SAT-460 Cushing Syndrome due to Primary Bilateral Macronodular Aԁrеnаl Hyperplasia (PBMAH) with Aberrant Adrenal Expression of Beta-adrenergic Receptors

Abstract Disclosure: A.N. Lim: None. D. Tran: None. C. Hurtado: None. Background: Primary bilateral macronodular adrenal hyperplasia (PBMAH) is a rare cause of Cushing syndrome, with select patients found to express aberrant аԁreոal beta-adrenergic receptors. We present a case partially responsive to beta-adrenergic receptor blockade therapy prior to unilateral adrenalectomy. Clinical case: A 45-year-old woman was referred to endocrine clinic for abnormally thickened bilateral adrenal glands on computed tomography angiography (CTA). She reported long-standing hypertension uncontrolled on multiple oral medications. She had signs of Cushing syndrome including dorsocervical and supraclavicular fat pads, purple abdominal striae, and weight gain. Initial tests revealed elevated 24 hr urinary free cortisol (189.8 mcg/24 hr, n<50 mcg/24 hr), abnormal cortisol after 1 mg dexamethasone overnight test (18.5 mcg/dL, n<2 mcg/dL), low ACTH concentration (7 pg/mL, n 6-50 pg/mL), and low DHEAS (14 mcg/dL, n 15-205 mcg/dL). Further studies revealed normal plasma aldosterone concentration (6 ng/dL, n<21), normal plasma renin activity (0.87 ng/mL/hr, n<5.82 ng/mL/hr), and normal plasma aldosterone to renin ratio (6.9, n<28.9). A multiphase adrenal CT scan revealed multiple nodules in the bilateral enlarged adrenal glands (left adrenal gland measured 5 x 4 cm, right adrenal gland measured 4 x 3 cm) and thus the patient was diagnosed with PBMAH. Genetic testing revealed classic ARMC5 (armadillo repeat-containing 5) positive germline mutation. Interestingly, after initiation of beta blockade with propranolol, the patient had improvement in her hypertension and 24 hr urinary free cortisol (from 189.8 mcg/24 hr to 65.0 mcg/24 hr, n<50 mcg/24 hr). Dynamic testing for aberrant receptors was not available in our institution, but because of this initial response, empiric treatment with beta blockade was optimized to maximum dose to evaluate for complete response. Given persistently suppressed ACTH (<5 pg/mL, n 6-50 pg/mL), suppressed DHEAS (11 mcg/dL, n 15-205 mcg/dL), persistent hypertension, and continued mildly elevated 24 hr urinary free cortisol (68.9 mcg/24 hr, n<50 mcg/24 hr) on maximum propranolol dose, left unilateral adrenalectomy (of the larger adrenal gland) was pursued. Post-operatively, the patient transiently required a steroid taper. Repeat labs off steroids and beta-blockers showed a normal 24 hr urinary free cortisol (5 mcg/24 hr, n<50 mcg/24 hr). Conclusion: This is a case demonstrating the efficacy of beta blockade in Cushing syndrome due to PBMAH with likely aberrant adrenal expression of beta-adrenergic receptors. The case highlights the possibility of empiric treatment with beta blockers if testing for aberrant receptors is not available. The case also demonstrates the utility of unilateral adrenalectomy in PBMAH with the goal of restoration of urinary free cortisol levels without necessitating lifelong glucocorticoid replacement. Presentation: Saturday, July 12, 2025