Pituitary, Thyroid & Adrenal Disorders

Neither clinical nor subclinical hypothyroidism was associated with mild cognitive impairment in a large, population-based study.

Among almost 2,000 elderly subjects, mild cognitive impairment (MCI) was present in 16% of those with normal thyroid function, 17% of those with clinical hypothyroidism, and 18% of those with subclinical hypothyroidism, Dr. Ajay K. Parsaik and his colleagues reported in the Dec. 30 issue of JAMA Neurology (doi:10.1001/jamaneurol.2013.5402).

The findings question the usefulness of pursuing thyroid status as a possible contributor to MCI, wrote Dr. Parsaik of the department of psychiatry and behavior sciences, University of Texas Medical School, Houston, and his coauthors.

"Cognitive decline and thyroid dysfunction are common in the elderly, and a widely held view is that hypothyroidism is a reversible risk factor for cognitive impairment, even though several studies have shown no such association. Our population-based findings also argue against an association and suggest that neither clinical nor subclinical hypothyroidism is a risk factor for MCI. .... This raises questions about the need for routine testing of thyroid function as a part of the diagnostic work-up in patients with MCI."

The team examined thyroid function and cognitive status among 1,904 elderly subjects who were included in the Olmsted County (Minn.) health care records database. Most (1,588; 83%) were cognitively normal; 316 had MCI. Those with MCI were older (82 vs. 80 years), less educated (13 vs. 14 years), and more often carriers of the apolipoprotein E4 risk gene (30% vs. 22%).

Medical comorbidities, including hypertension, coronary artery disease, diabetes, stroke, and depression were significantly more common among those with MCI.

Most subjects (1,450) had normal thyroid function. Of these, 84% were cognitively normal and 16% had MCI.

Clinical hypothyroidism was present in 313; of these, 83% were cognitively normal, and 17% had MCI. All subjects were taking thyroid replacement therapy.

Subclinical hypothyroidism was present in 141; of these, 83% were cognitively normal and 18% had MCI. None of these subjects were getting thyroid replacement therapy.

In an analysis that controlled for age, education, sex, APOE E4 status, depression, and medical comorbidities, MCI was not significantly associated with either clinical or subclinical hypothyroidism. There was no significant interaction between APOE E4 status and hypothyroidism.

The authors noted that their findings should be validated in a larger, longitudinal study in a more varied population.

The study was sponsored by the National Institutes of Health. Dr. Parsaik had no financial disclosures. One of the coauthors, Dr. Bradley Boeve, reported multiple disclosures, some with pharmaceutical companies.

msullivan@frontlinemedcom.com

Neither clinical nor subclinical hypothyroidism was associated with mild cognitive impairment in a large, population-based study.

Among almost 2,000 elderly subjects, mild cognitive impairment (MCI) was present in 16% of those with normal thyroid function, 17% of those with clinical hypothyroidism, and 18% of those with subclinical hypothyroidism, Dr. Ajay K. Parsaik and his colleagues reported in the Dec. 30 issue of JAMA Neurology (doi:10.1001/jamaneurol.2013.5402).

The findings question the usefulness of pursuing thyroid status as a possible contributor to MCI, wrote Dr. Parsaik of the department of psychiatry and behavior sciences, University of Texas Medical School, Houston, and his coauthors.

"Cognitive decline and thyroid dysfunction are common in the elderly, and a widely held view is that hypothyroidism is a reversible risk factor for cognitive impairment, even though several studies have shown no such association. Our population-based findings also argue against an association and suggest that neither clinical nor subclinical hypothyroidism is a risk factor for MCI. .... This raises questions about the need for routine testing of thyroid function as a part of the diagnostic work-up in patients with MCI."

The team examined thyroid function and cognitive status among 1,904 elderly subjects who were included in the Olmsted County (Minn.) health care records database. Most (1,588; 83%) were cognitively normal; 316 had MCI. Those with MCI were older (82 vs. 80 years), less educated (13 vs. 14 years), and more often carriers of the apolipoprotein E4 risk gene (30% vs. 22%).

Medical comorbidities, including hypertension, coronary artery disease, diabetes, stroke, and depression were significantly more common among those with MCI.

Most subjects (1,450) had normal thyroid function. Of these, 84% were cognitively normal and 16% had MCI.

Clinical hypothyroidism was present in 313; of these, 83% were cognitively normal, and 17% had MCI. All subjects were taking thyroid replacement therapy.

Subclinical hypothyroidism was present in 141; of these, 83% were cognitively normal and 18% had MCI. None of these subjects were getting thyroid replacement therapy.

In an analysis that controlled for age, education, sex, APOE E4 status, depression, and medical comorbidities, MCI was not significantly associated with either clinical or subclinical hypothyroidism. There was no significant interaction between APOE E4 status and hypothyroidism.

The authors noted that their findings should be validated in a larger, longitudinal study in a more varied population.

The study was sponsored by the National Institutes of Health. Dr. Parsaik had no financial disclosures. One of the coauthors, Dr. Bradley Boeve, reported multiple disclosures, some with pharmaceutical companies.

msullivan@frontlinemedcom.com

Neither clinical nor subclinical hypothyroidism was associated with mild cognitive impairment in a large, population-based study.

Among almost 2,000 elderly subjects, mild cognitive impairment (MCI) was present in 16% of those with normal thyroid function, 17% of those with clinical hypothyroidism, and 18% of those with subclinical hypothyroidism, Dr. Ajay K. Parsaik and his colleagues reported in the Dec. 30 issue of JAMA Neurology (doi:10.1001/jamaneurol.2013.5402).

The findings question the usefulness of pursuing thyroid status as a possible contributor to MCI, wrote Dr. Parsaik of the department of psychiatry and behavior sciences, University of Texas Medical School, Houston, and his coauthors.

"Cognitive decline and thyroid dysfunction are common in the elderly, and a widely held view is that hypothyroidism is a reversible risk factor for cognitive impairment, even though several studies have shown no such association. Our population-based findings also argue against an association and suggest that neither clinical nor subclinical hypothyroidism is a risk factor for MCI. .... This raises questions about the need for routine testing of thyroid function as a part of the diagnostic work-up in patients with MCI."

The team examined thyroid function and cognitive status among 1,904 elderly subjects who were included in the Olmsted County (Minn.) health care records database. Most (1,588; 83%) were cognitively normal; 316 had MCI. Those with MCI were older (82 vs. 80 years), less educated (13 vs. 14 years), and more often carriers of the apolipoprotein E4 risk gene (30% vs. 22%).

Medical comorbidities, including hypertension, coronary artery disease, diabetes, stroke, and depression were significantly more common among those with MCI.

Most subjects (1,450) had normal thyroid function. Of these, 84% were cognitively normal and 16% had MCI.

Clinical hypothyroidism was present in 313; of these, 83% were cognitively normal, and 17% had MCI. All subjects were taking thyroid replacement therapy.

Subclinical hypothyroidism was present in 141; of these, 83% were cognitively normal and 18% had MCI. None of these subjects were getting thyroid replacement therapy.

In an analysis that controlled for age, education, sex, APOE E4 status, depression, and medical comorbidities, MCI was not significantly associated with either clinical or subclinical hypothyroidism. There was no significant interaction between APOE E4 status and hypothyroidism.

The authors noted that their findings should be validated in a larger, longitudinal study in a more varied population.

The study was sponsored by the National Institutes of Health. Dr. Parsaik had no financial disclosures. One of the coauthors, Dr. Bradley Boeve, reported multiple disclosures, some with pharmaceutical companies.

msullivan@frontlinemedcom.com

Sorafenib’s approval has been expanded to include late-stage differentiated thyroid cancer, the Food and Drug Administration announced on Nov. 22.

The kinase inhibitor was approved for the treatment of "locally recurrent or metastatic, progressive, differentiated thyroid carcinoma refractory to radioactive iodine treatment," according to the prescribing information.

The expedited approval –completed in 6 months – was based on a study of 417 people with locally recurrent or metastatic, progressive differentiated thyroid cancer that had not responded to radioactive iodine treatment. Subjects were randomized to 400 mg of sorafenib twice a day or placebo. The median progression-free survival was 10.8 months among those on sorafenib and 5.8 months among those on placebo, a statistically significant 41% difference.

Diarrhea, fatigue, infection, alopecia, hand-foot skin reaction, rash, weight loss, decreased appetite, nausea, gastrointestinal and abdominal pains, and hypertension were among the most common adverse effects associated with treatment, according to the FDA. In addition, thyroid stimulating hormone, which can promote thyroid cancer, "is more likely to become elevated while on treatment with Nexavar, requiring adjustment of thyroid hormone replacement therapy," the statement said.

Sorafenib, marketed as Nexavar by Bayer HealthCare Pharmaceuticals was approved for treating advanced renal cell carcinoma in 2005 and for unresectable hepatocellular carcinoma in 2007.

emechcatie@frontlinemedcom.com

Sorafenib’s approval has been expanded to include late-stage differentiated thyroid cancer, the Food and Drug Administration announced on Nov. 22.

The kinase inhibitor was approved for the treatment of "locally recurrent or metastatic, progressive, differentiated thyroid carcinoma refractory to radioactive iodine treatment," according to the prescribing information.

The expedited approval –completed in 6 months – was based on a study of 417 people with locally recurrent or metastatic, progressive differentiated thyroid cancer that had not responded to radioactive iodine treatment. Subjects were randomized to 400 mg of sorafenib twice a day or placebo. The median progression-free survival was 10.8 months among those on sorafenib and 5.8 months among those on placebo, a statistically significant 41% difference.

Diarrhea, fatigue, infection, alopecia, hand-foot skin reaction, rash, weight loss, decreased appetite, nausea, gastrointestinal and abdominal pains, and hypertension were among the most common adverse effects associated with treatment, according to the FDA. In addition, thyroid stimulating hormone, which can promote thyroid cancer, "is more likely to become elevated while on treatment with Nexavar, requiring adjustment of thyroid hormone replacement therapy," the statement said.

Sorafenib, marketed as Nexavar by Bayer HealthCare Pharmaceuticals was approved for treating advanced renal cell carcinoma in 2005 and for unresectable hepatocellular carcinoma in 2007.

emechcatie@frontlinemedcom.com

Sorafenib’s approval has been expanded to include late-stage differentiated thyroid cancer, the Food and Drug Administration announced on Nov. 22.

The kinase inhibitor was approved for the treatment of "locally recurrent or metastatic, progressive, differentiated thyroid carcinoma refractory to radioactive iodine treatment," according to the prescribing information.

The expedited approval –completed in 6 months – was based on a study of 417 people with locally recurrent or metastatic, progressive differentiated thyroid cancer that had not responded to radioactive iodine treatment. Subjects were randomized to 400 mg of sorafenib twice a day or placebo. The median progression-free survival was 10.8 months among those on sorafenib and 5.8 months among those on placebo, a statistically significant 41% difference.

Diarrhea, fatigue, infection, alopecia, hand-foot skin reaction, rash, weight loss, decreased appetite, nausea, gastrointestinal and abdominal pains, and hypertension were among the most common adverse effects associated with treatment, according to the FDA. In addition, thyroid stimulating hormone, which can promote thyroid cancer, "is more likely to become elevated while on treatment with Nexavar, requiring adjustment of thyroid hormone replacement therapy," the statement said.

Sorafenib, marketed as Nexavar by Bayer HealthCare Pharmaceuticals was approved for treating advanced renal cell carcinoma in 2005 and for unresectable hepatocellular carcinoma in 2007.

emechcatie@frontlinemedcom.com

SAN DIEGO – The prevalence of unsuspected primary hyperparathyroidism among patients diagnosed with fibromyalgia was 11% in a small exploratory study, Dr. Michael Tsoukas reported at the annual meeting of the American College of Rheumatology.

That’s roughly 100-fold greater than the prevalence of primary hyperparathyroidism in the general population, noted Dr. Tsoukas of McGill University, Montreal.

The classic symptoms of primary hyperparathyroidism include musculoskeletal pain, fatigue, mood disorders, and sleep disturbances, a clinical picture closely mimicking that of fibromyalgia, he observed.

Dr. Tsoukas presented a retrospective study of a convenience sample of 38 consecutive patients with a primary diagnosis of fibromyalgia attending a multidisciplinary tertiary care pain center where physicians obtained routine blood tests. Four of the 38, or 11%, met criteria for the biochemical diagnosis of hyperthyroidism. Two had what’s known as normohormonal hyperparathyroidism, marked by a serum ionized calcium elevated above 1.32 mmol/L or 5.3 mg/dL, with inappropriately high parathyroid hormone levels. The other two had a parathyroid hormone level in excess of 9.3 pmol/L or 93 pg/mL, with inappropriately nonsuppressed calcium.

This was a pilot study. Four cases of unsuspected hyperparathyroidism hardly make for a definitive study. But this was the first study to look at hyperparathyroidism in fibromyalgia patients, and given how common fibromyalgia is and the difficulties and frustrations often encountered in its treatment, these intriguing preliminary findings warrant large, prospective, multicenter studies to further clarify the relationship between these two disorders with closely similar symptoms, Dr. Tsoukas concluded.

He reported having no financial conflicts of interest in this unfunded study.

bjancin@frontlinemedcom.com

SAN DIEGO – The prevalence of unsuspected primary hyperparathyroidism among patients diagnosed with fibromyalgia was 11% in a small exploratory study, Dr. Michael Tsoukas reported at the annual meeting of the American College of Rheumatology.

That’s roughly 100-fold greater than the prevalence of primary hyperparathyroidism in the general population, noted Dr. Tsoukas of McGill University, Montreal.

The classic symptoms of primary hyperparathyroidism include musculoskeletal pain, fatigue, mood disorders, and sleep disturbances, a clinical picture closely mimicking that of fibromyalgia, he observed.

Dr. Tsoukas presented a retrospective study of a convenience sample of 38 consecutive patients with a primary diagnosis of fibromyalgia attending a multidisciplinary tertiary care pain center where physicians obtained routine blood tests. Four of the 38, or 11%, met criteria for the biochemical diagnosis of hyperthyroidism. Two had what’s known as normohormonal hyperparathyroidism, marked by a serum ionized calcium elevated above 1.32 mmol/L or 5.3 mg/dL, with inappropriately high parathyroid hormone levels. The other two had a parathyroid hormone level in excess of 9.3 pmol/L or 93 pg/mL, with inappropriately nonsuppressed calcium.

This was a pilot study. Four cases of unsuspected hyperparathyroidism hardly make for a definitive study. But this was the first study to look at hyperparathyroidism in fibromyalgia patients, and given how common fibromyalgia is and the difficulties and frustrations often encountered in its treatment, these intriguing preliminary findings warrant large, prospective, multicenter studies to further clarify the relationship between these two disorders with closely similar symptoms, Dr. Tsoukas concluded.

He reported having no financial conflicts of interest in this unfunded study.

bjancin@frontlinemedcom.com

SAN DIEGO – The prevalence of unsuspected primary hyperparathyroidism among patients diagnosed with fibromyalgia was 11% in a small exploratory study, Dr. Michael Tsoukas reported at the annual meeting of the American College of Rheumatology.

That’s roughly 100-fold greater than the prevalence of primary hyperparathyroidism in the general population, noted Dr. Tsoukas of McGill University, Montreal.

The classic symptoms of primary hyperparathyroidism include musculoskeletal pain, fatigue, mood disorders, and sleep disturbances, a clinical picture closely mimicking that of fibromyalgia, he observed.

Dr. Tsoukas presented a retrospective study of a convenience sample of 38 consecutive patients with a primary diagnosis of fibromyalgia attending a multidisciplinary tertiary care pain center where physicians obtained routine blood tests. Four of the 38, or 11%, met criteria for the biochemical diagnosis of hyperthyroidism. Two had what’s known as normohormonal hyperparathyroidism, marked by a serum ionized calcium elevated above 1.32 mmol/L or 5.3 mg/dL, with inappropriately high parathyroid hormone levels. The other two had a parathyroid hormone level in excess of 9.3 pmol/L or 93 pg/mL, with inappropriately nonsuppressed calcium.

This was a pilot study. Four cases of unsuspected hyperparathyroidism hardly make for a definitive study. But this was the first study to look at hyperparathyroidism in fibromyalgia patients, and given how common fibromyalgia is and the difficulties and frustrations often encountered in its treatment, these intriguing preliminary findings warrant large, prospective, multicenter studies to further clarify the relationship between these two disorders with closely similar symptoms, Dr. Tsoukas concluded.

He reported having no financial conflicts of interest in this unfunded study.

bjancin@frontlinemedcom.com

ISTANBUL, TURKEY – Patients with hidradenitis suppurativa have a sharply increased prevalence of the metabolic syndrome, according to the first case-control study to examine the relationship.

Metabolic syndrome is known to be associated with increased cardiovascular risk, which may be particularly high in patients with hidradenitis suppurativa (HS), a dermatologic disease with an estimated prevalence of 1%-4%, because they develop metabolic syndrome at a much younger age than do individuals without the dermatologic disease, Dr. Wolfram Sterry said at the annual congress of the European Academy of Dermatology and Venereology.

He presented highlights from a single-center, case-control study that comprised 80 patients with HS with a mean 12-year disease duration and 100 age- and gender-matched controls. Patients’ mean age was 40 years (PLoS One 2012 [doi:10.1371/journal.pone.0031810]).

The prevalence of metabolic syndrome was 40% in the HS group and 13% in controls, for an adjusted 4.5-fold increased likelihood, reported Dr. Sterry, professor and chairman of the department of dermatology at Charité University Hospital, Berlin.

Of the five metabolic derangements used in defining the metabolic syndrome, four were significantly more prevalent in subjects with HS. They were 5.9-fold more likely than were matched controls to have central obesity, 4.1-fold more likely to have hyperglycemia, 4.6-fold more likely to have low HDL cholesterol, and 2.2-fold more likely to be hypertriglyceridemic. Hypertension was present in 48% of HS patients and 35% of controls, a difference that did not achieve statistical significance.

Of note, HS patients with metabolic syndrome had more pronounced metabolic abnormalities than did controls with metabolic syndrome. While the definition of metabolic syndrome requires the presence of at least three of five metabolic alterations, half of all HS patients with metabolic syndrome met four or more of the criteria, compared with 39% of controls.

Moreover, metabolic syndrome occurred at a much younger age in subjects with HS than is typical in the general population or than was seen in controls. Indeed, 40% of HS patients under age 35 had metabolic syndrome, compared with none of the matched controls. Thus, the odds ratio for metabolic syndrome in HS patients aged 34 years or less was increased more than 20-fold compared with controls, while in the 35- to 44-year-old age group it was increased 6.2-fold, and in HS patients aged 45 and older it was 2-fold higher.

An increased prevalence of metabolic syndrome also has been documented in patients with psoriasis. But the prevalence of metabolic syndrome appears to be higher in HS patients and the metabolic disorder occurs at an earlier age than in psoriasis.

There was no correlation between duration or severity of HS and the prevalence of metabolic syndrome, according to Dr. Sterry. That’s an important message for physicians who see patients with the skin disease because it means such patients should be evaluated for metabolic syndrome early on, even if they have only moderate skin disease. After all, the elements of the metabolic syndrome are modifiable cardiovascular risk factors.

The lack of correlation between HS severity or duration and metabolic syndrome prevalence also has implications for the mechanism underlying the increased risk of metabolic syndrome in HS. When Dr. Sterry and coworkers compared the levels of metabolic syndrome parameters in the 42 patients with prior surgical treatment of their HS to the 38 patients who had not undergone surgery, they found no significant differences even though the surgical patients presumably had less inflammatory load. This led them to speculate that chronic inflammation may not be the major driver of the metabolic abnormalities in HS patients.

"It must be that a genetic predisposition for metabolic syndrome then induces the development of acne inversa [hidradenitis suppurativa] in predisposed individuals," Dr. Sterry said.

The proposed mechanism involves metabolic syndrome–induced poor blood circulation in the intertriginous axillary, perianal, and inguinal skin where HS most often occurs, with resultant increased interleukin-10 production by CD4-positive T cells. Interleukin-10, in turn, inhibits keratinocyte production of interleukins-20 and -22, which induce antimicrobial proteins in the skin. This would set the stage for HS, which is characterized by bacterial persistence in obstructed hair follicles, nodules, and fistulating sinuses.

Of course, this is speculation, Dr. Sterry was quick to acknowledge.

"Acne inversa is also known as hidradenitis suppurativa, apocrine acne, pyoderma fistulans significa ... If a disease has that many names, that’s always a sign that we don’t know too much about it," the dermatologist observed.

In a separate study presented at the EADV, investigators found that the most common comorbid conditions in a cohort of 154 patients with HS enrolled in a clinical trial of adalimumab (Humira) therapy were depression as defined by a score of 10 or more on the Patient Health Questionnaire–9, which had a prevalence of 42%; severe obesity marked by a body mass index of at least 40 kg/m², present in 28% of patients; and uncontrolled hypertension, which was present in 27%. However, the investigators did not look at metabolic syndrome.

Dr. Sterry reported having no financial conflicts regarding this unfunded case-control study.

bjancin@frontlinemedcom.com

ISTANBUL, TURKEY – Patients with hidradenitis suppurativa have a sharply increased prevalence of the metabolic syndrome, according to the first case-control study to examine the relationship.

Metabolic syndrome is known to be associated with increased cardiovascular risk, which may be particularly high in patients with hidradenitis suppurativa (HS), a dermatologic disease with an estimated prevalence of 1%-4%, because they develop metabolic syndrome at a much younger age than do individuals without the dermatologic disease, Dr. Wolfram Sterry said at the annual congress of the European Academy of Dermatology and Venereology.

He presented highlights from a single-center, case-control study that comprised 80 patients with HS with a mean 12-year disease duration and 100 age- and gender-matched controls. Patients’ mean age was 40 years (PLoS One 2012 [doi:10.1371/journal.pone.0031810]).

The prevalence of metabolic syndrome was 40% in the HS group and 13% in controls, for an adjusted 4.5-fold increased likelihood, reported Dr. Sterry, professor and chairman of the department of dermatology at Charité University Hospital, Berlin.

Of the five metabolic derangements used in defining the metabolic syndrome, four were significantly more prevalent in subjects with HS. They were 5.9-fold more likely than were matched controls to have central obesity, 4.1-fold more likely to have hyperglycemia, 4.6-fold more likely to have low HDL cholesterol, and 2.2-fold more likely to be hypertriglyceridemic. Hypertension was present in 48% of HS patients and 35% of controls, a difference that did not achieve statistical significance.

Of note, HS patients with metabolic syndrome had more pronounced metabolic abnormalities than did controls with metabolic syndrome. While the definition of metabolic syndrome requires the presence of at least three of five metabolic alterations, half of all HS patients with metabolic syndrome met four or more of the criteria, compared with 39% of controls.

Moreover, metabolic syndrome occurred at a much younger age in subjects with HS than is typical in the general population or than was seen in controls. Indeed, 40% of HS patients under age 35 had metabolic syndrome, compared with none of the matched controls. Thus, the odds ratio for metabolic syndrome in HS patients aged 34 years or less was increased more than 20-fold compared with controls, while in the 35- to 44-year-old age group it was increased 6.2-fold, and in HS patients aged 45 and older it was 2-fold higher.

An increased prevalence of metabolic syndrome also has been documented in patients with psoriasis. But the prevalence of metabolic syndrome appears to be higher in HS patients and the metabolic disorder occurs at an earlier age than in psoriasis.

There was no correlation between duration or severity of HS and the prevalence of metabolic syndrome, according to Dr. Sterry. That’s an important message for physicians who see patients with the skin disease because it means such patients should be evaluated for metabolic syndrome early on, even if they have only moderate skin disease. After all, the elements of the metabolic syndrome are modifiable cardiovascular risk factors.

The lack of correlation between HS severity or duration and metabolic syndrome prevalence also has implications for the mechanism underlying the increased risk of metabolic syndrome in HS. When Dr. Sterry and coworkers compared the levels of metabolic syndrome parameters in the 42 patients with prior surgical treatment of their HS to the 38 patients who had not undergone surgery, they found no significant differences even though the surgical patients presumably had less inflammatory load. This led them to speculate that chronic inflammation may not be the major driver of the metabolic abnormalities in HS patients.

"It must be that a genetic predisposition for metabolic syndrome then induces the development of acne inversa [hidradenitis suppurativa] in predisposed individuals," Dr. Sterry said.

The proposed mechanism involves metabolic syndrome–induced poor blood circulation in the intertriginous axillary, perianal, and inguinal skin where HS most often occurs, with resultant increased interleukin-10 production by CD4-positive T cells. Interleukin-10, in turn, inhibits keratinocyte production of interleukins-20 and -22, which induce antimicrobial proteins in the skin. This would set the stage for HS, which is characterized by bacterial persistence in obstructed hair follicles, nodules, and fistulating sinuses.

Of course, this is speculation, Dr. Sterry was quick to acknowledge.

"Acne inversa is also known as hidradenitis suppurativa, apocrine acne, pyoderma fistulans significa ... If a disease has that many names, that’s always a sign that we don’t know too much about it," the dermatologist observed.

In a separate study presented at the EADV, investigators found that the most common comorbid conditions in a cohort of 154 patients with HS enrolled in a clinical trial of adalimumab (Humira) therapy were depression as defined by a score of 10 or more on the Patient Health Questionnaire–9, which had a prevalence of 42%; severe obesity marked by a body mass index of at least 40 kg/m², present in 28% of patients; and uncontrolled hypertension, which was present in 27%. However, the investigators did not look at metabolic syndrome.

Dr. Sterry reported having no financial conflicts regarding this unfunded case-control study.

bjancin@frontlinemedcom.com

ISTANBUL, TURKEY – Patients with hidradenitis suppurativa have a sharply increased prevalence of the metabolic syndrome, according to the first case-control study to examine the relationship.

Metabolic syndrome is known to be associated with increased cardiovascular risk, which may be particularly high in patients with hidradenitis suppurativa (HS), a dermatologic disease with an estimated prevalence of 1%-4%, because they develop metabolic syndrome at a much younger age than do individuals without the dermatologic disease, Dr. Wolfram Sterry said at the annual congress of the European Academy of Dermatology and Venereology.

He presented highlights from a single-center, case-control study that comprised 80 patients with HS with a mean 12-year disease duration and 100 age- and gender-matched controls. Patients’ mean age was 40 years (PLoS One 2012 [doi:10.1371/journal.pone.0031810]).

The prevalence of metabolic syndrome was 40% in the HS group and 13% in controls, for an adjusted 4.5-fold increased likelihood, reported Dr. Sterry, professor and chairman of the department of dermatology at Charité University Hospital, Berlin.

Of the five metabolic derangements used in defining the metabolic syndrome, four were significantly more prevalent in subjects with HS. They were 5.9-fold more likely than were matched controls to have central obesity, 4.1-fold more likely to have hyperglycemia, 4.6-fold more likely to have low HDL cholesterol, and 2.2-fold more likely to be hypertriglyceridemic. Hypertension was present in 48% of HS patients and 35% of controls, a difference that did not achieve statistical significance.

Of note, HS patients with metabolic syndrome had more pronounced metabolic abnormalities than did controls with metabolic syndrome. While the definition of metabolic syndrome requires the presence of at least three of five metabolic alterations, half of all HS patients with metabolic syndrome met four or more of the criteria, compared with 39% of controls.

Moreover, metabolic syndrome occurred at a much younger age in subjects with HS than is typical in the general population or than was seen in controls. Indeed, 40% of HS patients under age 35 had metabolic syndrome, compared with none of the matched controls. Thus, the odds ratio for metabolic syndrome in HS patients aged 34 years or less was increased more than 20-fold compared with controls, while in the 35- to 44-year-old age group it was increased 6.2-fold, and in HS patients aged 45 and older it was 2-fold higher.

An increased prevalence of metabolic syndrome also has been documented in patients with psoriasis. But the prevalence of metabolic syndrome appears to be higher in HS patients and the metabolic disorder occurs at an earlier age than in psoriasis.

There was no correlation between duration or severity of HS and the prevalence of metabolic syndrome, according to Dr. Sterry. That’s an important message for physicians who see patients with the skin disease because it means such patients should be evaluated for metabolic syndrome early on, even if they have only moderate skin disease. After all, the elements of the metabolic syndrome are modifiable cardiovascular risk factors.

The lack of correlation between HS severity or duration and metabolic syndrome prevalence also has implications for the mechanism underlying the increased risk of metabolic syndrome in HS. When Dr. Sterry and coworkers compared the levels of metabolic syndrome parameters in the 42 patients with prior surgical treatment of their HS to the 38 patients who had not undergone surgery, they found no significant differences even though the surgical patients presumably had less inflammatory load. This led them to speculate that chronic inflammation may not be the major driver of the metabolic abnormalities in HS patients.

"It must be that a genetic predisposition for metabolic syndrome then induces the development of acne inversa [hidradenitis suppurativa] in predisposed individuals," Dr. Sterry said.

The proposed mechanism involves metabolic syndrome–induced poor blood circulation in the intertriginous axillary, perianal, and inguinal skin where HS most often occurs, with resultant increased interleukin-10 production by CD4-positive T cells. Interleukin-10, in turn, inhibits keratinocyte production of interleukins-20 and -22, which induce antimicrobial proteins in the skin. This would set the stage for HS, which is characterized by bacterial persistence in obstructed hair follicles, nodules, and fistulating sinuses.

Of course, this is speculation, Dr. Sterry was quick to acknowledge.

"Acne inversa is also known as hidradenitis suppurativa, apocrine acne, pyoderma fistulans significa ... If a disease has that many names, that’s always a sign that we don’t know too much about it," the dermatologist observed.

In a separate study presented at the EADV, investigators found that the most common comorbid conditions in a cohort of 154 patients with HS enrolled in a clinical trial of adalimumab (Humira) therapy were depression as defined by a score of 10 or more on the Patient Health Questionnaire–9, which had a prevalence of 42%; severe obesity marked by a body mass index of at least 40 kg/m², present in 28% of patients; and uncontrolled hypertension, which was present in 27%. However, the investigators did not look at metabolic syndrome.

Dr. Sterry reported having no financial conflicts regarding this unfunded case-control study.

bjancin@frontlinemedcom.com

The Endocrine Society and the American Association of Clinical Endocrinologists have released a series of recommendations that advise against unnecessary tests and procedures in patient diagnosis and treatment.

More than 30 health organizations have released or will release treatment guidelines as part of the American Board of Internal Medicine Foundation’s "Choosing Wisely" campaign, which is meant to educate patients and physicians about unnecessary and potentially harmful testing and treatment. The recommendation lists, expected to be completed by early 2014, are part of a series that hopes to "spark conversations between patients and physicians about what care is really necessary for specific conditions."

The Endocrine Society and AACE recommended the following:

• Avoid routine multiple daily self-glucose monitoring in adults with stable type 2 diabetes on agents that do not cause hypoglycemia. Such testing can be excessive for patients who are doing a good job of maintaining glycemic control, and testing results can become quite predictable. There are a number of exceptions, such as when a patient is sick or losing weight, or when new medications are added or hemoglobin A_1c values stray from targets.

• Don’t routinely measure 1,25-dihydroxyvitamin D unless the patient has hypercalcemia or decreased kidney function. In vitamin D deficiency, 1,25-dihydroxyvitamin D levels go up, not down. Serum levels of 1,25-dihyroxyvitamin D are regulated primarily by parathyroid hormone levels and have little connection to vitamin D stores. When trying to assess vitamin D stores or diagnose vitamin D deficiency (or toxicity), 25-hydroxyvitamin D is the correct test.

• Don’t routinely order a thyroid ultrasound in patients with abnormal thyroid function tests if there is no palpable abnormality of the thyroid gland. Nodules detected via ultrasound are usually unrelated to the abnormal thyroid function and may divert the clinical evaluation to assess the nodules, rather than the thyroid dysfunction.

• Don’t order a total or free T3 level when assessing levothyroxine (T4) dose in hypothyroid patients, as the blood level of total or free T3 may be misleading. With most patients, a normal TSH indicates a correct dose of T4.

• Don’t prescribe testosterone therapy unless there is strong biochemical evidence of testosterone deficiency. Many of the symptoms attributed to male hypogonadism are common in the normal male aging process or are the result of a comorbid condition. In addition, testosterone therapy is expensive and has the potential for serious side effects in some patients. Total testosterone levels should be taken in the morning, and a low level should be confirmed on a different day.

mbock@frontlinemedcom.com

The Endocrine Society and the American Association of Clinical Endocrinologists have released a series of recommendations that advise against unnecessary tests and procedures in patient diagnosis and treatment.

More than 30 health organizations have released or will release treatment guidelines as part of the American Board of Internal Medicine Foundation’s "Choosing Wisely" campaign, which is meant to educate patients and physicians about unnecessary and potentially harmful testing and treatment. The recommendation lists, expected to be completed by early 2014, are part of a series that hopes to "spark conversations between patients and physicians about what care is really necessary for specific conditions."

The Endocrine Society and AACE recommended the following:

• Avoid routine multiple daily self-glucose monitoring in adults with stable type 2 diabetes on agents that do not cause hypoglycemia. Such testing can be excessive for patients who are doing a good job of maintaining glycemic control, and testing results can become quite predictable. There are a number of exceptions, such as when a patient is sick or losing weight, or when new medications are added or hemoglobin A_1c values stray from targets.

• Don’t routinely measure 1,25-dihydroxyvitamin D unless the patient has hypercalcemia or decreased kidney function. In vitamin D deficiency, 1,25-dihydroxyvitamin D levels go up, not down. Serum levels of 1,25-dihyroxyvitamin D are regulated primarily by parathyroid hormone levels and have little connection to vitamin D stores. When trying to assess vitamin D stores or diagnose vitamin D deficiency (or toxicity), 25-hydroxyvitamin D is the correct test.

• Don’t routinely order a thyroid ultrasound in patients with abnormal thyroid function tests if there is no palpable abnormality of the thyroid gland. Nodules detected via ultrasound are usually unrelated to the abnormal thyroid function and may divert the clinical evaluation to assess the nodules, rather than the thyroid dysfunction.

• Don’t order a total or free T3 level when assessing levothyroxine (T4) dose in hypothyroid patients, as the blood level of total or free T3 may be misleading. With most patients, a normal TSH indicates a correct dose of T4.

• Don’t prescribe testosterone therapy unless there is strong biochemical evidence of testosterone deficiency. Many of the symptoms attributed to male hypogonadism are common in the normal male aging process or are the result of a comorbid condition. In addition, testosterone therapy is expensive and has the potential for serious side effects in some patients. Total testosterone levels should be taken in the morning, and a low level should be confirmed on a different day.

mbock@frontlinemedcom.com

The Endocrine Society and the American Association of Clinical Endocrinologists have released a series of recommendations that advise against unnecessary tests and procedures in patient diagnosis and treatment.

More than 30 health organizations have released or will release treatment guidelines as part of the American Board of Internal Medicine Foundation’s "Choosing Wisely" campaign, which is meant to educate patients and physicians about unnecessary and potentially harmful testing and treatment. The recommendation lists, expected to be completed by early 2014, are part of a series that hopes to "spark conversations between patients and physicians about what care is really necessary for specific conditions."

The Endocrine Society and AACE recommended the following:

• Avoid routine multiple daily self-glucose monitoring in adults with stable type 2 diabetes on agents that do not cause hypoglycemia. Such testing can be excessive for patients who are doing a good job of maintaining glycemic control, and testing results can become quite predictable. There are a number of exceptions, such as when a patient is sick or losing weight, or when new medications are added or hemoglobin A_1c values stray from targets.

• Don’t routinely measure 1,25-dihydroxyvitamin D unless the patient has hypercalcemia or decreased kidney function. In vitamin D deficiency, 1,25-dihydroxyvitamin D levels go up, not down. Serum levels of 1,25-dihyroxyvitamin D are regulated primarily by parathyroid hormone levels and have little connection to vitamin D stores. When trying to assess vitamin D stores or diagnose vitamin D deficiency (or toxicity), 25-hydroxyvitamin D is the correct test.

• Don’t routinely order a thyroid ultrasound in patients with abnormal thyroid function tests if there is no palpable abnormality of the thyroid gland. Nodules detected via ultrasound are usually unrelated to the abnormal thyroid function and may divert the clinical evaluation to assess the nodules, rather than the thyroid dysfunction.

• Don’t order a total or free T3 level when assessing levothyroxine (T4) dose in hypothyroid patients, as the blood level of total or free T3 may be misleading. With most patients, a normal TSH indicates a correct dose of T4.

• Don’t prescribe testosterone therapy unless there is strong biochemical evidence of testosterone deficiency. Many of the symptoms attributed to male hypogonadism are common in the normal male aging process or are the result of a comorbid condition. In addition, testosterone therapy is expensive and has the potential for serious side effects in some patients. Total testosterone levels should be taken in the morning, and a low level should be confirmed on a different day.

mbock@frontlinemedcom.com

SAN FRANCISCO – Transcutaneous biopsy of adrenocortical carcinomas did not improve diagnosis or survival, and potentially harmed 11% of patients, in a study of 74 patients.

The study fills a gap behind general recommendations against biopsy of single adrenal masses in the absence of another known malignancy or metastasis, which had been based on fears that biopsy would spread the tumor but lacked clinical evidence, Andrew Williams said in a poster presentation at the annual meeting of the Endocrine Society.

Among 74 patients with adrenocortical carcinoma who had undergone transcutaneous biopsy of an adrenal mass between 1991 and 2011, the sensitivity of the biopsy for the final pathological diagnosis of the disease was 84% at best and as low as 51% in community settings, the retrospective review of electronic medical records found.

Among the 36 patients with stage I-III disease (confined to the adrenal gland) at the time of diagnosis, the biopsy did not significantly change choices regarding adjuvant therapy, compared with 254 patients with stage I-III disease who did not undergo transcutaneous biopsy. The baseline characteristics of these two groups were similar except that patients in the biopsy group were significantly less likely to be secreting hormones (28%) compared with the no-biopsy group (59%).

"Single adrenal masses with malignant characteristics invariably should be treated surgically, making biopsy an unnecessary procedure," reported Mr. Williams, a medical student at the University of Michigan, Ann Arbor, and his associates.

Complications from transcutaneous biopsy in 11% of all patients consisted mainly of bleeding-related events but with one potentially fatal event – needle track metastasis in one patient.

"Single adrenal masses with malignant characteristics invariably should be treated surgically, making biopsy an unnecessary procedure."

Rates of overall and tumor-free survival did not differ significantly between patients who did or did not undergo transcutaneous biopsy in either univariate analysis or multivariate analyses adjusting for age, sex, cortisol production, and adjuvant therapies.

Adrenocortical carcinomas are rare cancers with high rates of recurrence and mortality. Cumulative survival rates in the study decreased steadily to roughly 80% at 1 year, 60% at 3 years, and less than 50% at 5 years.

"Biopsy of adrenocortical carcinomas at stages confined to the adrenal gland does not significantly influence survival," Mr. Williams concluded in the poster. "Adrenal biopsy should only be considered in patients with metastasized disease and unclear tumor origin, only if it may alter the therapeutic approach and only if the adrenal is the easiest site to biopsy."

Patients who underwent biopsy in the study had a median age of 52 years (ranging from 17 to 77 years), and 54% were female. The cohort was 84% white.

Mr. Williams reported having no financial disclosures. Coinvestigator Dr. Gary D. Hammer, also at the University of Michigan, disclosed financial associations with Atterocor, Orphagen Pharmaceuticals, Embera NeuroTherapeutics, HRA Pharma, Corcept Therapeutics, Isis, and OSI-Astella.

sboschert@frontlinemedcom.com

On Twitter @sherryboschert

SAN FRANCISCO – Transcutaneous biopsy of adrenocortical carcinomas did not improve diagnosis or survival, and potentially harmed 11% of patients, in a study of 74 patients.

The study fills a gap behind general recommendations against biopsy of single adrenal masses in the absence of another known malignancy or metastasis, which had been based on fears that biopsy would spread the tumor but lacked clinical evidence, Andrew Williams said in a poster presentation at the annual meeting of the Endocrine Society.

Among 74 patients with adrenocortical carcinoma who had undergone transcutaneous biopsy of an adrenal mass between 1991 and 2011, the sensitivity of the biopsy for the final pathological diagnosis of the disease was 84% at best and as low as 51% in community settings, the retrospective review of electronic medical records found.

Among the 36 patients with stage I-III disease (confined to the adrenal gland) at the time of diagnosis, the biopsy did not significantly change choices regarding adjuvant therapy, compared with 254 patients with stage I-III disease who did not undergo transcutaneous biopsy. The baseline characteristics of these two groups were similar except that patients in the biopsy group were significantly less likely to be secreting hormones (28%) compared with the no-biopsy group (59%).

"Single adrenal masses with malignant characteristics invariably should be treated surgically, making biopsy an unnecessary procedure," reported Mr. Williams, a medical student at the University of Michigan, Ann Arbor, and his associates.

Complications from transcutaneous biopsy in 11% of all patients consisted mainly of bleeding-related events but with one potentially fatal event – needle track metastasis in one patient.

"Single adrenal masses with malignant characteristics invariably should be treated surgically, making biopsy an unnecessary procedure."

Rates of overall and tumor-free survival did not differ significantly between patients who did or did not undergo transcutaneous biopsy in either univariate analysis or multivariate analyses adjusting for age, sex, cortisol production, and adjuvant therapies.

Adrenocortical carcinomas are rare cancers with high rates of recurrence and mortality. Cumulative survival rates in the study decreased steadily to roughly 80% at 1 year, 60% at 3 years, and less than 50% at 5 years.

"Biopsy of adrenocortical carcinomas at stages confined to the adrenal gland does not significantly influence survival," Mr. Williams concluded in the poster. "Adrenal biopsy should only be considered in patients with metastasized disease and unclear tumor origin, only if it may alter the therapeutic approach and only if the adrenal is the easiest site to biopsy."

Patients who underwent biopsy in the study had a median age of 52 years (ranging from 17 to 77 years), and 54% were female. The cohort was 84% white.

Mr. Williams reported having no financial disclosures. Coinvestigator Dr. Gary D. Hammer, also at the University of Michigan, disclosed financial associations with Atterocor, Orphagen Pharmaceuticals, Embera NeuroTherapeutics, HRA Pharma, Corcept Therapeutics, Isis, and OSI-Astella.

sboschert@frontlinemedcom.com

On Twitter @sherryboschert

SAN FRANCISCO – Transcutaneous biopsy of adrenocortical carcinomas did not improve diagnosis or survival, and potentially harmed 11% of patients, in a study of 74 patients.

The study fills a gap behind general recommendations against biopsy of single adrenal masses in the absence of another known malignancy or metastasis, which had been based on fears that biopsy would spread the tumor but lacked clinical evidence, Andrew Williams said in a poster presentation at the annual meeting of the Endocrine Society.

Among 74 patients with adrenocortical carcinoma who had undergone transcutaneous biopsy of an adrenal mass between 1991 and 2011, the sensitivity of the biopsy for the final pathological diagnosis of the disease was 84% at best and as low as 51% in community settings, the retrospective review of electronic medical records found.

Among the 36 patients with stage I-III disease (confined to the adrenal gland) at the time of diagnosis, the biopsy did not significantly change choices regarding adjuvant therapy, compared with 254 patients with stage I-III disease who did not undergo transcutaneous biopsy. The baseline characteristics of these two groups were similar except that patients in the biopsy group were significantly less likely to be secreting hormones (28%) compared with the no-biopsy group (59%).

"Single adrenal masses with malignant characteristics invariably should be treated surgically, making biopsy an unnecessary procedure," reported Mr. Williams, a medical student at the University of Michigan, Ann Arbor, and his associates.

Complications from transcutaneous biopsy in 11% of all patients consisted mainly of bleeding-related events but with one potentially fatal event – needle track metastasis in one patient.

"Single adrenal masses with malignant characteristics invariably should be treated surgically, making biopsy an unnecessary procedure."

Rates of overall and tumor-free survival did not differ significantly between patients who did or did not undergo transcutaneous biopsy in either univariate analysis or multivariate analyses adjusting for age, sex, cortisol production, and adjuvant therapies.

Adrenocortical carcinomas are rare cancers with high rates of recurrence and mortality. Cumulative survival rates in the study decreased steadily to roughly 80% at 1 year, 60% at 3 years, and less than 50% at 5 years.

"Biopsy of adrenocortical carcinomas at stages confined to the adrenal gland does not significantly influence survival," Mr. Williams concluded in the poster. "Adrenal biopsy should only be considered in patients with metastasized disease and unclear tumor origin, only if it may alter the therapeutic approach and only if the adrenal is the easiest site to biopsy."

Patients who underwent biopsy in the study had a median age of 52 years (ranging from 17 to 77 years), and 54% were female. The cohort was 84% white.

Mr. Williams reported having no financial disclosures. Coinvestigator Dr. Gary D. Hammer, also at the University of Michigan, disclosed financial associations with Atterocor, Orphagen Pharmaceuticals, Embera NeuroTherapeutics, HRA Pharma, Corcept Therapeutics, Isis, and OSI-Astella.

sboschert@frontlinemedcom.com

On Twitter @sherryboschert

Thyroid nodules that include microcalcifications, are larger than 2 cm in size, and have an entirely solid composition on ultrasound imaging are the most likely to be cancerous, according to a report published online Aug. 26 in JAMA Internal Medicine.

A patient’s risk of having primary thyroid cancer ranges from 0.2% when a nodule’s ultrasound image has none of the three characteristics to 1.8% if a nodule has one of the characteristics, 6.2% if a nodule has two of the characteristics, and 96% if a nodule has all three characteristics, said Dr. Rebecca Smith-Bindman of the department of radiology and biomedical imaging, University of California, San Francisco, and her associates.

"Ours is the first study, to our knowledge, that permits estimating this risk," they noted (JAMA Intern. Med. 2013 Aug. 26 [doi:10.1001/jamainternmed.2013.9245]).

Thyroid nodules are extremely common, but almost all of them are benign, so it is crucial to identify which ones may be malignant and to biopsy them, and to avoid subjecting low-risk patients to unnecessary biopsy.

Cindy Chew/UCSF

To determine which features on ultrasound correspond with cancer risk, Dr. Smith-Bindman and her colleagues performed a retrospective case-control study involving 8,806 consecutive patients who underwent 11,618 thyroid ultrasound examinations at the university from January 2000 through March 2005.

The patients who were found to have primary thyroid cancer during up to 7 years of follow-up were identified using data in a comprehensive cancer registry. Those 96 patients were matched for age, sex, and year of ultrasound examination to 369 control subjects who did not have primary thyroid cancer.

Two of the researchers who were blinded to the subjects’ cancer status independently assessed the number and size of all the thyroid nodules that were imaged in the study population and performed a detailed analysis of numerous ultrasound characteristics that might possibly correlate with the presence of malignancy. The agreement between those two reviewers in the categorization of the specific ultrasound image characteristics was "good to outstanding."

"We considered many nodule characteristics endorsed by other authors, but when put into the multiple-predictor models, most of the characteristics were not significantly associated with cancer risk," the researchers said.

In the initial univariable analysis of the data, several ultrasonographic traits were significantly associated with the likelihood that a thyroid nodule harbored cancer.

Microcalcifications had the strongest association with malignancy: They were found in 38.2% of cancerous nodules, compared with only 5.4% of benign nodules. Thus, if microcalcifications were present in a nodule, the chances were seven times greater that the nodule was cancerous, Dr. Smith-Bindman and her coworkers reported.

In the study analysis, the size of the nodule on ultrasound also correlated with cancer risk, with the odds of malignancy increasing as nodule size increased. A size of 2 cm appeared to be a good cutoff point, because nodules larger than 2 cm were much more likely than nodules smaller than 1 cm to be cancerous, with an odds ratio of 3.1.

Several other characteristics correlated with cancer risk in the analysis, but did so to a lesser degree. Coarse calcifications, solid (vs. cystic or mixed) nodule composition, hyperechoic nodule echogenicity, central vascularity, ill-defined or lobulated nodule margins, and taller-than-wide nodule shape all raised the risk of malignancy, with odds ratios ranging from 1.6 to 2.9.

Traits not associated with cancer risk included rim calcifications, comet-tail artifacts, peripheral vascularity, and the presence of a "halo," they said.

In a multivariable analysis, only three nodule characteristics remained significantly associated with cancer risk. The presence of microcalcifications had an odds ratio of 8.1, size larger than 2 cm had an odds ratio of 3.6, and an entirely solid composition had an odds ratio of 4.0, Dr. Smith-Bindman and her associates said.

The findings remained robust through a series of sensitivity analyses.

The investigators found that performing a biopsy only if two of the three characteristics were present would yield a much greater diagnostic sensitivity and specificity than the current practice of biopsying all thyroid nodules larger than 5 mm.

"Compared with existing guidelines ... adoption of this more stringent rule requiring two abnormal [ultrasound] characteristics to prompt biopsy would reduce unnecessary biopsies by 90% while maintaining a low risk of cancer [0.5%] in patients in whom biopsy is deferred," they wrote.

In contrast, requiring all three nodule characteristics to be present before performing a biopsy would detect only a small proportion of thyroid cancers, they added.

In the study, simple cysts never indicated the presence of cancer. Such thyroid cysts should be considered "essentially never malignant" and should not be biopsied, Dr. Smith-Bindman and her associates said.

"The main strength of our study is the large sample size and the linkage of the cohort with data from a comprehensive cancer registry, which allows accurate assessment of the true underlying prevalence of cancer," the researchers noted.

The overall prevalence of primary thyroid cancer was 1.5% in the study population. In contrast, most previous studies have cited a prevalence rate closer to 20%. "All previous studies have inflated the association between nodule characteristics and cancer risk because they limited their analyses to nodules that underwent biopsy," the investigators said.

The National Cancer Institute and the University of California, San Francisco, supported the study. No financial conflicts of interest were reported.

Thyroid nodules that include microcalcifications, are larger than 2 cm in size, and have an entirely solid composition on ultrasound imaging are the most likely to be cancerous, according to a report published online Aug. 26 in JAMA Internal Medicine.

A patient’s risk of having primary thyroid cancer ranges from 0.2% when a nodule’s ultrasound image has none of the three characteristics to 1.8% if a nodule has one of the characteristics, 6.2% if a nodule has two of the characteristics, and 96% if a nodule has all three characteristics, said Dr. Rebecca Smith-Bindman of the department of radiology and biomedical imaging, University of California, San Francisco, and her associates.

"Ours is the first study, to our knowledge, that permits estimating this risk," they noted (JAMA Intern. Med. 2013 Aug. 26 [doi:10.1001/jamainternmed.2013.9245]).

Thyroid nodules are extremely common, but almost all of them are benign, so it is crucial to identify which ones may be malignant and to biopsy them, and to avoid subjecting low-risk patients to unnecessary biopsy.

Cindy Chew/UCSF

To determine which features on ultrasound correspond with cancer risk, Dr. Smith-Bindman and her colleagues performed a retrospective case-control study involving 8,806 consecutive patients who underwent 11,618 thyroid ultrasound examinations at the university from January 2000 through March 2005.

The patients who were found to have primary thyroid cancer during up to 7 years of follow-up were identified using data in a comprehensive cancer registry. Those 96 patients were matched for age, sex, and year of ultrasound examination to 369 control subjects who did not have primary thyroid cancer.

Two of the researchers who were blinded to the subjects’ cancer status independently assessed the number and size of all the thyroid nodules that were imaged in the study population and performed a detailed analysis of numerous ultrasound characteristics that might possibly correlate with the presence of malignancy. The agreement between those two reviewers in the categorization of the specific ultrasound image characteristics was "good to outstanding."

"We considered many nodule characteristics endorsed by other authors, but when put into the multiple-predictor models, most of the characteristics were not significantly associated with cancer risk," the researchers said.

In the initial univariable analysis of the data, several ultrasonographic traits were significantly associated with the likelihood that a thyroid nodule harbored cancer.

Microcalcifications had the strongest association with malignancy: They were found in 38.2% of cancerous nodules, compared with only 5.4% of benign nodules. Thus, if microcalcifications were present in a nodule, the chances were seven times greater that the nodule was cancerous, Dr. Smith-Bindman and her coworkers reported.

In the study analysis, the size of the nodule on ultrasound also correlated with cancer risk, with the odds of malignancy increasing as nodule size increased. A size of 2 cm appeared to be a good cutoff point, because nodules larger than 2 cm were much more likely than nodules smaller than 1 cm to be cancerous, with an odds ratio of 3.1.

Several other characteristics correlated with cancer risk in the analysis, but did so to a lesser degree. Coarse calcifications, solid (vs. cystic or mixed) nodule composition, hyperechoic nodule echogenicity, central vascularity, ill-defined or lobulated nodule margins, and taller-than-wide nodule shape all raised the risk of malignancy, with odds ratios ranging from 1.6 to 2.9.

Traits not associated with cancer risk included rim calcifications, comet-tail artifacts, peripheral vascularity, and the presence of a "halo," they said.

In a multivariable analysis, only three nodule characteristics remained significantly associated with cancer risk. The presence of microcalcifications had an odds ratio of 8.1, size larger than 2 cm had an odds ratio of 3.6, and an entirely solid composition had an odds ratio of 4.0, Dr. Smith-Bindman and her associates said.

The findings remained robust through a series of sensitivity analyses.

The investigators found that performing a biopsy only if two of the three characteristics were present would yield a much greater diagnostic sensitivity and specificity than the current practice of biopsying all thyroid nodules larger than 5 mm.

"Compared with existing guidelines ... adoption of this more stringent rule requiring two abnormal [ultrasound] characteristics to prompt biopsy would reduce unnecessary biopsies by 90% while maintaining a low risk of cancer [0.5%] in patients in whom biopsy is deferred," they wrote.

In contrast, requiring all three nodule characteristics to be present before performing a biopsy would detect only a small proportion of thyroid cancers, they added.

In the study, simple cysts never indicated the presence of cancer. Such thyroid cysts should be considered "essentially never malignant" and should not be biopsied, Dr. Smith-Bindman and her associates said.

"The main strength of our study is the large sample size and the linkage of the cohort with data from a comprehensive cancer registry, which allows accurate assessment of the true underlying prevalence of cancer," the researchers noted.

The overall prevalence of primary thyroid cancer was 1.5% in the study population. In contrast, most previous studies have cited a prevalence rate closer to 20%. "All previous studies have inflated the association between nodule characteristics and cancer risk because they limited their analyses to nodules that underwent biopsy," the investigators said.

The National Cancer Institute and the University of California, San Francisco, supported the study. No financial conflicts of interest were reported.

Thyroid nodules that include microcalcifications, are larger than 2 cm in size, and have an entirely solid composition on ultrasound imaging are the most likely to be cancerous, according to a report published online Aug. 26 in JAMA Internal Medicine.

A patient’s risk of having primary thyroid cancer ranges from 0.2% when a nodule’s ultrasound image has none of the three characteristics to 1.8% if a nodule has one of the characteristics, 6.2% if a nodule has two of the characteristics, and 96% if a nodule has all three characteristics, said Dr. Rebecca Smith-Bindman of the department of radiology and biomedical imaging, University of California, San Francisco, and her associates.

"Ours is the first study, to our knowledge, that permits estimating this risk," they noted (JAMA Intern. Med. 2013 Aug. 26 [doi:10.1001/jamainternmed.2013.9245]).

Thyroid nodules are extremely common, but almost all of them are benign, so it is crucial to identify which ones may be malignant and to biopsy them, and to avoid subjecting low-risk patients to unnecessary biopsy.

Cindy Chew/UCSF

To determine which features on ultrasound correspond with cancer risk, Dr. Smith-Bindman and her colleagues performed a retrospective case-control study involving 8,806 consecutive patients who underwent 11,618 thyroid ultrasound examinations at the university from January 2000 through March 2005.

The patients who were found to have primary thyroid cancer during up to 7 years of follow-up were identified using data in a comprehensive cancer registry. Those 96 patients were matched for age, sex, and year of ultrasound examination to 369 control subjects who did not have primary thyroid cancer.

Two of the researchers who were blinded to the subjects’ cancer status independently assessed the number and size of all the thyroid nodules that were imaged in the study population and performed a detailed analysis of numerous ultrasound characteristics that might possibly correlate with the presence of malignancy. The agreement between those two reviewers in the categorization of the specific ultrasound image characteristics was "good to outstanding."

"We considered many nodule characteristics endorsed by other authors, but when put into the multiple-predictor models, most of the characteristics were not significantly associated with cancer risk," the researchers said.

In the initial univariable analysis of the data, several ultrasonographic traits were significantly associated with the likelihood that a thyroid nodule harbored cancer.

Microcalcifications had the strongest association with malignancy: They were found in 38.2% of cancerous nodules, compared with only 5.4% of benign nodules. Thus, if microcalcifications were present in a nodule, the chances were seven times greater that the nodule was cancerous, Dr. Smith-Bindman and her coworkers reported.

In the study analysis, the size of the nodule on ultrasound also correlated with cancer risk, with the odds of malignancy increasing as nodule size increased. A size of 2 cm appeared to be a good cutoff point, because nodules larger than 2 cm were much more likely than nodules smaller than 1 cm to be cancerous, with an odds ratio of 3.1.

Several other characteristics correlated with cancer risk in the analysis, but did so to a lesser degree. Coarse calcifications, solid (vs. cystic or mixed) nodule composition, hyperechoic nodule echogenicity, central vascularity, ill-defined or lobulated nodule margins, and taller-than-wide nodule shape all raised the risk of malignancy, with odds ratios ranging from 1.6 to 2.9.

Traits not associated with cancer risk included rim calcifications, comet-tail artifacts, peripheral vascularity, and the presence of a "halo," they said.

In a multivariable analysis, only three nodule characteristics remained significantly associated with cancer risk. The presence of microcalcifications had an odds ratio of 8.1, size larger than 2 cm had an odds ratio of 3.6, and an entirely solid composition had an odds ratio of 4.0, Dr. Smith-Bindman and her associates said.

The findings remained robust through a series of sensitivity analyses.

The investigators found that performing a biopsy only if two of the three characteristics were present would yield a much greater diagnostic sensitivity and specificity than the current practice of biopsying all thyroid nodules larger than 5 mm.

"Compared with existing guidelines ... adoption of this more stringent rule requiring two abnormal [ultrasound] characteristics to prompt biopsy would reduce unnecessary biopsies by 90% while maintaining a low risk of cancer [0.5%] in patients in whom biopsy is deferred," they wrote.

In contrast, requiring all three nodule characteristics to be present before performing a biopsy would detect only a small proportion of thyroid cancers, they added.

In the study, simple cysts never indicated the presence of cancer. Such thyroid cysts should be considered "essentially never malignant" and should not be biopsied, Dr. Smith-Bindman and her associates said.

"The main strength of our study is the large sample size and the linkage of the cohort with data from a comprehensive cancer registry, which allows accurate assessment of the true underlying prevalence of cancer," the researchers noted.

The overall prevalence of primary thyroid cancer was 1.5% in the study population. In contrast, most previous studies have cited a prevalence rate closer to 20%. "All previous studies have inflated the association between nodule characteristics and cancer risk because they limited their analyses to nodules that underwent biopsy," the investigators said.

The National Cancer Institute and the University of California, San Francisco, supported the study. No financial conflicts of interest were reported.

SAN FRANCISCO – Higher free thyroxine levels may predict all-cause mortality in older men who do not have thyroid disease, researchers from Perth, Australia, have found.

From 2001 to 2004, they checked levels of thyroid hormones in 3,888 community-dwelling men in Perth 70-89 years old and free of thyroid disease, then followed them for a mean of 6.4 years; 837 (22%) died through 2010.

Men who died had baseline thyroid-stimulating hormone (TSH) levels comparable to those who did not (2.4 vs. 2.3 mIU/L), but significantly higher mean baseline free thyroxine (FT4) levels (16.2 vs. 15.8 pmol/L).

After adjustment for age, smoking, body mass index, waist-to-hip ratio, creatinine, hypertension, diabetes, dyslipidemia, and cardiovascular disease, higher baseline FT4 levels – of at least 17.32 pmol/L – increased the risk of all-cause mortality significantly, by 21%. Baseline TSH levels did not predict mortality.

The finding has "made us think much more carefully about thyroid hormone. This is observational data, and we need to look at it a bit more thoroughly, but it’s certainly shifted us away from thinking that if a man’s [TSH] level is good," there’s nothing to worry about, said lead investigator Dr. Bu Yeap, an endocrinologist and professor at the University of Western Australia, Fremantle.

"The point for physicians might be that if they see someone in clinic with a normal TSH, and a free T4 that’s in the high end of the normal range, that should be a trigger to look very carefully at that man’s underlying health and see if there are any risk factors for cardiovascular disease or any other ill health that can be carefully addressed and managed. The standard workup" now probably doesn’t always include FT4, Dr. Yeap said at the Endocrine Society’s annual meeting.

"Others have published studies saying there’s actually no mortality association with free T4. I think we are seeing this now because we have a large cohort of men and a large number of deaths, so we have a better chance of seeing an association if it’s present," Dr. Yeap said.

It’s unknown for now what the men died of. "We are still cleaning the data for the cause-specific mortality," he said.

Even so, the relationship still held true when men with subclinical hyper- or hypothyroidism were excluded from the analysis; higher baseline FT4 remained independently associated with all-cause mortality in 3,445 euthyroid men (adjusted HR, 1.21).

Free T4 "may be a biomarker. It may be a contributing factor. If it’s a contributing factor, it’s probably that the body is seeing a marginal excess of thyroid hormone for a long period of time. We know that excess thyroid hormone is bad for the cardiovascular system; having more free T4 may actually be deleterious to other body systems, as well," Dr. Yeap said.

The men were members of the Health in Men Study, an ongoing observational study of older men in Western Australia.

Dr. Yeap and the other investigators had no disclosures. Foundations and the Australian government funded the work.

aotto@frontlinemedcom.com

SAN FRANCISCO – Higher free thyroxine levels may predict all-cause mortality in older men who do not have thyroid disease, researchers from Perth, Australia, have found.

From 2001 to 2004, they checked levels of thyroid hormones in 3,888 community-dwelling men in Perth 70-89 years old and free of thyroid disease, then followed them for a mean of 6.4 years; 837 (22%) died through 2010.

Men who died had baseline thyroid-stimulating hormone (TSH) levels comparable to those who did not (2.4 vs. 2.3 mIU/L), but significantly higher mean baseline free thyroxine (FT4) levels (16.2 vs. 15.8 pmol/L).

After adjustment for age, smoking, body mass index, waist-to-hip ratio, creatinine, hypertension, diabetes, dyslipidemia, and cardiovascular disease, higher baseline FT4 levels – of at least 17.32 pmol/L – increased the risk of all-cause mortality significantly, by 21%. Baseline TSH levels did not predict mortality.

The finding has "made us think much more carefully about thyroid hormone. This is observational data, and we need to look at it a bit more thoroughly, but it’s certainly shifted us away from thinking that if a man’s [TSH] level is good," there’s nothing to worry about, said lead investigator Dr. Bu Yeap, an endocrinologist and professor at the University of Western Australia, Fremantle.

"The point for physicians might be that if they see someone in clinic with a normal TSH, and a free T4 that’s in the high end of the normal range, that should be a trigger to look very carefully at that man’s underlying health and see if there are any risk factors for cardiovascular disease or any other ill health that can be carefully addressed and managed. The standard workup" now probably doesn’t always include FT4, Dr. Yeap said at the Endocrine Society’s annual meeting.

"Others have published studies saying there’s actually no mortality association with free T4. I think we are seeing this now because we have a large cohort of men and a large number of deaths, so we have a better chance of seeing an association if it’s present," Dr. Yeap said.

It’s unknown for now what the men died of. "We are still cleaning the data for the cause-specific mortality," he said.

Even so, the relationship still held true when men with subclinical hyper- or hypothyroidism were excluded from the analysis; higher baseline FT4 remained independently associated with all-cause mortality in 3,445 euthyroid men (adjusted HR, 1.21).

Free T4 "may be a biomarker. It may be a contributing factor. If it’s a contributing factor, it’s probably that the body is seeing a marginal excess of thyroid hormone for a long period of time. We know that excess thyroid hormone is bad for the cardiovascular system; having more free T4 may actually be deleterious to other body systems, as well," Dr. Yeap said.

The men were members of the Health in Men Study, an ongoing observational study of older men in Western Australia.

Dr. Yeap and the other investigators had no disclosures. Foundations and the Australian government funded the work.

aotto@frontlinemedcom.com

SAN FRANCISCO – Higher free thyroxine levels may predict all-cause mortality in older men who do not have thyroid disease, researchers from Perth, Australia, have found.

From 2001 to 2004, they checked levels of thyroid hormones in 3,888 community-dwelling men in Perth 70-89 years old and free of thyroid disease, then followed them for a mean of 6.4 years; 837 (22%) died through 2010.

Men who died had baseline thyroid-stimulating hormone (TSH) levels comparable to those who did not (2.4 vs. 2.3 mIU/L), but significantly higher mean baseline free thyroxine (FT4) levels (16.2 vs. 15.8 pmol/L).

After adjustment for age, smoking, body mass index, waist-to-hip ratio, creatinine, hypertension, diabetes, dyslipidemia, and cardiovascular disease, higher baseline FT4 levels – of at least 17.32 pmol/L – increased the risk of all-cause mortality significantly, by 21%. Baseline TSH levels did not predict mortality.

The finding has "made us think much more carefully about thyroid hormone. This is observational data, and we need to look at it a bit more thoroughly, but it’s certainly shifted us away from thinking that if a man’s [TSH] level is good," there’s nothing to worry about, said lead investigator Dr. Bu Yeap, an endocrinologist and professor at the University of Western Australia, Fremantle.

"The point for physicians might be that if they see someone in clinic with a normal TSH, and a free T4 that’s in the high end of the normal range, that should be a trigger to look very carefully at that man’s underlying health and see if there are any risk factors for cardiovascular disease or any other ill health that can be carefully addressed and managed. The standard workup" now probably doesn’t always include FT4, Dr. Yeap said at the Endocrine Society’s annual meeting.

"Others have published studies saying there’s actually no mortality association with free T4. I think we are seeing this now because we have a large cohort of men and a large number of deaths, so we have a better chance of seeing an association if it’s present," Dr. Yeap said.

It’s unknown for now what the men died of. "We are still cleaning the data for the cause-specific mortality," he said.

Even so, the relationship still held true when men with subclinical hyper- or hypothyroidism were excluded from the analysis; higher baseline FT4 remained independently associated with all-cause mortality in 3,445 euthyroid men (adjusted HR, 1.21).

Free T4 "may be a biomarker. It may be a contributing factor. If it’s a contributing factor, it’s probably that the body is seeing a marginal excess of thyroid hormone for a long period of time. We know that excess thyroid hormone is bad for the cardiovascular system; having more free T4 may actually be deleterious to other body systems, as well," Dr. Yeap said.

The men were members of the Health in Men Study, an ongoing observational study of older men in Western Australia.

Dr. Yeap and the other investigators had no disclosures. Foundations and the Australian government funded the work.

aotto@frontlinemedcom.com

SAN FRANCISCO – A majority of 22 patients with metastatic, inoperable pheochromocytoma or paraganglioma had stable disease or complete resolution 6 months after receiving the first dose of treatment with the radioisotope ¹³¹I-meta-iodobenzylguanidine.

Treatment with ¹³¹I-meta-iodobenzylguanidine (¹³¹I-MIBG) appears to be safe and was associated with disease stabilization or improvement, which makes it a useful therapeutic tool either alone or with external beam radiotherapy and chemotherapy for patients with metastatic pheochromocytoma or paraganglioma, according to Dr. Matthew A. Rutherford of Glasgow (Scotland) Royal Infirmary and his associates.

In general, approximately 10% of cases of pheochromocytoma and paraganglioma metastasize. Optimal treatment of these cases has been controversial as the tumors are rare and there is no standard therapy.

The researchers reviewed the experience of one tertiary center in offering treatment with ¹³¹I-MIBG from 1986 to 2011.

The 12 patients with metastatic pheochromocytoma and 10 patients with metastatic paraganglioma received a total of 68 doses of ¹³¹I-MIBG, a type of radioactive iodine. The average dose was 9,835 MBq (range, 5,000-11,300).

One year after starting therapy, 16 of the 22 patients were alive. The average survival time after the first dose of ¹³¹I-MIBG was more than 7 years (86 months), Dr. Rutherford reported in a featured poster presentation at the Endocrine Society’s Annual Meeting.

At the 6-month follow-up after starting ¹³¹I-MIBG treatment, one patient had complete resolution of disease as assessed by symptoms, biochemical assessment of catecholamine excretion rate, and tumor size, Dr. Rutherford reported.

Four patients (18%) had partial responses in symptoms. A partial biochemical or tumor response, defined as greater than a 50% reduction in catecholamine excretion rate or tumor bulk, was seen in one patient (5%) biochemically and three patients (14%) by tumor size.

Stable disease was defined as no change in symptoms, biochemical markers, or tumor bulk, or less than a 25% increase in tumor bulk or catecholamine excretion rate. Thirteen patients had stable symptoms, 11 had stable biochemical results, and 13 had stable tumor size.

Progressive disease was identified by increased symptoms in two patients, by a greater than a 25% increase in catecholamine excretion rate in two patients, and by a greater than 50% increase in tumor size in two patients. There were no 6-month data for two patients regarding symptoms, for seven patients regarding biochemical assessment, and for three patients regarding tumor bulk.

Eleven (50%) reported having no adverse effects from ¹³¹I-MIBG, seven (32%) had nausea and vomiting, and five (23%) developed transient bone marrow defects. There were no severe adverse events related to treatment.

Fourteen patients had no treatment other than ¹³¹I-MIBG (64%), while five patients also underwent chemotherapy, one had radiotherapy, and two patients underwent chemoradiotherapy.

Bone was the most common site of metastasis (nine patients), followed by lymph nodes (eight patients) and liver (five patients), with local invasion in two patients.

The patients’ mean age was 45 years (range, 15-77 years). Nine of the 22 were male. They were followed according to a defined protocol, with repeat hormonal evaluation and imaging within 6 months of starting ¹³¹I-MIBG treatment when possible.

Genetic testing identified four patients who were positive for the succinate dehydrogenase B gene (SDHB) and four with no identified genetic mutation. The other 14 patients were not tested for genetic mutations; 7 of them were older than the institution’s age cut-off for routine genetic testing.

Dr. Rutherford reported having no financial disclosures.

sboschert@frontlinemedcom.com

On Twitter @sherryboschert

SAN FRANCISCO – A majority of 22 patients with metastatic, inoperable pheochromocytoma or paraganglioma had stable disease or complete resolution 6 months after receiving the first dose of treatment with the radioisotope ¹³¹I-meta-iodobenzylguanidine.

Treatment with ¹³¹I-meta-iodobenzylguanidine (¹³¹I-MIBG) appears to be safe and was associated with disease stabilization or improvement, which makes it a useful therapeutic tool either alone or with external beam radiotherapy and chemotherapy for patients with metastatic pheochromocytoma or paraganglioma, according to Dr. Matthew A. Rutherford of Glasgow (Scotland) Royal Infirmary and his associates.

In general, approximately 10% of cases of pheochromocytoma and paraganglioma metastasize. Optimal treatment of these cases has been controversial as the tumors are rare and there is no standard therapy.

The researchers reviewed the experience of one tertiary center in offering treatment with ¹³¹I-MIBG from 1986 to 2011.

The 12 patients with metastatic pheochromocytoma and 10 patients with metastatic paraganglioma received a total of 68 doses of ¹³¹I-MIBG, a type of radioactive iodine. The average dose was 9,835 MBq (range, 5,000-11,300).

One year after starting therapy, 16 of the 22 patients were alive. The average survival time after the first dose of ¹³¹I-MIBG was more than 7 years (86 months), Dr. Rutherford reported in a featured poster presentation at the Endocrine Society’s Annual Meeting.

At the 6-month follow-up after starting ¹³¹I-MIBG treatment, one patient had complete resolution of disease as assessed by symptoms, biochemical assessment of catecholamine excretion rate, and tumor size, Dr. Rutherford reported.

Four patients (18%) had partial responses in symptoms. A partial biochemical or tumor response, defined as greater than a 50% reduction in catecholamine excretion rate or tumor bulk, was seen in one patient (5%) biochemically and three patients (14%) by tumor size.

Stable disease was defined as no change in symptoms, biochemical markers, or tumor bulk, or less than a 25% increase in tumor bulk or catecholamine excretion rate. Thirteen patients had stable symptoms, 11 had stable biochemical results, and 13 had stable tumor size.

Progressive disease was identified by increased symptoms in two patients, by a greater than a 25% increase in catecholamine excretion rate in two patients, and by a greater than 50% increase in tumor size in two patients. There were no 6-month data for two patients regarding symptoms, for seven patients regarding biochemical assessment, and for three patients regarding tumor bulk.

Eleven (50%) reported having no adverse effects from ¹³¹I-MIBG, seven (32%) had nausea and vomiting, and five (23%) developed transient bone marrow defects. There were no severe adverse events related to treatment.

Fourteen patients had no treatment other than ¹³¹I-MIBG (64%), while five patients also underwent chemotherapy, one had radiotherapy, and two patients underwent chemoradiotherapy.

Bone was the most common site of metastasis (nine patients), followed by lymph nodes (eight patients) and liver (five patients), with local invasion in two patients.

The patients’ mean age was 45 years (range, 15-77 years). Nine of the 22 were male. They were followed according to a defined protocol, with repeat hormonal evaluation and imaging within 6 months of starting ¹³¹I-MIBG treatment when possible.

Genetic testing identified four patients who were positive for the succinate dehydrogenase B gene (SDHB) and four with no identified genetic mutation. The other 14 patients were not tested for genetic mutations; 7 of them were older than the institution’s age cut-off for routine genetic testing.

Dr. Rutherford reported having no financial disclosures.

sboschert@frontlinemedcom.com

On Twitter @sherryboschert

SAN FRANCISCO – A majority of 22 patients with metastatic, inoperable pheochromocytoma or paraganglioma had stable disease or complete resolution 6 months after receiving the first dose of treatment with the radioisotope ¹³¹I-meta-iodobenzylguanidine.

Treatment with ¹³¹I-meta-iodobenzylguanidine (¹³¹I-MIBG) appears to be safe and was associated with disease stabilization or improvement, which makes it a useful therapeutic tool either alone or with external beam radiotherapy and chemotherapy for patients with metastatic pheochromocytoma or paraganglioma, according to Dr. Matthew A. Rutherford of Glasgow (Scotland) Royal Infirmary and his associates.

In general, approximately 10% of cases of pheochromocytoma and paraganglioma metastasize. Optimal treatment of these cases has been controversial as the tumors are rare and there is no standard therapy.

The researchers reviewed the experience of one tertiary center in offering treatment with ¹³¹I-MIBG from 1986 to 2011.

The 12 patients with metastatic pheochromocytoma and 10 patients with metastatic paraganglioma received a total of 68 doses of ¹³¹I-MIBG, a type of radioactive iodine. The average dose was 9,835 MBq (range, 5,000-11,300).

One year after starting therapy, 16 of the 22 patients were alive. The average survival time after the first dose of ¹³¹I-MIBG was more than 7 years (86 months), Dr. Rutherford reported in a featured poster presentation at the Endocrine Society’s Annual Meeting.

At the 6-month follow-up after starting ¹³¹I-MIBG treatment, one patient had complete resolution of disease as assessed by symptoms, biochemical assessment of catecholamine excretion rate, and tumor size, Dr. Rutherford reported.

Four patients (18%) had partial responses in symptoms. A partial biochemical or tumor response, defined as greater than a 50% reduction in catecholamine excretion rate or tumor bulk, was seen in one patient (5%) biochemically and three patients (14%) by tumor size.

Stable disease was defined as no change in symptoms, biochemical markers, or tumor bulk, or less than a 25% increase in tumor bulk or catecholamine excretion rate. Thirteen patients had stable symptoms, 11 had stable biochemical results, and 13 had stable tumor size.

Progressive disease was identified by increased symptoms in two patients, by a greater than a 25% increase in catecholamine excretion rate in two patients, and by a greater than 50% increase in tumor size in two patients. There were no 6-month data for two patients regarding symptoms, for seven patients regarding biochemical assessment, and for three patients regarding tumor bulk.

Eleven (50%) reported having no adverse effects from ¹³¹I-MIBG, seven (32%) had nausea and vomiting, and five (23%) developed transient bone marrow defects. There were no severe adverse events related to treatment.

Fourteen patients had no treatment other than ¹³¹I-MIBG (64%), while five patients also underwent chemotherapy, one had radiotherapy, and two patients underwent chemoradiotherapy.

Bone was the most common site of metastasis (nine patients), followed by lymph nodes (eight patients) and liver (five patients), with local invasion in two patients.

The patients’ mean age was 45 years (range, 15-77 years). Nine of the 22 were male. They were followed according to a defined protocol, with repeat hormonal evaluation and imaging within 6 months of starting ¹³¹I-MIBG treatment when possible.

Genetic testing identified four patients who were positive for the succinate dehydrogenase B gene (SDHB) and four with no identified genetic mutation. The other 14 patients were not tested for genetic mutations; 7 of them were older than the institution’s age cut-off for routine genetic testing.

Dr. Rutherford reported having no financial disclosures.

sboschert@frontlinemedcom.com

On Twitter @sherryboschert