Steroid profiling and circadian cortisol secretion in patients with mild autonomous cortisol secretion: a cross-sectional study
Open accessAbstract
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.
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The use of multiple samples from blood, saliva, or subcutaneous tissue can construct a dynamic cortisol profile that offers more detailed insight into the circadian rhythm of cortisol secretion.
“The use of multiple samples—from blood, saliva, or subcutaneous tissue—can construct a dynamic cortisol profile that offers more detailed insight into the circadian rhythm of cortisol secretion (30, 88, 94).”
From Measuring cortisol in Cushing syndrome: diagnosis, monitoring, and cortisol circadian rhythm improvement. (2026) · cites this paper as [94]
Patients with mild CS or MACS may present with normal total 24-hour urinary cortisol production but have a disrupted cortisol circadian rhythm, often characterized by excess cortisol secretion during bedtime hours, as detected by an uncontrolled LNSC measurement.
“Patients with mild CS or MACS may present with normal total 24-hour urinary cortisol production but have a disrupted cortisol circadian rhythm, often characterized by excess cortisol secretion during bedtime hours, as detected by an uncontrolled LNSC measurement (94).”
From Measuring cortisol in Cushing syndrome: diagnosis, monitoring, and cortisol circadian rhythm improvement. (2026) · cites this paper as [94]
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- Authors
- Saini, J., Singh, S., Ebbehoj, A., Zhang, C. D., Nathani, R., Fell, V., Atkinson, E., Achenbach, S., Rivard, A., Singh, R., Grebe, S., & Bancos, I.
- Affiliations
- Mayo Clinic (US)
- Department of Clinical Medicine, Aarhus University , Aarhus 8200 ,
- Corresponding author
- Bancos, Irina
- ORCID
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2024-07-09
- Volume
- 110
- Issue
- 2
- Pages
- 542-553
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- PMC
- PMC11747667
- OpenAlex
- W4400448335
- Cited by
- 20
- References
- 34
- Citations by year
- 2026: 13 · 2025: 6 · 2024: 1
- FWCI
- 6.59
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases
- National Institute of Aging
- National Institutes of Health (K23DK121888, R03DK132121, R03AG71934)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Health Sciences › Medicine › Surgery › Adrenal and Paraganglionic Tumors
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal Regulation and Hypertension
- Keywords
- mild autonomous cortisol secretion, Cushing's syndrome, free cortisol, 24-hour urine collection, dexamethasone suppression test
- MeSH terms
- Adult, Aged, Androgens, Circadian Rhythm, Cross-Sectional Studies, Female, Glucocorticoids, Humans, Hydrocortisone, Male, Middle Aged, Steroids, Case-Control Studies, Metabolome
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