Froedtert and MCW researchers investigate Cushing syndrome incidence in bariatric surgery patients

Researchers at the Medical College of Wisconsin determined that Cushing syndrome, an endocrine disorder, may be the potential cause for weight gain and metabolic complications for patients who have undergone bariatric surgery for obesity. The study, published in the journal Obesity Surgery, was conducted by Ty B. Carroll, MD, assistant professor of endocrinology; James W. Findling, MD, FACP, professor of endocrinology ; and Bradley R. Javorsky, MD, assistant professor of endocrinology. The physicians practice at Froedtert Hospital in Wauwatosa and Community Memorial Hospital in Menomonee Falls.

Cushing syndrome can occur when the human body is exposed to high levels of cortisol for an extended period of time. Cortisol is a hormone in the body which affects blood pressure regulation and cardiovascular system functions. Cortisol also helps regulate the body’s conversion of proteins, carbohydrates and fats from diet into usable energy. However, when the level of cortisol becomes too high, Cushing syndrome can develop.

Cushing syndrome is associated with a variety of symptoms including weight gain and fatty tissue deposits in the body. According to the American Association of Neurological Surgeons, 10 to 15 million people are affected each year by Cushing syndrome.

Bariatric surgery is a procedure performed to help with extreme cases of obesity. Weight loss is achieved by reducing the size of the stomach with a gastric band, removal of a portion of the stomach or resecting and rerouting the small intestine to a small stomach pouch. Bariatric surgery is often used as an option for individuals unable to lose weight through diet and exercise, or have serious health problems caused by obesity.

According to the American Society for Metabolic and Bariatric Surgery, 179,000 bariatric surgeries were performed in the U.S. in 2013. However, despite successes in normal weight loss cases, bariatric surgery does not provide long term weight loss for individuals diagnosed with Cushing syndrome. Cushing syndrome often goes undiagnosed as a potential cause for weight gain and metabolic complications until after the surgery is performed.

MCW researchers in this study analyzed the incidence of Cushing syndrome in patients who underwent bariatric surgery for weight loss. During the investigation, the researchers performed a retrospective chart review on a series of 16 patients diagnosed with Cushing syndrome from five tertiary care centers in the U.S. who underwent bariatric surgery. The results from the study found 12 of the analyzed patients were not diagnosed with Cushing syndrome prior to their bariatric surgery. The remaining four patients had Cushing syndrome surgery prior to bariatric surgery, without recognition that their Cushing syndrome was persistent until after the weight loss surgery. The findings from the research indicate that Cushing syndrome may be often overlooked in patients undergoing bariatric surgery.

According to the researchers, testing for Cushing syndrome should be performed prior to bariatric surgery in patients with persistent hypertension, diabetes mellitus or excessive weight regain.


Use late-night salivary cortisol to catch recurrent Cushing’s


CHICAGO – Late-night salivary cortisol exceeded normal limits in 10 women with recurrent Cushing’s disease a mean of 3.5 years after transsphenoidal surgery, but their urinary free cortisol remained in normal limits, according to a retrospective review from the Medical College of Wisconsin, Milwaukee.

That adds strength to the notion that late-night salivary cortisol (LNSC) catches recurrent Cushing’s that’s missed by urinary free cortisol, even though UFC remains a standard screening approach in some places.

The study is tiny and retrospective, but at the joint meeting of the International Congress of Endocrinology and the Endocrine Society, lead investigator Dr. Ty Carroll explained why the findings still matter, and also why two LNSC measurements are better than one.


Long-term mifepristone associated with endometrial thickening, bleeding

SAN FRANCISCO – Long-term mifepristone therapy for Cushing’s syndrome was associated with endometrial thickening, with some women showing histologic changes consistent with progesterone receptor modulator–associated endometrial changes, in two studies of a total of 35 patients.

The women received 300-1,200 mg/day of mifepristone in the 24-week open-label Study of the Efficacy and Safety of Mifepristone in the Treatment of Endogenous Cushing’s Syndrome (SEISMIC) and in an extension of the study in 18 patients who continued for a median of 27 months (range, 14-43 months).

Mifeprex is used, with misoprostol, to end an early pregnancy (within 49 days of the start of a woman’s last menstrual period), according to the Food and Drug Administration’s website. The treatment of Cushing’s syndrome is an off-label use.

Transvaginal ultrasounds in 26 women at baseline and 27 women after the start of the study showed that mifepristone use was associated with endometrial thickening, especially in premenopausal women. The endometrium thickened by more than 5 mm in 8 of 26 premenopausal women (31%) and in two of nine postmenopausal women (22%), with thickening of more than 10 mm in 4 premenopausal women (15%) and one postmenopausal woman (11%), Dr. Ty Carroll reported.

Four (22%) of the 18 women in the extension study who’d been on mifepristone for 14 or more weeks and who had endometrial thickening greater than 20 mm developed clinically relevant endometrial bleeding and underwent hysterectomy (three patients) or dilation and curettage. The endometrial thickening ranged from 25 to 55 mm in these women, who remained on mifepristone therapy throughout the studies, Dr. Carroll and his associates reported in a featured poster presentation at the annual meeting of the Endocrine Society.

“Gynecologic consultation may be required in patients with persistent endometrial bleeding,” said Dr. Carroll of the Medical College of Wisconsin, Milwaukee.

Vaginal bleeding of any kind occurred in 10 premenopausal women (38.5%) and two postmenopausal patients (7%). Three premenopausal women reported minor bleeding upon starting mifepristone, and one premenopausal woman reported minor bleeding after stopping mifepristone. Two premenopausal and two postmenopausal women reported intermittent, self-limited spotting or bleeding during treatment.

Bleeding did not always occur following endometrial thickening. Three patients with endometrial thickening greater than 20 mm after 6 months reported no bleeding.

Mifepristone use was not associated with precancerous endometrial lesions. In 33 endometrial biopsies obtained from 15 patients (11 premenopausal and 4 postmenopausal women), 31 biopsies (94%) had benign histology with variable findings of inactive, atrophic, disordered, or mixed-pattern endometrium, and 18 biopsies (56%) showed findings of progesterone receptor modulator–associated endometrial changes. Simple hyperplasia in one patient could not be confirmed on a repeat biopsy, and complex atypical endometrial hyperplasia in a second patient was thought to have existed prior to the study, Dr. Carroll reported. No patients showed evidence of endometrial carcinoma.

Previous studies have reported progesterone receptor modulator–associated endometrial changes from the use of mifepristone, a competitive progesterone receptor antagonist, in doses of 5-200 mg/day that are not associated with glucocorticoid receptor antagonism.

In the current study, median endometrial thickness for the premenopausal women was 5 mm at baseline and 11 mm at 6 months, and for postmenopausal women, was 3 mm at baseline and 6.4 mm at 6 months. The gain was statistically significant for premenopausal but not postmenopausal women. Endometrial thickness continued to increase in the extension study.

The SEISMIC study included adult females with endogenous Cushing’s syndrome and type 2 diabetes or impaired glucose function and/or hypertension. It excluded premenopausal women with an endometrial thickness greater than 20 mm, postmenopausal women with an endometrial thickness greater than 5 mm, patients with ovarian cysts with diameters measuring greater than 5 cm (premenopausal) or 2 cm (postmenopausal), or women with free fluid pockets greater than 4 cm. Premenopausal participants had a mean age of 39 years, and postmenopausal participants had a mean age of 57 years.

Dr. Carroll has been a speaker and researcher for Corcept Therapeutics, which markets mifepristone. His coinvestigators were employees, contractors, or consultants for Corcept, which provided some funding for the study.

By: SHERRY BOSCHERT, Clinical Endocrinology News Digital Network

On Twitter @sherryboschert

From Clinical Endocrinology News

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