Samples from adrenalectomies of 51 patients were studied: patients with CS with (n = 13) and without (n = 32) PRKAR1A mutations and a comparison group with aldosterone-producing adenomas (APAs) (n = 6).
Cortisol-producing hyperplasia of the adrenal glands is caused by two distinct syndromes, both of which have been directly or indirectly associated with protein kinase A signaling: (i) primary pigmented nodular adrenocortical disease (PPNAD) (a micronodular form of bilateral adrenal hyperplasia), either isolated (rarely) or in the context of Carney complex, is caused (in most cases) by mutations of the PRKAR1A gene; and (ii) ACTH-independent macronodular adrenal hyperplasia (AIMAH), or massive macronodular adrenal disease (MMAD), has been associated with aberrant (ectopic) expression, and presumably regulation, of various G protein-coupled receptors.