Endocrine Abstracts

Glucocorticoids play a significant role in immune modulation and regulation of inflammation. In patients with endogenous glucocorticoid excess (Cushing’s syndrome [CS]) multiple haematological alterations are recognized, such as neutrophil leukocytosis, lymphopenia, and eosinopenia, often leading to severe clinical complications. However, little is known in patients with mild autonomous cortisol secretion (MACS). Serum inflammation-based scores may reliably reflect systemic inflammation and predict outcomes in several diseases. The aim of this study was to evaluate inflammation-based scores in patients with ACTH-independent cortisol excess and investigate their relationship with cortisol hypersecretion levels. A cohort of 391 patients (median age 61 years, 59.6% women) was evaluated: 231 patients with nonfunctioning adrenocortical tumors (NFAT), 138 with MACS (serum cortisol after 1-mg overnight dexamethasone suppression test >50 nmol/l and absence of typical CS features), and 22 with CS. Patients with other types of benign adrenal tumours (e.g. myelolipoma), phaeochromocytoma, active malignancies, infections, and autoimmune or haematological diseases were excluded. We evaluated the cortisol profile and the following inflammation-based scores at initial diagnosis: Neutrophil-to-Lymphocyte Ratio (NLR), Lymphocyte-to-Monocyte Ratio (LMR), Platelet-to-Lymphocyte Ratio (PLR), Systemic Immune-Inflammation Index (SII, obtained by multiplying absolute platelet count and NLR), and Prognostic Nutrition Index (PNI, calculated by serum albumin and lymphocyte count reflecting immune-related nutritional status). Data are expressed as median (interquartile range). Serum cortisol after 1-mg overnight dexamethasone positively correlated with NLR (r=0.283) and SII (r=0.225) and negatively with LMR (r=-0.23) (each P<0.001). NLR, SII and LMR significantly differed among the three groups of patients, while PLR and PNI were similar among CS, MACS and NFAT. In particular, NLR and SII were significantly higher in both CS [3.80(1.92-4.37) and 859.6(459.7-1355.2)] and MACS [2.71(2.05-3.60) and 730(485.9-961.5)] compared to NFAT [2.21(1.68-2.94) and 562.9(412.1-837.6)] (P=0.001 and P<0.001 for NLR and P=0.002 and P=0.01 for SII, respectively). On the contrary, LMR was lower in patients with CS [2.23(1.82-3.47)] and MACS [3.12(2.42-4.5)] than in those with NFAT [3.62(2.85-4.55)], but also significantly lower in CS compared to MACS, all P<0.05. In conclusion, the neutrophil-based scores (NLR and SII) and monocyte-based score (LMR) correlated with the degree of endogenous cortisol excess being altered in both patients with ACTH-independent CS and MACS. Moreover, LMR was the only score that showed a significant difference between CS and MACS. These findings suggest that, similar to overt CS, mild autonomous cortisol excess also influences the immune system function which can contribute to the MACS-associated comorbidities.