Sistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSPFRAGOSO, Maria Candida Barisson VillaresCAVALCANTE, Isadora PontesFERREIRA, Amanda MenesesMARIANI, Beatriz Marinho de PaulaLOTFI, Claudimara Ferini Pacicco2018-11-212018-11-212018PRESSE MEDICALE, v.47, n.43319, Special Issue, p.E139-E149, 20180755-4982https://observatorio.fm.usp.br/handle/OPI/29672Recent advances in molecular genetics investigations of primary macronodular adrenal hyperplasia (PMAH) have been providing new insights for the research on this issue. The cAMP-dependent pathway is physiologically triggered by ACTH and its receptor, MC2-R, in adrenocortical cells. Different mechanisms of this cascade may be altered in some functioning adrenal cortical disorders. Activating somatic mutations of the GNAS gene (known as gsp oncogene) which encodes the stimulatory G protein alpha-subunit (Gs alpha) have been found in a small number of adrenocortical secreting adenomas and rarely in PMAH. Lately, ARMC5 was linked to the cyclic AMP signaling pathway, which could be implicated in all of mechanisms of cortisol-secreting by macronodules adrenal hyperplasia and the molecular defects in: G protein aberrant receptors; MC2R; GNAS; PRKAR1A; PDE11A; PDE8B. Around 50 % of patient's relatives with PMAH and 30 % of apparently sporadic hypercortisolism carried ARMC5 mutations. Therefore, PMAH is genetically determined more frequently than previously believed. This review summarizes the most important molecular mechanisms involved in PMAH.engrestrictedAccessmultiple endocrine neoplasiafamilial adenomatous polyposisrenal-cell cancermalignant adrenocortical tumorsgastric-inhibitory polypeptidehydratase germline mutationcushings-syndromearmc5 mutationshereditary leiomyomatosisarmadillo-repeatarticleCopyright MASSON EDITEUR10.1016/j.lpm.2018.07.002Medicine, General & Internal2213-0276