Evidence for dopaminergic stimulation of growth velocity in some hypopituitary children.

Abstract

The purpose of this study was to determine if endogenous hGH release, hence growth, in hypopituitary children could be potentiated by therapy with dopaminergic (DA) drugs namely, L-dopa or bromocriptine. The effect of DA therapy on other endocrine function was also examined. Subjects were nine prepubertal children (four girls and five boys) with bone ages (BA) ranging from 1.5-9.5 yr. They were diagnosed as having idiopathic GH deficiency on the basis of: 1) failure to grow at normal rates 2) lack of GH response to two provocative stimuli (oral L-dopa, and insulin-induced hypoglycemia) and 3) low somatomedin-C concentrations for sex and age. They were divided into two groups. Group I (n = 4) received L-dopa (15 mg/kg, orally, every 6 h) for 6 months. Group II (n = 5) received bromocriptine (1.25 mg, orally, every 12 h) for 6 months. At the end of 6 months of DA therapy, both groups received human GH (hGH) im (0.1 IU/kg, thrice weekly) for 6 months. The growth rate in group I increased to 5.7 +/- 0.6 (+/- SE) cm/yr during the 6 months from a pretreatment rate of 3.4 +/- 0.2 cm/yr. Individual increments ranged from 30-94% above pretreatment growth rates. Three of the four children had significantly increased height increments, and two children achieved growth rates normal for their BA. Similarly, the growth rate in group II increased to 4.8 +/- 0.8 cm/yr from the pretreatment rate of 2.9 +/- 0.3 cm/yr. Individual increments ranged from 46-100% above pretreatment growth rates. Three children in group II had significantly increased height increments, and two children had normal growth rates for BA. The growth increments during L-dopa therapy occurred in the three children who had significant increases in hGH and somatomedin-C; of the three children with significant growth increments during bromocriptine therapy, two had increases in somatomedin-C, and one achieved a normal peak hGH value. hGH therapy caused further acceleration of growth velocities in the majority of patients. DA therapy had no significant effect on basal gonadotropin, gonadal steroids, T4, TSH, or morning cortisol concentrations in the majority of children compared with their pretreatment values. The following conclusions were reached. Dopaminergic therapy by itself, i.e. L-dopa or bromocriptine administration, induced linear growth in some hypopituitary children without significantly affecting basal concentrations of LH, FSH, gonadal steroids, T4, TSH, or cortisol. The effect this therapy could have in potentiating exogenous GH and/or possible GRH therapy is worthy of further investigation.