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/m 2 ⅐d; ϳ0.045 mg/kg/d), group B (first year, 4 IU/m 2 ⅐d; thereafter 6 IU/m 2 ⅐d), or group C (first year, 4 IU/m 2 ⅐d; second year, 6 IU/m 2 ⅐d; thereafter, 8 IU/m 2 ⅐d). After a minimum of 4 yr of GH treatment, at a mean age of 12.7 ؎ 0.7 yr, low dose micronized 17␤-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. (2), subnormal levels of GH and IGF-I have been reported (3, 4). It has been postulated that a diminished sensitivity for growth factors might explain their growth retardation (5, 6). Nevertheless, GH treatment in a supraphysiological dosage has been shown to accelerate growth (4, 7). Another clinical feature in most girls with TS is the absence of spontaneous pubertal development, for which estrogen substitution is necessary. Although GH treatment for short stature in TS is now an accepted treatment in many countries, reports on final height are inconsistent (8,9), and which dosage to use and which age to start puberty induction are issues of debate.Previously, we have demonstrated that long-term GH treatment in TS leads to normalization of height (4, 10). This study shows final height (FH) results in 60 girls with TS treated in a randomized dose-response trial comparing 3 dosage schedules. In addition, we show the effect of low dose estrogen treatment begun at a relatively ...

As Northern Europeans are currently the tallest people in the world, specific growth charts for girls with Turner's Syndrome from this area are needed. Based on height and weight measurements from 598 girls with Turner's Syndrome (372 from the Netherlands, 108 from Denmark, 118 from Sweden) not treated with growth-promoting substances and without signs of spontaneous puberty, we constructed growth charts for height-for-age, height-velocity-for-age, weight-for-age, weight-for-height and Body Mass Index for age. Reference tables and regression equations for mean and standard deviation are provided allowing calculation of Standard Deviation Scores. The height and height velocity curves show a low birth length, gradual deviation from the normal percentile curves without pubertal growth spurt, and a prolonged growth until the early 20s. Mean adult height was 146.9 +/- 7.8 cm. Mean weight-for-age was lower than in normal reference children but height-adjusted weight was higher, except in infancy and early childhood. Further studies are required on the factors influencing the weight-height relationship in Turner's Syndrome.

During long-term GH treatment in short SGA children, fat percentage SDS decreased and BMAD(LS) SDS increased. These effects of GH treatment were most prominent in children who started treatment at a younger age and in those with greater height gain during GH treatment. LBM SDS(height )remained around 0 SDS in GH-treated children, but declined to low normal values in untreated controls.

Three years of GH treatment in short children born SGA results in a normalization of height during childhood. Also, bone maturation increased proportionately to the height gain. At start, mean values of BMD and BMAD were significantly reduced but normalized during GH treatment. We did not find an indication to treat very short SGA children (H SDS < or = -3.00) with a higher GH dose. We rather suggest to start GH treatment at an early age in order to achieve a normal height before puberty starts.

A cephalometric study was performed in 19 patients with Turner's syndrome, aged 8.7–16.5 years. A lateral roentgencephalogram was taken before and after two years of treatment with biosynthetic growth hormone in a dose of 24 IU/m2/week. During two years of growth hormone treatment, the mandibular length increased mainly due to vertical growth. The initially posteriorly rotated mandible showed an anterior rotation, although the normal position was not reached. The other linear measurements and angles did not change during treatment. No indications were found for an increase in the disproportionate growth or for excessive chin growth as a sign of acromegaly during growth hormone treatment. In conclusion, growth hormone treatment in patients with Turner's syndrome resulted in an increase in mandibular length, mainly due to vertical growth of the ramus and in the anterior rotation of the mandible.

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Our study shows that high-dose GH treatment in short SGA children results in high serum GH and IGF-I levels in most children. We recommend monitoring IGF-I levels during GH therapy to ensure that these remain within the normal range.

To optimize the growth promoting effect of growth hormone (GH), 65 previously untreated girls with Turner syndrome (TS), chronological age (CA) 2-11 yr, were randomized into 3 dosage regimen groups: A, B, and C, with a daily recombinant-human GH dose during 4 study years of 4-4-4-4, 4-6-6-6, and 4-6-8-8 IU/m2 b.s. The first GH dosage increase in groups B and C resulted in a significantly higher mean height velocity (HV) compared with constant dose group A. During the third year, when the dose was raised again only in group C, mean HV was significantly higher in groups B and C than in group A, and in group C compared with group B. In year 4 only group C mean HV remained significantly higher than group A. The pattern of change in HSDSCA (Dutch-Swedish-Danish Turner references) was identical; however, in year 4 mean delta HSDSCA in group B also remained significantly higher than group A. After 4 yr GH treatment, the following was determined. 1) The mean delta HSDSCA was significantly higher for groups B and C compared with group A, but not significantly different between groups B and C. 2) Although significantly higher compared with estimated values for untreated Dutch girls with TS, bone maturation of the GH treated girls was not significantly different between groups. 3) It was positively related with the degree of bone age (BA) retardation at start of study and negatively with baseline CA. 4) Both the modified Index of Potential Height (mIPHRUS) and a recently developed Turner-specific final height (FH) prediction method (PTSRUS), based on regression coefficients for H, CA, and bone age, showed significant increases in mean FH prediction, without significant differences between groups. PTSRUS values were markedly higher than the mIPHRUS values. Dose dependency could be shown for the area under the curve (AUC) for GH, but delta HSDSCA was not linearly related with AUC. Baseline GH binding protein (BP) levels were in 84% of the cases within the normal age range; the decrease in mean levels after 6 months GH was not significant. Mean insulin-like growth factor I (IGF-I) and IGFBP-3 plasma levels increased significantly, without significant differences between groups. delta HSDSCA during GH was dependent on IGF-I plasma levels at baseline and during the study period, beta-0.002 and beta-0.0004. Thus, a stepwise GH-dosing approach reduced the "waning" effect of the growth response after 4 yr treatment without undue bone maturation. FH prediction was not significantly different between treatment groups. Irrespective of the GH dose used, initiation of GH treatment at a younger age was beneficial after 4 yr GH when expressed as actual cm gained or as gain in FH prediction, but was not statistically significant when expressed as delta HSDSCA over the study period.