Postoperative serum cortisol and Cushing disease recurrence in patients with corticotroph adenomas
Abstract
CONTEXT: In Cushing disease, the association between the rate of serum cortisol decline and recurrent disease after corticotroph adenoma removal has not been adequately characterized. OBJECTIVE: To analyze postoperative serum cortisol and recurrence rates in Cushing disease. METHODS: Patients with Cushing disease and pathology-confirmed corticotroph adenoma were retrospectively studied. Cortisol halving time was estimated using exponential decay modeling. Halving time, first postoperative cortisol, and nadir cortisol values were collected using immediate postoperative inpatient laboratory data. Recurrence and time-to-recurrence were estimated and compared among cortisol variables. RESULTS: A total of 320 patients met inclusion/exclusion criteria for final analysis, and 26 of those patients developed recurrent disease. Median follow-up time was 25 months (95% CI, 19-28 months), and 62 patients had ≥ 5 years follow-up time. Higher first postoperative cortisol and higher nadir were associated with increased risk of recurrence. Patients who had a first postoperative cortisol ≥ 50 µg/dL were 4.1 times more likely to recur than those with a first postoperative cortisol < 50 µg/dL (HR 4.1, 1.8-9.2; P = .0003). Halving time was not associated with recurrence (HR 1.7, 0.8-3.8, P = .18). Patients with a nadir cortisol ≥2 µg/dL were 6.6 times more likely to recur than those with a nadir cortisol of < 2 µg/dL (HR 6.6, 2.6-16.6, P < .0001). CONCLUSION: Postoperative nadir serum cortisol is the most important cortisol variable associated with recurrence and time-to-recurrence. Compared to first postoperative cortisol and cortisol halving time, a nadir < 2 µg/dL showed the strongest association with long-term remission and typically occurs within the first 24 to 48 hours after surgery.
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A lower postoperative serum cortisol nadir (<2 μg/dL) is associated with long-term remission and delayed recurrence.
“More recent evidence has identified that a lower postoperative serum cortisol nadir (<2 µg/dL) is associated with long-term remission and delayed recurrence (125, 126).”
From Measuring cortisol in Cushing syndrome: diagnosis, monitoring, and cortisol circadian rhythm improvement. (2026) · cites this paper as [125]
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- Authors
- Catalino, M. P., Moore, D. T., Ironside, N., Munoz, A. R., Coley, J., Jonas, R., Kearns, K., Min, L., Vance, M. L., Jane, J. A., & Laws, E. R.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- University of Virginia (US)
- Harvard University (US)
- University of Virginia Health System (US)
- Brigham and Women's Hospital (US)
- Corresponding author
- Catalino, Michael P
- ORCID
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2023-06-08
- Volume
- 108
- Issue
- 12
- Pages
- 3287-3294
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W4379928255
- Cited by
- 11
- References
- 42
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 2 · 2023: 1
- FWCI
- 2.25
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pituitary Gland Disorders and Treatments
- Health Sciences › Medicine › Surgery › Adrenal and Paraganglionic Tumors
- Health Sciences › Medicine › Epidemiology › Neuroendocrine Tumor Research Advances
- Keywords
- Cushing's disease, corticotroph adenoma, recurrence, adrenalectomy, remission prediction, hypercortisolism
- MeSH terms
- Adenoma, Humans, Hydrocortisone, Neoplasm Recurrence, Local, Recurrence, Retrospective Studies, Pituitary ACTH Hypersecretion, ACTH-Secreting Pituitary Adenoma
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