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Turn down the androgens to treat female pattern hair loss
NEW YORK – Antiandrogen hormones can help stabilize, and even improve, female pattern hair loss.
The pathophysiology of the disorder is unknown, but treatment is based on the assumption that women must be like men, at least when it comes to losing their hair. Intuitively, decreasing androgens should help correct the problem.
The answer, though, is a complicated mix of yes and maybe, Dr. Rochelle Torgerson said at the American Academy of Dermatology summer meeting.
“It used to be assumed that pattern hair loss in women was just the same as it is in men,” said Dr. Torgerson of the Mayo Clinic in Rochester, Minn. “Now there is some evidence that’s not true. In 2010, for example, this was seen in a woman with complete androgen insensitivity syndrome, so in her, androgens were not affecting hair follicles. There must be a place for estrogen.”
Further complicating the picture is the fact that no hormonal medications have FDA approval for hair loss in women, and their use has a history of conflicting data in clinical studies. Still, they remain the cornerstone for treating this physically and emotionally challenging problem.
The initial challenge is simply what to label it at the first visit.
“I have no problem with term ‘androgenetic alopecia,’ since that is what women are seeing when they first look on the Internet for information. But I do try to transition them to ‘female pattern hair loss.’ And I never – ever – use the term ‘male pattern baldness.’ It has a huge impact on women.”
The disease is a progressive miniaturization of the hair follicle over time. The growing cycle slows and the resting phase lengthens. There is progressive thinning over the vertex. Some women may keep most of their frontal hairline, but the vast majority do say it’s thinner than it was.
Spironolactone and oral contraceptives with spironolactone analogues are Dr. Torgerson’s go-to medications for first-line treatment. For spironolactone, she prefers a dose of 100-200 mg/day. Some women experience gastrointestinal upset, dizziness, cramps, breast tenderness, and spotting with these medications.
Her choice for an oral contraceptive is the combination of 20 mcg ethinyl estradiol plus drospirenone, but any oral contraceptive approved for acne may work.
Finasteride and dutasteride are approved for pattern hair loss in men, but not in women. Both inhibit 5 alpha-reductase type II. Dutasteride is more potent that finasteride and also inhibits type 1 alpha-reductase; both of these enzymes convert testosterone into the more potent dihydrotestosterone. The side-effect profile is more moderate than that of spironolactone, but both of the drugs have had mixed results in clinical trials.
One problem with the finasteride trials has been the variation in dosing. The least positive studies used the lowest dose of 1.25 mg. As the dosage increased to 2.5 mg and 5 mg, the benefit increased.
Despite her support for hormonal therapies, Dr. Torgerson doesn’t rely upon them alone – she supports them with the direct action of a 5% minoxidil foam. In addition to prescribing effective therapy, she urges women to actually be patient and to have realistic expectations.
Most women expect dramatic improvement in a short time. “I have no idea where that expectation comes from. This is a slow progressive condition. I agree with them that it’s completely unsexy to have the head of hair they do at that time. But if, in 3 years, they have this same head of hair, that’s going to be an amazing success. And once they have that expectation in their mind, they are usually happy with any other results that they see.”
Dr. Torgerson had no financial conflicts with regard to her presentation.
On Twitter @Alz_Gal
NEW YORK – Antiandrogen hormones can help stabilize, and even improve, female pattern hair loss.
The pathophysiology of the disorder is unknown, but treatment is based on the assumption that women must be like men, at least when it comes to losing their hair. Intuitively, decreasing androgens should help correct the problem.
The answer, though, is a complicated mix of yes and maybe, Dr. Rochelle Torgerson said at the American Academy of Dermatology summer meeting.
“It used to be assumed that pattern hair loss in women was just the same as it is in men,” said Dr. Torgerson of the Mayo Clinic in Rochester, Minn. “Now there is some evidence that’s not true. In 2010, for example, this was seen in a woman with complete androgen insensitivity syndrome, so in her, androgens were not affecting hair follicles. There must be a place for estrogen.”
Further complicating the picture is the fact that no hormonal medications have FDA approval for hair loss in women, and their use has a history of conflicting data in clinical studies. Still, they remain the cornerstone for treating this physically and emotionally challenging problem.
The initial challenge is simply what to label it at the first visit.
“I have no problem with term ‘androgenetic alopecia,’ since that is what women are seeing when they first look on the Internet for information. But I do try to transition them to ‘female pattern hair loss.’ And I never – ever – use the term ‘male pattern baldness.’ It has a huge impact on women.”
The disease is a progressive miniaturization of the hair follicle over time. The growing cycle slows and the resting phase lengthens. There is progressive thinning over the vertex. Some women may keep most of their frontal hairline, but the vast majority do say it’s thinner than it was.
Spironolactone and oral contraceptives with spironolactone analogues are Dr. Torgerson’s go-to medications for first-line treatment. For spironolactone, she prefers a dose of 100-200 mg/day. Some women experience gastrointestinal upset, dizziness, cramps, breast tenderness, and spotting with these medications.
Her choice for an oral contraceptive is the combination of 20 mcg ethinyl estradiol plus drospirenone, but any oral contraceptive approved for acne may work.
Finasteride and dutasteride are approved for pattern hair loss in men, but not in women. Both inhibit 5 alpha-reductase type II. Dutasteride is more potent that finasteride and also inhibits type 1 alpha-reductase; both of these enzymes convert testosterone into the more potent dihydrotestosterone. The side-effect profile is more moderate than that of spironolactone, but both of the drugs have had mixed results in clinical trials.
One problem with the finasteride trials has been the variation in dosing. The least positive studies used the lowest dose of 1.25 mg. As the dosage increased to 2.5 mg and 5 mg, the benefit increased.
Despite her support for hormonal therapies, Dr. Torgerson doesn’t rely upon them alone – she supports them with the direct action of a 5% minoxidil foam. In addition to prescribing effective therapy, she urges women to actually be patient and to have realistic expectations.
Most women expect dramatic improvement in a short time. “I have no idea where that expectation comes from. This is a slow progressive condition. I agree with them that it’s completely unsexy to have the head of hair they do at that time. But if, in 3 years, they have this same head of hair, that’s going to be an amazing success. And once they have that expectation in their mind, they are usually happy with any other results that they see.”
Dr. Torgerson had no financial conflicts with regard to her presentation.
On Twitter @Alz_Gal
NEW YORK – Antiandrogen hormones can help stabilize, and even improve, female pattern hair loss.
The pathophysiology of the disorder is unknown, but treatment is based on the assumption that women must be like men, at least when it comes to losing their hair. Intuitively, decreasing androgens should help correct the problem.
The answer, though, is a complicated mix of yes and maybe, Dr. Rochelle Torgerson said at the American Academy of Dermatology summer meeting.
“It used to be assumed that pattern hair loss in women was just the same as it is in men,” said Dr. Torgerson of the Mayo Clinic in Rochester, Minn. “Now there is some evidence that’s not true. In 2010, for example, this was seen in a woman with complete androgen insensitivity syndrome, so in her, androgens were not affecting hair follicles. There must be a place for estrogen.”
Further complicating the picture is the fact that no hormonal medications have FDA approval for hair loss in women, and their use has a history of conflicting data in clinical studies. Still, they remain the cornerstone for treating this physically and emotionally challenging problem.
The initial challenge is simply what to label it at the first visit.
“I have no problem with term ‘androgenetic alopecia,’ since that is what women are seeing when they first look on the Internet for information. But I do try to transition them to ‘female pattern hair loss.’ And I never – ever – use the term ‘male pattern baldness.’ It has a huge impact on women.”
The disease is a progressive miniaturization of the hair follicle over time. The growing cycle slows and the resting phase lengthens. There is progressive thinning over the vertex. Some women may keep most of their frontal hairline, but the vast majority do say it’s thinner than it was.
Spironolactone and oral contraceptives with spironolactone analogues are Dr. Torgerson’s go-to medications for first-line treatment. For spironolactone, she prefers a dose of 100-200 mg/day. Some women experience gastrointestinal upset, dizziness, cramps, breast tenderness, and spotting with these medications.
Her choice for an oral contraceptive is the combination of 20 mcg ethinyl estradiol plus drospirenone, but any oral contraceptive approved for acne may work.
Finasteride and dutasteride are approved for pattern hair loss in men, but not in women. Both inhibit 5 alpha-reductase type II. Dutasteride is more potent that finasteride and also inhibits type 1 alpha-reductase; both of these enzymes convert testosterone into the more potent dihydrotestosterone. The side-effect profile is more moderate than that of spironolactone, but both of the drugs have had mixed results in clinical trials.
One problem with the finasteride trials has been the variation in dosing. The least positive studies used the lowest dose of 1.25 mg. As the dosage increased to 2.5 mg and 5 mg, the benefit increased.
Despite her support for hormonal therapies, Dr. Torgerson doesn’t rely upon them alone – she supports them with the direct action of a 5% minoxidil foam. In addition to prescribing effective therapy, she urges women to actually be patient and to have realistic expectations.
Most women expect dramatic improvement in a short time. “I have no idea where that expectation comes from. This is a slow progressive condition. I agree with them that it’s completely unsexy to have the head of hair they do at that time. But if, in 3 years, they have this same head of hair, that’s going to be an amazing success. And once they have that expectation in their mind, they are usually happy with any other results that they see.”
Dr. Torgerson had no financial conflicts with regard to her presentation.
On Twitter @Alz_Gal
EXPERT ANALYSIS FROM THE AAD SUMMER ACADEMY 2015
New treatment target for hypothyroid elderly
ESTES PARK, COLO. – The latest major guidelines on management of hypothyroidism create a new, looser treatment target for older patients.
“This is a departure from the message we’ve given many times in the past. Elderly people seem to tolerate slight degrees of hypothyroidism and may actually benefit from it,” Dr. Michael T. McDermott said at a conference on internal medicine sponsored by the University of Colorado.
The American Thyroid Association guidelines issued late last year (Thyroid. 2014 Dec;24[12]:1670-75) raise the target serum TSH to 4-6 mIU/L in hypothyroid individuals age 70 or older. The target serum TSH in nonelderly, nonpregnant patients remains unchanged at 0.5-4.5 mIU/L, noted Dr. McDermott, professor of medicine and director of endocrinology and diabetes practice at the University of Colorado Hospital, Aurora.
“The slightly higher TSH treatment target in elderly patients is very heavily evidence-based. Studies showed that people over age 70 often did worse if their TSH was maintained in the low end of the normal range, and that people whose TSH was maintained up to about 6 mIU/L didn’t seem to have any adverse effects from that. It’s kind of a moving target: we’ll probably see the data reevaluated over time. But I think it’s clear that normal elderly people have a normal TSH that’s slightly higher,” according to the endocrinologist.
The starting dose of levothyroxine (LT4) in older patients is 25-50 mcg/day. The TSH level should be rechecked after 6 weeks in patients with overt hypothyroidism and 6-10 weeks in those with subclinical hypothyroidism, with LT4 then being titrated in the elderly until it’s in the 4-6 mIU/L range.
Speaking of subclinical hypothyroidism, which is defined by an elevated TSH but a normal free T4 level, four studies now show the same thing: While subclinical hypothyroidism is independently associated with increased cardiovascular mortality in patients under age 65, it does not carry any increased cardiovascular mortality risk in older individuals. The first of these studies, a meta-analysis of 15 clinical trials totalling 2,531 subclinically hypothyroid patients and more than 26,000 controls, found a 37% increase in cardiovascular mortality in patients younger than 65 with subclinical hypothyroidism, but no increase in older people with the disorder (J Clin Endocrinol Metab. 2008 Aug;93[8]:2998-3007).
“We don’t know why that is, but it’s the reason the recommended TSH range when treating people for subclinical or overt hypothyroidism has now changed in people over age 70,” Dr. McDermott explained.
The consensus recommendations of the American Thyroid Association and the American Association of Clinical Endocrinologists advise treatment of subclinical hypothyroidism involving a TSH level greater than 10.0 mIU/L. In patients with lesser elevations of TSH, however, clinical judgment is critical in deciding whether to treat or monitor.
“If the person has symptoms, treatment is very reasonable. You should know, however, that one-third of people who have a TSH of 4.5-10.0 mIU/L will have a normal TSH 1 year later if you don’t treat them. So if they’re not symptomatic you may usually monitor these patients,” he said.
While LT4 remains the treatment of choice for hypothyroidism, 16% of patients have persistent symptoms despite optimal LT4 therapy. They appear to benefit from a combination of LT4 and liothyronine (LT3) given in a 10:1 ratio. Because LT3 lasts for only about 8 hours, it’s best administered twice daily. Thyroid tests should be obtained before the medication is taken because triiodothyronine (T3) levels rise abruptly in response to a dose.
Dr. McDermott reported having no financial conflicts of interest.
ESTES PARK, COLO. – The latest major guidelines on management of hypothyroidism create a new, looser treatment target for older patients.
“This is a departure from the message we’ve given many times in the past. Elderly people seem to tolerate slight degrees of hypothyroidism and may actually benefit from it,” Dr. Michael T. McDermott said at a conference on internal medicine sponsored by the University of Colorado.
The American Thyroid Association guidelines issued late last year (Thyroid. 2014 Dec;24[12]:1670-75) raise the target serum TSH to 4-6 mIU/L in hypothyroid individuals age 70 or older. The target serum TSH in nonelderly, nonpregnant patients remains unchanged at 0.5-4.5 mIU/L, noted Dr. McDermott, professor of medicine and director of endocrinology and diabetes practice at the University of Colorado Hospital, Aurora.
“The slightly higher TSH treatment target in elderly patients is very heavily evidence-based. Studies showed that people over age 70 often did worse if their TSH was maintained in the low end of the normal range, and that people whose TSH was maintained up to about 6 mIU/L didn’t seem to have any adverse effects from that. It’s kind of a moving target: we’ll probably see the data reevaluated over time. But I think it’s clear that normal elderly people have a normal TSH that’s slightly higher,” according to the endocrinologist.
The starting dose of levothyroxine (LT4) in older patients is 25-50 mcg/day. The TSH level should be rechecked after 6 weeks in patients with overt hypothyroidism and 6-10 weeks in those with subclinical hypothyroidism, with LT4 then being titrated in the elderly until it’s in the 4-6 mIU/L range.
Speaking of subclinical hypothyroidism, which is defined by an elevated TSH but a normal free T4 level, four studies now show the same thing: While subclinical hypothyroidism is independently associated with increased cardiovascular mortality in patients under age 65, it does not carry any increased cardiovascular mortality risk in older individuals. The first of these studies, a meta-analysis of 15 clinical trials totalling 2,531 subclinically hypothyroid patients and more than 26,000 controls, found a 37% increase in cardiovascular mortality in patients younger than 65 with subclinical hypothyroidism, but no increase in older people with the disorder (J Clin Endocrinol Metab. 2008 Aug;93[8]:2998-3007).
“We don’t know why that is, but it’s the reason the recommended TSH range when treating people for subclinical or overt hypothyroidism has now changed in people over age 70,” Dr. McDermott explained.
The consensus recommendations of the American Thyroid Association and the American Association of Clinical Endocrinologists advise treatment of subclinical hypothyroidism involving a TSH level greater than 10.0 mIU/L. In patients with lesser elevations of TSH, however, clinical judgment is critical in deciding whether to treat or monitor.
“If the person has symptoms, treatment is very reasonable. You should know, however, that one-third of people who have a TSH of 4.5-10.0 mIU/L will have a normal TSH 1 year later if you don’t treat them. So if they’re not symptomatic you may usually monitor these patients,” he said.
While LT4 remains the treatment of choice for hypothyroidism, 16% of patients have persistent symptoms despite optimal LT4 therapy. They appear to benefit from a combination of LT4 and liothyronine (LT3) given in a 10:1 ratio. Because LT3 lasts for only about 8 hours, it’s best administered twice daily. Thyroid tests should be obtained before the medication is taken because triiodothyronine (T3) levels rise abruptly in response to a dose.
Dr. McDermott reported having no financial conflicts of interest.
ESTES PARK, COLO. – The latest major guidelines on management of hypothyroidism create a new, looser treatment target for older patients.
“This is a departure from the message we’ve given many times in the past. Elderly people seem to tolerate slight degrees of hypothyroidism and may actually benefit from it,” Dr. Michael T. McDermott said at a conference on internal medicine sponsored by the University of Colorado.
The American Thyroid Association guidelines issued late last year (Thyroid. 2014 Dec;24[12]:1670-75) raise the target serum TSH to 4-6 mIU/L in hypothyroid individuals age 70 or older. The target serum TSH in nonelderly, nonpregnant patients remains unchanged at 0.5-4.5 mIU/L, noted Dr. McDermott, professor of medicine and director of endocrinology and diabetes practice at the University of Colorado Hospital, Aurora.
“The slightly higher TSH treatment target in elderly patients is very heavily evidence-based. Studies showed that people over age 70 often did worse if their TSH was maintained in the low end of the normal range, and that people whose TSH was maintained up to about 6 mIU/L didn’t seem to have any adverse effects from that. It’s kind of a moving target: we’ll probably see the data reevaluated over time. But I think it’s clear that normal elderly people have a normal TSH that’s slightly higher,” according to the endocrinologist.
The starting dose of levothyroxine (LT4) in older patients is 25-50 mcg/day. The TSH level should be rechecked after 6 weeks in patients with overt hypothyroidism and 6-10 weeks in those with subclinical hypothyroidism, with LT4 then being titrated in the elderly until it’s in the 4-6 mIU/L range.
Speaking of subclinical hypothyroidism, which is defined by an elevated TSH but a normal free T4 level, four studies now show the same thing: While subclinical hypothyroidism is independently associated with increased cardiovascular mortality in patients under age 65, it does not carry any increased cardiovascular mortality risk in older individuals. The first of these studies, a meta-analysis of 15 clinical trials totalling 2,531 subclinically hypothyroid patients and more than 26,000 controls, found a 37% increase in cardiovascular mortality in patients younger than 65 with subclinical hypothyroidism, but no increase in older people with the disorder (J Clin Endocrinol Metab. 2008 Aug;93[8]:2998-3007).
“We don’t know why that is, but it’s the reason the recommended TSH range when treating people for subclinical or overt hypothyroidism has now changed in people over age 70,” Dr. McDermott explained.
The consensus recommendations of the American Thyroid Association and the American Association of Clinical Endocrinologists advise treatment of subclinical hypothyroidism involving a TSH level greater than 10.0 mIU/L. In patients with lesser elevations of TSH, however, clinical judgment is critical in deciding whether to treat or monitor.
“If the person has symptoms, treatment is very reasonable. You should know, however, that one-third of people who have a TSH of 4.5-10.0 mIU/L will have a normal TSH 1 year later if you don’t treat them. So if they’re not symptomatic you may usually monitor these patients,” he said.
While LT4 remains the treatment of choice for hypothyroidism, 16% of patients have persistent symptoms despite optimal LT4 therapy. They appear to benefit from a combination of LT4 and liothyronine (LT3) given in a 10:1 ratio. Because LT3 lasts for only about 8 hours, it’s best administered twice daily. Thyroid tests should be obtained before the medication is taken because triiodothyronine (T3) levels rise abruptly in response to a dose.
Dr. McDermott reported having no financial conflicts of interest.
EXPERT ANALYSIS FROM THE ANNUAL INTERNAL MEDICINE PROGRAM
ESTIMABL trial: Current rhTSH cost outweighs benefits
The thyroid ablation rate with recombinant human thyroid stimulating hormone injections, or rhTSH, was shown in the randomized phase III Etude Stimulation Ablation trial to be similar to that with thyroid hormone withdrawal when used with either 1.1 or 3.7 GBq iodine-131 in patients with thyroid cancer, but a new analysis of data from the trial shows that the use of rhTSH would not be cost effective.
While rhTSH was associated with stable health-related quality of life and was more effective than thyroid hormone withdrawal (THW) with respect to quality-adjusted life-years (mean increase of 0.013 vs. THW), it is far more expensive, and a cost-effectiveness analysis showed that at a willingness-to-pay threshold of $53,300 per QALY, the probability that rhTSH would be cost effective was 47% when direct costs were considered. This increased to 70% when the cost of rhTSH was lowered by 30%, Isabelle Borget, Pharm.D., Ph.D., of Gustave Roussy, Villejuif, France, and her colleagues reported online in the Journal of Clinical Oncology.
Using 1.1 rather than 3.7 GBq of iodine-131 decreased efficacy slightly (mean decrease of 0.007 QALY), but also reduced costs by $1,018, and the probability of cost-effectiveness at the lower iodine-131 level was 65%, the investigators said (J Clin Oncol. 2015 Aug 3. doi: 10.1200/JCO.2015.61.6722).
Although rhTSH was not associated with the transient deterioration in health-related quality of life seen with thyroid hormone withdrawal in the first few months of treatment, it was cost effective only when the price was reduced by 30%; lower iodine-131 activity also reduced overall costs, they concluded.
Dr. Borget reported receiving honoraria from Roche and Janssen-Cilag, and travel, accommodations, and expenses from Janssen-Cilag. Several coauthors reported relationships with Genzyme, Sanofi, Novartis, and/or GE Healthcare, including receiving research support, honoraria, travel/accommodations/expenses, and/or serving as a consultant or advisor.
The thyroid ablation rate with recombinant human thyroid stimulating hormone injections, or rhTSH, was shown in the randomized phase III Etude Stimulation Ablation trial to be similar to that with thyroid hormone withdrawal when used with either 1.1 or 3.7 GBq iodine-131 in patients with thyroid cancer, but a new analysis of data from the trial shows that the use of rhTSH would not be cost effective.
While rhTSH was associated with stable health-related quality of life and was more effective than thyroid hormone withdrawal (THW) with respect to quality-adjusted life-years (mean increase of 0.013 vs. THW), it is far more expensive, and a cost-effectiveness analysis showed that at a willingness-to-pay threshold of $53,300 per QALY, the probability that rhTSH would be cost effective was 47% when direct costs were considered. This increased to 70% when the cost of rhTSH was lowered by 30%, Isabelle Borget, Pharm.D., Ph.D., of Gustave Roussy, Villejuif, France, and her colleagues reported online in the Journal of Clinical Oncology.
Using 1.1 rather than 3.7 GBq of iodine-131 decreased efficacy slightly (mean decrease of 0.007 QALY), but also reduced costs by $1,018, and the probability of cost-effectiveness at the lower iodine-131 level was 65%, the investigators said (J Clin Oncol. 2015 Aug 3. doi: 10.1200/JCO.2015.61.6722).
Although rhTSH was not associated with the transient deterioration in health-related quality of life seen with thyroid hormone withdrawal in the first few months of treatment, it was cost effective only when the price was reduced by 30%; lower iodine-131 activity also reduced overall costs, they concluded.
Dr. Borget reported receiving honoraria from Roche and Janssen-Cilag, and travel, accommodations, and expenses from Janssen-Cilag. Several coauthors reported relationships with Genzyme, Sanofi, Novartis, and/or GE Healthcare, including receiving research support, honoraria, travel/accommodations/expenses, and/or serving as a consultant or advisor.
The thyroid ablation rate with recombinant human thyroid stimulating hormone injections, or rhTSH, was shown in the randomized phase III Etude Stimulation Ablation trial to be similar to that with thyroid hormone withdrawal when used with either 1.1 or 3.7 GBq iodine-131 in patients with thyroid cancer, but a new analysis of data from the trial shows that the use of rhTSH would not be cost effective.
While rhTSH was associated with stable health-related quality of life and was more effective than thyroid hormone withdrawal (THW) with respect to quality-adjusted life-years (mean increase of 0.013 vs. THW), it is far more expensive, and a cost-effectiveness analysis showed that at a willingness-to-pay threshold of $53,300 per QALY, the probability that rhTSH would be cost effective was 47% when direct costs were considered. This increased to 70% when the cost of rhTSH was lowered by 30%, Isabelle Borget, Pharm.D., Ph.D., of Gustave Roussy, Villejuif, France, and her colleagues reported online in the Journal of Clinical Oncology.
Using 1.1 rather than 3.7 GBq of iodine-131 decreased efficacy slightly (mean decrease of 0.007 QALY), but also reduced costs by $1,018, and the probability of cost-effectiveness at the lower iodine-131 level was 65%, the investigators said (J Clin Oncol. 2015 Aug 3. doi: 10.1200/JCO.2015.61.6722).
Although rhTSH was not associated with the transient deterioration in health-related quality of life seen with thyroid hormone withdrawal in the first few months of treatment, it was cost effective only when the price was reduced by 30%; lower iodine-131 activity also reduced overall costs, they concluded.
Dr. Borget reported receiving honoraria from Roche and Janssen-Cilag, and travel, accommodations, and expenses from Janssen-Cilag. Several coauthors reported relationships with Genzyme, Sanofi, Novartis, and/or GE Healthcare, including receiving research support, honoraria, travel/accommodations/expenses, and/or serving as a consultant or advisor.
FROM THE JOURNAL OF CLINICAL ONCOLOGY
Key clinical point: Recombinant human thyroid-stimulating hormone injections are as effective as thyroid hormone withdrawal for thyroid ablation, but are not cost-effective, according to a new analysis of data from the Etude Stimulation Ablation (ESTIMABL) trial.
Major finding: At a willingness-to-pay threshold of $53,300 per QALY, the probability of rhTSH cost-effectiveness was 47%.
Data source: The randomized phase III ESTIMABL Trial involving 752 patients.
Disclosures: Dr. Borget reported receiving honoraria from Roche and Janssen-Cilag, and travel, accommodations, and expenses from Janssen-Cilag. Several coauthors reported relationships with Genzyme, Sanofi, Novartis, and/or GE Healthcare, including receiving research support, honoraria, travel/accommodations/expenses, and/or serving as a consultant or advisor.
New Cushing’s guidelines emphasize team approach
New clinical practice guidelines for the treatment of Cushing’s syndrome stress coordinated care and patient involvement, and solidify an evidence-based treatment path for surgical and medical treatment options. The Endocrine Society released the guidelines, which were developed in conjunction with the European Society of Endocrinology (J Clin Endocrinol Metab. 2015 Aug;100[8]:2807-2831).
Dr. Lynette Nieman, chair of the task force that developed the guidelines, commented in an interview that the guidelines don’t really contain new or controversial elements, but they do help clarify existing best practices. “This is not a common diagnosis, but it is very important to understand how to handle this disorder,” said Dr. Nieman of the program in reproductive and adult endocrinology at the Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Md. “Cushing’s syndrome really needs to be treated with a team approach and by expert surgeons and expert endocrinologists,” she said.
In establishing treatment goals, the guidelines emphasize clinically based treatment, only recommending normalization of cortisol levels or action when overt Cushing’s syndrome (CS) and an established diagnosis exist (grade 1 recommendation). “Surgical resection of the causal lesion(s) is generally the first-line approach,” said Dr. Nieman and coauthors (grade 1 recommendation). Medical management of comorbidities and sequelae of hypercortisolism should always accompany any medical or surgical treatment. The guidelines also provide for emergent surgical or medical management of hypercortisolism if life-threatening complications are present (grade 1 recommendation).
Adjunctive management is directed at a patient-centered, multidisciplinary approach to address potential cortisol-dependent comorbidities. These may include hypertension and dyslipidemia, diabetes, electrolyte disturbances, increased infection risk, osteoporosis and deconditioning, and psychiatric illnesses (ungraded best practice recommendation). Additionally, the guidelines recommend perioperative prophylaxis for venous thromboembolism for CS patients (grade 2 recommendation).
For Cushing’s disease (CD), the guidelines recommend excision of ectopic and adrenal lesions, barring contraindications or low likelihood of successful surgery, with unilateral adrenal resection by an experienced adrenal surgeon recommended in benign unilateral disease. Ectopic adrenocorticotropic hormone (ACTH)–secreting tumors should be resected, with local node dissection as appropriate. Transsphenoidal selective adenomectomy is the recommended treatment for CD in adults and children, and should be performed by an experienced pituitary surgeon. Serum sodium should be measured several times during the first 2 weeks after surgery, and free T4 and prolactin by no more than 2 weeks after surgery (all grade 1 recommendations).
The task force recommends an MRI by 3 months after transsphenoidal surgery (ungraded best practice recommendation). When adrenal disorders are bilateral, the task force recommends surgical resection and medical therapy to block aberrant hormone receptors (grade 2 recommendation).
Carrying through the theme of an individualized, patient-centered approach, the task force recommends individualized postoperative management depending on postoperative cortisol levels. Persistent and overt postsurgical hypercortisolism should be treated, while patients with eucortisolism should have serum or salivary cortisol measured late at night. Patients with ACTH-dependent CS should be screened for recurrence of hypercortisolism (all grade 1 recommendations).
Glucocorticoid replacement, when required for hypocortisolemic patients, should be accompanied by appropriate patient education. When patients have an intact adrenal gland remaining, hypothalamic-pituitary-adrenal (HPA) axis recovery should be assessed at follow-up, so glucocorticoids can be stopped when recovery occurs. Other pituitary hormone deficiencies may occur, and care should include assessing the need to treat these deficiencies as well (all grade 1 recommendations).
In the difficult cases where surgery is not possible or does not cure ACTH-dependent CS, shared patient decision making is recommended to choose among the various second-line therapies that may be of benefit (grade 2 recommendation).
Therapy choices may include bilateral adrenalectomy, reserved for occult or metastatic ectopic ACTH secretion, or in an emergency situation where the procedure may be lifesaving (grade 2 recommendation); repeat transsphenoidal surgery when imaging or the clinical picture points to a new lesion or incomplete resection (grade 2 recommendation); radiation therapy or radiosurgery for those who fail transsphenoidal surgery or whose CD recurs, or where mass effect may be of concern (grade 1-2 recommendations; and medical treatment with steroidogenesis inhibitors in limited circumstances (grade 1 recommendation).
Specific medical treatment recommendations include the use of steroidogenesis inhibitors after transsphenoidal surgery for patients with CD or to treat occult or metastatic cases of ectopic ACTH secretion, and as an adjunct in adrenocortical carcinoma (grade 1 recommendation). The task force, in the discussion accompanying the guidelines, lists pros and cons of the various medical choices in order to present a balanced view of medical treatment options, said Dr. Nieman.
The long-term follow-up of individuals with CS should include screening and treating for the comorbidities that may persist even after successful surgery. Follow-up should be lifelong, with each comorbidity followed to resolution and ongoing vigilance for recurrence (except in patients with successfully resected low-attenuation adrenal adenomas – grade 1 recommendation).
In an interview, Dr. Rebecca S. Sippel of the University of Wisconsin–Madison brought an endocrine surgeon’s perspective to the guidelines, agreeing that the document generally reflects accepted practice. She also agreed that the interdisciplinary approach advocated by the task force is critical. “It’s important that discharge planning is done in a systematic way, so there’s systematic follow-up of patients after excision,” she said. She noted that CS patients on her service all receive an endocrine consult while they are inpatients to ensure adequate discharge planning.
Future research directions recommended by Dr. Nieman and the task force coauthors include identification of markers that will “explain the variable clinical effect of steroids among individuals,” with the goal of achieving better quantification of treatment effect and tracking response and remission. Health care–related quality of life is negatively affected by CS even after resolution to eucortisolism in many patients, so the guidelines recommend further research into quality of life and cognitive problems experienced by individuals with CS. Dr. Nieman specifically called for more multisite research, noting that diagnoses of Cushing’s disease and Cushing’s syndrome are rare, and etiologies are varied. “In order to get the numbers we need to do good research, we will need to cooperate,” she said.
All authors of the clinical practice guidelines had financial disclosures; a complete listing of disclosures and the task force’s methodology for resolving conflicts may be found in the downloadable guidelines.
On Twitter @karioakes
New clinical practice guidelines for the treatment of Cushing’s syndrome stress coordinated care and patient involvement, and solidify an evidence-based treatment path for surgical and medical treatment options. The Endocrine Society released the guidelines, which were developed in conjunction with the European Society of Endocrinology (J Clin Endocrinol Metab. 2015 Aug;100[8]:2807-2831).
Dr. Lynette Nieman, chair of the task force that developed the guidelines, commented in an interview that the guidelines don’t really contain new or controversial elements, but they do help clarify existing best practices. “This is not a common diagnosis, but it is very important to understand how to handle this disorder,” said Dr. Nieman of the program in reproductive and adult endocrinology at the Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Md. “Cushing’s syndrome really needs to be treated with a team approach and by expert surgeons and expert endocrinologists,” she said.
In establishing treatment goals, the guidelines emphasize clinically based treatment, only recommending normalization of cortisol levels or action when overt Cushing’s syndrome (CS) and an established diagnosis exist (grade 1 recommendation). “Surgical resection of the causal lesion(s) is generally the first-line approach,” said Dr. Nieman and coauthors (grade 1 recommendation). Medical management of comorbidities and sequelae of hypercortisolism should always accompany any medical or surgical treatment. The guidelines also provide for emergent surgical or medical management of hypercortisolism if life-threatening complications are present (grade 1 recommendation).
Adjunctive management is directed at a patient-centered, multidisciplinary approach to address potential cortisol-dependent comorbidities. These may include hypertension and dyslipidemia, diabetes, electrolyte disturbances, increased infection risk, osteoporosis and deconditioning, and psychiatric illnesses (ungraded best practice recommendation). Additionally, the guidelines recommend perioperative prophylaxis for venous thromboembolism for CS patients (grade 2 recommendation).
For Cushing’s disease (CD), the guidelines recommend excision of ectopic and adrenal lesions, barring contraindications or low likelihood of successful surgery, with unilateral adrenal resection by an experienced adrenal surgeon recommended in benign unilateral disease. Ectopic adrenocorticotropic hormone (ACTH)–secreting tumors should be resected, with local node dissection as appropriate. Transsphenoidal selective adenomectomy is the recommended treatment for CD in adults and children, and should be performed by an experienced pituitary surgeon. Serum sodium should be measured several times during the first 2 weeks after surgery, and free T4 and prolactin by no more than 2 weeks after surgery (all grade 1 recommendations).
The task force recommends an MRI by 3 months after transsphenoidal surgery (ungraded best practice recommendation). When adrenal disorders are bilateral, the task force recommends surgical resection and medical therapy to block aberrant hormone receptors (grade 2 recommendation).
Carrying through the theme of an individualized, patient-centered approach, the task force recommends individualized postoperative management depending on postoperative cortisol levels. Persistent and overt postsurgical hypercortisolism should be treated, while patients with eucortisolism should have serum or salivary cortisol measured late at night. Patients with ACTH-dependent CS should be screened for recurrence of hypercortisolism (all grade 1 recommendations).
Glucocorticoid replacement, when required for hypocortisolemic patients, should be accompanied by appropriate patient education. When patients have an intact adrenal gland remaining, hypothalamic-pituitary-adrenal (HPA) axis recovery should be assessed at follow-up, so glucocorticoids can be stopped when recovery occurs. Other pituitary hormone deficiencies may occur, and care should include assessing the need to treat these deficiencies as well (all grade 1 recommendations).
In the difficult cases where surgery is not possible or does not cure ACTH-dependent CS, shared patient decision making is recommended to choose among the various second-line therapies that may be of benefit (grade 2 recommendation).
Therapy choices may include bilateral adrenalectomy, reserved for occult or metastatic ectopic ACTH secretion, or in an emergency situation where the procedure may be lifesaving (grade 2 recommendation); repeat transsphenoidal surgery when imaging or the clinical picture points to a new lesion or incomplete resection (grade 2 recommendation); radiation therapy or radiosurgery for those who fail transsphenoidal surgery or whose CD recurs, or where mass effect may be of concern (grade 1-2 recommendations; and medical treatment with steroidogenesis inhibitors in limited circumstances (grade 1 recommendation).
Specific medical treatment recommendations include the use of steroidogenesis inhibitors after transsphenoidal surgery for patients with CD or to treat occult or metastatic cases of ectopic ACTH secretion, and as an adjunct in adrenocortical carcinoma (grade 1 recommendation). The task force, in the discussion accompanying the guidelines, lists pros and cons of the various medical choices in order to present a balanced view of medical treatment options, said Dr. Nieman.
The long-term follow-up of individuals with CS should include screening and treating for the comorbidities that may persist even after successful surgery. Follow-up should be lifelong, with each comorbidity followed to resolution and ongoing vigilance for recurrence (except in patients with successfully resected low-attenuation adrenal adenomas – grade 1 recommendation).
In an interview, Dr. Rebecca S. Sippel of the University of Wisconsin–Madison brought an endocrine surgeon’s perspective to the guidelines, agreeing that the document generally reflects accepted practice. She also agreed that the interdisciplinary approach advocated by the task force is critical. “It’s important that discharge planning is done in a systematic way, so there’s systematic follow-up of patients after excision,” she said. She noted that CS patients on her service all receive an endocrine consult while they are inpatients to ensure adequate discharge planning.
Future research directions recommended by Dr. Nieman and the task force coauthors include identification of markers that will “explain the variable clinical effect of steroids among individuals,” with the goal of achieving better quantification of treatment effect and tracking response and remission. Health care–related quality of life is negatively affected by CS even after resolution to eucortisolism in many patients, so the guidelines recommend further research into quality of life and cognitive problems experienced by individuals with CS. Dr. Nieman specifically called for more multisite research, noting that diagnoses of Cushing’s disease and Cushing’s syndrome are rare, and etiologies are varied. “In order to get the numbers we need to do good research, we will need to cooperate,” she said.
All authors of the clinical practice guidelines had financial disclosures; a complete listing of disclosures and the task force’s methodology for resolving conflicts may be found in the downloadable guidelines.
On Twitter @karioakes
New clinical practice guidelines for the treatment of Cushing’s syndrome stress coordinated care and patient involvement, and solidify an evidence-based treatment path for surgical and medical treatment options. The Endocrine Society released the guidelines, which were developed in conjunction with the European Society of Endocrinology (J Clin Endocrinol Metab. 2015 Aug;100[8]:2807-2831).
Dr. Lynette Nieman, chair of the task force that developed the guidelines, commented in an interview that the guidelines don’t really contain new or controversial elements, but they do help clarify existing best practices. “This is not a common diagnosis, but it is very important to understand how to handle this disorder,” said Dr. Nieman of the program in reproductive and adult endocrinology at the Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Md. “Cushing’s syndrome really needs to be treated with a team approach and by expert surgeons and expert endocrinologists,” she said.
In establishing treatment goals, the guidelines emphasize clinically based treatment, only recommending normalization of cortisol levels or action when overt Cushing’s syndrome (CS) and an established diagnosis exist (grade 1 recommendation). “Surgical resection of the causal lesion(s) is generally the first-line approach,” said Dr. Nieman and coauthors (grade 1 recommendation). Medical management of comorbidities and sequelae of hypercortisolism should always accompany any medical or surgical treatment. The guidelines also provide for emergent surgical or medical management of hypercortisolism if life-threatening complications are present (grade 1 recommendation).
Adjunctive management is directed at a patient-centered, multidisciplinary approach to address potential cortisol-dependent comorbidities. These may include hypertension and dyslipidemia, diabetes, electrolyte disturbances, increased infection risk, osteoporosis and deconditioning, and psychiatric illnesses (ungraded best practice recommendation). Additionally, the guidelines recommend perioperative prophylaxis for venous thromboembolism for CS patients (grade 2 recommendation).
For Cushing’s disease (CD), the guidelines recommend excision of ectopic and adrenal lesions, barring contraindications or low likelihood of successful surgery, with unilateral adrenal resection by an experienced adrenal surgeon recommended in benign unilateral disease. Ectopic adrenocorticotropic hormone (ACTH)–secreting tumors should be resected, with local node dissection as appropriate. Transsphenoidal selective adenomectomy is the recommended treatment for CD in adults and children, and should be performed by an experienced pituitary surgeon. Serum sodium should be measured several times during the first 2 weeks after surgery, and free T4 and prolactin by no more than 2 weeks after surgery (all grade 1 recommendations).
The task force recommends an MRI by 3 months after transsphenoidal surgery (ungraded best practice recommendation). When adrenal disorders are bilateral, the task force recommends surgical resection and medical therapy to block aberrant hormone receptors (grade 2 recommendation).
Carrying through the theme of an individualized, patient-centered approach, the task force recommends individualized postoperative management depending on postoperative cortisol levels. Persistent and overt postsurgical hypercortisolism should be treated, while patients with eucortisolism should have serum or salivary cortisol measured late at night. Patients with ACTH-dependent CS should be screened for recurrence of hypercortisolism (all grade 1 recommendations).
Glucocorticoid replacement, when required for hypocortisolemic patients, should be accompanied by appropriate patient education. When patients have an intact adrenal gland remaining, hypothalamic-pituitary-adrenal (HPA) axis recovery should be assessed at follow-up, so glucocorticoids can be stopped when recovery occurs. Other pituitary hormone deficiencies may occur, and care should include assessing the need to treat these deficiencies as well (all grade 1 recommendations).
In the difficult cases where surgery is not possible or does not cure ACTH-dependent CS, shared patient decision making is recommended to choose among the various second-line therapies that may be of benefit (grade 2 recommendation).
Therapy choices may include bilateral adrenalectomy, reserved for occult or metastatic ectopic ACTH secretion, or in an emergency situation where the procedure may be lifesaving (grade 2 recommendation); repeat transsphenoidal surgery when imaging or the clinical picture points to a new lesion or incomplete resection (grade 2 recommendation); radiation therapy or radiosurgery for those who fail transsphenoidal surgery or whose CD recurs, or where mass effect may be of concern (grade 1-2 recommendations; and medical treatment with steroidogenesis inhibitors in limited circumstances (grade 1 recommendation).
Specific medical treatment recommendations include the use of steroidogenesis inhibitors after transsphenoidal surgery for patients with CD or to treat occult or metastatic cases of ectopic ACTH secretion, and as an adjunct in adrenocortical carcinoma (grade 1 recommendation). The task force, in the discussion accompanying the guidelines, lists pros and cons of the various medical choices in order to present a balanced view of medical treatment options, said Dr. Nieman.
The long-term follow-up of individuals with CS should include screening and treating for the comorbidities that may persist even after successful surgery. Follow-up should be lifelong, with each comorbidity followed to resolution and ongoing vigilance for recurrence (except in patients with successfully resected low-attenuation adrenal adenomas – grade 1 recommendation).
In an interview, Dr. Rebecca S. Sippel of the University of Wisconsin–Madison brought an endocrine surgeon’s perspective to the guidelines, agreeing that the document generally reflects accepted practice. She also agreed that the interdisciplinary approach advocated by the task force is critical. “It’s important that discharge planning is done in a systematic way, so there’s systematic follow-up of patients after excision,” she said. She noted that CS patients on her service all receive an endocrine consult while they are inpatients to ensure adequate discharge planning.
Future research directions recommended by Dr. Nieman and the task force coauthors include identification of markers that will “explain the variable clinical effect of steroids among individuals,” with the goal of achieving better quantification of treatment effect and tracking response and remission. Health care–related quality of life is negatively affected by CS even after resolution to eucortisolism in many patients, so the guidelines recommend further research into quality of life and cognitive problems experienced by individuals with CS. Dr. Nieman specifically called for more multisite research, noting that diagnoses of Cushing’s disease and Cushing’s syndrome are rare, and etiologies are varied. “In order to get the numbers we need to do good research, we will need to cooperate,” she said.
All authors of the clinical practice guidelines had financial disclosures; a complete listing of disclosures and the task force’s methodology for resolving conflicts may be found in the downloadable guidelines.
On Twitter @karioakes
FROM THE JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM
Tumor location, radiotherapy predict neuroendocrine dysfunction after pediatric glioma
Tumor location and radiotherapy, respectively, predict the speed of onset and density of long-term neuroendocrinopathy following pediatric glioma, report Dr. Hoong-Wei Gan and coauthors at University College London Institute of Child Health.
In a longitudinal study of 166 children with a median age of 4.9 years at diagnosis, progression-free status and endocrine event–free survival (EEFS) were 47.2% and 20.8%, respectively, despite high overall survival of 81%.
Growth hormone deficiency was the most common disorder (40.3%), followed by central precocious puberty (26%), gonadotropin (20.4%), thyroid-stimulating hormone (13.3%), and adrenocorticotropic hormone (13.3%) deficiencies. Hypothalamic involvement was associated with earlier onset of dysfunction (P < .001), whereas radiotherapy predicted density (P < .001), Dr. Gan and colleagues reported.
The reduction in EEFS is “concerning given the lack of a corresponding improvement in survival,” the authors said.
“Minimizing future endocrine, visual, and cognitive morbidity remains an important therapeutic goal in managing these tumors,” they added. “Optimal treatment strategy for these benign lesions remains elusive; while the absence of longitudinal neuroendocrine morbidity data limits our understanding of their etiology and evolution.”
Read the full report at J Clin Endocrinol Metab. 2015 Jul 28. doi: 10.1210/jc.2015-2028.
Tumor location and radiotherapy, respectively, predict the speed of onset and density of long-term neuroendocrinopathy following pediatric glioma, report Dr. Hoong-Wei Gan and coauthors at University College London Institute of Child Health.
In a longitudinal study of 166 children with a median age of 4.9 years at diagnosis, progression-free status and endocrine event–free survival (EEFS) were 47.2% and 20.8%, respectively, despite high overall survival of 81%.
Growth hormone deficiency was the most common disorder (40.3%), followed by central precocious puberty (26%), gonadotropin (20.4%), thyroid-stimulating hormone (13.3%), and adrenocorticotropic hormone (13.3%) deficiencies. Hypothalamic involvement was associated with earlier onset of dysfunction (P < .001), whereas radiotherapy predicted density (P < .001), Dr. Gan and colleagues reported.
The reduction in EEFS is “concerning given the lack of a corresponding improvement in survival,” the authors said.
“Minimizing future endocrine, visual, and cognitive morbidity remains an important therapeutic goal in managing these tumors,” they added. “Optimal treatment strategy for these benign lesions remains elusive; while the absence of longitudinal neuroendocrine morbidity data limits our understanding of their etiology and evolution.”
Read the full report at J Clin Endocrinol Metab. 2015 Jul 28. doi: 10.1210/jc.2015-2028.
Tumor location and radiotherapy, respectively, predict the speed of onset and density of long-term neuroendocrinopathy following pediatric glioma, report Dr. Hoong-Wei Gan and coauthors at University College London Institute of Child Health.
In a longitudinal study of 166 children with a median age of 4.9 years at diagnosis, progression-free status and endocrine event–free survival (EEFS) were 47.2% and 20.8%, respectively, despite high overall survival of 81%.
Growth hormone deficiency was the most common disorder (40.3%), followed by central precocious puberty (26%), gonadotropin (20.4%), thyroid-stimulating hormone (13.3%), and adrenocorticotropic hormone (13.3%) deficiencies. Hypothalamic involvement was associated with earlier onset of dysfunction (P < .001), whereas radiotherapy predicted density (P < .001), Dr. Gan and colleagues reported.
The reduction in EEFS is “concerning given the lack of a corresponding improvement in survival,” the authors said.
“Minimizing future endocrine, visual, and cognitive morbidity remains an important therapeutic goal in managing these tumors,” they added. “Optimal treatment strategy for these benign lesions remains elusive; while the absence of longitudinal neuroendocrine morbidity data limits our understanding of their etiology and evolution.”
Read the full report at J Clin Endocrinol Metab. 2015 Jul 28. doi: 10.1210/jc.2015-2028.
Extreme weight states may activate the HPA axis
Cortisol measures in women vary across the weight spectrum, with the lowest levels occurring in overweight-class 1 obese women, and the highest levels occurring in those with anorexia nervosa, according to findings from a cross-sectional study.
Cortisol levels rise with more significant obesity – but not to levels as high as those seen in women with anorexia nervosa, suggesting that extreme underweight and overweight states may activate the hypothalamic-pituitary-adrenal (HPA) axis and that hypercortisolemia may contribute to increased adiposity in those with caloric excess, Dr. Melanie Schorr and her colleagues at Massachusetts General Hospital and Harvard Medical School, Boston, reported online in the Journal of Clinical Endocrinology & Metabolism.
Among the 60 women, aged 18-45 years, who were included in the study, 21 were overweight/obese, 18 had anorexia nervosa, and 21 were of normal weight. A U-shaped relationship was seen between cortisol measures and body mass index (most notably between urinary free cortisol/creatinine clearance [UFC/CrCl] and BMI and between mean overnight serum cortisol and BMI, r = 0.55 and 0.66, respectively), and between cortisol measures and visceral adipose tissue and total fat mass (for example, r = 0.50 for UFC/CrCl and adipose tissue, and 0.61 for UFC/CrCl and total fat mass), and either no relationship or a weak negative linear relationship was observed between lean mass and cortisol measures (for example, r = –0.34 for UFC/CrCL and lean mass). The latter “may be because it is the adipose component that is associated with cortisol measures or because hypercortisolemia contributes to muscle wasting,” the investigators wrote (J. Clin. Endocrinol. Metab. 2015 July [doi:10.1210/JC.2015-2078]).
They also noted that cortisol measures were negatively associated with bone mineral density across the weight spectrum between urinary free cortisol/creatinine clearance and lean body mass, suggesting that “relative hypercortisolemia may contribute to bone loss in the setting of both caloric restriction and excess.”
“Given the fact that obesity has reached epidemic proportions and significantly increases the risk of the metabolic syndrome and cardiovascular disease among other comorbidities, insight into the factors that contribute to obesity and/or its complications may have important therapeutic implications,” they concluded.
The authors reported having no disclosures.
Cortisol measures in women vary across the weight spectrum, with the lowest levels occurring in overweight-class 1 obese women, and the highest levels occurring in those with anorexia nervosa, according to findings from a cross-sectional study.
Cortisol levels rise with more significant obesity – but not to levels as high as those seen in women with anorexia nervosa, suggesting that extreme underweight and overweight states may activate the hypothalamic-pituitary-adrenal (HPA) axis and that hypercortisolemia may contribute to increased adiposity in those with caloric excess, Dr. Melanie Schorr and her colleagues at Massachusetts General Hospital and Harvard Medical School, Boston, reported online in the Journal of Clinical Endocrinology & Metabolism.
Among the 60 women, aged 18-45 years, who were included in the study, 21 were overweight/obese, 18 had anorexia nervosa, and 21 were of normal weight. A U-shaped relationship was seen between cortisol measures and body mass index (most notably between urinary free cortisol/creatinine clearance [UFC/CrCl] and BMI and between mean overnight serum cortisol and BMI, r = 0.55 and 0.66, respectively), and between cortisol measures and visceral adipose tissue and total fat mass (for example, r = 0.50 for UFC/CrCl and adipose tissue, and 0.61 for UFC/CrCl and total fat mass), and either no relationship or a weak negative linear relationship was observed between lean mass and cortisol measures (for example, r = –0.34 for UFC/CrCL and lean mass). The latter “may be because it is the adipose component that is associated with cortisol measures or because hypercortisolemia contributes to muscle wasting,” the investigators wrote (J. Clin. Endocrinol. Metab. 2015 July [doi:10.1210/JC.2015-2078]).
They also noted that cortisol measures were negatively associated with bone mineral density across the weight spectrum between urinary free cortisol/creatinine clearance and lean body mass, suggesting that “relative hypercortisolemia may contribute to bone loss in the setting of both caloric restriction and excess.”
“Given the fact that obesity has reached epidemic proportions and significantly increases the risk of the metabolic syndrome and cardiovascular disease among other comorbidities, insight into the factors that contribute to obesity and/or its complications may have important therapeutic implications,” they concluded.
The authors reported having no disclosures.
Cortisol measures in women vary across the weight spectrum, with the lowest levels occurring in overweight-class 1 obese women, and the highest levels occurring in those with anorexia nervosa, according to findings from a cross-sectional study.
Cortisol levels rise with more significant obesity – but not to levels as high as those seen in women with anorexia nervosa, suggesting that extreme underweight and overweight states may activate the hypothalamic-pituitary-adrenal (HPA) axis and that hypercortisolemia may contribute to increased adiposity in those with caloric excess, Dr. Melanie Schorr and her colleagues at Massachusetts General Hospital and Harvard Medical School, Boston, reported online in the Journal of Clinical Endocrinology & Metabolism.
Among the 60 women, aged 18-45 years, who were included in the study, 21 were overweight/obese, 18 had anorexia nervosa, and 21 were of normal weight. A U-shaped relationship was seen between cortisol measures and body mass index (most notably between urinary free cortisol/creatinine clearance [UFC/CrCl] and BMI and between mean overnight serum cortisol and BMI, r = 0.55 and 0.66, respectively), and between cortisol measures and visceral adipose tissue and total fat mass (for example, r = 0.50 for UFC/CrCl and adipose tissue, and 0.61 for UFC/CrCl and total fat mass), and either no relationship or a weak negative linear relationship was observed between lean mass and cortisol measures (for example, r = –0.34 for UFC/CrCL and lean mass). The latter “may be because it is the adipose component that is associated with cortisol measures or because hypercortisolemia contributes to muscle wasting,” the investigators wrote (J. Clin. Endocrinol. Metab. 2015 July [doi:10.1210/JC.2015-2078]).
They also noted that cortisol measures were negatively associated with bone mineral density across the weight spectrum between urinary free cortisol/creatinine clearance and lean body mass, suggesting that “relative hypercortisolemia may contribute to bone loss in the setting of both caloric restriction and excess.”
“Given the fact that obesity has reached epidemic proportions and significantly increases the risk of the metabolic syndrome and cardiovascular disease among other comorbidities, insight into the factors that contribute to obesity and/or its complications may have important therapeutic implications,” they concluded.
The authors reported having no disclosures.
FROM THE JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
Key clinical point: The variation in cortisol measures suggest that extreme underweight and overweight states may activate the hypothalamic-pituitary-adrenal axis.
Major finding: A U-shaped relationship was seen between cortisol measures and BMI (most notably between urinary free cortisol/creatinine clearance [UFC/CrCl] and BMI, and between mean overnight serum cortisol and BMI, R = 0.55 and 0.66, respectively).
Data source: A cross-sectional study of 60 women.
Disclosures: The authors reported having no disclosures.
Moderate THST was most effective at treating thyroid cancer
Moderate thyroid hormone suppression therapy (THST) is associated with the best outcomes for patients with all stages of thyroid cancer, according to a prospective analysis of a multi-institutional registry published in the Journal of Clinical Endocrinology & Metabolism.
The researchers examined the outcomes of initial treatment for 4,941 patients with differentiated thyroid cancer (DTC), according to registry data from the National Thyroid Cancer Treatment Cooperative Study Group. The treatments included total/near total thyroidectomy (T/NTT), postoperative radioactive iodine-131 (131I), and THST. The median duration between treatment and follow-up for a patient was 6 years, with follow-up information available for all but 94 (1.9%) of the patients in the cohort.
Overall improvement was noted in stage III patients who received 131I (risk ratio, 0.66; P = .04) and stage IV patients who received both T/NTT and 131I (RR, 0.66; P = .049). In all stages, moderate THST was associated with significantly improved overall survival (RR stages I-IV: 0.13, 0.09, 0.13, and 0.33, respectively) and disease-free survival (DFS) (RR stages I-III: 0.52, 0.40, and 0.18, respectively); no additional survival benefit was achieved with more aggressive THST, even when distant metastatic disease was diagnosed during follow-up.
Lower initial stage and moderate THST were independent predictors of improved overall survival during follow-up years 1-3.
Consistent with previous research, this study also showed that T/NTT followed by 131I is associated with benefit in high-risk, but not low-risk patients.
“We report for the first time, in multivariate analysis of primary treatments for DTC, across all stages, only THST was associated with both improved stage-adjusted OS and DFS,” noted Dr. Aubrey A. Carhill and his colleagues.
“This analysis of the larger, more mature registry database extends and refines earlier observations regarding the impact of initial therapies on patient outcomes and further justifies the need for prospective, long-term, controlled studies,” the researchers noted.
Read the full study in the Journal of Clinical Endocrinology & Metabolism (doi:10.1210/JC.2015-1346).
Moderate thyroid hormone suppression therapy (THST) is associated with the best outcomes for patients with all stages of thyroid cancer, according to a prospective analysis of a multi-institutional registry published in the Journal of Clinical Endocrinology & Metabolism.
The researchers examined the outcomes of initial treatment for 4,941 patients with differentiated thyroid cancer (DTC), according to registry data from the National Thyroid Cancer Treatment Cooperative Study Group. The treatments included total/near total thyroidectomy (T/NTT), postoperative radioactive iodine-131 (131I), and THST. The median duration between treatment and follow-up for a patient was 6 years, with follow-up information available for all but 94 (1.9%) of the patients in the cohort.
Overall improvement was noted in stage III patients who received 131I (risk ratio, 0.66; P = .04) and stage IV patients who received both T/NTT and 131I (RR, 0.66; P = .049). In all stages, moderate THST was associated with significantly improved overall survival (RR stages I-IV: 0.13, 0.09, 0.13, and 0.33, respectively) and disease-free survival (DFS) (RR stages I-III: 0.52, 0.40, and 0.18, respectively); no additional survival benefit was achieved with more aggressive THST, even when distant metastatic disease was diagnosed during follow-up.
Lower initial stage and moderate THST were independent predictors of improved overall survival during follow-up years 1-3.
Consistent with previous research, this study also showed that T/NTT followed by 131I is associated with benefit in high-risk, but not low-risk patients.
“We report for the first time, in multivariate analysis of primary treatments for DTC, across all stages, only THST was associated with both improved stage-adjusted OS and DFS,” noted Dr. Aubrey A. Carhill and his colleagues.
“This analysis of the larger, more mature registry database extends and refines earlier observations regarding the impact of initial therapies on patient outcomes and further justifies the need for prospective, long-term, controlled studies,” the researchers noted.
Read the full study in the Journal of Clinical Endocrinology & Metabolism (doi:10.1210/JC.2015-1346).
Moderate thyroid hormone suppression therapy (THST) is associated with the best outcomes for patients with all stages of thyroid cancer, according to a prospective analysis of a multi-institutional registry published in the Journal of Clinical Endocrinology & Metabolism.
The researchers examined the outcomes of initial treatment for 4,941 patients with differentiated thyroid cancer (DTC), according to registry data from the National Thyroid Cancer Treatment Cooperative Study Group. The treatments included total/near total thyroidectomy (T/NTT), postoperative radioactive iodine-131 (131I), and THST. The median duration between treatment and follow-up for a patient was 6 years, with follow-up information available for all but 94 (1.9%) of the patients in the cohort.
Overall improvement was noted in stage III patients who received 131I (risk ratio, 0.66; P = .04) and stage IV patients who received both T/NTT and 131I (RR, 0.66; P = .049). In all stages, moderate THST was associated with significantly improved overall survival (RR stages I-IV: 0.13, 0.09, 0.13, and 0.33, respectively) and disease-free survival (DFS) (RR stages I-III: 0.52, 0.40, and 0.18, respectively); no additional survival benefit was achieved with more aggressive THST, even when distant metastatic disease was diagnosed during follow-up.
Lower initial stage and moderate THST were independent predictors of improved overall survival during follow-up years 1-3.
Consistent with previous research, this study also showed that T/NTT followed by 131I is associated with benefit in high-risk, but not low-risk patients.
“We report for the first time, in multivariate analysis of primary treatments for DTC, across all stages, only THST was associated with both improved stage-adjusted OS and DFS,” noted Dr. Aubrey A. Carhill and his colleagues.
“This analysis of the larger, more mature registry database extends and refines earlier observations regarding the impact of initial therapies on patient outcomes and further justifies the need for prospective, long-term, controlled studies,” the researchers noted.
Read the full study in the Journal of Clinical Endocrinology & Metabolism (doi:10.1210/JC.2015-1346).
New guidelines focus on pediatric thyroid nodules and cancer
The evaluation and treatment of thyroid nodules in children should differ from evaluation and treatment in adults in that ultrasound characteristics and clinical context should be used rather than size alone to identify nodules that warrant fine-needle aspiration, according to new pediatric-specific guidelines from the American Thyroid Association.
The Management Guidelines for Children with Thyroid Nodules and Differentiated Thyroid Cancer – the first-ever guidelines for the evaluation and management of thyroid nodules and cancer in children – also note that fine-needle aspiration (FNA) in children should be performed under ultrasound guidance, that preoperative FNA of a hyperfunctioning nodule in a child is not warranted as long as the lesion is removed, that a diffusely infiltrative form of papillary thyroid cancer may occur in children and should be considered in a clinically suspicious gland, and that surgery (lobectomy plus isthmusectomy) is favored over repeat FNA for most nodules with indeterminate cytology, Dr. Gary L. Francis of Virginia Commonwealth University and Children’s Hospital of Richmond, Va., and his colleagues from the American Thyroid Association Guidelines Task Force on Pediatric Thyroid Cancer determined based on an extensive literature search.
Together this guidance with respect to thyroid nodules represents just one of 34 recommendations contained in the guidelines, which, according to the authors, represent “the current optimal care for children and adolescents with these conditions.”
The guidelines were published in the July issue of Thyroid (2015;25:716-59).
Previous guidelines were geared toward adults, but thyroid neoplasms in children differ from those in adults with respect to pathophysiology, clinical presentation, and long-term outcomes. Further, therapy that may be appropriate in adults may not be appropriate for children at low risk for death but higher risk of long-term harm from certain treatments, they said.
For example, recent studies with long-term follow-up revealed an increase in all-cause mortality for survivors of childhood differentiated thyroid cancer (DTC), primarily caused by second malignancies in children treated with radiation.
“These observations, coupled with a better understanding of the excellent prognosis associated with pediatric DTC, have now prompted the American Thyroid Association to specifically address treatment of children with benign and malignant thyroid tumors,” they wrote.
While the task force acknowledged a paucity of randomized, double-blind, controlled clinical trials involving children with DTC, they note that “retrospective analysis of therapeutic options has led to a reconsideration of the former concept that all children with DTC should be similarly treated and has provided the opportunity ... to broaden the scope of acceptable therapy in an attempt to provide aggressive therapy when warranted and to limit overtreatment to those children who are unlikely to benefit.”
In addition to addressing the evaluation and management of thyroid nodules, the guidelines also address DTC, including preoperative staging, surgical management, postoperative staging, the role of radioactive iodine therapy, and goals for thyrotropin suppression. Management algorithms are proposed, and separate recommendations for papillary and follicular thyroid cancers are provided.
The authors note that since DTC recurrence has been reported as long as 40 years after initial therapy, children with DTC should be “followed for life, albeit with decreasing intensity for those with no evidence for disease.”
The guidelines are timely, as Surveillance, Epidemiology and End Results (SEER) program data indicate that new cases of thyroid cancer in persons under the age of 20 years represent 1.8% of all thyroid malignancies diagnosed in the United States, and that the incidence appears to be increasing.
Among 15- to 19-year old adolescents, thyroid cancer is the eighth most frequently diagnosed cancer, and it is the second most common cancer among girls, the authors said, noting that adolescents have a 10-fold greater incidence than do younger children, and that there is a female to male preponderance.
The development of pediatric-specific guidelines was critical, according to guidelines coauthor, Dr. Peter Angelos, professor of surgery and surgical ethics and chief of endocrine surgery at the University of Chicago Medicine and Biological Sciences.
“As they say, ‘children are not just small adults,’ ” he said in an interview.
In addition to the guidance provided on which types of nodules should be evaluated in children (since size alone should not be used to dictate who undergoes biopsy), a highlight of the guidelines is a recommendation that children with thyroid cancer be treated by multidisciplinary teams of physician in high-volume centers, he said.
“Thyroid cancer in children is different than in adults in that children have much higher rates of involved lymph nodes, but their overall prognosis is excellent despite the frequency of involved nodes. This confluence of findings pushes surgeons to do more aggressive operations to clear lymph nodes. This is a good thing, but unfortunately, can lead to higher complication rates (things such as permanently low calcium levels in the blood),” he said, adding that “the implications of finding a high-volume thyroid cancer surgeon with experience in thyroid cancer surgery on children are very significant and the guidelines make some recommendations about how many operations are necessary to constitute high volume.”
The push to limit the use of radioactive iodine in children further underscores the need for an experienced surgeon, he said.
“In an effort to avoid exposing children to radiation, surgeons are further pushed to be more aggressive in the operating room. Thus, it becomes even more important to see an experienced surgeon so that complications can be minimized. Even a seemingly ‘mild’ complication can be devastating for a child who will likely have to live with that complication for decades to come since the prognosis for thyroid cancer is so good,” he said.
An important potential benefit of treatment at centers with multidisciplinary interest and expertise is facilitation of additional research, particularly in areas of uncertainty, including the proper use of 131I, the interpretation of thyroglobulin (Tg) and TgAb (antibody) levels, the role of prospective ultrasound monitoring in presymptomatic children at risk for thyroid neoplasia, the use of novel targeted therapies for advanced disease that fails to respond to 131I, and the long-term psychosocial impacts of the disease on children and their families, the guideline authors said.
“These areas require well-designed long-term, multicenter studies that will be difficult to perform because of the rarity of pediatric DTC and the prolonged follow-up required to reach meaningful endpoints. Further research should be facilitated by ensuring that children with DTC are treated when possible at centers with multidisciplinary interest and expertise in this disease,” they concluded.
The guidelines were funded by the American Thyroid Association and ThyCa: Thyroid Cancer Survivors’ Association. Dr. Francis reported serving as an adviser to ThyCa and receiving research support from Grifols, Novo Nordisk, and the Juvenile Diabetes Research Foundation. Other authors reported relationships (consulting, receiving research support, and/or serving as a speaker) with Akrimax, IBSA Institut Biochimique, Pfizer, Novo Nordisk, Eli Lilly, AstraZeneca, Bayer Healthcare, Genzyme, Sobi, Henning, and Merck, and ThyCa.
The evaluation and treatment of thyroid nodules in children should differ from evaluation and treatment in adults in that ultrasound characteristics and clinical context should be used rather than size alone to identify nodules that warrant fine-needle aspiration, according to new pediatric-specific guidelines from the American Thyroid Association.
The Management Guidelines for Children with Thyroid Nodules and Differentiated Thyroid Cancer – the first-ever guidelines for the evaluation and management of thyroid nodules and cancer in children – also note that fine-needle aspiration (FNA) in children should be performed under ultrasound guidance, that preoperative FNA of a hyperfunctioning nodule in a child is not warranted as long as the lesion is removed, that a diffusely infiltrative form of papillary thyroid cancer may occur in children and should be considered in a clinically suspicious gland, and that surgery (lobectomy plus isthmusectomy) is favored over repeat FNA for most nodules with indeterminate cytology, Dr. Gary L. Francis of Virginia Commonwealth University and Children’s Hospital of Richmond, Va., and his colleagues from the American Thyroid Association Guidelines Task Force on Pediatric Thyroid Cancer determined based on an extensive literature search.
Together this guidance with respect to thyroid nodules represents just one of 34 recommendations contained in the guidelines, which, according to the authors, represent “the current optimal care for children and adolescents with these conditions.”
The guidelines were published in the July issue of Thyroid (2015;25:716-59).
Previous guidelines were geared toward adults, but thyroid neoplasms in children differ from those in adults with respect to pathophysiology, clinical presentation, and long-term outcomes. Further, therapy that may be appropriate in adults may not be appropriate for children at low risk for death but higher risk of long-term harm from certain treatments, they said.
For example, recent studies with long-term follow-up revealed an increase in all-cause mortality for survivors of childhood differentiated thyroid cancer (DTC), primarily caused by second malignancies in children treated with radiation.
“These observations, coupled with a better understanding of the excellent prognosis associated with pediatric DTC, have now prompted the American Thyroid Association to specifically address treatment of children with benign and malignant thyroid tumors,” they wrote.
While the task force acknowledged a paucity of randomized, double-blind, controlled clinical trials involving children with DTC, they note that “retrospective analysis of therapeutic options has led to a reconsideration of the former concept that all children with DTC should be similarly treated and has provided the opportunity ... to broaden the scope of acceptable therapy in an attempt to provide aggressive therapy when warranted and to limit overtreatment to those children who are unlikely to benefit.”
In addition to addressing the evaluation and management of thyroid nodules, the guidelines also address DTC, including preoperative staging, surgical management, postoperative staging, the role of radioactive iodine therapy, and goals for thyrotropin suppression. Management algorithms are proposed, and separate recommendations for papillary and follicular thyroid cancers are provided.
The authors note that since DTC recurrence has been reported as long as 40 years after initial therapy, children with DTC should be “followed for life, albeit with decreasing intensity for those with no evidence for disease.”
The guidelines are timely, as Surveillance, Epidemiology and End Results (SEER) program data indicate that new cases of thyroid cancer in persons under the age of 20 years represent 1.8% of all thyroid malignancies diagnosed in the United States, and that the incidence appears to be increasing.
Among 15- to 19-year old adolescents, thyroid cancer is the eighth most frequently diagnosed cancer, and it is the second most common cancer among girls, the authors said, noting that adolescents have a 10-fold greater incidence than do younger children, and that there is a female to male preponderance.
The development of pediatric-specific guidelines was critical, according to guidelines coauthor, Dr. Peter Angelos, professor of surgery and surgical ethics and chief of endocrine surgery at the University of Chicago Medicine and Biological Sciences.
“As they say, ‘children are not just small adults,’ ” he said in an interview.
In addition to the guidance provided on which types of nodules should be evaluated in children (since size alone should not be used to dictate who undergoes biopsy), a highlight of the guidelines is a recommendation that children with thyroid cancer be treated by multidisciplinary teams of physician in high-volume centers, he said.
“Thyroid cancer in children is different than in adults in that children have much higher rates of involved lymph nodes, but their overall prognosis is excellent despite the frequency of involved nodes. This confluence of findings pushes surgeons to do more aggressive operations to clear lymph nodes. This is a good thing, but unfortunately, can lead to higher complication rates (things such as permanently low calcium levels in the blood),” he said, adding that “the implications of finding a high-volume thyroid cancer surgeon with experience in thyroid cancer surgery on children are very significant and the guidelines make some recommendations about how many operations are necessary to constitute high volume.”
The push to limit the use of radioactive iodine in children further underscores the need for an experienced surgeon, he said.
“In an effort to avoid exposing children to radiation, surgeons are further pushed to be more aggressive in the operating room. Thus, it becomes even more important to see an experienced surgeon so that complications can be minimized. Even a seemingly ‘mild’ complication can be devastating for a child who will likely have to live with that complication for decades to come since the prognosis for thyroid cancer is so good,” he said.
An important potential benefit of treatment at centers with multidisciplinary interest and expertise is facilitation of additional research, particularly in areas of uncertainty, including the proper use of 131I, the interpretation of thyroglobulin (Tg) and TgAb (antibody) levels, the role of prospective ultrasound monitoring in presymptomatic children at risk for thyroid neoplasia, the use of novel targeted therapies for advanced disease that fails to respond to 131I, and the long-term psychosocial impacts of the disease on children and their families, the guideline authors said.
“These areas require well-designed long-term, multicenter studies that will be difficult to perform because of the rarity of pediatric DTC and the prolonged follow-up required to reach meaningful endpoints. Further research should be facilitated by ensuring that children with DTC are treated when possible at centers with multidisciplinary interest and expertise in this disease,” they concluded.
The guidelines were funded by the American Thyroid Association and ThyCa: Thyroid Cancer Survivors’ Association. Dr. Francis reported serving as an adviser to ThyCa and receiving research support from Grifols, Novo Nordisk, and the Juvenile Diabetes Research Foundation. Other authors reported relationships (consulting, receiving research support, and/or serving as a speaker) with Akrimax, IBSA Institut Biochimique, Pfizer, Novo Nordisk, Eli Lilly, AstraZeneca, Bayer Healthcare, Genzyme, Sobi, Henning, and Merck, and ThyCa.
The evaluation and treatment of thyroid nodules in children should differ from evaluation and treatment in adults in that ultrasound characteristics and clinical context should be used rather than size alone to identify nodules that warrant fine-needle aspiration, according to new pediatric-specific guidelines from the American Thyroid Association.
The Management Guidelines for Children with Thyroid Nodules and Differentiated Thyroid Cancer – the first-ever guidelines for the evaluation and management of thyroid nodules and cancer in children – also note that fine-needle aspiration (FNA) in children should be performed under ultrasound guidance, that preoperative FNA of a hyperfunctioning nodule in a child is not warranted as long as the lesion is removed, that a diffusely infiltrative form of papillary thyroid cancer may occur in children and should be considered in a clinically suspicious gland, and that surgery (lobectomy plus isthmusectomy) is favored over repeat FNA for most nodules with indeterminate cytology, Dr. Gary L. Francis of Virginia Commonwealth University and Children’s Hospital of Richmond, Va., and his colleagues from the American Thyroid Association Guidelines Task Force on Pediatric Thyroid Cancer determined based on an extensive literature search.
Together this guidance with respect to thyroid nodules represents just one of 34 recommendations contained in the guidelines, which, according to the authors, represent “the current optimal care for children and adolescents with these conditions.”
The guidelines were published in the July issue of Thyroid (2015;25:716-59).
Previous guidelines were geared toward adults, but thyroid neoplasms in children differ from those in adults with respect to pathophysiology, clinical presentation, and long-term outcomes. Further, therapy that may be appropriate in adults may not be appropriate for children at low risk for death but higher risk of long-term harm from certain treatments, they said.
For example, recent studies with long-term follow-up revealed an increase in all-cause mortality for survivors of childhood differentiated thyroid cancer (DTC), primarily caused by second malignancies in children treated with radiation.
“These observations, coupled with a better understanding of the excellent prognosis associated with pediatric DTC, have now prompted the American Thyroid Association to specifically address treatment of children with benign and malignant thyroid tumors,” they wrote.
While the task force acknowledged a paucity of randomized, double-blind, controlled clinical trials involving children with DTC, they note that “retrospective analysis of therapeutic options has led to a reconsideration of the former concept that all children with DTC should be similarly treated and has provided the opportunity ... to broaden the scope of acceptable therapy in an attempt to provide aggressive therapy when warranted and to limit overtreatment to those children who are unlikely to benefit.”
In addition to addressing the evaluation and management of thyroid nodules, the guidelines also address DTC, including preoperative staging, surgical management, postoperative staging, the role of radioactive iodine therapy, and goals for thyrotropin suppression. Management algorithms are proposed, and separate recommendations for papillary and follicular thyroid cancers are provided.
The authors note that since DTC recurrence has been reported as long as 40 years after initial therapy, children with DTC should be “followed for life, albeit with decreasing intensity for those with no evidence for disease.”
The guidelines are timely, as Surveillance, Epidemiology and End Results (SEER) program data indicate that new cases of thyroid cancer in persons under the age of 20 years represent 1.8% of all thyroid malignancies diagnosed in the United States, and that the incidence appears to be increasing.
Among 15- to 19-year old adolescents, thyroid cancer is the eighth most frequently diagnosed cancer, and it is the second most common cancer among girls, the authors said, noting that adolescents have a 10-fold greater incidence than do younger children, and that there is a female to male preponderance.
The development of pediatric-specific guidelines was critical, according to guidelines coauthor, Dr. Peter Angelos, professor of surgery and surgical ethics and chief of endocrine surgery at the University of Chicago Medicine and Biological Sciences.
“As they say, ‘children are not just small adults,’ ” he said in an interview.
In addition to the guidance provided on which types of nodules should be evaluated in children (since size alone should not be used to dictate who undergoes biopsy), a highlight of the guidelines is a recommendation that children with thyroid cancer be treated by multidisciplinary teams of physician in high-volume centers, he said.
“Thyroid cancer in children is different than in adults in that children have much higher rates of involved lymph nodes, but their overall prognosis is excellent despite the frequency of involved nodes. This confluence of findings pushes surgeons to do more aggressive operations to clear lymph nodes. This is a good thing, but unfortunately, can lead to higher complication rates (things such as permanently low calcium levels in the blood),” he said, adding that “the implications of finding a high-volume thyroid cancer surgeon with experience in thyroid cancer surgery on children are very significant and the guidelines make some recommendations about how many operations are necessary to constitute high volume.”
The push to limit the use of radioactive iodine in children further underscores the need for an experienced surgeon, he said.
“In an effort to avoid exposing children to radiation, surgeons are further pushed to be more aggressive in the operating room. Thus, it becomes even more important to see an experienced surgeon so that complications can be minimized. Even a seemingly ‘mild’ complication can be devastating for a child who will likely have to live with that complication for decades to come since the prognosis for thyroid cancer is so good,” he said.
An important potential benefit of treatment at centers with multidisciplinary interest and expertise is facilitation of additional research, particularly in areas of uncertainty, including the proper use of 131I, the interpretation of thyroglobulin (Tg) and TgAb (antibody) levels, the role of prospective ultrasound monitoring in presymptomatic children at risk for thyroid neoplasia, the use of novel targeted therapies for advanced disease that fails to respond to 131I, and the long-term psychosocial impacts of the disease on children and their families, the guideline authors said.
“These areas require well-designed long-term, multicenter studies that will be difficult to perform because of the rarity of pediatric DTC and the prolonged follow-up required to reach meaningful endpoints. Further research should be facilitated by ensuring that children with DTC are treated when possible at centers with multidisciplinary interest and expertise in this disease,” they concluded.
The guidelines were funded by the American Thyroid Association and ThyCa: Thyroid Cancer Survivors’ Association. Dr. Francis reported serving as an adviser to ThyCa and receiving research support from Grifols, Novo Nordisk, and the Juvenile Diabetes Research Foundation. Other authors reported relationships (consulting, receiving research support, and/or serving as a speaker) with Akrimax, IBSA Institut Biochimique, Pfizer, Novo Nordisk, Eli Lilly, AstraZeneca, Bayer Healthcare, Genzyme, Sobi, Henning, and Merck, and ThyCa.
FROM THYROID
ICM exposure associated with higher risk of thyroid dysfunction
After adjusting for variables, patients with iodinated contrast media (ICM) exposure had a significantly higher risk of thyroid dysfunction (hazard ratio, 1.46; 95% confidence interval, 1.29-1.66), compared with that of patients in the non-ICM exposure group, wrote the authors of a newly published study in the Journal of Clinical Endocrinology & Metabolism.
Lead author Dr. Edy Kornelius and associates examined 19,642 cases and 78,568 matched controls, recruited from the general population in Taiwan, in a 6-year cohort study. A total of 383 ICM-exposed patients had thyroid dysfunction (cumulative risk: 1.9%), compared with 1,252 patients without ICM exposure (cumulative risk: 1.5%). The number needed to harm (NNH) was 1 for every 250 people, the investigators noted.
In the subgroup analysis, the adjusted hazard ratios of hyperthyroidism and hypothyroidism were 1.22 (95% CI, 1.04-1.44) and 2.00 (95% CI, 1.65-2.44) when compared with controls. Patients with a higher Charlson’s Comorbidity Index were generally at a higher risk of thyroid dysfunction.
“In this study, we found a 22% increased risk of hyperthyroidism in ICM-exposed patients,” the authors wrote. “Although ICM-related imaging and interventional studies improve the disease diagnosis rate and quality of health, physicians should be aware of the complications of ICM and should apply it cautiously in clinical practice.”
For the full article, click here: J. Clin. Endocrinol. Metab. 2015 (doi:10.1210/JC.2015-2329).
After adjusting for variables, patients with iodinated contrast media (ICM) exposure had a significantly higher risk of thyroid dysfunction (hazard ratio, 1.46; 95% confidence interval, 1.29-1.66), compared with that of patients in the non-ICM exposure group, wrote the authors of a newly published study in the Journal of Clinical Endocrinology & Metabolism.
Lead author Dr. Edy Kornelius and associates examined 19,642 cases and 78,568 matched controls, recruited from the general population in Taiwan, in a 6-year cohort study. A total of 383 ICM-exposed patients had thyroid dysfunction (cumulative risk: 1.9%), compared with 1,252 patients without ICM exposure (cumulative risk: 1.5%). The number needed to harm (NNH) was 1 for every 250 people, the investigators noted.
In the subgroup analysis, the adjusted hazard ratios of hyperthyroidism and hypothyroidism were 1.22 (95% CI, 1.04-1.44) and 2.00 (95% CI, 1.65-2.44) when compared with controls. Patients with a higher Charlson’s Comorbidity Index were generally at a higher risk of thyroid dysfunction.
“In this study, we found a 22% increased risk of hyperthyroidism in ICM-exposed patients,” the authors wrote. “Although ICM-related imaging and interventional studies improve the disease diagnosis rate and quality of health, physicians should be aware of the complications of ICM and should apply it cautiously in clinical practice.”
For the full article, click here: J. Clin. Endocrinol. Metab. 2015 (doi:10.1210/JC.2015-2329).
After adjusting for variables, patients with iodinated contrast media (ICM) exposure had a significantly higher risk of thyroid dysfunction (hazard ratio, 1.46; 95% confidence interval, 1.29-1.66), compared with that of patients in the non-ICM exposure group, wrote the authors of a newly published study in the Journal of Clinical Endocrinology & Metabolism.
Lead author Dr. Edy Kornelius and associates examined 19,642 cases and 78,568 matched controls, recruited from the general population in Taiwan, in a 6-year cohort study. A total of 383 ICM-exposed patients had thyroid dysfunction (cumulative risk: 1.9%), compared with 1,252 patients without ICM exposure (cumulative risk: 1.5%). The number needed to harm (NNH) was 1 for every 250 people, the investigators noted.
In the subgroup analysis, the adjusted hazard ratios of hyperthyroidism and hypothyroidism were 1.22 (95% CI, 1.04-1.44) and 2.00 (95% CI, 1.65-2.44) when compared with controls. Patients with a higher Charlson’s Comorbidity Index were generally at a higher risk of thyroid dysfunction.
“In this study, we found a 22% increased risk of hyperthyroidism in ICM-exposed patients,” the authors wrote. “Although ICM-related imaging and interventional studies improve the disease diagnosis rate and quality of health, physicians should be aware of the complications of ICM and should apply it cautiously in clinical practice.”
For the full article, click here: J. Clin. Endocrinol. Metab. 2015 (doi:10.1210/JC.2015-2329).
Gene-testing predictive value can depend on institutional cancer prevalence
Molecular profiling may be useful to thyroid surgeons in a variety of scenarios, but results should be interpreted with proper knowledge of cancer prevalence at the clinician’s institution, report Dr. Robert L. Ferris and coauthors of the University of Pittsburgh Cancer Institute.
A large, prospective single-center study examined seven-gene mutational panel performance, and found that for the AUS/FLUS cytologic category, mutation identification had a positive predictive value of 88% for histologic cancers, with a false-positive rate of 12%, the authors said.
Results from two analyses of the gene expression classifier (GEC) test emphasized the importance of cancer prevalence at the institution in interpretation of negative predictive value (NPV) and positive predictive value (PPV). In the first study, though the overall calculated sensitivity for GEC was 94%, the high malignancy rate at the institution resulted in a lower estimated NPV of 90%. The second study found an estimated sensitivity and specificity to be 83% and 10%, respectively, and decreases in estimated NPV (94%) and PPV (16%), Dr. Ferris and his colleagues reported.
“Given the well established and frequently dramatic variations in cancer prevalence in thyroid cytology specimens, clinicians are urged to be aware of the prevalence of disease by cytologic category in their tested patients and carefully consider how local disease prevalence may change PPV and NPV of molecular diagnostic tests when applied to their unique clinical practice,” the authors said in the report.
Additionally, “the use of molecular profiling in cytologic indeterminate categories should be interpreted judiciously and with discretion by the clinician, who must be aware of institutional cytopathologic performance results, as well as the individual clinical and sonographic factors for each patient,” they concluded.
Read the full article in Thyroid (doi/pdf/10.1089/thy.2014.0502).
Molecular profiling may be useful to thyroid surgeons in a variety of scenarios, but results should be interpreted with proper knowledge of cancer prevalence at the clinician’s institution, report Dr. Robert L. Ferris and coauthors of the University of Pittsburgh Cancer Institute.
A large, prospective single-center study examined seven-gene mutational panel performance, and found that for the AUS/FLUS cytologic category, mutation identification had a positive predictive value of 88% for histologic cancers, with a false-positive rate of 12%, the authors said.
Results from two analyses of the gene expression classifier (GEC) test emphasized the importance of cancer prevalence at the institution in interpretation of negative predictive value (NPV) and positive predictive value (PPV). In the first study, though the overall calculated sensitivity for GEC was 94%, the high malignancy rate at the institution resulted in a lower estimated NPV of 90%. The second study found an estimated sensitivity and specificity to be 83% and 10%, respectively, and decreases in estimated NPV (94%) and PPV (16%), Dr. Ferris and his colleagues reported.
“Given the well established and frequently dramatic variations in cancer prevalence in thyroid cytology specimens, clinicians are urged to be aware of the prevalence of disease by cytologic category in their tested patients and carefully consider how local disease prevalence may change PPV and NPV of molecular diagnostic tests when applied to their unique clinical practice,” the authors said in the report.
Additionally, “the use of molecular profiling in cytologic indeterminate categories should be interpreted judiciously and with discretion by the clinician, who must be aware of institutional cytopathologic performance results, as well as the individual clinical and sonographic factors for each patient,” they concluded.
Read the full article in Thyroid (doi/pdf/10.1089/thy.2014.0502).
Molecular profiling may be useful to thyroid surgeons in a variety of scenarios, but results should be interpreted with proper knowledge of cancer prevalence at the clinician’s institution, report Dr. Robert L. Ferris and coauthors of the University of Pittsburgh Cancer Institute.
A large, prospective single-center study examined seven-gene mutational panel performance, and found that for the AUS/FLUS cytologic category, mutation identification had a positive predictive value of 88% for histologic cancers, with a false-positive rate of 12%, the authors said.
Results from two analyses of the gene expression classifier (GEC) test emphasized the importance of cancer prevalence at the institution in interpretation of negative predictive value (NPV) and positive predictive value (PPV). In the first study, though the overall calculated sensitivity for GEC was 94%, the high malignancy rate at the institution resulted in a lower estimated NPV of 90%. The second study found an estimated sensitivity and specificity to be 83% and 10%, respectively, and decreases in estimated NPV (94%) and PPV (16%), Dr. Ferris and his colleagues reported.
“Given the well established and frequently dramatic variations in cancer prevalence in thyroid cytology specimens, clinicians are urged to be aware of the prevalence of disease by cytologic category in their tested patients and carefully consider how local disease prevalence may change PPV and NPV of molecular diagnostic tests when applied to their unique clinical practice,” the authors said in the report.
Additionally, “the use of molecular profiling in cytologic indeterminate categories should be interpreted judiciously and with discretion by the clinician, who must be aware of institutional cytopathologic performance results, as well as the individual clinical and sonographic factors for each patient,” they concluded.
Read the full article in Thyroid (doi/pdf/10.1089/thy.2014.0502).
