The frequency of ARMC5 Mutation in incidental nodules in the adrenal gland associated with subclinical hypercortisolism

• Grant number: 15/06146-2
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: July 01, 2016
• End date: December 31, 2018
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Maria Candida Barisson Villares Fragoso
• Grantee: Beatriz Marinho de Paula Mariani
• Host Institution: Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated research grant: 15/50192-9 - Advances in the understanding of the pathophysiology of primary adrenocortical hyperplasia macronodular - PMAH (GP-PMAH), AP.TEM

Abstract

Primary macronodular adrenal hyperplasia is a rare cause of Cushing's syndrome and is more often diagnosed as bilateral adrenal incidentalomas with subclinical cortisol production. Current findings indicate that bilateral macronodular adrenal hyperplasia is more frequent and genetically determined than previously believed. Considering the role of paracrine adrenocorticotropic hormone production on cortisol secretion, the previous nomenclature of adrenocorticotropic hormone-independent macronodular adrenal hyperplasia (AIMAH) appears inappropriate, and the presence of development of adrenal assynchronic nodules, this disease should now be named primary macronodular adrenal hyperplasia (PMAH).Over the last two decades, different studies supported multiple molecular mechanisms may be involved in the pathogenesis of PMAH, suggesting that it may be a heterogeneous group of diseases with a common presentation. Recently, the molecular genetic investigations of PMAH provided new insights for future research on adrenal disorders. The identification of a genetic basis for PMAH permits an earlier diagnosis and to improve the management of this disease. In addition, the fact of PMAH developed in assynchronic patern around 38% of the cases, an investigation of the frequency in a cohort of incidental unilateral adrenal nodule is necessary. This project proposes a functional investigation of the ARMC5 gene in cells culture of PMAH and an international collaborative task force with the ENSAT group (European Network Study of Adrenal Tumors) coordinated by Professor Massimo Terzolo, to study a germline and somatic mutatiosns of ARMC5 gene on a substantially large number of patients with unilateral adrenal nodule.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

MARIANI, BEATRIZ MARINHO DE PAULA; NISHI, MIRIAN YUMIE; WANICHI, INGRID QUEVEDO; BRONDANI, VANIA BALDERRAMA; LACOMBE, AMANDA MENESES FERREIRA; CHARCHAR, HELAINE; PEREIRA, MARIA ADELAIDE ALBERGARIA; SROUGI, VICTOR; TANNO, FABIO YOSHIAKI; CECCATO, FILIPPO; et al. Allelic Variants of ARMC5 in Patients With Adrenal Incidentalomas and in Patients With Cushing's Syndrome Associated With Bilateral Adrenal Nodules. FRONTIERS IN ENDOCRINOLOGY, v. 11, FEB 7 2020. (15/06146-2, 15/50192-9)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

MARIANI, Beatriz Marinho de Paula. Analysis of the allelic variants of the armadillo repeat containing 5 (ARMC5) gene in patients with adrenal incidentalomas. 2019. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD) São Paulo.