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Can caffeine improve thyroid function?
“Although the causal relationship between caffeine intake and thyroid function requires further verification, as an easily obtainable and widely consumed dietary ingredient, caffeine is a potential candidate for improving thyroid health in people with metabolic disorders,” reported the authors in the study, published in Nutritional Journal.
Caffeine intake, within established healthy ranges, showed a nonlinear association with thyroid levels.
Moderate caffeine intake has been associated with reducing the risk of metabolic disorders in addition to showing some mental health benefits. However, research on its effects on thyroid hormone, which importantly plays a key role in systemic metabolism and neurologic development, is lacking.
To investigate the effects, Yu Zhou, of the Department of Rehabilitation Medicine, School of Health, Fujian Medical University, Fuzhou, China, and colleagues evaluated data from the National Health and Nutrition Examination Survey (NHANES) III 2007-2012 study involving 2,582 participants for whom data were available regarding medical conditions, dietary intake, thyroid function, and demographic background.
The participants were divided into three subgroups based on sex, age, body mass index, hyperglycemia, hypertension, and cardio-cerebral vascular disease (CVD).
Group 1 (n = 208) was the most metabolically unhealthy. Patients in that group had the highest BMI and were of oldest age. In addition, that group had higher rates of hypertension, hyperglycemia, and CVD, but, notably, it had the lowest level of caffeine consumption.
In group 2 (n = 543), all participants were current smokers, and 90.4% had a habit of drinking alcohol. That group also had the highest percentage of men.
Group 3 (n = 1,183) was the most metabolically healthy, with more women, younger age, and lowest BMI. No participants in that group had hyperglycemia, hypertension, or CVD.
Group 1, the most metabolically unhealthy, had the highest serum thyroid-stimulating hormone (TSH) levels. Of note, while participants with thyroid diseases were initially excluded from the analysis, higher TSH levels are predictive of subclinical hypothyroidism or progression to overt hypothyroidism.
Overall, there was no association between caffeine and TSH levels.
However, a subgroup analysis of the groups showed that in group 1, caffeine intake correlated with TSH nonlinearly (P = .0019), with minimal average consumption of caffeine (< 9.97 mg/d). There was an association with slightly higher TSH levels (P = .035) after adjustment for age, sex, race, drink, disease state, micronutrients, and macronutrients.
However, in higher, moderate amounts of caffeine consumption (9.97 – 264.97 mg/d), there was an inverse association, with lower TSH (P = .001).
There was no association between daily caffeine consumption of more than 264.97 mg and TSH levels.
For context, a typical 8-ounce cup of coffee generally contains 80-100 mg of caffeine, and the Food and Drug Administration indicates that 400 mg/d of caffeine is safe for healthy adults.
Group 2 consumed the highest amount of caffeine. Notably, that group had the lowest serum TSH levels of the three groups. There were no significant associations between caffeine consumption and TSH levels in group 2 or group 3.
There were no significant associations between caffeine consumption and levels of serum FT4 or FT3, also linked to thyroid dysfunction, in any of the groups.
The findings show that “caffeine consumption was correlated with serum TSH nonlinearly, and when taken in moderate amounts (9.97-264.97 mg/d), caffeine demonstrated a positive correlation with serum TSH levels in patients with metabolic disorders,” the authors concluded.
Mechanisms?
Caffeine is believed to modulate pituitary hormone secretion, which has been shown to influence the hypothalamic-pituitary-adrenal axis. The authors speculated that caffeine could potentially affect thyroid activity by affecting pituitary function.
“However, the effects of transient and chronic caffeine administration on human thyroid function need to be verified further, and the related mechanisms remain unclear,” they noted.
Commenting on the study, Maik Pietzner, PhD, of the Berlin Institute of Health, noted that an important limitation of the study is that various patient groups were excluded, including those with abnormal TSH levels.
“What makes me wonder is the high number of exclusions and the focus on very specific groups of people. This almost certainly introduces bias, e.g., what is specific to people not reporting coffee consumption,” Dr. Pietzner said.
Furthermore, “we already know that patients with poor metabolic health do also have slight variations in thyroid hormone levels and also have different dietary patterns,” he explained.
“So reverse confounding might occur in which the poor metabolic health is associated with both poor thyroid hormone levels and coffee consumption,” Dr. Pietzner said.
He also noted the “somewhat odd” finding that the group with the highest metabolic disorders had the lowest coffee consumption, yet the highest TSH levels.
“My guess would be that this might also be a chance finding, given that the distribution of TSH values is very skewed, which can have a strong effect in linear regression models,” Dr. Pietzner said.
In general, “the evidence generated by the study is rather weak, but there is good evidence that higher coffee consumption is linked to better metabolic health, although the exact mechanisms is not known, if indeed causal,” Dr. Pietzner added. “Prospective studies are needed to evaluate whether higher coffee consumption indeed lowers the risk for thyroid disease.”
A version of this article first appeared on Medscape.com.
“Although the causal relationship between caffeine intake and thyroid function requires further verification, as an easily obtainable and widely consumed dietary ingredient, caffeine is a potential candidate for improving thyroid health in people with metabolic disorders,” reported the authors in the study, published in Nutritional Journal.
Caffeine intake, within established healthy ranges, showed a nonlinear association with thyroid levels.
Moderate caffeine intake has been associated with reducing the risk of metabolic disorders in addition to showing some mental health benefits. However, research on its effects on thyroid hormone, which importantly plays a key role in systemic metabolism and neurologic development, is lacking.
To investigate the effects, Yu Zhou, of the Department of Rehabilitation Medicine, School of Health, Fujian Medical University, Fuzhou, China, and colleagues evaluated data from the National Health and Nutrition Examination Survey (NHANES) III 2007-2012 study involving 2,582 participants for whom data were available regarding medical conditions, dietary intake, thyroid function, and demographic background.
The participants were divided into three subgroups based on sex, age, body mass index, hyperglycemia, hypertension, and cardio-cerebral vascular disease (CVD).
Group 1 (n = 208) was the most metabolically unhealthy. Patients in that group had the highest BMI and were of oldest age. In addition, that group had higher rates of hypertension, hyperglycemia, and CVD, but, notably, it had the lowest level of caffeine consumption.
In group 2 (n = 543), all participants were current smokers, and 90.4% had a habit of drinking alcohol. That group also had the highest percentage of men.
Group 3 (n = 1,183) was the most metabolically healthy, with more women, younger age, and lowest BMI. No participants in that group had hyperglycemia, hypertension, or CVD.
Group 1, the most metabolically unhealthy, had the highest serum thyroid-stimulating hormone (TSH) levels. Of note, while participants with thyroid diseases were initially excluded from the analysis, higher TSH levels are predictive of subclinical hypothyroidism or progression to overt hypothyroidism.
Overall, there was no association between caffeine and TSH levels.
However, a subgroup analysis of the groups showed that in group 1, caffeine intake correlated with TSH nonlinearly (P = .0019), with minimal average consumption of caffeine (< 9.97 mg/d). There was an association with slightly higher TSH levels (P = .035) after adjustment for age, sex, race, drink, disease state, micronutrients, and macronutrients.
However, in higher, moderate amounts of caffeine consumption (9.97 – 264.97 mg/d), there was an inverse association, with lower TSH (P = .001).
There was no association between daily caffeine consumption of more than 264.97 mg and TSH levels.
For context, a typical 8-ounce cup of coffee generally contains 80-100 mg of caffeine, and the Food and Drug Administration indicates that 400 mg/d of caffeine is safe for healthy adults.
Group 2 consumed the highest amount of caffeine. Notably, that group had the lowest serum TSH levels of the three groups. There were no significant associations between caffeine consumption and TSH levels in group 2 or group 3.
There were no significant associations between caffeine consumption and levels of serum FT4 or FT3, also linked to thyroid dysfunction, in any of the groups.
The findings show that “caffeine consumption was correlated with serum TSH nonlinearly, and when taken in moderate amounts (9.97-264.97 mg/d), caffeine demonstrated a positive correlation with serum TSH levels in patients with metabolic disorders,” the authors concluded.
Mechanisms?
Caffeine is believed to modulate pituitary hormone secretion, which has been shown to influence the hypothalamic-pituitary-adrenal axis. The authors speculated that caffeine could potentially affect thyroid activity by affecting pituitary function.
“However, the effects of transient and chronic caffeine administration on human thyroid function need to be verified further, and the related mechanisms remain unclear,” they noted.
Commenting on the study, Maik Pietzner, PhD, of the Berlin Institute of Health, noted that an important limitation of the study is that various patient groups were excluded, including those with abnormal TSH levels.
“What makes me wonder is the high number of exclusions and the focus on very specific groups of people. This almost certainly introduces bias, e.g., what is specific to people not reporting coffee consumption,” Dr. Pietzner said.
Furthermore, “we already know that patients with poor metabolic health do also have slight variations in thyroid hormone levels and also have different dietary patterns,” he explained.
“So reverse confounding might occur in which the poor metabolic health is associated with both poor thyroid hormone levels and coffee consumption,” Dr. Pietzner said.
He also noted the “somewhat odd” finding that the group with the highest metabolic disorders had the lowest coffee consumption, yet the highest TSH levels.
“My guess would be that this might also be a chance finding, given that the distribution of TSH values is very skewed, which can have a strong effect in linear regression models,” Dr. Pietzner said.
In general, “the evidence generated by the study is rather weak, but there is good evidence that higher coffee consumption is linked to better metabolic health, although the exact mechanisms is not known, if indeed causal,” Dr. Pietzner added. “Prospective studies are needed to evaluate whether higher coffee consumption indeed lowers the risk for thyroid disease.”
A version of this article first appeared on Medscape.com.
“Although the causal relationship between caffeine intake and thyroid function requires further verification, as an easily obtainable and widely consumed dietary ingredient, caffeine is a potential candidate for improving thyroid health in people with metabolic disorders,” reported the authors in the study, published in Nutritional Journal.
Caffeine intake, within established healthy ranges, showed a nonlinear association with thyroid levels.
Moderate caffeine intake has been associated with reducing the risk of metabolic disorders in addition to showing some mental health benefits. However, research on its effects on thyroid hormone, which importantly plays a key role in systemic metabolism and neurologic development, is lacking.
To investigate the effects, Yu Zhou, of the Department of Rehabilitation Medicine, School of Health, Fujian Medical University, Fuzhou, China, and colleagues evaluated data from the National Health and Nutrition Examination Survey (NHANES) III 2007-2012 study involving 2,582 participants for whom data were available regarding medical conditions, dietary intake, thyroid function, and demographic background.
The participants were divided into three subgroups based on sex, age, body mass index, hyperglycemia, hypertension, and cardio-cerebral vascular disease (CVD).
Group 1 (n = 208) was the most metabolically unhealthy. Patients in that group had the highest BMI and were of oldest age. In addition, that group had higher rates of hypertension, hyperglycemia, and CVD, but, notably, it had the lowest level of caffeine consumption.
In group 2 (n = 543), all participants were current smokers, and 90.4% had a habit of drinking alcohol. That group also had the highest percentage of men.
Group 3 (n = 1,183) was the most metabolically healthy, with more women, younger age, and lowest BMI. No participants in that group had hyperglycemia, hypertension, or CVD.
Group 1, the most metabolically unhealthy, had the highest serum thyroid-stimulating hormone (TSH) levels. Of note, while participants with thyroid diseases were initially excluded from the analysis, higher TSH levels are predictive of subclinical hypothyroidism or progression to overt hypothyroidism.
Overall, there was no association between caffeine and TSH levels.
However, a subgroup analysis of the groups showed that in group 1, caffeine intake correlated with TSH nonlinearly (P = .0019), with minimal average consumption of caffeine (< 9.97 mg/d). There was an association with slightly higher TSH levels (P = .035) after adjustment for age, sex, race, drink, disease state, micronutrients, and macronutrients.
However, in higher, moderate amounts of caffeine consumption (9.97 – 264.97 mg/d), there was an inverse association, with lower TSH (P = .001).
There was no association between daily caffeine consumption of more than 264.97 mg and TSH levels.
For context, a typical 8-ounce cup of coffee generally contains 80-100 mg of caffeine, and the Food and Drug Administration indicates that 400 mg/d of caffeine is safe for healthy adults.
Group 2 consumed the highest amount of caffeine. Notably, that group had the lowest serum TSH levels of the three groups. There were no significant associations between caffeine consumption and TSH levels in group 2 or group 3.
There were no significant associations between caffeine consumption and levels of serum FT4 or FT3, also linked to thyroid dysfunction, in any of the groups.
The findings show that “caffeine consumption was correlated with serum TSH nonlinearly, and when taken in moderate amounts (9.97-264.97 mg/d), caffeine demonstrated a positive correlation with serum TSH levels in patients with metabolic disorders,” the authors concluded.
Mechanisms?
Caffeine is believed to modulate pituitary hormone secretion, which has been shown to influence the hypothalamic-pituitary-adrenal axis. The authors speculated that caffeine could potentially affect thyroid activity by affecting pituitary function.
“However, the effects of transient and chronic caffeine administration on human thyroid function need to be verified further, and the related mechanisms remain unclear,” they noted.
Commenting on the study, Maik Pietzner, PhD, of the Berlin Institute of Health, noted that an important limitation of the study is that various patient groups were excluded, including those with abnormal TSH levels.
“What makes me wonder is the high number of exclusions and the focus on very specific groups of people. This almost certainly introduces bias, e.g., what is specific to people not reporting coffee consumption,” Dr. Pietzner said.
Furthermore, “we already know that patients with poor metabolic health do also have slight variations in thyroid hormone levels and also have different dietary patterns,” he explained.
“So reverse confounding might occur in which the poor metabolic health is associated with both poor thyroid hormone levels and coffee consumption,” Dr. Pietzner said.
He also noted the “somewhat odd” finding that the group with the highest metabolic disorders had the lowest coffee consumption, yet the highest TSH levels.
“My guess would be that this might also be a chance finding, given that the distribution of TSH values is very skewed, which can have a strong effect in linear regression models,” Dr. Pietzner said.
In general, “the evidence generated by the study is rather weak, but there is good evidence that higher coffee consumption is linked to better metabolic health, although the exact mechanisms is not known, if indeed causal,” Dr. Pietzner added. “Prospective studies are needed to evaluate whether higher coffee consumption indeed lowers the risk for thyroid disease.”
A version of this article first appeared on Medscape.com.
FROM NUTRITIONAL JOURNAL
T3 in hypothyroidism gets extra recommendation: British medical groups
New recommendations from the Joint British Thyroid Association/Society add to the increasingly general consensus that liothyronine (LT3) may be useful in combination with standard levothyroxine (LT4) in the treatment of hypothyroidism in some patients whose symptoms persist after standard treatment, despite a lack of evidence of benefit in clinical trials.
“Most patients with primary hypothyroidism respond well to levothyroxine replacement therapy,” recommends the joint association in the consensus statement, by Rupa Ahluwalia, MBBS, MD, of Norfolk and Norwich University Hospitals NHS Trust, United Kingdom, and colleagues, recently published in Clinical Endocrinology.
they wrote.
The ongoing debate over the use of LT3/LT4 combination therapy has persisted for more than 2 decades, with at least 16 randomized controlled trials and four meta-analyses failing to show any significant benefit of the combined regimen in key quality of life and cognitive function outcomes compared with LT4 monotherapy. However, many patients continue to report benefits with combination therapy, so the issue has not been laid to rest.
Wilmar M. Wiersinga, MD, PhD, emeritus professor of endocrinology at the University of Amsterdam, said in an interview: “The scientific community is divided as to whether or not the LT4/LT3 combination therapy has any value whatsoever, whereas the pressure from individual patients and patient associations on physicians – both general practitioners and specialists/endocrinologists – can be very high [in terms of] demanding prescriptions for the combination therapy.
“I welcome this joint statement very much because it provides guidance, especially for clinicians, on a hotly debated issue,” he said.
Persistent symptoms drive pursuit of alternatives
T4 refers to the hormone thyroxine made in the body, and LT4 to the pharmaceutical replacement product for that hormone, levothyroxine. Similarly, T3 refers to the hormone triiodothyronine, made in the body and a precursor to thyroxine, and LT3 refers to its pharmaceutical replacement, liothyronine.
Driving the continued demand from some patients with hypothyroidism and interest among clinicians is the relatively high proportion of patients who continue to experience symptoms even after the normalization of biochemical levels after treatment with LT4, which resolves symptoms in most patients within weeks of therapy.
Those who don’t improve report common ongoing symptoms: fatigue, sleepiness, memory problems, cognitive difficulties (brain fog), and weight gain.
However, with 60% of people commonly having one or more of the same symptoms even when their thyroid levels are normal, pinpointing the actual causes is a challenge, the societies report.
In the absence of other diagnoses, clinicians often turn to alternative treatment strategies, which, as well as addition of LT3 to LT4, also include the use of desiccated thyroid extract (DTE).
DTE was the medication first used to treat hypothyroidism years ago, originally made from pig glands. There are now several prescription medications made from the desiccated (dried) thyroid glands of animals, including brands such as Armour Thyroid, NP Thyroid, and WP Thyroid.
The practice of prescribing combination therapy has already been deemed acceptable by both the European Thyroid Association (ETA) and American Thyroid Association (ATA). The latter recommended in its 2014 guidelines that the combination of LT3/LT4 therapy may be trialed in exceptional circumstances or among patients who fail to improve with LT4 alone.
In following suit, the new Joint British Thyroid Association/Society consensus statement cautions that, first and foremost, “most patients with hypothyroidism should be treated with levothyroxine alone.”
However, combination LT3/LT4 therapy may be considered an option under key important conditions, including:
- When a diagnosis of overt hypothyroidism (documented TSH ≥ 10 mU/L and/or low FT4 pretreatment with thyroid replacement hormones) is established. If overt hypothyroidism cannot be confirmed, patients are recommended to first have a trial without LT4 and a repeat serum TSH after 6 weeks.
- For patients with overt hypothyroidism, prior to consideration of LT3, the dose of LT4 should be optimized to a TSH in the target range of 0.3-2.0 mU/L for 3 to 6 months. In some patients, it may be acceptable to have serum TSH below reference range (e.g., 0.1-0.3 mU/L), but not fully suppressed in the long term, instead of starting LT3.
- A trial of combination therapy may be warranted with confirmed overt hypothyroidism and persistent symptoms despite LT4 treatment and the exclusion of other comorbidities.
- Clinicians should not feel obliged to start LT3 or continue LT3 medication provided by other health care practitioners or accessed without medical advice if they judge this not to be in the patient’s best interest.
- When opting for LT3, a minimum of 3 to 6 months on the combination therapy should be considered before determining response to the trial, and for assessment, monitoring with serum TSH only is recommended.
- Patients should be counseled regarding the risk of arrhythmias, accelerated bone loss, and stroke associated with iatrogenic hyperthyroidism and the need for long-term monitoring.
- Given the short half-life of LT3, splitting doses across 24 hours is recommended for many people.
The joint association does not recommend the use of desiccated thyroid extract (which appears to be surprisingly on the rise, as recently reported).
Reasons for persistent symptoms are murky; don’t forget menopause
The key reason for the emphasis on making sure patients have overt hypothyroidism before trying LT3 is that patients are often treated with LT4 despite not even having hypothyroidism to begin with.
“In reality, many patients with subclinical hypothyroidism [TSH 5-10 mU/L] are now treated with levothyroxine, fueling a rise in its use, such that it is now the third most frequently prescribed medication in the United Kingdom,” the authors explained.
“In contrast, few patients are advised to seek lifestyle and exercise changes, despite the fact that there is positive evidence to support their benefits,” they continued.
In a recent podcast, Anthony Bianco, MD, a past president of the ATA, underscored another important factor complicating the ability to make conclusive hypothyroidism diagnoses in women: menopause.
“In my experience, the most confusing factor [in treatment decisions] is menopausal syndrome,” he said.
“The symptoms are very similar. Most patients with hypothyroidism are women. Are we getting close to menopause? Are we dealing with this? Is estrogen replacement therapy an option for this woman? Should we consult a colleague?” Dr. Bianco explained.
And there are other possibilities, including anemia, iron deficiency, other autoimmune diseases, and diabetes, he added.
“Exclude everything that you know,” Dr. Bianco said. “Use your common sense.”
Although the new statement echoes other guidelines, the recommendations are helpful amid the ever-present debate, said Dr. Wiersinga, the endocrinologist from the Netherlands.
Because of the pressure to try combination therapy, from patients and patient associations, the statement’s position that doctors must stand by their clinical judgment is important, he noted.
“I think many doctors would welcome the recommendation that doctors are not obliged to prescribe any medication that they believe is not in the patient’s best interest, and, in particular, that ‘doctors have no obligation to continue to provide prescriptions for LT3 or desiccated thyroid extract that have been started by other health care practitioners or accessed without medical advice if they judge this not to be in the patient’s best interest,’” he asserted.
“Also, the recommendation that an endocrinologist should be involved when a trial of T3 is considered is very valuable,” he added, noting the potential scenario of patients going to a general practitioner if turned down by a specialist for LT3.
An international consensus statement published by members of the ATA, ETA, and British Thyroid Association in 2021 further set forth recommendations for the development of future trials of LT3/LT4 combination therapy to establish more conclusive guidance.
Senior author Simon H. Pearce has reported receiving speaker fees from IBSA, Merck, Quidel, Berlin-Chemie, and consulting for Apitope/Worg and Immunovant/Roivant on issues unrelated to T3. The other authors of the consensus statement have reported no relevant financial relationships. Dr. Wiersinga has reporting consulting for Prolevi Bio.
A version of this article first appeared on Medscape.com.
New recommendations from the Joint British Thyroid Association/Society add to the increasingly general consensus that liothyronine (LT3) may be useful in combination with standard levothyroxine (LT4) in the treatment of hypothyroidism in some patients whose symptoms persist after standard treatment, despite a lack of evidence of benefit in clinical trials.
“Most patients with primary hypothyroidism respond well to levothyroxine replacement therapy,” recommends the joint association in the consensus statement, by Rupa Ahluwalia, MBBS, MD, of Norfolk and Norwich University Hospitals NHS Trust, United Kingdom, and colleagues, recently published in Clinical Endocrinology.
they wrote.
The ongoing debate over the use of LT3/LT4 combination therapy has persisted for more than 2 decades, with at least 16 randomized controlled trials and four meta-analyses failing to show any significant benefit of the combined regimen in key quality of life and cognitive function outcomes compared with LT4 monotherapy. However, many patients continue to report benefits with combination therapy, so the issue has not been laid to rest.
Wilmar M. Wiersinga, MD, PhD, emeritus professor of endocrinology at the University of Amsterdam, said in an interview: “The scientific community is divided as to whether or not the LT4/LT3 combination therapy has any value whatsoever, whereas the pressure from individual patients and patient associations on physicians – both general practitioners and specialists/endocrinologists – can be very high [in terms of] demanding prescriptions for the combination therapy.
“I welcome this joint statement very much because it provides guidance, especially for clinicians, on a hotly debated issue,” he said.
Persistent symptoms drive pursuit of alternatives
T4 refers to the hormone thyroxine made in the body, and LT4 to the pharmaceutical replacement product for that hormone, levothyroxine. Similarly, T3 refers to the hormone triiodothyronine, made in the body and a precursor to thyroxine, and LT3 refers to its pharmaceutical replacement, liothyronine.
Driving the continued demand from some patients with hypothyroidism and interest among clinicians is the relatively high proportion of patients who continue to experience symptoms even after the normalization of biochemical levels after treatment with LT4, which resolves symptoms in most patients within weeks of therapy.
Those who don’t improve report common ongoing symptoms: fatigue, sleepiness, memory problems, cognitive difficulties (brain fog), and weight gain.
However, with 60% of people commonly having one or more of the same symptoms even when their thyroid levels are normal, pinpointing the actual causes is a challenge, the societies report.
In the absence of other diagnoses, clinicians often turn to alternative treatment strategies, which, as well as addition of LT3 to LT4, also include the use of desiccated thyroid extract (DTE).
DTE was the medication first used to treat hypothyroidism years ago, originally made from pig glands. There are now several prescription medications made from the desiccated (dried) thyroid glands of animals, including brands such as Armour Thyroid, NP Thyroid, and WP Thyroid.
The practice of prescribing combination therapy has already been deemed acceptable by both the European Thyroid Association (ETA) and American Thyroid Association (ATA). The latter recommended in its 2014 guidelines that the combination of LT3/LT4 therapy may be trialed in exceptional circumstances or among patients who fail to improve with LT4 alone.
In following suit, the new Joint British Thyroid Association/Society consensus statement cautions that, first and foremost, “most patients with hypothyroidism should be treated with levothyroxine alone.”
However, combination LT3/LT4 therapy may be considered an option under key important conditions, including:
- When a diagnosis of overt hypothyroidism (documented TSH ≥ 10 mU/L and/or low FT4 pretreatment with thyroid replacement hormones) is established. If overt hypothyroidism cannot be confirmed, patients are recommended to first have a trial without LT4 and a repeat serum TSH after 6 weeks.
- For patients with overt hypothyroidism, prior to consideration of LT3, the dose of LT4 should be optimized to a TSH in the target range of 0.3-2.0 mU/L for 3 to 6 months. In some patients, it may be acceptable to have serum TSH below reference range (e.g., 0.1-0.3 mU/L), but not fully suppressed in the long term, instead of starting LT3.
- A trial of combination therapy may be warranted with confirmed overt hypothyroidism and persistent symptoms despite LT4 treatment and the exclusion of other comorbidities.
- Clinicians should not feel obliged to start LT3 or continue LT3 medication provided by other health care practitioners or accessed without medical advice if they judge this not to be in the patient’s best interest.
- When opting for LT3, a minimum of 3 to 6 months on the combination therapy should be considered before determining response to the trial, and for assessment, monitoring with serum TSH only is recommended.
- Patients should be counseled regarding the risk of arrhythmias, accelerated bone loss, and stroke associated with iatrogenic hyperthyroidism and the need for long-term monitoring.
- Given the short half-life of LT3, splitting doses across 24 hours is recommended for many people.
The joint association does not recommend the use of desiccated thyroid extract (which appears to be surprisingly on the rise, as recently reported).
Reasons for persistent symptoms are murky; don’t forget menopause
The key reason for the emphasis on making sure patients have overt hypothyroidism before trying LT3 is that patients are often treated with LT4 despite not even having hypothyroidism to begin with.
“In reality, many patients with subclinical hypothyroidism [TSH 5-10 mU/L] are now treated with levothyroxine, fueling a rise in its use, such that it is now the third most frequently prescribed medication in the United Kingdom,” the authors explained.
“In contrast, few patients are advised to seek lifestyle and exercise changes, despite the fact that there is positive evidence to support their benefits,” they continued.
In a recent podcast, Anthony Bianco, MD, a past president of the ATA, underscored another important factor complicating the ability to make conclusive hypothyroidism diagnoses in women: menopause.
“In my experience, the most confusing factor [in treatment decisions] is menopausal syndrome,” he said.
“The symptoms are very similar. Most patients with hypothyroidism are women. Are we getting close to menopause? Are we dealing with this? Is estrogen replacement therapy an option for this woman? Should we consult a colleague?” Dr. Bianco explained.
And there are other possibilities, including anemia, iron deficiency, other autoimmune diseases, and diabetes, he added.
“Exclude everything that you know,” Dr. Bianco said. “Use your common sense.”
Although the new statement echoes other guidelines, the recommendations are helpful amid the ever-present debate, said Dr. Wiersinga, the endocrinologist from the Netherlands.
Because of the pressure to try combination therapy, from patients and patient associations, the statement’s position that doctors must stand by their clinical judgment is important, he noted.
“I think many doctors would welcome the recommendation that doctors are not obliged to prescribe any medication that they believe is not in the patient’s best interest, and, in particular, that ‘doctors have no obligation to continue to provide prescriptions for LT3 or desiccated thyroid extract that have been started by other health care practitioners or accessed without medical advice if they judge this not to be in the patient’s best interest,’” he asserted.
“Also, the recommendation that an endocrinologist should be involved when a trial of T3 is considered is very valuable,” he added, noting the potential scenario of patients going to a general practitioner if turned down by a specialist for LT3.
An international consensus statement published by members of the ATA, ETA, and British Thyroid Association in 2021 further set forth recommendations for the development of future trials of LT3/LT4 combination therapy to establish more conclusive guidance.
Senior author Simon H. Pearce has reported receiving speaker fees from IBSA, Merck, Quidel, Berlin-Chemie, and consulting for Apitope/Worg and Immunovant/Roivant on issues unrelated to T3. The other authors of the consensus statement have reported no relevant financial relationships. Dr. Wiersinga has reporting consulting for Prolevi Bio.
A version of this article first appeared on Medscape.com.
New recommendations from the Joint British Thyroid Association/Society add to the increasingly general consensus that liothyronine (LT3) may be useful in combination with standard levothyroxine (LT4) in the treatment of hypothyroidism in some patients whose symptoms persist after standard treatment, despite a lack of evidence of benefit in clinical trials.
“Most patients with primary hypothyroidism respond well to levothyroxine replacement therapy,” recommends the joint association in the consensus statement, by Rupa Ahluwalia, MBBS, MD, of Norfolk and Norwich University Hospitals NHS Trust, United Kingdom, and colleagues, recently published in Clinical Endocrinology.
they wrote.
The ongoing debate over the use of LT3/LT4 combination therapy has persisted for more than 2 decades, with at least 16 randomized controlled trials and four meta-analyses failing to show any significant benefit of the combined regimen in key quality of life and cognitive function outcomes compared with LT4 monotherapy. However, many patients continue to report benefits with combination therapy, so the issue has not been laid to rest.
Wilmar M. Wiersinga, MD, PhD, emeritus professor of endocrinology at the University of Amsterdam, said in an interview: “The scientific community is divided as to whether or not the LT4/LT3 combination therapy has any value whatsoever, whereas the pressure from individual patients and patient associations on physicians – both general practitioners and specialists/endocrinologists – can be very high [in terms of] demanding prescriptions for the combination therapy.
“I welcome this joint statement very much because it provides guidance, especially for clinicians, on a hotly debated issue,” he said.
Persistent symptoms drive pursuit of alternatives
T4 refers to the hormone thyroxine made in the body, and LT4 to the pharmaceutical replacement product for that hormone, levothyroxine. Similarly, T3 refers to the hormone triiodothyronine, made in the body and a precursor to thyroxine, and LT3 refers to its pharmaceutical replacement, liothyronine.
Driving the continued demand from some patients with hypothyroidism and interest among clinicians is the relatively high proportion of patients who continue to experience symptoms even after the normalization of biochemical levels after treatment with LT4, which resolves symptoms in most patients within weeks of therapy.
Those who don’t improve report common ongoing symptoms: fatigue, sleepiness, memory problems, cognitive difficulties (brain fog), and weight gain.
However, with 60% of people commonly having one or more of the same symptoms even when their thyroid levels are normal, pinpointing the actual causes is a challenge, the societies report.
In the absence of other diagnoses, clinicians often turn to alternative treatment strategies, which, as well as addition of LT3 to LT4, also include the use of desiccated thyroid extract (DTE).
DTE was the medication first used to treat hypothyroidism years ago, originally made from pig glands. There are now several prescription medications made from the desiccated (dried) thyroid glands of animals, including brands such as Armour Thyroid, NP Thyroid, and WP Thyroid.
The practice of prescribing combination therapy has already been deemed acceptable by both the European Thyroid Association (ETA) and American Thyroid Association (ATA). The latter recommended in its 2014 guidelines that the combination of LT3/LT4 therapy may be trialed in exceptional circumstances or among patients who fail to improve with LT4 alone.
In following suit, the new Joint British Thyroid Association/Society consensus statement cautions that, first and foremost, “most patients with hypothyroidism should be treated with levothyroxine alone.”
However, combination LT3/LT4 therapy may be considered an option under key important conditions, including:
- When a diagnosis of overt hypothyroidism (documented TSH ≥ 10 mU/L and/or low FT4 pretreatment with thyroid replacement hormones) is established. If overt hypothyroidism cannot be confirmed, patients are recommended to first have a trial without LT4 and a repeat serum TSH after 6 weeks.
- For patients with overt hypothyroidism, prior to consideration of LT3, the dose of LT4 should be optimized to a TSH in the target range of 0.3-2.0 mU/L for 3 to 6 months. In some patients, it may be acceptable to have serum TSH below reference range (e.g., 0.1-0.3 mU/L), but not fully suppressed in the long term, instead of starting LT3.
- A trial of combination therapy may be warranted with confirmed overt hypothyroidism and persistent symptoms despite LT4 treatment and the exclusion of other comorbidities.
- Clinicians should not feel obliged to start LT3 or continue LT3 medication provided by other health care practitioners or accessed without medical advice if they judge this not to be in the patient’s best interest.
- When opting for LT3, a minimum of 3 to 6 months on the combination therapy should be considered before determining response to the trial, and for assessment, monitoring with serum TSH only is recommended.
- Patients should be counseled regarding the risk of arrhythmias, accelerated bone loss, and stroke associated with iatrogenic hyperthyroidism and the need for long-term monitoring.
- Given the short half-life of LT3, splitting doses across 24 hours is recommended for many people.
The joint association does not recommend the use of desiccated thyroid extract (which appears to be surprisingly on the rise, as recently reported).
Reasons for persistent symptoms are murky; don’t forget menopause
The key reason for the emphasis on making sure patients have overt hypothyroidism before trying LT3 is that patients are often treated with LT4 despite not even having hypothyroidism to begin with.
“In reality, many patients with subclinical hypothyroidism [TSH 5-10 mU/L] are now treated with levothyroxine, fueling a rise in its use, such that it is now the third most frequently prescribed medication in the United Kingdom,” the authors explained.
“In contrast, few patients are advised to seek lifestyle and exercise changes, despite the fact that there is positive evidence to support their benefits,” they continued.
In a recent podcast, Anthony Bianco, MD, a past president of the ATA, underscored another important factor complicating the ability to make conclusive hypothyroidism diagnoses in women: menopause.
“In my experience, the most confusing factor [in treatment decisions] is menopausal syndrome,” he said.
“The symptoms are very similar. Most patients with hypothyroidism are women. Are we getting close to menopause? Are we dealing with this? Is estrogen replacement therapy an option for this woman? Should we consult a colleague?” Dr. Bianco explained.
And there are other possibilities, including anemia, iron deficiency, other autoimmune diseases, and diabetes, he added.
“Exclude everything that you know,” Dr. Bianco said. “Use your common sense.”
Although the new statement echoes other guidelines, the recommendations are helpful amid the ever-present debate, said Dr. Wiersinga, the endocrinologist from the Netherlands.
Because of the pressure to try combination therapy, from patients and patient associations, the statement’s position that doctors must stand by their clinical judgment is important, he noted.
“I think many doctors would welcome the recommendation that doctors are not obliged to prescribe any medication that they believe is not in the patient’s best interest, and, in particular, that ‘doctors have no obligation to continue to provide prescriptions for LT3 or desiccated thyroid extract that have been started by other health care practitioners or accessed without medical advice if they judge this not to be in the patient’s best interest,’” he asserted.
“Also, the recommendation that an endocrinologist should be involved when a trial of T3 is considered is very valuable,” he added, noting the potential scenario of patients going to a general practitioner if turned down by a specialist for LT3.
An international consensus statement published by members of the ATA, ETA, and British Thyroid Association in 2021 further set forth recommendations for the development of future trials of LT3/LT4 combination therapy to establish more conclusive guidance.
Senior author Simon H. Pearce has reported receiving speaker fees from IBSA, Merck, Quidel, Berlin-Chemie, and consulting for Apitope/Worg and Immunovant/Roivant on issues unrelated to T3. The other authors of the consensus statement have reported no relevant financial relationships. Dr. Wiersinga has reporting consulting for Prolevi Bio.
A version of this article first appeared on Medscape.com.
FROM CLINICAL ENDOCRINOLOGY
Surgery, radioactive iodine for hyperthyroidism up survival
CHICAGO – new data from a large cohort study suggest.
“I think this is something we need to take into our discussions with patients because treatment for hyperthyroidism is very much individualized decision-making ... The effects on mortality are not usually one of the factors we discuss there. But now, we have strong data from a very large cohort of patients indicating that this is something that does need to be discussed,” lead author Kristien Boelaert, MD, who is the current president of the British Thyroid Association, said in an interview.
Dr. Boelaert presented the findings of the EGRET (Weight Changes, Cardio-Metabolic Risks and Mortality in Patients With Hyperthyroidism) study at the Annual Meeting of the Endocrine Society.
Other notable findings from EGRET were that the patients on antithyroid medication were thinner than expected, suggesting undertreatment, and that no differences were found for major adverse cardiac events (MACE) across the treatment options, leaving unexplained the reasons for the increased mortality in the medicated group.
Asked to comment, session moderator Spyridoula Maraka, MD, said: “I think this is very important work because so far when we counsel our patients about the different treatment modalities we focus more on risk for recurrence and other short-term outcomes.”
“But these data give us a bigger perspective on mortality and cardiovascular outcomes ... We haven’t had such good quality data to accurately counsel our patients,” added Dr. Maraka, of the University of Arkansas for Medical Sciences, Little Rock.
Mortality higher for medication-treated, but why?
“Hyperthyroidism or an overactive thyroid gland is common, affecting up to 3% of the population, and is associated with long-term adverse cardiac and metabolic consequences. The optimal treatment choice remains unclear,” explained Dr. Boelaert, professor of endocrinology at the University of Birmingham, England, outlining the reasons they conducted the EGRET study.
The study population was 55,318 patients (77% women) with newly diagnosed hyperthyroidism identified from a U.K. population-based primary care electronic health record database. Of those, 77.8% were treated with antithyroid medication, 14.6% with radioactive iodine, and 7.8% with surgery (total or hemithyroidectomy). The health records were linked with national mortality data and Health Survey England data on body mass index (BMI) for comparison.
Dr. Boelaert noted that the trial design “is the best we have” because a randomized clinical trial comparing hyperthyroid treatments would be extremely difficult given the need to individualize therapy and the impossibility of blinding. On the other hand, with the current study, “it’s certainly the largest patient group we’ve looked at.”
Over an average 12.1 years of follow-up, the proportion of patients who died was 14.1% in the medication group, 18.7% of those who had radioiodine therapy, and 9.2% of those who underwent surgery.
Compared with the number who would have been expected to die based on the general background population, the likelihood of reduced life expectancy for the treated groups was increased 2.10-fold for radioiodine, 2.13-fold for surgery, and 2.71-fold for medication. All were significantly higher than the general population (P < .0001).
After further adjustment for multiple confounders, mortality risk was reduced in patients treated with radioiodine (by 13%) or surgery (by 20%), compared with those treated with antithyroid medication, both significant reductions (P < .0001).
After exclusion of the 3.9% with baseline cardiovascular disease, MACE (defined as cardiovascular death or hospitalization for stroke or myocardial infarction) occurred in 9.9%, 13.4%, and 8.0% of the medication, radioiodine, and surgery groups, respectively.
After adjustments, there were no differences in MACE, compared with medications, with hazard ratios of 1.00 (P = .94) for radioactive iodine and 0.97 for surgery (P = .61).
“We were expecting to see a reduction in cardiovascular events, as previous studies suggest that radioactive iodine patients have fewer cardiovascular deaths. We did not see that but our protocol wasn’t set up to get every single specific cause of death. That will require further ongoing analysis,” said Dr. Boelaert.
Weight gain: Worth it for longer life
Compared with the background population, thyroidectomy was associated with an increased likelihood of developing obesity (BMI > 30 kg/m2) in both men (odds ratio, 1.56; P < .001), and women (OR, 1.27; P < .001), while radioiodine increased obesity risk in women (OR, 1.12; P < .001) but not in men (OR, 1.03; P = .55).
Among the women, those treated with antithyroid medications had an average 0.28 kg/m2 lower BMI, compared with the background population, and those treated with surgery had a 0.83 kg/m2 higher BMI. Both differences were significant (P < .001).
The BMI differences were not significant for radioactive iodine in women and for medications and radioactive iodine in men, although the men treated surgically also had a significantly higher BMI (1.09 kg/m2; P < .001).
“The patients on antithyroid drugs were lighter than we would expect. I think that’s ongoing hyperthyroidism. I strongly believe that ... to get rid of hyperthyroidism you have to make patients hypothyroid ... It’s really important that you get good control,” Dr. Boelaert commented.
Dr. Maraka, who is also endocrine section chief of the Arkansas Veteran’s Healthcare System, Little Rock, commented: “[Dr. Boelaert’s] concern is that the patients on antithyroid drugs are not adequately controlled, and we know very well that uncontrolled hyperthyroidism is associated with increased mortality and increased cardiovascular outcomes. This suggests that if patients are on antithyroid medications, they should at least be monitored very well.”
Regarding the possible cause of the increased mortality, if not cardiovascular, Dr. Maraka also pointed out that typically once antithyroid medications are stopped, about half of patients will stay in remission and the other half will return to hyperthyroidism.
“It might be that this kind of ‘yo-yo’ is what’s actually leading to the increased mortality, compared to patients who had definitive treatment and this problem was taken care of. This is speculation but it might be what we’re seeing,” Dr. Maraka observed.
The BMI differences worked out to a weight gain with surgery of approximately 2.1 kg (4.6 lb) for a woman with a height of 160 cm and 2.4 kg for 170 cm. Among men, those differences were 3.2 kg and 3.5 kg for heights of 170 cm and 190 cm, respectively.
Dr. Boelaert said, “I think we should discuss this with patients. They will say they don’t want to get fat, but the absolute weight gain is ... not that much.”
“I personally think that 2 kg is not a big price to pay to live longer. I hope that’s what we’ll be telling our patients in clinic in the next few years after we get this published.”
Dr. Boelaert and Dr. Maraka have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
CHICAGO – new data from a large cohort study suggest.
“I think this is something we need to take into our discussions with patients because treatment for hyperthyroidism is very much individualized decision-making ... The effects on mortality are not usually one of the factors we discuss there. But now, we have strong data from a very large cohort of patients indicating that this is something that does need to be discussed,” lead author Kristien Boelaert, MD, who is the current president of the British Thyroid Association, said in an interview.
Dr. Boelaert presented the findings of the EGRET (Weight Changes, Cardio-Metabolic Risks and Mortality in Patients With Hyperthyroidism) study at the Annual Meeting of the Endocrine Society.
Other notable findings from EGRET were that the patients on antithyroid medication were thinner than expected, suggesting undertreatment, and that no differences were found for major adverse cardiac events (MACE) across the treatment options, leaving unexplained the reasons for the increased mortality in the medicated group.
Asked to comment, session moderator Spyridoula Maraka, MD, said: “I think this is very important work because so far when we counsel our patients about the different treatment modalities we focus more on risk for recurrence and other short-term outcomes.”
“But these data give us a bigger perspective on mortality and cardiovascular outcomes ... We haven’t had such good quality data to accurately counsel our patients,” added Dr. Maraka, of the University of Arkansas for Medical Sciences, Little Rock.
Mortality higher for medication-treated, but why?
“Hyperthyroidism or an overactive thyroid gland is common, affecting up to 3% of the population, and is associated with long-term adverse cardiac and metabolic consequences. The optimal treatment choice remains unclear,” explained Dr. Boelaert, professor of endocrinology at the University of Birmingham, England, outlining the reasons they conducted the EGRET study.
The study population was 55,318 patients (77% women) with newly diagnosed hyperthyroidism identified from a U.K. population-based primary care electronic health record database. Of those, 77.8% were treated with antithyroid medication, 14.6% with radioactive iodine, and 7.8% with surgery (total or hemithyroidectomy). The health records were linked with national mortality data and Health Survey England data on body mass index (BMI) for comparison.
Dr. Boelaert noted that the trial design “is the best we have” because a randomized clinical trial comparing hyperthyroid treatments would be extremely difficult given the need to individualize therapy and the impossibility of blinding. On the other hand, with the current study, “it’s certainly the largest patient group we’ve looked at.”
Over an average 12.1 years of follow-up, the proportion of patients who died was 14.1% in the medication group, 18.7% of those who had radioiodine therapy, and 9.2% of those who underwent surgery.
Compared with the number who would have been expected to die based on the general background population, the likelihood of reduced life expectancy for the treated groups was increased 2.10-fold for radioiodine, 2.13-fold for surgery, and 2.71-fold for medication. All were significantly higher than the general population (P < .0001).
After further adjustment for multiple confounders, mortality risk was reduced in patients treated with radioiodine (by 13%) or surgery (by 20%), compared with those treated with antithyroid medication, both significant reductions (P < .0001).
After exclusion of the 3.9% with baseline cardiovascular disease, MACE (defined as cardiovascular death or hospitalization for stroke or myocardial infarction) occurred in 9.9%, 13.4%, and 8.0% of the medication, radioiodine, and surgery groups, respectively.
After adjustments, there were no differences in MACE, compared with medications, with hazard ratios of 1.00 (P = .94) for radioactive iodine and 0.97 for surgery (P = .61).
“We were expecting to see a reduction in cardiovascular events, as previous studies suggest that radioactive iodine patients have fewer cardiovascular deaths. We did not see that but our protocol wasn’t set up to get every single specific cause of death. That will require further ongoing analysis,” said Dr. Boelaert.
Weight gain: Worth it for longer life
Compared with the background population, thyroidectomy was associated with an increased likelihood of developing obesity (BMI > 30 kg/m2) in both men (odds ratio, 1.56; P < .001), and women (OR, 1.27; P < .001), while radioiodine increased obesity risk in women (OR, 1.12; P < .001) but not in men (OR, 1.03; P = .55).
Among the women, those treated with antithyroid medications had an average 0.28 kg/m2 lower BMI, compared with the background population, and those treated with surgery had a 0.83 kg/m2 higher BMI. Both differences were significant (P < .001).
The BMI differences were not significant for radioactive iodine in women and for medications and radioactive iodine in men, although the men treated surgically also had a significantly higher BMI (1.09 kg/m2; P < .001).
“The patients on antithyroid drugs were lighter than we would expect. I think that’s ongoing hyperthyroidism. I strongly believe that ... to get rid of hyperthyroidism you have to make patients hypothyroid ... It’s really important that you get good control,” Dr. Boelaert commented.
Dr. Maraka, who is also endocrine section chief of the Arkansas Veteran’s Healthcare System, Little Rock, commented: “[Dr. Boelaert’s] concern is that the patients on antithyroid drugs are not adequately controlled, and we know very well that uncontrolled hyperthyroidism is associated with increased mortality and increased cardiovascular outcomes. This suggests that if patients are on antithyroid medications, they should at least be monitored very well.”
Regarding the possible cause of the increased mortality, if not cardiovascular, Dr. Maraka also pointed out that typically once antithyroid medications are stopped, about half of patients will stay in remission and the other half will return to hyperthyroidism.
“It might be that this kind of ‘yo-yo’ is what’s actually leading to the increased mortality, compared to patients who had definitive treatment and this problem was taken care of. This is speculation but it might be what we’re seeing,” Dr. Maraka observed.
The BMI differences worked out to a weight gain with surgery of approximately 2.1 kg (4.6 lb) for a woman with a height of 160 cm and 2.4 kg for 170 cm. Among men, those differences were 3.2 kg and 3.5 kg for heights of 170 cm and 190 cm, respectively.
Dr. Boelaert said, “I think we should discuss this with patients. They will say they don’t want to get fat, but the absolute weight gain is ... not that much.”
“I personally think that 2 kg is not a big price to pay to live longer. I hope that’s what we’ll be telling our patients in clinic in the next few years after we get this published.”
Dr. Boelaert and Dr. Maraka have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
CHICAGO – new data from a large cohort study suggest.
“I think this is something we need to take into our discussions with patients because treatment for hyperthyroidism is very much individualized decision-making ... The effects on mortality are not usually one of the factors we discuss there. But now, we have strong data from a very large cohort of patients indicating that this is something that does need to be discussed,” lead author Kristien Boelaert, MD, who is the current president of the British Thyroid Association, said in an interview.
Dr. Boelaert presented the findings of the EGRET (Weight Changes, Cardio-Metabolic Risks and Mortality in Patients With Hyperthyroidism) study at the Annual Meeting of the Endocrine Society.
Other notable findings from EGRET were that the patients on antithyroid medication were thinner than expected, suggesting undertreatment, and that no differences were found for major adverse cardiac events (MACE) across the treatment options, leaving unexplained the reasons for the increased mortality in the medicated group.
Asked to comment, session moderator Spyridoula Maraka, MD, said: “I think this is very important work because so far when we counsel our patients about the different treatment modalities we focus more on risk for recurrence and other short-term outcomes.”
“But these data give us a bigger perspective on mortality and cardiovascular outcomes ... We haven’t had such good quality data to accurately counsel our patients,” added Dr. Maraka, of the University of Arkansas for Medical Sciences, Little Rock.
Mortality higher for medication-treated, but why?
“Hyperthyroidism or an overactive thyroid gland is common, affecting up to 3% of the population, and is associated with long-term adverse cardiac and metabolic consequences. The optimal treatment choice remains unclear,” explained Dr. Boelaert, professor of endocrinology at the University of Birmingham, England, outlining the reasons they conducted the EGRET study.
The study population was 55,318 patients (77% women) with newly diagnosed hyperthyroidism identified from a U.K. population-based primary care electronic health record database. Of those, 77.8% were treated with antithyroid medication, 14.6% with radioactive iodine, and 7.8% with surgery (total or hemithyroidectomy). The health records were linked with national mortality data and Health Survey England data on body mass index (BMI) for comparison.
Dr. Boelaert noted that the trial design “is the best we have” because a randomized clinical trial comparing hyperthyroid treatments would be extremely difficult given the need to individualize therapy and the impossibility of blinding. On the other hand, with the current study, “it’s certainly the largest patient group we’ve looked at.”
Over an average 12.1 years of follow-up, the proportion of patients who died was 14.1% in the medication group, 18.7% of those who had radioiodine therapy, and 9.2% of those who underwent surgery.
Compared with the number who would have been expected to die based on the general background population, the likelihood of reduced life expectancy for the treated groups was increased 2.10-fold for radioiodine, 2.13-fold for surgery, and 2.71-fold for medication. All were significantly higher than the general population (P < .0001).
After further adjustment for multiple confounders, mortality risk was reduced in patients treated with radioiodine (by 13%) or surgery (by 20%), compared with those treated with antithyroid medication, both significant reductions (P < .0001).
After exclusion of the 3.9% with baseline cardiovascular disease, MACE (defined as cardiovascular death or hospitalization for stroke or myocardial infarction) occurred in 9.9%, 13.4%, and 8.0% of the medication, radioiodine, and surgery groups, respectively.
After adjustments, there were no differences in MACE, compared with medications, with hazard ratios of 1.00 (P = .94) for radioactive iodine and 0.97 for surgery (P = .61).
“We were expecting to see a reduction in cardiovascular events, as previous studies suggest that radioactive iodine patients have fewer cardiovascular deaths. We did not see that but our protocol wasn’t set up to get every single specific cause of death. That will require further ongoing analysis,” said Dr. Boelaert.
Weight gain: Worth it for longer life
Compared with the background population, thyroidectomy was associated with an increased likelihood of developing obesity (BMI > 30 kg/m2) in both men (odds ratio, 1.56; P < .001), and women (OR, 1.27; P < .001), while radioiodine increased obesity risk in women (OR, 1.12; P < .001) but not in men (OR, 1.03; P = .55).
Among the women, those treated with antithyroid medications had an average 0.28 kg/m2 lower BMI, compared with the background population, and those treated with surgery had a 0.83 kg/m2 higher BMI. Both differences were significant (P < .001).
The BMI differences were not significant for radioactive iodine in women and for medications and radioactive iodine in men, although the men treated surgically also had a significantly higher BMI (1.09 kg/m2; P < .001).
“The patients on antithyroid drugs were lighter than we would expect. I think that’s ongoing hyperthyroidism. I strongly believe that ... to get rid of hyperthyroidism you have to make patients hypothyroid ... It’s really important that you get good control,” Dr. Boelaert commented.
Dr. Maraka, who is also endocrine section chief of the Arkansas Veteran’s Healthcare System, Little Rock, commented: “[Dr. Boelaert’s] concern is that the patients on antithyroid drugs are not adequately controlled, and we know very well that uncontrolled hyperthyroidism is associated with increased mortality and increased cardiovascular outcomes. This suggests that if patients are on antithyroid medications, they should at least be monitored very well.”
Regarding the possible cause of the increased mortality, if not cardiovascular, Dr. Maraka also pointed out that typically once antithyroid medications are stopped, about half of patients will stay in remission and the other half will return to hyperthyroidism.
“It might be that this kind of ‘yo-yo’ is what’s actually leading to the increased mortality, compared to patients who had definitive treatment and this problem was taken care of. This is speculation but it might be what we’re seeing,” Dr. Maraka observed.
The BMI differences worked out to a weight gain with surgery of approximately 2.1 kg (4.6 lb) for a woman with a height of 160 cm and 2.4 kg for 170 cm. Among men, those differences were 3.2 kg and 3.5 kg for heights of 170 cm and 190 cm, respectively.
Dr. Boelaert said, “I think we should discuss this with patients. They will say they don’t want to get fat, but the absolute weight gain is ... not that much.”
“I personally think that 2 kg is not a big price to pay to live longer. I hope that’s what we’ll be telling our patients in clinic in the next few years after we get this published.”
Dr. Boelaert and Dr. Maraka have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT ENDO 2023
Scripts surge for desiccated thyroid extract to treat hypothyroidism
new research has found.
Nationwide MarketScan claims data reveal that, among first-time thyroid hormone prescriptions, those for DTE rose from 5.4% in 2010 to 10.2% in 2020. At the same time, prescriptions for first-line levothyroxine dropped from 91.8% to 87.2%. Prescriptions for liothyronine (LT3), primarily in combination with levothyroxine, remained at about 2% throughout the decade.
The nonlevothyroxine therapies were more commonly prescribed in the West and Southwestern United States, while levothyroxine monotherapy was more frequent in the Northwest and upper Midwest, and also in states with higher densities of primary care physicians and endocrinologists.
The magnitude of this shift in first-line treatment was unexpected.
“We were frankly quite surprised to see that difference in just 10 years,” lead author Matthew Ettleson, MD, of the University of Chicago, said in an interview.
Asked to comment, session moderator Elizabeth N. Pearce, MD, professor of medicine at Boston University Medical Center, said she also found the dramatic shift to DTE surprising.
“It’s unclear why since there hasn’t been a shift in the science or in the guidelines over the last decade. ... I think we need to understand better what is driving this, who the patients are who are seeking it out, and which providers are the primary drivers of these prescriptions,” she said.
Dr. Ettleson presented the findings at the annual meeting of the Endocrine Society. The results were simultaneously published in the Journal of Clinical Endocrinology and Metabolism.
Why the increase in desiccated thyroid extract?
Current guidelines by the American Thyroid Association recommend levothyroxine, a synthetic form of thyroxine (T4) monotherapy, as the standard of care for treating hypothyroidism. However, approximately 10%-20% of levothyroxine-treated patients report bothersome symptoms despite normalization of thyroid-stimulating hormone (TSH) levels.
In 2021, the ATA, along with European and British thyroid societies, issued a consensus statement noting that new trials of triiodothyronine (T3)/T4 combination therapy were “justified.”
However, the MarketScan data were gathered before that statement came out, which doesn’t mention desiccated thyroid extract, “so that’s a bit of a head-scratcher,” Ettleson said.
He said one possibility may be the existence of online materials saying negative things about levothyroxine, so that “people who are just learning about hypothyroidism might already be primed to think about alternative treatments.” Moreover, some patients may view DTE as more “natural” than levothyroxine.
Dr. Ettleson also noted that the distinct geographic variation “didn’t seem random. ... So not only was there a doubling overall but there’s a variation in practice patterns across the country. I don’t have an explanation for that, but I think it’s important to recognize in the medical community that there are these big differences.”
Endocrinologists not as keen to prescribe DTE or T3
Residence in a state with higher endocrinologist density (3.0/100,000 population) was associated with a decreased likelihood of receiving T3 (adjusted odds ratio, 0.33; P < .001) or DTE therapy (aOR, 0.18; P < .001).
Residence in large central metro zones was associated with an increased likelihood of receiving T3 (aOR, 1.32; P < .001) or DTE therapy (aOR, 1.05; P < .008, respectively).
Dr. Pearce observed: “I don’t see DTE in Boston. It’s mostly in the South and Southwest.”
She said she doubted that endocrinologists were the primary prescribers of DTE, as many endocrinologists are “wary” of the pig thyroid–derived product because its T4 to T3 ratio is about 4:1, in contrast to the ratio in humans of 13-14:1.
Thus, DTE contains a much higher proportion of the active hormone T3. It is also much shorter acting, with a half-life of a few hours, compared to a few days for T4, she explained.
“We don’t really know what long-term safety effects are but it’s probably a less physiologic way of dosing thyroid hormone than ... either levothyroxine or levothyroxine in combination with a lower T3 proportion,” she said.
Just trying to understand
Dr. Ettleson emphasized that the goal of his research wasn’t to reverse the trend but to better understand it.
Nonetheless, he also noted, “now that we know there are more patients taking DTE, we need to start looking at rates of atrial fibrillation, fracture, heart failure, and other possible outcomes in this population and compare them with levothyroxine and nonthyroid populations to make sure that it is as safe as levothyroxine.”
“There are no data to suggest increased risk, especially if TSH is monitored and stays in the normal range, but there’s very little data for over 5 or 10 years on DTE-treated patients. We need the data,” he emphasized.
Meanwhile, he’s working on a survey of endocrinologists and non-endocrinologists to ask if they’ve prescribed DTE, and if so, why, and whether it’s because patients asked for it. “There’s a lot more work to be done, but I think it’s exciting. It’s important to see how patients are being treated in the real world ... and understand why it’s happening and what the outcomes are.”
Dr. Ettleson and Dr. Pearce have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
new research has found.
Nationwide MarketScan claims data reveal that, among first-time thyroid hormone prescriptions, those for DTE rose from 5.4% in 2010 to 10.2% in 2020. At the same time, prescriptions for first-line levothyroxine dropped from 91.8% to 87.2%. Prescriptions for liothyronine (LT3), primarily in combination with levothyroxine, remained at about 2% throughout the decade.
The nonlevothyroxine therapies were more commonly prescribed in the West and Southwestern United States, while levothyroxine monotherapy was more frequent in the Northwest and upper Midwest, and also in states with higher densities of primary care physicians and endocrinologists.
The magnitude of this shift in first-line treatment was unexpected.
“We were frankly quite surprised to see that difference in just 10 years,” lead author Matthew Ettleson, MD, of the University of Chicago, said in an interview.
Asked to comment, session moderator Elizabeth N. Pearce, MD, professor of medicine at Boston University Medical Center, said she also found the dramatic shift to DTE surprising.
“It’s unclear why since there hasn’t been a shift in the science or in the guidelines over the last decade. ... I think we need to understand better what is driving this, who the patients are who are seeking it out, and which providers are the primary drivers of these prescriptions,” she said.
Dr. Ettleson presented the findings at the annual meeting of the Endocrine Society. The results were simultaneously published in the Journal of Clinical Endocrinology and Metabolism.
Why the increase in desiccated thyroid extract?
Current guidelines by the American Thyroid Association recommend levothyroxine, a synthetic form of thyroxine (T4) monotherapy, as the standard of care for treating hypothyroidism. However, approximately 10%-20% of levothyroxine-treated patients report bothersome symptoms despite normalization of thyroid-stimulating hormone (TSH) levels.
In 2021, the ATA, along with European and British thyroid societies, issued a consensus statement noting that new trials of triiodothyronine (T3)/T4 combination therapy were “justified.”
However, the MarketScan data were gathered before that statement came out, which doesn’t mention desiccated thyroid extract, “so that’s a bit of a head-scratcher,” Ettleson said.
He said one possibility may be the existence of online materials saying negative things about levothyroxine, so that “people who are just learning about hypothyroidism might already be primed to think about alternative treatments.” Moreover, some patients may view DTE as more “natural” than levothyroxine.
Dr. Ettleson also noted that the distinct geographic variation “didn’t seem random. ... So not only was there a doubling overall but there’s a variation in practice patterns across the country. I don’t have an explanation for that, but I think it’s important to recognize in the medical community that there are these big differences.”
Endocrinologists not as keen to prescribe DTE or T3
Residence in a state with higher endocrinologist density (3.0/100,000 population) was associated with a decreased likelihood of receiving T3 (adjusted odds ratio, 0.33; P < .001) or DTE therapy (aOR, 0.18; P < .001).
Residence in large central metro zones was associated with an increased likelihood of receiving T3 (aOR, 1.32; P < .001) or DTE therapy (aOR, 1.05; P < .008, respectively).
Dr. Pearce observed: “I don’t see DTE in Boston. It’s mostly in the South and Southwest.”
She said she doubted that endocrinologists were the primary prescribers of DTE, as many endocrinologists are “wary” of the pig thyroid–derived product because its T4 to T3 ratio is about 4:1, in contrast to the ratio in humans of 13-14:1.
Thus, DTE contains a much higher proportion of the active hormone T3. It is also much shorter acting, with a half-life of a few hours, compared to a few days for T4, she explained.
“We don’t really know what long-term safety effects are but it’s probably a less physiologic way of dosing thyroid hormone than ... either levothyroxine or levothyroxine in combination with a lower T3 proportion,” she said.
Just trying to understand
Dr. Ettleson emphasized that the goal of his research wasn’t to reverse the trend but to better understand it.
Nonetheless, he also noted, “now that we know there are more patients taking DTE, we need to start looking at rates of atrial fibrillation, fracture, heart failure, and other possible outcomes in this population and compare them with levothyroxine and nonthyroid populations to make sure that it is as safe as levothyroxine.”
“There are no data to suggest increased risk, especially if TSH is monitored and stays in the normal range, but there’s very little data for over 5 or 10 years on DTE-treated patients. We need the data,” he emphasized.
Meanwhile, he’s working on a survey of endocrinologists and non-endocrinologists to ask if they’ve prescribed DTE, and if so, why, and whether it’s because patients asked for it. “There’s a lot more work to be done, but I think it’s exciting. It’s important to see how patients are being treated in the real world ... and understand why it’s happening and what the outcomes are.”
Dr. Ettleson and Dr. Pearce have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
new research has found.
Nationwide MarketScan claims data reveal that, among first-time thyroid hormone prescriptions, those for DTE rose from 5.4% in 2010 to 10.2% in 2020. At the same time, prescriptions for first-line levothyroxine dropped from 91.8% to 87.2%. Prescriptions for liothyronine (LT3), primarily in combination with levothyroxine, remained at about 2% throughout the decade.
The nonlevothyroxine therapies were more commonly prescribed in the West and Southwestern United States, while levothyroxine monotherapy was more frequent in the Northwest and upper Midwest, and also in states with higher densities of primary care physicians and endocrinologists.
The magnitude of this shift in first-line treatment was unexpected.
“We were frankly quite surprised to see that difference in just 10 years,” lead author Matthew Ettleson, MD, of the University of Chicago, said in an interview.
Asked to comment, session moderator Elizabeth N. Pearce, MD, professor of medicine at Boston University Medical Center, said she also found the dramatic shift to DTE surprising.
“It’s unclear why since there hasn’t been a shift in the science or in the guidelines over the last decade. ... I think we need to understand better what is driving this, who the patients are who are seeking it out, and which providers are the primary drivers of these prescriptions,” she said.
Dr. Ettleson presented the findings at the annual meeting of the Endocrine Society. The results were simultaneously published in the Journal of Clinical Endocrinology and Metabolism.
Why the increase in desiccated thyroid extract?
Current guidelines by the American Thyroid Association recommend levothyroxine, a synthetic form of thyroxine (T4) monotherapy, as the standard of care for treating hypothyroidism. However, approximately 10%-20% of levothyroxine-treated patients report bothersome symptoms despite normalization of thyroid-stimulating hormone (TSH) levels.
In 2021, the ATA, along with European and British thyroid societies, issued a consensus statement noting that new trials of triiodothyronine (T3)/T4 combination therapy were “justified.”
However, the MarketScan data were gathered before that statement came out, which doesn’t mention desiccated thyroid extract, “so that’s a bit of a head-scratcher,” Ettleson said.
He said one possibility may be the existence of online materials saying negative things about levothyroxine, so that “people who are just learning about hypothyroidism might already be primed to think about alternative treatments.” Moreover, some patients may view DTE as more “natural” than levothyroxine.
Dr. Ettleson also noted that the distinct geographic variation “didn’t seem random. ... So not only was there a doubling overall but there’s a variation in practice patterns across the country. I don’t have an explanation for that, but I think it’s important to recognize in the medical community that there are these big differences.”
Endocrinologists not as keen to prescribe DTE or T3
Residence in a state with higher endocrinologist density (3.0/100,000 population) was associated with a decreased likelihood of receiving T3 (adjusted odds ratio, 0.33; P < .001) or DTE therapy (aOR, 0.18; P < .001).
Residence in large central metro zones was associated with an increased likelihood of receiving T3 (aOR, 1.32; P < .001) or DTE therapy (aOR, 1.05; P < .008, respectively).
Dr. Pearce observed: “I don’t see DTE in Boston. It’s mostly in the South and Southwest.”
She said she doubted that endocrinologists were the primary prescribers of DTE, as many endocrinologists are “wary” of the pig thyroid–derived product because its T4 to T3 ratio is about 4:1, in contrast to the ratio in humans of 13-14:1.
Thus, DTE contains a much higher proportion of the active hormone T3. It is also much shorter acting, with a half-life of a few hours, compared to a few days for T4, she explained.
“We don’t really know what long-term safety effects are but it’s probably a less physiologic way of dosing thyroid hormone than ... either levothyroxine or levothyroxine in combination with a lower T3 proportion,” she said.
Just trying to understand
Dr. Ettleson emphasized that the goal of his research wasn’t to reverse the trend but to better understand it.
Nonetheless, he also noted, “now that we know there are more patients taking DTE, we need to start looking at rates of atrial fibrillation, fracture, heart failure, and other possible outcomes in this population and compare them with levothyroxine and nonthyroid populations to make sure that it is as safe as levothyroxine.”
“There are no data to suggest increased risk, especially if TSH is monitored and stays in the normal range, but there’s very little data for over 5 or 10 years on DTE-treated patients. We need the data,” he emphasized.
Meanwhile, he’s working on a survey of endocrinologists and non-endocrinologists to ask if they’ve prescribed DTE, and if so, why, and whether it’s because patients asked for it. “There’s a lot more work to be done, but I think it’s exciting. It’s important to see how patients are being treated in the real world ... and understand why it’s happening and what the outcomes are.”
Dr. Ettleson and Dr. Pearce have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM ENDO 2023
Over half of pregnant patients not properly screened for thyroid disease
BALTIMORE – Less than half of the pregnant patients who met the criteria for thyroid screening were actually screened by their clinician, according to a retrospective cohort study presented at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists in Baltimore. Those who met criteria and did receive screening had higher live birth rates and lower miscarriage rates than those who met the criteria but did not undergo screening, the study found.
“These results suggest that improving thyroid screening adherence may lead to improved pregnancy outcomes,” lead author Allan Dong, MD, of Advocate Lutheran General Hospital in Des Plaines, Ill., told attendees. “However, following targeted screening guidelines can be difficult for clinicians. In practice, universal screening for diabetes and pregnancy may provide more comprehensive screening coverage and potentially lead to improved outcomes.”
Instead of universal screening for thyroid disease, ACOG and the American Thyroid Association recommend targeted screening of high-risk patients, though ATA’s criteria are substantially broader than ACOG’s. But, Dr. Dong told attendees, “guidelines are only beneficial if they are followed appropriately,” and Ob.Gyns. have limited time to screen for risk factors in the midst of other clinical priorities. So he aimed to learn whether Ob.Gyns. were following the guidelines of either organization in screening people at higher risk for thyroid disease.
Dr. Dong and his coauthor, Melisa Lott, DO, reviewed the charts of all 1,025 patients who presented at their institution for new obstetrical visits in 2020 to determine which ones had risk factors that would qualify them for screening under ATA or ACOG guidelines. ACOG’s screening criteria included having a personal or family history of thyroid disease or type 1 diabetes, or there being clinical suspicion for thyroid disease. ATA’s screening criteria included the following:
- Personal or family history of thyroid disease.
- History of head or neck radiation.
- History of a prior thyroid surgery.
- Over age 30.
- Any autoimmune disease.
- A body mass index greater than 40 kg/m2.
- History of pregnancy loss, preterm delivery, or infertility.
- Recently used amiodarone lithium or iodine-based contrast.
- Lived in an area of known iodine deficiency.
- Clinical suspicion of thyroid disease.
ATA screening criteria identified four times as many patients requiring screening than did ACOG criteria, Dr. Dong noted. Of the 198 patients who met ACOG’s criteria, 43.9% were screened with thyroid function testing. Meanwhile, 826 patients – including all those who met ACOG’s criteria – met ATA’s criteria for screening, but only 13.1% of them underwent thyroid function testing.
Live birth rates were significantly higher among patients who met ATA criteria and were screened (92.6%) than among patients who met ATA criteria but were not screened (83.3%, P = .006). Similarly, the miscarriage rate was 4.6% in patients who met ATA criteria and were screened, compared to 12.4% in patients who met the criteria but did not undergo thyroid function testing (P = .009).
“A similar difference, although not statistically significant, was noted when comparing patients who were screened appropriately per ACOG criteria with those who met criteria for screening but were not screened,” Dr. Dong told attendees. “However, our study was underpowered to detect this difference due to the lower number of patients who meet criteria for screening under ACOG guidelines.”
The researchers did not find any significant difference in preterm delivery rates.
Anna Whelan, MD, of Women & Infants Hospital of Brown University, Providence, R.I., was not involved in the study but viewed the poster and pointed out that many of the patients, if seen by a primary care provider prior to pregnancy, would likely have been screened by their PCP. The rate of underscreening therefore suggests that patients “are not getting good, consistent primary care because there’s a lack of primary care physicians,” Dr. Whelan said in an interview.
In addition, she added, “maybe not all obstetricians and those providing care, such as midwives and other providers, are aware of the [ATA] guidelines on who should be screened.” She added that additional education about thyroid screening guidelines might be helpful for providers.
Dr. Dong reported being a stock shareholder in 3M, AbbVie, General Electric, Johnson & Johnson, Medtronic, Pfizer, and Viking Therapeutics. Dr. Whelan had no disclosures.
BALTIMORE – Less than half of the pregnant patients who met the criteria for thyroid screening were actually screened by their clinician, according to a retrospective cohort study presented at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists in Baltimore. Those who met criteria and did receive screening had higher live birth rates and lower miscarriage rates than those who met the criteria but did not undergo screening, the study found.
“These results suggest that improving thyroid screening adherence may lead to improved pregnancy outcomes,” lead author Allan Dong, MD, of Advocate Lutheran General Hospital in Des Plaines, Ill., told attendees. “However, following targeted screening guidelines can be difficult for clinicians. In practice, universal screening for diabetes and pregnancy may provide more comprehensive screening coverage and potentially lead to improved outcomes.”
Instead of universal screening for thyroid disease, ACOG and the American Thyroid Association recommend targeted screening of high-risk patients, though ATA’s criteria are substantially broader than ACOG’s. But, Dr. Dong told attendees, “guidelines are only beneficial if they are followed appropriately,” and Ob.Gyns. have limited time to screen for risk factors in the midst of other clinical priorities. So he aimed to learn whether Ob.Gyns. were following the guidelines of either organization in screening people at higher risk for thyroid disease.
Dr. Dong and his coauthor, Melisa Lott, DO, reviewed the charts of all 1,025 patients who presented at their institution for new obstetrical visits in 2020 to determine which ones had risk factors that would qualify them for screening under ATA or ACOG guidelines. ACOG’s screening criteria included having a personal or family history of thyroid disease or type 1 diabetes, or there being clinical suspicion for thyroid disease. ATA’s screening criteria included the following:
- Personal or family history of thyroid disease.
- History of head or neck radiation.
- History of a prior thyroid surgery.
- Over age 30.
- Any autoimmune disease.
- A body mass index greater than 40 kg/m2.
- History of pregnancy loss, preterm delivery, or infertility.
- Recently used amiodarone lithium or iodine-based contrast.
- Lived in an area of known iodine deficiency.
- Clinical suspicion of thyroid disease.
ATA screening criteria identified four times as many patients requiring screening than did ACOG criteria, Dr. Dong noted. Of the 198 patients who met ACOG’s criteria, 43.9% were screened with thyroid function testing. Meanwhile, 826 patients – including all those who met ACOG’s criteria – met ATA’s criteria for screening, but only 13.1% of them underwent thyroid function testing.
Live birth rates were significantly higher among patients who met ATA criteria and were screened (92.6%) than among patients who met ATA criteria but were not screened (83.3%, P = .006). Similarly, the miscarriage rate was 4.6% in patients who met ATA criteria and were screened, compared to 12.4% in patients who met the criteria but did not undergo thyroid function testing (P = .009).
“A similar difference, although not statistically significant, was noted when comparing patients who were screened appropriately per ACOG criteria with those who met criteria for screening but were not screened,” Dr. Dong told attendees. “However, our study was underpowered to detect this difference due to the lower number of patients who meet criteria for screening under ACOG guidelines.”
The researchers did not find any significant difference in preterm delivery rates.
Anna Whelan, MD, of Women & Infants Hospital of Brown University, Providence, R.I., was not involved in the study but viewed the poster and pointed out that many of the patients, if seen by a primary care provider prior to pregnancy, would likely have been screened by their PCP. The rate of underscreening therefore suggests that patients “are not getting good, consistent primary care because there’s a lack of primary care physicians,” Dr. Whelan said in an interview.
In addition, she added, “maybe not all obstetricians and those providing care, such as midwives and other providers, are aware of the [ATA] guidelines on who should be screened.” She added that additional education about thyroid screening guidelines might be helpful for providers.
Dr. Dong reported being a stock shareholder in 3M, AbbVie, General Electric, Johnson & Johnson, Medtronic, Pfizer, and Viking Therapeutics. Dr. Whelan had no disclosures.
BALTIMORE – Less than half of the pregnant patients who met the criteria for thyroid screening were actually screened by their clinician, according to a retrospective cohort study presented at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists in Baltimore. Those who met criteria and did receive screening had higher live birth rates and lower miscarriage rates than those who met the criteria but did not undergo screening, the study found.
“These results suggest that improving thyroid screening adherence may lead to improved pregnancy outcomes,” lead author Allan Dong, MD, of Advocate Lutheran General Hospital in Des Plaines, Ill., told attendees. “However, following targeted screening guidelines can be difficult for clinicians. In practice, universal screening for diabetes and pregnancy may provide more comprehensive screening coverage and potentially lead to improved outcomes.”
Instead of universal screening for thyroid disease, ACOG and the American Thyroid Association recommend targeted screening of high-risk patients, though ATA’s criteria are substantially broader than ACOG’s. But, Dr. Dong told attendees, “guidelines are only beneficial if they are followed appropriately,” and Ob.Gyns. have limited time to screen for risk factors in the midst of other clinical priorities. So he aimed to learn whether Ob.Gyns. were following the guidelines of either organization in screening people at higher risk for thyroid disease.
Dr. Dong and his coauthor, Melisa Lott, DO, reviewed the charts of all 1,025 patients who presented at their institution for new obstetrical visits in 2020 to determine which ones had risk factors that would qualify them for screening under ATA or ACOG guidelines. ACOG’s screening criteria included having a personal or family history of thyroid disease or type 1 diabetes, or there being clinical suspicion for thyroid disease. ATA’s screening criteria included the following:
- Personal or family history of thyroid disease.
- History of head or neck radiation.
- History of a prior thyroid surgery.
- Over age 30.
- Any autoimmune disease.
- A body mass index greater than 40 kg/m2.
- History of pregnancy loss, preterm delivery, or infertility.
- Recently used amiodarone lithium or iodine-based contrast.
- Lived in an area of known iodine deficiency.
- Clinical suspicion of thyroid disease.
ATA screening criteria identified four times as many patients requiring screening than did ACOG criteria, Dr. Dong noted. Of the 198 patients who met ACOG’s criteria, 43.9% were screened with thyroid function testing. Meanwhile, 826 patients – including all those who met ACOG’s criteria – met ATA’s criteria for screening, but only 13.1% of them underwent thyroid function testing.
Live birth rates were significantly higher among patients who met ATA criteria and were screened (92.6%) than among patients who met ATA criteria but were not screened (83.3%, P = .006). Similarly, the miscarriage rate was 4.6% in patients who met ATA criteria and were screened, compared to 12.4% in patients who met the criteria but did not undergo thyroid function testing (P = .009).
“A similar difference, although not statistically significant, was noted when comparing patients who were screened appropriately per ACOG criteria with those who met criteria for screening but were not screened,” Dr. Dong told attendees. “However, our study was underpowered to detect this difference due to the lower number of patients who meet criteria for screening under ACOG guidelines.”
The researchers did not find any significant difference in preterm delivery rates.
Anna Whelan, MD, of Women & Infants Hospital of Brown University, Providence, R.I., was not involved in the study but viewed the poster and pointed out that many of the patients, if seen by a primary care provider prior to pregnancy, would likely have been screened by their PCP. The rate of underscreening therefore suggests that patients “are not getting good, consistent primary care because there’s a lack of primary care physicians,” Dr. Whelan said in an interview.
In addition, she added, “maybe not all obstetricians and those providing care, such as midwives and other providers, are aware of the [ATA] guidelines on who should be screened.” She added that additional education about thyroid screening guidelines might be helpful for providers.
Dr. Dong reported being a stock shareholder in 3M, AbbVie, General Electric, Johnson & Johnson, Medtronic, Pfizer, and Viking Therapeutics. Dr. Whelan had no disclosures.
FROM ACOG 2023
TransCon PTH nears U.S. approval for hypoparathyroidism?
SEATTLE –
Findings from 110-week phase 2 data for the once-daily investigational parathyroid hormone (PTH) replacement drug were recently presented at the annual scientific & clinical congress of the American Association of Clinical Endocrinology.
Overall, the drug was associated with independence from conventional calcium and active vitamin D therapy in most patients at 110 weeks, with no discontinuations due to adverse effects.
“Patients with hypoparathyroidism have low serum calcium levels and struggle with quality of life and biochemical abnormalities. The data from the TransCon PTH studies seem to show that a lot of these abnormalities can be reversed,” presenter Mishaela R. Rubin, MD, said in an interview.
Other PTH replacement therapies such as Nupara (now discontinued) and teriparatide (off-label) have been used in some patients with hypoparathyroidism.
However, “[TransCon PTH] is delivered in such a way as to have a prolonged half-life, so that’s kind of a special benefit that it has,” added Dr. Rubin of the division of endocrinology and metabolic bone disease, department of medicine, Columbia University, New York.
Asked to comment, session moderator Thanh Hoang, DO, of Walter Reed National Military Medical Center, Silver Spring, Md., said: “I think it’s a very promising medication because right now we don’t have a lot of options ... I think it would help a lot of patients.”
Approval denied, company addressing concerns
On May 1, the Food and Drug Administration issued a complete response letter, signaling denial of approval for the TransCon PTH, citing concerns related to manufacturing control of the product’s drug/device combination product, but not about the product’s safety and efficacy, according to an Ascendis statement.
The company is now working with the FDA to address these issues and is awaiting a European Union decision later this year.
The FDA did not request that the company conduct further clinical trials of TransCon PTH, which now include published 26-week phase 2 and phase 3 data along with the current longer-term phase 2 data presented at AACE.
“The company has said that they’re hopeful the issues will be addressable and that the FDA did not have any concerns about safety,” Dr. Rubin said in an interview.
Calcium normalized, bone turnover improved
Dr. Rubin presented long-term efficacy and safety data from the Phase 2 PaTH Forward trial, which involved 57 of the initial 59 participants who completed week 110 of an open-label extension of the trial.
During the first 4 weeks, patients had been randomized to TransCon PTH at fixed doses of 15 µg/day, 18 µg/day, 21 µg/day, or placebo. After week 4, all patients switched to TransCon PTH titrated to doses of 6-60 µg/day along with conventional therapy, with the goal of maintaining normocalcemia.
Participants were a mean age of 50 years, 81% were women, and 92% were White. Causes of hypoparathyroidism were neck surgery in 80%, autoimmune disease in 2%, and idiopathic disease in 19%. Disease duration was 12 years (range 1-39), and all were taking conventional therapy including calcium and active vitamin D (calcitriol or alfacaldiol).
At 110 weeks, all 57 patients were able to stop taking active vitamin D, and 53 of the 57 (93%) patients achieved independence from conventional therapy, defined as taking 0 µg/day of active vitamin D and no more than 600 mg/day of calcium (the dietary supplement dose). A total of 44 (77%) patients were not taking any calcium or active vitamin D.
“This really establishes the durability up to 2 years of keeping people off conventional therapy,” Dr. Rubin said during her presentation.
There was an initial uptick to 9.4 mg/dL in mean serum calcium, as some participants were still taking active vitamin D, but that dropped to 8.9 mg/dL by week 26. Mean 24-hour urine calcium dropped from 428 mg/day at baseline to 173 mg/day by week 26. Both serum calcium and urine calcium remained in the normal range through week 110 in all patients, at 8.6 mg/dL and 167 mg/day, respectively.
“This is a really important outcome because we know that high urine calcium in these patients sets them at risk for going on to develop nephrocalcinosis, nephrolithiasis, and ultimately, chronic kidney disease,” Dr. Rubin said.
Serum levels of two bone formation markers peaked at 12 weeks after initiation of TransCon PTH. Both trended downward thereafter through week 110 to levels approximating those of age- and sex-matched controls.
“Both markers started off low, consistent with hypoparathyroidism, but with initiation of TransCon PTH we see a robust increase in bone turnover markers, almost as if the bone is ‘waking up,’ if you will. And this is consistent with calcium being mobilized from the skeleton and going into the circulation,” Dr. Rubin explained.
Bone mineral density assessed by dual-energy x-ray absorptiometry normalized, primarily in the first 26 weeks. For lumbar spine L1-L4, mean Z-scores dropped from 1.6 to 1.0 at 26 weeks and down to 0.7 by week 100. For total hip, those values were 1.0, 0.6, and 0.4, respectively. The values approached age- and sex-matched norms, Dr. Rubin noted, to “perhaps where their skeleton would be if they hadn’t had hypoparathyroidism.”
Overall 56 of the 57 (94.9%) patients reported treatment-emergent adverse events, of which 25 (42.4%) were treatment related and none were deemed serious. There were no treatment-emergent adverse events related to hypercalcemia or hypocalcemia leading to health care visits or hospitalization, none leading to discontinuation of study drug, and none to death.
“So overall, a reassuring safety profile,” Dr. Rubin said. “We look forward to presenting the next 2 years’ worth of data to the end of the open-label extension study.”
Dr. Rubin is a paid researcher for Ascendis, which funded the study. Dr. Hoang has reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
SEATTLE –
Findings from 110-week phase 2 data for the once-daily investigational parathyroid hormone (PTH) replacement drug were recently presented at the annual scientific & clinical congress of the American Association of Clinical Endocrinology.
Overall, the drug was associated with independence from conventional calcium and active vitamin D therapy in most patients at 110 weeks, with no discontinuations due to adverse effects.
“Patients with hypoparathyroidism have low serum calcium levels and struggle with quality of life and biochemical abnormalities. The data from the TransCon PTH studies seem to show that a lot of these abnormalities can be reversed,” presenter Mishaela R. Rubin, MD, said in an interview.
Other PTH replacement therapies such as Nupara (now discontinued) and teriparatide (off-label) have been used in some patients with hypoparathyroidism.
However, “[TransCon PTH] is delivered in such a way as to have a prolonged half-life, so that’s kind of a special benefit that it has,” added Dr. Rubin of the division of endocrinology and metabolic bone disease, department of medicine, Columbia University, New York.
Asked to comment, session moderator Thanh Hoang, DO, of Walter Reed National Military Medical Center, Silver Spring, Md., said: “I think it’s a very promising medication because right now we don’t have a lot of options ... I think it would help a lot of patients.”
Approval denied, company addressing concerns
On May 1, the Food and Drug Administration issued a complete response letter, signaling denial of approval for the TransCon PTH, citing concerns related to manufacturing control of the product’s drug/device combination product, but not about the product’s safety and efficacy, according to an Ascendis statement.
The company is now working with the FDA to address these issues and is awaiting a European Union decision later this year.
The FDA did not request that the company conduct further clinical trials of TransCon PTH, which now include published 26-week phase 2 and phase 3 data along with the current longer-term phase 2 data presented at AACE.
“The company has said that they’re hopeful the issues will be addressable and that the FDA did not have any concerns about safety,” Dr. Rubin said in an interview.
Calcium normalized, bone turnover improved
Dr. Rubin presented long-term efficacy and safety data from the Phase 2 PaTH Forward trial, which involved 57 of the initial 59 participants who completed week 110 of an open-label extension of the trial.
During the first 4 weeks, patients had been randomized to TransCon PTH at fixed doses of 15 µg/day, 18 µg/day, 21 µg/day, or placebo. After week 4, all patients switched to TransCon PTH titrated to doses of 6-60 µg/day along with conventional therapy, with the goal of maintaining normocalcemia.
Participants were a mean age of 50 years, 81% were women, and 92% were White. Causes of hypoparathyroidism were neck surgery in 80%, autoimmune disease in 2%, and idiopathic disease in 19%. Disease duration was 12 years (range 1-39), and all were taking conventional therapy including calcium and active vitamin D (calcitriol or alfacaldiol).
At 110 weeks, all 57 patients were able to stop taking active vitamin D, and 53 of the 57 (93%) patients achieved independence from conventional therapy, defined as taking 0 µg/day of active vitamin D and no more than 600 mg/day of calcium (the dietary supplement dose). A total of 44 (77%) patients were not taking any calcium or active vitamin D.
“This really establishes the durability up to 2 years of keeping people off conventional therapy,” Dr. Rubin said during her presentation.
There was an initial uptick to 9.4 mg/dL in mean serum calcium, as some participants were still taking active vitamin D, but that dropped to 8.9 mg/dL by week 26. Mean 24-hour urine calcium dropped from 428 mg/day at baseline to 173 mg/day by week 26. Both serum calcium and urine calcium remained in the normal range through week 110 in all patients, at 8.6 mg/dL and 167 mg/day, respectively.
“This is a really important outcome because we know that high urine calcium in these patients sets them at risk for going on to develop nephrocalcinosis, nephrolithiasis, and ultimately, chronic kidney disease,” Dr. Rubin said.
Serum levels of two bone formation markers peaked at 12 weeks after initiation of TransCon PTH. Both trended downward thereafter through week 110 to levels approximating those of age- and sex-matched controls.
“Both markers started off low, consistent with hypoparathyroidism, but with initiation of TransCon PTH we see a robust increase in bone turnover markers, almost as if the bone is ‘waking up,’ if you will. And this is consistent with calcium being mobilized from the skeleton and going into the circulation,” Dr. Rubin explained.
Bone mineral density assessed by dual-energy x-ray absorptiometry normalized, primarily in the first 26 weeks. For lumbar spine L1-L4, mean Z-scores dropped from 1.6 to 1.0 at 26 weeks and down to 0.7 by week 100. For total hip, those values were 1.0, 0.6, and 0.4, respectively. The values approached age- and sex-matched norms, Dr. Rubin noted, to “perhaps where their skeleton would be if they hadn’t had hypoparathyroidism.”
Overall 56 of the 57 (94.9%) patients reported treatment-emergent adverse events, of which 25 (42.4%) were treatment related and none were deemed serious. There were no treatment-emergent adverse events related to hypercalcemia or hypocalcemia leading to health care visits or hospitalization, none leading to discontinuation of study drug, and none to death.
“So overall, a reassuring safety profile,” Dr. Rubin said. “We look forward to presenting the next 2 years’ worth of data to the end of the open-label extension study.”
Dr. Rubin is a paid researcher for Ascendis, which funded the study. Dr. Hoang has reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
SEATTLE –
Findings from 110-week phase 2 data for the once-daily investigational parathyroid hormone (PTH) replacement drug were recently presented at the annual scientific & clinical congress of the American Association of Clinical Endocrinology.
Overall, the drug was associated with independence from conventional calcium and active vitamin D therapy in most patients at 110 weeks, with no discontinuations due to adverse effects.
“Patients with hypoparathyroidism have low serum calcium levels and struggle with quality of life and biochemical abnormalities. The data from the TransCon PTH studies seem to show that a lot of these abnormalities can be reversed,” presenter Mishaela R. Rubin, MD, said in an interview.
Other PTH replacement therapies such as Nupara (now discontinued) and teriparatide (off-label) have been used in some patients with hypoparathyroidism.
However, “[TransCon PTH] is delivered in such a way as to have a prolonged half-life, so that’s kind of a special benefit that it has,” added Dr. Rubin of the division of endocrinology and metabolic bone disease, department of medicine, Columbia University, New York.
Asked to comment, session moderator Thanh Hoang, DO, of Walter Reed National Military Medical Center, Silver Spring, Md., said: “I think it’s a very promising medication because right now we don’t have a lot of options ... I think it would help a lot of patients.”
Approval denied, company addressing concerns
On May 1, the Food and Drug Administration issued a complete response letter, signaling denial of approval for the TransCon PTH, citing concerns related to manufacturing control of the product’s drug/device combination product, but not about the product’s safety and efficacy, according to an Ascendis statement.
The company is now working with the FDA to address these issues and is awaiting a European Union decision later this year.
The FDA did not request that the company conduct further clinical trials of TransCon PTH, which now include published 26-week phase 2 and phase 3 data along with the current longer-term phase 2 data presented at AACE.
“The company has said that they’re hopeful the issues will be addressable and that the FDA did not have any concerns about safety,” Dr. Rubin said in an interview.
Calcium normalized, bone turnover improved
Dr. Rubin presented long-term efficacy and safety data from the Phase 2 PaTH Forward trial, which involved 57 of the initial 59 participants who completed week 110 of an open-label extension of the trial.
During the first 4 weeks, patients had been randomized to TransCon PTH at fixed doses of 15 µg/day, 18 µg/day, 21 µg/day, or placebo. After week 4, all patients switched to TransCon PTH titrated to doses of 6-60 µg/day along with conventional therapy, with the goal of maintaining normocalcemia.
Participants were a mean age of 50 years, 81% were women, and 92% were White. Causes of hypoparathyroidism were neck surgery in 80%, autoimmune disease in 2%, and idiopathic disease in 19%. Disease duration was 12 years (range 1-39), and all were taking conventional therapy including calcium and active vitamin D (calcitriol or alfacaldiol).
At 110 weeks, all 57 patients were able to stop taking active vitamin D, and 53 of the 57 (93%) patients achieved independence from conventional therapy, defined as taking 0 µg/day of active vitamin D and no more than 600 mg/day of calcium (the dietary supplement dose). A total of 44 (77%) patients were not taking any calcium or active vitamin D.
“This really establishes the durability up to 2 years of keeping people off conventional therapy,” Dr. Rubin said during her presentation.
There was an initial uptick to 9.4 mg/dL in mean serum calcium, as some participants were still taking active vitamin D, but that dropped to 8.9 mg/dL by week 26. Mean 24-hour urine calcium dropped from 428 mg/day at baseline to 173 mg/day by week 26. Both serum calcium and urine calcium remained in the normal range through week 110 in all patients, at 8.6 mg/dL and 167 mg/day, respectively.
“This is a really important outcome because we know that high urine calcium in these patients sets them at risk for going on to develop nephrocalcinosis, nephrolithiasis, and ultimately, chronic kidney disease,” Dr. Rubin said.
Serum levels of two bone formation markers peaked at 12 weeks after initiation of TransCon PTH. Both trended downward thereafter through week 110 to levels approximating those of age- and sex-matched controls.
“Both markers started off low, consistent with hypoparathyroidism, but with initiation of TransCon PTH we see a robust increase in bone turnover markers, almost as if the bone is ‘waking up,’ if you will. And this is consistent with calcium being mobilized from the skeleton and going into the circulation,” Dr. Rubin explained.
Bone mineral density assessed by dual-energy x-ray absorptiometry normalized, primarily in the first 26 weeks. For lumbar spine L1-L4, mean Z-scores dropped from 1.6 to 1.0 at 26 weeks and down to 0.7 by week 100. For total hip, those values were 1.0, 0.6, and 0.4, respectively. The values approached age- and sex-matched norms, Dr. Rubin noted, to “perhaps where their skeleton would be if they hadn’t had hypoparathyroidism.”
Overall 56 of the 57 (94.9%) patients reported treatment-emergent adverse events, of which 25 (42.4%) were treatment related and none were deemed serious. There were no treatment-emergent adverse events related to hypercalcemia or hypocalcemia leading to health care visits or hospitalization, none leading to discontinuation of study drug, and none to death.
“So overall, a reassuring safety profile,” Dr. Rubin said. “We look forward to presenting the next 2 years’ worth of data to the end of the open-label extension study.”
Dr. Rubin is a paid researcher for Ascendis, which funded the study. Dr. Hoang has reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
AT AACE 2023
Noninvasive skin test may aid in Cushing diagnosis
SEATTLE – new research suggests.
Tissue accumulation of AGEs – harmful compounds formed by glycation of macromolecules – has been implicated in aging, diabetes, and cardiovascular disease. Now, in a new single-center prospective study, a group of 208 patients with endogenous hypercortisolism was found to have significantly higher median tissue AGE levels than 103 reference subjects without hypercortisolism.
The findings were presented at the annual meeting of the American Association of Clinical Endocrinology by Rashi Sandooja, MD, an endocrinology fellow at the Mayo Clinic, Rochester, Minn.
“Diagnosis of endogenous hypercortisolism can be quite challenging. Often patients can have nonspecific symptoms with biochemical testing being equivocal. In these situations, new biomarkers of hypercortisolism such as AGE measurement could potentially be useful,” Dr. Sandooja said in an interview.
“After proper validation, it could help clinicians in cases which may not be straightforward and could serve as an additional” instrument in the toolkit to reach a conclusive diagnosis, she added.
Asked to comment, session moderator Anupam Kotwal, MD, said in an interview: “I think it’s very exciting data. ... I envision its use in mild autonomous cortisol secretion, where there are not a lot of overt Cushing features but they may have a small adrenal mass. ... It might be used to guide care when there’s not a clear-cut answer.”
However, he cautioned that more validation is needed to determine the correlates of AGEs by different etiologies and magnitudes of cortisol excess.
Moreover, “skin can become thin in hypercortisolism, so is [the reader device] just detecting it more with skin testing? I think a blood test for validation would be a very good next step,” added Dr. Kotwal, who is an assistant professor in the division of diabetes, endocrinology and metabolism at the University of Nebraska, Omaha.
More work will be needed
Future directions for research should include adding a longitudinal arm and looking at the impact on AGE after patients undergo curative surgery and achieve remission, Dr. Sandooja explained.
“It will be interesting to see if AGE levels continue to be persistently high or decrease after patients achieve sustained remission of hypercortisolism. We are also interested in whether AGE measurement at baseline, prior to surgery may be associated with glucocorticoid withdrawal, myopathy, and metabolic outcomes following the surgery.”
Dr. Kotwal observed: “If the answer is clear for Cushing disease, I don’t know what extra information this would give. Maybe they would monitor people more closely afterward. It would be useful to see, but I think the first low-hanging fruit is use it in a way to guide the care of patients where we’re unclear as to whether initial treatment of this [mild autonomous cortisol secretion] is going to improve their outcomes.”
But, he added, “keeping in mind issues of skin ... we don’t want to distract clinicians and patients from using the tried and tested methods of characterizing Cushing syndrome. I’m always hesitant to bring something into practice before there is a little more information on how it can be used.”
Dr. Sandooja and Dr. Kotwal reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
SEATTLE – new research suggests.
Tissue accumulation of AGEs – harmful compounds formed by glycation of macromolecules – has been implicated in aging, diabetes, and cardiovascular disease. Now, in a new single-center prospective study, a group of 208 patients with endogenous hypercortisolism was found to have significantly higher median tissue AGE levels than 103 reference subjects without hypercortisolism.
The findings were presented at the annual meeting of the American Association of Clinical Endocrinology by Rashi Sandooja, MD, an endocrinology fellow at the Mayo Clinic, Rochester, Minn.
“Diagnosis of endogenous hypercortisolism can be quite challenging. Often patients can have nonspecific symptoms with biochemical testing being equivocal. In these situations, new biomarkers of hypercortisolism such as AGE measurement could potentially be useful,” Dr. Sandooja said in an interview.
“After proper validation, it could help clinicians in cases which may not be straightforward and could serve as an additional” instrument in the toolkit to reach a conclusive diagnosis, she added.
Asked to comment, session moderator Anupam Kotwal, MD, said in an interview: “I think it’s very exciting data. ... I envision its use in mild autonomous cortisol secretion, where there are not a lot of overt Cushing features but they may have a small adrenal mass. ... It might be used to guide care when there’s not a clear-cut answer.”
However, he cautioned that more validation is needed to determine the correlates of AGEs by different etiologies and magnitudes of cortisol excess.
Moreover, “skin can become thin in hypercortisolism, so is [the reader device] just detecting it more with skin testing? I think a blood test for validation would be a very good next step,” added Dr. Kotwal, who is an assistant professor in the division of diabetes, endocrinology and metabolism at the University of Nebraska, Omaha.
More work will be needed
Future directions for research should include adding a longitudinal arm and looking at the impact on AGE after patients undergo curative surgery and achieve remission, Dr. Sandooja explained.
“It will be interesting to see if AGE levels continue to be persistently high or decrease after patients achieve sustained remission of hypercortisolism. We are also interested in whether AGE measurement at baseline, prior to surgery may be associated with glucocorticoid withdrawal, myopathy, and metabolic outcomes following the surgery.”
Dr. Kotwal observed: “If the answer is clear for Cushing disease, I don’t know what extra information this would give. Maybe they would monitor people more closely afterward. It would be useful to see, but I think the first low-hanging fruit is use it in a way to guide the care of patients where we’re unclear as to whether initial treatment of this [mild autonomous cortisol secretion] is going to improve their outcomes.”
But, he added, “keeping in mind issues of skin ... we don’t want to distract clinicians and patients from using the tried and tested methods of characterizing Cushing syndrome. I’m always hesitant to bring something into practice before there is a little more information on how it can be used.”
Dr. Sandooja and Dr. Kotwal reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
SEATTLE – new research suggests.
Tissue accumulation of AGEs – harmful compounds formed by glycation of macromolecules – has been implicated in aging, diabetes, and cardiovascular disease. Now, in a new single-center prospective study, a group of 208 patients with endogenous hypercortisolism was found to have significantly higher median tissue AGE levels than 103 reference subjects without hypercortisolism.
The findings were presented at the annual meeting of the American Association of Clinical Endocrinology by Rashi Sandooja, MD, an endocrinology fellow at the Mayo Clinic, Rochester, Minn.
“Diagnosis of endogenous hypercortisolism can be quite challenging. Often patients can have nonspecific symptoms with biochemical testing being equivocal. In these situations, new biomarkers of hypercortisolism such as AGE measurement could potentially be useful,” Dr. Sandooja said in an interview.
“After proper validation, it could help clinicians in cases which may not be straightforward and could serve as an additional” instrument in the toolkit to reach a conclusive diagnosis, she added.
Asked to comment, session moderator Anupam Kotwal, MD, said in an interview: “I think it’s very exciting data. ... I envision its use in mild autonomous cortisol secretion, where there are not a lot of overt Cushing features but they may have a small adrenal mass. ... It might be used to guide care when there’s not a clear-cut answer.”
However, he cautioned that more validation is needed to determine the correlates of AGEs by different etiologies and magnitudes of cortisol excess.
Moreover, “skin can become thin in hypercortisolism, so is [the reader device] just detecting it more with skin testing? I think a blood test for validation would be a very good next step,” added Dr. Kotwal, who is an assistant professor in the division of diabetes, endocrinology and metabolism at the University of Nebraska, Omaha.
More work will be needed
Future directions for research should include adding a longitudinal arm and looking at the impact on AGE after patients undergo curative surgery and achieve remission, Dr. Sandooja explained.
“It will be interesting to see if AGE levels continue to be persistently high or decrease after patients achieve sustained remission of hypercortisolism. We are also interested in whether AGE measurement at baseline, prior to surgery may be associated with glucocorticoid withdrawal, myopathy, and metabolic outcomes following the surgery.”
Dr. Kotwal observed: “If the answer is clear for Cushing disease, I don’t know what extra information this would give. Maybe they would monitor people more closely afterward. It would be useful to see, but I think the first low-hanging fruit is use it in a way to guide the care of patients where we’re unclear as to whether initial treatment of this [mild autonomous cortisol secretion] is going to improve their outcomes.”
But, he added, “keeping in mind issues of skin ... we don’t want to distract clinicians and patients from using the tried and tested methods of characterizing Cushing syndrome. I’m always hesitant to bring something into practice before there is a little more information on how it can be used.”
Dr. Sandooja and Dr. Kotwal reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT AACE 2023
Radiofrequency ablation successful in small thyroid cancers
SEATTLE –
RFA is increasingly gaining favor as a less-invasive alternative to surgery for patients with large, symptomatic, benign thyroid nodules in the United States and elsewhere and for the treatment of thyroid microcarcinomas in other countries, particularly South Korea and China.
Now, new findings from eight patients seen at the Mayo Clinic are the first to be reported for use of RFA for PTMC in the United States, Kharisa Rachmasari, MD, an endocrinology fellow at Mayo, said at the annual scientific & clinical congress of the American Association of Clinical Endocrinology.
Papillary thyroid cancers of 10 mm or less are the most common thyroid cancers, and their incidence is rising. They are commonly discovered incidentally in the setting of increased cross-sectional imaging. These tiny cancers are typically indolent, and they are associated with an excellent prognosis. In the United States, standard management is either surveillance or surgery, whereas RFA has been used in Europe and Asia for more than a decade, Dr. Rachmasari said.
“There has been some hesitancy when it comes to cancer, because there’s no guarantee that we can do it in such a clean way as is done with surgery, where you can actually confirm a negative margin in pathology. And the follow-up is easier as well. With RFA, the PTMC is still there, and you can only follow it with ultrasound, not biochemically with thyroglobulin or certain biomarkers,” she said in an interview.
Nonetheless, for these eight patients who underwent the procedure at Mayo’s ablation clinic, where interventional radiologists team up with endocrinologists, there were no serious adverse events, and no further interventions were required during 24 months of follow-up, she reported.
Asked to comment, session moderator Anupam Kotwal, MD, assistant professor in the division of diabetes, endocrinology and metabolism at the University of Nebraska, Omaha, said, “It’s very novel. We talk about balancing the comorbidities that come from treatment of thyroid cancer, but at the same time we want to treat it appropriately ... And of course, there are patient factors. Some may prefer to have the cancer completely out, while others are okay with watching and are against any cuts in their neck. This comes as kind of a middle ground.”
But, Dr. Kotwal added, “[Investigators] definitely need to do a bit more work, especially in the population that may be at higher risk of cancer spread, such as those with a family history of thyroid cancer. We still don’t know how autoimmune disease influences cancer progression.”
He said that if RFA is to be used for PTMC, “I think it has to be done at a center that specializes in multidisciplinary care of thyroid cancers where there are not only the experts in doing the RFA procedure but also surgical expertise, in case a complication does happen, like a vocal cord injury. Or if the cancer is growing, they can expedite getting the person that appropriate treatment.”
An alternative to waiting vs. surgery?
The eight patients were seen at Mayo Clinic between July 2020 and February 2023. All had papillary thyroid carcinoma that was confirmed cytologically via fine-needle biopsy and single lesions without lymph node metastasis. All patients had been offered RFA as an alternative to either surgery or active surveillance.
Seven patients were female, and one was male (mean age, 53 years). All were euthyroid at baseline, and two were receiving thyroid hormone therapy. The mean diameter of their nodules was 9.5 mm, and the mean volume was 0.3 mL.
For the first six patients, the procedure was conducted under general anesthesia; deep sedation was used for the next patient, and moderate sedation was used for the most recent. “As we learn more and gain more experience, patients nowadays have moderate sedation,” she explained.
The active tip size was 10 mm for five patients and 7 mm with three. The radiofrequency power that was delivered ranged from 25 to 45 watts. The median ablation duration was 6 minutes and ranged from 2 to 14.5. “Patients usually stay in the suite about half an hour, so it’s a quick procedure, and the patient can go home on the same day,” Dr. Rachmasari said.
Following the procedure, the ablated area increased in size during the first 3-6 months because the ablation was applied beyond the cancer margins in an attempt to ensure a negative margin, as is done surgically. By 18 months, the ablated area had shrunk and resolved.
All patients remained euthyroid in 18-24 months’ follow-up, none had any cervical adenopathy, and none required subsequent intervention.
No significant adverse events were observed during or after the RFA procedure. A few patients complained of erythema and soreness around the area of the procedure, but this resolved with over-the-counter analgesia.
Longer follow-up will be necessary to detect any recurrence, Dr. Rachmasari noted.
Dr. Kotwal pointed out that lack of reimbursement for RFA has contributed to the slow adoption of RFA overall for the treatment of thyroid nodules in the United States, but added, “I think that will change quickly, especially with more and more data coming out about large benign nodules ... I think at least from the benign nodule standpoint, with discussions happening at national meetings and societies, it should push the payers to cover.”
Overall, he said, “If you have a complication or it affects quality of life, all of those things add to the cost. So if you can use a procedure early on to prevent increasing size of either the big nodule or reduce the size of a big nodule, or even a small cancer, and give that person months or years, even if they ultimately need surgery, I think that’s still a benefit for their quality of life. But again, we have to take patient factors into account.”
Dr. Rachmasari and Dr. Kotwal have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
SEATTLE –
RFA is increasingly gaining favor as a less-invasive alternative to surgery for patients with large, symptomatic, benign thyroid nodules in the United States and elsewhere and for the treatment of thyroid microcarcinomas in other countries, particularly South Korea and China.
Now, new findings from eight patients seen at the Mayo Clinic are the first to be reported for use of RFA for PTMC in the United States, Kharisa Rachmasari, MD, an endocrinology fellow at Mayo, said at the annual scientific & clinical congress of the American Association of Clinical Endocrinology.
Papillary thyroid cancers of 10 mm or less are the most common thyroid cancers, and their incidence is rising. They are commonly discovered incidentally in the setting of increased cross-sectional imaging. These tiny cancers are typically indolent, and they are associated with an excellent prognosis. In the United States, standard management is either surveillance or surgery, whereas RFA has been used in Europe and Asia for more than a decade, Dr. Rachmasari said.
“There has been some hesitancy when it comes to cancer, because there’s no guarantee that we can do it in such a clean way as is done with surgery, where you can actually confirm a negative margin in pathology. And the follow-up is easier as well. With RFA, the PTMC is still there, and you can only follow it with ultrasound, not biochemically with thyroglobulin or certain biomarkers,” she said in an interview.
Nonetheless, for these eight patients who underwent the procedure at Mayo’s ablation clinic, where interventional radiologists team up with endocrinologists, there were no serious adverse events, and no further interventions were required during 24 months of follow-up, she reported.
Asked to comment, session moderator Anupam Kotwal, MD, assistant professor in the division of diabetes, endocrinology and metabolism at the University of Nebraska, Omaha, said, “It’s very novel. We talk about balancing the comorbidities that come from treatment of thyroid cancer, but at the same time we want to treat it appropriately ... And of course, there are patient factors. Some may prefer to have the cancer completely out, while others are okay with watching and are against any cuts in their neck. This comes as kind of a middle ground.”
But, Dr. Kotwal added, “[Investigators] definitely need to do a bit more work, especially in the population that may be at higher risk of cancer spread, such as those with a family history of thyroid cancer. We still don’t know how autoimmune disease influences cancer progression.”
He said that if RFA is to be used for PTMC, “I think it has to be done at a center that specializes in multidisciplinary care of thyroid cancers where there are not only the experts in doing the RFA procedure but also surgical expertise, in case a complication does happen, like a vocal cord injury. Or if the cancer is growing, they can expedite getting the person that appropriate treatment.”
An alternative to waiting vs. surgery?
The eight patients were seen at Mayo Clinic between July 2020 and February 2023. All had papillary thyroid carcinoma that was confirmed cytologically via fine-needle biopsy and single lesions without lymph node metastasis. All patients had been offered RFA as an alternative to either surgery or active surveillance.
Seven patients were female, and one was male (mean age, 53 years). All were euthyroid at baseline, and two were receiving thyroid hormone therapy. The mean diameter of their nodules was 9.5 mm, and the mean volume was 0.3 mL.
For the first six patients, the procedure was conducted under general anesthesia; deep sedation was used for the next patient, and moderate sedation was used for the most recent. “As we learn more and gain more experience, patients nowadays have moderate sedation,” she explained.
The active tip size was 10 mm for five patients and 7 mm with three. The radiofrequency power that was delivered ranged from 25 to 45 watts. The median ablation duration was 6 minutes and ranged from 2 to 14.5. “Patients usually stay in the suite about half an hour, so it’s a quick procedure, and the patient can go home on the same day,” Dr. Rachmasari said.
Following the procedure, the ablated area increased in size during the first 3-6 months because the ablation was applied beyond the cancer margins in an attempt to ensure a negative margin, as is done surgically. By 18 months, the ablated area had shrunk and resolved.
All patients remained euthyroid in 18-24 months’ follow-up, none had any cervical adenopathy, and none required subsequent intervention.
No significant adverse events were observed during or after the RFA procedure. A few patients complained of erythema and soreness around the area of the procedure, but this resolved with over-the-counter analgesia.
Longer follow-up will be necessary to detect any recurrence, Dr. Rachmasari noted.
Dr. Kotwal pointed out that lack of reimbursement for RFA has contributed to the slow adoption of RFA overall for the treatment of thyroid nodules in the United States, but added, “I think that will change quickly, especially with more and more data coming out about large benign nodules ... I think at least from the benign nodule standpoint, with discussions happening at national meetings and societies, it should push the payers to cover.”
Overall, he said, “If you have a complication or it affects quality of life, all of those things add to the cost. So if you can use a procedure early on to prevent increasing size of either the big nodule or reduce the size of a big nodule, or even a small cancer, and give that person months or years, even if they ultimately need surgery, I think that’s still a benefit for their quality of life. But again, we have to take patient factors into account.”
Dr. Rachmasari and Dr. Kotwal have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
SEATTLE –
RFA is increasingly gaining favor as a less-invasive alternative to surgery for patients with large, symptomatic, benign thyroid nodules in the United States and elsewhere and for the treatment of thyroid microcarcinomas in other countries, particularly South Korea and China.
Now, new findings from eight patients seen at the Mayo Clinic are the first to be reported for use of RFA for PTMC in the United States, Kharisa Rachmasari, MD, an endocrinology fellow at Mayo, said at the annual scientific & clinical congress of the American Association of Clinical Endocrinology.
Papillary thyroid cancers of 10 mm or less are the most common thyroid cancers, and their incidence is rising. They are commonly discovered incidentally in the setting of increased cross-sectional imaging. These tiny cancers are typically indolent, and they are associated with an excellent prognosis. In the United States, standard management is either surveillance or surgery, whereas RFA has been used in Europe and Asia for more than a decade, Dr. Rachmasari said.
“There has been some hesitancy when it comes to cancer, because there’s no guarantee that we can do it in such a clean way as is done with surgery, where you can actually confirm a negative margin in pathology. And the follow-up is easier as well. With RFA, the PTMC is still there, and you can only follow it with ultrasound, not biochemically with thyroglobulin or certain biomarkers,” she said in an interview.
Nonetheless, for these eight patients who underwent the procedure at Mayo’s ablation clinic, where interventional radiologists team up with endocrinologists, there were no serious adverse events, and no further interventions were required during 24 months of follow-up, she reported.
Asked to comment, session moderator Anupam Kotwal, MD, assistant professor in the division of diabetes, endocrinology and metabolism at the University of Nebraska, Omaha, said, “It’s very novel. We talk about balancing the comorbidities that come from treatment of thyroid cancer, but at the same time we want to treat it appropriately ... And of course, there are patient factors. Some may prefer to have the cancer completely out, while others are okay with watching and are against any cuts in their neck. This comes as kind of a middle ground.”
But, Dr. Kotwal added, “[Investigators] definitely need to do a bit more work, especially in the population that may be at higher risk of cancer spread, such as those with a family history of thyroid cancer. We still don’t know how autoimmune disease influences cancer progression.”
He said that if RFA is to be used for PTMC, “I think it has to be done at a center that specializes in multidisciplinary care of thyroid cancers where there are not only the experts in doing the RFA procedure but also surgical expertise, in case a complication does happen, like a vocal cord injury. Or if the cancer is growing, they can expedite getting the person that appropriate treatment.”
An alternative to waiting vs. surgery?
The eight patients were seen at Mayo Clinic between July 2020 and February 2023. All had papillary thyroid carcinoma that was confirmed cytologically via fine-needle biopsy and single lesions without lymph node metastasis. All patients had been offered RFA as an alternative to either surgery or active surveillance.
Seven patients were female, and one was male (mean age, 53 years). All were euthyroid at baseline, and two were receiving thyroid hormone therapy. The mean diameter of their nodules was 9.5 mm, and the mean volume was 0.3 mL.
For the first six patients, the procedure was conducted under general anesthesia; deep sedation was used for the next patient, and moderate sedation was used for the most recent. “As we learn more and gain more experience, patients nowadays have moderate sedation,” she explained.
The active tip size was 10 mm for five patients and 7 mm with three. The radiofrequency power that was delivered ranged from 25 to 45 watts. The median ablation duration was 6 minutes and ranged from 2 to 14.5. “Patients usually stay in the suite about half an hour, so it’s a quick procedure, and the patient can go home on the same day,” Dr. Rachmasari said.
Following the procedure, the ablated area increased in size during the first 3-6 months because the ablation was applied beyond the cancer margins in an attempt to ensure a negative margin, as is done surgically. By 18 months, the ablated area had shrunk and resolved.
All patients remained euthyroid in 18-24 months’ follow-up, none had any cervical adenopathy, and none required subsequent intervention.
No significant adverse events were observed during or after the RFA procedure. A few patients complained of erythema and soreness around the area of the procedure, but this resolved with over-the-counter analgesia.
Longer follow-up will be necessary to detect any recurrence, Dr. Rachmasari noted.
Dr. Kotwal pointed out that lack of reimbursement for RFA has contributed to the slow adoption of RFA overall for the treatment of thyroid nodules in the United States, but added, “I think that will change quickly, especially with more and more data coming out about large benign nodules ... I think at least from the benign nodule standpoint, with discussions happening at national meetings and societies, it should push the payers to cover.”
Overall, he said, “If you have a complication or it affects quality of life, all of those things add to the cost. So if you can use a procedure early on to prevent increasing size of either the big nodule or reduce the size of a big nodule, or even a small cancer, and give that person months or years, even if they ultimately need surgery, I think that’s still a benefit for their quality of life. But again, we have to take patient factors into account.”
Dr. Rachmasari and Dr. Kotwal have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
AT AACE 2023
Seasonal variation in thyroid hormone TSH may lead to overprescribing
Seasonal variation in one of the hormones used to monitor thyroid function could in turn lead to false diagnoses of subclinical hypothyroidism and unnecessary prescriptions of levothyroxine, according to Yale clinical chemist Joe M. El-Khoury, PhD.
A Japanese study of more than 7,000 healthy individuals showed that thyrotropin-stimulating hormone (TSH) varies widely throughout the seasons, he said, peaking in the northern hemisphere’s winter months (January to February) with its low in the summer months (June to August). That paper was published last year in the Journal of the Endocrine Society.
But free thyroxine (FT4) levels in the Japanese population remained relatively stable, he wrote in a letter recently published in Clinical Chemistry.
“If you end up with a mildly elevated TSH result and a normal FT4, try getting retested 2-3 months later to make sure this is not a seasonal artifact or transient increase before prescribing/taking levothyroxine unnecessarily,” advised Dr. El-Khoury, director of Yale University’s Clinical Chemistry Laboratory, New Haven, Conn.
“Because the [population-based, laboratory] reference ranges don’t account for seasonal variation, we’re flagging a significant number of people as high TSH when they’re normal, and physicians are prescribing levothyroxine inappropriately to healthy people who don’t need it,” he told this news organization, adding that overtreatment can be harmful, particularly for elderly people.
This seasonal variation in TSH could account for between a third to a half of the 90% of all levothyroxine prescriptions that were found to be unnecessary, according to a U.S. study in 2021, Dr. El-Khoury added.
In a comment, Trisha Cubb, MD, said that Dr. El-Khoury’s letter “raises a good point, that we really need to look at our reference ranges, especially when more and more studies are showing that so many thyroid hormone prescriptions may not be necessary.”
Dr. Cubb, thyroid section director and assistant professor of clinical medicine at Weill Cornell Medical College/Houston Methodist Academic Institute, Texas, also agrees with Dr. El-Khoury’s suggestion to repeat lab results in some instances.
“I think repeating results, especially in our patients with subclinical disease, is important,” she noted.
And she pointed out that seasonal variation isn’t the only relevant variable. “We also know that multiple clinical factors like pregnancy status, coexisting comorbidities, or age can all influence what we as clinicians consider an acceptable TSH range in an individual patient.” And other medications, such as steroids, or supplements like biotin, “can all affect thyroid lab values,” she noted.
“Ensuring that minor abnormalities aren’t transient is important prior to initiating medical therapy. With any medical therapy there are possible side effects, along with time, cost, [and] monitoring, all of which can be associated with thyroid hormone replacement.”
TSH reference ranges should be adapted for subpopulations
Dr. El-Khoury explained that to get an idea of how big the seasonal differences in TSH observed in the Japanese study were, “the upper end of the population they tracked goes from 5.2 [mIU/L] in January to 3.4 [mIU/L] in August. So you have almost a 2-unit change in concentration that can happen in the reference population. But laboratory reference ranges, or ‘normal ranges,’ are usually fixed and don’t change by season.”
The higher the TSH, the more likely a person is to have hypothyroidism. Major recent studies have found no benefit of levothyroxine treatment with TSH levels below 7.0-10.0 mIU/L, he said.
“So, I suggest that the limit should be 7.0 [mIU/L] to be safe, but it could be as high as 10 [mIU/L]. In any case, let’s shift the mindset to clinical outcome–based treatment cutoffs,” he said, noting that this approach is currently used for decisions on cholesterol-lowering therapy or vitamin D supplementation, for example.
Regarding this suggestion of using a TSH cutoff of 7 mIU/L to diagnose subclinical hypothyroidism, Dr. Cubb said: “It really depends on the specific population. In an elderly patient, a higher TSH may be of less clinical concern when compared to a female who is actively trying to get pregnant.
“Overall, I think we do need to better understand what appropriate TSH ranges are in specific subpopulations, and then with time, make this more understandable and available for general medicine as well as subspecialty providers to be able to utilize,” she noted.
Regarding the particular Japanese findings cited by Dr. El-Khoury, Dr. Cubb observed that this was a very specific study population, “so we would need more data showing that this is more generalizable.”
And she noted that there’s also diurnal variation in TSH. “In the [Japanese] paper, patients had their thyroid labs drawn between 8:00 a.m. and 9:00 a.m. in a fasting state. Oftentimes in the U.S., thyroid labs are not drawn at specific times or [during] fasting. I think this is one of many factors that should be considered.”
Acknowledging seasonal variation would be a start
But overall, Dr. Cubb said that both the Japanese study and Dr. El-Khoury’s letter highlight “how season, in and of itself, which is not something we usually think about, can affect thyroid lab results. I believe as more data come out, more generalizable data, that’s how evidence-based guidelines are generated over time.”
According to Dr. El-Khoury, fixing the laboratory reference range issues would likely require a joint effort of professional medical societies, reference laboratories, and assay manufacturers. But with seasonal variation, that might be a difficult task.
“The problem is, in laboratory medicine, we don’t have rules for an analyte that changes by season to do anything different. My goal is to get people to at least acknowledge this is a problem and do something,” he concluded.
Dr. El-Khoury and Dr. Cubb have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Seasonal variation in one of the hormones used to monitor thyroid function could in turn lead to false diagnoses of subclinical hypothyroidism and unnecessary prescriptions of levothyroxine, according to Yale clinical chemist Joe M. El-Khoury, PhD.
A Japanese study of more than 7,000 healthy individuals showed that thyrotropin-stimulating hormone (TSH) varies widely throughout the seasons, he said, peaking in the northern hemisphere’s winter months (January to February) with its low in the summer months (June to August). That paper was published last year in the Journal of the Endocrine Society.
But free thyroxine (FT4) levels in the Japanese population remained relatively stable, he wrote in a letter recently published in Clinical Chemistry.
“If you end up with a mildly elevated TSH result and a normal FT4, try getting retested 2-3 months later to make sure this is not a seasonal artifact or transient increase before prescribing/taking levothyroxine unnecessarily,” advised Dr. El-Khoury, director of Yale University’s Clinical Chemistry Laboratory, New Haven, Conn.
“Because the [population-based, laboratory] reference ranges don’t account for seasonal variation, we’re flagging a significant number of people as high TSH when they’re normal, and physicians are prescribing levothyroxine inappropriately to healthy people who don’t need it,” he told this news organization, adding that overtreatment can be harmful, particularly for elderly people.
This seasonal variation in TSH could account for between a third to a half of the 90% of all levothyroxine prescriptions that were found to be unnecessary, according to a U.S. study in 2021, Dr. El-Khoury added.
In a comment, Trisha Cubb, MD, said that Dr. El-Khoury’s letter “raises a good point, that we really need to look at our reference ranges, especially when more and more studies are showing that so many thyroid hormone prescriptions may not be necessary.”
Dr. Cubb, thyroid section director and assistant professor of clinical medicine at Weill Cornell Medical College/Houston Methodist Academic Institute, Texas, also agrees with Dr. El-Khoury’s suggestion to repeat lab results in some instances.
“I think repeating results, especially in our patients with subclinical disease, is important,” she noted.
And she pointed out that seasonal variation isn’t the only relevant variable. “We also know that multiple clinical factors like pregnancy status, coexisting comorbidities, or age can all influence what we as clinicians consider an acceptable TSH range in an individual patient.” And other medications, such as steroids, or supplements like biotin, “can all affect thyroid lab values,” she noted.
“Ensuring that minor abnormalities aren’t transient is important prior to initiating medical therapy. With any medical therapy there are possible side effects, along with time, cost, [and] monitoring, all of which can be associated with thyroid hormone replacement.”
TSH reference ranges should be adapted for subpopulations
Dr. El-Khoury explained that to get an idea of how big the seasonal differences in TSH observed in the Japanese study were, “the upper end of the population they tracked goes from 5.2 [mIU/L] in January to 3.4 [mIU/L] in August. So you have almost a 2-unit change in concentration that can happen in the reference population. But laboratory reference ranges, or ‘normal ranges,’ are usually fixed and don’t change by season.”
The higher the TSH, the more likely a person is to have hypothyroidism. Major recent studies have found no benefit of levothyroxine treatment with TSH levels below 7.0-10.0 mIU/L, he said.
“So, I suggest that the limit should be 7.0 [mIU/L] to be safe, but it could be as high as 10 [mIU/L]. In any case, let’s shift the mindset to clinical outcome–based treatment cutoffs,” he said, noting that this approach is currently used for decisions on cholesterol-lowering therapy or vitamin D supplementation, for example.
Regarding this suggestion of using a TSH cutoff of 7 mIU/L to diagnose subclinical hypothyroidism, Dr. Cubb said: “It really depends on the specific population. In an elderly patient, a higher TSH may be of less clinical concern when compared to a female who is actively trying to get pregnant.
“Overall, I think we do need to better understand what appropriate TSH ranges are in specific subpopulations, and then with time, make this more understandable and available for general medicine as well as subspecialty providers to be able to utilize,” she noted.
Regarding the particular Japanese findings cited by Dr. El-Khoury, Dr. Cubb observed that this was a very specific study population, “so we would need more data showing that this is more generalizable.”
And she noted that there’s also diurnal variation in TSH. “In the [Japanese] paper, patients had their thyroid labs drawn between 8:00 a.m. and 9:00 a.m. in a fasting state. Oftentimes in the U.S., thyroid labs are not drawn at specific times or [during] fasting. I think this is one of many factors that should be considered.”
Acknowledging seasonal variation would be a start
But overall, Dr. Cubb said that both the Japanese study and Dr. El-Khoury’s letter highlight “how season, in and of itself, which is not something we usually think about, can affect thyroid lab results. I believe as more data come out, more generalizable data, that’s how evidence-based guidelines are generated over time.”
According to Dr. El-Khoury, fixing the laboratory reference range issues would likely require a joint effort of professional medical societies, reference laboratories, and assay manufacturers. But with seasonal variation, that might be a difficult task.
“The problem is, in laboratory medicine, we don’t have rules for an analyte that changes by season to do anything different. My goal is to get people to at least acknowledge this is a problem and do something,” he concluded.
Dr. El-Khoury and Dr. Cubb have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Seasonal variation in one of the hormones used to monitor thyroid function could in turn lead to false diagnoses of subclinical hypothyroidism and unnecessary prescriptions of levothyroxine, according to Yale clinical chemist Joe M. El-Khoury, PhD.
A Japanese study of more than 7,000 healthy individuals showed that thyrotropin-stimulating hormone (TSH) varies widely throughout the seasons, he said, peaking in the northern hemisphere’s winter months (January to February) with its low in the summer months (June to August). That paper was published last year in the Journal of the Endocrine Society.
But free thyroxine (FT4) levels in the Japanese population remained relatively stable, he wrote in a letter recently published in Clinical Chemistry.
“If you end up with a mildly elevated TSH result and a normal FT4, try getting retested 2-3 months later to make sure this is not a seasonal artifact or transient increase before prescribing/taking levothyroxine unnecessarily,” advised Dr. El-Khoury, director of Yale University’s Clinical Chemistry Laboratory, New Haven, Conn.
“Because the [population-based, laboratory] reference ranges don’t account for seasonal variation, we’re flagging a significant number of people as high TSH when they’re normal, and physicians are prescribing levothyroxine inappropriately to healthy people who don’t need it,” he told this news organization, adding that overtreatment can be harmful, particularly for elderly people.
This seasonal variation in TSH could account for between a third to a half of the 90% of all levothyroxine prescriptions that were found to be unnecessary, according to a U.S. study in 2021, Dr. El-Khoury added.
In a comment, Trisha Cubb, MD, said that Dr. El-Khoury’s letter “raises a good point, that we really need to look at our reference ranges, especially when more and more studies are showing that so many thyroid hormone prescriptions may not be necessary.”
Dr. Cubb, thyroid section director and assistant professor of clinical medicine at Weill Cornell Medical College/Houston Methodist Academic Institute, Texas, also agrees with Dr. El-Khoury’s suggestion to repeat lab results in some instances.
“I think repeating results, especially in our patients with subclinical disease, is important,” she noted.
And she pointed out that seasonal variation isn’t the only relevant variable. “We also know that multiple clinical factors like pregnancy status, coexisting comorbidities, or age can all influence what we as clinicians consider an acceptable TSH range in an individual patient.” And other medications, such as steroids, or supplements like biotin, “can all affect thyroid lab values,” she noted.
“Ensuring that minor abnormalities aren’t transient is important prior to initiating medical therapy. With any medical therapy there are possible side effects, along with time, cost, [and] monitoring, all of which can be associated with thyroid hormone replacement.”
TSH reference ranges should be adapted for subpopulations
Dr. El-Khoury explained that to get an idea of how big the seasonal differences in TSH observed in the Japanese study were, “the upper end of the population they tracked goes from 5.2 [mIU/L] in January to 3.4 [mIU/L] in August. So you have almost a 2-unit change in concentration that can happen in the reference population. But laboratory reference ranges, or ‘normal ranges,’ are usually fixed and don’t change by season.”
The higher the TSH, the more likely a person is to have hypothyroidism. Major recent studies have found no benefit of levothyroxine treatment with TSH levels below 7.0-10.0 mIU/L, he said.
“So, I suggest that the limit should be 7.0 [mIU/L] to be safe, but it could be as high as 10 [mIU/L]. In any case, let’s shift the mindset to clinical outcome–based treatment cutoffs,” he said, noting that this approach is currently used for decisions on cholesterol-lowering therapy or vitamin D supplementation, for example.
Regarding this suggestion of using a TSH cutoff of 7 mIU/L to diagnose subclinical hypothyroidism, Dr. Cubb said: “It really depends on the specific population. In an elderly patient, a higher TSH may be of less clinical concern when compared to a female who is actively trying to get pregnant.
“Overall, I think we do need to better understand what appropriate TSH ranges are in specific subpopulations, and then with time, make this more understandable and available for general medicine as well as subspecialty providers to be able to utilize,” she noted.
Regarding the particular Japanese findings cited by Dr. El-Khoury, Dr. Cubb observed that this was a very specific study population, “so we would need more data showing that this is more generalizable.”
And she noted that there’s also diurnal variation in TSH. “In the [Japanese] paper, patients had their thyroid labs drawn between 8:00 a.m. and 9:00 a.m. in a fasting state. Oftentimes in the U.S., thyroid labs are not drawn at specific times or [during] fasting. I think this is one of many factors that should be considered.”
Acknowledging seasonal variation would be a start
But overall, Dr. Cubb said that both the Japanese study and Dr. El-Khoury’s letter highlight “how season, in and of itself, which is not something we usually think about, can affect thyroid lab results. I believe as more data come out, more generalizable data, that’s how evidence-based guidelines are generated over time.”
According to Dr. El-Khoury, fixing the laboratory reference range issues would likely require a joint effort of professional medical societies, reference laboratories, and assay manufacturers. But with seasonal variation, that might be a difficult task.
“The problem is, in laboratory medicine, we don’t have rules for an analyte that changes by season to do anything different. My goal is to get people to at least acknowledge this is a problem and do something,” he concluded.
Dr. El-Khoury and Dr. Cubb have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM CLINICAL CHEMISTRY
Parathyroidectomy does not preserve kidney function in seniors
Early parathyroidectomy within 1 year of diagnosis of primary hyperparathyroidism (PHPT) did not reduce the risk of a sustained decline in kidney function, measured by a decline in estimated glomerular filtration rate (eGFR) of at least 50%, compared with observation (no surgery) in adults aged 60 and older.
Early parathyroidectomy was, however, associated with a reduced adjusted risk of this decline in kidney function in patients with newly diagnosed PHPT who were younger than age 60.
The findings, based on data from close to 43,000 veterans, were published online in Annals of Internal Medicine.
“The important takeaway from our study is that for older adults [age 60 or older] with primary hyperparathyroidism, preservation of kidney function should not be a primary consideration when making decisions about whether to undergo parathyroidectomy,” lead author Carolyn D. Seib, MD, told this news organization.
“It is important that physicians also discuss with their patients the potential long-term benefits of parathyroidectomy related to a reduced risk of fractures, kidney stones, and cardiovascular disease, and improved quality of life, in addition to the need for lifelong surveillance if surgery is declined, weighing these against an individual patient’s risk of surgery,” said Dr. Seib, a surgeon at Palo Alto (Calif.) VA Medical Center.
“However, in patients younger than 60, early parathyroidectomy may prevent progression to chronic kidney disease (CKD) and should be more strongly considered,” she noted.
Parathyroidectomy, she observed, is a low-risk outpatient surgery for most adults.
“Potential complications of surgery include temporary or permanent hoarseness, hypoparathyroidism (low postoperative parathyroid function), bleeding requiring return to the operating room, and complications related to general anesthesia, all of which are rare,” said Dr. Seib.
“Surgery by a high-volume surgeon is associated with a reduced risk of complications, so patients should seek out an experienced parathyroid surgeon,” she emphasized.
Moreover, parathyroidectomy is the only treatment for primary hyperparathyroidism.
Does parathyroidectomy slow loss of kidney function?
Multidisciplinary guidelines recommend parathyroidectomy, at least in part to mitigate the risk for, and effects related to, the progression of CKD in patients with PHPT and an eGFR below 60 mL/min per 1.73 m2, the researchers wrote.
However, whether parathyroidectomy slows the loss of kidney function in adults with PHPT is not clear.
Guidelines also state that “observation for PHPT disease progression can be considered when patients have no obvious end organ damage (i.e., eGFR > 60 mL/min per 1.73 m2, normal bone mineral density, and no history of kidney stones or fractures),” Dr. Seib noted.
To address the evidence gap, the researchers emulated a randomized target trial using observational data.
In this type of study, Dr. Seib explained, “although patients aren’t randomly assigned to a treatment, complex statistical methods are used to adjust for baseline confounders in an attempt to emulate random treatment assignment and account for bias that may affect the timing of when patients receive treatment.”
Using national Veterans Health Administration data, researchers identified 43,697 veterans with a new biochemical diagnosis of PHPT, defined as elevated parathyroid hormone (> 65 ng/mL) within 6 months of an elevated serum calcium level (> 32.55 mmol/L or >10.2 mg/dL), from 2000 to 2019.
Of these patients, 3,804 underwent parathyroidectomy within 1 year of diagnosis of PHPT, and 39,893 did not, and instead, a watchful waiting approach was adopted.
To be included in the analysis, patients had to have an eGFR above 30 mL/min per 1.73 m2 for 12 months before PHPT diagnosis to exclude secondary or tertiary hyperparathyroidism.
The primary outcome was a sustained decline in eGFR of at least 50% from baseline.
In the overall cohort, patients had a mean pretreatment eGFR of 71.8 mL/min per 1.73 m2. The mean age of patients was 67, 88% were men, and 68% were White.
After a median follow-up of 4.9 years, 6.7% of the patients had a decline in eGFR of at least 50%.
The cumulative incidence of this decline in eGFR was 5.1% at 5 years and 10.8% at 10 years in patients who had had early parathyroidectomy compared with 5.1% and 12.0%, respectively, in patients who did not undergo surgery.
In the overall population, the risk of at least a 50% decline in eGFR was similar in the early parathyroidectomy group versus the observation group (adjusted hazard ratio [HR], 0.98, 95% confidence interval [CI], 0.82-1.16).
However, diving deeper showed that parathyroidectomy was associated with a reduced risk of the primary outcome among patients younger than 60 years (adjusted HR, 0.75, 95% CI, 0.59-0.93) but not among those aged 60 or older (adjusted HR, 1.08, 95% CI, 0.87-1.34).
“When participating in shared decision-making for older adults [age 60 and older] with PHPT, clinicians should not consider parathyroidectomy for potential benefits of preservation of kidney function,” the researchers reiterated.
“For younger patients, clinicians should discuss the potential benefit of parathyroidectomy to reduce the risk for CKD and associated complications in adults with PHPT,” they concluded.
The study was funded by the National Institute on Aging. The authors reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Early parathyroidectomy within 1 year of diagnosis of primary hyperparathyroidism (PHPT) did not reduce the risk of a sustained decline in kidney function, measured by a decline in estimated glomerular filtration rate (eGFR) of at least 50%, compared with observation (no surgery) in adults aged 60 and older.
Early parathyroidectomy was, however, associated with a reduced adjusted risk of this decline in kidney function in patients with newly diagnosed PHPT who were younger than age 60.
The findings, based on data from close to 43,000 veterans, were published online in Annals of Internal Medicine.
“The important takeaway from our study is that for older adults [age 60 or older] with primary hyperparathyroidism, preservation of kidney function should not be a primary consideration when making decisions about whether to undergo parathyroidectomy,” lead author Carolyn D. Seib, MD, told this news organization.
“It is important that physicians also discuss with their patients the potential long-term benefits of parathyroidectomy related to a reduced risk of fractures, kidney stones, and cardiovascular disease, and improved quality of life, in addition to the need for lifelong surveillance if surgery is declined, weighing these against an individual patient’s risk of surgery,” said Dr. Seib, a surgeon at Palo Alto (Calif.) VA Medical Center.
“However, in patients younger than 60, early parathyroidectomy may prevent progression to chronic kidney disease (CKD) and should be more strongly considered,” she noted.
Parathyroidectomy, she observed, is a low-risk outpatient surgery for most adults.
“Potential complications of surgery include temporary or permanent hoarseness, hypoparathyroidism (low postoperative parathyroid function), bleeding requiring return to the operating room, and complications related to general anesthesia, all of which are rare,” said Dr. Seib.
“Surgery by a high-volume surgeon is associated with a reduced risk of complications, so patients should seek out an experienced parathyroid surgeon,” she emphasized.
Moreover, parathyroidectomy is the only treatment for primary hyperparathyroidism.
Does parathyroidectomy slow loss of kidney function?
Multidisciplinary guidelines recommend parathyroidectomy, at least in part to mitigate the risk for, and effects related to, the progression of CKD in patients with PHPT and an eGFR below 60 mL/min per 1.73 m2, the researchers wrote.
However, whether parathyroidectomy slows the loss of kidney function in adults with PHPT is not clear.
Guidelines also state that “observation for PHPT disease progression can be considered when patients have no obvious end organ damage (i.e., eGFR > 60 mL/min per 1.73 m2, normal bone mineral density, and no history of kidney stones or fractures),” Dr. Seib noted.
To address the evidence gap, the researchers emulated a randomized target trial using observational data.
In this type of study, Dr. Seib explained, “although patients aren’t randomly assigned to a treatment, complex statistical methods are used to adjust for baseline confounders in an attempt to emulate random treatment assignment and account for bias that may affect the timing of when patients receive treatment.”
Using national Veterans Health Administration data, researchers identified 43,697 veterans with a new biochemical diagnosis of PHPT, defined as elevated parathyroid hormone (> 65 ng/mL) within 6 months of an elevated serum calcium level (> 32.55 mmol/L or >10.2 mg/dL), from 2000 to 2019.
Of these patients, 3,804 underwent parathyroidectomy within 1 year of diagnosis of PHPT, and 39,893 did not, and instead, a watchful waiting approach was adopted.
To be included in the analysis, patients had to have an eGFR above 30 mL/min per 1.73 m2 for 12 months before PHPT diagnosis to exclude secondary or tertiary hyperparathyroidism.
The primary outcome was a sustained decline in eGFR of at least 50% from baseline.
In the overall cohort, patients had a mean pretreatment eGFR of 71.8 mL/min per 1.73 m2. The mean age of patients was 67, 88% were men, and 68% were White.
After a median follow-up of 4.9 years, 6.7% of the patients had a decline in eGFR of at least 50%.
The cumulative incidence of this decline in eGFR was 5.1% at 5 years and 10.8% at 10 years in patients who had had early parathyroidectomy compared with 5.1% and 12.0%, respectively, in patients who did not undergo surgery.
In the overall population, the risk of at least a 50% decline in eGFR was similar in the early parathyroidectomy group versus the observation group (adjusted hazard ratio [HR], 0.98, 95% confidence interval [CI], 0.82-1.16).
However, diving deeper showed that parathyroidectomy was associated with a reduced risk of the primary outcome among patients younger than 60 years (adjusted HR, 0.75, 95% CI, 0.59-0.93) but not among those aged 60 or older (adjusted HR, 1.08, 95% CI, 0.87-1.34).
“When participating in shared decision-making for older adults [age 60 and older] with PHPT, clinicians should not consider parathyroidectomy for potential benefits of preservation of kidney function,” the researchers reiterated.
“For younger patients, clinicians should discuss the potential benefit of parathyroidectomy to reduce the risk for CKD and associated complications in adults with PHPT,” they concluded.
The study was funded by the National Institute on Aging. The authors reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Early parathyroidectomy within 1 year of diagnosis of primary hyperparathyroidism (PHPT) did not reduce the risk of a sustained decline in kidney function, measured by a decline in estimated glomerular filtration rate (eGFR) of at least 50%, compared with observation (no surgery) in adults aged 60 and older.
Early parathyroidectomy was, however, associated with a reduced adjusted risk of this decline in kidney function in patients with newly diagnosed PHPT who were younger than age 60.
The findings, based on data from close to 43,000 veterans, were published online in Annals of Internal Medicine.
“The important takeaway from our study is that for older adults [age 60 or older] with primary hyperparathyroidism, preservation of kidney function should not be a primary consideration when making decisions about whether to undergo parathyroidectomy,” lead author Carolyn D. Seib, MD, told this news organization.
“It is important that physicians also discuss with their patients the potential long-term benefits of parathyroidectomy related to a reduced risk of fractures, kidney stones, and cardiovascular disease, and improved quality of life, in addition to the need for lifelong surveillance if surgery is declined, weighing these against an individual patient’s risk of surgery,” said Dr. Seib, a surgeon at Palo Alto (Calif.) VA Medical Center.
“However, in patients younger than 60, early parathyroidectomy may prevent progression to chronic kidney disease (CKD) and should be more strongly considered,” she noted.
Parathyroidectomy, she observed, is a low-risk outpatient surgery for most adults.
“Potential complications of surgery include temporary or permanent hoarseness, hypoparathyroidism (low postoperative parathyroid function), bleeding requiring return to the operating room, and complications related to general anesthesia, all of which are rare,” said Dr. Seib.
“Surgery by a high-volume surgeon is associated with a reduced risk of complications, so patients should seek out an experienced parathyroid surgeon,” she emphasized.
Moreover, parathyroidectomy is the only treatment for primary hyperparathyroidism.
Does parathyroidectomy slow loss of kidney function?
Multidisciplinary guidelines recommend parathyroidectomy, at least in part to mitigate the risk for, and effects related to, the progression of CKD in patients with PHPT and an eGFR below 60 mL/min per 1.73 m2, the researchers wrote.
However, whether parathyroidectomy slows the loss of kidney function in adults with PHPT is not clear.
Guidelines also state that “observation for PHPT disease progression can be considered when patients have no obvious end organ damage (i.e., eGFR > 60 mL/min per 1.73 m2, normal bone mineral density, and no history of kidney stones or fractures),” Dr. Seib noted.
To address the evidence gap, the researchers emulated a randomized target trial using observational data.
In this type of study, Dr. Seib explained, “although patients aren’t randomly assigned to a treatment, complex statistical methods are used to adjust for baseline confounders in an attempt to emulate random treatment assignment and account for bias that may affect the timing of when patients receive treatment.”
Using national Veterans Health Administration data, researchers identified 43,697 veterans with a new biochemical diagnosis of PHPT, defined as elevated parathyroid hormone (> 65 ng/mL) within 6 months of an elevated serum calcium level (> 32.55 mmol/L or >10.2 mg/dL), from 2000 to 2019.
Of these patients, 3,804 underwent parathyroidectomy within 1 year of diagnosis of PHPT, and 39,893 did not, and instead, a watchful waiting approach was adopted.
To be included in the analysis, patients had to have an eGFR above 30 mL/min per 1.73 m2 for 12 months before PHPT diagnosis to exclude secondary or tertiary hyperparathyroidism.
The primary outcome was a sustained decline in eGFR of at least 50% from baseline.
In the overall cohort, patients had a mean pretreatment eGFR of 71.8 mL/min per 1.73 m2. The mean age of patients was 67, 88% were men, and 68% were White.
After a median follow-up of 4.9 years, 6.7% of the patients had a decline in eGFR of at least 50%.
The cumulative incidence of this decline in eGFR was 5.1% at 5 years and 10.8% at 10 years in patients who had had early parathyroidectomy compared with 5.1% and 12.0%, respectively, in patients who did not undergo surgery.
In the overall population, the risk of at least a 50% decline in eGFR was similar in the early parathyroidectomy group versus the observation group (adjusted hazard ratio [HR], 0.98, 95% confidence interval [CI], 0.82-1.16).
However, diving deeper showed that parathyroidectomy was associated with a reduced risk of the primary outcome among patients younger than 60 years (adjusted HR, 0.75, 95% CI, 0.59-0.93) but not among those aged 60 or older (adjusted HR, 1.08, 95% CI, 0.87-1.34).
“When participating in shared decision-making for older adults [age 60 and older] with PHPT, clinicians should not consider parathyroidectomy for potential benefits of preservation of kidney function,” the researchers reiterated.
“For younger patients, clinicians should discuss the potential benefit of parathyroidectomy to reduce the risk for CKD and associated complications in adults with PHPT,” they concluded.
The study was funded by the National Institute on Aging. The authors reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM ANNALS OF INTERNAL MEDICINE