Hexarelin as a test of pituitary reserve in patients with pituitary disease

BACKGROUND The insulin tolerance test (ITT) is the reference standard for t he diagnosis of cortisol and growth hormone (GH) deficiency, but problems h ave occurred in small children in inexperienced hands and it is contraindic ated in patients with cardiac disease and epilepsy. Hexarelin is a growth h ormone-releasing peptide with GH-, ACTH/cortisol- and prolactin-releasing e ffects which involve both hypothalamic and direct pituitary mechanisms. We therefore investigated whether it could be used to test GH and ACTH/cortiso l reserve in patients with pituitary disease. METHODS AND SUBJECTS The changes in GH and cortisol in response to insulin- induced hypoglycaemia (intravenous human Actrapid 0.15 IU/kg) and hexarelin (2 mu g/kg) in 19 patients with possible pituitary disease (5 males, mean age 39 years, range 21-70) were compared. The patients' responses during th e hexarelin test were also compared to normal ranges of GH and cortisol res ponses established in healthy volunteers following hexarelin administration , RESULTS AND DISCUSSION GH peak levels were significantly higher after hexar elin than after hypoglycaemia (mean +/- SEM; 67.1 +/- 16 vs. 26.9 +/- 6.8 m U/I respectively; P < 0.001), while cortisol levels were significantly lowe r (420 +/- 34 vs. 605 +/- 50 nmol/l; P < 0.001). The peak responses of both hormones correlated significantly between the hexarelin and insulin-induce d hypoglycaemia tests (r = 0.80, P < 0.001 for cortisol). Peak GH levels af ter hexarelin and ITT showed a significant positive correlation with IGF-I levels (r = 0.84 and r = 0.77, P < 0.001 for both). All patients with a sub normal GH response to hexarelin (<41.4 mU/I) had a peak GH response to ITT of <9 mU/I, and only one patient had a normal (although borderline) respons e to hexarelin with a subnormal GH response to the ITT. Although 17 of the 19 patients had corresponding cortisol responses to hexarelin and the ITT t est (either failing or passing both), two patients had normal cortisol resp onses to hexarelin but subnormal responses to the ITT, A peak serum cortiso l level following hypoglycaemia of >580 nmol/l is indicative of normal cort isol reserve, as established in patients undergoing surgery; only five of t he normal volunteers and one of the thirteen patients with a normal ACTH/co rtisol reserve on ITT had a peak cortisol >580 nmol/l in response to hexare lin CONCLUSION Adult patients who have a subnormal peak GH response to hexareli n are likely to be GH deficient on an insulin tolerance test. However, our data suggest that the hexarelin test is not a useful test of ACTH/cortisol reserve. The hexarelin test could be a useful first/screening test to diagn ose adult GH deficiency, particularly in patients in whom an insulin tolera nce test is contraindicated or who are already ACTH deficient and in whom t he GH reserve alone is of interest.