Language

English

Publication Date

1-21-2025

Journal

The Journal of Clinical Endocrinology & Metabolism

DOI

10.1210/clinem/dgae468

PMID

38981002

PMCID

PMC11747667

PubMedCentral® Posted Date

7-9-2024

PubMedCentral® Full Text Version

Post-print

Abstract

Context: Mild autonomous cortisol secretion (MACS) is diagnosed based on postdexamethasone cortisol >1.8 µg/dL. Scarce evidence exists on steroid circadian secretion and steroid metabolome in MACS.

Objective: To characterize 24-hour (h) urine steroid metabolome in patients with MACS and determine circadian differences in urine steroid profiling and cortisol concentrations in patients with MACS vs referent subjects.

Methods: Cross-sectional study, 2018-2023, at a referral center. Patients with MACS and age-, sex-, body mass index-, and menopausal status-matched referent subjects were included. Urine was collected over a 24 hour period as separate daytime and nighttime collections. High-resolution mass spectrometry assay was used to measure 25 steroids. A subgroup of patients and referent subjects was admitted for serum measurements of free and total cortisol every 2 hours. Outcomes were steroids, steroid sums, and ratios.

Results: Patients with MACS (n = 72) had lower µg/24 hour median androgens (2084 vs 3283, P < .001), higher glucocorticoids (15 754 vs 12936, P < .001), and higher glucocorticoid/androgen ratio (8.7 vs 3.9, P < .001) than referent subjects. Patients also had lower steroid day/night ratios than referent subjects, reflecting a higher relative nocturnal steroid production in MACS. In a subgroup of 12 patients with MACS and 10 referent subjects, the 24-hour areas under the curve for total and free serum cortisol were similar. However, evening mean total (5.3 vs 4.0 µg/dL, P = .056) and free (0.2 vs 0.1 µg/dL, P = .035) cortisol was higher in patients vs referent subjects.

Conclusion: Patients with MACS demonstrate an abnormal urine steroid metabolome, with a high glucocorticoid to androgen ratio, and a higher nocturnal steroid production.

Keywords

Humans, Cross-Sectional Studies, Hydrocortisone, Female, Male, Middle Aged, Circadian Rhythm, Adult, Steroids, Aged, Glucocorticoids, Case-Control Studies, adrenal adenoma, adrenal mass, diagnosis, circadian, steroid signature, cortisol, hypercortisolism

Published Open-Access

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