Growth response and levels of growth factors after two years growth hormone treatment are similar for a once and twice daily injection regimen in girls with Turner syndrome. (Dutch Working Group on Growth Hormone).
GH is known to improve height velocity in girls with Turner syndrome (TS) but the optimal dosage regimen has yet to be defined.


OBJECTIVE
We attempted to improve the growth response by trying to mimic normal pulsatile GH secretion more closely.


METHODS
In a 2-year study the effect of fractionated twice daily (BID) was compared with once daily (OD) s.c. injections of a total GH dose of 6 IU/m2/day. BID injections were administered as two-thirds at bedtime and one-third in the morning. The subjects concurrently received low dose ethinyl oestradiol (0.05 mg/kg/day, orally).


METHODS
Nineteen girls with TS aged 11 years or over, who were previously involved in a 10-week GH cross-over study.


METHODS
Height and bone age were evaluated in relation to untreated Turner reference data. Final height (FH) was predicted using the Bayley and Pinneau (BP) method, the modified index of Potential Height (mIPHRUS), and a recently developed Turner-specific method (PTSRUS) based on regression coefficients for height (H), chronological age (CA) and bone age (BA). Plasma levels of GH, GHBP, IGF-1, and IGFBP-3 were determined by RIA.


RESULTS
After 2 years treatment the growth response expressed as HV, HVSDS, the change in HSDSCA, the gain in height over estimated untreated values and in FH prediction all showed significant improvements. Although mean values tended to be higher with OD injections, significant differences between groups were not found. Bone maturation was similar between groups and compared with untreated estimated values. Independent of treatment group, the change in HSDSCA after 2 years of GH treatment was related negatively to the baseline CA and HSDSCA, and positively to BA delay at baseline. After 18 months of GH treatment the significant decrease in GHBP plasma levels observed after 6 months was no longer significant. In contrast, IGF-1 and IGFBP-3 plasma levels and the IGF-1 to IGFBP-3 ratio increased significantly during 18 months GH therapy. None of these growth related factors showed a difference between groups in their 18 months change. Relevant side-effects were not observed during the first 2 years of GH treatment.


CONCLUSIONS
The present growth data are in conformity with the data of the earlier 24-hour GH profiles. The growth response and plasma levels of growth related factors after 2 years GH on a total dose of 6 IU/m2/day in combination with low-dose oestrogens were not significantly different between the once daily and the twice daily GH injection regimen.
van Teunenbroek
A
A
Department of Pediatrics, Sophia Children's Hospital, Rotterdam, The Netherlands.
de Muinck Keizer-Schrama
S
S
Stijnen
T
T
Waelkens
J
J
Wit
J M
JM
Vulsma
T
T
Gerver
W J
WJ
Reeser
H
H
Delemarre-van de Waal
H
H
Jansen
M
M
Drop
S
S
D000293:Adolescent; D002352:Carrier Proteins / Q000097:blood; D018592:Cross-Over Studies; D004334:Drug Administration Schedule; D004997:Ethinyl Estradiol / Q000627:therapeutic use; D005260:Female; D006128:Growth / Q000187:drug effects*; D013006:Growth Hormone / Q000008:administration & dosage* / Q000097:blood / Q000627:therapeutic use; D006133:Growth Substances / Q000097:blood*; D006801:Humans; D007275:Injections, Intravenous; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D012044:Regression Analysis; D014424:Turner Syndrome / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology
D002352:Carrier Proteins; D006133:Growth Substances; D018972:Insulin-Like Growth Factor Binding Protein 3; D004997:Ethinyl Estradiol; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; C051815:somatotropin-binding protein