Accuracy of final height prediction and effect of growth-reductive therapy in 362 constitutionally tall children.

Height reduction by means of treatment with high doses of sex steroids in constitutionally tall stature (CTS) is a well known, though still controversial, therapy. The establishment of the effect of such therapy is dependent on the height prediction method applied. We evaluated the reliability of various prediction methods together with the subjective clinician's judgment in 143 untreated children (55 boys and 88 girls) with CTS and the effect of height-reductive therapy in 249 tall children (60 boys and 159 girls) treated with high doses of sex hormones (cases). For this purpose, we compared the predicted adult height with the attained height at a mean adult age of 25 yr and adjusted the therapeutic effect for differences in bone age (BA), chronological age (CA), and height prediction between untreated and treated children. At the time of the height prediction, controls were significantly shorter, had more advanced estimated BAs (except for the BA according to Greulich and Pyle in boys), had lower target heights, and had smaller adult height predictions compared with the CTS patients (P < 0.05). At the time of the follow-up, CTS patients were significantly taller than controls for both boys and girls (P < 0.02). In controls, a large variability was found for the errors of prediction of the various prediction methods and in relation to CA. The prediction according to Bailey and Pinneau systematically overestimated adult height in CTS children, whereas the other prediction methods (Tanner-Whitehouse prediction and index of potential height) systematically underestimated final height. The mean (SD) absolute errors of the prediction methods varied from 2.3 (1.8) to 5.3 (4.3) cm in boys and from 2.0 (1.9) to 3.7 (3.5) cm in girls. They were significantly negatively correlated with CA (r = [minus 0.27 to -0.65; P < 0.05), except for the Tanner-Whitehouse prediction in boys, indicating that height prognosis is more reliable with increasing CA. In addition, experienced clinicians gave accurate height predictions by evaluating the growth chart of the child while taking into account various clinical parameters, such as CA, BA, and pubertal stage. The effect of sex hormone therapy was assessed by means of multiple regression analysis while adjusting for differences in height prediction, CA, and BA at the start of therapy between treated and untreated children. The mean (SD) adjusted effect varied from -0.5 (2.4) to 0.3 (1.4) cm in boys and from -0.6 (2.1) to 2.4 (1.4) cm in girls. The adjusted height reduction was dependent on the BA at the time of start of sex hormone therapy and was more pronounced when treatment was started at a younger BA. In boys, the treatment effect was significantly negative at BAs exceeding 14-15 yr. After cessation of therapy, additional mean (SD) growth of 2.4 (1.2) and 2.7 (1.1) cm was observed for boys and girls, respectively. The mean (SD) BA according to Greulich and Pyle at that time was 17.1 (0.7) yr for boys and 15.2 (0.6) yr for girls. These data demonstrate that height prediction in children with CTS is inaccurate in boys, but clinically acceptable in girls. With increasing age, height prognosis became more accurate. Overall, the height-reducing effect of high doses of sex hormones in children with CTS was limited, especially in boys. However, a significant effect of treatment was observed when treatment was started at BAs less than 14-15 yr, depending on the method of BA assessment. In boys, treatment appeared to be contraindicated at BAs older than 14-15 yr, because androgen administration caused extra growth instead of growth inhibition. It is recommended that referral should take place early, preferably before puberty, for careful monitoring of growth and height prediction. Moreover, it is recommended not to discontinue therapy before complete closure of the epiphyses of the hand has occurred to avoid considerable posttreatment growth.

Two-year results of treatment with methionyl human growth hormone in children with Turner syndrome. Dutch Growth Hormone Working Group.

Methionyl growth hormone (somatrem) in a daily dosage of 4 IU/m2 body surface area was administered to 16 girls with Turner syndrome. Low dose ethinyl estradiol (0.1 microgram/kg body weight) was added in girls aged 13 years or more. Mean (SD) height velocity increased from 3.4 (0.9) to 7.2 (1.7) and 5.3 (1.3) cm/year in the first and second year, respectively. Bone age advanced 1.8 years over 2 years and predicted adult height was increased. Apart from the occurrence of anti-GH antibodies there were no side effects. In conclusion, somatrem is an efficacious and safe therapy for short stature in Turner syndrome over a period of 2 years. Longer follow-up is needed before conclusions about its effect on final height can be drawn.

Effects of two years of methionyl growth hormone therapy in two dosage regimens in prepubertal children with short stature, subnormal growth rate, and normal growth hormone response to secretagogues. (Dutch Growth Hormone Working Group).

Thirty short, slowly growing children with normal plasma growth hormone response to standard provocation tests were randomly assigned to a group (n = 20) undergoing therapy with methionyl growth hormone, 2 IU/m2 subcutaneously once daily, (group 1) or a control group (n = 10, group 2). The mean (+/- SD) height velocity increment in group 1 was 3.0 +/- 1.9 cm/yr in the first year, compared with -0.2 +/- 0.7 cm/yr in group 2. Of the 18 children who completed the first year of treatment, 12 had a height velocity increment of more than 2 cm/yr and 11 of them continued treatment for a second year (group 1A). The remaining six children also reached height velocities greater than the mean for bone age, but because of a low height velocity increment they were termed nonresponders and their growth hormone dosage was increased to 4 IU/m2/day (group 1B). Of the 10 children in the control group, seven received authentic biosynthetic growth hormone in the second year of the study (group 2); the remaining three received no therapy (group 3). The mean height velocities (measured in centimeters per year) before and during the first and second years of therapy were 3.6, 7.6, and 6.1 in group 1A; 5.7, 6.9, and 7.3 in group 1B; 4.2, 4.0, and 6.7 in group 2; and 5.0, 4.9, and 5.2 in group 3. The effect of doubling the dosage was a further increase of 1.9 cm/yr. Bone age advance paralleled growth acceleration, resulting in an unchanged height standard deviation score for bone age and ambiguous results on final height prediction. Growth hormone therapy in such short children appears to be safe and efficacious in increasing growth velocity for 2 years, but its efficacy in terms of increasing final height is uncertain.