MON-473 - An Oral GnRH Antagonist to Treat Mild Autonomous Cortisol Secretion Due to Adrenal Adenomas in Postmenopausal Women

Introduction: Mild autonomous cortisol secretion (MACS) is more common in women than in men, particularly after menopause. This predominance may be due to elevated LH levels after menopause that stimulate the adrenal cortex and drive tumorigenesis. We aimed to evaluate the efficacy of Elagolix, a GnRH antagonist, as a treatment for MACS in postmenopausal women.

Methods: We included postmenopausal women with benign appearing adenomas on CT scan, absence of clinical features of Cushing’s Syndrome, abnormal 1mg dexamethasone suppression test (DST) with elevations in either late night salivary cortisol (LNSC) or 24-hour urine free cortisol (UFC). Elagolix 200mg daily was administered for 6 months. Primary endpoints included adrenal adenoma size and cortisol secretion as measured by 1mg DST, LNSC, and 24-hour UFC. Secondary endpoints included change in body composition, fasting glucose and scores of The Cushing’s Quality of Life (QOL), Beck Depression and State Trait Anxiety Inventory questionnaires. We also studied the immunohistochemical (IHC) expression of LH/hCG-receptors (LH/hCG-R) in adrenal adenomas from two of four participants who underwent unilateral adrenalectomy several years after the study period. Staining was performed for 11β-hydroxylase (CYP11B1), aldosterone synthase (CYP11B2), and cytochrome B5 (CYB5) expression in adenomas and adjacent normal gland.

Results: Four participants were enrolled. At baseline, all had bilateral adenomas, abnormal 1 mg DST, and elevated LNSC. LNSC normalized in all subjects, but there was no difference in pre- and post-treatment 1mg DST, adenoma size, or fasting glucoses at the end of the 6 month study period. Two participants had DEXA scans to assess body fat composition, which showed a slight decrease in total and truncal fat. Mean scores on all QOL metrics improved. No adverse effects were observed. Two participants had a unilateral adrenalectomy several years after completion of this study. IHC staining of adenomas showed positive LH/hCG-R, CYP11B1, and CYB5 expression, and no expression of CYP11B2. One participant had an elevated aldosterone to renin ratio (ARR) prior to surgery. Adjacent normal adrenal cortex from this participant’s surgical specimen revealed aldosterone producing micronodules (APMs) that expressed LH/hCG-R.

Conclusions: Elagolix may be an effective treatment for MACS in postmenopausal adenomas. IHC confirmed the presence of LH/hCG-R in resected adenomas (2/4 participants) that serve as a target for this therapy. Interestingly, in one participant with evidence of both MACS and primary aldosteronism, IHC staining showed no expression of CYP11B2 in the adenoma but did reveal LH/hCG-R expression in adjacent APMs. This indicates that LH/hCG-R may also drive aldosterone production from APMs in some postmenopausal women.

*Unless otherwise noted, all abstracts presented at ENDO must not be released to the press or the public until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.*