Nine Months' Subcutaneous Therapy with Synthetic Growth Hormone Releasing Factor in Children with Short Stature

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Abstract
: The growth promoting potential of GRF(1–29)NH2 was studied in nine boys with short stature over three periods of 3 months. Their short stature was due to partial hGH deficiency/hGH neurosecretory dysfunction and was diagnosed by arginine and insulin stimulation tests and hGH nocturnal profiles. Four patients (Group I) were given GRF, 3–4 μg/kg s.c. b.d. during the first period of 3 months, and after an interval of 1 month, the same dose once daily during the second treatment period of 3 months. Five patients (Group II) were given GRF, 3–4 μg/kg s.c., once daily during the first and b.d. during the second 3 months of therapy. After a second interval of 1 month without any GRF treatment, the third 3‐month period for both groups consisted of one daily injection of GRF, 8–10 μg/kg s.c. at 19.00 hours. Total body height and lower leg length were measured by stadiometry and knemometry, respectively. GRF intravenous bolus tests were performed in each patient following fasting, before and at the end of the first and second 3‐month periods. Serum IGF–1 and urinary hydroxyproline excretion were determined monthly. Stadiometric growth rate, determined over the whole study period of 11 months including the treatment‐free intervals, increased from 4.92 cm/year to 5.97 cm/year (p>0.05). Mean knemometric growth rates increased from 0.28 mm/week before therapy, to 0.35 mm/week during the one injection/day period at low dose, to 0.39 mm/week (p<0.05) during the b.d. period, and to 0.40 mm/week during the last 3 months of high‐dose GRF given once daily. IGF‐1 levels increased during GRF therapy and were highest during the high‐dose period. Urinary hydroxyproline excretion and peak plasma hGH levels after intravenous GRF did not correlate with the GRF dose administered in any of the treatment phases. GRF dose and frequency of administration were probably suboptimal in this group of patients; higher dose frequencies might be necessary to achieve growth rates comparable with those observed during hGH substitution therapy.