Abstract
Background: Endogenous hypercortisolism of adrenal origin is commonly associated with immune suppression. However, these patients also have signs characteristic of chronic inflammatory diseases. Better understanding of the mechanisms that alter the functioning of the immune system would allow for the development of a patient-centered approach to the treatment of corticotropin-independent endogenous Cushing's syndrome (CS).
 Aim: To assess the association between full blood count and gas chromatography-mass spectrometry-based urinary steroid excretion in patients with adrenal masses depending on malignancy grade and presence of hypercortisolism.
 Materials and methods: We retrospectively analyzed data from 42 patients with adrenal masses who had not received chemotherapy. The median age of the patients was 54 [Q25; Q75: 37; 63] years, and 76% of them were female. Preoperatively, all patients had hematology tests with differential leukocyte count. Steroid metabolome was assessed with Shimadzu GCMS-TQ8050 gas chromatography-mass spectrometer.
 Results: Twelve (12) patients had adrenocortical cancer (ACC) and CS, 9 patients had ACC without CS, 11 had adrenocortical adenomas (ACA) and CS, and 10 patients had ACA without CS. ACC patients had a higher neutrophil-to-lymphocyte ratio (NLR) than those with ACA: 3.35 [2.5; 6.3] vs 1.99 [1.41; 2.65] (р = 0.001). There was a linear correlation between NLR and serum cortisol levels after the 1 mg overnight dexamethasone suppression test (r = 0.41, p = 0.01), urinary excretion of 5β-tetrahydrocortisol (5β-THF) (r = 0.71, p 0.001) and 11β-hydroxyandrosterone (11β-OH-An) (r = 0.74, p 0.001). The ACC patients without CS had lower 5β-THF urinary excretion values, compared to ACA with CS patients: 931 [616; 1610] and 3139 [1480; 4375] mcg/24h, respectively (р = 0.007). 11β-OH-An urinary excretion in ACC patients without CS was higher than in ACA patients with CS: 1170 [806; 1266] и 602 [320; 739] mcg/24h (р = 0.007). The NLR cut-off value for adrenal mass malignancy in patients with CS exceeded 2.72 (sensitivity 90.0%, specificity 80.0%), and for the patients without hypercortisolism was above 1.92 (sensitivity 71.4%, specificity 100.0%).
 Conclusion: This is the first association identification between NLR, which is the marker of systemic inflammation, inflammation, and urinary excretion of 11β-OH-An, a metabolite of 11-hydroxyandrostenedione (a member of 11-oxygenated androgen family). This extends our understanding of the impact of hormonal activity of adrenal mass cells on the immune system.
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