Portal de Periódicos da CAPES

Adrenal Pathophysiology: Lessons from the Carney Complex

2005; Karger Publishers; Volume: 64; Issue: 3 Linguagem: Inglês

10.1159/000088586

1663-2826

Lionel Groussin, Laure Cazabat, Fernande René-Corail, Eric Jullian, Jérôme Bertherat,

Vascular Tumors and Angiosarcomas

The Carney complex (CNC) is a dominantly inherited syndrome responsible mainly for spotty skin pigmentation (lentiginosis), endocrine overactivity, and cardiac myxomas. Adrenocorticotropic hormone independent Cushing’s syndrome due to primary pigmented nodular adrenocortical disease (PPNAD) is a main characteristic of CNC. PPNAD is a very rare cause of Cushing’s syndrome due to a primary bilateral adrenal defect that can be also observed in some patients without other CNC manifestations nor familial history. One of the putative CNC genes, located on 17q22-24, has been identified as the regulatory subunit R1A of protein kinase A <i>(PRKAR1A)</i>. Heterozygous inactivating mutations of <i>PRKAR1A</i> have been reported initially in about 45% of the CNC index cases and could be found in about 80% of the CNC families presenting mainly with Cushing’s syndrome. <i>PRKAR1A</i> is a key component of the cyclic AMP signaling pathway that has been implicated in endocrine tumorigenesis and could, at least partly, function as a tumor suppressor gene. Interestingly, patients with isolated PPNAD and no familial history of CNC can also present a germline de novo mutation of <i>PRKAR1A</i>. Somatic mutations of <i>PRKAR1A</i> have been found in PPNAD as a mechanism of inactivation of the wild-type allele, in a patient already presenting a germline mutation, and in a subset of sporadic secreting adrenocortical adenomas with clinical, hormonal, and pathological features quite similar to PPNAD. This review will summarize the recent findings on CNC from the perspective of the pathophysiology of adrenal Cushing’s syndrome and PPNAD.