Endocrine Abstracts

Context: Endogenous Cushing syndrome (CS) is associated with hematological abnormalities. Nevertheless, conflicting data have been reported on erythropoiesis. Some studies reported an association between CS and anemia in men, whereas others described erythrocytosis in affected patients. Furthermore, it is unclear whether there are CS subtype-specific changes in red blood cells (RBC) parameters.

Objective: To investigate sex and subtype-specific changes in RBC in a large cohort of patients with CS at initial diagnosis and after curative surgery.

Design: Retrospective, monocentric study including 210 patients (females, n=162; males, n=48; median age 49 and 48, respectively) with ACTH-dependent (Cushing’s disease (CD), n=85; ectopic CS (ECS), n=31) and ACTH-independent CS (cortisol-producing adrenocortical adenoma, n=46; adrenocortical carcinoma n=48)). These patients were matched 1:1 for sex and age with patients suffering from either hormonally inactive pituitary microadenomas (n=117) or adrenal incidentalomas (n=93). RBC parameters were evaluated at initial diagnosis and after surgical cure of CS (at 3 months, 12 months, and ≥24 months).

Results: Women with active CS had higher hematocrit (median 42.3 vs 40.4%), hemoglobin (14.1 vs 13.8g/dl), and mean corpuscular volume (MCV) (91.1 vs 87.8fl) than female controls (all P<0.005). Women with CD showed higher hematocrit (43.3 vs 36.1%), RBC count (4.8 vs 4.0n*106/µl), and hemoglobin (14.3 vs 12.2 g/dl) than those with ECS (all P<0.0005). The same differences were found if women with ECS due to malignant tumors were excluded from the analysis. Men with active CS had lower hematocrit (42.9 vs 44.7%), RBC count (4.8 vs 5.1n*106/µl), and hemoglobin (14.2 vs 15.4g/dl), but higher MCV (90.8 vs 87.5fl) than controls (all P<0.05). 20 out of 48 men with CS (42%) had hemoglobin levels below the normal range. In men with CS, no subtype specific differences but a negative correlation between 24h-urinary free cortisol and hematocrit, RBC count, and hemoglobin (r=-0.426, r=-0.477, r=-0.347, P<0.05) were identified. Compared to baseline, hemoglobin decreased in both women (-8.3%) and men (-5.8%) three months after remission from CS.

Conclusion: CS is characterized by pronounced sexual and subtype-specific changes in erythropoiesis. Women s with CS showed higher hematocrit and hemoglobin levels compared to controls. In contrast, men with CS had lower hematocrit/hemoglobin levels, which further decreased in the first months after remission. Therefore, anemia should be considered as a potential complication of CS in males. In females with CS, differences in RBC parameters may allow for a first subtype differentiation between CD and ECS.