[Clinical and molecular aspects of the ACTH-independent bilateral macronodular adrenal hyperplasia].
AIMAH is a clinical condition characterized by the presence of adrenal macronodules even in the absence of ACTH. Usually the clinical overt syndrome only becomes apparent after several decades of life; this is probably due to the low steroidogenic enzyme capacity of the hyperplastic tissue. However, in asymptomatic individuals in whom the AIMAH was incidentally discovered, the HHA axis is usually disrupted. In the great majority of AIMAH cases, cortisol secretion is aberrantly regulated by hormones such as GIP, AVP, beta-adrenergic agonists, LH/hCG and in some cases by serotonin, acting through their specific receptors. The molecular mechanisms responsible by ectopic expression of such hormone receptors and/or their aberrant coupling to steroidogenesis are still largely unknown. Although this aberrant expression may have an important role in the augmented cell proliferation initiation, as well as in the steroidogenesis, it is probable that additional genetic events involving cell cycle regulation, adhesion and transcription occur. In rare cases GNAS1 mutations not related to McCune-Albright syndrome may be found in this condition. In some patients, the presence of aberrant hormone receptors creates the possibility of specific pharmacological treatment, isolated or associated with unilateral adrenalectomy.
Antonini
Sonir R
SR
Departamento de Pediatria, Hospital das Clínicas, Faculdade de Medicina de Ribeirão Preto, USP. srrantonini@hotmail.com
Fragoso
Maria Cândida
MC
Lacroix
André
A
D000311:Adrenal Glands / Q000473:pathology* / Q000503:physiopathology; D000324:Adrenocorticotropic Hormone; D002864:Chromogranins; D003480:Cushing Syndrome / Q000188:drug therapy / Q000503:physiopathology; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics; D006801:Humans; D006965:Hyperplasia / Q000235:genetics / Q000503:physiopathology; D009154:Mutation; D015398:Signal Transduction; D014667:Vasopressins / Q000627:therapeutic use
D002864:Chromogranins; D014667:Vasopressins; D000324:Adrenocorticotropic Hormone; C406732:GNAS protein, human; D019205:GTP-Binding Protein alpha Subunits, Gs