Ghrelin is able to stimulate HPA axis in both humans and animals. Exaggerated ACTH and cortisol responses to ghrelin have been shown in patients with CD. Here we studied the role of ghrelin alone or in combination with CRH in the diagnosis of CD. In 21 CD patient (18 female, age 49.8±10.2 years, BMI 29.8±0.8 kg/m2, ten macroadenomas 11 microadenomas) we performed: i) ghrelin test (100 μg iv bolus) ii) CRH test (100 μg iv bolus) and iii) ghrelin+CRH, in random order, one week apart. We also included 8 (seven female, age 40.6±5.3 years, BMI 29.9±1.2 kg/m2) control subjects (C) in the study. Peak ACTH, cortisol, PRL and GH responses to ghrelin and/or CRH were evaluated (mean±S.E.). At baseline, ACTH (CD: 71.2±15.6 ng/l; C: 18.9±4.1 ng/l; P<0.01) and cortisol levels (CD: 643.1±41.7 nmol/l; C: 316.4±23.7 nmol/l P<0.01) were significantly higher in CD vs C. After ghrelin administration peak ACTH (CD: 192.3±40.4 ng/l vs C: 71±30.9 ng/l, P<0.01) and cortisol responses (CD: 979.8±46.5 nmol/l vs C: 529.3±74.8 P<0.01) were significantly higher in CD compared with C but similar with ACTH (CD: 179±26.5 ng/l vs C: 59.8±12.3 ng/l, P<0.01) and cortisol responses (CD: 1088.7±51.4 nmol/l vs C: 677.3±71.3 nmol/l, P<0.01) to CRH in both patients with CD and controls. Following the co-administration of ghrelin+CRH an additive ACTH response was observed in both groups (CD: 384.1±74.2 ng/l; C: 176.3±48.5 ng/l) but at a different level. ACTH and cortisol responses, during all three tests, were similar in CD patients with micro- and those with macroadenomas. After stimulation with ghrelin the peak PRL responses (CD: 1046.6±179.7 mU/l; C: 998.4±222.4 mIU/l; P>0.05) were similar in CD compared to C, while GH responses (CD: 21.2±3.7 mIU/l; C: 54.6±9.1 mU/l; P<0.05) were significantly lower in CD. Our results show that ACTH and cortisol secretion remain regulated and responsive to trophic stimuli in patients with CD, which are characterised by exaggerated ACTH and cortisol responses to ghrelin and CRH. Additive ACTH responses to the combined ghrelin+CRH administration, suggest that their ACTH releasing activities may be mediated independently in both patients and controls.
Disclosure: This work was supported by the Serbian Ministry of Science Grant project number 175033