Nodule density on CT-scan correlates with CYP11B1 expression in a patient with ARMC5 mutated primary bilateral macronodular adrenal hyperplasia.

Abstract

Purpose: Primary bilateral macronodular adrenal hyperplasia (PBMAH) is a rare subtype of Cushing's syndrome, with some cases exhibiting a familial aggregation tendency. The heterogenous expression of CYP11B1 mRNA among multiple adrenal nodules in PBMAH had not been previously reported. This study aims to investigate the correlation between CYP11B1 mRNA expression and Hounsfield unit (Hu) density in computed tomography (CT) scans in a patient with ARMC5 mutated PBMAH.

Methods: A 47-year-old male came to our hospital for headache and hypertension. He was diagnosed as PBMAH later and received adrenalectomy. DNA sequencing was performed on the patient's peripheral blood, his relatives' peripheral blood, and the patient's adrenal tissues. Additionally, four different adrenal nodules from the patient were collected to explore the relationship between CYP11B1 mRNA expression and Hu density in CT scanning.

Results: A family with autosomal dominant inherited PBMAH was identified. Second generation sequencing of peripheral blood and Sanger sequencing of adrenal tissues identified a novel ARMC5 pathogenic variant, c.1865-2_1865-1del, which was also present in the patient's brother, sister and nephew. The patient's adrenal was enlarged diffusely but cushingoid feature was not severe. The adrenal imaging showed bilateral macronodules resembling adrenal tumors. Notably, the Hu values varied significantly among different nodules, and interestingly, the CYP11B1 mRNA expression was found to be parallel to the Hu values.

Conclusions: We reported a family of PBMAH with novel ARMC5 pathogenic variant. The index patient exhibited heterogeneous adrenal nodules with distinct Hu values and CYP11B1 mRNA levels.