Update on primary bilateral macronodular adrenal hyperplasia (PBMAH)

Area of Science:

• Endocrinology
• Genetics
• Oncology

Background:

• Primary bilateral macronodular adrenal hyperplasia (PBMAH) is a rare adrenal disorder characterized by bilateral adrenal macronodules (>1 cm).
• It can lead to variable levels of cortisol excess, presenting as overt or subclinical Cushing syndrome.
• Increasing incidental diagnoses via abdominal imaging highlight the need for better understanding and management.

Purpose of the Study:

• To investigate the genetic underpinnings of PBMAH, focusing on potential inherited predispositions.
• To clarify the role of specific gene mutations in the pathogenesis of this heterogeneous condition.
• To inform diagnostic and therapeutic strategies for patients with PBMAH.

Main Methods:

• Review of clinical, biochemical, and imaging data for PBMAH diagnosis.
• Genetic analysis to identify germline mutations in candidate genes, particularly ARMC5.
• Assessment of genotype-phenotype correlations.

Main Results:

• Germline heterozygous inactivating mutations in the ARMC5 gene were identified in approximately 25% of apparently sporadic PBMAH cases.
• These mutations suggest a genetic predisposition contributing to the development of bilateral adrenal hyperplasia.
• The findings underscore the importance of genetic assessment in PBMAH.

Conclusions:

• ARMC5 mutations are a significant genetic factor in a subset of PBMAH patients.
• Accurate diagnosis relies on rigorous biochemical and imaging assessments.
• Treatment is indicated for symptomatic patients, with evolving therapeutic options including unilateral adrenalectomy and medical management.