A multicenter experience on the prevalence of ARMC5 mutations in patients with primary bilateral macronodular adrenal hyperplasia: from genetic characterization to clinical phenotype

N. M. Albiger, D. Regazzo, B. Rubin, A. M. Ferrara, S. Rizzati, E. Taschin, F. Ceccato, G. Arnaldi, F. Pecori Giraldi, A. Stigliano, L. Cerquetti, F. Grimaldi, E. de Menis, M. Boscaro, M. Iacobone, G. Occhi, C. Scaroni

Research output: Contribution to journalArticlepeer-review

Abstract

ARMC5 mutations have recently been identified as a common genetic cause of primary bilateral macronodular adrenal hyperplasia (PBMAH). We aimed to assess the prevalence of ARMC5 germline mutations and correlate genotype with phenotype in a large cohort of PBMAH patients. A multicenter study was performed, collecting patients from different endocrinology units in Italy. Seventy-one PBMAH patients were screened for small mutations and large rearrangements in the ARMC5 gene: 53 were cortisol-secreting (two with a family history of adrenal hyperplasia) and 18 were non-secreting cases of PBMAH. Non-mutated and mutated patients’ clinical phenotypes were compared and related to the type of mutation. A likely causative germline ARMC5 mutation was only identified in cortisol-secreting PBMAH patients (one with a family history of adrenal hyperplasia and ten apparently sporadic cases). Screening in eight first-degree relatives of three index cases revealed four carriers of an ARMC5 mutation. Evidence of a second hit at somatic level was identified in five nodules. Mutated patients had higher cortisol levels (p = 0.062), and more severe hypertension and diabetes (p <0.05). Adrenal glands were significantly larger, with a multinodular phenotype, in the mutant group (p <0.01). No correlation emerged between type of mutation and clinical parameters. ARMC5 mutations are frequent in cortisol-secreting PBMAH and seem to be associated with a particular pattern of the adrenal masses. Their identification may have implications for the clinical care of PBMAH cases and their relatives.

Original languageEnglish
Pages (from-to)1-10
Number of pages10
JournalEndocrine
DOIs
Publication statusAccepted/In press - Apr 19 2016

Keywords

  • ARMC5
  • Cushing’s syndrome
  • Genotype to phenotype correlation
  • Primary bilateral macronodular adrenal hyperplasia

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

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