Once versus twice daily injections of growth hormone in children with idiopathic short stature M Phillip, E Hershkovitz, O Belotserkovsky, E Leiberman, Y Limoni and Z Zadik 1 Paediatric Diagnostic and Therapeutic Centre, Soroka University Medical Centre Beer-Sheva, Israel and Endocrine Unit 1 , Kaplan Hospital Rehovot, Israel Phillip M, Hershkovitz E, Belotserkovsky O, Leiberman E, Limoni Y, Zadik Z. Once versus twice daily injections of growth hormone in children with idiopathic short stature. Acta Pædiatr 1997; 87: 518–20. Stockholm. ISSN 0803–5253 The aim of this study was to compare the growth response of 22 short pre-pubertal children without growth hormone deficiency, treated with a single daily growth hormone injection (group A), to the growth response of 27 similar children, treated with the same daily dose divided into 2 subcutaneous injections per day (group B), for 1 y, in a randomized study. GH treatment significantly promoted growth parameters, height standard deviation score and height velocity standard deviation score in both groups. Serum insulin-like growth factor I was also increased. There were no significant differences in growth response, serum IGF-I levels, or the advance in bone age between the two study groups after 1 y of GH therapy. We conclude that twice daily s.c. growth hormone injections provide no advantages over once daily injection of the same dose in promoting the linear growth of short children without growth hormone deficiency. Dosage, growth hormone, short stature M Phillip, Paediatric Diagnostic and Therapeutic Centre, Soroka Medical Centre, P.O. Box 151, Beer- Sheva, Israel The wide availability of recombinant human growth hor- mone has promoted renewed interest in the safest and most effective dosages and schedules for growth hormone administration in children with growth hormone deficiency or with idiopathic short stature. In normal growing chil- dren, growth hormone is released into the circulation in episodic bursts throughout the day (1). Several studies have suggested that certain schedules of growth hormone administration such as evening administration and contin- uous subcutaneous administration, could simulate plasma GH concentrations observed under physiological condi- tions (2, 3). Moreover, daily GH administration was super- ior to three-times weekly GH treatment in promoting growth in growth hormone deficient children (4). The aim of this study was to compare the growth- promoting effects of a single daily dose of GH to that of the same dose divided into twice daily injections in prepubertal short children without GH deficiency. Subjects and methods Subjects Forty-nine short (-2 SD for age and gender) prepubertal children (40M), aged 6–12 y were treated with GH for 1 y. Pertinent clinical data of participants are given in Table 1. All children were healthy without any metabolic, endocrine, or chronic disease. None of the children was receiving chronic medication. All the children had a normal response to clonidine- or arginine-provocative tests (10 ng/ml). Protocol The participants were treated with Norditropin (Novo- Nordisk, Gentofte, Denmark) or Biotropin (Bio-Technology General, Israel) 0.1 U/kg/d. The children were randomly allocated to be treated with a single injection daily (group A, n ¼ 22) or two equal daily doses (group B, n ¼ 27). Only data from children who remained prepubertal throughout the treatment period (Tanner stage I) were evaluated in the study. Compliance to the treatment was evaluated by counting empty GH vials. Parental written consent was obtained, and the hospital human subjects committee approved the study. Serum IGF-I levels were measured after acid extraction and chromatography by radioimmunoassay kit (Incstar Corpora- tion, Stillwater, MN, USA). The intra-assay and interassay coefficient of variations were less than 10% and 15%, respectively. Z-scores for height, age and height velocity were com- puted at baseline and after 1 y of GH therapy for each child relative to the National Centre for Health statistics growth charts (5). Student’s t- test was used in the intra- and inter-group comparisons. The statistical analysis of IGF-I was performed on square root transformed data because this transformation gave the best approximation to a normal distribution. Results The groups were similar in their pretreatment age, bone age, HtSDS, HvSDS and IGF-I levels (Table 1). GH treatment Acta Pædiatr 87: 518–20. 1998 Scandinavian University Press 1998. ISSN 0803-5253