Endocrine Abstracts

Background: Several stimulatory tests for differential diagnosis of ACTH dependent Cushing’s syndrome are avilable, CRH being the most valuable test in patients with Cushing’s disease (CD). Exaggerated responses to ghrelin have also been shown in patients with CD mainly due to overexpression of GHS receptors on corticotrope tumor cells. However, the effects of combined stimulation with CRH+ghrelin on ACTH and cortisol secretion have not been tested before in these patients.

Objective: To compare ACTH and cortisol responses to ghrelin, CRH and CRH+ghrelin in patients with Cushing’s disease.

Patients and methods: Six consequtive patients with diagnosed CD were included in the study. All patients were females, mean age 54.8±16.7 years, with microadenomas on magnetic resonance imaging. Ghrelin test (1 μg/kg of body weight, i.v. bolus), CRH test (100 μg i.v. bolus) and combined CRH+ghrelin test were performed at least a week apart in random fashion. Blood was sampled at 0, 15, 30, 45, 60 and 90 min. Plasma ACTH (Cisbio Bioassays, France) and cortisol (Cisbio Bioassays, France) responses were measured and compared in all three tests. GH and prolactin (PRL) responses were also measured.

Results: Baseline mean ACTH and cortisol values were 31.5±32.9 pg/ml and 562.5±257.4 nmol/l respectively. No significant differences were found between peak ACTH and cortisol responses during ghrelin (ACTH 200.5±344.9 pg/ml, cortisol 846.2±351.9 nmol/l) and CRH stimulation (ACTH 90.7±72.2 pg/ml and cortisol 1070.9±141.9 nmol/l). However, significantly higher peak ACTH (359.6±593 pg/ml, P<0.05) and cortisol (1312.8±117.1 nmol/l, P<0.05) responses were found after combined stimulation with CRH+ghrelin compared to CRH test alone, suggesting a synergistic effect. Significant mean GH (peak 13 ng/ml) and PRL (peak 909.6 mU/l) responses were also noted after stimulation with CRH+ghrelin.

Conclusion: Combined stimulation with CRH+ghrelin exerts synergistic effect on ACTH and cortisol release in patients with CD. Combined stimulation with CRH+ghrelin is more powerful test than CRH alone.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.