ADRENOCORTICOTROPIC HORMONE-INDEPENDENT ADRENAL-HYPERPLASIA

Cushing's syndrome with bilateral adrenal hyperplasia usually is cause d by chronic adrenocorticotropic hormone (ACTH) stimulation of the adr enal cortex. Until recently, the existence of ACTH-independent bilater al adrenal hyperplasia has not been firmly established. Evidence that such disorders do exist has accumulated, and in some instances, the me chanism is understood. Bilateral adrenalectomy is most often the appro priate therapy. Activation of the adrenocortical adenylate cyclase sys tem by ACTH-independent mechanisms will cause ACTH-independent Cushing 's syndrome with bilateral adrenal hyperplasia. Increased cAMP activat es downstream signaling and subsequently cell division and cortisol pr oduction. In food-dependent Cushing's syndrome there is functional evi dence for ectopic gastric-inhibitory peptide receptor expression in th e adrenal cortex. Food ingestion stimulates gastric-inhibitory peptide release and activates the adrenal adenylate cyclase system. ACTH-inde pendent Cushing's syndrome with bilateral hyperplasia may be the initi al presentation of the McCune-Albright syndrome. A R201C or R201H subs titution in the alpha subunit of G(s) constitutively activates adenyla te cyclase. In other variants of ACTH-independent adrenal hyperplasia, the mechanisms are less defined. Primary pigmented nodular adrenocort ical disease may occur sporadically or in a familial form, and activat ing adrenal antibodies have been postulated in its etiology. ACTH-inde pendent bilateral macronodular adrenal hyperplasia is characterized by marked adrenal gland enlargement with multiple large nodules. Its eti ology is unknown.