ADRENAL CORTEX AND MEDULLA: Edited by Irina BancosApproach to patients with bilateral adrenal incidentalomasVassiliadi, Dimitra A.; Partsalaki, Eirini; Tsagarakis, StylianosAuthor Information Department of Endocrinology, Diabetes, and Metabolism, National Expertise Center for Rare Endocrine Disorders, Evangelismos Hospital, Athens, Greece Correspondence to Dimitra A. Vassiliadi, MD, PhD, Department of Endocrinology, Diabetes, and Metabolism, National Expertise Center for Rare Endocrine Disorders, Evangelismos Hospital, 45–47 Ipsilantou St, 106 76 Athens, Greece. Tel: +30 210 7201825; fax: +30 213 2041828; e-mail: email@example.com Current Opinion in Endocrinology & Diabetes and Obesity: June 2020 - Volume 27 - Issue 3 - p 125-131 doi: 10.1097/MED.0000000000000536 Buy Metrics Abstract Purpose of review The current review provides a summary on the most recent developments regarding the cause, work-up and management of bilateral adrenal incidentalomas (BAI). Recent findings The recent ENS@T/ESE guidelines provide comprehensive directions on the evaluation and management of patients with adrenal incidentalomas with special focus on those with bilateral tumours. Intraadrenal ACTH synthesis that may locally stimulate cortisol secretion challenging the traditionally used term ‘ACTH-independent’. Inactivating mutations of a new tumour suppressor gene, armadillo repeat containing 5 (ARMC5), are implicated in a number of patients, especially those with multiple macronodules (bilateral macronodular hyperplasia) and evidence of hypercortisolism. Loss-of-function mutations of the glucocorticoid receptor gene (NR3C1) consist a new possible genetic cause of BAIs. Regarding management an increasing number of studies provide data on the benefits and safety of unilateral rather than bilateral adrenalectomy. There is also emerging data on the beneficial use of steroidogenesis inhibitors in a dosing schedule that aims to mimic the normal cortisol rhythm with promising short-term results, but the long-term clinical benefits of this approach remain to be demonstrated. Summary The diagnostic approach consists of imaging and hormonal evaluation. Imaging characterization should be done separately for each lesion. Hormonal evaluation includes testing for primary aldosteronism, pheochromocytoma and evaluation for autonomous cortisol secretion, using the 1-mg overnight dexamethasone suppression test. Midnight cortisol or 24-h urinary-free cortisol may aid in establishing the degree of cortisol excess. In patients with hypercortisolism ACTH levels should be measured to establish ACTH-independency. The appropriate management of BAI associated with cortisol excess remains controversial. Bilateral adrenalectomy results in lifetime steroid dependency and is better reserved only for patients with overt and severe hypercortisolism. Unilateral adrenalectomy might be considered in selected patients. Medical therapy is not an established approach yet but it may be considered when control of hypercortisolism is desired, but surgery is not an option. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.