Heterogeneous circulating miRNA profiles of PBMAH

Area of Science:

• Endocrinology
• Molecular Biology
• Genomics

Background:

• Primary bilateral macronodular adrenal hyperplasia (PBMAH) is a rare cause of Cushing syndrome, often presenting as bilateral adrenal incidentalomas with subclinical cortisol production.
• Circulating microRNAs (miRNAs) are known biomarkers for adrenocortical adenomas, but their expression in PBMAH remains uninvestigated.

Purpose of the Study:

• To investigate and characterize the circulating miRNA expression profiles in patients with PBMAH.
• To compare these profiles with those found in patients with non-functioning adrenocortical adenoma (NFA) and cortisol-producing adrenocortical adenoma (CPA).

Main Methods:

• Plasma samples were collected from patients diagnosed with NFA (4), CPA (5), and PBMAH (5).
• Comprehensive miRNA profiling was performed on these samples.
• Quantitative reverse transcription-polymerase chain reaction (RT-PCR) was employed to validate the expression of selected miRNAs.

Main Results:

• Hierarchical clustering revealed distinct miRNA expression signatures for PBMAH, separate from NFA and CPA samples.
• A total of 135 differentially expressed miRNAs distinguished PBMAH from other adenoma types.
• Specific miRNAs (hsa-miR-1180-3p, hsa-miR-4732-5p, hsa-let-7b-5p) showed significant differential expression between PBMAH and adenomas (P ≤ 0.019).
• PBMAH samples could be classified into two subtypes based on miRNA profiles, with subtype 2 exhibiting distinct expression patterns compared to adenomas.

Conclusions:

• A specific circulating miRNA signature has been identified for PBMAH.
• The observed subtype-based miRNA profiles suggest underlying pathophysiological heterogeneity within PBMAH.