants, of whom 23.8% had type 1 diabetes, 17.7% had LADA, and 16.8% had type 2.

At the end of year 4, serum concentrations were available for 844 participants who had no history of thyroid disease and normal baseline TSH. Over the course of the follow-up period (5,694 patient-years), 25 participants (3%) with normal baseline TSH levels had a first hospitalization for thyroid disease or started thyroid medication, including 2.8% of those with type 1 diabetes and 3.1% of those with type 2. Of the remaining 819 participants who did not have baseline thyroid disease, 3.4% developed subclinical hypothyroidism, 0.2% developed overt hypothyroidism, and 0.5% developed subclinical hyperthyroidism. In each case, there was no statistically significant difference in risk of developing thyroid dysfunction by diabetes type.

“The incidence of any new thyroid disease, including those [participants] with an abnormal follow-up TSH and those with known incident thyroid disease, was 59/844 (7.0%) during [4 years] of follow-up,” the authors noted. “The total incidence of new overt disease was 3.2% (27/844), with 7.4% (2/27) of these patients unaware of the condition. All of the patients with LADA remained euthyroid during follow-up.”

Among the limitations of the study, the authors noted, were that the identification of participants with thyroid disease depended on the available documentation in the databases the researchers used, they were not able to establish pretreatment of thyroid function in most participants with incident thyroid dysfunction, and they did not record free T3.

“Thyroid dysfunction, whether diagnosed or detected on biochemical screening, is common in diabetes regardless of type,” the authors wrote. “Subclinical hypothyroidism is the commonest form [of thyroid dysfunction], and it has a variable course. This latter observation alone makes an argument for periodic biochemical screening in all people with diabetes (not just type 1) as part of routine management.”

However, in an interview, Robert Eckel, MD, professor of medicine at University of Colorado at Denver, Aurora, said that the authors’ suggestion for routine thyroid function testing of patients with any type of diabetes may be premature. He noted that the study lacked a control group, making it difficult to justify a change in practice.

“My take-home message is that the current guidelines are probably not modified by [these findings], but the idea that 17% [of individuals with diabetes] have thyroid disease is worth noting. However, the absence of a control group limits changing recommendations based on this particular study,” said Dr. Eckel, who is also current president, medicine and science, of the ADA.

The study was supported by the National Health and Medical Research Council of Australia and the Spinnaker Health Research Foundation. The study authors did not disclose an financial conflicts.

SOURCE: Peters KE et al. Clin Endocrinol. 2020 Jan 27. doi: 10.1111/cen.14164.

Thyroid dysfunction is common in patients with diabetes, with a prevalence of around 17%, according to a new analysis of an Australian population.

The results add to the debate over whether patients with diabetes should undergo clinical or biochemical screening for thyroid dysfunction. The American Diabetes Association and U.K. National Institute for Health and Care Excellence guidelines do not recommend general thyroid function monitoring in type 2 diabetes, but the authors of the new study noted concerns that thyroid dysfunction could have metabolic consequences in type 2 disease.

Although the prevalence of undiagnosed thyroid disease in participants with type 2 diabetes was similar to that found in the general Australian population, the researchers, led by Kristen E. Peters, PhD, MedSc, and Timothy M.E. Davis, BMedSc MB, DPhil, of the University of Western Australia, Perth, noted in an article in Clinical Endocrinology that thyroid disease may worsen cardiometabolic risk factors, potentially giving it more significance in this population.

For their study, the researchers analyzed longitudinal data from 1,617 participants in the Fremantle Diabetes Study Phase II, of whom 8.0% had type 1 diabetes, 87.1% had type 2 diabetes, and 4.9% had latent autoimmune diabetes of adults (LADA).

All of the participants filled out questionnaires and underwent baseline fasting biochemical tests and were invited to return for biennial clinical and biochemical measures and to complete biennial questionnaires that were mailed to them. The participants were followed from 2008-2011 (baseline/recruitment period) to 2016. At baseline, 11.7% of the sample (189 of 1,617) had known thyroid disease, based on previous hospitalization of self-reported thyroid medication. Thyroid disease was more prevalent in women than in men (20.4% vs. 3.8%; P less than .001), and there was a nonsignificant trend for a higher prevalence of thyroid disease in participants with type 1 disease, compared with LADA and type 2 (16.9%, 11.4%, and 11.2%, respectively).

Among the 1,428 participants with no documented thyroid disease, 93 (6.5%) were found to have an abnormal thyroid-stimulating hormone (TSH) at baseline testing. Of those 93 participants, 79 had type 2 diabetes, 9 had type 1, and 5 had LADA; across all diabetes types, 5.1% of the participants had subclinical hypothyroidism, 1.1% had overt hypothyroidism, 0.1% had subclinical hyperthyroidism, and 0.2% had overt hyperthyroidism.

Overall, the baseline prevalence of any thyroid disease, known or previously undiagnosed, was 17.4% – 282 of 1,617 participants, of whom 23.8% had type 1 diabetes, 17.7% had LADA, and 16.8% had type 2.

At the end of year 4, serum concentrations were available for 844 participants who had no history of thyroid disease and normal baseline TSH. Over the course of the follow-up period (5,694 patient-years), 25 participants (3%) with normal baseline TSH levels had a first hospitalization for thyroid disease or started thyroid medication, including 2.8% of those with type 1 diabetes and 3.1% of those with type 2. Of the remaining 819 participants who did not have baseline thyroid disease, 3.4% developed subclinical hypothyroidism, 0.2% developed overt hypothyroidism, and 0.5% developed subclinical hyperthyroidism. In each case, there was no statistically significant difference in risk of developing thyroid dysfunction by diabetes type.

“The incidence of any new thyroid disease, including those [participants] with an abnormal follow-up TSH and those with known incident thyroid disease, was 59/844 (7.0%) during [4 years] of follow-up,” the authors noted. “The total incidence of new overt disease was 3.2% (27/844), with 7.4% (2/27) of these patients unaware of the condition. All of the patients with LADA remained euthyroid during follow-up.”

Among the limitations of the study, the authors noted, were that the identification of participants with thyroid disease depended on the available documentation in the databases the researchers used, they were not able to establish pretreatment of thyroid function in most participants with incident thyroid dysfunction, and they did not record free T3.

“Thyroid dysfunction, whether diagnosed or detected on biochemical screening, is common in diabetes regardless of type,” the authors wrote. “Subclinical hypothyroidism is the commonest form [of thyroid dysfunction], and it has a variable course. This latter observation alone makes an argument for periodic biochemical screening in all people with diabetes (not just type 1) as part of routine management.”

However, in an interview, Robert Eckel, MD, professor of medicine at University of Colorado at Denver, Aurora, said that the authors’ suggestion for routine thyroid function testing of patients with any type of diabetes may be premature. He noted that the study lacked a control group, making it difficult to justify a change in practice.

“My take-home message is that the current guidelines are probably not modified by [these findings], but the idea that 17% [of individuals with diabetes] have thyroid disease is worth noting. However, the absence of a control group limits changing recommendations based on this particular study,” said Dr. Eckel, who is also current president, medicine and science, of the ADA.

The study was supported by the National Health and Medical Research Council of Australia and the Spinnaker Health Research Foundation. The study authors did not disclose an financial conflicts.

SOURCE: Peters KE et al. Clin Endocrinol. 2020 Jan 27. doi: 10.1111/cen.14164.

New UK guidelines for the treatment of hyperthyroidism, including Graves’ disease, place heavier emphasis on the use of radioactive iodine as the frontline treatment for patients unlikely to remain remission-free on the medications, as opposed to the alternative of antithyroid medications as a first choice.
 

“Our evidence reviews indicated that radioactive iodine is the most clinically and cost-effective treatment for hyperthyroidism,” senior author Kristien Boelaert, MD, PhD, who led the guideline committee, said in an interview.

“Recommending the use of radioactive iodine as first-line treatment for adults with Graves’ disease is a change to current practice and should reduce the variation between centers as to when radioactive iodine is considered appropriate,” the guidelines further state.

The new recommendations on hyperthyroidism are part of broader guidelines on thyroid disease by the UK National Institute for Health and Care Excellence (NICE), which concludes that radioactive iodine results in cure in as many as 90% of hyperthyroidism cases.

The recommendations were published in a guideline summary in BMJ by research fellow Melina Vasileiou of the National Guideline Centre, Royal College of Physicians, London, and colleagues.

Current guidelines in the United Kingdom and Europe typically call for radioactive iodine to be reserved for use as a definitive treatment only after relapse following antithyroid medication treatment. The latest European Thyroid Association guidelines were published in 2018.

Elsewhere guidelines vary, with many, including those by the American Thyroid Association (ATA) – the most recent published in 2016 – generally calling for treatment with either antithyroid medications, radioactive iodine, or total thyroidectomy, in the absence of any contraindications to each treatment option.

“The U.S. tends to use more radioactive iodine, while Europe, Latin America, and Japan lean more toward (perhaps longer) use of antithyroid medications,” Angela Leung, MD, associate clinical professor of medicine in the division of endocrinology, diabetes, and metabolism, department of medicine, University of California, Los Angeles, said in an interview.

“Preferences of deciding which treatment option, which may involve more than one option if antithyroid medications are used initially, depend on a variety of factors related to patient desire, comorbidities, and availability of the therapy,” she explained.

Concerns including worsening thyroid eye disease, cardiovascular disease, and development of secondary cancers have caused some hesitation in the use of frontline radioiodine therapy.

And one notably controversial article, published last year, suggested a link between radioactive iodine therapy and an increased risk of cancer mortality. However, as reported by Medscape Medical News, the article spurred debate, with the Society for Endocrinology and British Thyroid Association issuing a joint statement urging caution in interpretation of the findings.

Evidence supporting first-line radioactive iodine

Patients treated with radioactive iodine take a single tablet that contains iodine and a low dose of radiation, which is absorbed by the thyroid. After taking the treatment patients are advised to avoid prolonged close contact with children and pregnant women for a few days or weeks and to avoid getting pregnant or fathering a child for several months. The treatment is likely to lead to an underactive thyroid gland that will require ongoing treatment with thyroid hormone replacement.

In providing evidence in favor of the benefits of radioactive iodine over the risks, the new NICE guidelines cite five randomized controlled trials of people with hyperthyroid disease, which, though defined as “low quality” evidence, collectively indicate that long-term outcomes were improved with radioactive iodine treatment compared with antithyroid drugs – despite the former having a higher risk of thyroid eye disease (also known as Graves’ ophthalmopathy).

In addition, eight nonrandomized studies show no evidence of a clinically important increase in cancer diagnoses or deaths between people treated with radioactive iodine or surgery, or between people treated with radioactive iodine and healthy controls, the guideline committee notes.

“The strongest arguments (in favor of radioactive iodine as a first-line therapy) were the likelihood of inducing remission of Graves’ disease with radioactive iodine, the finding that radioiodine is a safe treatment (confirmed in the safety review undertaken by NICE), and the reduction in the need for patients to remain on antithyroid drugs, which may have significant side effects and treatment which usually requires repeated hospital visits or follow-up under a hospital service,” said Dr. Boelaert.

The new guideline does recommend that antithyroid medication is acceptable as the first-line treatment among patients considered likely to achieve remission.

Dr. Leung explains that the percentage of patients with Graves’ disease who can achieve remission with antithyroid drugs ranges from 30% to 50%. She noted some evidence does suggest the long-term use of the drugs may be acceptable.

“There are some data that ... report the relative safety of long-term use of antithyroid drugs (beyond 24 months) for both Graves’ disease and autonomous thyroid nodules,” Dr. Leung elaborated.

Pregnancy concerns and cost-effectiveness of radioactive iodine

Radioactive iodine therapy is meanwhile not suitable if malignancy is suspected, if the patient is pregnant or trying to become pregnant, or if the patient has active thyroid eye disease, the experts agree.

Dr. Leung noted that although “it is generally advised to not treat Graves’ disease with radioiodine if there is concurrent thyroid eye disease, steroids are a proven effective therapy to decrease this risk in select patients.”

And among pregnant patients, “antithyroid medications should be minimally used in the lowest possible doses,” Dr. Leung said, although she added that, despite their potential risks, the drugs “represent a viable option” for this patient population.

“Also, many would actually advocate for total thyroidectomy in women who are thinking of pregnancy in the near future,” she noted.

Another factor of relevance in the guideline recommendations – cost – also favors radioactive iodine, the committee noted.

“Economic evidence showed that radioactive iodine was the most cost-effective intervention,” the committee pointed out.

Trabs advised for determination of hyperthyroidism cause

The new U.K. guidelines further underscore the importance of establishing the underlying cause of hyperthyroidism to ensure appropriate treatment, and the preferred method for doing so is the measurement of thyroid-stimulating hormone receptor antibodies (TRAbs).

“It is important to identify the underlying cause of thyrotoxicosis through measurement of TRAbs, or radioisotope scanning, in order to distinguish hyperthyroidism from transient causes of thyrotoxicosis such as transient thyroiditis, which only requires supportive treatment,” explained Dr. Boelaert, consultant endocrinologist and director of the National Institute for Health Research Integrated Academic Training Program at the Institute of Applied Health Research, University of Birmingham (England).

“In addition, this will help distinguish Graves’ disease from toxic nodular hyperthyroidism, which is important as antithyroid drugs are not effective in inducing a cure in the latter,” she explained.

Meanwhile, the new guidelines further note that although use of diagnostic ultrasound is informative when palpation suggests thyroid nodules, it is of limited diagnostic value for Graves’ disease.

“The recommendation (suggests that) thyroid ultrasonography should only be offered if there is a palpable thyroid nodule,” Dr. Boelaert noted.

She concluded: “There has been uncertainty in the U.K. about the best treatment for hyperthyroidism despite radioactive iodine being the most common first-line treatment for this condition in the United States. We are very pleased to have been able to work with NICE to provide clear new guidance which we hope will improve outcomes for patients with this condition.”

The National Guideline Centre was commissioned and funded by NICE to develop the guideline. No authors received specific funding to write the summary. Dr. Boelaert has reported no relevant financial relationships. Disclosures for the other authors are listed in the article.
 

This article first appeared on Medscape.com.

New UK guidelines for the treatment of hyperthyroidism, including Graves’ disease, place heavier emphasis on the use of radioactive iodine as the frontline treatment for patients unlikely to remain remission-free on the medications, as opposed to the alternative of antithyroid medications as a first choice.
 

“Our evidence reviews indicated that radioactive iodine is the most clinically and cost-effective treatment for hyperthyroidism,” senior author Kristien Boelaert, MD, PhD, who led the guideline committee, said in an interview.

“Recommending the use of radioactive iodine as first-line treatment for adults with Graves’ disease is a change to current practice and should reduce the variation between centers as to when radioactive iodine is considered appropriate,” the guidelines further state.

The new recommendations on hyperthyroidism are part of broader guidelines on thyroid disease by the UK National Institute for Health and Care Excellence (NICE), which concludes that radioactive iodine results in cure in as many as 90% of hyperthyroidism cases.

The recommendations were published in a guideline summary in BMJ by research fellow Melina Vasileiou of the National Guideline Centre, Royal College of Physicians, London, and colleagues.

Current guidelines in the United Kingdom and Europe typically call for radioactive iodine to be reserved for use as a definitive treatment only after relapse following antithyroid medication treatment. The latest European Thyroid Association guidelines were published in 2018.

Elsewhere guidelines vary, with many, including those by the American Thyroid Association (ATA) – the most recent published in 2016 – generally calling for treatment with either antithyroid medications, radioactive iodine, or total thyroidectomy, in the absence of any contraindications to each treatment option.

“The U.S. tends to use more radioactive iodine, while Europe, Latin America, and Japan lean more toward (perhaps longer) use of antithyroid medications,” Angela Leung, MD, associate clinical professor of medicine in the division of endocrinology, diabetes, and metabolism, department of medicine, University of California, Los Angeles, said in an interview.

“Preferences of deciding which treatment option, which may involve more than one option if antithyroid medications are used initially, depend on a variety of factors related to patient desire, comorbidities, and availability of the therapy,” she explained.

Concerns including worsening thyroid eye disease, cardiovascular disease, and development of secondary cancers have caused some hesitation in the use of frontline radioiodine therapy.

And one notably controversial article, published last year, suggested a link between radioactive iodine therapy and an increased risk of cancer mortality. However, as reported by Medscape Medical News, the article spurred debate, with the Society for Endocrinology and British Thyroid Association issuing a joint statement urging caution in interpretation of the findings.

Evidence supporting first-line radioactive iodine

Patients treated with radioactive iodine take a single tablet that contains iodine and a low dose of radiation, which is absorbed by the thyroid. After taking the treatment patients are advised to avoid prolonged close contact with children and pregnant women for a few days or weeks and to avoid getting pregnant or fathering a child for several months. The treatment is likely to lead to an underactive thyroid gland that will require ongoing treatment with thyroid hormone replacement.

In providing evidence in favor of the benefits of radioactive iodine over the risks, the new NICE guidelines cite five randomized controlled trials of people with hyperthyroid disease, which, though defined as “low quality” evidence, collectively indicate that long-term outcomes were improved with radioactive iodine treatment compared with antithyroid drugs – despite the former having a higher risk of thyroid eye disease (also known as Graves’ ophthalmopathy).

In addition, eight nonrandomized studies show no evidence of a clinically important increase in cancer diagnoses or deaths between people treated with radioactive iodine or surgery, or between people treated with radioactive iodine and healthy controls, the guideline committee notes.

“The strongest arguments (in favor of radioactive iodine as a first-line therapy) were the likelihood of inducing remission of Graves’ disease with radioactive iodine, the finding that radioiodine is a safe treatment (confirmed in the safety review undertaken by NICE), and the reduction in the need for patients to remain on antithyroid drugs, which may have significant side effects and treatment which usually requires repeated hospital visits or follow-up under a hospital service,” said Dr. Boelaert.

The new guideline does recommend that antithyroid medication is acceptable as the first-line treatment among patients considered likely to achieve remission.

Dr. Leung explains that the percentage of patients with Graves’ disease who can achieve remission with antithyroid drugs ranges from 30% to 50%. She noted some evidence does suggest the long-term use of the drugs may be acceptable.

“There are some data that ... report the relative safety of long-term use of antithyroid drugs (beyond 24 months) for both Graves’ disease and autonomous thyroid nodules,” Dr. Leung elaborated.

Pregnancy concerns and cost-effectiveness of radioactive iodine

Radioactive iodine therapy is meanwhile not suitable if malignancy is suspected, if the patient is pregnant or trying to become pregnant, or if the patient has active thyroid eye disease, the experts agree.

Dr. Leung noted that although “it is generally advised to not treat Graves’ disease with radioiodine if there is concurrent thyroid eye disease, steroids are a proven effective therapy to decrease this risk in select patients.”

And among pregnant patients, “antithyroid medications should be minimally used in the lowest possible doses,” Dr. Leung said, although she added that, despite their potential risks, the drugs “represent a viable option” for this patient population.

“Also, many would actually advocate for total thyroidectomy in women who are thinking of pregnancy in the near future,” she noted.

Another factor of relevance in the guideline recommendations – cost – also favors radioactive iodine, the committee noted.

“Economic evidence showed that radioactive iodine was the most cost-effective intervention,” the committee pointed out.

Trabs advised for determination of hyperthyroidism cause

The new U.K. guidelines further underscore the importance of establishing the underlying cause of hyperthyroidism to ensure appropriate treatment, and the preferred method for doing so is the measurement of thyroid-stimulating hormone receptor antibodies (TRAbs).

“It is important to identify the underlying cause of thyrotoxicosis through measurement of TRAbs, or radioisotope scanning, in order to distinguish hyperthyroidism from transient causes of thyrotoxicosis such as transient thyroiditis, which only requires supportive treatment,” explained Dr. Boelaert, consultant endocrinologist and director of the National Institute for Health Research Integrated Academic Training Program at the Institute of Applied Health Research, University of Birmingham (England).

“In addition, this will help distinguish Graves’ disease from toxic nodular hyperthyroidism, which is important as antithyroid drugs are not effective in inducing a cure in the latter,” she explained.

Meanwhile, the new guidelines further note that although use of diagnostic ultrasound is informative when palpation suggests thyroid nodules, it is of limited diagnostic value for Graves’ disease.

“The recommendation (suggests that) thyroid ultrasonography should only be offered if there is a palpable thyroid nodule,” Dr. Boelaert noted.

She concluded: “There has been uncertainty in the U.K. about the best treatment for hyperthyroidism despite radioactive iodine being the most common first-line treatment for this condition in the United States. We are very pleased to have been able to work with NICE to provide clear new guidance which we hope will improve outcomes for patients with this condition.”

The National Guideline Centre was commissioned and funded by NICE to develop the guideline. No authors received specific funding to write the summary. Dr. Boelaert has reported no relevant financial relationships. Disclosures for the other authors are listed in the article.
 

This article first appeared on Medscape.com.

New UK guidelines for the treatment of hyperthyroidism, including Graves’ disease, place heavier emphasis on the use of radioactive iodine as the frontline treatment for patients unlikely to remain remission-free on the medications, as opposed to the alternative of antithyroid medications as a first choice.
 

“Our evidence reviews indicated that radioactive iodine is the most clinically and cost-effective treatment for hyperthyroidism,” senior author Kristien Boelaert, MD, PhD, who led the guideline committee, said in an interview.

“Recommending the use of radioactive iodine as first-line treatment for adults with Graves’ disease is a change to current practice and should reduce the variation between centers as to when radioactive iodine is considered appropriate,” the guidelines further state.

The new recommendations on hyperthyroidism are part of broader guidelines on thyroid disease by the UK National Institute for Health and Care Excellence (NICE), which concludes that radioactive iodine results in cure in as many as 90% of hyperthyroidism cases.

The recommendations were published in a guideline summary in BMJ by research fellow Melina Vasileiou of the National Guideline Centre, Royal College of Physicians, London, and colleagues.

Current guidelines in the United Kingdom and Europe typically call for radioactive iodine to be reserved for use as a definitive treatment only after relapse following antithyroid medication treatment. The latest European Thyroid Association guidelines were published in 2018.

Elsewhere guidelines vary, with many, including those by the American Thyroid Association (ATA) – the most recent published in 2016 – generally calling for treatment with either antithyroid medications, radioactive iodine, or total thyroidectomy, in the absence of any contraindications to each treatment option.

“The U.S. tends to use more radioactive iodine, while Europe, Latin America, and Japan lean more toward (perhaps longer) use of antithyroid medications,” Angela Leung, MD, associate clinical professor of medicine in the division of endocrinology, diabetes, and metabolism, department of medicine, University of California, Los Angeles, said in an interview.

“Preferences of deciding which treatment option, which may involve more than one option if antithyroid medications are used initially, depend on a variety of factors related to patient desire, comorbidities, and availability of the therapy,” she explained.

Concerns including worsening thyroid eye disease, cardiovascular disease, and development of secondary cancers have caused some hesitation in the use of frontline radioiodine therapy.

And one notably controversial article, published last year, suggested a link between radioactive iodine therapy and an increased risk of cancer mortality. However, as reported by Medscape Medical News, the article spurred debate, with the Society for Endocrinology and British Thyroid Association issuing a joint statement urging caution in interpretation of the findings.

Evidence supporting first-line radioactive iodine

Patients treated with radioactive iodine take a single tablet that contains iodine and a low dose of radiation, which is absorbed by the thyroid. After taking the treatment patients are advised to avoid prolonged close contact with children and pregnant women for a few days or weeks and to avoid getting pregnant or fathering a child for several months. The treatment is likely to lead to an underactive thyroid gland that will require ongoing treatment with thyroid hormone replacement.

In providing evidence in favor of the benefits of radioactive iodine over the risks, the new NICE guidelines cite five randomized controlled trials of people with hyperthyroid disease, which, though defined as “low quality” evidence, collectively indicate that long-term outcomes were improved with radioactive iodine treatment compared with antithyroid drugs – despite the former having a higher risk of thyroid eye disease (also known as Graves’ ophthalmopathy).

In addition, eight nonrandomized studies show no evidence of a clinically important increase in cancer diagnoses or deaths between people treated with radioactive iodine or surgery, or between people treated with radioactive iodine and healthy controls, the guideline committee notes.

“The strongest arguments (in favor of radioactive iodine as a first-line therapy) were the likelihood of inducing remission of Graves’ disease with radioactive iodine, the finding that radioiodine is a safe treatment (confirmed in the safety review undertaken by NICE), and the reduction in the need for patients to remain on antithyroid drugs, which may have significant side effects and treatment which usually requires repeated hospital visits or follow-up under a hospital service,” said Dr. Boelaert.

The new guideline does recommend that antithyroid medication is acceptable as the first-line treatment among patients considered likely to achieve remission.

Dr. Leung explains that the percentage of patients with Graves’ disease who can achieve remission with antithyroid drugs ranges from 30% to 50%. She noted some evidence does suggest the long-term use of the drugs may be acceptable.

“There are some data that ... report the relative safety of long-term use of antithyroid drugs (beyond 24 months) for both Graves’ disease and autonomous thyroid nodules,” Dr. Leung elaborated.

Pregnancy concerns and cost-effectiveness of radioactive iodine

Radioactive iodine therapy is meanwhile not suitable if malignancy is suspected, if the patient is pregnant or trying to become pregnant, or if the patient has active thyroid eye disease, the experts agree.

Dr. Leung noted that although “it is generally advised to not treat Graves’ disease with radioiodine if there is concurrent thyroid eye disease, steroids are a proven effective therapy to decrease this risk in select patients.”

And among pregnant patients, “antithyroid medications should be minimally used in the lowest possible doses,” Dr. Leung said, although she added that, despite their potential risks, the drugs “represent a viable option” for this patient population.

“Also, many would actually advocate for total thyroidectomy in women who are thinking of pregnancy in the near future,” she noted.

Another factor of relevance in the guideline recommendations – cost – also favors radioactive iodine, the committee noted.

“Economic evidence showed that radioactive iodine was the most cost-effective intervention,” the committee pointed out.

Trabs advised for determination of hyperthyroidism cause

The new U.K. guidelines further underscore the importance of establishing the underlying cause of hyperthyroidism to ensure appropriate treatment, and the preferred method for doing so is the measurement of thyroid-stimulating hormone receptor antibodies (TRAbs).

“It is important to identify the underlying cause of thyrotoxicosis through measurement of TRAbs, or radioisotope scanning, in order to distinguish hyperthyroidism from transient causes of thyrotoxicosis such as transient thyroiditis, which only requires supportive treatment,” explained Dr. Boelaert, consultant endocrinologist and director of the National Institute for Health Research Integrated Academic Training Program at the Institute of Applied Health Research, University of Birmingham (England).

“In addition, this will help distinguish Graves’ disease from toxic nodular hyperthyroidism, which is important as antithyroid drugs are not effective in inducing a cure in the latter,” she explained.

Meanwhile, the new guidelines further note that although use of diagnostic ultrasound is informative when palpation suggests thyroid nodules, it is of limited diagnostic value for Graves’ disease.

“The recommendation (suggests that) thyroid ultrasonography should only be offered if there is a palpable thyroid nodule,” Dr. Boelaert noted.

She concluded: “There has been uncertainty in the U.K. about the best treatment for hyperthyroidism despite radioactive iodine being the most common first-line treatment for this condition in the United States. We are very pleased to have been able to work with NICE to provide clear new guidance which we hope will improve outcomes for patients with this condition.”

The National Guideline Centre was commissioned and funded by NICE to develop the guideline. No authors received specific funding to write the summary. Dr. Boelaert has reported no relevant financial relationships. Disclosures for the other authors are listed in the article.
 

This article first appeared on Medscape.com.