Endocrinology

While TikTok overflows with images of influencers making “adrenal cocktails” to combat what they call adrenal fatigue, the Endocrine Society says “no scientific proof exists to support adrenal fatigue as a true medical condition.”

Even before influencers began touting it on social media, a 2016 systematic review concluded that there is “no substantiation that adrenal fatigue” is an actual medical condition. Therefore, adrenal fatigue is still a myth.

Lynette Nieman, MD, Senior Investigator and Chief of the Endocrinology Consultation Service at the National Institutes of Health Clinical Center, Bethesda, Maryland, concurs.

“There is no scientific evidence that adrenal fatigue exists or causes [general] fatigue, depression, or the many common symptoms that are said to result from this condition,” she told this news organization via email.

Still, the term has gained currency among not only social media influencers who blame it for everything from cortisol surges to estrogen imbalances but also functional and integrative medical practitioners as an explanation for chronic dysfunction related to stress. 
 

Adrenal Fatigue, Burnout, or Adrenal Insufficiency?

Rather than “adrenal fatigue,” Marcelo Campos, MD, a primary care doctor at Atrius Health, said he prefers the medical term “burnout.”

Use of “burnout” shifts attention to the brain’s role in stress-related chronic dysfunction rather than the adrenal glands, said Dr. Campos, who also teaches at Harvard Medical School, Cambridge, Massachusetts.

More specifically still, the focuses might shift to the stress-response via the hypothalamic-pituitary-adrenocortical axis and its role in reducing levels of these cortisol and dehydroepiandrosterone sulfate.

He points out that part of the reason for the misuse of the term adrenal fatigue arises from the fact that burnout is often only associated with work stress.

“Recently, the ICD-11 [International Classification of Diseases-11] recognized burnout as a disease but focused only on work stress as a cause. The truth is that people can be burned out for many other reasons,” said Dr. Campos.

The Endocrine Society notes on their webpage dedicated to the topic that “adrenal fatigue” as a term, relates to long-term mental, emotional, or physical stress.

“The problem is not the adrenals — it is the exposure to stress in the brain. The brain — only one organ — is responsible for 40% of energy consumption in the body. As you can imagine, if you are under constant stress, you run out of gas very quickly and cannot function well,” he explained.

Adrenal fatigue theory suggests that, under stress, the adrenal glands produce too many short bursts of cortisol resulting in overall reduced cortisol levels and a feeling of being drained.

“As with many other psychiatric diseases, we do not have a way to measure biomarkers in the brain. The testing for cortisol does not work because it fluctuates too much from time to time. So, it is not reliable or reproducible,” Dr. Campos said. 

This leads to the ongoing question of the best way to test and diagnose adrenal fatigue, whether it should be via blood, urine and/or saliva. And even if that is determined, there are still questions about the best time to test, how often, what the normal ranges are and how reliable the tests are.

While adrenal fatigue is not a recognized condition, adrenal insufficiency is medically recognized, resulting from an inability of the adrenal glands to make the life-essential hormones aldosterone and/or cortisol, with symptoms that include fatigue, belly pain, nausea, vomiting, diarrhea, and joint aches.

“Adrenal cocktails are not an effective treatment for adrenal insufficiency because they do not replace the missing hormones,” Dr. Nieman stated, pointing out that anyone with symptoms of adrenal insufficiency needs to see an endocrinologist.

Pratibha Rao, MD, MPH, an endocrinologist at the Cleveland Clinic, Ohio, and medical director of the Adrenal Center at Cleveland Clinic, agreed, advising that if people continue to feel exhausted beyond their normal exertion, then they should get checked for signs of adrenal insufficiency.

“In primary adrenal insufficiency, you can actually start seeing darkening of the gums and of the skin on the palms of the hands or the soles of your feet. Sometimes people can feel dizzy or experience some loss of consciousness,” she said. “If it’s sudden and severe, you may crave salt or have extreme heat or cold intolerance.”

Recognizing and Managing Patient Frustration

The lack of formal diagnostic criteria and medical evidence, however, doesn’t mean that such symptoms as fatigue and depression don’t present, often causing significant distress for patients. While the symptoms might not be associated with the adrenal glands, they still need addressing — but how that is done is, in essence, a bone of contention.

Dr. Rao empathizes with the situation that many people, often young women, find themselves in.

“Patients are frustrated. They’ve gone to multiple doctors across the country, and they feel convinced they have adrenal fatigue, but no medical doctor has endorsed it. They end up coming to us with a cry that has so often gone unanswered.”

This issue also highlights that there are millions of people experiencing mental, emotional, and physical distress of unknown cause who seek help, many of whom believe it is related to their adrenal gland function.

But rather than turning to a social media cure, Dr. Rao stresses that people would benefit more from paying greater attention to following a healthy lifestyle than regularly consuming sugar-rich drinks claimed to offer a solution. Adrenal cocktails are energy-rich, frothy blends of orange juice, coconut milk, cream of tartar, and Himalayan salt.

“We truly are what we eat, and we are what we think,” she noted.

The body is a miraculous machine, but “we forget that it does need maintenance,” Dr. Rao said. “Up to age 30, the body is so forgiving with drugs, alcohol, or whatever insult we do to it, but after the third decade, slowly every cell starts to degenerate instead of growing. We start to see the ill or beneficial effects of lifestyle habits.” 

“We insult the body, and then we say, ‘oh, I have fatigue’ and seek a quick fix,” she added. “Everyone wants instant gratification.”

Dr. Rao cautioned that adrenal cocktails could be dangerous for someone who has other medical conditions.

“If someone has kidney disease, uncontrolled hypertension, or diabetes, for example, then adrenal cocktails are definitely not safe,” Dr. Rao said. “Loading up with potassium and sodium, which is found in high quantities in adrenal cocktails, will actually worsen any kidney damage, while consuming so much sugar will cause an unregulated rise in blood sugar and further damage in someone with diabetes.”

Dr. Rao also stressed that nonprofessional advice given on social media could take patient people down the wrong path with associated danger.

A version of this article appeared on Medscape.com.

While TikTok overflows with images of influencers making “adrenal cocktails” to combat what they call adrenal fatigue, the Endocrine Society says “no scientific proof exists to support adrenal fatigue as a true medical condition.”

Even before influencers began touting it on social media, a 2016 systematic review concluded that there is “no substantiation that adrenal fatigue” is an actual medical condition. Therefore, adrenal fatigue is still a myth.

Lynette Nieman, MD, Senior Investigator and Chief of the Endocrinology Consultation Service at the National Institutes of Health Clinical Center, Bethesda, Maryland, concurs.

“There is no scientific evidence that adrenal fatigue exists or causes [general] fatigue, depression, or the many common symptoms that are said to result from this condition,” she told this news organization via email.

Still, the term has gained currency among not only social media influencers who blame it for everything from cortisol surges to estrogen imbalances but also functional and integrative medical practitioners as an explanation for chronic dysfunction related to stress. 
 

Adrenal Fatigue, Burnout, or Adrenal Insufficiency?

Rather than “adrenal fatigue,” Marcelo Campos, MD, a primary care doctor at Atrius Health, said he prefers the medical term “burnout.”

Use of “burnout” shifts attention to the brain’s role in stress-related chronic dysfunction rather than the adrenal glands, said Dr. Campos, who also teaches at Harvard Medical School, Cambridge, Massachusetts.

More specifically still, the focuses might shift to the stress-response via the hypothalamic-pituitary-adrenocortical axis and its role in reducing levels of these cortisol and dehydroepiandrosterone sulfate.

He points out that part of the reason for the misuse of the term adrenal fatigue arises from the fact that burnout is often only associated with work stress.

“Recently, the ICD-11 [International Classification of Diseases-11] recognized burnout as a disease but focused only on work stress as a cause. The truth is that people can be burned out for many other reasons,” said Dr. Campos.

The Endocrine Society notes on their webpage dedicated to the topic that “adrenal fatigue” as a term, relates to long-term mental, emotional, or physical stress.

“The problem is not the adrenals — it is the exposure to stress in the brain. The brain — only one organ — is responsible for 40% of energy consumption in the body. As you can imagine, if you are under constant stress, you run out of gas very quickly and cannot function well,” he explained.

Adrenal fatigue theory suggests that, under stress, the adrenal glands produce too many short bursts of cortisol resulting in overall reduced cortisol levels and a feeling of being drained.

“As with many other psychiatric diseases, we do not have a way to measure biomarkers in the brain. The testing for cortisol does not work because it fluctuates too much from time to time. So, it is not reliable or reproducible,” Dr. Campos said. 

This leads to the ongoing question of the best way to test and diagnose adrenal fatigue, whether it should be via blood, urine and/or saliva. And even if that is determined, there are still questions about the best time to test, how often, what the normal ranges are and how reliable the tests are.

While adrenal fatigue is not a recognized condition, adrenal insufficiency is medically recognized, resulting from an inability of the adrenal glands to make the life-essential hormones aldosterone and/or cortisol, with symptoms that include fatigue, belly pain, nausea, vomiting, diarrhea, and joint aches.

“Adrenal cocktails are not an effective treatment for adrenal insufficiency because they do not replace the missing hormones,” Dr. Nieman stated, pointing out that anyone with symptoms of adrenal insufficiency needs to see an endocrinologist.

Pratibha Rao, MD, MPH, an endocrinologist at the Cleveland Clinic, Ohio, and medical director of the Adrenal Center at Cleveland Clinic, agreed, advising that if people continue to feel exhausted beyond their normal exertion, then they should get checked for signs of adrenal insufficiency.

“In primary adrenal insufficiency, you can actually start seeing darkening of the gums and of the skin on the palms of the hands or the soles of your feet. Sometimes people can feel dizzy or experience some loss of consciousness,” she said. “If it’s sudden and severe, you may crave salt or have extreme heat or cold intolerance.”

Recognizing and Managing Patient Frustration

The lack of formal diagnostic criteria and medical evidence, however, doesn’t mean that such symptoms as fatigue and depression don’t present, often causing significant distress for patients. While the symptoms might not be associated with the adrenal glands, they still need addressing — but how that is done is, in essence, a bone of contention.

Dr. Rao empathizes with the situation that many people, often young women, find themselves in.

“Patients are frustrated. They’ve gone to multiple doctors across the country, and they feel convinced they have adrenal fatigue, but no medical doctor has endorsed it. They end up coming to us with a cry that has so often gone unanswered.”

This issue also highlights that there are millions of people experiencing mental, emotional, and physical distress of unknown cause who seek help, many of whom believe it is related to their adrenal gland function.

But rather than turning to a social media cure, Dr. Rao stresses that people would benefit more from paying greater attention to following a healthy lifestyle than regularly consuming sugar-rich drinks claimed to offer a solution. Adrenal cocktails are energy-rich, frothy blends of orange juice, coconut milk, cream of tartar, and Himalayan salt.

“We truly are what we eat, and we are what we think,” she noted.

The body is a miraculous machine, but “we forget that it does need maintenance,” Dr. Rao said. “Up to age 30, the body is so forgiving with drugs, alcohol, or whatever insult we do to it, but after the third decade, slowly every cell starts to degenerate instead of growing. We start to see the ill or beneficial effects of lifestyle habits.” 

“We insult the body, and then we say, ‘oh, I have fatigue’ and seek a quick fix,” she added. “Everyone wants instant gratification.”

Dr. Rao cautioned that adrenal cocktails could be dangerous for someone who has other medical conditions.

“If someone has kidney disease, uncontrolled hypertension, or diabetes, for example, then adrenal cocktails are definitely not safe,” Dr. Rao said. “Loading up with potassium and sodium, which is found in high quantities in adrenal cocktails, will actually worsen any kidney damage, while consuming so much sugar will cause an unregulated rise in blood sugar and further damage in someone with diabetes.”

Dr. Rao also stressed that nonprofessional advice given on social media could take patient people down the wrong path with associated danger.

A version of this article appeared on Medscape.com.

While TikTok overflows with images of influencers making “adrenal cocktails” to combat what they call adrenal fatigue, the Endocrine Society says “no scientific proof exists to support adrenal fatigue as a true medical condition.”

Even before influencers began touting it on social media, a 2016 systematic review concluded that there is “no substantiation that adrenal fatigue” is an actual medical condition. Therefore, adrenal fatigue is still a myth.

Lynette Nieman, MD, Senior Investigator and Chief of the Endocrinology Consultation Service at the National Institutes of Health Clinical Center, Bethesda, Maryland, concurs.

“There is no scientific evidence that adrenal fatigue exists or causes [general] fatigue, depression, or the many common symptoms that are said to result from this condition,” she told this news organization via email.

Still, the term has gained currency among not only social media influencers who blame it for everything from cortisol surges to estrogen imbalances but also functional and integrative medical practitioners as an explanation for chronic dysfunction related to stress. 
 

Adrenal Fatigue, Burnout, or Adrenal Insufficiency?

Rather than “adrenal fatigue,” Marcelo Campos, MD, a primary care doctor at Atrius Health, said he prefers the medical term “burnout.”

Use of “burnout” shifts attention to the brain’s role in stress-related chronic dysfunction rather than the adrenal glands, said Dr. Campos, who also teaches at Harvard Medical School, Cambridge, Massachusetts.

More specifically still, the focuses might shift to the stress-response via the hypothalamic-pituitary-adrenocortical axis and its role in reducing levels of these cortisol and dehydroepiandrosterone sulfate.

He points out that part of the reason for the misuse of the term adrenal fatigue arises from the fact that burnout is often only associated with work stress.

“Recently, the ICD-11 [International Classification of Diseases-11] recognized burnout as a disease but focused only on work stress as a cause. The truth is that people can be burned out for many other reasons,” said Dr. Campos.

The Endocrine Society notes on their webpage dedicated to the topic that “adrenal fatigue” as a term, relates to long-term mental, emotional, or physical stress.

“The problem is not the adrenals — it is the exposure to stress in the brain. The brain — only one organ — is responsible for 40% of energy consumption in the body. As you can imagine, if you are under constant stress, you run out of gas very quickly and cannot function well,” he explained.

Adrenal fatigue theory suggests that, under stress, the adrenal glands produce too many short bursts of cortisol resulting in overall reduced cortisol levels and a feeling of being drained.

“As with many other psychiatric diseases, we do not have a way to measure biomarkers in the brain. The testing for cortisol does not work because it fluctuates too much from time to time. So, it is not reliable or reproducible,” Dr. Campos said. 

This leads to the ongoing question of the best way to test and diagnose adrenal fatigue, whether it should be via blood, urine and/or saliva. And even if that is determined, there are still questions about the best time to test, how often, what the normal ranges are and how reliable the tests are.

While adrenal fatigue is not a recognized condition, adrenal insufficiency is medically recognized, resulting from an inability of the adrenal glands to make the life-essential hormones aldosterone and/or cortisol, with symptoms that include fatigue, belly pain, nausea, vomiting, diarrhea, and joint aches.

“Adrenal cocktails are not an effective treatment for adrenal insufficiency because they do not replace the missing hormones,” Dr. Nieman stated, pointing out that anyone with symptoms of adrenal insufficiency needs to see an endocrinologist.

Pratibha Rao, MD, MPH, an endocrinologist at the Cleveland Clinic, Ohio, and medical director of the Adrenal Center at Cleveland Clinic, agreed, advising that if people continue to feel exhausted beyond their normal exertion, then they should get checked for signs of adrenal insufficiency.

“In primary adrenal insufficiency, you can actually start seeing darkening of the gums and of the skin on the palms of the hands or the soles of your feet. Sometimes people can feel dizzy or experience some loss of consciousness,” she said. “If it’s sudden and severe, you may crave salt or have extreme heat or cold intolerance.”

Recognizing and Managing Patient Frustration

The lack of formal diagnostic criteria and medical evidence, however, doesn’t mean that such symptoms as fatigue and depression don’t present, often causing significant distress for patients. While the symptoms might not be associated with the adrenal glands, they still need addressing — but how that is done is, in essence, a bone of contention.

Dr. Rao empathizes with the situation that many people, often young women, find themselves in.

“Patients are frustrated. They’ve gone to multiple doctors across the country, and they feel convinced they have adrenal fatigue, but no medical doctor has endorsed it. They end up coming to us with a cry that has so often gone unanswered.”

This issue also highlights that there are millions of people experiencing mental, emotional, and physical distress of unknown cause who seek help, many of whom believe it is related to their adrenal gland function.

But rather than turning to a social media cure, Dr. Rao stresses that people would benefit more from paying greater attention to following a healthy lifestyle than regularly consuming sugar-rich drinks claimed to offer a solution. Adrenal cocktails are energy-rich, frothy blends of orange juice, coconut milk, cream of tartar, and Himalayan salt.

“We truly are what we eat, and we are what we think,” she noted.

The body is a miraculous machine, but “we forget that it does need maintenance,” Dr. Rao said. “Up to age 30, the body is so forgiving with drugs, alcohol, or whatever insult we do to it, but after the third decade, slowly every cell starts to degenerate instead of growing. We start to see the ill or beneficial effects of lifestyle habits.” 

“We insult the body, and then we say, ‘oh, I have fatigue’ and seek a quick fix,” she added. “Everyone wants instant gratification.”

Dr. Rao cautioned that adrenal cocktails could be dangerous for someone who has other medical conditions.

“If someone has kidney disease, uncontrolled hypertension, or diabetes, for example, then adrenal cocktails are definitely not safe,” Dr. Rao said. “Loading up with potassium and sodium, which is found in high quantities in adrenal cocktails, will actually worsen any kidney damage, while consuming so much sugar will cause an unregulated rise in blood sugar and further damage in someone with diabetes.”

Dr. Rao also stressed that nonprofessional advice given on social media could take patient people down the wrong path with associated danger.

A version of this article appeared on Medscape.com.

TOPLINE:

Continued denosumab treatment is associated with a lower risk for diabetes in adults with osteoporosis older than 65 years, found a large-scale cohort study in Taiwan.

METHODOLOGY:

• Denosumab, used in osteoporosis treatment, has been suggested to improve glycemic parameters, but clinical evidence of its effects on diabetes risk is limited and inconsistent.
• Using data from Taiwan’s National Health Insurance Research Database (NHIRD), the study asked if continued denosumab treatment (60 mg) for osteoporosis reduced the risk for diabetes compared to those who discontinued denosumab.
• Researchers included all new users of denosumab between 2012 and 2019 who had no prior history of malignant neoplasms, Paget disease, or diabetes requiring antidiabetic medication.
• Patients in the treatment group (n = 34,255), who received a second dose of denosumab within 225 days, were 1:1 propensity matched with a control group (n = 34,255) of patients who had discontinued denosumab after the first dose.
• The 68,510 patients (mean age, 77.7 years; 84.3% women) were followed up for a mean of 1.9 years. The primary outcome was new-onset diabetes that required treatment with any antidiabetic drug.

TAKEAWAY:

• Continued denosumab treatment vs its discontinuation was associated with a lower risk for incident diabetes (hazard ratio [HR], 0.84; 95% CI, 0.78-0.90).
• In patients aged 65 years or older who were on continued treatment of denosumab, the risk for diabetes was lower (HR, 0.80; 95% CI, 0.75-0.85) but not among those younger than 65 years.
• A reduced risk for diabetes with continued denosumab treatment was observed in both men (HR, 0.85; 95% CI, 0.73-0.97) and women (HR, 0.81; 95% CI, 0.76-0.86).
• Lower diabetes risk with continued denosumab treatment was observed regardless of comorbidities, such as dyslipidemia, hypertension, ischemic heart disease, or kidney failure.

IN PRACTICE:

“Given the high osteoporosis prevalence, the extensive use of antiosteoporosis medications, and the negative effect of diabetes on both patient health and healthcare system burdens in the global aging population, our findings possess substantial clinical and public health significance,” the authors wrote.

SOURCE:

This study was led by Huei-Kai Huang, MD, Department of Family Medicine and Department of Medical Research, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan, and published online in JAMA Network Open.

LIMITATIONS:

The research used claims-based data, so some clinical details, such as lifestyle, substance use, prediabetes weight status, and laboratory results, were not included. Owing to the anonymity policy of the NHIRD, patients could not be directly evaluated to validate incident diabetes. The study included the Taiwanese population, so the findings may not be generalizable to other populations. In Taiwan, the threshold for reimbursement of initiating denosumab treatment for osteoporosis includes below-normal bone density scores and a hip or vertebral fracture.

DISCLOSURES:

This study was supported by grants from the National Science and Technology Council of Taiwan and the National Health Research Institutes of Taiwan and a grant from the Buddhist Tzu Chi Medical Foundation. The corresponding author and a coauthor disclosed receiving funds from Amgen, Novartis, Pfizer, Sanofi, Takeda, and AbbVie, all outside the submitted work.

A version of this article appeared on Medscape.com.

TOPLINE:

Continued denosumab treatment is associated with a lower risk for diabetes in adults with osteoporosis older than 65 years, found a large-scale cohort study in Taiwan.

METHODOLOGY:

• Denosumab, used in osteoporosis treatment, has been suggested to improve glycemic parameters, but clinical evidence of its effects on diabetes risk is limited and inconsistent.
• Using data from Taiwan’s National Health Insurance Research Database (NHIRD), the study asked if continued denosumab treatment (60 mg) for osteoporosis reduced the risk for diabetes compared to those who discontinued denosumab.
• Researchers included all new users of denosumab between 2012 and 2019 who had no prior history of malignant neoplasms, Paget disease, or diabetes requiring antidiabetic medication.
• Patients in the treatment group (n = 34,255), who received a second dose of denosumab within 225 days, were 1:1 propensity matched with a control group (n = 34,255) of patients who had discontinued denosumab after the first dose.
• The 68,510 patients (mean age, 77.7 years; 84.3% women) were followed up for a mean of 1.9 years. The primary outcome was new-onset diabetes that required treatment with any antidiabetic drug.

TAKEAWAY:

• Continued denosumab treatment vs its discontinuation was associated with a lower risk for incident diabetes (hazard ratio [HR], 0.84; 95% CI, 0.78-0.90).
• In patients aged 65 years or older who were on continued treatment of denosumab, the risk for diabetes was lower (HR, 0.80; 95% CI, 0.75-0.85) but not among those younger than 65 years.
• A reduced risk for diabetes with continued denosumab treatment was observed in both men (HR, 0.85; 95% CI, 0.73-0.97) and women (HR, 0.81; 95% CI, 0.76-0.86).
• Lower diabetes risk with continued denosumab treatment was observed regardless of comorbidities, such as dyslipidemia, hypertension, ischemic heart disease, or kidney failure.

IN PRACTICE:

“Given the high osteoporosis prevalence, the extensive use of antiosteoporosis medications, and the negative effect of diabetes on both patient health and healthcare system burdens in the global aging population, our findings possess substantial clinical and public health significance,” the authors wrote.

SOURCE:

This study was led by Huei-Kai Huang, MD, Department of Family Medicine and Department of Medical Research, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan, and published online in JAMA Network Open.

LIMITATIONS:

The research used claims-based data, so some clinical details, such as lifestyle, substance use, prediabetes weight status, and laboratory results, were not included. Owing to the anonymity policy of the NHIRD, patients could not be directly evaluated to validate incident diabetes. The study included the Taiwanese population, so the findings may not be generalizable to other populations. In Taiwan, the threshold for reimbursement of initiating denosumab treatment for osteoporosis includes below-normal bone density scores and a hip or vertebral fracture.

DISCLOSURES:

This study was supported by grants from the National Science and Technology Council of Taiwan and the National Health Research Institutes of Taiwan and a grant from the Buddhist Tzu Chi Medical Foundation. The corresponding author and a coauthor disclosed receiving funds from Amgen, Novartis, Pfizer, Sanofi, Takeda, and AbbVie, all outside the submitted work.

A version of this article appeared on Medscape.com.

TOPLINE:

Continued denosumab treatment is associated with a lower risk for diabetes in adults with osteoporosis older than 65 years, found a large-scale cohort study in Taiwan.

METHODOLOGY:

• Denosumab, used in osteoporosis treatment, has been suggested to improve glycemic parameters, but clinical evidence of its effects on diabetes risk is limited and inconsistent.
• Using data from Taiwan’s National Health Insurance Research Database (NHIRD), the study asked if continued denosumab treatment (60 mg) for osteoporosis reduced the risk for diabetes compared to those who discontinued denosumab.
• Researchers included all new users of denosumab between 2012 and 2019 who had no prior history of malignant neoplasms, Paget disease, or diabetes requiring antidiabetic medication.
• Patients in the treatment group (n = 34,255), who received a second dose of denosumab within 225 days, were 1:1 propensity matched with a control group (n = 34,255) of patients who had discontinued denosumab after the first dose.
• The 68,510 patients (mean age, 77.7 years; 84.3% women) were followed up for a mean of 1.9 years. The primary outcome was new-onset diabetes that required treatment with any antidiabetic drug.

TAKEAWAY:

• Continued denosumab treatment vs its discontinuation was associated with a lower risk for incident diabetes (hazard ratio [HR], 0.84; 95% CI, 0.78-0.90).
• In patients aged 65 years or older who were on continued treatment of denosumab, the risk for diabetes was lower (HR, 0.80; 95% CI, 0.75-0.85) but not among those younger than 65 years.
• A reduced risk for diabetes with continued denosumab treatment was observed in both men (HR, 0.85; 95% CI, 0.73-0.97) and women (HR, 0.81; 95% CI, 0.76-0.86).
• Lower diabetes risk with continued denosumab treatment was observed regardless of comorbidities, such as dyslipidemia, hypertension, ischemic heart disease, or kidney failure.

IN PRACTICE:

“Given the high osteoporosis prevalence, the extensive use of antiosteoporosis medications, and the negative effect of diabetes on both patient health and healthcare system burdens in the global aging population, our findings possess substantial clinical and public health significance,” the authors wrote.

SOURCE:

This study was led by Huei-Kai Huang, MD, Department of Family Medicine and Department of Medical Research, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan, and published online in JAMA Network Open.

LIMITATIONS:

The research used claims-based data, so some clinical details, such as lifestyle, substance use, prediabetes weight status, and laboratory results, were not included. Owing to the anonymity policy of the NHIRD, patients could not be directly evaluated to validate incident diabetes. The study included the Taiwanese population, so the findings may not be generalizable to other populations. In Taiwan, the threshold for reimbursement of initiating denosumab treatment for osteoporosis includes below-normal bone density scores and a hip or vertebral fracture.

DISCLOSURES:

This study was supported by grants from the National Science and Technology Council of Taiwan and the National Health Research Institutes of Taiwan and a grant from the Buddhist Tzu Chi Medical Foundation. The corresponding author and a coauthor disclosed receiving funds from Amgen, Novartis, Pfizer, Sanofi, Takeda, and AbbVie, all outside the submitted work.

A version of this article appeared on Medscape.com.

TOPLINE:

The risk of developing gynecologic cancer is lower in women with hyperthyroidism than in those without it, found a large study. 

METHODOLOGY:

• Thyroid disease and altered thyroid hormone expression can affect ovulation, endometrial physiology, and estrogen levels, but studies of the association with gynecologic cancer risk have conflicting results.
• This population-based cohort study used data from the Taiwan National Health Insurance Research Database to identify women (mean age, 44 years) who were diagnosed with thyroid disease between January 2000 and December 2018.
• Propensity scores were used to pair 296,872 women with hyperthyroidism and 44,852 with hypothyroidism in a 1:1 ratio with an equal number of individuals without thyroid disorders.
• The cohort was followed up from the date of first diagnosis of hypothyroidism or hyperthyroidism until the diagnosis of gynecologic cancers (endometrial cancer, uterine corpus cancer, and ovarian cancer), death, or the end of 2018.

TAKEAWAY:

• Women with hyperthyroidism had a lower risk for all gynecologic cancers than those without hyperthyroidism (adjusted hazard ratio [aHR], 0.86; P = .0084).
• The risk of developing gynecologic cancer was lower among women with hyperthyroidism aged 20-40 years (aHR, 0.72; P = .0043) but not among those aged > 40 years.
• The reduced risk for gynecologic cancers associated with hyperthyroidism persisted even beyond 6 years of follow-up (aHR, 0.75; P < .001).
• A trend toward a slightly increased risk for gynecologic cancer was observed among women with hypothyroidism; however, the association was not statistically significant.

IN PRACTICE:

The findings may alert oncologists and healthcare decision-makers toward gynecologic cancer trends and prompt further research to understand the mechanism by which thyroid hormone regulates reproductive function, the authors noted.

SOURCE:

This study was led by John Hang Leung from the Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, Taiwan, and published online in Scientific Reports.

LIMITATIONS:

The study data were obtained from administrative claims databases, so there is a possibility of underestimation or overestimation. Lifestyle factors such as obesity and alcoholism are difficult to measure, so the risk for gynecologic cancers linked to thyroid dysfunction may have been underestimated. Furthermore, because of nonavailability of laboratory data, thyroid hormone status at diagnosis could not be linked to gynecological cancer risk.

DISCLOSURES:

This study was supported by An-Nan Hospital, China Medical University, Tainan, Taiwan. The authors declared no financial interests or conflicts related to the study.

A version of this article appeared on Medscape.com.

TOPLINE:

The risk of developing gynecologic cancer is lower in women with hyperthyroidism than in those without it, found a large study. 

METHODOLOGY:

• Thyroid disease and altered thyroid hormone expression can affect ovulation, endometrial physiology, and estrogen levels, but studies of the association with gynecologic cancer risk have conflicting results.
• This population-based cohort study used data from the Taiwan National Health Insurance Research Database to identify women (mean age, 44 years) who were diagnosed with thyroid disease between January 2000 and December 2018.
• Propensity scores were used to pair 296,872 women with hyperthyroidism and 44,852 with hypothyroidism in a 1:1 ratio with an equal number of individuals without thyroid disorders.
• The cohort was followed up from the date of first diagnosis of hypothyroidism or hyperthyroidism until the diagnosis of gynecologic cancers (endometrial cancer, uterine corpus cancer, and ovarian cancer), death, or the end of 2018.

TAKEAWAY:

• Women with hyperthyroidism had a lower risk for all gynecologic cancers than those without hyperthyroidism (adjusted hazard ratio [aHR], 0.86; P = .0084).
• The risk of developing gynecologic cancer was lower among women with hyperthyroidism aged 20-40 years (aHR, 0.72; P = .0043) but not among those aged > 40 years.
• The reduced risk for gynecologic cancers associated with hyperthyroidism persisted even beyond 6 years of follow-up (aHR, 0.75; P < .001).
• A trend toward a slightly increased risk for gynecologic cancer was observed among women with hypothyroidism; however, the association was not statistically significant.

IN PRACTICE:

The findings may alert oncologists and healthcare decision-makers toward gynecologic cancer trends and prompt further research to understand the mechanism by which thyroid hormone regulates reproductive function, the authors noted.

SOURCE:

This study was led by John Hang Leung from the Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, Taiwan, and published online in Scientific Reports.

LIMITATIONS:

The study data were obtained from administrative claims databases, so there is a possibility of underestimation or overestimation. Lifestyle factors such as obesity and alcoholism are difficult to measure, so the risk for gynecologic cancers linked to thyroid dysfunction may have been underestimated. Furthermore, because of nonavailability of laboratory data, thyroid hormone status at diagnosis could not be linked to gynecological cancer risk.

DISCLOSURES:

This study was supported by An-Nan Hospital, China Medical University, Tainan, Taiwan. The authors declared no financial interests or conflicts related to the study.

A version of this article appeared on Medscape.com.

TOPLINE:

The risk of developing gynecologic cancer is lower in women with hyperthyroidism than in those without it, found a large study. 

METHODOLOGY:

• Thyroid disease and altered thyroid hormone expression can affect ovulation, endometrial physiology, and estrogen levels, but studies of the association with gynecologic cancer risk have conflicting results.
• This population-based cohort study used data from the Taiwan National Health Insurance Research Database to identify women (mean age, 44 years) who were diagnosed with thyroid disease between January 2000 and December 2018.
• Propensity scores were used to pair 296,872 women with hyperthyroidism and 44,852 with hypothyroidism in a 1:1 ratio with an equal number of individuals without thyroid disorders.
• The cohort was followed up from the date of first diagnosis of hypothyroidism or hyperthyroidism until the diagnosis of gynecologic cancers (endometrial cancer, uterine corpus cancer, and ovarian cancer), death, or the end of 2018.

TAKEAWAY:

• Women with hyperthyroidism had a lower risk for all gynecologic cancers than those without hyperthyroidism (adjusted hazard ratio [aHR], 0.86; P = .0084).
• The risk of developing gynecologic cancer was lower among women with hyperthyroidism aged 20-40 years (aHR, 0.72; P = .0043) but not among those aged > 40 years.
• The reduced risk for gynecologic cancers associated with hyperthyroidism persisted even beyond 6 years of follow-up (aHR, 0.75; P < .001).
• A trend toward a slightly increased risk for gynecologic cancer was observed among women with hypothyroidism; however, the association was not statistically significant.

IN PRACTICE:

The findings may alert oncologists and healthcare decision-makers toward gynecologic cancer trends and prompt further research to understand the mechanism by which thyroid hormone regulates reproductive function, the authors noted.

SOURCE:

This study was led by John Hang Leung from the Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, Taiwan, and published online in Scientific Reports.

LIMITATIONS:

The study data were obtained from administrative claims databases, so there is a possibility of underestimation or overestimation. Lifestyle factors such as obesity and alcoholism are difficult to measure, so the risk for gynecologic cancers linked to thyroid dysfunction may have been underestimated. Furthermore, because of nonavailability of laboratory data, thyroid hormone status at diagnosis could not be linked to gynecological cancer risk.

DISCLOSURES:

This study was supported by An-Nan Hospital, China Medical University, Tainan, Taiwan. The authors declared no financial interests or conflicts related to the study.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) announced the removal of the endocrine-disrupting chemicals (EDCs) per- and polyfluoroalkyl substances (PFAS) from food packaging.

Issued on February 28, 2024, “this means the major source of dietary exposure to PFAS from food packaging like fast-food wrappers, microwave popcorn bags, take-out paperboard containers, and pet food bags is being eliminated,” the FDA said in a statement.

In 2020, the FDA had secured commitments from manufacturers to stop selling products containing PFAS used in the food packaging for grease-proofing. “Today’s announcement marks the fulfillment of these voluntary commitments,” according to the agency.

PFAS, a class of thousands of chemicals also called “forever chemicals” are widely used in consumer and industrial products. People may be exposed via contaminated food packaging (although perhaps no longer in the United States) or occupationally. Studies have found that some PFAS disrupt hormones including estrogen and testosterone, whereas others may impair thyroid function.
 

Endocrine Society Report Sounds the Alarm About PFAS and Others

The FDA’s announcement came just 2 days after the Endocrine Society issued a new alarm about the human health dangers from environmental EDCs including PFAS in a report covering the latest science.

“Endocrine disrupting chemicals” are individual substances or mixtures that can interfere with natural hormonal function, leading to disease or even death. Many are ubiquitous in the modern environment and contribute to a wide range of human diseases.

The new report Endocrine Disrupting Chemicals: Threats to Human Health was issued jointly with the International Pollutants Elimination Network (IPEN), a global advocacy organization. It’s an update to the Endocrine Society’s 2015 report, providing new data on the endocrine-disrupting substances previously covered and adding four EDCs not discussed in that document: Pesticides, plastics, PFAS, and children’s products containing arsenic.

At a briefing held during the United Nations Environment Assembly meeting in Nairobi, Kenya, last week, the new report’s lead author Andrea C. Gore, PhD, of the University of Texas at Austin, noted, “A well-established body of scientific research indicates that endocrine-disrupting chemicals that are part of our daily lives are making us more susceptible to reproductive disorders, cancer, diabetes, obesity, heart disease, and other serious health conditions.”

Added Dr. Gore, who is also a member of the Endocrine Society’s Board of Directors, “These chemicals pose particularly serious risks to pregnant women and children. Now is the time for the UN Environment Assembly and other global policymakers to take action to address this threat to public health.”

While the science has been emerging rapidly, global and national chemical control policies haven’t kept up, the authors said. Of particular concern is that EDCs behave differently from other chemicals in many ways, including that even very low-dose exposures can pose health threats, but policies thus far haven’t dealt with that aspect.

Moreover, “the effects of low doses cannot be predicted by the effects observed at high doses. This means there may be no safe dose for exposure to EDCs,” according to the report.

Exposures can come from household products, including furniture, toys, and food packages, as well as electronics building materials and cosmetics. These chemicals are also in the outdoor environment, via pesticides, air pollution, and industrial waste.

“IPEN and the Endocrine Society call for chemical regulations based on the most modern scientific understanding of how hormones act and how EDCs can perturb these actions. We work to educate policy makers in global, regional, and national government assemblies and help ensure that regulations correlate with current scientific understanding,” they said in the report.
 

New Data on Four Classes of EDCs

Chapters of the report summarized the latest information about the science of EDCs and their links to endocrine disease and real-world exposure. It included a special section about “EDCs throughout the plastics life cycle” and a summary of the links between EDCs and climate change.

The report reviewed three pesticides, including the world’s most heavily applied herbicide, glycophosphate. Exposures can occur directly from the air, water, dust, and food residues. Recent data linked glycophosphate to adverse reproductive health outcomes.

Two toxic plastic chemicals, phthalates and bisphenols, are present in personal care products, among others. Emerging evidence links them with impaired neurodevelopment, leading to impaired cognitive function, learning, attention, and impulsivity.

Arsenic has long been linked to human health conditions including cancer, but more recent evidence finds it can disrupt multiple endocrine systems and lead to metabolic conditions including diabetes, reproductive dysfunction, and cardiovascular and neurocognitive conditions.

The special section about plastics noted that they are made from fossil fuels and chemicals, including many toxic substances that are known or suspected EDCs. People who live near plastic production facilities or waste dumps may be at greatest risk, but anyone can be exposed using any plastic product. Plastic waste disposal is increasingly problematic and often foisted on lower- and middle-income countries.
 

‘Additional Education and Awareness-Raising Among Stakeholders Remain Necessary’

Policies aimed at reducing human health risks from EDCs have included the 2022 Plastics Treaty, a resolution adopted by 175 countries at the United Nations Environmental Assembly that “may be a significant step toward global control of plastics and elimination of threats from exposures to EDCs in plastics,” the report said.

The authors added, “While significant progress has been made in recent years connecting scientific advances on EDCs with health-protective policies, additional education and awareness-raising among stakeholders remain necessary to achieve a safer and more sustainable environment that minimizes exposure to these harmful chemicals.”

The document was produced with financial contributions from the Government of Sweden, the Tides Foundation, Passport Foundation, and other donors.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) announced the removal of the endocrine-disrupting chemicals (EDCs) per- and polyfluoroalkyl substances (PFAS) from food packaging.

Issued on February 28, 2024, “this means the major source of dietary exposure to PFAS from food packaging like fast-food wrappers, microwave popcorn bags, take-out paperboard containers, and pet food bags is being eliminated,” the FDA said in a statement.

In 2020, the FDA had secured commitments from manufacturers to stop selling products containing PFAS used in the food packaging for grease-proofing. “Today’s announcement marks the fulfillment of these voluntary commitments,” according to the agency.

PFAS, a class of thousands of chemicals also called “forever chemicals” are widely used in consumer and industrial products. People may be exposed via contaminated food packaging (although perhaps no longer in the United States) or occupationally. Studies have found that some PFAS disrupt hormones including estrogen and testosterone, whereas others may impair thyroid function.
 

Endocrine Society Report Sounds the Alarm About PFAS and Others

The FDA’s announcement came just 2 days after the Endocrine Society issued a new alarm about the human health dangers from environmental EDCs including PFAS in a report covering the latest science.

“Endocrine disrupting chemicals” are individual substances or mixtures that can interfere with natural hormonal function, leading to disease or even death. Many are ubiquitous in the modern environment and contribute to a wide range of human diseases.

The new report Endocrine Disrupting Chemicals: Threats to Human Health was issued jointly with the International Pollutants Elimination Network (IPEN), a global advocacy organization. It’s an update to the Endocrine Society’s 2015 report, providing new data on the endocrine-disrupting substances previously covered and adding four EDCs not discussed in that document: Pesticides, plastics, PFAS, and children’s products containing arsenic.

At a briefing held during the United Nations Environment Assembly meeting in Nairobi, Kenya, last week, the new report’s lead author Andrea C. Gore, PhD, of the University of Texas at Austin, noted, “A well-established body of scientific research indicates that endocrine-disrupting chemicals that are part of our daily lives are making us more susceptible to reproductive disorders, cancer, diabetes, obesity, heart disease, and other serious health conditions.”

Added Dr. Gore, who is also a member of the Endocrine Society’s Board of Directors, “These chemicals pose particularly serious risks to pregnant women and children. Now is the time for the UN Environment Assembly and other global policymakers to take action to address this threat to public health.”

While the science has been emerging rapidly, global and national chemical control policies haven’t kept up, the authors said. Of particular concern is that EDCs behave differently from other chemicals in many ways, including that even very low-dose exposures can pose health threats, but policies thus far haven’t dealt with that aspect.

Moreover, “the effects of low doses cannot be predicted by the effects observed at high doses. This means there may be no safe dose for exposure to EDCs,” according to the report.

Exposures can come from household products, including furniture, toys, and food packages, as well as electronics building materials and cosmetics. These chemicals are also in the outdoor environment, via pesticides, air pollution, and industrial waste.

“IPEN and the Endocrine Society call for chemical regulations based on the most modern scientific understanding of how hormones act and how EDCs can perturb these actions. We work to educate policy makers in global, regional, and national government assemblies and help ensure that regulations correlate with current scientific understanding,” they said in the report.
 

New Data on Four Classes of EDCs

Chapters of the report summarized the latest information about the science of EDCs and their links to endocrine disease and real-world exposure. It included a special section about “EDCs throughout the plastics life cycle” and a summary of the links between EDCs and climate change.

The report reviewed three pesticides, including the world’s most heavily applied herbicide, glycophosphate. Exposures can occur directly from the air, water, dust, and food residues. Recent data linked glycophosphate to adverse reproductive health outcomes.

Two toxic plastic chemicals, phthalates and bisphenols, are present in personal care products, among others. Emerging evidence links them with impaired neurodevelopment, leading to impaired cognitive function, learning, attention, and impulsivity.

Arsenic has long been linked to human health conditions including cancer, but more recent evidence finds it can disrupt multiple endocrine systems and lead to metabolic conditions including diabetes, reproductive dysfunction, and cardiovascular and neurocognitive conditions.

The special section about plastics noted that they are made from fossil fuels and chemicals, including many toxic substances that are known or suspected EDCs. People who live near plastic production facilities or waste dumps may be at greatest risk, but anyone can be exposed using any plastic product. Plastic waste disposal is increasingly problematic and often foisted on lower- and middle-income countries.
 

‘Additional Education and Awareness-Raising Among Stakeholders Remain Necessary’

Policies aimed at reducing human health risks from EDCs have included the 2022 Plastics Treaty, a resolution adopted by 175 countries at the United Nations Environmental Assembly that “may be a significant step toward global control of plastics and elimination of threats from exposures to EDCs in plastics,” the report said.

The authors added, “While significant progress has been made in recent years connecting scientific advances on EDCs with health-protective policies, additional education and awareness-raising among stakeholders remain necessary to achieve a safer and more sustainable environment that minimizes exposure to these harmful chemicals.”

The document was produced with financial contributions from the Government of Sweden, the Tides Foundation, Passport Foundation, and other donors.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) announced the removal of the endocrine-disrupting chemicals (EDCs) per- and polyfluoroalkyl substances (PFAS) from food packaging.

Issued on February 28, 2024, “this means the major source of dietary exposure to PFAS from food packaging like fast-food wrappers, microwave popcorn bags, take-out paperboard containers, and pet food bags is being eliminated,” the FDA said in a statement.

In 2020, the FDA had secured commitments from manufacturers to stop selling products containing PFAS used in the food packaging for grease-proofing. “Today’s announcement marks the fulfillment of these voluntary commitments,” according to the agency.

PFAS, a class of thousands of chemicals also called “forever chemicals” are widely used in consumer and industrial products. People may be exposed via contaminated food packaging (although perhaps no longer in the United States) or occupationally. Studies have found that some PFAS disrupt hormones including estrogen and testosterone, whereas others may impair thyroid function.
 

Endocrine Society Report Sounds the Alarm About PFAS and Others

The FDA’s announcement came just 2 days after the Endocrine Society issued a new alarm about the human health dangers from environmental EDCs including PFAS in a report covering the latest science.

“Endocrine disrupting chemicals” are individual substances or mixtures that can interfere with natural hormonal function, leading to disease or even death. Many are ubiquitous in the modern environment and contribute to a wide range of human diseases.

The new report Endocrine Disrupting Chemicals: Threats to Human Health was issued jointly with the International Pollutants Elimination Network (IPEN), a global advocacy organization. It’s an update to the Endocrine Society’s 2015 report, providing new data on the endocrine-disrupting substances previously covered and adding four EDCs not discussed in that document: Pesticides, plastics, PFAS, and children’s products containing arsenic.

At a briefing held during the United Nations Environment Assembly meeting in Nairobi, Kenya, last week, the new report’s lead author Andrea C. Gore, PhD, of the University of Texas at Austin, noted, “A well-established body of scientific research indicates that endocrine-disrupting chemicals that are part of our daily lives are making us more susceptible to reproductive disorders, cancer, diabetes, obesity, heart disease, and other serious health conditions.”

Added Dr. Gore, who is also a member of the Endocrine Society’s Board of Directors, “These chemicals pose particularly serious risks to pregnant women and children. Now is the time for the UN Environment Assembly and other global policymakers to take action to address this threat to public health.”

While the science has been emerging rapidly, global and national chemical control policies haven’t kept up, the authors said. Of particular concern is that EDCs behave differently from other chemicals in many ways, including that even very low-dose exposures can pose health threats, but policies thus far haven’t dealt with that aspect.

Moreover, “the effects of low doses cannot be predicted by the effects observed at high doses. This means there may be no safe dose for exposure to EDCs,” according to the report.

Exposures can come from household products, including furniture, toys, and food packages, as well as electronics building materials and cosmetics. These chemicals are also in the outdoor environment, via pesticides, air pollution, and industrial waste.

“IPEN and the Endocrine Society call for chemical regulations based on the most modern scientific understanding of how hormones act and how EDCs can perturb these actions. We work to educate policy makers in global, regional, and national government assemblies and help ensure that regulations correlate with current scientific understanding,” they said in the report.
 

New Data on Four Classes of EDCs

Chapters of the report summarized the latest information about the science of EDCs and their links to endocrine disease and real-world exposure. It included a special section about “EDCs throughout the plastics life cycle” and a summary of the links between EDCs and climate change.

The report reviewed three pesticides, including the world’s most heavily applied herbicide, glycophosphate. Exposures can occur directly from the air, water, dust, and food residues. Recent data linked glycophosphate to adverse reproductive health outcomes.

Two toxic plastic chemicals, phthalates and bisphenols, are present in personal care products, among others. Emerging evidence links them with impaired neurodevelopment, leading to impaired cognitive function, learning, attention, and impulsivity.

Arsenic has long been linked to human health conditions including cancer, but more recent evidence finds it can disrupt multiple endocrine systems and lead to metabolic conditions including diabetes, reproductive dysfunction, and cardiovascular and neurocognitive conditions.

The special section about plastics noted that they are made from fossil fuels and chemicals, including many toxic substances that are known or suspected EDCs. People who live near plastic production facilities or waste dumps may be at greatest risk, but anyone can be exposed using any plastic product. Plastic waste disposal is increasingly problematic and often foisted on lower- and middle-income countries.
 

‘Additional Education and Awareness-Raising Among Stakeholders Remain Necessary’

Policies aimed at reducing human health risks from EDCs have included the 2022 Plastics Treaty, a resolution adopted by 175 countries at the United Nations Environmental Assembly that “may be a significant step toward global control of plastics and elimination of threats from exposures to EDCs in plastics,” the report said.

The authors added, “While significant progress has been made in recent years connecting scientific advances on EDCs with health-protective policies, additional education and awareness-raising among stakeholders remain necessary to achieve a safer and more sustainable environment that minimizes exposure to these harmful chemicals.”

The document was produced with financial contributions from the Government of Sweden, the Tides Foundation, Passport Foundation, and other donors.

A version of this article appeared on Medscape.com.

TOPLINE:

A national study in Israel demonstrates the feasibility and diagnostic benefits of rapid trio genome sequencing in critically ill neonates.

METHODOLOGY:

• Researchers conducted a prospective, multicenter cohort study from October 2021 to December 2022, involving all Israeli medical genetics institutes and neonatal intensive care units.
• A total of 130 critically ill neonates suspected of having a genetic disorder were enrolled, with rapid genome sequencing results expected within 10 days.

TAKEAWAY:

• Rapid trio genome sequencing diagnosed 50% of the neonates with disease-causing variants, including 12 chromosomal and 52 monogenic conditions.
• Another 11% had variants of unknown significance that were suspected to be disease-causing, and 1% had a novel gene suspected of causing disease.
• The mean turnaround time for the rapid reports was 7 days, demonstrating the feasibility of implementing rapid genome sequencing in a national healthcare setting, the researchers said.
• Genomic testing led to a change in clinical management for 22% of the neonates, which shows the clinical utility of this approach to diagnosis, they said.

IN PRACTICE:

Genetic testing may identify patients who are candidates for precision medical treatment and inform family planning, which is “critical for families with a severely affected or deceased child,” the study authors wrote.

SOURCE:

The corresponding author for the study was Daphna Marom, MD, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel. It was published online on February 22, 2024, in JAMA Network Open.

LIMITATIONS:

The study’s reliance on voluntary participation may have introduced referral bias, potentially affecting the diagnostic rates. The long-term impact of diagnosis on survival, growth, and development remains to be evaluated. Bioinformatics tools have limitations, as shown by the missed detection of maternal uniparental disomy in one case of a hypotonic infant with Prader-Willi syndrome, the researchers noted. Clinical judgment is still essential, they said.

DISCLOSURES:

The study was sponsored by a collaboration between the Israeli Ministry of Health, Illumina, and the Genomics Center at the Tel Aviv Sourasky Medical Center. Illumina provided reagents, bioinformatics tools, and editorial assistance. Study authors disclosed financial ties to Illumina.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article appeared on Medscape.com.

TOPLINE:

A national study in Israel demonstrates the feasibility and diagnostic benefits of rapid trio genome sequencing in critically ill neonates.

METHODOLOGY:

• Researchers conducted a prospective, multicenter cohort study from October 2021 to December 2022, involving all Israeli medical genetics institutes and neonatal intensive care units.
• A total of 130 critically ill neonates suspected of having a genetic disorder were enrolled, with rapid genome sequencing results expected within 10 days.

TAKEAWAY:

• Rapid trio genome sequencing diagnosed 50% of the neonates with disease-causing variants, including 12 chromosomal and 52 monogenic conditions.
• Another 11% had variants of unknown significance that were suspected to be disease-causing, and 1% had a novel gene suspected of causing disease.
• The mean turnaround time for the rapid reports was 7 days, demonstrating the feasibility of implementing rapid genome sequencing in a national healthcare setting, the researchers said.
• Genomic testing led to a change in clinical management for 22% of the neonates, which shows the clinical utility of this approach to diagnosis, they said.

IN PRACTICE:

Genetic testing may identify patients who are candidates for precision medical treatment and inform family planning, which is “critical for families with a severely affected or deceased child,” the study authors wrote.

SOURCE:

The corresponding author for the study was Daphna Marom, MD, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel. It was published online on February 22, 2024, in JAMA Network Open.

LIMITATIONS:

The study’s reliance on voluntary participation may have introduced referral bias, potentially affecting the diagnostic rates. The long-term impact of diagnosis on survival, growth, and development remains to be evaluated. Bioinformatics tools have limitations, as shown by the missed detection of maternal uniparental disomy in one case of a hypotonic infant with Prader-Willi syndrome, the researchers noted. Clinical judgment is still essential, they said.

DISCLOSURES:

The study was sponsored by a collaboration between the Israeli Ministry of Health, Illumina, and the Genomics Center at the Tel Aviv Sourasky Medical Center. Illumina provided reagents, bioinformatics tools, and editorial assistance. Study authors disclosed financial ties to Illumina.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article appeared on Medscape.com.

TOPLINE:

A national study in Israel demonstrates the feasibility and diagnostic benefits of rapid trio genome sequencing in critically ill neonates.

METHODOLOGY:

• Researchers conducted a prospective, multicenter cohort study from October 2021 to December 2022, involving all Israeli medical genetics institutes and neonatal intensive care units.
• A total of 130 critically ill neonates suspected of having a genetic disorder were enrolled, with rapid genome sequencing results expected within 10 days.

TAKEAWAY:

• Rapid trio genome sequencing diagnosed 50% of the neonates with disease-causing variants, including 12 chromosomal and 52 monogenic conditions.
• Another 11% had variants of unknown significance that were suspected to be disease-causing, and 1% had a novel gene suspected of causing disease.
• The mean turnaround time for the rapid reports was 7 days, demonstrating the feasibility of implementing rapid genome sequencing in a national healthcare setting, the researchers said.
• Genomic testing led to a change in clinical management for 22% of the neonates, which shows the clinical utility of this approach to diagnosis, they said.

IN PRACTICE:

Genetic testing may identify patients who are candidates for precision medical treatment and inform family planning, which is “critical for families with a severely affected or deceased child,” the study authors wrote.

SOURCE:

The corresponding author for the study was Daphna Marom, MD, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel. It was published online on February 22, 2024, in JAMA Network Open.

LIMITATIONS:

The study’s reliance on voluntary participation may have introduced referral bias, potentially affecting the diagnostic rates. The long-term impact of diagnosis on survival, growth, and development remains to be evaluated. Bioinformatics tools have limitations, as shown by the missed detection of maternal uniparental disomy in one case of a hypotonic infant with Prader-Willi syndrome, the researchers noted. Clinical judgment is still essential, they said.

DISCLOSURES:

The study was sponsored by a collaboration between the Israeli Ministry of Health, Illumina, and the Genomics Center at the Tel Aviv Sourasky Medical Center. Illumina provided reagents, bioinformatics tools, and editorial assistance. Study authors disclosed financial ties to Illumina.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article appeared on Medscape.com.

Patients with Cushing disease have an increased risk for new-onset autoimmune disease in the 3 years after surgical remission, according to a new retrospective study published on February 20 in Annals of Internal Medicine.

Outcomes for patients with Cushing disease were compared against those with nonfunctioning pituitary adenomas (NFPAs). New-onset autoimmune disease occurred in 10.4% with Cushing disease and 1.6% among patients with NFPA (hazard ratio, 7.80; 95% CI, 2.88-21.10).

“Understanding and recognizing new and recurrent autoimmune disease in this setting is important to avoid misclassifying such patients with glucocorticoid withdrawal syndrome, which could result in failure to treat underlying autoimmune disease, as well as erroneous diagnosis of steroid withdrawal cases,” wrote Dennis Delasi Nyanyo of Massachusetts General Hospital and Harvard Medical School, Boston, and colleagues.

Given the general population’s annual incidence of major autoimmune diseases, estimated at about 100 cases per 100,000 people, and the 3-year incidence of 10.4% found in this study’s cohort, “our findings suggest that Cushing disease remission may trigger development of autoimmune disease,” the authors wrote.
 

Monitor Patients With Family History of Autoimmune Disease?

The study results were not necessarily surprising to Anthony P. Heaney, MD, PhD, an endocrinologist and professor of medicine at the University of California, Los Angeles, because past research has raised similar questions. The authors’ suggestion that the rapid postsurgical drop in cortisol that occurs as a result of treating Cushing disease becomes some sort of autoimmune trigger is interesting but remains speculative, Dr. Heaney pointed out.

If future evidence supports that possibility, “it would suggest, in terms of managing those patients in the postoperative setting, that there may be some merit to giving them higher concentrations of glucocorticoids for a short period of time,” Dr. Heaney said, thereby bringing their levels down more gradually rather than taking them off a cliff, in a sense. Or, if more evidence bears out the authors’ hypothesis, another approach might be treating patients with medicine to bring down the cortisol before surgery, though there are challenges to that approach, Dr. Heaney said.

At the same time, those who developed new autoimmune disease remain a small subset of patients with Cushing disease, so such approaches may become only potentially appropriate to consider in patients with risk factors, such as a family history of autoimmune disease.

The researchers conducted a retrospective chart review of adult patients who underwent transsphenoidal surgery for either Cushing disease or NFPA at Massachusetts General Hospital between 2005 and 2019.

The study involved 194 patients with Cushing disease who had postsurgical remission and at least one follow-up visit with a pituitary expert and 92 patients with NFPA who were matched to patients with Cushing disease based on age and sex. The authors regarded autoimmune disease diagnosed within 36 months of the surgery to be temporally associated with Cushing disease remission. Among the autoimmune diseases considered were “rheumatoid arthritis, Sjögren syndrome, systemic lupus erythematosus, autoimmune thyroiditis, celiac disease, psoriasis, vitiligo, autoimmune neuropathy, multiple sclerosis, myasthenia gravis, and ulcerative colitis.”

Patients differed in average body mass index and tumor size, but family history of autoimmune disease was similar in both groups. Average BMI was 34.5 in the Cushing group and 29.5 in the NFPA group. Average tumor size was 5.7 mm in the Cushing group and 21.3 mm in the NFPA group.

Before surgery, 2.9% of patients with Cushing disease and 15.4% of patients with NFPA had central hypothyroidism, and 8% in the Cushing group and 56.8% in the NFPA group had hyperprolactinemia. Central adrenal insufficiency occurred in 11% with NFPA and in all with Cushing disease, by definition.

After surgery, 93.8% in the Cushing group and 16.5% in the NFPA group had adrenal insufficiency. In addition, patients with Cushing disease had lower postsurgical nadir serum cortisol levels (63.8 nmol/L) than those with NFPA (282.3 nmol/L).

Of the 17 patients with Cushing disease — all women — who developed autoimmune disease within 3 years, 6 had a personal history of autoimmune disease and 7 had a family history of it. In addition, 41.2% of them had adrenal insufficiency when they developed the new autoimmune disease. Among the diseases were six autoimmune thyroiditis cases, three Sjögren syndrome cases, and two autoimmune seronegative spondyloarthropathy.

Dr. Heaney said he found it interesting that more than half of the new autoimmune diseases in patients with Cushing disease were related to the thyroid. “In this kind of setting, where you have a patient who has been producing too much steroid over a period of time and then you take that away, it’s almost like you release a brake on the TSH [thyroid-stimulating hormone],” Dr. Heaney said. “So, there’s probably some rebound in TSH that occurs, and that could be driving the thyroiditis, to some extent, that we see in these patients.”

Only one patient with NFPA developed new-onset autoimmune disease, a woman who developed Graves disease 22 months after surgery. When the researchers excluded patients in both groups with central hypothyroidism, new-onset autoimmune disease was still significantly higher (11.4%) in the Cushing group than in the NFPA group (1.9%; HR, 7.02; 95% CI, 2.54-19.39).
 

Could Postoperative Adrenal Insufficiency Contribute to Risk?

Within the Cushing cohort, those who developed autoimmune disease had a lower BMI (31.8 vs 34.8) and larger tumor size (7.2 vs 5.6 mm) than those who didn’t develop new autoimmune disease. Patients who developed autoimmune disease also had a lower baseline urine free cortisol ratio (2.7 vs 6.3) before surgery and more family history of autoimmune disease (41.2% vs 20.9%) than those who didn’t develop one.

“The higher prevalence of adrenal insufficiency and the lower nadir serum cortisol levels in the Cushing disease group suggest that the postoperative adrenal insufficiency in the Cushing disease group might have contributed to autoimmune disease pathogenesis,” the authors wrote. “This finding is clinically significant because cortisol plays a pivotal role in modulating the immune system.”

Most postoperative management among patients with Cushing disease was similar, with all but one patient receiving 0.5 or 1 mg daily dexamethasone within the first week after surgery. (The one outlier received 5 mg daily prednisone.) However, fewer patients who developed autoimmune disease (17.6%) received supraphysiologic doses of glucocorticoid — equivalent to at least 25 mg hydrocortisone — compared with patients who didn’t develop autoimmune disease (41.8%).

“Although the daily average hydrocortisone equivalent replacement doses within the first month and during long-term follow-up were within the physiologic range in both subgroups, patients with Cushing disease who had autoimmune disease received slightly lower doses of glucocorticoid replacement within the first month after surgery,” the authors reported. “The immediate postoperative period might be a critical window where supraphysiologic glucocorticoids seem to be protective with regard to development of autoimmune disease,” they wrote, though they acknowledged the study’s retrospective design as a limitation in drawing that conclusion.

At the least, they suggested that new symptoms in patients with Cushing disease, particularly those with a family history of autoimmune disease, should prompt investigation of potential autoimmune disease.

Recordati Rare Diseases funded the study. The research was also conducted with support from Harvard Catalyst (the Harvard Clinical and Translational Science Center) as well as financial contributions from Harvard University and its affiliated academic healthcare centers. One author reported holding stocks in Pfizer and Amgen, and another reported receiving consulting fees from Corcept. Dr. Heaney reported receiving institutional grants for trials from Corcept, Ascendis, Crinetics, and Sparrow Pharm; serving on the advisory board for Xeris, Recordati, Corcept, Novo Nordisk, Lundbeck, and Crinetics; and serving as a speaker for Chiesi, Novo Nordisk, and Corcept.
 

A version of this article appeared on Medscape.com.

Patients with Cushing disease have an increased risk for new-onset autoimmune disease in the 3 years after surgical remission, according to a new retrospective study published on February 20 in Annals of Internal Medicine.

Outcomes for patients with Cushing disease were compared against those with nonfunctioning pituitary adenomas (NFPAs). New-onset autoimmune disease occurred in 10.4% with Cushing disease and 1.6% among patients with NFPA (hazard ratio, 7.80; 95% CI, 2.88-21.10).

“Understanding and recognizing new and recurrent autoimmune disease in this setting is important to avoid misclassifying such patients with glucocorticoid withdrawal syndrome, which could result in failure to treat underlying autoimmune disease, as well as erroneous diagnosis of steroid withdrawal cases,” wrote Dennis Delasi Nyanyo of Massachusetts General Hospital and Harvard Medical School, Boston, and colleagues.

Given the general population’s annual incidence of major autoimmune diseases, estimated at about 100 cases per 100,000 people, and the 3-year incidence of 10.4% found in this study’s cohort, “our findings suggest that Cushing disease remission may trigger development of autoimmune disease,” the authors wrote.
 

Monitor Patients With Family History of Autoimmune Disease?

The study results were not necessarily surprising to Anthony P. Heaney, MD, PhD, an endocrinologist and professor of medicine at the University of California, Los Angeles, because past research has raised similar questions. The authors’ suggestion that the rapid postsurgical drop in cortisol that occurs as a result of treating Cushing disease becomes some sort of autoimmune trigger is interesting but remains speculative, Dr. Heaney pointed out.

If future evidence supports that possibility, “it would suggest, in terms of managing those patients in the postoperative setting, that there may be some merit to giving them higher concentrations of glucocorticoids for a short period of time,” Dr. Heaney said, thereby bringing their levels down more gradually rather than taking them off a cliff, in a sense. Or, if more evidence bears out the authors’ hypothesis, another approach might be treating patients with medicine to bring down the cortisol before surgery, though there are challenges to that approach, Dr. Heaney said.

At the same time, those who developed new autoimmune disease remain a small subset of patients with Cushing disease, so such approaches may become only potentially appropriate to consider in patients with risk factors, such as a family history of autoimmune disease.

The researchers conducted a retrospective chart review of adult patients who underwent transsphenoidal surgery for either Cushing disease or NFPA at Massachusetts General Hospital between 2005 and 2019.

The study involved 194 patients with Cushing disease who had postsurgical remission and at least one follow-up visit with a pituitary expert and 92 patients with NFPA who were matched to patients with Cushing disease based on age and sex. The authors regarded autoimmune disease diagnosed within 36 months of the surgery to be temporally associated with Cushing disease remission. Among the autoimmune diseases considered were “rheumatoid arthritis, Sjögren syndrome, systemic lupus erythematosus, autoimmune thyroiditis, celiac disease, psoriasis, vitiligo, autoimmune neuropathy, multiple sclerosis, myasthenia gravis, and ulcerative colitis.”

Patients differed in average body mass index and tumor size, but family history of autoimmune disease was similar in both groups. Average BMI was 34.5 in the Cushing group and 29.5 in the NFPA group. Average tumor size was 5.7 mm in the Cushing group and 21.3 mm in the NFPA group.

Before surgery, 2.9% of patients with Cushing disease and 15.4% of patients with NFPA had central hypothyroidism, and 8% in the Cushing group and 56.8% in the NFPA group had hyperprolactinemia. Central adrenal insufficiency occurred in 11% with NFPA and in all with Cushing disease, by definition.

After surgery, 93.8% in the Cushing group and 16.5% in the NFPA group had adrenal insufficiency. In addition, patients with Cushing disease had lower postsurgical nadir serum cortisol levels (63.8 nmol/L) than those with NFPA (282.3 nmol/L).

Of the 17 patients with Cushing disease — all women — who developed autoimmune disease within 3 years, 6 had a personal history of autoimmune disease and 7 had a family history of it. In addition, 41.2% of them had adrenal insufficiency when they developed the new autoimmune disease. Among the diseases were six autoimmune thyroiditis cases, three Sjögren syndrome cases, and two autoimmune seronegative spondyloarthropathy.

Dr. Heaney said he found it interesting that more than half of the new autoimmune diseases in patients with Cushing disease were related to the thyroid. “In this kind of setting, where you have a patient who has been producing too much steroid over a period of time and then you take that away, it’s almost like you release a brake on the TSH [thyroid-stimulating hormone],” Dr. Heaney said. “So, there’s probably some rebound in TSH that occurs, and that could be driving the thyroiditis, to some extent, that we see in these patients.”

Only one patient with NFPA developed new-onset autoimmune disease, a woman who developed Graves disease 22 months after surgery. When the researchers excluded patients in both groups with central hypothyroidism, new-onset autoimmune disease was still significantly higher (11.4%) in the Cushing group than in the NFPA group (1.9%; HR, 7.02; 95% CI, 2.54-19.39).
 

Could Postoperative Adrenal Insufficiency Contribute to Risk?

Within the Cushing cohort, those who developed autoimmune disease had a lower BMI (31.8 vs 34.8) and larger tumor size (7.2 vs 5.6 mm) than those who didn’t develop new autoimmune disease. Patients who developed autoimmune disease also had a lower baseline urine free cortisol ratio (2.7 vs 6.3) before surgery and more family history of autoimmune disease (41.2% vs 20.9%) than those who didn’t develop one.

“The higher prevalence of adrenal insufficiency and the lower nadir serum cortisol levels in the Cushing disease group suggest that the postoperative adrenal insufficiency in the Cushing disease group might have contributed to autoimmune disease pathogenesis,” the authors wrote. “This finding is clinically significant because cortisol plays a pivotal role in modulating the immune system.”

Most postoperative management among patients with Cushing disease was similar, with all but one patient receiving 0.5 or 1 mg daily dexamethasone within the first week after surgery. (The one outlier received 5 mg daily prednisone.) However, fewer patients who developed autoimmune disease (17.6%) received supraphysiologic doses of glucocorticoid — equivalent to at least 25 mg hydrocortisone — compared with patients who didn’t develop autoimmune disease (41.8%).

“Although the daily average hydrocortisone equivalent replacement doses within the first month and during long-term follow-up were within the physiologic range in both subgroups, patients with Cushing disease who had autoimmune disease received slightly lower doses of glucocorticoid replacement within the first month after surgery,” the authors reported. “The immediate postoperative period might be a critical window where supraphysiologic glucocorticoids seem to be protective with regard to development of autoimmune disease,” they wrote, though they acknowledged the study’s retrospective design as a limitation in drawing that conclusion.

At the least, they suggested that new symptoms in patients with Cushing disease, particularly those with a family history of autoimmune disease, should prompt investigation of potential autoimmune disease.

Recordati Rare Diseases funded the study. The research was also conducted with support from Harvard Catalyst (the Harvard Clinical and Translational Science Center) as well as financial contributions from Harvard University and its affiliated academic healthcare centers. One author reported holding stocks in Pfizer and Amgen, and another reported receiving consulting fees from Corcept. Dr. Heaney reported receiving institutional grants for trials from Corcept, Ascendis, Crinetics, and Sparrow Pharm; serving on the advisory board for Xeris, Recordati, Corcept, Novo Nordisk, Lundbeck, and Crinetics; and serving as a speaker for Chiesi, Novo Nordisk, and Corcept.
 

A version of this article appeared on Medscape.com.

Patients with Cushing disease have an increased risk for new-onset autoimmune disease in the 3 years after surgical remission, according to a new retrospective study published on February 20 in Annals of Internal Medicine.

Outcomes for patients with Cushing disease were compared against those with nonfunctioning pituitary adenomas (NFPAs). New-onset autoimmune disease occurred in 10.4% with Cushing disease and 1.6% among patients with NFPA (hazard ratio, 7.80; 95% CI, 2.88-21.10).

“Understanding and recognizing new and recurrent autoimmune disease in this setting is important to avoid misclassifying such patients with glucocorticoid withdrawal syndrome, which could result in failure to treat underlying autoimmune disease, as well as erroneous diagnosis of steroid withdrawal cases,” wrote Dennis Delasi Nyanyo of Massachusetts General Hospital and Harvard Medical School, Boston, and colleagues.

Given the general population’s annual incidence of major autoimmune diseases, estimated at about 100 cases per 100,000 people, and the 3-year incidence of 10.4% found in this study’s cohort, “our findings suggest that Cushing disease remission may trigger development of autoimmune disease,” the authors wrote.
 

Monitor Patients With Family History of Autoimmune Disease?

The study results were not necessarily surprising to Anthony P. Heaney, MD, PhD, an endocrinologist and professor of medicine at the University of California, Los Angeles, because past research has raised similar questions. The authors’ suggestion that the rapid postsurgical drop in cortisol that occurs as a result of treating Cushing disease becomes some sort of autoimmune trigger is interesting but remains speculative, Dr. Heaney pointed out.

If future evidence supports that possibility, “it would suggest, in terms of managing those patients in the postoperative setting, that there may be some merit to giving them higher concentrations of glucocorticoids for a short period of time,” Dr. Heaney said, thereby bringing their levels down more gradually rather than taking them off a cliff, in a sense. Or, if more evidence bears out the authors’ hypothesis, another approach might be treating patients with medicine to bring down the cortisol before surgery, though there are challenges to that approach, Dr. Heaney said.

At the same time, those who developed new autoimmune disease remain a small subset of patients with Cushing disease, so such approaches may become only potentially appropriate to consider in patients with risk factors, such as a family history of autoimmune disease.

The researchers conducted a retrospective chart review of adult patients who underwent transsphenoidal surgery for either Cushing disease or NFPA at Massachusetts General Hospital between 2005 and 2019.

The study involved 194 patients with Cushing disease who had postsurgical remission and at least one follow-up visit with a pituitary expert and 92 patients with NFPA who were matched to patients with Cushing disease based on age and sex. The authors regarded autoimmune disease diagnosed within 36 months of the surgery to be temporally associated with Cushing disease remission. Among the autoimmune diseases considered were “rheumatoid arthritis, Sjögren syndrome, systemic lupus erythematosus, autoimmune thyroiditis, celiac disease, psoriasis, vitiligo, autoimmune neuropathy, multiple sclerosis, myasthenia gravis, and ulcerative colitis.”

Patients differed in average body mass index and tumor size, but family history of autoimmune disease was similar in both groups. Average BMI was 34.5 in the Cushing group and 29.5 in the NFPA group. Average tumor size was 5.7 mm in the Cushing group and 21.3 mm in the NFPA group.

Before surgery, 2.9% of patients with Cushing disease and 15.4% of patients with NFPA had central hypothyroidism, and 8% in the Cushing group and 56.8% in the NFPA group had hyperprolactinemia. Central adrenal insufficiency occurred in 11% with NFPA and in all with Cushing disease, by definition.

After surgery, 93.8% in the Cushing group and 16.5% in the NFPA group had adrenal insufficiency. In addition, patients with Cushing disease had lower postsurgical nadir serum cortisol levels (63.8 nmol/L) than those with NFPA (282.3 nmol/L).

Of the 17 patients with Cushing disease — all women — who developed autoimmune disease within 3 years, 6 had a personal history of autoimmune disease and 7 had a family history of it. In addition, 41.2% of them had adrenal insufficiency when they developed the new autoimmune disease. Among the diseases were six autoimmune thyroiditis cases, three Sjögren syndrome cases, and two autoimmune seronegative spondyloarthropathy.

Dr. Heaney said he found it interesting that more than half of the new autoimmune diseases in patients with Cushing disease were related to the thyroid. “In this kind of setting, where you have a patient who has been producing too much steroid over a period of time and then you take that away, it’s almost like you release a brake on the TSH [thyroid-stimulating hormone],” Dr. Heaney said. “So, there’s probably some rebound in TSH that occurs, and that could be driving the thyroiditis, to some extent, that we see in these patients.”

Only one patient with NFPA developed new-onset autoimmune disease, a woman who developed Graves disease 22 months after surgery. When the researchers excluded patients in both groups with central hypothyroidism, new-onset autoimmune disease was still significantly higher (11.4%) in the Cushing group than in the NFPA group (1.9%; HR, 7.02; 95% CI, 2.54-19.39).
 

Could Postoperative Adrenal Insufficiency Contribute to Risk?

Within the Cushing cohort, those who developed autoimmune disease had a lower BMI (31.8 vs 34.8) and larger tumor size (7.2 vs 5.6 mm) than those who didn’t develop new autoimmune disease. Patients who developed autoimmune disease also had a lower baseline urine free cortisol ratio (2.7 vs 6.3) before surgery and more family history of autoimmune disease (41.2% vs 20.9%) than those who didn’t develop one.

“The higher prevalence of adrenal insufficiency and the lower nadir serum cortisol levels in the Cushing disease group suggest that the postoperative adrenal insufficiency in the Cushing disease group might have contributed to autoimmune disease pathogenesis,” the authors wrote. “This finding is clinically significant because cortisol plays a pivotal role in modulating the immune system.”

Most postoperative management among patients with Cushing disease was similar, with all but one patient receiving 0.5 or 1 mg daily dexamethasone within the first week after surgery. (The one outlier received 5 mg daily prednisone.) However, fewer patients who developed autoimmune disease (17.6%) received supraphysiologic doses of glucocorticoid — equivalent to at least 25 mg hydrocortisone — compared with patients who didn’t develop autoimmune disease (41.8%).

“Although the daily average hydrocortisone equivalent replacement doses within the first month and during long-term follow-up were within the physiologic range in both subgroups, patients with Cushing disease who had autoimmune disease received slightly lower doses of glucocorticoid replacement within the first month after surgery,” the authors reported. “The immediate postoperative period might be a critical window where supraphysiologic glucocorticoids seem to be protective with regard to development of autoimmune disease,” they wrote, though they acknowledged the study’s retrospective design as a limitation in drawing that conclusion.

At the least, they suggested that new symptoms in patients with Cushing disease, particularly those with a family history of autoimmune disease, should prompt investigation of potential autoimmune disease.

Recordati Rare Diseases funded the study. The research was also conducted with support from Harvard Catalyst (the Harvard Clinical and Translational Science Center) as well as financial contributions from Harvard University and its affiliated academic healthcare centers. One author reported holding stocks in Pfizer and Amgen, and another reported receiving consulting fees from Corcept. Dr. Heaney reported receiving institutional grants for trials from Corcept, Ascendis, Crinetics, and Sparrow Pharm; serving on the advisory board for Xeris, Recordati, Corcept, Novo Nordisk, Lundbeck, and Crinetics; and serving as a speaker for Chiesi, Novo Nordisk, and Corcept.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Selenium supplementation is associated with improvements in key thyroid measures in patients with Hashimoto thyroiditis who are not treated with thyroid hormone replacement therapy, research from a new meta-analysis showed.

METHODOLOGY:

• For the systematic review and meta-analysis, 35 randomized controlled trials were identified that included evaluation of selenium supplementation’s effects on thyroid function.
• The studies focused on a variety of key thyroid function measures, including thyroid-stimulating hormone (TSH), free and total thyroxine (fT4, T4), free and total triiodothyronine (fT3, T3), thyroid antibodies, safety, and other factors.
• Stratified analyses were conducted to evaluate key factors including the dose and duration of selenium supplementation; patients’ thyroid status, age, gender, treatment with hormone replacement, and selenium status, such as deficiency or sufficiency; and other factors.
• While patients’ selenium levels at baseline were reported in only about half of the studies, among those that did have the data, the vast majority — 89% of cohorts — were selenium deficient.
• The study populations ranged from 31 to 364 and included children, adolescents, and adults.

TAKEAWAY:

• The analysis showed selenium supplementation to be significantly associated with decreased TSH in patients who were not treated with thyroid hormone replacement therapy (standardized mean difference [SMD], −0.21 in seven cohorts, involving 869 participants).
• Improvements associated with selenium replacement were also observed regardless of whether patients were on thyroid hormone replacement therapy in terms of decreases in thyroid peroxidase antibodies (TPOAb) (SMD, −0.96 in 29 cohorts, involving 2358 participants) and malondialdehyde (SMD, −1.16 in three cohorts, involving 248 participants).
• Overall, selenium supplementation had no significant effects on other notable thyroid measures, including fT4, T4, fT3, T3, thyroglobulin antibody (TGAb), thyroid volume, interleukin 2, or interleukin 10. However, when the analysis only included adults aged 18 and older, the selenium supplementation was linked to reductions in TSH and TPOAb, as well as increases in fT4 levels.
• Importantly, no significant differences were observed in terms of adverse effects between the studies’ intervention and control groups at selenium supplementation doses ranging from 80 to 400 μg/d for up to 12 months (odds ratio, 0.89 in 16 cohorts, involving 1339 participants).
• The authors determined that the certainty of evidence, overall, was moderate.

IN PRACTICE:

The results regarding effects of selenium on TSH “add to the existing knowledge in this field by demonstrating an effect of selenium supplementation on lowering TSH levels exclusively in Hashimoto thyroiditis patients without thyroid hormone replacement therapy,” the authors wrote. Furthermore, “our study reaffirmed the results of six prior meta-analyses reporting an effect of selenium in reducing TPOAb levels,” they added. “The inclusion of 31 cohorts enhanced statistical power compared to the previous meta-analyses, which included a maximum of nine cohorts.” “Our study suggests that selenium supplementation is safe and holds potential as a disease-modifying factor for Hashimoto thyroiditis–associated hypothyroidism,” the authors reported. “Further research is needed to confirm its efficacy, fully understand its mechanism of action, and elucidate its cost-effectiveness.”

SOURCE:

The study’s first author was Valentina V. Huwiler, MSc, of the Department of Diabetes, Endocrinology, Nutritional Medicine and Metabolism, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland. The study was published in Thyroid.

LIMITATIONS:

Due to variations in assays used in the different studies for measures including TPOAb and TGAb, the authors used SMD instead of the mean difference typically recommended when varying assays are used; however, only the effect size can be interpreted and not the clinical significance, the authors noted. Serum selenium concentrations may vary based on the analytical technique. Data on participants’ dietary habits and compliance with study regimens were not available.

DISCLOSURES:

The authors had no disclosures to report.

A version of this article appeared on Medscape.com.

TOPLINE:

Selenium supplementation is associated with improvements in key thyroid measures in patients with Hashimoto thyroiditis who are not treated with thyroid hormone replacement therapy, research from a new meta-analysis showed.

METHODOLOGY:

• For the systematic review and meta-analysis, 35 randomized controlled trials were identified that included evaluation of selenium supplementation’s effects on thyroid function.
• The studies focused on a variety of key thyroid function measures, including thyroid-stimulating hormone (TSH), free and total thyroxine (fT4, T4), free and total triiodothyronine (fT3, T3), thyroid antibodies, safety, and other factors.
• Stratified analyses were conducted to evaluate key factors including the dose and duration of selenium supplementation; patients’ thyroid status, age, gender, treatment with hormone replacement, and selenium status, such as deficiency or sufficiency; and other factors.
• While patients’ selenium levels at baseline were reported in only about half of the studies, among those that did have the data, the vast majority — 89% of cohorts — were selenium deficient.
• The study populations ranged from 31 to 364 and included children, adolescents, and adults.

TAKEAWAY:

• The analysis showed selenium supplementation to be significantly associated with decreased TSH in patients who were not treated with thyroid hormone replacement therapy (standardized mean difference [SMD], −0.21 in seven cohorts, involving 869 participants).
• Improvements associated with selenium replacement were also observed regardless of whether patients were on thyroid hormone replacement therapy in terms of decreases in thyroid peroxidase antibodies (TPOAb) (SMD, −0.96 in 29 cohorts, involving 2358 participants) and malondialdehyde (SMD, −1.16 in three cohorts, involving 248 participants).
• Overall, selenium supplementation had no significant effects on other notable thyroid measures, including fT4, T4, fT3, T3, thyroglobulin antibody (TGAb), thyroid volume, interleukin 2, or interleukin 10. However, when the analysis only included adults aged 18 and older, the selenium supplementation was linked to reductions in TSH and TPOAb, as well as increases in fT4 levels.
• Importantly, no significant differences were observed in terms of adverse effects between the studies’ intervention and control groups at selenium supplementation doses ranging from 80 to 400 μg/d for up to 12 months (odds ratio, 0.89 in 16 cohorts, involving 1339 participants).
• The authors determined that the certainty of evidence, overall, was moderate.

IN PRACTICE:

The results regarding effects of selenium on TSH “add to the existing knowledge in this field by demonstrating an effect of selenium supplementation on lowering TSH levels exclusively in Hashimoto thyroiditis patients without thyroid hormone replacement therapy,” the authors wrote. Furthermore, “our study reaffirmed the results of six prior meta-analyses reporting an effect of selenium in reducing TPOAb levels,” they added. “The inclusion of 31 cohorts enhanced statistical power compared to the previous meta-analyses, which included a maximum of nine cohorts.” “Our study suggests that selenium supplementation is safe and holds potential as a disease-modifying factor for Hashimoto thyroiditis–associated hypothyroidism,” the authors reported. “Further research is needed to confirm its efficacy, fully understand its mechanism of action, and elucidate its cost-effectiveness.”

SOURCE:

The study’s first author was Valentina V. Huwiler, MSc, of the Department of Diabetes, Endocrinology, Nutritional Medicine and Metabolism, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland. The study was published in Thyroid.

LIMITATIONS:

Due to variations in assays used in the different studies for measures including TPOAb and TGAb, the authors used SMD instead of the mean difference typically recommended when varying assays are used; however, only the effect size can be interpreted and not the clinical significance, the authors noted. Serum selenium concentrations may vary based on the analytical technique. Data on participants’ dietary habits and compliance with study regimens were not available.

DISCLOSURES:

The authors had no disclosures to report.

A version of this article appeared on Medscape.com.

TOPLINE:

Selenium supplementation is associated with improvements in key thyroid measures in patients with Hashimoto thyroiditis who are not treated with thyroid hormone replacement therapy, research from a new meta-analysis showed.

METHODOLOGY:

• For the systematic review and meta-analysis, 35 randomized controlled trials were identified that included evaluation of selenium supplementation’s effects on thyroid function.
• The studies focused on a variety of key thyroid function measures, including thyroid-stimulating hormone (TSH), free and total thyroxine (fT4, T4), free and total triiodothyronine (fT3, T3), thyroid antibodies, safety, and other factors.
• Stratified analyses were conducted to evaluate key factors including the dose and duration of selenium supplementation; patients’ thyroid status, age, gender, treatment with hormone replacement, and selenium status, such as deficiency or sufficiency; and other factors.
• While patients’ selenium levels at baseline were reported in only about half of the studies, among those that did have the data, the vast majority — 89% of cohorts — were selenium deficient.
• The study populations ranged from 31 to 364 and included children, adolescents, and adults.

TAKEAWAY:

• The analysis showed selenium supplementation to be significantly associated with decreased TSH in patients who were not treated with thyroid hormone replacement therapy (standardized mean difference [SMD], −0.21 in seven cohorts, involving 869 participants).
• Improvements associated with selenium replacement were also observed regardless of whether patients were on thyroid hormone replacement therapy in terms of decreases in thyroid peroxidase antibodies (TPOAb) (SMD, −0.96 in 29 cohorts, involving 2358 participants) and malondialdehyde (SMD, −1.16 in three cohorts, involving 248 participants).
• Overall, selenium supplementation had no significant effects on other notable thyroid measures, including fT4, T4, fT3, T3, thyroglobulin antibody (TGAb), thyroid volume, interleukin 2, or interleukin 10. However, when the analysis only included adults aged 18 and older, the selenium supplementation was linked to reductions in TSH and TPOAb, as well as increases in fT4 levels.
• Importantly, no significant differences were observed in terms of adverse effects between the studies’ intervention and control groups at selenium supplementation doses ranging from 80 to 400 μg/d for up to 12 months (odds ratio, 0.89 in 16 cohorts, involving 1339 participants).
• The authors determined that the certainty of evidence, overall, was moderate.

IN PRACTICE:

The results regarding effects of selenium on TSH “add to the existing knowledge in this field by demonstrating an effect of selenium supplementation on lowering TSH levels exclusively in Hashimoto thyroiditis patients without thyroid hormone replacement therapy,” the authors wrote. Furthermore, “our study reaffirmed the results of six prior meta-analyses reporting an effect of selenium in reducing TPOAb levels,” they added. “The inclusion of 31 cohorts enhanced statistical power compared to the previous meta-analyses, which included a maximum of nine cohorts.” “Our study suggests that selenium supplementation is safe and holds potential as a disease-modifying factor for Hashimoto thyroiditis–associated hypothyroidism,” the authors reported. “Further research is needed to confirm its efficacy, fully understand its mechanism of action, and elucidate its cost-effectiveness.”

SOURCE:

The study’s first author was Valentina V. Huwiler, MSc, of the Department of Diabetes, Endocrinology, Nutritional Medicine and Metabolism, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland. The study was published in Thyroid.

LIMITATIONS:

Due to variations in assays used in the different studies for measures including TPOAb and TGAb, the authors used SMD instead of the mean difference typically recommended when varying assays are used; however, only the effect size can be interpreted and not the clinical significance, the authors noted. Serum selenium concentrations may vary based on the analytical technique. Data on participants’ dietary habits and compliance with study regimens were not available.

DISCLOSURES:

The authors had no disclosures to report.

A version of this article appeared on Medscape.com.

Santé Publique France (SPF), the French national public health agency, has released the findings of the PEPS’PE study, which was launched in 2021. The study aims to prioritize, following extensive consultation, the health effects to be monitored for their potential link to endocrine disruptors (EDs). Out of 59 health effects suspected to be associated with exposure to EDs, 21 have been considered a priority for surveillance. Based on these results and others, SPF will expand the scope of the Agency’s surveillance by incorporating new pathologies.

As part of its environmental health program and the National Strategy on EDs, SPF has been conducting surveillance related to EDs targeting reproductive health since 2015. To incorporate new scientific knowledge, the PEPS’PE project aims to prioritize health effects related to EDs and identify health events to integrate into the agency’s current surveillance. The 59 health effects suspected to be associated with exposure to EDs were to be evaluated based on two criteria: The weight of evidence and the epidemiological and societal impact of the health effect. A diverse panel of international experts and French stakeholders in the field of EDs classified 21 health effects as a priority for surveillance.

Among these effects, six reproductive health effects are already monitored in the surveillance program: Cryptorchidism, hypospadias, early puberty, testicular cancer, alteration of sperm quality, and endometriosis. In addition, infertility and decreased fertility (which are not currently monitored for their link to EDs) have been included.

Metabolic effects (including overweight and obesity, cardiovascular diseases, type 2 diabetes, and metabolic syndrome), child neurodevelopmental disorders (including behavioral disorders, intellectual deficits, and attention-deficit disorders), cancers (including breast cancer, prostate cancer, lymphomas, and leukemias in children), and asthma have also been highlighted.

Furthermore, 22 effects were considered low priorities or deemed nonpriorities when, for example, they presented weak or moderate evidence with varying levels of interest in implementing surveillance. Finally, 16 health effects could not be prioritized because of a lack of scientific experts on these topics and a failure to achieve consensus (eg, bone disorders, adrenal disorders, and skin and eye disorders). Consensus was sought during this consultation using a Delphi method.

“These results indicate the need to expand the scope of the Agency’s surveillance beyond reproductive health, incorporating new pathologies when surveillance data are available,” SPF declared in a press release.

“With the initial decision elements obtained through this study, Santé Publique France will analyze the feasibility of implementing surveillance for effects classified as priorities.”
 

This article was translated from the Medscape French edition. A version of this article appeared on Medscape.com.

Santé Publique France (SPF), the French national public health agency, has released the findings of the PEPS’PE study, which was launched in 2021. The study aims to prioritize, following extensive consultation, the health effects to be monitored for their potential link to endocrine disruptors (EDs). Out of 59 health effects suspected to be associated with exposure to EDs, 21 have been considered a priority for surveillance. Based on these results and others, SPF will expand the scope of the Agency’s surveillance by incorporating new pathologies.

As part of its environmental health program and the National Strategy on EDs, SPF has been conducting surveillance related to EDs targeting reproductive health since 2015. To incorporate new scientific knowledge, the PEPS’PE project aims to prioritize health effects related to EDs and identify health events to integrate into the agency’s current surveillance. The 59 health effects suspected to be associated with exposure to EDs were to be evaluated based on two criteria: The weight of evidence and the epidemiological and societal impact of the health effect. A diverse panel of international experts and French stakeholders in the field of EDs classified 21 health effects as a priority for surveillance.

Among these effects, six reproductive health effects are already monitored in the surveillance program: Cryptorchidism, hypospadias, early puberty, testicular cancer, alteration of sperm quality, and endometriosis. In addition, infertility and decreased fertility (which are not currently monitored for their link to EDs) have been included.

Metabolic effects (including overweight and obesity, cardiovascular diseases, type 2 diabetes, and metabolic syndrome), child neurodevelopmental disorders (including behavioral disorders, intellectual deficits, and attention-deficit disorders), cancers (including breast cancer, prostate cancer, lymphomas, and leukemias in children), and asthma have also been highlighted.

Furthermore, 22 effects were considered low priorities or deemed nonpriorities when, for example, they presented weak or moderate evidence with varying levels of interest in implementing surveillance. Finally, 16 health effects could not be prioritized because of a lack of scientific experts on these topics and a failure to achieve consensus (eg, bone disorders, adrenal disorders, and skin and eye disorders). Consensus was sought during this consultation using a Delphi method.

“These results indicate the need to expand the scope of the Agency’s surveillance beyond reproductive health, incorporating new pathologies when surveillance data are available,” SPF declared in a press release.

“With the initial decision elements obtained through this study, Santé Publique France will analyze the feasibility of implementing surveillance for effects classified as priorities.”
 

This article was translated from the Medscape French edition. A version of this article appeared on Medscape.com.

Santé Publique France (SPF), the French national public health agency, has released the findings of the PEPS’PE study, which was launched in 2021. The study aims to prioritize, following extensive consultation, the health effects to be monitored for their potential link to endocrine disruptors (EDs). Out of 59 health effects suspected to be associated with exposure to EDs, 21 have been considered a priority for surveillance. Based on these results and others, SPF will expand the scope of the Agency’s surveillance by incorporating new pathologies.

As part of its environmental health program and the National Strategy on EDs, SPF has been conducting surveillance related to EDs targeting reproductive health since 2015. To incorporate new scientific knowledge, the PEPS’PE project aims to prioritize health effects related to EDs and identify health events to integrate into the agency’s current surveillance. The 59 health effects suspected to be associated with exposure to EDs were to be evaluated based on two criteria: The weight of evidence and the epidemiological and societal impact of the health effect. A diverse panel of international experts and French stakeholders in the field of EDs classified 21 health effects as a priority for surveillance.

Among these effects, six reproductive health effects are already monitored in the surveillance program: Cryptorchidism, hypospadias, early puberty, testicular cancer, alteration of sperm quality, and endometriosis. In addition, infertility and decreased fertility (which are not currently monitored for their link to EDs) have been included.

Metabolic effects (including overweight and obesity, cardiovascular diseases, type 2 diabetes, and metabolic syndrome), child neurodevelopmental disorders (including behavioral disorders, intellectual deficits, and attention-deficit disorders), cancers (including breast cancer, prostate cancer, lymphomas, and leukemias in children), and asthma have also been highlighted.

Furthermore, 22 effects were considered low priorities or deemed nonpriorities when, for example, they presented weak or moderate evidence with varying levels of interest in implementing surveillance. Finally, 16 health effects could not be prioritized because of a lack of scientific experts on these topics and a failure to achieve consensus (eg, bone disorders, adrenal disorders, and skin and eye disorders). Consensus was sought during this consultation using a Delphi method.

“These results indicate the need to expand the scope of the Agency’s surveillance beyond reproductive health, incorporating new pathologies when surveillance data are available,” SPF declared in a press release.

“With the initial decision elements obtained through this study, Santé Publique France will analyze the feasibility of implementing surveillance for effects classified as priorities.”
 

This article was translated from the Medscape French edition. A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved a wearable belt device for postmenopausal women with osteopenia, the precursor to osteoporosis, according to the company’s manufacturer, Bone Health Technologies.

According to the company, the device (Osteoboost) is the first nonpharmacologic device-based, prescription-only treatment for postmenopausal women with low bone density. It has not been tested for ability to reduce fracture risk.

Bone Health Technologies

The device is worn around the hips and delivers calibrated mild vibrations to the hips and lumbar spine to help preserve bone strength and density. A vibration pack is mounted to the back of the belt.

FDA approval, announced on January 18, was based on the findings of a National Institutes of Health–funded double-blinded, sham-controlled study of 126 women with low bone density conducted at the University of Nebraska Medical Center in Omaha. The data were shared at the 2023 Endocrine Society and American Society for Bone and Mineral Research annual meetings and published in the Journal of the Endocrine Society.

Lead investigator Laura D. Bilek, PT, PhD, associate dean for research and associate professor at the University of Nebraska, and colleagues wrote that the primary outcome measurement was the change in vertebral strength measured by CT scans for women who used the device a minimum of three times per week compared with a sham group who wore a belt that emitted sound but had no vibrations.

Compressive strength and volumetric density of the first lumbar vertebra were analyzed.

In the active-belt group, women lost, on average, 0.48% bone strength, while those in the sham group lost nearly 2.84% (P = .014), about five times as much. Results also showed that participants in the active treatment group who used the device three times per week lost 0.29% bone mineral density (BMD) compared with the 1.97% BMD lost in the control group. No adverse events were reported in the study.

Sonali Khandelwal, MD, a rheumatologist at Rush University in Chicago, told this news organization there’s considerable fear among some patients about long-term use of available medications for bone health, “so any modality that is nontherapeutic — not a pill — is always exciting.”

The endpoints of the study are one good measure, she said, but she emphasized that it will be important to show that the improved bone density from the belt that is described in this study “is a true marker of decreased fracture risk.”

Because there are no apparent side effects, she said it may be effective in combination with weight-bearing exercise, vitamin D and calcium, and/or medication, depending on severity of bone loss.

Current medications on the market for osteoporosis have been shown to improve bone strength and reduce fracture risk, she noted.

“It could help; I just don’t think we have enough evidence that it will completely treat the bone loss,” Dr. Khandelwal said.

She said she sees the potential population most interested in the belt as premenopausal women with a family history of bone loss who may not meet the level of bone loss for medical management but are interested in prevention.

“I also think of individuals who might already meet medication needs but are completely averse to being on medication,” she said. The bulk of her practice is treating bone loss, she said, estimating that 20% of her patients do not want to be on medication.

Bone Health Technologies CEO Laura Yecies, MBA, told this news organization the company has not yet set the price for the device and noted that because it will be available by prescription only, out-of-pocket costs and copays will differ. She said the company expects to begin shipping later this year. Requests for update notifications can be made at the company’s website.

Dr. Bilek told this news organization the device was tested for a year, so it’s unclear how long people with osteopenia would need to wear the belt for maximum benefit.

The theory behind the mechanism of action, she said, “is that the vibration actually inhibits the cells [osteoclasts] that take away bone mass.”

The researchers included only postmenopausal women with osteopenia in the study, but Dr. Bilek said she would like to test the device on other groups, such as men with prostate cancer getting testosterone-blocking therapy, which can result in loss of bone density. An estimated 34 million people in the United States have osteopenia.

Dr. Bilek said a next step for the study is to enroll a more diverse cohort at an additional center to test the device because most of the women in this one were White.

She noted that women’s bone mass peaks at age 30 and then starts to decline.

“When women hit menopause, there’s a really rapid decline [in bone strength] for the next 5-7 years and then the decline levels off. If we can slow that decline, hopefully that woman’s bone density is maintained at a higher level throughout their life,” Dr. Bilek said.

Dr. Bilek is a scientific adviser to Bone Health Technologies. She and many coauthors of the study received grants or fees from the company and own stock in or are employees of the company. Ms. Yecies is the founder and CEO of Bone Health Technologies. Dr. Khandelwal had no relevant financial relationships.

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

The US Food and Drug Administration (FDA) has approved a wearable belt device for postmenopausal women with osteopenia, the precursor to osteoporosis, according to the company’s manufacturer, Bone Health Technologies.

According to the company, the device (Osteoboost) is the first nonpharmacologic device-based, prescription-only treatment for postmenopausal women with low bone density. It has not been tested for ability to reduce fracture risk.

Bone Health Technologies

The device is worn around the hips and delivers calibrated mild vibrations to the hips and lumbar spine to help preserve bone strength and density. A vibration pack is mounted to the back of the belt.

FDA approval, announced on January 18, was based on the findings of a National Institutes of Health–funded double-blinded, sham-controlled study of 126 women with low bone density conducted at the University of Nebraska Medical Center in Omaha. The data were shared at the 2023 Endocrine Society and American Society for Bone and Mineral Research annual meetings and published in the Journal of the Endocrine Society.

Lead investigator Laura D. Bilek, PT, PhD, associate dean for research and associate professor at the University of Nebraska, and colleagues wrote that the primary outcome measurement was the change in vertebral strength measured by CT scans for women who used the device a minimum of three times per week compared with a sham group who wore a belt that emitted sound but had no vibrations.

Compressive strength and volumetric density of the first lumbar vertebra were analyzed.

In the active-belt group, women lost, on average, 0.48% bone strength, while those in the sham group lost nearly 2.84% (P = .014), about five times as much. Results also showed that participants in the active treatment group who used the device three times per week lost 0.29% bone mineral density (BMD) compared with the 1.97% BMD lost in the control group. No adverse events were reported in the study.

Sonali Khandelwal, MD, a rheumatologist at Rush University in Chicago, told this news organization there’s considerable fear among some patients about long-term use of available medications for bone health, “so any modality that is nontherapeutic — not a pill — is always exciting.”

The endpoints of the study are one good measure, she said, but she emphasized that it will be important to show that the improved bone density from the belt that is described in this study “is a true marker of decreased fracture risk.”

Because there are no apparent side effects, she said it may be effective in combination with weight-bearing exercise, vitamin D and calcium, and/or medication, depending on severity of bone loss.

Current medications on the market for osteoporosis have been shown to improve bone strength and reduce fracture risk, she noted.

“It could help; I just don’t think we have enough evidence that it will completely treat the bone loss,” Dr. Khandelwal said.

She said she sees the potential population most interested in the belt as premenopausal women with a family history of bone loss who may not meet the level of bone loss for medical management but are interested in prevention.

“I also think of individuals who might already meet medication needs but are completely averse to being on medication,” she said. The bulk of her practice is treating bone loss, she said, estimating that 20% of her patients do not want to be on medication.

Bone Health Technologies CEO Laura Yecies, MBA, told this news organization the company has not yet set the price for the device and noted that because it will be available by prescription only, out-of-pocket costs and copays will differ. She said the company expects to begin shipping later this year. Requests for update notifications can be made at the company’s website.

Dr. Bilek told this news organization the device was tested for a year, so it’s unclear how long people with osteopenia would need to wear the belt for maximum benefit.

The theory behind the mechanism of action, she said, “is that the vibration actually inhibits the cells [osteoclasts] that take away bone mass.”

The researchers included only postmenopausal women with osteopenia in the study, but Dr. Bilek said she would like to test the device on other groups, such as men with prostate cancer getting testosterone-blocking therapy, which can result in loss of bone density. An estimated 34 million people in the United States have osteopenia.

Dr. Bilek said a next step for the study is to enroll a more diverse cohort at an additional center to test the device because most of the women in this one were White.

She noted that women’s bone mass peaks at age 30 and then starts to decline.

“When women hit menopause, there’s a really rapid decline [in bone strength] for the next 5-7 years and then the decline levels off. If we can slow that decline, hopefully that woman’s bone density is maintained at a higher level throughout their life,” Dr. Bilek said.

Dr. Bilek is a scientific adviser to Bone Health Technologies. She and many coauthors of the study received grants or fees from the company and own stock in or are employees of the company. Ms. Yecies is the founder and CEO of Bone Health Technologies. Dr. Khandelwal had no relevant financial relationships.

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

The US Food and Drug Administration (FDA) has approved a wearable belt device for postmenopausal women with osteopenia, the precursor to osteoporosis, according to the company’s manufacturer, Bone Health Technologies.

According to the company, the device (Osteoboost) is the first nonpharmacologic device-based, prescription-only treatment for postmenopausal women with low bone density. It has not been tested for ability to reduce fracture risk.

Bone Health Technologies

The device is worn around the hips and delivers calibrated mild vibrations to the hips and lumbar spine to help preserve bone strength and density. A vibration pack is mounted to the back of the belt.

FDA approval, announced on January 18, was based on the findings of a National Institutes of Health–funded double-blinded, sham-controlled study of 126 women with low bone density conducted at the University of Nebraska Medical Center in Omaha. The data were shared at the 2023 Endocrine Society and American Society for Bone and Mineral Research annual meetings and published in the Journal of the Endocrine Society.

Lead investigator Laura D. Bilek, PT, PhD, associate dean for research and associate professor at the University of Nebraska, and colleagues wrote that the primary outcome measurement was the change in vertebral strength measured by CT scans for women who used the device a minimum of three times per week compared with a sham group who wore a belt that emitted sound but had no vibrations.

Compressive strength and volumetric density of the first lumbar vertebra were analyzed.

In the active-belt group, women lost, on average, 0.48% bone strength, while those in the sham group lost nearly 2.84% (P = .014), about five times as much. Results also showed that participants in the active treatment group who used the device three times per week lost 0.29% bone mineral density (BMD) compared with the 1.97% BMD lost in the control group. No adverse events were reported in the study.

Sonali Khandelwal, MD, a rheumatologist at Rush University in Chicago, told this news organization there’s considerable fear among some patients about long-term use of available medications for bone health, “so any modality that is nontherapeutic — not a pill — is always exciting.”

The endpoints of the study are one good measure, she said, but she emphasized that it will be important to show that the improved bone density from the belt that is described in this study “is a true marker of decreased fracture risk.”

Because there are no apparent side effects, she said it may be effective in combination with weight-bearing exercise, vitamin D and calcium, and/or medication, depending on severity of bone loss.

Current medications on the market for osteoporosis have been shown to improve bone strength and reduce fracture risk, she noted.

“It could help; I just don’t think we have enough evidence that it will completely treat the bone loss,” Dr. Khandelwal said.

She said she sees the potential population most interested in the belt as premenopausal women with a family history of bone loss who may not meet the level of bone loss for medical management but are interested in prevention.

“I also think of individuals who might already meet medication needs but are completely averse to being on medication,” she said. The bulk of her practice is treating bone loss, she said, estimating that 20% of her patients do not want to be on medication.

Bone Health Technologies CEO Laura Yecies, MBA, told this news organization the company has not yet set the price for the device and noted that because it will be available by prescription only, out-of-pocket costs and copays will differ. She said the company expects to begin shipping later this year. Requests for update notifications can be made at the company’s website.

Dr. Bilek told this news organization the device was tested for a year, so it’s unclear how long people with osteopenia would need to wear the belt for maximum benefit.

The theory behind the mechanism of action, she said, “is that the vibration actually inhibits the cells [osteoclasts] that take away bone mass.”

The researchers included only postmenopausal women with osteopenia in the study, but Dr. Bilek said she would like to test the device on other groups, such as men with prostate cancer getting testosterone-blocking therapy, which can result in loss of bone density. An estimated 34 million people in the United States have osteopenia.

Dr. Bilek said a next step for the study is to enroll a more diverse cohort at an additional center to test the device because most of the women in this one were White.

She noted that women’s bone mass peaks at age 30 and then starts to decline.

“When women hit menopause, there’s a really rapid decline [in bone strength] for the next 5-7 years and then the decline levels off. If we can slow that decline, hopefully that woman’s bone density is maintained at a higher level throughout their life,” Dr. Bilek said.

Dr. Bilek is a scientific adviser to Bone Health Technologies. She and many coauthors of the study received grants or fees from the company and own stock in or are employees of the company. Ms. Yecies is the founder and CEO of Bone Health Technologies. Dr. Khandelwal had no relevant financial relationships.

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

The US Food and Drug Administration (FDA) has added a boxed warning to the label of the osteoporosis drug denosumab (Prolia) about increased risk for severe hypocalcemia in patients with advanced chronic kidney disease (CKD). 

Denosumab is a monoclonal antibody, indicated for the treatment of postmenopausal women with osteoporosis who are at increased risk for fracture for whom other treatments aren’t effective or can’t be tolerated. It’s also indicated to increase bone mass in men with osteoporosis at high risk for fracture, treat glucocorticoid-induced osteoporosis in men and women at high risk for fracture, increase bone mass in men at high risk for fracture receiving androgen-deprivation therapy for nonmetastatic prostate cancer, and increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer.

This new warning updates a November 2022 alert based on preliminary evidence for a “substantial risk” for hypocalcemia in patients with CKD on dialysis. 

Upon further examination of the data from two trials including more than 500,000 denosumab-treated women with CKD, the FDA concluded that severe hypocalcemia appears to be more common in those with CKD who also have mineral and bone disorder (CKD-MBD). And, for patients with advanced CKD taking denosumab, “severe hypocalcemia resulted in serious harm, including hospitalization, life-threatening events, and death.” 

Most of the severe hypocalcemia events occurred 2-10 weeks after denosumab injection, with the greatest risk during weeks 2-5.

The new warning advises healthcare professionals to assess patients’ kidney function before prescribing denosumab, and for those with advanced CKD, “consider the risk of severe hypocalcemia with Prolia in the context of other available treatments for osteoporosis.”

If the drug is still being considered for those patients for initial or continued use, calcium blood levels should be checked, and patients should be evaluated for CKD-MBD. Prior to prescribing denosumab in these patients, CKD-MBD should be properly managed, hypocalcemia corrected, and patients supplemented with calcium and activated vitamin D to decrease the risk for severe hypocalcemia and associated complications.

“Treatment with denosumab in patients with advanced CKD, including those on dialysis, and particularly patients with diagnosed CKD-MBD should involve a health care provider with expertise in the diagnosis and management of CKD-MBD,” the FDA advises. 

Once denosumab is administered, close monitoring of blood calcium levels and prompt hypocalcemia management is essential to prevent complications including seizures or arrythmias. Patients should be advised to promptly report symptoms that could be consistent with hypocalcemia, including confusion, seizures, irregular heartbeat, fainting, muscle spasms or weakness, face twitching, tingling, or numbness anywhere in the body. 

In 2022, an estimated 2.2 million Prolia prefilled syringes were sold by the manufacturer to US healthcare settings.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has added a boxed warning to the label of the osteoporosis drug denosumab (Prolia) about increased risk for severe hypocalcemia in patients with advanced chronic kidney disease (CKD). 

Denosumab is a monoclonal antibody, indicated for the treatment of postmenopausal women with osteoporosis who are at increased risk for fracture for whom other treatments aren’t effective or can’t be tolerated. It’s also indicated to increase bone mass in men with osteoporosis at high risk for fracture, treat glucocorticoid-induced osteoporosis in men and women at high risk for fracture, increase bone mass in men at high risk for fracture receiving androgen-deprivation therapy for nonmetastatic prostate cancer, and increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer.

This new warning updates a November 2022 alert based on preliminary evidence for a “substantial risk” for hypocalcemia in patients with CKD on dialysis. 

Upon further examination of the data from two trials including more than 500,000 denosumab-treated women with CKD, the FDA concluded that severe hypocalcemia appears to be more common in those with CKD who also have mineral and bone disorder (CKD-MBD). And, for patients with advanced CKD taking denosumab, “severe hypocalcemia resulted in serious harm, including hospitalization, life-threatening events, and death.” 

Most of the severe hypocalcemia events occurred 2-10 weeks after denosumab injection, with the greatest risk during weeks 2-5.

The new warning advises healthcare professionals to assess patients’ kidney function before prescribing denosumab, and for those with advanced CKD, “consider the risk of severe hypocalcemia with Prolia in the context of other available treatments for osteoporosis.”

If the drug is still being considered for those patients for initial or continued use, calcium blood levels should be checked, and patients should be evaluated for CKD-MBD. Prior to prescribing denosumab in these patients, CKD-MBD should be properly managed, hypocalcemia corrected, and patients supplemented with calcium and activated vitamin D to decrease the risk for severe hypocalcemia and associated complications.

“Treatment with denosumab in patients with advanced CKD, including those on dialysis, and particularly patients with diagnosed CKD-MBD should involve a health care provider with expertise in the diagnosis and management of CKD-MBD,” the FDA advises. 

Once denosumab is administered, close monitoring of blood calcium levels and prompt hypocalcemia management is essential to prevent complications including seizures or arrythmias. Patients should be advised to promptly report symptoms that could be consistent with hypocalcemia, including confusion, seizures, irregular heartbeat, fainting, muscle spasms or weakness, face twitching, tingling, or numbness anywhere in the body. 

In 2022, an estimated 2.2 million Prolia prefilled syringes were sold by the manufacturer to US healthcare settings.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has added a boxed warning to the label of the osteoporosis drug denosumab (Prolia) about increased risk for severe hypocalcemia in patients with advanced chronic kidney disease (CKD). 

Denosumab is a monoclonal antibody, indicated for the treatment of postmenopausal women with osteoporosis who are at increased risk for fracture for whom other treatments aren’t effective or can’t be tolerated. It’s also indicated to increase bone mass in men with osteoporosis at high risk for fracture, treat glucocorticoid-induced osteoporosis in men and women at high risk for fracture, increase bone mass in men at high risk for fracture receiving androgen-deprivation therapy for nonmetastatic prostate cancer, and increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer.

This new warning updates a November 2022 alert based on preliminary evidence for a “substantial risk” for hypocalcemia in patients with CKD on dialysis. 

Upon further examination of the data from two trials including more than 500,000 denosumab-treated women with CKD, the FDA concluded that severe hypocalcemia appears to be more common in those with CKD who also have mineral and bone disorder (CKD-MBD). And, for patients with advanced CKD taking denosumab, “severe hypocalcemia resulted in serious harm, including hospitalization, life-threatening events, and death.” 

Most of the severe hypocalcemia events occurred 2-10 weeks after denosumab injection, with the greatest risk during weeks 2-5.

The new warning advises healthcare professionals to assess patients’ kidney function before prescribing denosumab, and for those with advanced CKD, “consider the risk of severe hypocalcemia with Prolia in the context of other available treatments for osteoporosis.”

If the drug is still being considered for those patients for initial or continued use, calcium blood levels should be checked, and patients should be evaluated for CKD-MBD. Prior to prescribing denosumab in these patients, CKD-MBD should be properly managed, hypocalcemia corrected, and patients supplemented with calcium and activated vitamin D to decrease the risk for severe hypocalcemia and associated complications.

“Treatment with denosumab in patients with advanced CKD, including those on dialysis, and particularly patients with diagnosed CKD-MBD should involve a health care provider with expertise in the diagnosis and management of CKD-MBD,” the FDA advises. 

Once denosumab is administered, close monitoring of blood calcium levels and prompt hypocalcemia management is essential to prevent complications including seizures or arrythmias. Patients should be advised to promptly report symptoms that could be consistent with hypocalcemia, including confusion, seizures, irregular heartbeat, fainting, muscle spasms or weakness, face twitching, tingling, or numbness anywhere in the body. 

In 2022, an estimated 2.2 million Prolia prefilled syringes were sold by the manufacturer to US healthcare settings.

A version of this article appeared on Medscape.com.