1 SHORT TERY ESDOCRINE, METABOLIC AND GROWTH EFFECTS OF GRF 1-29 TREATMENT IN GRF-DEFICIENT SHORT CHILDREN

Abstract

To assess the growth promoting potential of GRF, we studied so far 4 boys (age 5 - 13 yrs) with short stature (height SDS -2.2 to -3.8) due to partial HGH deficiency, diagnosed by arginin and insulin stimulation tests and nocturnal HGH secretion profile. None of them received any prior hormonal therapy. Before, after 2 weeks and at the end of 12 weeks of GRF therapy, each child had an i.v. GRF 1-29 bolus test (2 μg/kg, AM, fasted) with determination of plasma HGH, basal serum somatomedin C (SMC) and urinary hydroxyproline excretion (OHP). Lower leg length, measured by knemometry was determined under standard conditions once a week for 3 - 15 months before and twice a week during GRF treatment. Synthetic GRF 1-29 was given s.c. in a dose of 3 - 4 μg/kg b.i.d., at 0700 and 1900 h. After 2 weeks of GRF treatment, the peak HGH response after GRF i.v. stimulation increased from (means) 31 to 74 ng/ml. SMC increased from 1.07 to 2.25 IU/ml and OHP from 119 to 210 μg/mg creatinine. Knemometric growth rate increased by 1.6 to 2.8-fold from (means) 0.44 to 0.93 mm/week. Such increased growth rates were never observed in any of these patients during the pretreatment period. The knemometric growth patterns during CRF therapy appear to be similar to those observed during the initiation of HGH substitution therapy. Our preliminary data suggest that GRF 1-29, given s.c. twice daily, induces longitudinal growth via increased endogenous HGH and SMC secretion and thus may be of therapeutic value in GRF deficient short children.