FRI266 Medical Management Of Cushing’s Syndrome Caused By Primary Bilateral Macronodular Adrenal Hyperplasia (PBMA) With Low Dose Of Ketoconazole
Authors: Hatfield Jennifer S , Godar Cassandra M , Vietor Nicole O , Hoang Thanh D , Shakir Mohamed K M 
Published: October 2023

Disclosure: J.S. Hatfield: None. C.M. Godar: None. N.O. Vietor: None. T.D. Hoang: None. M.K. Shakir: None.

Introduction: Primary bilateral macronodular adrenal hyperplasia (PBMA) is an uncommon cause of endogenous Cushing's syndrome, defined as both adrenal glands with multiple nodules &gt; 10mm in diameter. It often presents as incidentally found, bilateral, macronodular adrenal glands in patients between 40-60 years of age, frequently with only mild cortisol elevation. Although surgical treatment is recommended in these patients, we report the effectiveness of low-dose ketoconazole to control excessive cortisol secretion. Clinical Case: A 62 y/o woman with type 2 diabetes mellitus and hypertension was found to have bilateral adrenal nodules in 2010 while undergoing evaluation for abdominal pain. An adrenal CT scan confirmed bilateral adrenal nodules (largest left adrenal nodule 3.2cm x 2.9cm and right adrenal nodule 1.0cm x 1.0 cm). She was first referred for endocrine biochemical evaluation nearly 9 years later. Cortisol after 1mg dexamethasone suppression test was 17.3 mcg/dL, with corresponding ACTH of 3.1 pg/mL and dexamethasone of 310 ng/d, 24H urine cortisol 61 mcg/24 hr (6-42), 11 pm salivary cortisol 0.141, 0.133, 0.142 mcg/dL, and DHEA-S 11.4 mcg/dL (18.9-205.0). Biochemical evaluation for pheochromocytoma and primary hyperaldosteronism were negative. Serum 17-Hydroxyprogesterone 27 ng/dL was normal. Clinically, beyond her hypertension and diabetes she has no stigmata of hypercortisolism. Her type 2 diabetes with HbA1c of 7.8 is controlled with sitagliptin, insulin glargine and correctional lispro, and hypertension is treated with lisinopril. Due to the patient’s hesitancy for surgery, she was initiated on fluconazole which initially normalized urine cortisol levels (24H cortisol 20 mcg/24hr), though a rise to 70 mcg/24hr was noted after 6 months of treatment. She was transitioned to ketoconazole 200mg BID with resultant lowering of cortisol. Treatment was complicated by severe body aches that impaired ambulation, and symptoms resolved after decrease of ketoconazole to 100mg daily and rosuvastatin from 10mg to 5mg daily. Urine cortisol has remained in the normal range (15-22 mcg/24hr) for the last 2.5 years with no further side effects from ketoconazole. Discussion: Our patient’s clinical features suggest a diagnosis of PBMA. Most patients with PBMA have only mild elevation of cortisol levels and present with bilateral adrenal incidentalomas as seen in our patient. The classical features of Cushing's syndrome may be absent, and the nodular adrenals are frequently identified when abdominal imaging is performed for unrelated reasons. The amount of cortisol secretion is often sufficient to produce mild or overt Cushing’s syndrome. Although surgical treatment was considered, our patient was successfully treated with low-dose ketoconazole and thus, this may be an option in patients with mild PBMA-related Cushing’s syndrome.

Presentation: Friday, June 16, 2023