Optimizing diagnostic strategies for central adrenal insufficiency in pituitary disease

Central adrenal insufficiency (CAI) affects a significant number of patients with pituitary disease, and a missed diagnosis can be fatal. The optimal diagnostic algorithm, however, is still controversial. Here, we present a single-centre study with the systematic use of the overnight metyrapone test (OMT) and the short synacthen test (SST) in a large cohort of patients with pituitary disease.

We conducted a retrospective analysis of 161 patients with pituitary disease or after pituitary surgery and suspected CAI. Data from OMT (n = 134), SST (n = 156), and long-term clinical outcomes (n = 97) were evaluated.

Validated in the sub-cohort with available clinical outcome evaluation after a mean of 2.7 years, 11-desoxycortisol (11-DOF, cut-off >200 nmol/L) in the OMT achieved a sensitivity of 100% and a specificity of 94%. Adrenocorticotropic hormone measurement offered no additional diagnostic benefit. Cortisol in the SST (cut-off >450 nmol/L after 30 min) showed an inferior sensitivity of 75.0% and a specificity of 80.2%. To assess the usefulness of the tests in pre-classified risk groups according to the recently proposed CAI-Score, we calculated CAI subgroup prevalence as well as positive/negative predictive value (NPV) for the SST in each risk group. In the low-risk group (CAI-Score = 0), the SST achieved a high NPV (0.99), while showing no clear benefit in the other groups.

This study reaffirms the value of 11-DOF in the OMT as a reliable diagnostic tool for CAI, while confirming the limitations of the SST. These data indicate to consider SST as a single test procedure for low-risk patients.