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Endocrine Abstracts (2018) 56 S17.2 | DOI: 10.1530/endoabs.56.S17.2

ECE2018 Symposia Recent advances in Primary Adrenal Macronodular Hyperplasia (3 abstracts)

Genetics of Primary Bilateral Macronodular Adrenal Hyperplasia: when and what to test

Rossella Libé


France.


Primary Bilateral Macronodular Adrenal Hyperplasia (PBMAH) consists of bilateral development of adrenocortical macronodules causing various level of cortisol excess independently of circulating ACTH. It can be diagnosed after investigations of clinical signs of Cushing’s syndrome, but nowadays more often after the investigation of an adrenal incidentaloma in patients with sub-clinical Cushing. Indeed, 10 to 15% of adrenal incidentalomas are bilateral, corresponding mostly to PBMAH. Several observations suggest a genetic origin of PBMAH: case reports of familial forms, the bilateral and multifocal nature of the adrenal nodules. Genes involved in the cAMP/protein kinase A (PKA) signaling pathway, (GNAS) or as modifying gene (PDE11A4) have been reported as causing the disease. In rare cases PBMAH is observed in patients with hereditary familial tumor syndromes including adenomatous polyposis coli gene (APC), MEN1 (Menin) and Hereditary Leiomyomatosis and Renal Cell Cancer (fumarate hydratase). However, most PBMAH patients do not present with such syndromic associations. In these more common patients the use of combined pan-genomic approaches led to the identification of a new tumor suppressor gene, ARMC5, as a frequent cause of sporadic or familial PBMAH (25–50% in the different series). This demonstrates that PBMAH is often genetically determined and brought some new perspectives for early diagnosis of the disease. Genetic screening for ARMC5 germline mutation could help better diagnosis and classification of patients with PBMAH. Familial screening would lead to the identification of the relatives of an index case with ARMC5 mutation at risk of Cushing’s syndrome development. Prospective follow-up will allow a better analysis of the development of PBMAH in such families. In conclusion, the genetic origin of PBMAH is now demonstrated in a significant proportion of the cases, offering new perspectives for pathophysiology, therapy and genetic screening.

Volume 56

20th European Congress of Endocrinology

Barcelona, Spain
19 May 2018 - 22 May 2018

European Society of Endocrinology 

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