The Development of Hypogonadotropic Hypogonadism After Starting Low Dose Mifepristone for Cushing’s Syndrome

Background: Mifepristone is an antiprogesterone that has been studied in females and has shown central effects including suppressing LH surges. There is a paucity of information about how it effects males. Clinical Case: 65-year-old male with bilateral adrenal macronodular hyperplasia noted on a past surveillance CT scan presented to endocrinology. He had a history of coronary artery disease, type 2 diabetes, obesity, and treated sleep apnea. He had progressively worsening abdominal weight gain, supraclavicular fat pads, thin bruising skin, and hypertension. He had several abnormal 1 mg overnight dexamethasone suppression tests (ACTH 3 & <1 pg/ml and cortisol 10 ug/dL & 11.1 ug/dL). He had several abnormal midnight salivary cortisol tests (109 ng/dL, 147ng/dL, and 152 ng/dL, reference <100 ng/dL). He elected to have medical treatment for his Cushing’s Syndrome after worsening hypertension and several episodes of hypertensive urgency. He was deemed a non-surgical candidate. He was started on mifepristone 300 mg/day and spironolactone 12.5 mg/day given eGFR 47 mL/min/1.73sq m. His mifepristone dose was dropped to 300 mg every other day after he had several episodes of orthostatic hypotension, nausea, and hot flashes. On lower dose mifepristone, his hypertension control improved without orthostatic hypotension or nausea. His hot flashes remained and he developed breast enlargement and tenderness. A repeat testosterone was found to be low, but the rest of his evaluation for gynecomastia was negative otherwise. His pre-treatment am testosterone was 281 ng/dL (normal 250–1100 ng/dL) and post mifepristone treatment am testosterone level was <7 ng/dL. He had suppressed gonadotrophins (LH <0.2 mIU/mL; normal 1.4–7.77 mIU/mL, FSH <0.2 mIU/mL; normal 2.5–17.1 mIU/mL), normal prolactin (PRL 11 ng/mL; normal 2.6–12 ng/mL) and a normal pituitary MRI. Conclusion: This is the first case demonstrating severe hypogonadotropic hypogonadism in a male using low dose mifepristone treatment for mild ACTH independent Cushing’s Syndrome. Reference: Escudero, E. and et al. Mifepristone Is an Effective Oral Alternative for the Prevention of Premature Luteinizing Hormone Surges and/or Premature Luteinization in Women Undergoing Controlled Ovarian Hyperstimulation for in Vitro Fertilization. J Clin Endocrinol Metab. 2005; 90(4):2081–2088.