Work

Routine blood-based immune signatures in endogenous Cushing’s syndrome: associations with cortisol excess and selected complication burden

Year: 2026

Type: article

Abstract: Background Routine blood-based markers capture glucocorticoid-related immune-cell redistribution, but whether these measures are associated with complementary biochemical measures of cortisol excess and clinical complication burden in endogenous Cushing’s syndrome remains unclear. Methods We included 202 patients with endogenous Cushing’s syndrome. Seven routine blood-based immune markers were examined in relation to 24h urinary free cortisol (24h-UFC), midnight serum cortisol, and 8 a.m. serum cortisol. Selected immune markers were further evaluated in relation to clinical complications. An exploratory complication-domain burden score comprised four domains: electrolyte involvement, hypertension, diabetes, and fracture. An exploratory cortisol-related immune score (CRIS) combined neutrophil-to-lymphocyte ratio (NLR), eosinophil depletion, and low prognostic nutritional index (PNI). Results All seven immune markers were significantly associated with each of the three biochemical cortisol measures after adjustment for age, sex, and aetiology, with NLR and absolute eosinophil count (AEC) showing the strongest and most consistent associations. For 24h-UFC, the adjusted coefficients were 0.647 for log-NLR and −0.687 for log(AEC + 0.01) per 1 SD increase. In primary complication analyses, significant associations after false-discovery rate (FDR) correction were observed for hypokalaemia, hypophosphataemia, diabetes, and fracture; for example, log-NLR was associated with hypophosphataemia (OR 2.86, 95% CI 1.39–6.33), while low PNI was associated with fracture (OR 2.52, 95% CI 1.60–3.96). Each 1 SD increase in CRIS was associated with a higher complication-domain burden score (IRR 1.20, 95% CI 1.07–1.35; P = 0.001). Conclusion Routine blood-based immune markers were associated with complementary biochemical measures of cortisol excess and selected clinical complications in endogenous Cushing’s syndrome. Eosinophil depletion and increased NLR were consistently associated with all three cortisol measures, whereas associations with clinical complications varied by marker and outcome. CRIS provided an exploratory integrative summary of cortisol-related immune alterations and selected complication-domain burden but requires external validation.

Source: Frontiers in Endocrinology

DOI: 10.3389/fendo.2026.1961986

Authors: Yunjia Cai, Shuwen Tan, Siyuan Liu, Miao Wang, Tiemin Liu, Guixia Wang

Institutions: Fudan University, First Hospital of Jilin University, State Key Laboratory of Genetic Engineering, People 's Hospital of Jilin Province

Language: English

Topic: Pituitary Gland Disorders and Treatments

Subfield: Endocrinology, Diabetes and Metabolism

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,801