A Novel Screening Approach for Cushings Syndrome

Screening for Cushings syndrome (CS) is currently advisable in patients with findings unusual for their age (such as type 2 diabetes, hypertension, and osteoporosis) and/or multiple features of CS. Despite using these known features of CS, pretest probability remains low at an estimated 3-9% in these populations. In this study, simple lab tests were evaluated for their ability to increase the pretest probability of CS prior to ordering 1mg dexamethasone suppression test (DST) and late night salivary test (LNST).

Methods:

A query was performed using the electronic medical records of an endocrine clinic in Arizona between 2017 to 2021. Test order searched was dexamethasone to identify patients with history of DST. Excluded patients were those without valid dexamethasone values or a CBC and CMP taken simultaneously. CS was assessed with DST of ≥1.8 ug/dL and/or LNST of ≥0.09 ug/dL. Markers evaluated were WBC/CO2 ratio (WCR), Neutrophil-platelet ratio, Sodium-potassium ratio, Sodium-CO2 ratio, Chloride-CO2 ratio, and Neutrophil-lymphocyte ratio (NLR) which had previously been studied by Wei wang et al.

Results:

Of 112 patients, 45 met inclusion criteria and 10 of those had abnormal DST ≥1.8ug/dL and/or LNST ≥0.09 ug/dL. Imaging taken retrospectively and prospectively showed 5 adrenal adenomas, 3 pituitary adenomas, and 2 unknown (pending imaging). Cutoff values for markers were determined empirically. NLR and WCR had statistical correlation to DST/LNST, the other markers did not. NLR was 100% sensitive and 50% specific using a cutoff value of ≥ 2.0. WCR was 90% sensitive and 97% specific using a cutoff value of ≥ 0.395. Combined, NLR and WCR correctly identified 9/10 patients with CS and 32/35 patients without CS. The sensitivity was 90% (60%-98% CI) and specificity was 91% (78%-97% CI). Statistical significance was verified with a two-sample t-test for unequal variances, t(35)=4.17, p< 0.01.

Discussion/Conclusion:

NLR and WCR had a significant correlation to abnormal DST and/or LNST results. If used prior to diagnostic testing these markers would have predicted results with 90% sensitivity and 91% specificity. The performance of these tests was above expected and could be used to increase pretest probability of CS. A significant benefit of these findings is that these labs are simple, inexpensive, and readily available nearly anywhere. Further studies should be completed using a larger sample size to validate these results and determine optimal cutoff values. If validated, these tests could provide a simple and effective way to screen large populations for CS which would be a milestone in the field of hypercortisolism.