Erythropoiesis in Cushing syndrome: sex-related and subtype-specific differences. Results from a monocentric study

Context: Cushing syndrome (CS) is associated with different hematological abnormalities. Nevertheless, conflicting data about erythropoiesis in CS have been reported. Furthermore, it is unclear whether CS sex and subtype-specific alterations in red blood cells (RBC) parameters are present.

Objective: To investigate sex and subtype-specific changes in RBC in patients with CS at initial diagnosis and after remission.

Design: Retrospective, monocentric study including 210 patients with CS (women, n = 162) matched 1:1 for sex and age to patients with pituitary microadenomas or adrenal incidentalomas (both hormonally inactive). RBC parameters were evaluated at initial diagnosis and after remission.

Results: Women with CS had higher hematocrit (median 42.2 vs 39.7%), hemoglobin (14.1 vs 13.4 g/dl) and mean corpuscular volume (MCV) (91.2 vs 87.9 fl) compared to the controls (all p < 0.0001). Women with Cushing disease (CD) showed higher hematocrit, RBC and hemoglobin levels than those with ectopic Cushing (ECS) (all p < 0.005). Men with CS had lower hematocrit (42.9 vs 44.7%), RBC count (4.8 vs 5.1n*10⁶/µl) and hemoglobin (14.2 vs 15.4 g/dl), but higher MCV (90.8 vs 87.5 fl) than controls (all p < 0.05). In men with CS, no subtype-specific differences were identified. Three months after remission hemoglobin decreased in both sexes.

Conclusion: CS is characterized by sexual and subtype-specific differences in RBC parameters. Compared to controls, women with CS showed higher hematocrit/hemoglobin levels, whereas men had lower hematocrit/hemoglobin, which further decreased directly after remission. Therefore, anemia should be considered as complication of CS in men. In women, differences in RBC parameters may help to differentiate CD from ECS.