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Department of Pediatrics, Division of Endocrinology, Erasmus University MC/Sophia Children’s Hospital (Y.K.v.P., S.M.P.F.d.M.K.-S., T.C.J.S., S.L.S.D.), 3015 GJ Rotterdam, The Netherlands; Department of Epidemiology and Biostatistics, Erasmus University MC (T.S.), 3015 GJ Rotterdam, The Netherlands; Wilhelmina Children’s Hospital (M.J.), 3584 EA Utrecht, The Netherlands; Sint Radboud University Hospital (B.J.O.), 6523 GA Nijmegen, The Netherlands; Free University Hospital (J.J.G.H.-N.), 1081 HV Amsterdam, The Netherlands; Academic Medical Center/Emma Children’s Hospital (T.V.), 1105 AZ Amsterdam, The Netherlands; Medical University Center (W.H.S.), 2333 ZA Leiden, The Netherlands; Beatrix Children’s Hospital (C.W.R.), 9713 GZ Groningen, The Netherlands; Juliana Children’s Hospital (H.M.R.), 2566 MJ The Hague, The Netherlands; Academic Hospital (W.J.G.), 6229 HX Maastricht, The Netherlands; Rijnland Hospital (J.J.G.), 2353 GA Leiderdorp, The Netherlands; and Canisius-Wilhelmina Hospital (C.R-W.), 6532 SZ Nijmegen, The Netherlands
Address all correspondence and requests for reprints to: Y. K. van Pareren, M.D., Erasmus MC/Sophia Children’s Hospital, Department of Pediatrics, Division of Endocrinology, Dr. Molewaterplein 60, 3015 GJ Rotterdam, The Netherlands. E-mail: vanpareren{at}zonnet.nl.
Although GH treatment for short stature in Turner syndrome is an accepted treatment in many countries, which GH dosage to use and which age to start puberty induction are issues of debate. This study shows final height (FH) in 60 girls with Turner syndrome treated in a randomized dose-response trial, combining GH treatment with low dose estrogens at a relatively young age.
Girls were randomly assigned to group A (4 IU/m2·d; 
0.045 mg/kg/d), group B (first year, 4 IU/m2·d; thereafter 6 IU/m2·d), or group C (first year, 4 IU/m2·d; second year, 6 IU/m2·d; thereafter, 8 IU/m2·d). After a minimum of 4 yr of GH treatment, at a mean age of 12.7 ± 0.7 yr, low dose micronized 17ß-estradiol was given orally. After a mean duration of GH treatment of 8.6 ± 1.9 yr, FH was reached at a mean age of 15.8 ± 0.9 yr. FH, expressed in centimeters or SD score, was 157.6 ± 6.5 or -1.6 ± 1.0 in group A, 162.9 ± 6.1 or -0.7 ± 1.0 in group B, and 163.6 ± 6.0 or -0.6 ± 1.0 in group C. The difference in FH in centimeters, corrected for height SD score and age at start of treatment, was significant between groups A and B [regression coefficient, 4.1; 95% confidence interval (CI), 1.4, 6.9; P < 0.01], and groups A and C (coefficient, 5.0; 95% CI, 2.3, 7.7; P < 0.001), but not between groups B and C (coefficient, 0.9; 95% CI, -1.8, 3.6). Fifty of the 60 girls (83%) had reached a normal FH (FH SD score, more than -2). After starting estrogen treatment, the decrease in height velocity (HV) changed significantly to a stable HV, without affecting bone maturation (change in bone age/change in chronological age). The following variables contributed significantly to predicting FH SD score: GH dose, height SD score (ref. normal girls), chronological age at start of treatment, and HV in the first year of GH treatment. GH treatment was well tolerated.
In conclusion, GH treatment leads to a normalization of FH in most girls, even when puberty is induced at a normal pubertal age. The optimal GH dosage depends on height and age at the start of treatment and first year HV.
This work was supported by Novo Nordisk A/S (Bagsvaerd, Denmark).
Abbreviations: BA, Bone age; CA, chronological age; CI, confidence interval; FH, final height; HV, height velocity; mPAH, modified projected adult height; TH, target height; TS, Turner syndrome.
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