Age and hematologic parameters can predict prolonged glucocorticoid replacement after remission of cushing disease and adrenal Cushing's syndrome: A nationwide cohort study.

PURPOSE: Duration of glucocorticoid (GC) replacement following curative treatment of endogenous Cushing’s syndrome (CS) is highly variable, with no validated markers to guide tapering or predict prolonged dependency. We evaluated clinical and hematologic predictors of GC duration, stratified by CS etiology and GC formulation. METHODS: This nationwide retrospective cohort included patients with endogenous CS diagnosed over 20 years (2000–2023) in the Clalit Health Services database from Israel. Patients with adrenal carcinoma or ectopic CS were excluded. Duration of GC therapy following curative pituitary or adrenal surgery was categorized as < 20 months or ≥ 20 months (median 19.3 months). Baseline hematologic indices including white blood cell count, neutrophil count, lymphocyte count, and neutrophil-to-lymphocyte ratio (NLR) were extracted/calculated from values recorded within 24 months prior to diagnosis. RESULTS: Among 103 patients (mean age 43.8 ± 13.7 years; 76.7% women), 41 had Cushing disease (CD) and 56 had adrenal CS. Fifty-one patients (49.5%) required ≥ 20 months of GC replacement. Patients requiring prolonged therapy were older (p = 0.0045) and had lower baseline neutrophils (p = 0.050) and NLR (p = 0.026), with significant hematologic differences seen in CD. Hydrocortisone use was associated with longer duration of GC replacement than prednisone. Overall survival did not differ by GC duration, but among CD patients, prolonged therapy was associated with lower survival (p = 0.045). CONCLUSION: Older age, and lower baseline neutrophils and NLR, were associated with prolonged postoperative GC replacement. These findings suggest that routine hematologic markers may help predict delayed recovery and guide individualized tapering strategies.