An analysis of the clinical and cost effectiveness of growth hormone replacement therapy before and during puberty: should we increase the dose?

AIM: To investigate the influence of growth hormone (GH) on linear growth before and during puberty in children with GH deficiency. METHODS: We analysed the relationship between pubertal growth and GH dose in a large dataset of children (n = 236) with GH deficiency using multiple linear regression and multilevel modelling with repeated measures analysis. Additionally, we examined the cost benefit of increasing doses of GH during puberty. RESULTS: Multilevel modelling revealed a highly significant role for GH dose in the pre-pubertal period (p < 0.001), but a non-significant effect on height gain after pubertal onset (p = 0.32). Important predictors of height gain after puberty onset included gender, age at puberty and number of injections of GH/week. Cost analysis showed that in an average child use of high dose GH, at an extra EUR 5,925 (GBP 4,753/USD 7,538)/year, would produce a height gain of 0.80 cm/year (above baseline growth) pre-pubertally, compared to only 0.20 cm/year post-puberty onset. CONCLUSIONS: The influence of GH dose on height gain after puberty onset is at best a modest one. Cost analysis shows use of high doses of GH post-puberty onset has significant cost implications without providing a worthwhile gain in adult height for children with GH deficiency.

Effect of triiodothyronine supplementation on thyrotropin-releasing hormone-induced growth hormone secretion in sex-linked dwarf and normal chicks.

The effect of a dietary triiodothyronine (T3) supplement, of either 0.1 or 0.5 microgram/g of feed, was studied on the thyrotropin-releasing hormone (TRH)-induced growth hormone (GH) secretion in sex-linked dwarf (dw) or normal (Dw) chicks of both sexes. In normal chicks, 0.1 microgram/g T3 decreased plasma GH levels before TRH as well as the GH increase after TRH, and 0.5 microgram/g T3 totally suppressed any response to TRH, either at 4 or at 7 weeks of age. Dwarf chicks were more sensitive to TRH than normals when receiving either 0 or 0.1 microgram/g T3; 0.5 microgram/g T3 abolished the difference between genotypes at 4 weeks of age but not so clearly at 7 weeks of age, where dwarf females showed a slight but still significant GH increase after TRH. Interactions between genotype, TRH injection, and T3 treatments were often significant at 4 weeks of age and even more at 7 weeks of age. Dwarf chicks receiving 0.1 microgram/g T3, expected to have normal plasma T3 levels, showed a higher GH response after TRH. This suggests that other hormones may be involved in the regulation of this response, particularly IGF-I, which is known to remain at a low level in T3-treated dwarf chicks.