It might be difficult to make a differential diagnosis of CS, an ACTH-dependent Cushing’s illness. While alternative noninvasive techniques, such as the high-dose dexamethasone suppression test (HDDST), offer mediocre diagnosis accuracy, the standard gold method of bilateral inferior petrosal sinus sampling (BIPSS) is costly and intrusive. For a study, researchers sought to identify a novel noninvasive practicable technique with improved diagnostic accuracies for diagnosing ACTH-dependent CS in settings where BIPSS is not feasible.

In the single-center retrospective analysis, 264 patients with Cushing’s disease (CD) and 47 individuals with ectopic ACTH secretion syndrome (EAS) were examined (2011–2021). The scoring model was built using the multivariate logistic model.

The final multivariable logistic regression model took into account these factors, which have a strong correlation with the differential diagnosis of ACTH-dependent CS: female (adjusted OR 3.030, 95% CI 1.229-7.471), hypokalemia (0.209, 0.076-0.576), ACTH (0.988, 0.982-0.994), MRI pituitary lesion positive (8.671, 3.521-21.352), and HDDST positive (2.768, 1.139-6.7 On the model, a noninvasive scoring system of -14 to -14 points was developed. The noninvasive scoring model’s AUC was considerably higher than HDDST’s (0.756, 95% CI 0.685-0.825, P=0.004), at 0.915 (95% CI 0.869-0.960). The model’s ideal threshold for diagnosing CD was ≥0. The noninvasive scoring model’s specificity was 80.9% (95% CI 67.5%-89.6%) and sensitivity was 91.3% (95% CI 87.3%-94.1%). The cutoff was more or around -10 with a specificity of 19.2% when the model’s sensitivity was 100%; it was more or around 13 with a sensitivity of 22.7% when the model’s specificity was 100%.

They created a noninvasive scoring model with superior diagnostic usefulness than HDDST in the same population to discriminate CD and EAS in ACTH-dependent CS patients. In regions where BIPSS is not accessible, CRH is difficult to get, or desmopressin stimulation is not often used, the noninvasive scoring model may be used. Additionally, it offered a triage tool for choosing patients who could profit most from doing another BIPSS test.