RELIABILITY OF THE CORTICOTROPIN RELEASING HORMONE STIMULATION TEST FOR DIFFERENTIATING BETWEEN ACTH DEPENDENT AND INDEPENDENT CUSHING SYNDROME

Abstract

Context: It is a challenge to determine the origin of Cushing syndrome (CS), especially in patients with low-normal adrenocorticotropic hormone (ACTH) concentrations.

Objective: To evaluate the reliability of the corticotropin-releasing hormone (CRH) stimulation test in patients with CS whose origin of disease was not clearly identified using ACTH values, the high-dose dexamethasone suppression test (HDDST), and imaging in a single tertiary referral center.

Design and methods: Twenty-one patients with CS who were admitted to the endocrinology-metabolism clinic between 2004 and 2016 whose ACTH concentrations were 5-20 pg/mL and needed CRH stimulation test were retrospectively assessed.

Results: Nine out of 21 patients were diagnosed as having Cushing's disease (CD) and 12/21 had adrenal CS. The CRH stimulation test had a sensitivity and specificity of 100% and 8%, and positive and negative predictive values of 100% and 45% according to the current diagnostic criteria, respectively. An increase in ACTH ≥115% at 15 minutes and cortisol ≥86% at 60 minutes after CRH were associated with the highest likelihood ratio. The sensitivity and specificity of ACTH was 67% and 83% (AUC=0.75±0.12, 95% CI: [0.5-0.9]; p=0.03), and for cortisol it was 75% and 78% (AUC=0.71±0.15, 95% CI: [0.5-0.9]; p=0.03). Cortisol suppression of more than 64% from basal level in the HDDST suggested CD with the highest likelihood ratio. When these cut-off values were used together, both tests were negative in the patients with CD.

Conclusion: The CRH stimulation test has low specificity to localize CS in patients with ACTH concentrations of 5-20 pg/mL according to the current diagnostic criteria. Different diagnostic criteria may be used in the CRH stimulation test and also in the HDDST in this group of patients.

Keywords: ACTH; CRH stimulation test; Cushing’s syndrome.

Figure 1.

ROC curve analysis of high-dose dexamethasone test (HDDST) with recently determined criteria.

Figure 2.

ACTH (a) and Cortisol (b) concentrations following CRH administration in patients with adrenal CS and CD.

Figure 3.

ROC curve analysis of ACTH (a) and cortisol (b) concentrations of corticotrophin- releasing hormone (CRH) test with recently determined criteria.

Figure 4.

The comparison of the diagnosis of the study population and the results of CRH and HDSST combinations performed according to newly determined criteria (ACTH increase of ≥115% at 15 min, and cortisol increase ≥86% at 60 min after the injection of ovine CRH and cortisol suppression of ≥64% after 8 mg dexamethasone).