AACE 2013

PHOENIX – The majority of benign thyroid nodules treated with laser ablation shrunk by more than half and the procedures had a low complication rate, according to a 2-year randomized trial in four centers in Italy.

The 200-patient study showed that the procedure was fairly well tolerated without general anesthesia, and cost about $400 in disposables per procedures, Dr. Enrico Papini said at the annual meeting of the American Association of Clinical Endocrinologists.

Previous published studies by Dr. Papini (Thyroid 2007;17:229-35) and other European groups (Thyroid 2006;16:763-8) have shown good outcomes for laser ablation of cold thyroid nodules. However, minimally invasive procedures for treating benign or malignant thyroid nodules, including percutaneous ethanol injection (PEI), radiofrequency ablation (RFA), and laser ablation (LA), have not been widely adopted by U.S. specialists, said Dr. Hossein Gharib, president-elect of the American Thyroid Association and past-president of AACE. And experience matters.

"PEI should be first-line therapy for symptomatic, benign cysts," said Dr. Gharib, who was not involved in the study. "It is easy to do, safe and very effective. LA and RFA are more complicated and should be performed only by personnel with experience and equipment."

Dr. Papini said that the procedure is performed by interventional radiologists or endocrinologists "who are fairly experienced in percutaneous injections, or at least in the use of fine-needle aspiration biopsy." He added that it takes about a month of training to be effective in the procedure.

Dr. Papini and colleagues compared the clinical and ultrasound changes in benign thyroid nodules by ultrasound-guided LA with those who were follow-up only. They also assessed side effects and the efficacy of the technique in different centers.

Two hundred consecutive patients with a solid thyroid nodule with a volume of more than 5 mL and less than 18 mL were referred to four thyroid centers and randomly assigned to a single LA treatment (101 patients) or follow-up (100 patients).

In the treatment group, clinicians performed LA with a 1.064-nm neodymium yttrium-aluminum garnet laser with 2 fibers, and an output power of 3 watts. Energy delivery was 3,600 Joules for nodules up to 13 mL, and 7,200 J for nodules larger than 13 mL. The treatment was outpatient, took less than 30 minutes, and was fairly well tolerated, said Dr. Papini. Volume and local symptoms changes were evaluated 1, 6, 12, and 24 months after LA.

There was no need for general anesthesia.

"You don’t need anesthesia," said Dr. Papini of Regina Apostolorum Hospital, Rome. "It’s very important that the patient can tell you if he feels pain. Because you have pain only if the high temperature approaches the thyroid capsule, so you can stop one of the fibers that may be closer to the border of the nodule."

The control group received no treatment affecting the thyroid gland. Clinical, laboratory, and ultrasound control were performed at baseline and every 6 months thereafter for 3 years.

Results showed that a progressive nodule volume reduction was found at 6 months (–50.7%), 12 (–57.3%), and 24 (–60.9%) months (P < .001). A reduction of more than 50% was observed in 73.6% of the cases (P < .001).

Volume reduction in LA was progressive until 12 months and remained stable until 24 months. The 24-month mean volume reduction in the difference centers was 41.6%, 63.2%, 61.5%, and 58.7%.

Cost of disposables was about $400 for each procedure, and efficacy and side effects were similar in different centers, Dr. Papini reported.

The presence of pressure symptoms complaint decreased from 31% to 1% of the cases. There were four complications, including one case of self-resolving vocal cord paresis, one infection, and two fevers.

Meanwhile, the control group showed a 21.9% volume increase in 24 months, but local symptoms did not change significantly.

Although the procedure had several advantages, including no cosmetic damage and no risk of hypothyroidism, it’s not without drawbacks. Dr. Papini said that the nodules are persistent and need careful cytologic evaluation and follow-up. Also, the operator needs to be well trained, as complications can be severe during the learning period. There’s also a potential for regrowth, although none were reported during the trial’s 3-year follow-up.

"Currently, RFA is used in some centers for hepatic but not thyroid lesions," said Dr. Gharib, who practices at Mayo Clinic, Rochester, Minn. "It is likely that in the near future we will see the application of these techniques for thyroid masses."

Dr. Papini and Dr. Gharib had no relevant disclosures.

[email protected]

On Twitter @NaseemSMiller

PHOENIX – The majority of benign thyroid nodules treated with laser ablation shrunk by more than half and the procedures had a low complication rate, according to a 2-year randomized trial in four centers in Italy.

The 200-patient study showed that the procedure was fairly well tolerated without general anesthesia, and cost about $400 in disposables per procedures, Dr. Enrico Papini said at the annual meeting of the American Association of Clinical Endocrinologists.

Previous published studies by Dr. Papini (Thyroid 2007;17:229-35) and other European groups (Thyroid 2006;16:763-8) have shown good outcomes for laser ablation of cold thyroid nodules. However, minimally invasive procedures for treating benign or malignant thyroid nodules, including percutaneous ethanol injection (PEI), radiofrequency ablation (RFA), and laser ablation (LA), have not been widely adopted by U.S. specialists, said Dr. Hossein Gharib, president-elect of the American Thyroid Association and past-president of AACE. And experience matters.

"PEI should be first-line therapy for symptomatic, benign cysts," said Dr. Gharib, who was not involved in the study. "It is easy to do, safe and very effective. LA and RFA are more complicated and should be performed only by personnel with experience and equipment."

Dr. Papini said that the procedure is performed by interventional radiologists or endocrinologists "who are fairly experienced in percutaneous injections, or at least in the use of fine-needle aspiration biopsy." He added that it takes about a month of training to be effective in the procedure.

Dr. Papini and colleagues compared the clinical and ultrasound changes in benign thyroid nodules by ultrasound-guided LA with those who were follow-up only. They also assessed side effects and the efficacy of the technique in different centers.

Two hundred consecutive patients with a solid thyroid nodule with a volume of more than 5 mL and less than 18 mL were referred to four thyroid centers and randomly assigned to a single LA treatment (101 patients) or follow-up (100 patients).

In the treatment group, clinicians performed LA with a 1.064-nm neodymium yttrium-aluminum garnet laser with 2 fibers, and an output power of 3 watts. Energy delivery was 3,600 Joules for nodules up to 13 mL, and 7,200 J for nodules larger than 13 mL. The treatment was outpatient, took less than 30 minutes, and was fairly well tolerated, said Dr. Papini. Volume and local symptoms changes were evaluated 1, 6, 12, and 24 months after LA.

There was no need for general anesthesia.

"You don’t need anesthesia," said Dr. Papini of Regina Apostolorum Hospital, Rome. "It’s very important that the patient can tell you if he feels pain. Because you have pain only if the high temperature approaches the thyroid capsule, so you can stop one of the fibers that may be closer to the border of the nodule."

The control group received no treatment affecting the thyroid gland. Clinical, laboratory, and ultrasound control were performed at baseline and every 6 months thereafter for 3 years.

Results showed that a progressive nodule volume reduction was found at 6 months (–50.7%), 12 (–57.3%), and 24 (–60.9%) months (P < .001). A reduction of more than 50% was observed in 73.6% of the cases (P < .001).

Volume reduction in LA was progressive until 12 months and remained stable until 24 months. The 24-month mean volume reduction in the difference centers was 41.6%, 63.2%, 61.5%, and 58.7%.

Cost of disposables was about $400 for each procedure, and efficacy and side effects were similar in different centers, Dr. Papini reported.

The presence of pressure symptoms complaint decreased from 31% to 1% of the cases. There were four complications, including one case of self-resolving vocal cord paresis, one infection, and two fevers.

Meanwhile, the control group showed a 21.9% volume increase in 24 months, but local symptoms did not change significantly.

Although the procedure had several advantages, including no cosmetic damage and no risk of hypothyroidism, it’s not without drawbacks. Dr. Papini said that the nodules are persistent and need careful cytologic evaluation and follow-up. Also, the operator needs to be well trained, as complications can be severe during the learning period. There’s also a potential for regrowth, although none were reported during the trial’s 3-year follow-up.

"Currently, RFA is used in some centers for hepatic but not thyroid lesions," said Dr. Gharib, who practices at Mayo Clinic, Rochester, Minn. "It is likely that in the near future we will see the application of these techniques for thyroid masses."

Dr. Papini and Dr. Gharib had no relevant disclosures.

[email protected]

On Twitter @NaseemSMiller

PHOENIX – The majority of benign thyroid nodules treated with laser ablation shrunk by more than half and the procedures had a low complication rate, according to a 2-year randomized trial in four centers in Italy.

The 200-patient study showed that the procedure was fairly well tolerated without general anesthesia, and cost about $400 in disposables per procedures, Dr. Enrico Papini said at the annual meeting of the American Association of Clinical Endocrinologists.

Previous published studies by Dr. Papini (Thyroid 2007;17:229-35) and other European groups (Thyroid 2006;16:763-8) have shown good outcomes for laser ablation of cold thyroid nodules. However, minimally invasive procedures for treating benign or malignant thyroid nodules, including percutaneous ethanol injection (PEI), radiofrequency ablation (RFA), and laser ablation (LA), have not been widely adopted by U.S. specialists, said Dr. Hossein Gharib, president-elect of the American Thyroid Association and past-president of AACE. And experience matters.

"PEI should be first-line therapy for symptomatic, benign cysts," said Dr. Gharib, who was not involved in the study. "It is easy to do, safe and very effective. LA and RFA are more complicated and should be performed only by personnel with experience and equipment."

Dr. Papini said that the procedure is performed by interventional radiologists or endocrinologists "who are fairly experienced in percutaneous injections, or at least in the use of fine-needle aspiration biopsy." He added that it takes about a month of training to be effective in the procedure.

Dr. Papini and colleagues compared the clinical and ultrasound changes in benign thyroid nodules by ultrasound-guided LA with those who were follow-up only. They also assessed side effects and the efficacy of the technique in different centers.

Two hundred consecutive patients with a solid thyroid nodule with a volume of more than 5 mL and less than 18 mL were referred to four thyroid centers and randomly assigned to a single LA treatment (101 patients) or follow-up (100 patients).

In the treatment group, clinicians performed LA with a 1.064-nm neodymium yttrium-aluminum garnet laser with 2 fibers, and an output power of 3 watts. Energy delivery was 3,600 Joules for nodules up to 13 mL, and 7,200 J for nodules larger than 13 mL. The treatment was outpatient, took less than 30 minutes, and was fairly well tolerated, said Dr. Papini. Volume and local symptoms changes were evaluated 1, 6, 12, and 24 months after LA.

There was no need for general anesthesia.

"You don’t need anesthesia," said Dr. Papini of Regina Apostolorum Hospital, Rome. "It’s very important that the patient can tell you if he feels pain. Because you have pain only if the high temperature approaches the thyroid capsule, so you can stop one of the fibers that may be closer to the border of the nodule."

The control group received no treatment affecting the thyroid gland. Clinical, laboratory, and ultrasound control were performed at baseline and every 6 months thereafter for 3 years.

Results showed that a progressive nodule volume reduction was found at 6 months (–50.7%), 12 (–57.3%), and 24 (–60.9%) months (P < .001). A reduction of more than 50% was observed in 73.6% of the cases (P < .001).

Volume reduction in LA was progressive until 12 months and remained stable until 24 months. The 24-month mean volume reduction in the difference centers was 41.6%, 63.2%, 61.5%, and 58.7%.

Cost of disposables was about $400 for each procedure, and efficacy and side effects were similar in different centers, Dr. Papini reported.

The presence of pressure symptoms complaint decreased from 31% to 1% of the cases. There were four complications, including one case of self-resolving vocal cord paresis, one infection, and two fevers.

Meanwhile, the control group showed a 21.9% volume increase in 24 months, but local symptoms did not change significantly.

Although the procedure had several advantages, including no cosmetic damage and no risk of hypothyroidism, it’s not without drawbacks. Dr. Papini said that the nodules are persistent and need careful cytologic evaluation and follow-up. Also, the operator needs to be well trained, as complications can be severe during the learning period. There’s also a potential for regrowth, although none were reported during the trial’s 3-year follow-up.

"Currently, RFA is used in some centers for hepatic but not thyroid lesions," said Dr. Gharib, who practices at Mayo Clinic, Rochester, Minn. "It is likely that in the near future we will see the application of these techniques for thyroid masses."

Dr. Papini and Dr. Gharib had no relevant disclosures.

[email protected]

On Twitter @NaseemSMiller

PHOENIX – Patients with type 1 diabetes who received high doses of once-daily insulin degludec had fewer episodes of nocturnal hypoglycemia compared with those who received a similar dose of insulin glargine, a meta-analysis of two randomized trials has shown.

"The issue is of particular concern in patients with high BMIs," said Dr. Helena Rodbard, who presented the unpublished study at the annual meeting of the American Association of Clinical Endocrinologists.

Insulin degludec is a new basal insulin with an ultralong and stable glucose-lowering effect. A previous prospective meta-analysis of phase IIIa trials comparing insulin degludec with insulin glargine showed that patients with type 1 diabetes who were on degludec had a statistically significant, 17% lower rate of nocturnal hypoglycemia across the entire treatment period and a 25% lower rate during the maintenance period (16 weeks onward), compared with those who took glargine (Diabetes Obes. Metab. 2013;15:175-84).

In their post-hoc meta-analysis, Dr. Rodbard and her colleagues compared the hypoglycemia rates for a subset of type 1 diabetes patients who required high doses of either degludec or glargine in two published trials (Lancet 2012;379:1489-97; J. Clin. Endocrinol. Metab. 2013;98:1154-62).

Nearly 25% of the patients – 235 out of a total of 950 patients in the two trials – received an end-of-trial basal insulin dose of more than 0.45 U/kg and were included in the meta-analysis.

The results showed that compared with glargine, degludec was associated with significantly lower rates of nocturnal confirmed hypoglycemia, by 36% in the full trial period (risk ratio [RR], 0.64) and by 44% in the maintenance period (RR, 0.56).

"Since patients taking higher doses of basal insulin have a longer duration of action than that seen in patients taking small doses of basal insulin, it is apparent that duration of action does not explain the benefit observed with insulin degludec," said Dr. Alan J. Garber, professor of medicine, biochemistry and molecular biology, and molecular and cellular biology at Baylor College of Medicine, Houston, and the immediate past president of the AACE. "Instead, the other dose-related characteristic of basal insulin, namely the [maximum serum concentration] of insulin, seems to explain this finding. Thus, if one basal insulin has a greater peak effect than another, it will have a greater hypoglycemic potential at higher as compared to lower doses. That is what we saw here and therefore explains the finding, owing most likely to the more definable peak of glargine compared to degludec." Dr. Garber was not involved in the study.

Meanwhile, the mean end-of-trial basal insulin dose was similar for degludec (0.63 U/kg) and glargine (0.65 U/kg). Patients also had similar mean end-of-trial hemoglobin A_1c values with degludec and glargine, at 7.41% and 7.55%, respectively.

The mean end-of-trial fasting plasma glucose levels were comparable between degludec (133 mg/dL) and glargine (136 mg/dL), at 133 mg/dL and 136 mg/dL. Also, rates of overall confirmed hypoglycemia (plasma glucose less than 56 mg/dL) did not differ significantly between the two insulins in either the full trial period or the maintenance period.

"These findings are consistent with results for the overall study population, confirming that [insulin degludec] is a well tolerated and effective basal insulin choice for patients with [type 1 diabetes] across the spectrum of insulin requirements," said Dr. Rodbard.

Dr. Rodbard is an adviser and speaker for, and has receiving research support from, several companies including AstraZeneca, Blondel, Eli Lily, Merck, Novo Nordisk, and Sanofi. Dr. Garber is a consultant/advisory board member, and/or is on the speakers bureaus, for Novo Nordisk, Daiichi Sankyo, Merck, Takeda, LipoScience, Boehringer Ingelheim, Sekris, and Lexicon.

[email protected]

On Twitter @NaseemSMiller

PHOENIX – Patients with type 1 diabetes who received high doses of once-daily insulin degludec had fewer episodes of nocturnal hypoglycemia compared with those who received a similar dose of insulin glargine, a meta-analysis of two randomized trials has shown.

"The issue is of particular concern in patients with high BMIs," said Dr. Helena Rodbard, who presented the unpublished study at the annual meeting of the American Association of Clinical Endocrinologists.

Insulin degludec is a new basal insulin with an ultralong and stable glucose-lowering effect. A previous prospective meta-analysis of phase IIIa trials comparing insulin degludec with insulin glargine showed that patients with type 1 diabetes who were on degludec had a statistically significant, 17% lower rate of nocturnal hypoglycemia across the entire treatment period and a 25% lower rate during the maintenance period (16 weeks onward), compared with those who took glargine (Diabetes Obes. Metab. 2013;15:175-84).

In their post-hoc meta-analysis, Dr. Rodbard and her colleagues compared the hypoglycemia rates for a subset of type 1 diabetes patients who required high doses of either degludec or glargine in two published trials (Lancet 2012;379:1489-97; J. Clin. Endocrinol. Metab. 2013;98:1154-62).

Nearly 25% of the patients – 235 out of a total of 950 patients in the two trials – received an end-of-trial basal insulin dose of more than 0.45 U/kg and were included in the meta-analysis.

The results showed that compared with glargine, degludec was associated with significantly lower rates of nocturnal confirmed hypoglycemia, by 36% in the full trial period (risk ratio [RR], 0.64) and by 44% in the maintenance period (RR, 0.56).

"Since patients taking higher doses of basal insulin have a longer duration of action than that seen in patients taking small doses of basal insulin, it is apparent that duration of action does not explain the benefit observed with insulin degludec," said Dr. Alan J. Garber, professor of medicine, biochemistry and molecular biology, and molecular and cellular biology at Baylor College of Medicine, Houston, and the immediate past president of the AACE. "Instead, the other dose-related characteristic of basal insulin, namely the [maximum serum concentration] of insulin, seems to explain this finding. Thus, if one basal insulin has a greater peak effect than another, it will have a greater hypoglycemic potential at higher as compared to lower doses. That is what we saw here and therefore explains the finding, owing most likely to the more definable peak of glargine compared to degludec." Dr. Garber was not involved in the study.

Meanwhile, the mean end-of-trial basal insulin dose was similar for degludec (0.63 U/kg) and glargine (0.65 U/kg). Patients also had similar mean end-of-trial hemoglobin A_1c values with degludec and glargine, at 7.41% and 7.55%, respectively.

The mean end-of-trial fasting plasma glucose levels were comparable between degludec (133 mg/dL) and glargine (136 mg/dL), at 133 mg/dL and 136 mg/dL. Also, rates of overall confirmed hypoglycemia (plasma glucose less than 56 mg/dL) did not differ significantly between the two insulins in either the full trial period or the maintenance period.

"These findings are consistent with results for the overall study population, confirming that [insulin degludec] is a well tolerated and effective basal insulin choice for patients with [type 1 diabetes] across the spectrum of insulin requirements," said Dr. Rodbard.

Dr. Rodbard is an adviser and speaker for, and has receiving research support from, several companies including AstraZeneca, Blondel, Eli Lily, Merck, Novo Nordisk, and Sanofi. Dr. Garber is a consultant/advisory board member, and/or is on the speakers bureaus, for Novo Nordisk, Daiichi Sankyo, Merck, Takeda, LipoScience, Boehringer Ingelheim, Sekris, and Lexicon.

[email protected]

On Twitter @NaseemSMiller

PHOENIX – Patients with type 1 diabetes who received high doses of once-daily insulin degludec had fewer episodes of nocturnal hypoglycemia compared with those who received a similar dose of insulin glargine, a meta-analysis of two randomized trials has shown.

"The issue is of particular concern in patients with high BMIs," said Dr. Helena Rodbard, who presented the unpublished study at the annual meeting of the American Association of Clinical Endocrinologists.

Insulin degludec is a new basal insulin with an ultralong and stable glucose-lowering effect. A previous prospective meta-analysis of phase IIIa trials comparing insulin degludec with insulin glargine showed that patients with type 1 diabetes who were on degludec had a statistically significant, 17% lower rate of nocturnal hypoglycemia across the entire treatment period and a 25% lower rate during the maintenance period (16 weeks onward), compared with those who took glargine (Diabetes Obes. Metab. 2013;15:175-84).

In their post-hoc meta-analysis, Dr. Rodbard and her colleagues compared the hypoglycemia rates for a subset of type 1 diabetes patients who required high doses of either degludec or glargine in two published trials (Lancet 2012;379:1489-97; J. Clin. Endocrinol. Metab. 2013;98:1154-62).

Nearly 25% of the patients – 235 out of a total of 950 patients in the two trials – received an end-of-trial basal insulin dose of more than 0.45 U/kg and were included in the meta-analysis.

The results showed that compared with glargine, degludec was associated with significantly lower rates of nocturnal confirmed hypoglycemia, by 36% in the full trial period (risk ratio [RR], 0.64) and by 44% in the maintenance period (RR, 0.56).

"Since patients taking higher doses of basal insulin have a longer duration of action than that seen in patients taking small doses of basal insulin, it is apparent that duration of action does not explain the benefit observed with insulin degludec," said Dr. Alan J. Garber, professor of medicine, biochemistry and molecular biology, and molecular and cellular biology at Baylor College of Medicine, Houston, and the immediate past president of the AACE. "Instead, the other dose-related characteristic of basal insulin, namely the [maximum serum concentration] of insulin, seems to explain this finding. Thus, if one basal insulin has a greater peak effect than another, it will have a greater hypoglycemic potential at higher as compared to lower doses. That is what we saw here and therefore explains the finding, owing most likely to the more definable peak of glargine compared to degludec." Dr. Garber was not involved in the study.

Meanwhile, the mean end-of-trial basal insulin dose was similar for degludec (0.63 U/kg) and glargine (0.65 U/kg). Patients also had similar mean end-of-trial hemoglobin A_1c values with degludec and glargine, at 7.41% and 7.55%, respectively.

The mean end-of-trial fasting plasma glucose levels were comparable between degludec (133 mg/dL) and glargine (136 mg/dL), at 133 mg/dL and 136 mg/dL. Also, rates of overall confirmed hypoglycemia (plasma glucose less than 56 mg/dL) did not differ significantly between the two insulins in either the full trial period or the maintenance period.

"These findings are consistent with results for the overall study population, confirming that [insulin degludec] is a well tolerated and effective basal insulin choice for patients with [type 1 diabetes] across the spectrum of insulin requirements," said Dr. Rodbard.

Dr. Rodbard is an adviser and speaker for, and has receiving research support from, several companies including AstraZeneca, Blondel, Eli Lily, Merck, Novo Nordisk, and Sanofi. Dr. Garber is a consultant/advisory board member, and/or is on the speakers bureaus, for Novo Nordisk, Daiichi Sankyo, Merck, Takeda, LipoScience, Boehringer Ingelheim, Sekris, and Lexicon.

[email protected]

On Twitter @NaseemSMiller

PHOENIX – The recently approved diabetes drug canagliflozin improved beta-cell function in patients with advanced type 2 diabetes inadequately controlled with metformin plus sulfonylurea, according to a phase III study.

Although some of the changes did not reach statistical significance, the mean value of all calculated measures of beta-cell function increased with two different canagliflozin doses, compared with placebo, the randomized, double-blind placebo-controlled study showed.

The finding is promising, said David Polidori, Ph.D., an employee of Janssen Research and Development, who presented the abstract at the annual meeting of the American Association of Clinical Endocrinologists.

Canagliflozin is a sodium glucose cotransporter 2 (SGLT2) inhibitor, which lowers plasma glucose by a renal mechanism. It also reduces the fasting and postprandial glucose hemoglobin A_1c levels.

Several animal studies have shown beneficial effects of SGLT2 inhibition on beta-cell mass or function. Other clinical studies have shown improvements in measures of beta-cell function with canagliflozin, including a 26-week phase III study with the drug as monotherapy, said Dr. Polidori. But it is not clear exactly how canagliflozin improves beta-cell function. "It may be due to the glucose toxicity. Or it may also be due to reducing the load on beta cells, the so-called unloading," he said.

The improvement in beta-cell function is worthwhile, said Dr. Alan Garber, outgoing AACE president, and professor of medicine, biochemistry, and molecular biology and molecular and cellular biology at Baylor College, Houston. "But it’s not unique to this drug."

Although both canagliflozin doses were generally well tolerated, patients in treatment groups reported higher rates of genital mycotic infections, urinary tract infections, and adverse events related to osmotic diuresis, compared with placebo. The adverse events led to few study discontinuations, said Dr. Polidori.

The SGLT2 class of drugs has been included in the recently updated AACE diabetes management algorithm, but with a note to use with caution. Dr. Garber, chair of the algorithm task force, said that the 10% risk of vulvovaginitis in women and 1% balanitis in men are not minor concerns to some patients, especially those at risk of recurrence. For men, balanitis means a trip to the emergency department, he said, "So a 1% risk requires a little bit of forethought on the part of the clinician before prescribing in at-risk patients for recurrence."

To assess the effect of canagliflozin on beta-cell function as an add-on therapy in patients with type 2 diabetes on metformin plus sulfonylurea, researchers conducted a 26-week study comparing patients on 100 mg and 300 mg of daily canaglifozin with placebo.

The study included 469 patients. A subset of them (168 patients) was given a meal tolerance test on day 1 and week 26. Their liquid meal contained 700 kcal and 100 g of glucose. Patients had a mean age of 57 years, an average HbA_1c level of 8%, a body mass index of 33 kg/m², and type 2 diabetes for an average of 10 years.

Their plasma glucose and serum C-peptide levels were measured at seven time points over a period of 3 hours.

Results showed that the mean ratio of C-peptide area under the curve (AUCc) to glucose (AUCg) increased by a mean of roughly 20% from a baseline of 132 with the 100-mg dosage and 123 with the 300-mg dosage to 160 and 152, respectively, at week 26. There was a small decrease of 3.4% in the placebo group. There was a roughly 27% difference between the canagliflozin and placebo groups that did not reach statistical significance (100 mg, P = .051; 300 mg, P = .056)

The mean insulin secretion rate at 9 mM glucose at week 26 increased significantly in the treatment groups, compared with a 12.2% decrease in the placebo group. There was a 55% difference from placebo in the 100-mg canagliflozin group (P = .02) and a 70% difference in the 300-mg (P = .007) canagliflozin group.

The mean beta-cell glucose sensitivity increased by roughly 20% from baseline in both treatment groups, but the increases were not statistically significant.

"This is 26-week data. It will be interesting to see longer-term data, and to see if this type of treatment can better prolong beta-cell function and hopefully slow the rate of progression of type 2 diabetes," said Dr. Polidori.

Dr. Polidori is an employee of Janssen Research and Development, which funded and supported the study. Dr. Garber is a consultant/advisory board member and/or is on the speakers bureaus for Novo Nordisk, Daiichi Sankyo, Merck, Takeda, LipoScience, Boehringer Ingelheim, Sekris, and Lexicon.

[email protected]

On Twitter @NaseemSMiller

PHOENIX – The recently approved diabetes drug canagliflozin improved beta-cell function in patients with advanced type 2 diabetes inadequately controlled with metformin plus sulfonylurea, according to a phase III study.

Although some of the changes did not reach statistical significance, the mean value of all calculated measures of beta-cell function increased with two different canagliflozin doses, compared with placebo, the randomized, double-blind placebo-controlled study showed.

The finding is promising, said David Polidori, Ph.D., an employee of Janssen Research and Development, who presented the abstract at the annual meeting of the American Association of Clinical Endocrinologists.

Canagliflozin is a sodium glucose cotransporter 2 (SGLT2) inhibitor, which lowers plasma glucose by a renal mechanism. It also reduces the fasting and postprandial glucose hemoglobin A_1c levels.

Several animal studies have shown beneficial effects of SGLT2 inhibition on beta-cell mass or function. Other clinical studies have shown improvements in measures of beta-cell function with canagliflozin, including a 26-week phase III study with the drug as monotherapy, said Dr. Polidori. But it is not clear exactly how canagliflozin improves beta-cell function. "It may be due to the glucose toxicity. Or it may also be due to reducing the load on beta cells, the so-called unloading," he said.

The improvement in beta-cell function is worthwhile, said Dr. Alan Garber, outgoing AACE president, and professor of medicine, biochemistry, and molecular biology and molecular and cellular biology at Baylor College, Houston. "But it’s not unique to this drug."

Although both canagliflozin doses were generally well tolerated, patients in treatment groups reported higher rates of genital mycotic infections, urinary tract infections, and adverse events related to osmotic diuresis, compared with placebo. The adverse events led to few study discontinuations, said Dr. Polidori.

The SGLT2 class of drugs has been included in the recently updated AACE diabetes management algorithm, but with a note to use with caution. Dr. Garber, chair of the algorithm task force, said that the 10% risk of vulvovaginitis in women and 1% balanitis in men are not minor concerns to some patients, especially those at risk of recurrence. For men, balanitis means a trip to the emergency department, he said, "So a 1% risk requires a little bit of forethought on the part of the clinician before prescribing in at-risk patients for recurrence."

To assess the effect of canagliflozin on beta-cell function as an add-on therapy in patients with type 2 diabetes on metformin plus sulfonylurea, researchers conducted a 26-week study comparing patients on 100 mg and 300 mg of daily canaglifozin with placebo.

The study included 469 patients. A subset of them (168 patients) was given a meal tolerance test on day 1 and week 26. Their liquid meal contained 700 kcal and 100 g of glucose. Patients had a mean age of 57 years, an average HbA_1c level of 8%, a body mass index of 33 kg/m², and type 2 diabetes for an average of 10 years.

Their plasma glucose and serum C-peptide levels were measured at seven time points over a period of 3 hours.

Results showed that the mean ratio of C-peptide area under the curve (AUCc) to glucose (AUCg) increased by a mean of roughly 20% from a baseline of 132 with the 100-mg dosage and 123 with the 300-mg dosage to 160 and 152, respectively, at week 26. There was a small decrease of 3.4% in the placebo group. There was a roughly 27% difference between the canagliflozin and placebo groups that did not reach statistical significance (100 mg, P = .051; 300 mg, P = .056)

The mean insulin secretion rate at 9 mM glucose at week 26 increased significantly in the treatment groups, compared with a 12.2% decrease in the placebo group. There was a 55% difference from placebo in the 100-mg canagliflozin group (P = .02) and a 70% difference in the 300-mg (P = .007) canagliflozin group.

The mean beta-cell glucose sensitivity increased by roughly 20% from baseline in both treatment groups, but the increases were not statistically significant.

"This is 26-week data. It will be interesting to see longer-term data, and to see if this type of treatment can better prolong beta-cell function and hopefully slow the rate of progression of type 2 diabetes," said Dr. Polidori.

Dr. Polidori is an employee of Janssen Research and Development, which funded and supported the study. Dr. Garber is a consultant/advisory board member and/or is on the speakers bureaus for Novo Nordisk, Daiichi Sankyo, Merck, Takeda, LipoScience, Boehringer Ingelheim, Sekris, and Lexicon.

[email protected]

On Twitter @NaseemSMiller

PHOENIX – The recently approved diabetes drug canagliflozin improved beta-cell function in patients with advanced type 2 diabetes inadequately controlled with metformin plus sulfonylurea, according to a phase III study.

Although some of the changes did not reach statistical significance, the mean value of all calculated measures of beta-cell function increased with two different canagliflozin doses, compared with placebo, the randomized, double-blind placebo-controlled study showed.

The finding is promising, said David Polidori, Ph.D., an employee of Janssen Research and Development, who presented the abstract at the annual meeting of the American Association of Clinical Endocrinologists.

Canagliflozin is a sodium glucose cotransporter 2 (SGLT2) inhibitor, which lowers plasma glucose by a renal mechanism. It also reduces the fasting and postprandial glucose hemoglobin A_1c levels.

Several animal studies have shown beneficial effects of SGLT2 inhibition on beta-cell mass or function. Other clinical studies have shown improvements in measures of beta-cell function with canagliflozin, including a 26-week phase III study with the drug as monotherapy, said Dr. Polidori. But it is not clear exactly how canagliflozin improves beta-cell function. "It may be due to the glucose toxicity. Or it may also be due to reducing the load on beta cells, the so-called unloading," he said.

The improvement in beta-cell function is worthwhile, said Dr. Alan Garber, outgoing AACE president, and professor of medicine, biochemistry, and molecular biology and molecular and cellular biology at Baylor College, Houston. "But it’s not unique to this drug."

Although both canagliflozin doses were generally well tolerated, patients in treatment groups reported higher rates of genital mycotic infections, urinary tract infections, and adverse events related to osmotic diuresis, compared with placebo. The adverse events led to few study discontinuations, said Dr. Polidori.

The SGLT2 class of drugs has been included in the recently updated AACE diabetes management algorithm, but with a note to use with caution. Dr. Garber, chair of the algorithm task force, said that the 10% risk of vulvovaginitis in women and 1% balanitis in men are not minor concerns to some patients, especially those at risk of recurrence. For men, balanitis means a trip to the emergency department, he said, "So a 1% risk requires a little bit of forethought on the part of the clinician before prescribing in at-risk patients for recurrence."

To assess the effect of canagliflozin on beta-cell function as an add-on therapy in patients with type 2 diabetes on metformin plus sulfonylurea, researchers conducted a 26-week study comparing patients on 100 mg and 300 mg of daily canaglifozin with placebo.

The study included 469 patients. A subset of them (168 patients) was given a meal tolerance test on day 1 and week 26. Their liquid meal contained 700 kcal and 100 g of glucose. Patients had a mean age of 57 years, an average HbA_1c level of 8%, a body mass index of 33 kg/m², and type 2 diabetes for an average of 10 years.

Their plasma glucose and serum C-peptide levels were measured at seven time points over a period of 3 hours.

Results showed that the mean ratio of C-peptide area under the curve (AUCc) to glucose (AUCg) increased by a mean of roughly 20% from a baseline of 132 with the 100-mg dosage and 123 with the 300-mg dosage to 160 and 152, respectively, at week 26. There was a small decrease of 3.4% in the placebo group. There was a roughly 27% difference between the canagliflozin and placebo groups that did not reach statistical significance (100 mg, P = .051; 300 mg, P = .056)

The mean insulin secretion rate at 9 mM glucose at week 26 increased significantly in the treatment groups, compared with a 12.2% decrease in the placebo group. There was a 55% difference from placebo in the 100-mg canagliflozin group (P = .02) and a 70% difference in the 300-mg (P = .007) canagliflozin group.

The mean beta-cell glucose sensitivity increased by roughly 20% from baseline in both treatment groups, but the increases were not statistically significant.

"This is 26-week data. It will be interesting to see longer-term data, and to see if this type of treatment can better prolong beta-cell function and hopefully slow the rate of progression of type 2 diabetes," said Dr. Polidori.

Dr. Polidori is an employee of Janssen Research and Development, which funded and supported the study. Dr. Garber is a consultant/advisory board member and/or is on the speakers bureaus for Novo Nordisk, Daiichi Sankyo, Merck, Takeda, LipoScience, Boehringer Ingelheim, Sekris, and Lexicon.

[email protected]

On Twitter @NaseemSMiller

PHOENIX – Patients who had higher rates of confirmed hypoglycemia also had greater daily variations in fasting blood glucose, regardless of diabetes type or insulin drug, according to a meta-analysis of seven trials on two long-acting basal insulin drugs.

"The data clearly show that the variation in plasma glucose is associated with hypoglycemia," said Dr. Bruce W. Bode, who presented the study at the annual meeting of the American Association of Clinical Endocrinologists.

Previous studies have shown that patients whose fasting blood glucose changes daily, due to pharmacokinetics and pharmacodynamics of basal insulin, have a difficult time adjusting their insulin dose. This, in turn, can put them at an increased risk of a hypoglycemic event. "We also need to look at what patients do and what they eat. We should look at what causes hypoglycemia in them," said Dr. Bode, a diabetes specialist at Atlanta Diabetes Associates.

The study analyzed data from seven open-label, randomized, treat-to-target published phase IIIa trials, which had compared once-daily insulin degludec (Novo Nordisk) and insulin glargine (Sanofi-Aventis).

Two trials included individuals with type 1 diabetes and five trials included those with type 2 diabetes. The trials had a 26- or 52-week duration. Daily within-subject variability (coefficient variance [CV%]) in self-measured prebreakfast plasma glucose was determined from three consecutive daily measurements made in the final week of each trial. The analysis did not compare degludec with glargine.

The CV% was compared between individuals with the highest rate of confirmed hypoglycemic events (top 25%) and those outside of this range (bottom 75%), using a linear mixed model.

Results showed that, in individuals with type 1 diabetes, the CV% ratio (top 25%/bottom 75%) was 1.33 for degludec and 1.25 for glargine, Dr. Bode said.

In insulin-experienced patients with type 2 diabetes receiving basal insulin plus oral antidiabetic therapy, the ratio was 1.33 for degludec and 1.46 for glargine, he said.

For insulin-naive patients with type 2 diabetes in whom basal insulin plus oral antidiabetic therapy was initiated in the trials, the ratios were 1.33 for degludec and 1.49 for glargine. Patients with type 2 diabetes on basal-bolus therapy had identical ratios of 1.65.

In the pooled data from type 2 diabetes trials, the ratio was 1.50 for degludec and 1.46 for glargine.

With both insulins, estimated day-to-day variability in prebreakfast plasma glucose was significantly higher for patients with the highest rates of confirmed hypoglycemia than for those with lower rates, regardless of diabetes type, type 2 diabetes treatment history, or insulin type (P less than .05), Dr. Bode reported.

Dr. Alan Garber, the outgoing AACE president and session moderator, said that "it will be interesting to go back and analyze the data to see what patient characteristics, irrespective of the type of insulin, predict great risk of variability."

Dr. Bode has been a speaker, consultant, and advisory board member for, and has received research funding from several companies, including Novo Nordisk, SanofiAventis, Eli Lily, and Medtronic. Dr. Garber is a consultant/advisory board member and/or on the speakers bureaus for Novo Nordisk, Daiichi Sankyo, Merck, Takeda, LipoScience, Boehringer Ingelheim, Sekris, and Lexicon.

[email protected]

On Twitter @NaseemSMiller

PHOENIX – Patients who had higher rates of confirmed hypoglycemia also had greater daily variations in fasting blood glucose, regardless of diabetes type or insulin drug, according to a meta-analysis of seven trials on two long-acting basal insulin drugs.

"The data clearly show that the variation in plasma glucose is associated with hypoglycemia," said Dr. Bruce W. Bode, who presented the study at the annual meeting of the American Association of Clinical Endocrinologists.

Previous studies have shown that patients whose fasting blood glucose changes daily, due to pharmacokinetics and pharmacodynamics of basal insulin, have a difficult time adjusting their insulin dose. This, in turn, can put them at an increased risk of a hypoglycemic event. "We also need to look at what patients do and what they eat. We should look at what causes hypoglycemia in them," said Dr. Bode, a diabetes specialist at Atlanta Diabetes Associates.

The study analyzed data from seven open-label, randomized, treat-to-target published phase IIIa trials, which had compared once-daily insulin degludec (Novo Nordisk) and insulin glargine (Sanofi-Aventis).

Two trials included individuals with type 1 diabetes and five trials included those with type 2 diabetes. The trials had a 26- or 52-week duration. Daily within-subject variability (coefficient variance [CV%]) in self-measured prebreakfast plasma glucose was determined from three consecutive daily measurements made in the final week of each trial. The analysis did not compare degludec with glargine.

The CV% was compared between individuals with the highest rate of confirmed hypoglycemic events (top 25%) and those outside of this range (bottom 75%), using a linear mixed model.

Results showed that, in individuals with type 1 diabetes, the CV% ratio (top 25%/bottom 75%) was 1.33 for degludec and 1.25 for glargine, Dr. Bode said.

In insulin-experienced patients with type 2 diabetes receiving basal insulin plus oral antidiabetic therapy, the ratio was 1.33 for degludec and 1.46 for glargine, he said.

For insulin-naive patients with type 2 diabetes in whom basal insulin plus oral antidiabetic therapy was initiated in the trials, the ratios were 1.33 for degludec and 1.49 for glargine. Patients with type 2 diabetes on basal-bolus therapy had identical ratios of 1.65.

In the pooled data from type 2 diabetes trials, the ratio was 1.50 for degludec and 1.46 for glargine.

With both insulins, estimated day-to-day variability in prebreakfast plasma glucose was significantly higher for patients with the highest rates of confirmed hypoglycemia than for those with lower rates, regardless of diabetes type, type 2 diabetes treatment history, or insulin type (P less than .05), Dr. Bode reported.

Dr. Alan Garber, the outgoing AACE president and session moderator, said that "it will be interesting to go back and analyze the data to see what patient characteristics, irrespective of the type of insulin, predict great risk of variability."

Dr. Bode has been a speaker, consultant, and advisory board member for, and has received research funding from several companies, including Novo Nordisk, SanofiAventis, Eli Lily, and Medtronic. Dr. Garber is a consultant/advisory board member and/or on the speakers bureaus for Novo Nordisk, Daiichi Sankyo, Merck, Takeda, LipoScience, Boehringer Ingelheim, Sekris, and Lexicon.

[email protected]

On Twitter @NaseemSMiller

PHOENIX – Patients who had higher rates of confirmed hypoglycemia also had greater daily variations in fasting blood glucose, regardless of diabetes type or insulin drug, according to a meta-analysis of seven trials on two long-acting basal insulin drugs.

"The data clearly show that the variation in plasma glucose is associated with hypoglycemia," said Dr. Bruce W. Bode, who presented the study at the annual meeting of the American Association of Clinical Endocrinologists.

Previous studies have shown that patients whose fasting blood glucose changes daily, due to pharmacokinetics and pharmacodynamics of basal insulin, have a difficult time adjusting their insulin dose. This, in turn, can put them at an increased risk of a hypoglycemic event. "We also need to look at what patients do and what they eat. We should look at what causes hypoglycemia in them," said Dr. Bode, a diabetes specialist at Atlanta Diabetes Associates.

The study analyzed data from seven open-label, randomized, treat-to-target published phase IIIa trials, which had compared once-daily insulin degludec (Novo Nordisk) and insulin glargine (Sanofi-Aventis).

Two trials included individuals with type 1 diabetes and five trials included those with type 2 diabetes. The trials had a 26- or 52-week duration. Daily within-subject variability (coefficient variance [CV%]) in self-measured prebreakfast plasma glucose was determined from three consecutive daily measurements made in the final week of each trial. The analysis did not compare degludec with glargine.

The CV% was compared between individuals with the highest rate of confirmed hypoglycemic events (top 25%) and those outside of this range (bottom 75%), using a linear mixed model.

Results showed that, in individuals with type 1 diabetes, the CV% ratio (top 25%/bottom 75%) was 1.33 for degludec and 1.25 for glargine, Dr. Bode said.

In insulin-experienced patients with type 2 diabetes receiving basal insulin plus oral antidiabetic therapy, the ratio was 1.33 for degludec and 1.46 for glargine, he said.

For insulin-naive patients with type 2 diabetes in whom basal insulin plus oral antidiabetic therapy was initiated in the trials, the ratios were 1.33 for degludec and 1.49 for glargine. Patients with type 2 diabetes on basal-bolus therapy had identical ratios of 1.65.

In the pooled data from type 2 diabetes trials, the ratio was 1.50 for degludec and 1.46 for glargine.

With both insulins, estimated day-to-day variability in prebreakfast plasma glucose was significantly higher for patients with the highest rates of confirmed hypoglycemia than for those with lower rates, regardless of diabetes type, type 2 diabetes treatment history, or insulin type (P less than .05), Dr. Bode reported.

Dr. Alan Garber, the outgoing AACE president and session moderator, said that "it will be interesting to go back and analyze the data to see what patient characteristics, irrespective of the type of insulin, predict great risk of variability."

Dr. Bode has been a speaker, consultant, and advisory board member for, and has received research funding from several companies, including Novo Nordisk, SanofiAventis, Eli Lily, and Medtronic. Dr. Garber is a consultant/advisory board member and/or on the speakers bureaus for Novo Nordisk, Daiichi Sankyo, Merck, Takeda, LipoScience, Boehringer Ingelheim, Sekris, and Lexicon.

[email protected]

On Twitter @NaseemSMiller

PHOENIX – Chronic marijuana use can be a potential cause for hypopituitarism, according to an unpublished case report, which relied on existing data about the effect of cannabis on the hypothalamic-pituitary-gonadal axis.

The case hints at a largely underrepresented problem, researchers said, especially as various states contemplate legalizing marijuana, which is currently the most commonly used illicit drug in the nation, said Dr. Richard Pinsker at the annual meeting of the American Association of Clinical Endocrinologists.

The 37-year-old man arrived at the emergency department of Jamaica (N.Y.) Hospital Medical Center in Queens in late 2012 complaining of shortness of breath, increasing fatigue, and loss of libido. The patient had low blood pressure, and physical examination revealed gynecomastia, bilateral atrophied testis, and bibasilar rales. He disclosed that he had used marijuana daily for 15 years.

After ruling out hemochromatosis, conducting a battery of hormonal tests, and an MRI, Dr. Pinsker and his colleagues diagnosed the patient with hypopituitarism. The culprit? Chronic marijuana use, they concluded after finding no other potential cause.

"I think it’s a thought-provoking study," said Dr. R. Mack Harrell, who will be the president-elect of the AACE this year. "We’ve known for many years, if you use a lot of cannabis, it suppresses the gonadal axis, and it’s been assumed that [cannabis’] only effect was on the gonadal axis. This poster poses the question of whether other pituitary hormones may be affected, and whether every pituitary hormone is at risk, so it’s hypothesis generating."

Dr. Pinsker, who is a practicing endocrinologist and the internal medicine residency program director at Jamaica Hospital Medical Center, said that the finding – and high rate of marijuana use – call for further research on the effect of chronic marijuana use on the endocrine system. He added that that physicians need to do a better job of obtaining a social history from their patients.

Tetrahydrocannabinol, or THC, which is the psychoactive ingredient of marijuana, can alter the hypothalamic-pituitary-gonadal axis either by acting directly on the hypothalamus and altering the gonadotropin-releasing hormone (GnRH) or by altering neural transmitters in the central nervous system, which affect the hypothalamus. The result is lowered luteinizing hormone (LH) and follicle-stimulating hormone (FSH), which lead to reduced testosterone production by Leydig cells of the testis.

Studies have shown cannabis exposure can result in impaired cortisol response to stress. Animal studies have shown that cannabinoids can suppress several hypothalamic-pituitary pathways, including the growth hormone, and the thyroid hormone, reported Dr. Hineshkumar Upadhyay, coauthor of the report.

Meanwhile, THC, which is lipid soluble, can remain stored in the fatty tissue and re-enter the blood stream at very low levels. This pharmacokinetics can cause chronic effect on organ systems even though it is used occasionally, researchers said.

In the case of the 37-year-old patient, researchers first suspected hemochromatosis, which they ruled out by iron studies and echocardiography. Hypopituitarism is rare in young people.

The patient had low levels of LH (0.2 mIU/mL), FSH (1.8 mIU/mL), and testosterone (22 ng/dL). His prolactin levels were high (53 ng/mL), an increase that confirms trouble in the hypothalamic-pituitary axis, said Dr. Pinsker.

Further endocrine chemistry showed that he had adrenocorticotropic hormone (ACTH) of 6 pg/mL and cortisol at 0 mcg/dL. At 60 minutes, following administration of cosyntropin, the levels changed to 6.4 pg/mL and 9.3 mcg/dL, respectively.

Additional tests revealed low levels of total T₃ (30 ng/dL), high T₃ resin reuptake (49%), low total T₄ (3.94 mcg/dL), normal free T₄ (0.97 ng/dL), and low TSH (0.22 mcIU/mL). Growth hormone was within normal limits (5.0 ng/mL), and insulinlike growth factor-1 was low (75 ng/mL; Z-score of –1.3).

MRI showed that the protuberant pituitary gland was slightly larger than the expected size, but there was no identified mass lesion, researchers reported.

Researchers started the patient on replacement hormones – 25 mg cortisone in the morning and 12.5 mg at bedtime, with 25 mcg levothyroxine daily. The patient’s fatigue and edema improved dramatically, they reported. As with other patients who abuse substances, they advised him to stop using marijuana.

Dr. Pinsker, who is also a colonel in the U.S. Army Reserve Medical Corps, said he was planning on collecting more cases before publishing the findings. He added the same mechanism could affect women as well. "We just haven’t looked at it," he said.

"I think it’ll be frightening if the use goes up" as more states make the drug legal "and the awareness does not follow it," he said.

Dr. Pinsker and Dr. Upadhyay had no disclosures.

[email protected]

On Twitter @NaseemSMiller

PHOENIX – Chronic marijuana use can be a potential cause for hypopituitarism, according to an unpublished case report, which relied on existing data about the effect of cannabis on the hypothalamic-pituitary-gonadal axis.

The case hints at a largely underrepresented problem, researchers said, especially as various states contemplate legalizing marijuana, which is currently the most commonly used illicit drug in the nation, said Dr. Richard Pinsker at the annual meeting of the American Association of Clinical Endocrinologists.

The 37-year-old man arrived at the emergency department of Jamaica (N.Y.) Hospital Medical Center in Queens in late 2012 complaining of shortness of breath, increasing fatigue, and loss of libido. The patient had low blood pressure, and physical examination revealed gynecomastia, bilateral atrophied testis, and bibasilar rales. He disclosed that he had used marijuana daily for 15 years.

After ruling out hemochromatosis, conducting a battery of hormonal tests, and an MRI, Dr. Pinsker and his colleagues diagnosed the patient with hypopituitarism. The culprit? Chronic marijuana use, they concluded after finding no other potential cause.

"I think it’s a thought-provoking study," said Dr. R. Mack Harrell, who will be the president-elect of the AACE this year. "We’ve known for many years, if you use a lot of cannabis, it suppresses the gonadal axis, and it’s been assumed that [cannabis’] only effect was on the gonadal axis. This poster poses the question of whether other pituitary hormones may be affected, and whether every pituitary hormone is at risk, so it’s hypothesis generating."

Dr. Pinsker, who is a practicing endocrinologist and the internal medicine residency program director at Jamaica Hospital Medical Center, said that the finding – and high rate of marijuana use – call for further research on the effect of chronic marijuana use on the endocrine system. He added that that physicians need to do a better job of obtaining a social history from their patients.

Tetrahydrocannabinol, or THC, which is the psychoactive ingredient of marijuana, can alter the hypothalamic-pituitary-gonadal axis either by acting directly on the hypothalamus and altering the gonadotropin-releasing hormone (GnRH) or by altering neural transmitters in the central nervous system, which affect the hypothalamus. The result is lowered luteinizing hormone (LH) and follicle-stimulating hormone (FSH), which lead to reduced testosterone production by Leydig cells of the testis.

Studies have shown cannabis exposure can result in impaired cortisol response to stress. Animal studies have shown that cannabinoids can suppress several hypothalamic-pituitary pathways, including the growth hormone, and the thyroid hormone, reported Dr. Hineshkumar Upadhyay, coauthor of the report.

Meanwhile, THC, which is lipid soluble, can remain stored in the fatty tissue and re-enter the blood stream at very low levels. This pharmacokinetics can cause chronic effect on organ systems even though it is used occasionally, researchers said.

In the case of the 37-year-old patient, researchers first suspected hemochromatosis, which they ruled out by iron studies and echocardiography. Hypopituitarism is rare in young people.

The patient had low levels of LH (0.2 mIU/mL), FSH (1.8 mIU/mL), and testosterone (22 ng/dL). His prolactin levels were high (53 ng/mL), an increase that confirms trouble in the hypothalamic-pituitary axis, said Dr. Pinsker.

Further endocrine chemistry showed that he had adrenocorticotropic hormone (ACTH) of 6 pg/mL and cortisol at 0 mcg/dL. At 60 minutes, following administration of cosyntropin, the levels changed to 6.4 pg/mL and 9.3 mcg/dL, respectively.

Additional tests revealed low levels of total T₃ (30 ng/dL), high T₃ resin reuptake (49%), low total T₄ (3.94 mcg/dL), normal free T₄ (0.97 ng/dL), and low TSH (0.22 mcIU/mL). Growth hormone was within normal limits (5.0 ng/mL), and insulinlike growth factor-1 was low (75 ng/mL; Z-score of –1.3).

MRI showed that the protuberant pituitary gland was slightly larger than the expected size, but there was no identified mass lesion, researchers reported.

Researchers started the patient on replacement hormones – 25 mg cortisone in the morning and 12.5 mg at bedtime, with 25 mcg levothyroxine daily. The patient’s fatigue and edema improved dramatically, they reported. As with other patients who abuse substances, they advised him to stop using marijuana.

Dr. Pinsker, who is also a colonel in the U.S. Army Reserve Medical Corps, said he was planning on collecting more cases before publishing the findings. He added the same mechanism could affect women as well. "We just haven’t looked at it," he said.

"I think it’ll be frightening if the use goes up" as more states make the drug legal "and the awareness does not follow it," he said.

Dr. Pinsker and Dr. Upadhyay had no disclosures.

[email protected]

On Twitter @NaseemSMiller

PHOENIX – Chronic marijuana use can be a potential cause for hypopituitarism, according to an unpublished case report, which relied on existing data about the effect of cannabis on the hypothalamic-pituitary-gonadal axis.

The case hints at a largely underrepresented problem, researchers said, especially as various states contemplate legalizing marijuana, which is currently the most commonly used illicit drug in the nation, said Dr. Richard Pinsker at the annual meeting of the American Association of Clinical Endocrinologists.

The 37-year-old man arrived at the emergency department of Jamaica (N.Y.) Hospital Medical Center in Queens in late 2012 complaining of shortness of breath, increasing fatigue, and loss of libido. The patient had low blood pressure, and physical examination revealed gynecomastia, bilateral atrophied testis, and bibasilar rales. He disclosed that he had used marijuana daily for 15 years.

After ruling out hemochromatosis, conducting a battery of hormonal tests, and an MRI, Dr. Pinsker and his colleagues diagnosed the patient with hypopituitarism. The culprit? Chronic marijuana use, they concluded after finding no other potential cause.

"I think it’s a thought-provoking study," said Dr. R. Mack Harrell, who will be the president-elect of the AACE this year. "We’ve known for many years, if you use a lot of cannabis, it suppresses the gonadal axis, and it’s been assumed that [cannabis’] only effect was on the gonadal axis. This poster poses the question of whether other pituitary hormones may be affected, and whether every pituitary hormone is at risk, so it’s hypothesis generating."

Dr. Pinsker, who is a practicing endocrinologist and the internal medicine residency program director at Jamaica Hospital Medical Center, said that the finding – and high rate of marijuana use – call for further research on the effect of chronic marijuana use on the endocrine system. He added that that physicians need to do a better job of obtaining a social history from their patients.

Tetrahydrocannabinol, or THC, which is the psychoactive ingredient of marijuana, can alter the hypothalamic-pituitary-gonadal axis either by acting directly on the hypothalamus and altering the gonadotropin-releasing hormone (GnRH) or by altering neural transmitters in the central nervous system, which affect the hypothalamus. The result is lowered luteinizing hormone (LH) and follicle-stimulating hormone (FSH), which lead to reduced testosterone production by Leydig cells of the testis.

Studies have shown cannabis exposure can result in impaired cortisol response to stress. Animal studies have shown that cannabinoids can suppress several hypothalamic-pituitary pathways, including the growth hormone, and the thyroid hormone, reported Dr. Hineshkumar Upadhyay, coauthor of the report.

Meanwhile, THC, which is lipid soluble, can remain stored in the fatty tissue and re-enter the blood stream at very low levels. This pharmacokinetics can cause chronic effect on organ systems even though it is used occasionally, researchers said.

In the case of the 37-year-old patient, researchers first suspected hemochromatosis, which they ruled out by iron studies and echocardiography. Hypopituitarism is rare in young people.

The patient had low levels of LH (0.2 mIU/mL), FSH (1.8 mIU/mL), and testosterone (22 ng/dL). His prolactin levels were high (53 ng/mL), an increase that confirms trouble in the hypothalamic-pituitary axis, said Dr. Pinsker.

Further endocrine chemistry showed that he had adrenocorticotropic hormone (ACTH) of 6 pg/mL and cortisol at 0 mcg/dL. At 60 minutes, following administration of cosyntropin, the levels changed to 6.4 pg/mL and 9.3 mcg/dL, respectively.

Additional tests revealed low levels of total T₃ (30 ng/dL), high T₃ resin reuptake (49%), low total T₄ (3.94 mcg/dL), normal free T₄ (0.97 ng/dL), and low TSH (0.22 mcIU/mL). Growth hormone was within normal limits (5.0 ng/mL), and insulinlike growth factor-1 was low (75 ng/mL; Z-score of –1.3).

MRI showed that the protuberant pituitary gland was slightly larger than the expected size, but there was no identified mass lesion, researchers reported.

Researchers started the patient on replacement hormones – 25 mg cortisone in the morning and 12.5 mg at bedtime, with 25 mcg levothyroxine daily. The patient’s fatigue and edema improved dramatically, they reported. As with other patients who abuse substances, they advised him to stop using marijuana.

Dr. Pinsker, who is also a colonel in the U.S. Army Reserve Medical Corps, said he was planning on collecting more cases before publishing the findings. He added the same mechanism could affect women as well. "We just haven’t looked at it," he said.

"I think it’ll be frightening if the use goes up" as more states make the drug legal "and the awareness does not follow it," he said.

Dr. Pinsker and Dr. Upadhyay had no disclosures.

[email protected]

On Twitter @NaseemSMiller

PHOENIX – Chronic marijuana use can be a potential cause for hypopituitarism, according to an unpublished case report, which relied on existing data about the effect of cannabis on the hypothalamic-pituitary-gonadal axis.

The case hints at a largely underrepresented problem, researchers said, especially as various states contemplate legalizing marijuana, which is currently the most commonly used illicit drug in the nation, said Dr. Richard Pinsker at the annual meeting of the American Association of Clinical Endocrinologists.

The 37-year-old man arrived at the emergency department of Jamaica (N.Y.) Hospital Medical Center in Queens in late 2012 complaining of shortness of breath, increasing fatigue, and loss of libido. The patient had low blood pressure, and physical examination revealed gynecomastia, bilateral atrophied testis, and bibasilar rales. He disclosed that he had used marijuana daily for 15 years.

After ruling out hemochromatosis, conducting a battery of hormonal tests, and an MRI, Dr. Pinsker and his colleagues diagnosed the patient with hypopituitarism. The culprit? Chronic marijuana use, they concluded after finding no other potential cause.

"I think it’s a thought-provoking study," said Dr. R. Mack Harrell, who will be the president-elect of the AACE this year. "We’ve known for many years, if you use a lot of cannabis, it suppresses the gonadal axis, and it’s been assumed that [cannabis’] only effect was on the gonadal axis. This poster poses the question of whether other pituitary hormones may be affected, and whether every pituitary hormone is at risk, so it’s hypothesis generating."

Dr. Pinsker, who is a practicing endocrinologist and the internal medicine residency program director at Jamaica Hospital Medical Center, said that the finding – and high rate of marijuana use – call for further research on the effect of chronic marijuana use on the endocrine system. He added that that physicians need to do a better job of obtaining a social history from their patients.

Tetrahydrocannabinol, or THC, which is the psychoactive ingredient of marijuana, can alter the hypothalamic-pituitary-gonadal axis either by acting directly on the hypothalamus and altering the gonadotropin-releasing hormone (GnRH) or by altering neural transmitters in the central nervous system, which affect the hypothalamus. The result is lowered luteinizing hormone (LH) and follicle-stimulating hormone (FSH), which lead to reduced testosterone production by Leydig cells of the testis.

Studies have shown cannabis exposure can result in impaired cortisol response to stress. Animal studies have shown that cannabinoids can suppress several hypothalamic-pituitary pathways, including the growth hormone, and the thyroid hormone, reported Dr. Hineshkumar Upadhyay, coauthor of the report.

Meanwhile, THC, which is lipid soluble, can remain stored in the fatty tissue and re-enter the blood stream at very low levels. This pharmacokinetics can cause chronic effect on organ systems even though it is used occasionally, researchers said.

In the case of the 37-year-old patient, researchers first suspected hemochromatosis, which they ruled out by iron studies and echocardiography. Hypopituitarism is rare in young people.

The patient had low levels of LH (0.2 mIU/mL), FSH (1.8 mIU/mL), and testosterone (22 ng/dL). His prolactin levels were high (53 ng/mL), an increase that confirms trouble in the hypothalamic-pituitary axis, said Dr. Pinsker.

Further endocrine chemistry showed that he had adrenocorticotropic hormone (ACTH) of 6 pg/mL and cortisol at 0 mcg/dL. At 60 minutes, following administration of cosyntropin, the levels changed to 6.4 pg/mL and 9.3 mcg/dL, respectively.

Additional tests revealed low levels of total T₃ (30 ng/dL), high T₃ resin reuptake (49%), low total T₄ (3.94 mcg/dL), normal free T₄ (0.97 ng/dL), and low TSH (0.22 mcIU/mL). Growth hormone was within normal limits (5.0 ng/mL), and insulinlike growth factor-1 was low (75 ng/mL; Z-score of –1.3).

MRI showed that the protuberant pituitary gland was slightly larger than the expected size, but there was no identified mass lesion, researchers reported.

Researchers started the patient on replacement hormones – 25 mg cortisone in the morning and 12.5 mg at bedtime, with 25 mcg levothyroxine daily. The patient’s fatigue and edema improved dramatically, they reported. As with other patients who abuse substances, they advised him to stop using marijuana.

Dr. Pinsker, who is also a colonel in the U.S. Army Reserve Medical Corps, said he was planning on collecting more cases before publishing the findings. He added the same mechanism could affect women as well. "We just haven’t looked at it," he said.

"I think it’ll be frightening if the use goes up" as more states make the drug legal "and the awareness does not follow it," he said.

Dr. Pinsker and Dr. Upadhyay had no disclosures.

[email protected]

On Twitter @NaseemSMiller

PHOENIX – Chronic marijuana use can be a potential cause for hypopituitarism, according to an unpublished case report, which relied on existing data about the effect of cannabis on the hypothalamic-pituitary-gonadal axis.

The case hints at a largely underrepresented problem, researchers said, especially as various states contemplate legalizing marijuana, which is currently the most commonly used illicit drug in the nation, said Dr. Richard Pinsker at the annual meeting of the American Association of Clinical Endocrinologists.

The 37-year-old man arrived at the emergency department of Jamaica (N.Y.) Hospital Medical Center in Queens in late 2012 complaining of shortness of breath, increasing fatigue, and loss of libido. The patient had low blood pressure, and physical examination revealed gynecomastia, bilateral atrophied testis, and bibasilar rales. He disclosed that he had used marijuana daily for 15 years.

After ruling out hemochromatosis, conducting a battery of hormonal tests, and an MRI, Dr. Pinsker and his colleagues diagnosed the patient with hypopituitarism. The culprit? Chronic marijuana use, they concluded after finding no other potential cause.

"I think it’s a thought-provoking study," said Dr. R. Mack Harrell, who will be the president-elect of the AACE this year. "We’ve known for many years, if you use a lot of cannabis, it suppresses the gonadal axis, and it’s been assumed that [cannabis’] only effect was on the gonadal axis. This poster poses the question of whether other pituitary hormones may be affected, and whether every pituitary hormone is at risk, so it’s hypothesis generating."

Dr. Pinsker, who is a practicing endocrinologist and the internal medicine residency program director at Jamaica Hospital Medical Center, said that the finding – and high rate of marijuana use – call for further research on the effect of chronic marijuana use on the endocrine system. He added that that physicians need to do a better job of obtaining a social history from their patients.

Tetrahydrocannabinol, or THC, which is the psychoactive ingredient of marijuana, can alter the hypothalamic-pituitary-gonadal axis either by acting directly on the hypothalamus and altering the gonadotropin-releasing hormone (GnRH) or by altering neural transmitters in the central nervous system, which affect the hypothalamus. The result is lowered luteinizing hormone (LH) and follicle-stimulating hormone (FSH), which lead to reduced testosterone production by Leydig cells of the testis.

Studies have shown cannabis exposure can result in impaired cortisol response to stress. Animal studies have shown that cannabinoids can suppress several hypothalamic-pituitary pathways, including the growth hormone, and the thyroid hormone, reported Dr. Hineshkumar Upadhyay, coauthor of the report.

Meanwhile, THC, which is lipid soluble, can remain stored in the fatty tissue and re-enter the blood stream at very low levels. This pharmacokinetics can cause chronic effect on organ systems even though it is used occasionally, researchers said.

In the case of the 37-year-old patient, researchers first suspected hemochromatosis, which they ruled out by iron studies and echocardiography. Hypopituitarism is rare in young people.

The patient had low levels of LH (0.2 mIU/mL), FSH (1.8 mIU/mL), and testosterone (22 ng/dL). His prolactin levels were high (53 ng/mL), an increase that confirms trouble in the hypothalamic-pituitary axis, said Dr. Pinsker.

Further endocrine chemistry showed that he had adrenocorticotropic hormone (ACTH) of 6 pg/mL and cortisol at 0 mcg/dL. At 60 minutes, following administration of cosyntropin, the levels changed to 6.4 pg/mL and 9.3 mcg/dL, respectively.

Additional tests revealed low levels of total T₃ (30 ng/dL), high T₃ resin reuptake (49%), low total T₄ (3.94 mcg/dL), normal free T₄ (0.97 ng/dL), and low TSH (0.22 mcIU/mL). Growth hormone was within normal limits (5.0 ng/mL), and insulinlike growth factor-1 was low (75 ng/mL; Z-score of –1.3).

MRI showed that the protuberant pituitary gland was slightly larger than the expected size, but there was no identified mass lesion, researchers reported.

Researchers started the patient on replacement hormones – 25 mg cortisone in the morning and 12.5 mg at bedtime, with 25 mcg levothyroxine daily. The patient’s fatigue and edema improved dramatically, they reported. As with other patients who abuse substances, they advised him to stop using marijuana.

Dr. Pinsker, who is also a colonel in the U.S. Army Reserve Medical Corps, said he was planning on collecting more cases before publishing the findings. He added the same mechanism could affect women as well. "We just haven’t looked at it," he said.

"I think it’ll be frightening if the use goes up" as more states make the drug legal "and the awareness does not follow it," he said.

Dr. Pinsker and Dr. Upadhyay had no disclosures.

[email protected]

On Twitter @NaseemSMiller

PHOENIX – Chronic marijuana use can be a potential cause for hypopituitarism, according to an unpublished case report, which relied on existing data about the effect of cannabis on the hypothalamic-pituitary-gonadal axis.

The case hints at a largely underrepresented problem, researchers said, especially as various states contemplate legalizing marijuana, which is currently the most commonly used illicit drug in the nation, said Dr. Richard Pinsker at the annual meeting of the American Association of Clinical Endocrinologists.

The 37-year-old man arrived at the emergency department of Jamaica (N.Y.) Hospital Medical Center in Queens in late 2012 complaining of shortness of breath, increasing fatigue, and loss of libido. The patient had low blood pressure, and physical examination revealed gynecomastia, bilateral atrophied testis, and bibasilar rales. He disclosed that he had used marijuana daily for 15 years.

After ruling out hemochromatosis, conducting a battery of hormonal tests, and an MRI, Dr. Pinsker and his colleagues diagnosed the patient with hypopituitarism. The culprit? Chronic marijuana use, they concluded after finding no other potential cause.

"I think it’s a thought-provoking study," said Dr. R. Mack Harrell, who will be the president-elect of the AACE this year. "We’ve known for many years, if you use a lot of cannabis, it suppresses the gonadal axis, and it’s been assumed that [cannabis’] only effect was on the gonadal axis. This poster poses the question of whether other pituitary hormones may be affected, and whether every pituitary hormone is at risk, so it’s hypothesis generating."

Dr. Pinsker, who is a practicing endocrinologist and the internal medicine residency program director at Jamaica Hospital Medical Center, said that the finding – and high rate of marijuana use – call for further research on the effect of chronic marijuana use on the endocrine system. He added that that physicians need to do a better job of obtaining a social history from their patients.

Tetrahydrocannabinol, or THC, which is the psychoactive ingredient of marijuana, can alter the hypothalamic-pituitary-gonadal axis either by acting directly on the hypothalamus and altering the gonadotropin-releasing hormone (GnRH) or by altering neural transmitters in the central nervous system, which affect the hypothalamus. The result is lowered luteinizing hormone (LH) and follicle-stimulating hormone (FSH), which lead to reduced testosterone production by Leydig cells of the testis.

Studies have shown cannabis exposure can result in impaired cortisol response to stress. Animal studies have shown that cannabinoids can suppress several hypothalamic-pituitary pathways, including the growth hormone, and the thyroid hormone, reported Dr. Hineshkumar Upadhyay, coauthor of the report.

Meanwhile, THC, which is lipid soluble, can remain stored in the fatty tissue and re-enter the blood stream at very low levels. This pharmacokinetics can cause chronic effect on organ systems even though it is used occasionally, researchers said.

In the case of the 37-year-old patient, researchers first suspected hemochromatosis, which they ruled out by iron studies and echocardiography. Hypopituitarism is rare in young people.

The patient had low levels of LH (0.2 mIU/mL), FSH (1.8 mIU/mL), and testosterone (22 ng/dL). His prolactin levels were high (53 ng/mL), an increase that confirms trouble in the hypothalamic-pituitary axis, said Dr. Pinsker.

Further endocrine chemistry showed that he had adrenocorticotropic hormone (ACTH) of 6 pg/mL and cortisol at 0 mcg/dL. At 60 minutes, following administration of cosyntropin, the levels changed to 6.4 pg/mL and 9.3 mcg/dL, respectively.

Additional tests revealed low levels of total T₃ (30 ng/dL), high T₃ resin reuptake (49%), low total T₄ (3.94 mcg/dL), normal free T₄ (0.97 ng/dL), and low TSH (0.22 mcIU/mL). Growth hormone was within normal limits (5.0 ng/mL), and insulinlike growth factor-1 was low (75 ng/mL; Z-score of –1.3).

MRI showed that the protuberant pituitary gland was slightly larger than the expected size, but there was no identified mass lesion, researchers reported.

Researchers started the patient on replacement hormones – 25 mg cortisone in the morning and 12.5 mg at bedtime, with 25 mcg levothyroxine daily. The patient’s fatigue and edema improved dramatically, they reported. As with other patients who abuse substances, they advised him to stop using marijuana.

Dr. Pinsker, who is also a colonel in the U.S. Army Reserve Medical Corps, said he was planning on collecting more cases before publishing the findings. He added the same mechanism could affect women as well. "We just haven’t looked at it," he said.

"I think it’ll be frightening if the use goes up" as more states make the drug legal "and the awareness does not follow it," he said.

Dr. Pinsker and Dr. Upadhyay had no disclosures.

[email protected]

On Twitter @NaseemSMiller