Hematological changes in Cushing’s disease from diagnosis to remission: comparison with non-functioning pituitary adenomas

Abstract

INTRODUCTION: Cushing's disease (CD) results in chronic hypercortisolism with multisystem complications. Although glucocorticoids affecthematopoiesis, sex-specific hematological alterations and their reversibility following treatment remain incompletely characterized.Most previous studies have compared patients with CD with healthy controls, limiting the ability to isolate cortisol-specific effects fromtumor- or surgery-related confounders. We investigated hematological parameters in patients with CD at diagnosis and after remission,using patients with non-functioning pituitary adenoma (NFA) as controls to specifically identify hypercortisolism-driven changes. MATERIAL AND METHODS: This retrospective study included 117 patients: 59 with CD and 58 with NFA who underwent transsphenoidal surgery. Complete blood count and hormonal parameters were evaluated at diagnosis and 3 months postoperatively. Changes in hematologicalparameters were compared between groups using repeated-measures analysis of variance, with subgroup analyses examiningremission status and sex-specific differences. RESULTS: At baseline, patients with CD showed significantly elevated white blood cell (WBC) counts (9.50 ± 2.67 vs. 7.32 ± 1.71 × 103/μL, p < 0.001), neutrophil counts (6.41 ± 2.35 vs. 4.30 ± 1.44 × 103/μL, p < 0.001), neutrophil-to-lymphocyte ratio (NLR) (3.27 ± 2.03 vs.2.04 ± 0.91, p < 0.001), and red blood cell (RBC) counts (4.70 ± 0.50 vs. 4.51 ± 0.46 × 106/μL, p = 0.03), with significantly lower eosinophilcounts (0.111 ± 0.093 vs. 0.166 ± 0.140 × 103/μL, p = 0.01) compared with NFA patients. No sex-specific differences were observed inbaseline hematological parameters within the CD group. At 3 months postoperatively, significant decreases in hemoglobin (p = 0.02),WBC (p < 0.001), neutrophil counts (p < 0.001), and NLR (p = 0.006) were observed in patients with CD compared with NFA controls. Importantly, the magnitude of postoperative reductions in WBC (p = 0.01) and neutrophil counts (p = 0.009), as well as increases in eosinophil counts (p = 0.03), was significantly associated with achieving biochemical remission. Neutrophil recovery was greater in women (p = 0.03). No correlations were found between baseline cortisol levels and hematological parameters. CONCLUSIONS: Cushing's disease demonstrates specific hematological alterations - elevated WBC, neutrophils, NLR, and RBC, with decreasedeosinophils - that are attributable to hypercortisolism rather than the presence of a pituitary tumor. These parameters normalizerapidly following surgical remission, with changes correlating with biochemical cure. Routine complete blood counts may serve as accessiblebiomarkers for monitoring disease activity and treatment response in CD.