Journal of Clinical Medicine, vol.14, no.22, 2025 (SCI-Expanded, Scopus)
Background/Objectives: Cushing’s syndrome (CS) is a rare endocrine disorder caused by chronic glucocorticoid excess. With the increasing recognition of mild autonomous cortisol secretion (MACS), clinical and biochemical differentiation between overt and mild forms has become more challenging. This study evaluated the clinical significance of the hemoglobin–albumin–lymphocyte–platelet (HALP) score in patients with Cushing’s disease (CD), adrenal Cushing’s syndrome (ACS), MACS, and nonfunctioning adrenal adenoma (NFA), focusing on its potential role in the preoperative evaluation and postoperative follow-up of hypercortisolism. Methods: We retrospectively analyzed 361 patients evaluated for cortisol excess between February 2019 and June 2025. Patients were categorized into four groups: CD, ACS, MACS, and NFA. Demographic, clinical, and hormonal parameters, as well as surgical outcomes, were recorded, and the HALP score was compared between the four groups. The diagnostic performance of the HALP score in differentiating overt Cushing’s syndrome (CD + ACS) from MACS/NFA was assessed using receiver operating characteristic (ROC) curve analysis. Postoperative changes in the HALP score were analyzed in surgically treated patients. Results: HALP scores were significantly lower in overt CS than in MACS and NFA. Using a threshold value of 40, the HALP score demonstrated 51.9% sensitivity and 90.4% specificity in differentiating CD/ACS from MACS/NFA. Among 68 operated patients, postoperative HALP data were available for 49 patients, for whom HALP scores significantly increased in both CD and ACS groups (p = 0.001 for each). Conclusions: The HALP score serves as a simple, cost-effective biomarker that reflects the combined hematologic and metabolic impact of cortisol excess. Significant postoperative improvement in the HALP score suggests its potential utility as a complementary tool in the preoperative assessment of hypercortisolism.