Effect of a Recombinant Human Growth Hormone Preparation on the Urinary 15Nitrogen Balance in Growth-Hormone-Deficient Children

Abstract

In 10 patients with idiopathic growth hormone (GH) deficiency (9 boys and 1 girl, aged 7.5–14.5 years, mean 12.1 ± 2.2 years), urinary ¹⁵N-balance studies were performed before and on recombinant hGH (2 × 3 IU/m² of body surface area subcutaneously on consecutive days). Before and on the 2nd day of recombinant hGH, 99% ¹⁵N-labeled ammonium chloride (0.05 g/kg, divided in 3 doses per day, corresponding to 389 ± 30 mg/m² of ¹⁵N) was administered and 24 h urine was collected. In urine, total nitrogen and the percentage of ¹⁵N were measured. From the ingested and excreted quantity, a urinary ¹⁵N balance was calculated. Mean ¹⁵N percentage from total N was 3.3 ± 0.5. In 9 patients, basal ¹⁵N balance was +79 ± 15 mg/m² or +2.9 ± 0.4 mg/kg. On recombinant hGH, it was +166 ± 16 mg/m² or +6.1 ± 0.6 mg/kg (p < 0.001). The recombinant hGH-induced positive ¹⁵N balance change was +87 ± 17 mg/m² or +3.2 ± 0.6 mg/kg. 1 patient with a higher basal ¹⁵N balance (+196 mg/m², +7.1 mg/kg) had no positive ¹⁵N balance change due to latent hypothalamic hypothyroidism. In previous similar studies with pituitary hGH, the change of ¹⁵N balance was +80 ± 27 mg/m² or +2.8 ± 1.1 mg/kg. It is concluded that the acute nitrogen-retaining effect of recombinant hGH is at least equal to that of pituitary hGH.

Stimulation of Nitrogen and Whole-Body Protein Metabolism in Growth Hormone-Deficient Children by Recombinant Human Growth Hormone: Relationship to Growth

“…Treatment with hGH has been shown to decrease uri nary nitrogen excretion in metabolic studies, using both classical metabolic and isotope (l5N) methods [4, [13][14][15][16][17]26], Previous work with rhGH has also demonstrated that the recombinant 22-kD hGH molecule exhibits the same biological behavior as pit-hGH when administered to GH-deficient children [27], The fall in urinary' nitrogen excretion in response to GH is mainly due to a decrease in the synthesis of urea [26,28] by shunting nitrogen from ureagenesis into growth-related processes via an increased hepatic synthesis and release of glutamate that is largely removed from the blood by sites located in the periphery [28].…”

“…Results of previous studies suggested that the response to long-term GH therapy may be better in patients with more marked metabolic responses to short-term GH administration [17,27], However, others have failed to discover a relationship between increases in HV during GH treatment and changes in nitrogen excre tion in response to GH administration [26,29,30], Simi larly, in our study, there was no correlation between the changes in nitrogen metabolism during short-term GH administration and the subsequent increase in HV during long-term GH therapy.…”

Whole Body Nitrogen Kinetics and Their Relationship to Growth in Short Children Treated with Recombinant Human Growth Hormone

“…The former approach is not new but the latter method has been little used (41)(42)(43)(44). Its potential advantages are several.…”

“…Small numbers of short children with growth hormone deficiency have been studied with I5N techniques in the past (41,42). More recently, Zachmann et al (43) used the I5N-retention test to show the biologic equivalency of recombinant and pituitary-derived hGH preparations.…”

Interrelations between Growth Hormone and Sex Hormones: Physiology and Therapeutic Consequences

“…After hGH. the balance became considerably more posi tive in the GH-dcficicnt patients [45], while in subjects with normal GH secretion, such as girls with Turner syn drome. it remained almost unchanged [46], When normal subjects were given testosterone, there was a marked l5N retention, which was in the same order of magnitude as that induced by hGH in the GH-deficient patients.…”