Impact of etiology, sex, diabetes mellitus and remission status on erythrocytic profile in patients with cushing’s syndrome: a large population database study

Abstract

The study aimed to characterize the erythrocytic pro le in patients with Cushing's syndrome (CS) versus controls from the normal population according to etiology, sex, presence of diabetes mellitus (DM) and hypercortisolemia remission status. MethodsThis retrospective cohort analysis compared erythrocytic parameters between patients with CS of pituitary (CD) and adrenal (aCS) etiology and age, sex, body mass index (BMI) and socioeconomic status-matched controls in a 1:5 ratio. Laboratory values at baseline were calculated as mean values during the year preceding CS diagnosis, and over one year thereafter. ResultsThe cohort included 397 CS patients (68.26% female; mean age 51.11 ± 16.85 years) and 1970 controls. Patients with CS had signi cantly higher baseline median levels of hemoglobin (Hgb) (13.70 g/dL vs. 13.12 g/dL [p < 0.0001]) and hematocrit (Hct) (41.64% vs. 39.80% [p < 0.0001]) compared to controls. These differences were observed for both CD and aCS and for both sexes. Patients who attained remission had Hgb and Hct levels comparable to controls (13.20 g/dL and 40.08% in patients with CD and aCS vs. 13.20 g/dL and 39.98% in controls). Meanwhile, those with persistent/recurrent disease maintained elevated levels. Patients with comorbid DM had similar Hgb but higher Hct (p = 0.0419), while patients without DM showed elevated erythrocytic values compared to controls (p < 0.0001). ConclusionOur data illustrates that erythrocytic parameters are directly in uenced by glucocorticoid excess as Hgb and Hct are higher in patients with CS, and normalize after remission. We have identi ed the in uence of DM on erythrocytic parameters in patients with CS for the rst time. ParticipantsAfter the initial screening of patients with an ICD-10 diagnosis of CS, cases had to meet one of the following criteria: (a) any recorded 24-hour urinary free cortisol (UFC) > 4 × upper limit of normal (ULN), (b) 24-hour UFC > 3 × ULN and a surgical intervention to remove the pituitary or adrenal adenoma, (c) a 24hour UFC > 2 × ULN and treatment with metyrapone, ketoconazole, osilodrostat, cabergoline, or pasireotide.Each diagnosis was retrospectively con rmed by the authors AA and YR during data collection, by a thorough review of documented biochemical and imaging test results, as well as information about management and follow-up. For each patient, the time of diagnosis was de ned as the earliest occurrence of either an elevated UFC result, the rst pituitary or adrenal gland resection, or the initial diagnosis of CS. Each patient with CS was paired with ve, age, sex, BMI and socioeconomic status-matched controls.All patients with adrenocorticotropic hormone (ACTH)-dependent CS were screened to con rm exclusion of ectopic CS. Patients with adrenocortical carcinoma that were identi ed within 5 years of CS detection or patients with ectopic CS were excluded from the study. De nitionsThe etiology of CS was established based on the available biochemical and radiological data, pharmacotherapy, radiotherapy, and surgical interventions for C...