Mass spectrometry-based steroid profiling in primary bilateral macronodular adrenocortical hyperplasia

Area of Science:

• Endocrinology
• Biochemistry
• Genetics

Background:

• Primary bilateral macronodular adrenocortical hyperplasia (PBMAH) is a condition affecting the adrenal glands.
• Distinct plasma steroid profiles and their correlation to PBMAH have not been previously investigated.
• Genetic factors, such as ARMC5 variants, may influence PBMAH development.

Purpose of the Study:

• To biochemically characterize PBMAH using plasma steroid profiling.
• To investigate the correlation between distinct steroid profiles and PBMAH.
• To explore the role of ARMC5 variants in PBMAH steroid profiles.

Main Methods:

• Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used for steroid profiling of 16 plasma steroids.
• Analysis included 36 PBMAH subjects, 19 adrenal Cushing's syndrome (ACS) subjects, and controls.
• Germline ARMC5 sequencing was performed on all PBMAH cases.

Main Results:

• PBMAH showed altered levels of 11-deoxycortisol, corticosterone, 11-deoxycorticosterone, 18-hydroxycortisol, aldosterone, progesterone, DHEA, and DHEA-S compared to controls.
• Significant differences in steroid profiles were observed between PBMAH subjects with and without pathogenic ARMC5 variants.
• Logistic regression identified DHEA, 11-deoxycortisol, 18-oxocortisol, and corticosterone as key distinguishing steroids.
• Discriminant analysis achieved high classification accuracy (95.2%) for all groups and 91.7% for PBMAH subjects based on ARMC5 variants using nine steroids.

Conclusions:

• PBMAH patients possess distinctive plasma steroid profiles.
• These profiles may offer a supplementary single-test screening method for PBMAH.
• Plasma steroid profiling, combined with genetic analysis, aids in understanding PBMAH pathophysiology.