White blood cell count: a valuable tool for suspecting Cushing's syndrome

Purpose: Simple screening tests to determine whether Cushing's syndrome (CS) should be ruled out are lacking. Tools that enable early diagnosis could reduce morbidity and associated sequelae. The potential of glucocorticoid-induced changes in the white blood cell (WBC) count for raising suspicion of CS is assessed.

Methods: This was a retrospective case‒control study. The WBC counts of 73 cases with CS and 146 matched controls were compared. The number of leukocytes (Leu), the number and percentage of neutrophils (N, Np), the number and percentage of lymphocytes (L, Lp), neutrophil-to-lymphocyte differences in the number and percentage (N-L, Np-Lp), neutrophil-to-lymphocyte ratio in the number and percentage (NLR, NLRp), and leukocyte-to-lymphocyte differences (Leu-L) were evaluated. The area under the ROC curve (AUC) was calculated for each of these parameters. Reference values were estimated that could help disclose occult CS.

Results: All ten parameters showed significant differences between cases and controls. The AUC was greater than 0.7 for all ten parameters, and was the best for the NLRp and Lp (AUC: 0.89). An Lp of 23.9% showed a diagnostic accuracy of 84.9% for the diagnosis of CS. The concordance of an Lp below 24% and more than 8000 leucocytes had a PPV of 78.2% for CS, while the pairing of an Lp over 24% and a Leu below 8000 cells had an NPV of 97.3% for CS.

Conclusion: WBC count assessment can be an effective tool to raise suspicion of CS, prompting diagnostic testing. This simple and universally available test may allow earlier diagnosis of CS before highly evolved phenotypes develop.