Defining a serum cortisol cutoff level post-CRH stimulation for diagnosing ACTH deficiency: A retrospective study validated by a nationwide registry

Abstract

Background: The corticotropin-releasing hormone (CRH) stimulation test is used to diagnose adrenocorticotropic hormone (ACTH) deficiency; however, the serum cortisol cutoff value indicating impaired response on this test (18 µg/dL [approximately 500 nmol/L]) was established from the insulin tolerance test. We aimed to define a serum cortisol cutoff after CRH stimulation to diagnose ACTH deficiency.

Methods: Patients who underwent CRH stimulation at Nagoya University Hospital from 2016 to 2022 were divided retrospectively into two groups based on the need for hydrocortisone replacement at final follow-up (discovery cohort). Plasma ACTH and serum cortisol levels were measured at baseline and 30, 60, 90, and 120 minutes post-CRH administration using a current monoclonal antibody-based cortisol assay. The optimal cortisol cutoffs at each time point were determined by receiver operating characteristic (ROC) analysis. These cutoffs were validated using a nationwide disease registry in Japan (validation cohort).

Results: In the discovery cohort (n = 227), cortisol levels were significantly higher in patients who did not receive hydrocortisone therapy (n = 136) than in those who did (n = 91) at all time points (p < 0.001). ROC analysis revealed that a 30-minute post-CRH cortisol level of 12.6 µg/dL (347.6 nmol/L) provided the best diagnostic performance to identify patients not requiring hydrocortisone therapy (sensitivity: 88.2%; specificity: 92.3%; AUC: 0.969). In the validation cohort (n = 52), this cutoff was confirmed as optimal (sensitivity: 81.0%; specificity: 86.4%; accuracy: 83.7%).

Conclusion: A 30-minute post-CRH serum cortisol level of 12.6 µg/dL is a useful cutoff for diagnosing ACTH deficiency.

Keywords: Adenohypophysis; corticorelin; corticotropin-releasing hormone; hydrocortisone; hypopituitarism.