Endocrine Abstracts

Primary bilateral macronodular adrenal hyperplasia (PBMAH) is a rare cause of Cushing’s syndrome (CS). It is a highly heterogeneous disease with multiple adrenal macronodules and variable levels of cortisol excess. The pathogenesis is complex and different mechanisms such as aberrant hormone receptors, local production of ACTH in adrenal tissues and genetic mutations have been identified. The approach is not well established. Nine patients with PBMAH who are currently followed in our department were identified. Six of them were females and the median age at diagnosis was 49.0 (range 33-64) years. All patients were investigated as a result of adrenal incidentalomas, with the exception of one patient that was studied for overt CS. At the time of diagnosis, two patients did not have clinical manifestations of CS. The most frequent signs were abdominal obesity (4/7), ecchymosis (3/7) and moon face (3/7). Median BMI was 28.2 (range 24.3–32.3) kg/m². All patients had hypertension, eight had dyslipidemia and seven had abnormal glycaemic metabolism (diabetes (3/7) and prediabetes (4/7)). Two cases had hypokalaemia (3.10 mEq/l). Median morning plasma cortisol after 1 mg dexamethasone overnight suppression test was 22.2 (range 1.60–27.60) µg/dl and median cortisol after low-dose dexamethasone suppression test (2 mg/day for 48 hours) was 14.4 (range 1.10-24.4) µg/dl. Median 24-h urinary free cortisol was 200.7 (range 59.4–520.1) µg/24 h [1.48 (range 0.34–3.80)-fold ULN]. Median late-night salivary cortisol was 0.73 (range 0.64–2.70) µg/dl [2.20 (range 2.00–8.13)-fold ULN]. Mean matinal ACTH level was 1.83±1.58 pg/ml and median DHEAS was 17.6 (range 3.8–90.0) μg/dl [ref. 35.4-256]. Primary aldosteronism had been diagnosed in one patient (aldosterone-to-renin ratio 7.26 ng/µg). Only one case had several nodules on one adrenal with an apparently normal contralateral gland. Median largest nodule size was 30.5 (range 20.0–39.0) mm. In two of four patients had found pathogenic mutations in the ARMC5 gene. Seven patients were screened for aberrant receptors: in three cases all tests were negative; in four patients had at least one test with a partial response (glucagon test was the most frequently positive). Seven patients underwent unilateral adrenalectomy. However, only two remain free of hypercortisolism (median follow-up 4.2 y). One patient underwent unilateral adrenalectomy recently. Two patients are under annual active surveillance and their comorbidities are controlled (median follow-up 7.5 y). PBMAH is a heterogeneous and challenging disease in terms of treatment. Unilateral adrenalectomy may be an option. However, patients are rarely free of hypercortisolism and require monitoring and management of comorbidities.