Endo 2014

CHICAGO – Two divergent pathways of hypothalamic-pituitary-testicular axis dysfunction underlie declining testosterone levels in aging men.

“There appear to be two separate tracks to primary hypogonadism marked by testicular dysfunction: secondary hypogonadism and compensated hypogonadism. Not only do they have different etiologies, they also have different clinical features and outcomes, and they therefore require different management strategies,” Dr. Frederick C. Wu said at the joint meeting of the International Congress of Endocrinology and the Endocrine Society.

He cited new data from the European Male Ageing Study (EMAS), a prospective observational cohort study of 3,369 community-dwelling men aged 40-79 years in eight countries. At baseline, they were categorized in four different biochemical classes: 78.4% were eugonadal; 9.6% had compensated hypogonadism marked by a normal serum testosterone level of 10.5 nmol/L or more but a serum luteinizing hormone value above 9.4 IU/L; 10.4% had secondary hypogonadism characterized by low serum testosterone and low serum LH due to pituitary or hypothalamic causes; and 1.7% had primary hypogonadism marked by a serum testosterone less than 10.5 nmol/L and LH greater than 9.4 IU/L due to a testicular condition.

Secondary hypogonadism is strongly associated with obesity and the development of symptoms of sexual dysfunction. Compensated hypogonadism is associated with aging but is independent of obesity. In EMAS, 2% of individuals with secondary hypogonadism progressed to primary hypogonadism during 4.3 years of follow-up.

Avoidance of obesity is “by far” the most important preventive measure to maintain normal testosterone in aging men; in EMAS, men who were not obese were 3.5-fold less likely to develop hypogonadism, Dr. Wu observed.

“Weight loss should be the first-line standard of care for obese men with low testosterone. The role of testosterone replacement remains unclear, and both modalities should be assessed in randomized controlled trials,” he said.

Dr. Wu added that he’d consider testosterone replacement therapy on a time-limited basis in patients with secondary hypogonadism unresponsive to lifestyle interventions. However, in patients with compensated hypogonadism, “there is no current indication for testosterone therapy.”

A key clinical message: Hypogonadism is a marker of poor health and increased mortality risk. During 4.3 years of prospective follow-up, the group with baseline primary hypogonadism had a 21% all-cause mortality rate, fourfold greater than the eugonadal group. Mortality was increased threefold in subjects with compensated hypogonadism and twofold in those with secondary hypogonadism, according to Dr. Wu, professor of medicine at the University of Manchester (England).

He focused particular attention on the group with compensated hypogonadism because this abnormality is a relatively new concept in endocrinology.

“It’s a concept similar to compensated hypothyroidism, but it hasn’t really been studied before to any extent in the gonadal axis,” Dr. Wu explained in an interview.

Compensated hypogonadism can be viewed as a transitional state during progression from eugonadism to primary hypogonadism. Affected aging men maintain normal testosterone levels by increasing their LH in order to compensate for testicular defects. Over a period of years, however, some of these men decompensate and progress to primary hypogonadism. In EMAS, this occurred at a rate of 1.4% per year. Compared with eugonadal men, men with compensated hypogonadism at baseline had a 10-fold greater risk of progressing to primary hypogonadism after adjustment for age, comorbid conditions, smoking status, and body mass index.

To date, no predictors of decompensation have been identified. However, elevated LH in older men with normal testosterone can be viewed as a highly sensitive biomarker for poor health and increased risk of mortality – and an opportunity for preventive intervention targeting cardiometabolic health, according to Dr. Wu.

The EMAS study was funded by the European Union. Dr. Wu reported serving on the speakers bureau for Bayer Schering Pharma.

[email protected]

CHICAGO – Two divergent pathways of hypothalamic-pituitary-testicular axis dysfunction underlie declining testosterone levels in aging men.

“There appear to be two separate tracks to primary hypogonadism marked by testicular dysfunction: secondary hypogonadism and compensated hypogonadism. Not only do they have different etiologies, they also have different clinical features and outcomes, and they therefore require different management strategies,” Dr. Frederick C. Wu said at the joint meeting of the International Congress of Endocrinology and the Endocrine Society.

He cited new data from the European Male Ageing Study (EMAS), a prospective observational cohort study of 3,369 community-dwelling men aged 40-79 years in eight countries. At baseline, they were categorized in four different biochemical classes: 78.4% were eugonadal; 9.6% had compensated hypogonadism marked by a normal serum testosterone level of 10.5 nmol/L or more but a serum luteinizing hormone value above 9.4 IU/L; 10.4% had secondary hypogonadism characterized by low serum testosterone and low serum LH due to pituitary or hypothalamic causes; and 1.7% had primary hypogonadism marked by a serum testosterone less than 10.5 nmol/L and LH greater than 9.4 IU/L due to a testicular condition.

Secondary hypogonadism is strongly associated with obesity and the development of symptoms of sexual dysfunction. Compensated hypogonadism is associated with aging but is independent of obesity. In EMAS, 2% of individuals with secondary hypogonadism progressed to primary hypogonadism during 4.3 years of follow-up.

Avoidance of obesity is “by far” the most important preventive measure to maintain normal testosterone in aging men; in EMAS, men who were not obese were 3.5-fold less likely to develop hypogonadism, Dr. Wu observed.

“Weight loss should be the first-line standard of care for obese men with low testosterone. The role of testosterone replacement remains unclear, and both modalities should be assessed in randomized controlled trials,” he said.

Dr. Wu added that he’d consider testosterone replacement therapy on a time-limited basis in patients with secondary hypogonadism unresponsive to lifestyle interventions. However, in patients with compensated hypogonadism, “there is no current indication for testosterone therapy.”

A key clinical message: Hypogonadism is a marker of poor health and increased mortality risk. During 4.3 years of prospective follow-up, the group with baseline primary hypogonadism had a 21% all-cause mortality rate, fourfold greater than the eugonadal group. Mortality was increased threefold in subjects with compensated hypogonadism and twofold in those with secondary hypogonadism, according to Dr. Wu, professor of medicine at the University of Manchester (England).

He focused particular attention on the group with compensated hypogonadism because this abnormality is a relatively new concept in endocrinology.

“It’s a concept similar to compensated hypothyroidism, but it hasn’t really been studied before to any extent in the gonadal axis,” Dr. Wu explained in an interview.

Compensated hypogonadism can be viewed as a transitional state during progression from eugonadism to primary hypogonadism. Affected aging men maintain normal testosterone levels by increasing their LH in order to compensate for testicular defects. Over a period of years, however, some of these men decompensate and progress to primary hypogonadism. In EMAS, this occurred at a rate of 1.4% per year. Compared with eugonadal men, men with compensated hypogonadism at baseline had a 10-fold greater risk of progressing to primary hypogonadism after adjustment for age, comorbid conditions, smoking status, and body mass index.

To date, no predictors of decompensation have been identified. However, elevated LH in older men with normal testosterone can be viewed as a highly sensitive biomarker for poor health and increased risk of mortality – and an opportunity for preventive intervention targeting cardiometabolic health, according to Dr. Wu.

The EMAS study was funded by the European Union. Dr. Wu reported serving on the speakers bureau for Bayer Schering Pharma.

[email protected]

CHICAGO – Two divergent pathways of hypothalamic-pituitary-testicular axis dysfunction underlie declining testosterone levels in aging men.

“There appear to be two separate tracks to primary hypogonadism marked by testicular dysfunction: secondary hypogonadism and compensated hypogonadism. Not only do they have different etiologies, they also have different clinical features and outcomes, and they therefore require different management strategies,” Dr. Frederick C. Wu said at the joint meeting of the International Congress of Endocrinology and the Endocrine Society.

He cited new data from the European Male Ageing Study (EMAS), a prospective observational cohort study of 3,369 community-dwelling men aged 40-79 years in eight countries. At baseline, they were categorized in four different biochemical classes: 78.4% were eugonadal; 9.6% had compensated hypogonadism marked by a normal serum testosterone level of 10.5 nmol/L or more but a serum luteinizing hormone value above 9.4 IU/L; 10.4% had secondary hypogonadism characterized by low serum testosterone and low serum LH due to pituitary or hypothalamic causes; and 1.7% had primary hypogonadism marked by a serum testosterone less than 10.5 nmol/L and LH greater than 9.4 IU/L due to a testicular condition.

Secondary hypogonadism is strongly associated with obesity and the development of symptoms of sexual dysfunction. Compensated hypogonadism is associated with aging but is independent of obesity. In EMAS, 2% of individuals with secondary hypogonadism progressed to primary hypogonadism during 4.3 years of follow-up.

Avoidance of obesity is “by far” the most important preventive measure to maintain normal testosterone in aging men; in EMAS, men who were not obese were 3.5-fold less likely to develop hypogonadism, Dr. Wu observed.

“Weight loss should be the first-line standard of care for obese men with low testosterone. The role of testosterone replacement remains unclear, and both modalities should be assessed in randomized controlled trials,” he said.

Dr. Wu added that he’d consider testosterone replacement therapy on a time-limited basis in patients with secondary hypogonadism unresponsive to lifestyle interventions. However, in patients with compensated hypogonadism, “there is no current indication for testosterone therapy.”

A key clinical message: Hypogonadism is a marker of poor health and increased mortality risk. During 4.3 years of prospective follow-up, the group with baseline primary hypogonadism had a 21% all-cause mortality rate, fourfold greater than the eugonadal group. Mortality was increased threefold in subjects with compensated hypogonadism and twofold in those with secondary hypogonadism, according to Dr. Wu, professor of medicine at the University of Manchester (England).

He focused particular attention on the group with compensated hypogonadism because this abnormality is a relatively new concept in endocrinology.

“It’s a concept similar to compensated hypothyroidism, but it hasn’t really been studied before to any extent in the gonadal axis,” Dr. Wu explained in an interview.

Compensated hypogonadism can be viewed as a transitional state during progression from eugonadism to primary hypogonadism. Affected aging men maintain normal testosterone levels by increasing their LH in order to compensate for testicular defects. Over a period of years, however, some of these men decompensate and progress to primary hypogonadism. In EMAS, this occurred at a rate of 1.4% per year. Compared with eugonadal men, men with compensated hypogonadism at baseline had a 10-fold greater risk of progressing to primary hypogonadism after adjustment for age, comorbid conditions, smoking status, and body mass index.

To date, no predictors of decompensation have been identified. However, elevated LH in older men with normal testosterone can be viewed as a highly sensitive biomarker for poor health and increased risk of mortality – and an opportunity for preventive intervention targeting cardiometabolic health, according to Dr. Wu.

The EMAS study was funded by the European Union. Dr. Wu reported serving on the speakers bureau for Bayer Schering Pharma.

[email protected]

CHICAGO – Testosterone replacement therapy may provide a pharmacologic alternative to bariatric surgery in severely obese hypogonadal men.

Mean body mass index in 46 hypogonadal men with grade III obesity dropped from 41.9 to 33.6 kg/m2 while they were receiving testosterone undecanoate at 1,000 mg by intramuscular injection every 12 weeks for up to 6 years, Farid Saad, Ph.D., reported at the joint meeting of the International Congress of Endocrinology and the Endocrine Society.

The subjects, with a mean age was 60 years, were culled from two prospective registries totaling 561 men with a serum total testosterone of 12.1 nmol/L or less along with symptoms of testosterone deficiency. These 46 men were selected for the analysis because a BMI of 40 kg/m² or more is an indication for bariatric surgery, and the impact of testosterone replacement in hypogonadal men with grade III obesity has not previously been studied, explained Dr. Saad, director of scientific affairs at Bayer Pharma in Berlin.

Mean body weight in this group decreased from 129 to 103 kg. Weight loss grew over time: The men averaged a 2.7% reduction in body weight after 1 year of testosterone therapy, 7.3% after 2 years, 10.9% after 3 years, 14.1% after 4 years, 17.4% after 5 years, and a 20.8% decrease from baseline body weight after 6 years of therapy.

Mean waist circumference shrunk from 118.4 cm at baseline to 106.5 cm.

On the basis of these long-term results, testosterone replacement therapy appears to be an effective means of achieving sustained weight loss in severely obese hypogonadal men, he concluded.

The registry study was funded by Bayer Pharma, which markets testosterone undecanoate as Aveed.

CHICAGO – Testosterone replacement therapy may provide a pharmacologic alternative to bariatric surgery in severely obese hypogonadal men.

Mean body mass index in 46 hypogonadal men with grade III obesity dropped from 41.9 to 33.6 kg/m2 while they were receiving testosterone undecanoate at 1,000 mg by intramuscular injection every 12 weeks for up to 6 years, Farid Saad, Ph.D., reported at the joint meeting of the International Congress of Endocrinology and the Endocrine Society.

The subjects, with a mean age was 60 years, were culled from two prospective registries totaling 561 men with a serum total testosterone of 12.1 nmol/L or less along with symptoms of testosterone deficiency. These 46 men were selected for the analysis because a BMI of 40 kg/m² or more is an indication for bariatric surgery, and the impact of testosterone replacement in hypogonadal men with grade III obesity has not previously been studied, explained Dr. Saad, director of scientific affairs at Bayer Pharma in Berlin.

Mean body weight in this group decreased from 129 to 103 kg. Weight loss grew over time: The men averaged a 2.7% reduction in body weight after 1 year of testosterone therapy, 7.3% after 2 years, 10.9% after 3 years, 14.1% after 4 years, 17.4% after 5 years, and a 20.8% decrease from baseline body weight after 6 years of therapy.

Mean waist circumference shrunk from 118.4 cm at baseline to 106.5 cm.

On the basis of these long-term results, testosterone replacement therapy appears to be an effective means of achieving sustained weight loss in severely obese hypogonadal men, he concluded.

The registry study was funded by Bayer Pharma, which markets testosterone undecanoate as Aveed.

CHICAGO – Testosterone replacement therapy may provide a pharmacologic alternative to bariatric surgery in severely obese hypogonadal men.

Mean body mass index in 46 hypogonadal men with grade III obesity dropped from 41.9 to 33.6 kg/m2 while they were receiving testosterone undecanoate at 1,000 mg by intramuscular injection every 12 weeks for up to 6 years, Farid Saad, Ph.D., reported at the joint meeting of the International Congress of Endocrinology and the Endocrine Society.

The subjects, with a mean age was 60 years, were culled from two prospective registries totaling 561 men with a serum total testosterone of 12.1 nmol/L or less along with symptoms of testosterone deficiency. These 46 men were selected for the analysis because a BMI of 40 kg/m² or more is an indication for bariatric surgery, and the impact of testosterone replacement in hypogonadal men with grade III obesity has not previously been studied, explained Dr. Saad, director of scientific affairs at Bayer Pharma in Berlin.

Mean body weight in this group decreased from 129 to 103 kg. Weight loss grew over time: The men averaged a 2.7% reduction in body weight after 1 year of testosterone therapy, 7.3% after 2 years, 10.9% after 3 years, 14.1% after 4 years, 17.4% after 5 years, and a 20.8% decrease from baseline body weight after 6 years of therapy.

Mean waist circumference shrunk from 118.4 cm at baseline to 106.5 cm.

On the basis of these long-term results, testosterone replacement therapy appears to be an effective means of achieving sustained weight loss in severely obese hypogonadal men, he concluded.

The registry study was funded by Bayer Pharma, which markets testosterone undecanoate as Aveed.

CHICAGO – Testosterone replacement therapy may provide a pharmacologic alternative to bariatric surgery in severely obese hypogonadal men.

Mean body mass index in 46 hypogonadal men with grade III obesity dropped from 41.9 to 33.6 kg/m2 while they were receiving testosterone undecanoate at 1,000 mg by intramuscular injection every 12 weeks for up to 6 years, Farid Saad, Ph.D., reported at the joint meeting of the International Congress of Endocrinology and the Endocrine Society.

The subjects, with a mean age was 60 years, were culled from two prospective registries totaling 561 men with a serum total testosterone of 12.1 nmol/L or less along with symptoms of testosterone deficiency. These 46 men were selected for the analysis because a BMI of 40 kg/m² or more is an indication for bariatric surgery, and the impact of testosterone replacement in hypogonadal men with grade III obesity has not previously been studied, explained Dr. Saad, director of scientific affairs at Bayer Pharma in Berlin.

Mean body weight in this group decreased from 129 to 103 kg. Weight loss grew over time: The men averaged a 2.7% reduction in body weight after 1 year of testosterone therapy, 7.3% after 2 years, 10.9% after 3 years, 14.1% after 4 years, 17.4% after 5 years, and a 20.8% decrease from baseline body weight after 6 years of therapy.

Mean waist circumference shrunk from 118.4 cm at baseline to 106.5 cm.

On the basis of these long-term results, testosterone replacement therapy appears to be an effective means of achieving sustained weight loss in severely obese hypogonadal men, he concluded.

The registry study was funded by Bayer Pharma, which markets testosterone undecanoate as Aveed.

[email protected]

CHICAGO – Testosterone replacement therapy may provide a pharmacologic alternative to bariatric surgery in severely obese hypogonadal men.

Mean body mass index in 46 hypogonadal men with grade III obesity dropped from 41.9 to 33.6 kg/m2 while they were receiving testosterone undecanoate at 1,000 mg by intramuscular injection every 12 weeks for up to 6 years, Farid Saad, Ph.D., reported at the joint meeting of the International Congress of Endocrinology and the Endocrine Society.

The subjects, with a mean age was 60 years, were culled from two prospective registries totaling 561 men with a serum total testosterone of 12.1 nmol/L or less along with symptoms of testosterone deficiency. These 46 men were selected for the analysis because a BMI of 40 kg/m² or more is an indication for bariatric surgery, and the impact of testosterone replacement in hypogonadal men with grade III obesity has not previously been studied, explained Dr. Saad, director of scientific affairs at Bayer Pharma in Berlin.

Mean body weight in this group decreased from 129 to 103 kg. Weight loss grew over time: The men averaged a 2.7% reduction in body weight after 1 year of testosterone therapy, 7.3% after 2 years, 10.9% after 3 years, 14.1% after 4 years, 17.4% after 5 years, and a 20.8% decrease from baseline body weight after 6 years of therapy.

Mean waist circumference shrunk from 118.4 cm at baseline to 106.5 cm.

On the basis of these long-term results, testosterone replacement therapy appears to be an effective means of achieving sustained weight loss in severely obese hypogonadal men, he concluded.

The registry study was funded by Bayer Pharma, which markets testosterone undecanoate as Aveed.

[email protected]

CHICAGO – Testosterone replacement therapy may provide a pharmacologic alternative to bariatric surgery in severely obese hypogonadal men.

Mean body mass index in 46 hypogonadal men with grade III obesity dropped from 41.9 to 33.6 kg/m2 while they were receiving testosterone undecanoate at 1,000 mg by intramuscular injection every 12 weeks for up to 6 years, Farid Saad, Ph.D., reported at the joint meeting of the International Congress of Endocrinology and the Endocrine Society.

The subjects, with a mean age was 60 years, were culled from two prospective registries totaling 561 men with a serum total testosterone of 12.1 nmol/L or less along with symptoms of testosterone deficiency. These 46 men were selected for the analysis because a BMI of 40 kg/m² or more is an indication for bariatric surgery, and the impact of testosterone replacement in hypogonadal men with grade III obesity has not previously been studied, explained Dr. Saad, director of scientific affairs at Bayer Pharma in Berlin.

Mean body weight in this group decreased from 129 to 103 kg. Weight loss grew over time: The men averaged a 2.7% reduction in body weight after 1 year of testosterone therapy, 7.3% after 2 years, 10.9% after 3 years, 14.1% after 4 years, 17.4% after 5 years, and a 20.8% decrease from baseline body weight after 6 years of therapy.

Mean waist circumference shrunk from 118.4 cm at baseline to 106.5 cm.

On the basis of these long-term results, testosterone replacement therapy appears to be an effective means of achieving sustained weight loss in severely obese hypogonadal men, he concluded.

The registry study was funded by Bayer Pharma, which markets testosterone undecanoate as Aveed.

[email protected]

CHICAGO – Growth hormone therapy appears to protect against fractures in adults with growth hormone deficiency and no history of osteoporosis, according to an analysis from the HypoCCS study.

In contrast, growth hormone (GH)-deficient patients with preexisting osteoporosis are another story. GH replacement didn’t affect fracture risk in that subgroup of participants in HypoCCS (the Hypopituitary Control and Complications Study), Christopher J. Child, Ph.D., reported at the joint meeting of the International Congress of Endocrinology and the Endocrine Society. It’s well established that GH-deficient adults have lower bone mass and a two- to fivefold increased risk of fractures, compared with controls. Moreover, GH replacement therapy has been shown to increase bone-mineral density and bone-mass density and produce salutary effects on bone turnover markers.

Bruce Jancin/Frontline Medical News

But HypoCCS is the first prospective controlled study to suggest long-term GH therapy actually prevents fractures in adults with GH deficiency, noted Dr. Child of Lilly Research Laboratories in Windlesham, England.

He presented a retrospective analysis of prospectively collected data from the observational study, which included 8,374 GH-treated adults and 1,267 untreated controls, all with GH deficiency alone or in combination with other pituitary hormone deficiencies.

During a mean follow-up of 4.6 years in the GH-treated group, the combined incidence of vertebral and nonvertebral fractures was 11.9/1,000 person-years, compared with 19.1/1,000 person-years in controls, for a 37% relative risk reduction. The risk of vertebral fractures was 45% lower in the GH-treated patients; nonvertebral fractures were decreased by 32%.

In a multivariate Cox proportionate regression analysis, the protective effect of GH replacement therapy remained significant after adjustment for the common fracture risk factors, including age greater than 60 years, female gender, depression, the use of corticosteroids, and increased body weight. Dr. Child stressed in an interview that physicians shouldn’t take these HypoCCS findings as the final word on the issue of whether growth hormone replacement prevents fractures in GH-deficient adults. While this is the first-ever analysis of fracture risk from a long-term adult GH replacement study, as in any nonrandomized observational study selection bias is a possibility. And data were lacking on several potentially important confounding factors, including participants’ alcohol and calcium intake, as well as their level of physical activity.

Still, he said, the notion that GH replacement therapy may have a reduction in fracture risk as a side benefit is attractive.

He is an employee of Eli Lilly, which funds HypoCCS.

[email protected]

CHICAGO – Growth hormone therapy appears to protect against fractures in adults with growth hormone deficiency and no history of osteoporosis, according to an analysis from the HypoCCS study.

In contrast, growth hormone (GH)-deficient patients with preexisting osteoporosis are another story. GH replacement didn’t affect fracture risk in that subgroup of participants in HypoCCS (the Hypopituitary Control and Complications Study), Christopher J. Child, Ph.D., reported at the joint meeting of the International Congress of Endocrinology and the Endocrine Society. It’s well established that GH-deficient adults have lower bone mass and a two- to fivefold increased risk of fractures, compared with controls. Moreover, GH replacement therapy has been shown to increase bone-mineral density and bone-mass density and produce salutary effects on bone turnover markers.

Bruce Jancin/Frontline Medical News

But HypoCCS is the first prospective controlled study to suggest long-term GH therapy actually prevents fractures in adults with GH deficiency, noted Dr. Child of Lilly Research Laboratories in Windlesham, England.

He presented a retrospective analysis of prospectively collected data from the observational study, which included 8,374 GH-treated adults and 1,267 untreated controls, all with GH deficiency alone or in combination with other pituitary hormone deficiencies.

During a mean follow-up of 4.6 years in the GH-treated group, the combined incidence of vertebral and nonvertebral fractures was 11.9/1,000 person-years, compared with 19.1/1,000 person-years in controls, for a 37% relative risk reduction. The risk of vertebral fractures was 45% lower in the GH-treated patients; nonvertebral fractures were decreased by 32%.

In a multivariate Cox proportionate regression analysis, the protective effect of GH replacement therapy remained significant after adjustment for the common fracture risk factors, including age greater than 60 years, female gender, depression, the use of corticosteroids, and increased body weight. Dr. Child stressed in an interview that physicians shouldn’t take these HypoCCS findings as the final word on the issue of whether growth hormone replacement prevents fractures in GH-deficient adults. While this is the first-ever analysis of fracture risk from a long-term adult GH replacement study, as in any nonrandomized observational study selection bias is a possibility. And data were lacking on several potentially important confounding factors, including participants’ alcohol and calcium intake, as well as their level of physical activity.

Still, he said, the notion that GH replacement therapy may have a reduction in fracture risk as a side benefit is attractive.

He is an employee of Eli Lilly, which funds HypoCCS.

[email protected]

CHICAGO – Growth hormone therapy appears to protect against fractures in adults with growth hormone deficiency and no history of osteoporosis, according to an analysis from the HypoCCS study.

In contrast, growth hormone (GH)-deficient patients with preexisting osteoporosis are another story. GH replacement didn’t affect fracture risk in that subgroup of participants in HypoCCS (the Hypopituitary Control and Complications Study), Christopher J. Child, Ph.D., reported at the joint meeting of the International Congress of Endocrinology and the Endocrine Society. It’s well established that GH-deficient adults have lower bone mass and a two- to fivefold increased risk of fractures, compared with controls. Moreover, GH replacement therapy has been shown to increase bone-mineral density and bone-mass density and produce salutary effects on bone turnover markers.

Bruce Jancin/Frontline Medical News

But HypoCCS is the first prospective controlled study to suggest long-term GH therapy actually prevents fractures in adults with GH deficiency, noted Dr. Child of Lilly Research Laboratories in Windlesham, England.

He presented a retrospective analysis of prospectively collected data from the observational study, which included 8,374 GH-treated adults and 1,267 untreated controls, all with GH deficiency alone or in combination with other pituitary hormone deficiencies.

During a mean follow-up of 4.6 years in the GH-treated group, the combined incidence of vertebral and nonvertebral fractures was 11.9/1,000 person-years, compared with 19.1/1,000 person-years in controls, for a 37% relative risk reduction. The risk of vertebral fractures was 45% lower in the GH-treated patients; nonvertebral fractures were decreased by 32%.

In a multivariate Cox proportionate regression analysis, the protective effect of GH replacement therapy remained significant after adjustment for the common fracture risk factors, including age greater than 60 years, female gender, depression, the use of corticosteroids, and increased body weight. Dr. Child stressed in an interview that physicians shouldn’t take these HypoCCS findings as the final word on the issue of whether growth hormone replacement prevents fractures in GH-deficient adults. While this is the first-ever analysis of fracture risk from a long-term adult GH replacement study, as in any nonrandomized observational study selection bias is a possibility. And data were lacking on several potentially important confounding factors, including participants’ alcohol and calcium intake, as well as their level of physical activity.

Still, he said, the notion that GH replacement therapy may have a reduction in fracture risk as a side benefit is attractive.

He is an employee of Eli Lilly, which funds HypoCCS.

[email protected]

CHICAGO – In very short children, the slight increase in adult height from growth hormone treatment comes at the cost of psychological well-being, at least at first, according to a prospective cohort study.

So far in the ongoing investigation, the parents of 12 children with growth hormone (GH) deficiency, defined as peak stimulated GH of less than 5 ng/mL, and 7 children with idiopathic short stature (ISS) filled out the Behavior Assessment System for Children, Second Edition (BASC-2) at baseline and after 9-12 months of GH treatment. The results were compared to what the parents of nine ISS children who were not treated reported on the assessment.

GH-deficient children grew a bit, moving from –2.3 to –1.9 standard deviations below growth chart means, and ISS children grew from –2.6 to –2.2 standard deviations. Untreated children remained about 2.5 standard deviations behind their peers.

There were no statistically significant differences in baseline BASC-2 scores. However, while untreated children improved from a mean baseline depression score of 63 to 55 points, depression scores in treated children rose from 59 to 63 points. Similarly, social withdrawal in untreated children improved from 52 to 47 points, but rose from 54 to 60 points in treated children, lead investigator Dr. Emily Walvoord reported at the joint meeting of the International Congress of Endocrinology and the Endocrine Society.

Scores below 60 are considered nonclinical, scores of 60-65 indicate risk, and scores above 65 indicate pathology, explained Dr. Walvoord, a pediatric endocrinologist at Indiana University in Indianapolis.

"For short, otherwise healthy children, ... daily injections, visits to the endocrinologist every 4-6 months, and repeated discussion [of] their height might exacerbate instead of improve psychosocial concerns about being different. This [study] raises concerns that psychosocial benefits may not be achieved despite improvements in height," she and her colleagues concluded.

"I worry that we are medicalizing these kids. The message we send them is, ‘You’re not okay; there’s something wrong with you because you are too short. So you have to get a shot every day, you have to go see the doctor, and we have to talk about your height all the time.’ That’s the message I worry they internalize," Dr. Walvoord said.

"Are we really helping them? We have to be very careful about what we think is the most important outcome. Is it making the kid an inch or two taller as an adult, or is it that they have better self-esteem and psychological functioning?" she said.

If nothing else, the findings highlight the need to remind children that they are more than a number on a growth curve, and that other things matter in life.

There were no between-group differences in parent-reported cognitive functioning at baseline or follow-up. Anxiety scores improved in both cohorts, falling from 58 to 54 points in treated children, and 52 to 47 in untreated children; the meaning of that finding is uncertain. In addition, "it is possible that there was a bias toward treatment of ISS children who had underlying emotional issues," the investigators noted.

The children in the study were about 11 years old on average, with no significant differences in age, sex, or initial height standard deviations between the two groups.

Dr. Walvoord is gathering results for 13 additional children; of the total 41 subjects, 25 are boys. She hopes to follow the children for more than a year, and split out results for GH-deficient and ISS patients.

Dr. Walvoord and her colleagues had no disclosures. She initiated the work, and Eli Lilly funded it at her request.

[email protected]

CHICAGO – In very short children, the slight increase in adult height from growth hormone treatment comes at the cost of psychological well-being, at least at first, according to a prospective cohort study.

So far in the ongoing investigation, the parents of 12 children with growth hormone (GH) deficiency, defined as peak stimulated GH of less than 5 ng/mL, and 7 children with idiopathic short stature (ISS) filled out the Behavior Assessment System for Children, Second Edition (BASC-2) at baseline and after 9-12 months of GH treatment. The results were compared to what the parents of nine ISS children who were not treated reported on the assessment.

GH-deficient children grew a bit, moving from –2.3 to –1.9 standard deviations below growth chart means, and ISS children grew from –2.6 to –2.2 standard deviations. Untreated children remained about 2.5 standard deviations behind their peers.

There were no statistically significant differences in baseline BASC-2 scores. However, while untreated children improved from a mean baseline depression score of 63 to 55 points, depression scores in treated children rose from 59 to 63 points. Similarly, social withdrawal in untreated children improved from 52 to 47 points, but rose from 54 to 60 points in treated children, lead investigator Dr. Emily Walvoord reported at the joint meeting of the International Congress of Endocrinology and the Endocrine Society.

Scores below 60 are considered nonclinical, scores of 60-65 indicate risk, and scores above 65 indicate pathology, explained Dr. Walvoord, a pediatric endocrinologist at Indiana University in Indianapolis.

"For short, otherwise healthy children, ... daily injections, visits to the endocrinologist every 4-6 months, and repeated discussion [of] their height might exacerbate instead of improve psychosocial concerns about being different. This [study] raises concerns that psychosocial benefits may not be achieved despite improvements in height," she and her colleagues concluded.

"I worry that we are medicalizing these kids. The message we send them is, ‘You’re not okay; there’s something wrong with you because you are too short. So you have to get a shot every day, you have to go see the doctor, and we have to talk about your height all the time.’ That’s the message I worry they internalize," Dr. Walvoord said.

"Are we really helping them? We have to be very careful about what we think is the most important outcome. Is it making the kid an inch or two taller as an adult, or is it that they have better self-esteem and psychological functioning?" she said.

If nothing else, the findings highlight the need to remind children that they are more than a number on a growth curve, and that other things matter in life.

There were no between-group differences in parent-reported cognitive functioning at baseline or follow-up. Anxiety scores improved in both cohorts, falling from 58 to 54 points in treated children, and 52 to 47 in untreated children; the meaning of that finding is uncertain. In addition, "it is possible that there was a bias toward treatment of ISS children who had underlying emotional issues," the investigators noted.

The children in the study were about 11 years old on average, with no significant differences in age, sex, or initial height standard deviations between the two groups.

Dr. Walvoord is gathering results for 13 additional children; of the total 41 subjects, 25 are boys. She hopes to follow the children for more than a year, and split out results for GH-deficient and ISS patients.

Dr. Walvoord and her colleagues had no disclosures. She initiated the work, and Eli Lilly funded it at her request.

[email protected]

CHICAGO – In very short children, the slight increase in adult height from growth hormone treatment comes at the cost of psychological well-being, at least at first, according to a prospective cohort study.

So far in the ongoing investigation, the parents of 12 children with growth hormone (GH) deficiency, defined as peak stimulated GH of less than 5 ng/mL, and 7 children with idiopathic short stature (ISS) filled out the Behavior Assessment System for Children, Second Edition (BASC-2) at baseline and after 9-12 months of GH treatment. The results were compared to what the parents of nine ISS children who were not treated reported on the assessment.

GH-deficient children grew a bit, moving from –2.3 to –1.9 standard deviations below growth chart means, and ISS children grew from –2.6 to –2.2 standard deviations. Untreated children remained about 2.5 standard deviations behind their peers.

There were no statistically significant differences in baseline BASC-2 scores. However, while untreated children improved from a mean baseline depression score of 63 to 55 points, depression scores in treated children rose from 59 to 63 points. Similarly, social withdrawal in untreated children improved from 52 to 47 points, but rose from 54 to 60 points in treated children, lead investigator Dr. Emily Walvoord reported at the joint meeting of the International Congress of Endocrinology and the Endocrine Society.

Scores below 60 are considered nonclinical, scores of 60-65 indicate risk, and scores above 65 indicate pathology, explained Dr. Walvoord, a pediatric endocrinologist at Indiana University in Indianapolis.

"For short, otherwise healthy children, ... daily injections, visits to the endocrinologist every 4-6 months, and repeated discussion [of] their height might exacerbate instead of improve psychosocial concerns about being different. This [study] raises concerns that psychosocial benefits may not be achieved despite improvements in height," she and her colleagues concluded.

"I worry that we are medicalizing these kids. The message we send them is, ‘You’re not okay; there’s something wrong with you because you are too short. So you have to get a shot every day, you have to go see the doctor, and we have to talk about your height all the time.’ That’s the message I worry they internalize," Dr. Walvoord said.

"Are we really helping them? We have to be very careful about what we think is the most important outcome. Is it making the kid an inch or two taller as an adult, or is it that they have better self-esteem and psychological functioning?" she said.

If nothing else, the findings highlight the need to remind children that they are more than a number on a growth curve, and that other things matter in life.

There were no between-group differences in parent-reported cognitive functioning at baseline or follow-up. Anxiety scores improved in both cohorts, falling from 58 to 54 points in treated children, and 52 to 47 in untreated children; the meaning of that finding is uncertain. In addition, "it is possible that there was a bias toward treatment of ISS children who had underlying emotional issues," the investigators noted.

The children in the study were about 11 years old on average, with no significant differences in age, sex, or initial height standard deviations between the two groups.

Dr. Walvoord is gathering results for 13 additional children; of the total 41 subjects, 25 are boys. She hopes to follow the children for more than a year, and split out results for GH-deficient and ISS patients.

Dr. Walvoord and her colleagues had no disclosures. She initiated the work, and Eli Lilly funded it at her request.

[email protected]

CHICAGO – An innovative multidisciplinary lifestyle intervention in youth with first-episode psychosis can prevent the marked weight gain and other adverse cardiometabolic effects that typically arise during the first months of treatment with antipsychotic agents.

"Antipsychotic-induced weight gain can be halted through individualized lifestyle and life-skills interventions. Weight stability in the face of antipsychotic therapy is a realistic and attainable goal," Dr. Katherine Samaras said at the joint meeting of the International Congress of Endocrinology and the Endocrine Society.

The multidisciplinary Australian effort, known as the Keeping the Body in Mind Program, is carried out by Dr. Samaras, an endocrinologist at St. Vincent’s Hospital in Sydney, Australia, together with a psychiatrist, a dietician, and an exercise physiologist. Their motivation in developing the program stems from studies documenting a 20-year life expectancy shortfall in patients with major mental illness, compared with the general population, which Dr. Sue Bailey, past president of the Royal College of Psychiatrists, has called "one of the biggest health scandals of our time."

In addition, as an endocrinologist Dr. Samaras was disturbed to see children and youth on antipsychotic agents in the diabetes clinic on virtually a daily basis. Her own clinical experience was underscored in a recent Tennessee Medicaid program study which found that 6- to 17-year-olds using antipsychotics were at more than threefold increased risk of type 2 diabetes. The risk was evident within the first year and grew with increasing cumulative dose (JAMA Psychiatry 2013;70:1067-75).

"As an endocrinologist, I expect youth with type 1 diabetes to have parity with respect to life expectancy, to maintain their current health, and to develop in education and life skills and have fulfilling life experiences. Imagine if we applied the diabetes care and prevention models we use every day in children with type 1 diabetes to youth with severe mental illness on antipsychotic medications," she mused.

The program is restricted to youth with first-episode psychosis who have been on antipsychotic medication for less than 4 weeks at enrollment. The program entailed weekly individualized counseling and monitoring by a dietician and an exercise physiologist, daily access to a gym converted from a staff conference room in the first-episode psychosis unit, and weekly group life-skills training classes in cooking, shopping, and budgeting.

"There may be very little family support for these people. They’re often living in shelters," Dr. Samaras explained.

She presented a 12-week pilot study involving 16 patients in the Keeping the Body in Mind Program and 12 sociodemographically similar controls in a more conventional Sydney first-episode psychosis program without lifestyle interventions. The subjects were 15-25 years old (mean age, 20 years). The most common psychiatric diagnosis was schizophreniform disorder, followed by bipolar disorder and major depression with psychotic features.

Over the course of 12 weeks, the lifestyle intervention group gained an average of 1.2 kg, compared with 7.3 kg in controls. Moreover, just 12% of the Keeping the Body in Mind Program participants experienced clinically significant weight gain, predefined by the investigators as a greater than 7% increase, compared with 75% of controls. Waist circumference, body mass index, lipids, blood pressure, and fasting blood glucose all remained essentially unchanged over time in the program participants. The group’s aerobic fitness as reflected in peak oxygen intake (VO_2max) improved significantly. In contrast, all of these cardiometabolic parameters deteriorated significantly in the control group.

Dr. Samaras noted that most antipsychotic-induced weight gain occurs relatively early in the course of chronic treatment: In one representative study, the average gain was 12 kg during the first 24 months, another 4 kg in the following year, and an additional 3 kg at the 4-year mark.

However, when asked how long young patients with a first episode of major mental illness should remain involved in a lifestyle intervention program such as Keeping the Body in Mind, she was adamant: "I believe that as long as they’re on an antipsychotic agent they should receive dietetic and exercise physiologist support. The key is for us to walk along the path every step of the way for as long as these people need antipsychotics, and not to abandon them to the neglect that I think has characterized the physical health care of mental patients."

The study was supported by the Mental Health and Drug and Alcohol Office of the Ministry of Health for New South Wales. The presenter reported having no financial conflicts.

[email protected]

CHICAGO – An innovative multidisciplinary lifestyle intervention in youth with first-episode psychosis can prevent the marked weight gain and other adverse cardiometabolic effects that typically arise during the first months of treatment with antipsychotic agents.

"Antipsychotic-induced weight gain can be halted through individualized lifestyle and life-skills interventions. Weight stability in the face of antipsychotic therapy is a realistic and attainable goal," Dr. Katherine Samaras said at the joint meeting of the International Congress of Endocrinology and the Endocrine Society.

The multidisciplinary Australian effort, known as the Keeping the Body in Mind Program, is carried out by Dr. Samaras, an endocrinologist at St. Vincent’s Hospital in Sydney, Australia, together with a psychiatrist, a dietician, and an exercise physiologist. Their motivation in developing the program stems from studies documenting a 20-year life expectancy shortfall in patients with major mental illness, compared with the general population, which Dr. Sue Bailey, past president of the Royal College of Psychiatrists, has called "one of the biggest health scandals of our time."

In addition, as an endocrinologist Dr. Samaras was disturbed to see children and youth on antipsychotic agents in the diabetes clinic on virtually a daily basis. Her own clinical experience was underscored in a recent Tennessee Medicaid program study which found that 6- to 17-year-olds using antipsychotics were at more than threefold increased risk of type 2 diabetes. The risk was evident within the first year and grew with increasing cumulative dose (JAMA Psychiatry 2013;70:1067-75).

"As an endocrinologist, I expect youth with type 1 diabetes to have parity with respect to life expectancy, to maintain their current health, and to develop in education and life skills and have fulfilling life experiences. Imagine if we applied the diabetes care and prevention models we use every day in children with type 1 diabetes to youth with severe mental illness on antipsychotic medications," she mused.

The program is restricted to youth with first-episode psychosis who have been on antipsychotic medication for less than 4 weeks at enrollment. The program entailed weekly individualized counseling and monitoring by a dietician and an exercise physiologist, daily access to a gym converted from a staff conference room in the first-episode psychosis unit, and weekly group life-skills training classes in cooking, shopping, and budgeting.

"There may be very little family support for these people. They’re often living in shelters," Dr. Samaras explained.

She presented a 12-week pilot study involving 16 patients in the Keeping the Body in Mind Program and 12 sociodemographically similar controls in a more conventional Sydney first-episode psychosis program without lifestyle interventions. The subjects were 15-25 years old (mean age, 20 years). The most common psychiatric diagnosis was schizophreniform disorder, followed by bipolar disorder and major depression with psychotic features.

Over the course of 12 weeks, the lifestyle intervention group gained an average of 1.2 kg, compared with 7.3 kg in controls. Moreover, just 12% of the Keeping the Body in Mind Program participants experienced clinically significant weight gain, predefined by the investigators as a greater than 7% increase, compared with 75% of controls. Waist circumference, body mass index, lipids, blood pressure, and fasting blood glucose all remained essentially unchanged over time in the program participants. The group’s aerobic fitness as reflected in peak oxygen intake (VO_2max) improved significantly. In contrast, all of these cardiometabolic parameters deteriorated significantly in the control group.

Dr. Samaras noted that most antipsychotic-induced weight gain occurs relatively early in the course of chronic treatment: In one representative study, the average gain was 12 kg during the first 24 months, another 4 kg in the following year, and an additional 3 kg at the 4-year mark.

However, when asked how long young patients with a first episode of major mental illness should remain involved in a lifestyle intervention program such as Keeping the Body in Mind, she was adamant: "I believe that as long as they’re on an antipsychotic agent they should receive dietetic and exercise physiologist support. The key is for us to walk along the path every step of the way for as long as these people need antipsychotics, and not to abandon them to the neglect that I think has characterized the physical health care of mental patients."

The study was supported by the Mental Health and Drug and Alcohol Office of the Ministry of Health for New South Wales. The presenter reported having no financial conflicts.

[email protected]

CHICAGO – An innovative multidisciplinary lifestyle intervention in youth with first-episode psychosis can prevent the marked weight gain and other adverse cardiometabolic effects that typically arise during the first months of treatment with antipsychotic agents.

"Antipsychotic-induced weight gain can be halted through individualized lifestyle and life-skills interventions. Weight stability in the face of antipsychotic therapy is a realistic and attainable goal," Dr. Katherine Samaras said at the joint meeting of the International Congress of Endocrinology and the Endocrine Society.

The multidisciplinary Australian effort, known as the Keeping the Body in Mind Program, is carried out by Dr. Samaras, an endocrinologist at St. Vincent’s Hospital in Sydney, Australia, together with a psychiatrist, a dietician, and an exercise physiologist. Their motivation in developing the program stems from studies documenting a 20-year life expectancy shortfall in patients with major mental illness, compared with the general population, which Dr. Sue Bailey, past president of the Royal College of Psychiatrists, has called "one of the biggest health scandals of our time."

In addition, as an endocrinologist Dr. Samaras was disturbed to see children and youth on antipsychotic agents in the diabetes clinic on virtually a daily basis. Her own clinical experience was underscored in a recent Tennessee Medicaid program study which found that 6- to 17-year-olds using antipsychotics were at more than threefold increased risk of type 2 diabetes. The risk was evident within the first year and grew with increasing cumulative dose (JAMA Psychiatry 2013;70:1067-75).

"As an endocrinologist, I expect youth with type 1 diabetes to have parity with respect to life expectancy, to maintain their current health, and to develop in education and life skills and have fulfilling life experiences. Imagine if we applied the diabetes care and prevention models we use every day in children with type 1 diabetes to youth with severe mental illness on antipsychotic medications," she mused.

The program is restricted to youth with first-episode psychosis who have been on antipsychotic medication for less than 4 weeks at enrollment. The program entailed weekly individualized counseling and monitoring by a dietician and an exercise physiologist, daily access to a gym converted from a staff conference room in the first-episode psychosis unit, and weekly group life-skills training classes in cooking, shopping, and budgeting.

"There may be very little family support for these people. They’re often living in shelters," Dr. Samaras explained.

She presented a 12-week pilot study involving 16 patients in the Keeping the Body in Mind Program and 12 sociodemographically similar controls in a more conventional Sydney first-episode psychosis program without lifestyle interventions. The subjects were 15-25 years old (mean age, 20 years). The most common psychiatric diagnosis was schizophreniform disorder, followed by bipolar disorder and major depression with psychotic features.

Over the course of 12 weeks, the lifestyle intervention group gained an average of 1.2 kg, compared with 7.3 kg in controls. Moreover, just 12% of the Keeping the Body in Mind Program participants experienced clinically significant weight gain, predefined by the investigators as a greater than 7% increase, compared with 75% of controls. Waist circumference, body mass index, lipids, blood pressure, and fasting blood glucose all remained essentially unchanged over time in the program participants. The group’s aerobic fitness as reflected in peak oxygen intake (VO_2max) improved significantly. In contrast, all of these cardiometabolic parameters deteriorated significantly in the control group.

Dr. Samaras noted that most antipsychotic-induced weight gain occurs relatively early in the course of chronic treatment: In one representative study, the average gain was 12 kg during the first 24 months, another 4 kg in the following year, and an additional 3 kg at the 4-year mark.

However, when asked how long young patients with a first episode of major mental illness should remain involved in a lifestyle intervention program such as Keeping the Body in Mind, she was adamant: "I believe that as long as they’re on an antipsychotic agent they should receive dietetic and exercise physiologist support. The key is for us to walk along the path every step of the way for as long as these people need antipsychotics, and not to abandon them to the neglect that I think has characterized the physical health care of mental patients."

The study was supported by the Mental Health and Drug and Alcohol Office of the Ministry of Health for New South Wales. The presenter reported having no financial conflicts.

[email protected]

CHICAGO – More liberal lipid targets in elderly patients and lower statin doses might offset the risk of memory decline associated with statin use in these patients, Australian investigators suggested.

Dr. Katherine Samaras and her associates did neuropsychometric testing on 377 subjects 70-90 years old who had been on statins for 2-22 years, and 301 controls who had not taken the drugs. They then repeated the assessments at 2 and 4 years, and calculated composite, normalized z scores for various cognitive functions.

The team found a significantly greater decline in memory z score from baseline among statin users at both 2 and 4 years (4-year z score –0.27 vs. –0.07).

However, statin use was not associated with greater 4-year declines in language, processing speed, or visuospatial or executive functions. Also, metabolic syndrome was not associated with accelerated cognitive decline, Dr. Samaras reported at the joint meeting of the International Congress of Endocrinology and the Endocrine Society.

The analysis controlled for age, sex, education, smoking, the presence of hypertension, diabetes, heart disease, stroke, obesity, and the presence of apolipoprotein E e4 genotype (APOEe4), which increases the risk for Alzheimer’s disease.

Previous stroke was significantly associated with an even greater memory decline among statin users. Smoking and APOEe4 seemed to be, as well, but the trends were not significant.

The subjects were part of the Sydney Memory and Ageing Study, a longitudinal cohort of community-dwelling, well elderly from the affluent part of Sydney. None had dementia.

The findings add weight to the Food and Drug Administration's warning about statin use and memory loss in 2012.

This has "made me look very closely at who I prescribe statins for. People do report cognitive changes" if asked, said Dr. Samaras of the Garvan Institute of Medical Research and the University of New South Wales in Sydney.

To forestall memory loss, "I wonder if we should have a greater range of appropriate lipid targets for the elderly, just as we have for hemoglobin A_1c," she said. For now, if an elderly person is "really tightly controlled and well under the benchmark we are trying to reach [with statins], then I reduce the dose," with appropriate follow-up, Dr. Samaras said.

Trials of lipid-lowering therapy should include formal cognitive measurements, as well. "As a prescriber, I’d like to know that data," she said.

The subjects in the study were about 80 years old on average, and about equally split between men and women. The average body mass index was 27.1 kg/m², and the average fasting glucose level was 5.6 mmol/L. Sixty percent of statin users and 45.9% of nonusers had metabolic syndrome; 15.2% of statin users and 5.5% of nonusers had diabetes.

Australia’s National Health and Medical Research Council funded the work. Dr. Samaras and her colleagues said they had no disclosures.

[email protected]

CHICAGO – More liberal lipid targets in elderly patients and lower statin doses might offset the risk of memory decline associated with statin use in these patients, Australian investigators suggested.

Dr. Katherine Samaras and her associates did neuropsychometric testing on 377 subjects 70-90 years old who had been on statins for 2-22 years, and 301 controls who had not taken the drugs. They then repeated the assessments at 2 and 4 years, and calculated composite, normalized z scores for various cognitive functions.

The team found a significantly greater decline in memory z score from baseline among statin users at both 2 and 4 years (4-year z score –0.27 vs. –0.07).

However, statin use was not associated with greater 4-year declines in language, processing speed, or visuospatial or executive functions. Also, metabolic syndrome was not associated with accelerated cognitive decline, Dr. Samaras reported at the joint meeting of the International Congress of Endocrinology and the Endocrine Society.

The analysis controlled for age, sex, education, smoking, the presence of hypertension, diabetes, heart disease, stroke, obesity, and the presence of apolipoprotein E e4 genotype (APOEe4), which increases the risk for Alzheimer’s disease.

Previous stroke was significantly associated with an even greater memory decline among statin users. Smoking and APOEe4 seemed to be, as well, but the trends were not significant.

The subjects were part of the Sydney Memory and Ageing Study, a longitudinal cohort of community-dwelling, well elderly from the affluent part of Sydney. None had dementia.

The findings add weight to the Food and Drug Administration's warning about statin use and memory loss in 2012.

This has "made me look very closely at who I prescribe statins for. People do report cognitive changes" if asked, said Dr. Samaras of the Garvan Institute of Medical Research and the University of New South Wales in Sydney.

To forestall memory loss, "I wonder if we should have a greater range of appropriate lipid targets for the elderly, just as we have for hemoglobin A_1c," she said. For now, if an elderly person is "really tightly controlled and well under the benchmark we are trying to reach [with statins], then I reduce the dose," with appropriate follow-up, Dr. Samaras said.

Trials of lipid-lowering therapy should include formal cognitive measurements, as well. "As a prescriber, I’d like to know that data," she said.

The subjects in the study were about 80 years old on average, and about equally split between men and women. The average body mass index was 27.1 kg/m², and the average fasting glucose level was 5.6 mmol/L. Sixty percent of statin users and 45.9% of nonusers had metabolic syndrome; 15.2% of statin users and 5.5% of nonusers had diabetes.

Australia’s National Health and Medical Research Council funded the work. Dr. Samaras and her colleagues said they had no disclosures.

[email protected]

CHICAGO – More liberal lipid targets in elderly patients and lower statin doses might offset the risk of memory decline associated with statin use in these patients, Australian investigators suggested.

Dr. Katherine Samaras and her associates did neuropsychometric testing on 377 subjects 70-90 years old who had been on statins for 2-22 years, and 301 controls who had not taken the drugs. They then repeated the assessments at 2 and 4 years, and calculated composite, normalized z scores for various cognitive functions.

The team found a significantly greater decline in memory z score from baseline among statin users at both 2 and 4 years (4-year z score –0.27 vs. –0.07).

However, statin use was not associated with greater 4-year declines in language, processing speed, or visuospatial or executive functions. Also, metabolic syndrome was not associated with accelerated cognitive decline, Dr. Samaras reported at the joint meeting of the International Congress of Endocrinology and the Endocrine Society.

The analysis controlled for age, sex, education, smoking, the presence of hypertension, diabetes, heart disease, stroke, obesity, and the presence of apolipoprotein E e4 genotype (APOEe4), which increases the risk for Alzheimer’s disease.

Previous stroke was significantly associated with an even greater memory decline among statin users. Smoking and APOEe4 seemed to be, as well, but the trends were not significant.

The subjects were part of the Sydney Memory and Ageing Study, a longitudinal cohort of community-dwelling, well elderly from the affluent part of Sydney. None had dementia.

The findings add weight to the Food and Drug Administration's warning about statin use and memory loss in 2012.

This has "made me look very closely at who I prescribe statins for. People do report cognitive changes" if asked, said Dr. Samaras of the Garvan Institute of Medical Research and the University of New South Wales in Sydney.

To forestall memory loss, "I wonder if we should have a greater range of appropriate lipid targets for the elderly, just as we have for hemoglobin A_1c," she said. For now, if an elderly person is "really tightly controlled and well under the benchmark we are trying to reach [with statins], then I reduce the dose," with appropriate follow-up, Dr. Samaras said.

Trials of lipid-lowering therapy should include formal cognitive measurements, as well. "As a prescriber, I’d like to know that data," she said.

The subjects in the study were about 80 years old on average, and about equally split between men and women. The average body mass index was 27.1 kg/m², and the average fasting glucose level was 5.6 mmol/L. Sixty percent of statin users and 45.9% of nonusers had metabolic syndrome; 15.2% of statin users and 5.5% of nonusers had diabetes.

Australia’s National Health and Medical Research Council funded the work. Dr. Samaras and her colleagues said they had no disclosures.

[email protected]

CHICAGO – Older adults who undergo Roux-en-Y gastric bypass are at risk for lessened bone mineral density for at least 2 years after their surgery and should be monitored appropriately for osteoporosis or fragility fractures, according to investigators from Massachusetts General Hospital in Boston.

Two years postoperatively, vertebral bone mineral density (BMD) in 30 patients was about 7% lower on quantitative computed tomography (QCT) and 6% lower on dual-energy x-ray absorptiometry (DXA) – both methods were used to ensure accuracy – when compared with 20 well-matched, morbidly obese controls. Total hip BMD was 6% lower on QCT and 10% lower on DXA. Femoral neck BMD was about 6% lower by both measures.

Biomarkers of bone turnover remained markedly elevated in surgery patients, as well, but unchanged in controls (C-telopeptide 0.65 ng/mL vs. 0.3 ng/mL; amino-terminal propeptide of type I collagen 65 ng/mL vs. 40 ng/mL). The findings were all statistically significant.

The groups started to separate early on BMD, and there’s concern that bone loss will continue for more than 2 years after surgery. Preoperatively, most Roux-en-Y gastric bypass patients have a higher than normal BMD, "so even a loss of 10% over 2 years is not going to put most of them in the osteopenic or osteoporotic range. The caveat now is that we are [offering surgery] to older patients and adolescents. Elderly patients are starting with lower bone mass, so there are concerns about [post-op] skeletal fragility. The oldest patient in our study was 72. She became osteoporotic after surgery because her bone density was low to begin with," said lead investigator Dr. Elaine W. Yu, an endocrinologist at Massachusetts General.

"In adolescents, there are implications for achieving peak bone mass. Even if you have a normal bone density 2 years after surgery, what’s going to happen in 10 years, 20 years?" she asked.

In short, "people should pay attention to bone density and bone loss and discuss this as one of the potential negative effects of bariatric surgery. For patients at risk, you should definitely consider serial bone density monitoring and osteoporosis therapy if needed," she said at the joint meeting of the International Society of Endocrinology and the Endocrine Society.

At baseline, both subjects and controls were about 47 years old and 270 pounds, with a mean a mean body mass index of 45 kg/m². About 85% were women. The study excluded patients with histories of bone disorders or use of bone-affecting medications.

Surgery patients lost a mean of about 85 pounds in the first 6 months; their weight loss then stabilized, but they continued to lose bone. Controls stayed about the same weight.

The findings can’t be explained by post-op calcium or vitamin D depletion. "These subjects were aggressively supplemented with both," and both groups maintained normal levels throughout the study. Also, there were no statistical differences in parathyroid hormone levels between the groups.

"Our theory is that there are changes in gut hormones after gastric bypass that have direct effects on bone, like ghrelin," Dr. Yu said.

The National Institutes of Health funded the work. Dr. Yu is a consultant for Amgen.

[email protected]

CHICAGO – Older adults who undergo Roux-en-Y gastric bypass are at risk for lessened bone mineral density for at least 2 years after their surgery and should be monitored appropriately for osteoporosis or fragility fractures, according to investigators from Massachusetts General Hospital in Boston.

Two years postoperatively, vertebral bone mineral density (BMD) in 30 patients was about 7% lower on quantitative computed tomography (QCT) and 6% lower on dual-energy x-ray absorptiometry (DXA) – both methods were used to ensure accuracy – when compared with 20 well-matched, morbidly obese controls. Total hip BMD was 6% lower on QCT and 10% lower on DXA. Femoral neck BMD was about 6% lower by both measures.

Biomarkers of bone turnover remained markedly elevated in surgery patients, as well, but unchanged in controls (C-telopeptide 0.65 ng/mL vs. 0.3 ng/mL; amino-terminal propeptide of type I collagen 65 ng/mL vs. 40 ng/mL). The findings were all statistically significant.

The groups started to separate early on BMD, and there’s concern that bone loss will continue for more than 2 years after surgery. Preoperatively, most Roux-en-Y gastric bypass patients have a higher than normal BMD, "so even a loss of 10% over 2 years is not going to put most of them in the osteopenic or osteoporotic range. The caveat now is that we are [offering surgery] to older patients and adolescents. Elderly patients are starting with lower bone mass, so there are concerns about [post-op] skeletal fragility. The oldest patient in our study was 72. She became osteoporotic after surgery because her bone density was low to begin with," said lead investigator Dr. Elaine W. Yu, an endocrinologist at Massachusetts General.

"In adolescents, there are implications for achieving peak bone mass. Even if you have a normal bone density 2 years after surgery, what’s going to happen in 10 years, 20 years?" she asked.

In short, "people should pay attention to bone density and bone loss and discuss this as one of the potential negative effects of bariatric surgery. For patients at risk, you should definitely consider serial bone density monitoring and osteoporosis therapy if needed," she said at the joint meeting of the International Society of Endocrinology and the Endocrine Society.

At baseline, both subjects and controls were about 47 years old and 270 pounds, with a mean a mean body mass index of 45 kg/m². About 85% were women. The study excluded patients with histories of bone disorders or use of bone-affecting medications.

Surgery patients lost a mean of about 85 pounds in the first 6 months; their weight loss then stabilized, but they continued to lose bone. Controls stayed about the same weight.

The findings can’t be explained by post-op calcium or vitamin D depletion. "These subjects were aggressively supplemented with both," and both groups maintained normal levels throughout the study. Also, there were no statistical differences in parathyroid hormone levels between the groups.

"Our theory is that there are changes in gut hormones after gastric bypass that have direct effects on bone, like ghrelin," Dr. Yu said.

The National Institutes of Health funded the work. Dr. Yu is a consultant for Amgen.

[email protected]

CHICAGO – Older adults who undergo Roux-en-Y gastric bypass are at risk for lessened bone mineral density for at least 2 years after their surgery and should be monitored appropriately for osteoporosis or fragility fractures, according to investigators from Massachusetts General Hospital in Boston.

Two years postoperatively, vertebral bone mineral density (BMD) in 30 patients was about 7% lower on quantitative computed tomography (QCT) and 6% lower on dual-energy x-ray absorptiometry (DXA) – both methods were used to ensure accuracy – when compared with 20 well-matched, morbidly obese controls. Total hip BMD was 6% lower on QCT and 10% lower on DXA. Femoral neck BMD was about 6% lower by both measures.

Biomarkers of bone turnover remained markedly elevated in surgery patients, as well, but unchanged in controls (C-telopeptide 0.65 ng/mL vs. 0.3 ng/mL; amino-terminal propeptide of type I collagen 65 ng/mL vs. 40 ng/mL). The findings were all statistically significant.

The groups started to separate early on BMD, and there’s concern that bone loss will continue for more than 2 years after surgery. Preoperatively, most Roux-en-Y gastric bypass patients have a higher than normal BMD, "so even a loss of 10% over 2 years is not going to put most of them in the osteopenic or osteoporotic range. The caveat now is that we are [offering surgery] to older patients and adolescents. Elderly patients are starting with lower bone mass, so there are concerns about [post-op] skeletal fragility. The oldest patient in our study was 72. She became osteoporotic after surgery because her bone density was low to begin with," said lead investigator Dr. Elaine W. Yu, an endocrinologist at Massachusetts General.

"In adolescents, there are implications for achieving peak bone mass. Even if you have a normal bone density 2 years after surgery, what’s going to happen in 10 years, 20 years?" she asked.

In short, "people should pay attention to bone density and bone loss and discuss this as one of the potential negative effects of bariatric surgery. For patients at risk, you should definitely consider serial bone density monitoring and osteoporosis therapy if needed," she said at the joint meeting of the International Society of Endocrinology and the Endocrine Society.

At baseline, both subjects and controls were about 47 years old and 270 pounds, with a mean a mean body mass index of 45 kg/m². About 85% were women. The study excluded patients with histories of bone disorders or use of bone-affecting medications.

Surgery patients lost a mean of about 85 pounds in the first 6 months; their weight loss then stabilized, but they continued to lose bone. Controls stayed about the same weight.

The findings can’t be explained by post-op calcium or vitamin D depletion. "These subjects were aggressively supplemented with both," and both groups maintained normal levels throughout the study. Also, there were no statistical differences in parathyroid hormone levels between the groups.

"Our theory is that there are changes in gut hormones after gastric bypass that have direct effects on bone, like ghrelin," Dr. Yu said.

The National Institutes of Health funded the work. Dr. Yu is a consultant for Amgen.

[email protected]

CHICAGO – More than half of patients who discontinue thiazide diuretics due to hypercalcemia will remain hypercalcemic even after stopping the drugs, and will eventually be diagnosed with primary hyperparathyroidism, according to a retrospective review from the Mayo Clinic in Rochester, Minn.

Those patients probably have subclinical primary hyperparathyroidism (PHP) disease before starting thiazides, and it may have contributed to their hypertension. In the study, PHP was likely unmasked by thiazide treatment, which reduces calcium excretion. "In our clinical practice, it’s not uncommon for us to stop thiazides, and then find calcium levels don’t normalize. Now we have data to confirm our clinical impression," said senior investigator Dr. Robert Wermers, an endocrinologist in the departments of endocrinology, diabetes, metabolism and nutrition at Mayo.

The finding is something to keep in mind when prescribing thiazides. In almost all patients, they were prescribed for hypertension. Hypercalcemia was an incidental finding in the study; none of the patients were symptomatic. Older women were most at risk for PHP, and surgery was the usual treatment, he said at the joint meeting of the International Congress of Endocrinology and the Endocrine Society.

In all, the team reviewed 220 patients diagnosed with thiazide-associated hypercalcemia between 1992 and 2010. They were a median of 68 years old; 190 (86%) were women.

Eighty-one (37%) of those patients were taken off the drug; hypercalcemia persisted in 49 (60%) patients, of whom 43 (88%) were subsequently diagnosed with PHP.

The findings suggest that "primary hyperparathyroidism is common in patients who develop hypercalcemia while taking thiazide diuretics," the investigators said.

Compared with the overall patient population of 220, those who were diagnosed with PHP had a slightly higher maximum serum calcium while on thiazides (mean 10.9 vs. 10.7 mg/dL) and had been on thiazides a shorter period of time when hypercalcemia was detected (median 2.9 vs. 3.9 years). More than 80% of the patients in both groups were women, and the mean age at onset of hypercalcemia was about 67 years. Serum calcium was normal in both groups before thiazide treatment (median 9.7 mg/dL for both groups).

Of the 139 (63%) patients who stayed on thiazides despite hypercalcemia, 71 (51%) remained hypercalcemic, seven (5%) were eventually diagnosed with PHP, and calcium normalized in 68 (48.9%).

The overall incidence of thiazide associated hypercalcemia was 17 cases per 100,000 person-years. The highest rate was 314.3/100,000 person-years in women 65-74 years old. The incidence started climbing in the mid-1990s and peaked in 1999 at 31.7 cases per 100,000 person-years, perhaps because the guidelines released at the time that called for increased osteoporosis screening. In 2010, the incidence was about 20 cases per 100,000 person-years.

The investigators have no disclosures, and had no outside funding for the project.

[email protected]

CHICAGO – More than half of patients who discontinue thiazide diuretics due to hypercalcemia will remain hypercalcemic even after stopping the drugs, and will eventually be diagnosed with primary hyperparathyroidism, according to a retrospective review from the Mayo Clinic in Rochester, Minn.

Those patients probably have subclinical primary hyperparathyroidism (PHP) disease before starting thiazides, and it may have contributed to their hypertension. In the study, PHP was likely unmasked by thiazide treatment, which reduces calcium excretion. "In our clinical practice, it’s not uncommon for us to stop thiazides, and then find calcium levels don’t normalize. Now we have data to confirm our clinical impression," said senior investigator Dr. Robert Wermers, an endocrinologist in the departments of endocrinology, diabetes, metabolism and nutrition at Mayo.

The finding is something to keep in mind when prescribing thiazides. In almost all patients, they were prescribed for hypertension. Hypercalcemia was an incidental finding in the study; none of the patients were symptomatic. Older women were most at risk for PHP, and surgery was the usual treatment, he said at the joint meeting of the International Congress of Endocrinology and the Endocrine Society.

In all, the team reviewed 220 patients diagnosed with thiazide-associated hypercalcemia between 1992 and 2010. They were a median of 68 years old; 190 (86%) were women.

Eighty-one (37%) of those patients were taken off the drug; hypercalcemia persisted in 49 (60%) patients, of whom 43 (88%) were subsequently diagnosed with PHP.

The findings suggest that "primary hyperparathyroidism is common in patients who develop hypercalcemia while taking thiazide diuretics," the investigators said.

Compared with the overall patient population of 220, those who were diagnosed with PHP had a slightly higher maximum serum calcium while on thiazides (mean 10.9 vs. 10.7 mg/dL) and had been on thiazides a shorter period of time when hypercalcemia was detected (median 2.9 vs. 3.9 years). More than 80% of the patients in both groups were women, and the mean age at onset of hypercalcemia was about 67 years. Serum calcium was normal in both groups before thiazide treatment (median 9.7 mg/dL for both groups).

Of the 139 (63%) patients who stayed on thiazides despite hypercalcemia, 71 (51%) remained hypercalcemic, seven (5%) were eventually diagnosed with PHP, and calcium normalized in 68 (48.9%).

The overall incidence of thiazide associated hypercalcemia was 17 cases per 100,000 person-years. The highest rate was 314.3/100,000 person-years in women 65-74 years old. The incidence started climbing in the mid-1990s and peaked in 1999 at 31.7 cases per 100,000 person-years, perhaps because the guidelines released at the time that called for increased osteoporosis screening. In 2010, the incidence was about 20 cases per 100,000 person-years.

The investigators have no disclosures, and had no outside funding for the project.

[email protected]

CHICAGO – More than half of patients who discontinue thiazide diuretics due to hypercalcemia will remain hypercalcemic even after stopping the drugs, and will eventually be diagnosed with primary hyperparathyroidism, according to a retrospective review from the Mayo Clinic in Rochester, Minn.

Those patients probably have subclinical primary hyperparathyroidism (PHP) disease before starting thiazides, and it may have contributed to their hypertension. In the study, PHP was likely unmasked by thiazide treatment, which reduces calcium excretion. "In our clinical practice, it’s not uncommon for us to stop thiazides, and then find calcium levels don’t normalize. Now we have data to confirm our clinical impression," said senior investigator Dr. Robert Wermers, an endocrinologist in the departments of endocrinology, diabetes, metabolism and nutrition at Mayo.

The finding is something to keep in mind when prescribing thiazides. In almost all patients, they were prescribed for hypertension. Hypercalcemia was an incidental finding in the study; none of the patients were symptomatic. Older women were most at risk for PHP, and surgery was the usual treatment, he said at the joint meeting of the International Congress of Endocrinology and the Endocrine Society.

In all, the team reviewed 220 patients diagnosed with thiazide-associated hypercalcemia between 1992 and 2010. They were a median of 68 years old; 190 (86%) were women.

Eighty-one (37%) of those patients were taken off the drug; hypercalcemia persisted in 49 (60%) patients, of whom 43 (88%) were subsequently diagnosed with PHP.

The findings suggest that "primary hyperparathyroidism is common in patients who develop hypercalcemia while taking thiazide diuretics," the investigators said.

Compared with the overall patient population of 220, those who were diagnosed with PHP had a slightly higher maximum serum calcium while on thiazides (mean 10.9 vs. 10.7 mg/dL) and had been on thiazides a shorter period of time when hypercalcemia was detected (median 2.9 vs. 3.9 years). More than 80% of the patients in both groups were women, and the mean age at onset of hypercalcemia was about 67 years. Serum calcium was normal in both groups before thiazide treatment (median 9.7 mg/dL for both groups).

Of the 139 (63%) patients who stayed on thiazides despite hypercalcemia, 71 (51%) remained hypercalcemic, seven (5%) were eventually diagnosed with PHP, and calcium normalized in 68 (48.9%).

The overall incidence of thiazide associated hypercalcemia was 17 cases per 100,000 person-years. The highest rate was 314.3/100,000 person-years in women 65-74 years old. The incidence started climbing in the mid-1990s and peaked in 1999 at 31.7 cases per 100,000 person-years, perhaps because the guidelines released at the time that called for increased osteoporosis screening. In 2010, the incidence was about 20 cases per 100,000 person-years.

The investigators have no disclosures, and had no outside funding for the project.

[email protected]