Introduction: In patients with ACTH-dependent hypercortisolism, the corticotropin-releasing-hormone (CRH) test and the high dose dexamethasone suppression test (HDDST) can be used to differentiate between pituitary ACTH production (Cushings disease) and ectopic ACTH production. The rationale is that a pituitary adenoma will show some response to CRH and ACTH whereas an ectopic source is less responsive to ACTH and CRH. However, there is discussion about the clinical utility of the CRH-test and the HDDST. Many endocrinologists consider bilateral inferior petrosal sinus sampling a superior test. However, inferior petrosal sinus sampling is not ubiquitously available, has a risk of cerebrovascular complications, and can give false positive results. In this study, we aimed to determine sensitivity and specificity of the CRH-test and HDDST.
Methods: We analyzed all CRH-tests and HDDSTs performed in the period 19932018 at the Amsterdam UMC (location AMC) in patients with biochemically confirmed endogenous hypercortisolism. For the CRH-test (100 ug intravenously), we used a 20% plasma cortisol increase and/or a 50% plasma ACTH increase from baseline as a cutoff. For the HDDST we used a 190 nmol/l decrease of plasma cortisol from baseline to the average of 6:457:15 h after infusion of 8.75 mg dexamethasone as a cutoff. In 2018 we reviewed all patient records, and we determined the final diagnosis by clinical follow-up.
Results: For 52 patients with hypercortisolism (out of 68 patients) who underwent the CRH-test and/or HDDST, a final diagnosis could be determined: Cushings disease (n=35), ectopic ACTH production (n=3) and adrenal cortisol production (n=14). To diagnose Cushings disease (versus ectopic ACTH production) using our pre-determined cutoff values, CRH-test derived cortisol values yield a sensitivity of 71% and a specificity of 100%, CRH-test derived ACTH values yield a sensitivity of 74% and a specificity of 100%, and the HDDST has a sensitivity of 97% and a specificity of 100%.
Conclusion: In patients with ACTH-dependent hypercortisolism, the HDDST excellently differentiates between Cushings disease and ectopic ACTH production, and may reduce the need for inferior petrosal sinus sampling.
18 May 2019 - 21 May 2019