Patients with dilated cardiomyopathy show reduction of the somatotroph responsiveness to GHRH both alone and combined with arginine

Objective: Altered function of the GH/IGF-I axis in patients with dilated c ardiomyopathy (DCM) has been reported. In fact, DCM patients show reduction of IGF-I levels, which could reflect slight peripheral GH resistance or, a lternatively, reduced somatotroph secretion, Spontaneous GH secretion has b een reported to be altered by some but not by other authors, whereas the GH response to GHRH, but not that to GH-releasing peptides, seems reduced in DCM patients. On the other hand, it is well known that the GH response to G HRH in humans is markedly potentiated by arginine (ARG), which probably act s via inhibition of hypothalamic somatostatin release: in fact the GHRH+ARG test is known as one of the most reliable to evaluate the maximal secretor y capacity of somatotroph cells. Methods: In order to further clarify the somatotroph function in DCM, in we ll-nourished patients with DCM (34 male, 4 female: age (mean +/- S.E.M.) 57 .8 +/- 1.1 years; body mass index (BMI) 24.6 +/- 0.6 kg/m(2); left ventricu lar ejection fraction 23.2 +/- 1.6%; New York Heart Association classificat ion I/1, II/17, III/18, IV/2) we studied the GH response to GHRH (1.0 mu g/ kg i.v.) alone or combined with ARG (0.5 g/kg i.v), The results in DCM pati ents were compared with those in age-matched control subjects (CS) (39 male , 7 female; age 55.9 +/- 1.0 years: BMI 23.2 +/- 0.3 kg/m(2)). Results: Mean IGF-I levels in DCM patients were lower than in CS (144.3 +/- 6.9 vs 175.1 +/- 8.4 mu g/l, P < 0.05) whereas basal GH levels were simila r in both groups (1.7 +/- 0.3 vs 1.7 +/- 0.3 mu g/l), The GH response to GH RH in DCM patients was lower (P < 0.05) than that in CS (GH peak 6.5 +/- 1. 2 vs 10.7 +/- 2.1 mu g/l). In both groups the GH response to GHRH + ARG was higher (P < 0.001) than that to GHRH alone. However, the GH response to GH RH + ARG in DCM patients remained clearly lower (P < 0.01) than that in CS (18.3 +/- 3.2 vs 34.1 +/- 4.6 mu g/l). The GH response to GHRH alone and co mbined with ARG was not associated with the severity of the disease. Conclusion: DCM patients show blunted GH responses to GHRH both alone and c ombined with ARG. Evidence that ARG does not restore the GH response to GHR H in DCM patients makes it unlikely that the somatotroph hyporesponsiveness to the neurohormone reflects hyperactivity of hypothalamic somatostatinerg ic neurons.