Aberrant cortisol regulations in bilateral macronodular adrenal hyperplasia: a frequent finding in a prospective study of 32 patients with overt or subclinical Cushing's syndrome

Context: ACTH-independent macronodular adrenal hyperplasia (AIMAH) is a rare and heterogeneous condition characterized by abnormal steroid production. Cortisol secretion can be regulated by aberrant hormone receptors. Objective: A large series of patients with AIMAH were evaluated to provide information on the prevalence and profile of aberrant regulations, in relation with the functional status. Design and patients: Thirty-two consecutive patients with AIMAH were prospectively studied: 10 had a Cushing's syndrome (CS), and 22 had a subclinical CS (SCS). Methods: A baseline endocrine evaluation was followed by an in vivo protocol in search of aberrant cortisol responses (seven provocative tests). An acute inhibition test with the somatostatin analog octreotide was also performed. Results: At least one aberrant cortisol response was identified in 28 of 32 (87%) patients. The overall prevalence of aberrant responses was independent of the functional status. Responses to the upright posture and to metoclopramide were frequently observed (67 and 56% respectively). A glucagon response was frequently observed in the SCS group (58%). A cortisol inhibition by octreotide was specifically found in the three CS patients who positively responded to the mixed meal, and was observed also in 12 of 13 (92%) patients with SCS. Conclusions: Cortisol responses indicative of aberrant receptor expression were highly prevalent in AIMAH. Thorough phenotyping of AIMAH may help uncover the underlying pathophysiology.