Mass Spectrometry-Based Adrenal and Peripheral Venous Steroid Profiling for Subtyping Primary Aldosteronism

Area of Science:

• Endocrinology
• Clinical Chemistry
• Mass Spectrometry

Background:

• Distinguishing aldosterone-producing adenomas (APAs) from bilateral adrenal hyperplasia (BAH) is crucial for primary aldosteronism treatment.
• Current diagnostic methods rely on adrenal venous sampling (AVS) with immunoassay-based aldosterone and cortisol measurements.
• There is a need for improved methods to accurately stratify patients with primary aldosteronism.

Purpose of the Study:

• To evaluate the utility of liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based steroid profiling for stratifying primary aldosteronism subtypes.
• To compare LC-MS/MS steroid measurements with traditional immunoassay methods in AVS.
• To explore the potential of peripheral plasma steroid concentrations for classifying APA versus BAH.

Main Methods:

• LC-MS/MS was used to measure 15 adrenal steroids in peripheral and adrenal venous plasma from 216 primary aldosteronism patients undergoing AVS.
• Patients were classified as BAH (n=90) or APA (n=126) based on immunoassay-derived aldosterone lateralization ratios.
• Steroid lateralization ratios and peripheral plasma concentrations were analyzed and compared between groups.

Main Results:

• LC-MS/MS demonstrated higher aldosterone lateralization ratios in APAs compared to immunoassay.
• Hybrid steroids (18-oxocortisol, 18-hydroxycortisol) showed lateralized secretion in a significant proportion of APA patients.
• Peripheral plasma steroid profiling, including 18-oxocortisol, cortisol, corticosterone, and dehydroepiandrosterone, correctly classified 80% of APA vs. BAH cases.

Conclusions:

• LC-MS/MS-based steroid profiling during AVS provides more accurate aldosterone lateralization ratios for APA diagnosis than immunoassay.
• LC-MS/MS enables multiple steroid measures to differentiate unilateral from bilateral aldosterone excess.
• Peripheral plasma steroid profiling using LC-MS/MS shows promise for non-invasive subtype classification of primary aldosteronism.