Endogenous dopaminergic dysfunction: a novel form of human growth hormone deficiency and short stature.

Abstract

The purpose of this study was to determine if combined therapy with dopaminergic drugs (DA), i.e. L-dopa or bromocriptine, and exogenous human GH (hGH) could increase growth velocity in hypopituitary children. Twelve prepubertal hypopituitary children (eight boys and four girls; bone age, 1.5-9.5 yr), divided into two groups, each received hGH alone, DA alone, and DA and hGH. Group I (n = 6) received L-dopa (15 mg/kg, orally) at 6-h-intervals during DA and combined DA and hGH therapy. Group II (n = 6) received bromocriptine (1.25 mg, orally) every 12 h during DA and combined DA and hGH therapy. Both groups were given hGH (0.1 IU/kg) three times per week during hGH and combined hGH and respective DA treatment. The study included three 6-month treatment periods of DA, hGH, and combined DA and hGH therapy. The mean growth rates (centimeters per 6 months, +/- SD) before treatment and during the three study periods for group I were 1.7 +/- 0.2, 3.3 +/- 0.8, 3.4 +/- 0.4, and 3.9 +/- 0.7, respectively. Group II results were 1.4 +/- 0.3, 2.3 +/- 0.8, 5 +/- 1.6, and 3.7 +/- 1.1. Mean and peak hGH concentrations, measured every 30 min for 9 h at the end of each study period, increased significantly in five patients, from 15 +/- 3 (+/- SE) ng/ml during hGH therapy to 30 +/- 5 ng/ml during DA and hGH treatment. The mean peak hGH values rose from 24 +/- 4 to 45 +/- 5 (+/- SE) ng/ml. In conclusion, addition of dopaminergic agents to hGH therapy potentiates growth in some hypopituitary children. The increased growth and hGH responses to L-dopa or bromocriptine suggest impaired endogenous GH release. Dopaminergic therapy alone or in combination with exogenous hGH may be efficacious in some hypopituitary children.