Advances in the understanding of the pathophysiology of primary adrenocortical hyperplasia macronodular - PMAH (GP-PMAH)

Abstract

Cushing syndrome (CS) results from chronic excess of cortisol production and represents and archetype of metabolic syndrome (MS). The MS is a condition defined as a complex of interconnected cardiovascular risk factors such as (obesity, diabetes, blood hypertension and dyslipidemia). It is estimated that 2/3 of CS patients fulfill the criteria for MS. PMAH is a cause of CS, usually diagnosed in 5th or 6th decades. The duration of exposure of cortisol excess and affinity to its receptor are determinant of cardiovascular risk. The mortality is higher among patients who have not received effective treatment for hypercortisolism than the patients who are cured thus there is a clinical imperative for early diagnosis and treatment. Last year the group from Prof. Jérôme Bertherat (France) and the group from Prof. Maria CBV Fragoso (Brazil), using different molecular approaches identified the gene related to PMAH, the ARMC5 (armadillo repeat containing 5). Germline mutations of ARMC5 were identified around 55% if familial cases and in 21% of sporadic cases. The unique functional study of ARMC5 was conducted by the France group in cell culture of adrenal cancer (NCI). The authors observed the apoptotic effect of the wide type of ARMC5. Our group have stored a bank of hyperplastic adrenal tissue (in liquid nitrogen – 180C) and their cell cultures respectively from patients with PMAH. This is opportunity to develop a collaborative study to characterize the culture cells of PMAH and perform new functional studies in these cells with and without ARMC5 mutations. (AU)