Carbohydrate metabolism during long-term growth hormone (GH) treatment andafter discontinuation of GH treatment in girls with turner syndrome participating in a randomized dose-response study

To assess possible side-effects of GH treatment with supraphysiological dos es on carbohydrate (CH) metabolism in girls with Turner syndrome (TS) durin g long term GH treatment and after discontinuation of GH treatment, the res ults of oral glucose tolerance tests and hemoglobin A,, measurements were a nalyzed in 68 girls with TS participating in a randomized dose-response tri al. These previously untreated girls, aged 2-11 yr, were randomly assigned to 1 of 3 GH dosage groups: group A, 4 IU/m(2). day (similar to 0.045 mg/kg . day); group B, first year,4 IU/m(2). day; thereafter, 6 IU/m(2). day (si milar to 0.0675 mg/kg . day); group C, first year, 4 IU/m(2). day; second g ear, 6 IU/m(2). day; thereafter, 8 IU/m(2). day (similar to 0.090 mg/kg . d ay). After the first 4 yr, girls 12 yr of age or older started with 5 mu g/ kg BW day 17 beta-estradiol for induction of puberty. To assess the effects of long term high dose GH treatment on CH metabolism, the 7-yr data from t he oral glucose tolerance tests in 9 girls of group C were evaluated (group C1). To determine whether the changes in CH metabolism during GH treatment would persist after discontinuation of GH treatment, the data for 28 girls who had reached adult height (group An = 9; group B, n = 10; group C, n = 9) were evaluated at baseline, after 4 yr of GH treatment, and 6 months aft er discontinuation of GH. Seven-year data for group C1 showed that glucose levels did not significant ly change during GH treatment, whereas fasting insulin levels as well as gl ucose-induced insulin levels increased significantly. The data for the 28 g irls who were treated with GH for a mean (sn) period of 85.3 (13.3) months demonstrated that the GH-induced higher insulin levels decreased to Values close to or equal to pretreatment Values after discontinuation of GH treatm ent. Changes in CH variables were not significantly related to the GH dose. Hemoglobin A(1c) levels never showed an abnormal value. The prevalence of impaired glucose tolerance was low, and none of the girls developed diabete s mellitus. In conclusion, long term GH treatment with dosages up to 8 IU/m(2) day in g irls with TS has no adverse effects an glucose levels, but induced higher l evels of insulin, indicating relative insulin resistance. The increased ins ulin levels during long term GH treatment decreased after discontinuation o f GH treatment to values close to or equal to pretreatment values. Although the reversibility of the effects of long term GH is reassuring the consequ ence of long term hyperinsulinism is still unknown.