Fax +41 61 306 12 34 E-Mail karger@karger.ch www.karger.com Mini Review Horm Res 2005;64:119–131 DOI: 10.1159/000088818 Clinical and Subclinical ACTH-Independent Macronodular Adrenal Hyperplasia and Aberrant Hormone Receptors Stavroula Christopoulos Isabelle Bourdeau André Lacroix Division of Endocrinology, Department of Medicine, Centre Hospitalier de l’Université de Montréal, Montréal, Canada AIMAH. When systematically screened, most patients with AIMAH and CS or subclinical CS exhibit an in vivo aberrant cortisol response to one or various ligands sug- gesting the presence of aberrant adrenal receptors. A protocol designed to screen patients for the presence of these aberrant receptors should be undertaken in all pa- tients with AIMAH. The identification of these receptors provides the potential for novel pharmacological thera- pies by suppressing the endogenous ligands or blocking the receptor with specific antagonists. Copyright © 2005 S. Karger AG, Basel Introduction Endogenous Cushing’s syndrome (CS) is due to pri- mary adrenal hypersecretion in approximately 15–20% of cases [1]. Unilateral adrenal pathology, in the form of adrenocortical adenomas or carcinomas, represents the large majority of adrenal CS. Bilateral adrenal pathology causing CS represents only 10–15% of all cases and in- cludes: (1) primary pigmented nodular adrenocortical disease (PPNAD) commonly associated with Carney complex; (2) ACTH-independent macronodular adrenal hyperplasia (AIMAH) [1], and rarely (3) bilateral adeno- mas or carcinomas. AIMAH is thus a very rare cause of CS representing less than 1% of its endogenous etiologies. In 1994, Lieberman et al. [2] reviewed 24 published cas- es. Since then, a much greater number of cases have been reported and the characteristics of this distinct entity Key Words Adrenocortical hyperplasia  ACTH-independent macronodular adrenal hyperplasia  Cushing’s syndrome, subclinical  Aberrant receptors Abstract ACTH-independent macronodular adrenal hyperplasia (AIMAH) is a very rare cause of endogenous Cushing’s syndrome (CS). In this review, the clinical characteristics, the pathophysiology, and the management of AIMAH are described. AIMAH typically presents with overt CS, but subclinical oversecretion of cortisol has been in- creasingly described. The diagnosis is suspected by adrenal nodular enlargement on conventional imaging following the demonstration of ACTH-independent hy- percortisolism. Final diagnosis is established by histo- logical examination of the adrenal tissue. Bilateral adre- nalectomy is the treatment of choice but unilateral adrenalectomy has been proposed in selected cases. In patients with subclinical CS, the decision to treat should be individualized. The pathophysiology of this condition has begun to be elucidated in recent years. Diverse aber- rant membrane-bound receptors expressed in a non- mutated form in the adrenal gland have been found to be implicated in the regulation of steroidogenesis in Published online: October 6, 2005 HORMONE RESEARCH André Lacroix, MD Division of Endocrinology, Hôtel-Dieu du CHUM 3840 Saint-Urbain Street, Montréal, Qué. H2W 1T8 (Canada) Tel. +1 514 890 8000 (ext 14930), Fax +1 514 412 7218 E-Mail andre.lacroix@umontreal.ca © 2005 S. Karger AG, Basel 0301–0163/05/0643–0119$22.00/0 Accessible online at: www.karger.com/hre This work was supported by a grant from the Canadian Institutes of Health Research (MA-10339).