van Teunenbroek A, de Muinck Keizer-Schrama S M, Stijnen T, Mouton J W, Blum W F, Mercado M, Baumann G, Drop S L
Department of Pediatrics, Sophia Children's Hospital/Erasmus University Medical School, Rotterdam, The Netherlands.
Clin Endocrinol (Oxf). 1993 Jul;39(1):77-84. doi: 10.1111/j.1365-2265.1993.tb01754.x.
The optimal dose and frequency of GH administration in Turner's syndrome is unknown. There is some evidence that a schedule which mimics normal pulsatile GH secretion may be more effective than a single daily dose. We therefore wished to study the influence of the frequency of GH administration on 24-hour GH profiles and levels of other growth-related factors in Turner's syndrome.
Four weeks after initiation of 0.05 microgram/kg/day ethinyl oestradiol, we compared twice daily (b.i.d.-fractionated dose) with once daily (o.d.) s.c. injections of 6 IU GH/m2/day in a 2-week cross-over design with a 2-week washout interval. Each treatment period was concluded with 24-hour GH profile tests. Pretreatment plasma/serum levels of GH, IGF-I, binding proteins for GH (GHBP) and IGF-I (IGFBP-3) were used as a basis for comparison of the levels found after each regimen. A one-compartment open model was used for estimation of pharmacokinetic parameters.
Ten previously untreated girls with Turner's syndrome aged > or = 11 years.
Plasma levels of GHBP by standardized binding assay; GH, IGF-I, and IGFBP-3 serum/plasma levels by radioimmunoassay.
There were significantly higher maximum GH levels and a greater area under the curve with o.d. than with b.i.d. GH, while GH clearance was greater with b.i.d. The pharmacokinetic values with o.d. injections were in conformity with values for healthy and GH-deficient children. Pretreatment GHBP levels tended to be high compared with values in healthy prepubertal children. These levels decreased with GH therapy, significantly so with b.i.d. GH only. There was a significant increase in levels of IGF-I and IGFBP-3, irrespective of regimen. The IGF-I to IGFBP-3 ratio, a possible indicator of the growth response, rose significantly and comparably with both regimens. There was no consistent diurnal variation with either regimen in GHBP, IGF-I or IGFBP-3 levels. Four-hourly levels of GH, GHBP, IGF-I and IGFBP-3 were not correlated.
Although the 24-hour profiles differed during once or twice daily administration of the same total growth hormone dose, the diurnal pattern and mean levels of factors involved in the biological effects of GH are comparable for both regimens.
