EFFECT OF GROWTH-HORMONE ADMINISTRATION FREQUENCY ON 24-HOUR GROWTH-HORMONE PROFILES AND LEVELS OF OTHER GROWTH-RELATED PARAMETERS IN GIRLSWITH TURNERS-SYNDROME

OBJECTIVE The optimal dose and frequency of GH administration in Turne r's syndrome is unknown. There is some evidence that a schedule which mimics normal pulsatile GH secretion may be more effective than a sing le daily dose. We therefore wished to study the influence of the frequ ency of GH administration on 24-hour GH profiles and levels of other g rowth-related factors in Turner's syndrome. DESIGN Four weeks after in itiation of 0.05 mug/kg/day ethinyl oestradiol, we compared twice dall y (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 in terval. Each treatment period was concluded with 24-hour GH profile te sts. Pretreatment plasma/serum levels of GH, IGF-I, binding proteins f or GH (GHBP) and IGF-I (IGFBP-3) were used as a basis for comparison o f the levels found after each regimen. A one-compartment open model wa s used for estimation of pharmacokinetic parameters. SUBJECTS Ten prev iously untreated girls with Turner's syndrome aged greater-than-or-equ al-to 11 years. MEASUREMENTS Plasma levels of GHBP by standardized bin ding assay; GH, IGF-I, and IGFBP-3 serum/plasma levels by radioimmunoa ssay. RESULTS 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 c learance 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 va lues in healthy prepubertal children. These levels decreased with GH t herapy, 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, r ose significantly and comparably with both regimens. There was no cons istent 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 co rrelated. CONCLUSIONS Although the 24-hour profiles differed during on ce or twice daily administration of the same total growth hormone dose , the diurnal pattern and mean levels of factors involved in the biolo gical effects of GH are comparable for both regimens.