Carbohydrate metabolism during growth hormone treatment and after discontinuation of growth hormone treatment in girls with Turner syndrome treated with once or twice daily growth hormone injections

OBJECTIVE To assess possible side-effects of treatment with supraphysiological GH dosages on carbohydrate (CH) metabolism in girls with Turner syndrome (TS) during GH treatment until adult height is reached as well as after discontinuation of GH treatment. DESIGN In a prospective, randomized injection frequency-response study, the effect of GH treatment in combination with low dose ethinyl oestradiol on CH metabolism was evaluated, comparing twice daily (BID) with once daily (OD) injections of a total GH dose of 6 U/m(2)/day until adult height was reached. PATIENTS Nineteen untreated girls with TS, mean (SD) pretreatment age 13.3 (1.7) (range 11.0-17.6) year. MEASUREMENTS Glucose and insulin concentrations during oral glucose tolerance tests (OGTT) were measured before and during GH treatment, as well as at 6 months after discontinuation of GH treatment. RESULTS GH treatment was discontinued after a mean of 43 (range 27-57) months. In one of the 19 girls, a different girl at each time point before, during and after discontinuation of GH treatment, the glucose response to OGTT after 120 minutes was above 7.8 mmol/l but below 11.1 mmol/l, indicating impaired glucose tolerance. None of the girls developed diabetes mellitus. Fasting glucose levels did not significantly change during, or after discontinuation of GH treatment. The 3 h area under the curve for time-concentration adjusted for fasting levels during the OGTT for glucose showed a significant decrease during GH treatment. In contrast to the glucose levels, GH treatment induced considerably higher insulin levels compared to pretreatment values. After discontinuation of GH insulin levels decreased to values comparable with pretreatment levels. None of these observed changes were different between the GH injection frequency groups. The changes in CH variables during and after discontinuation of GH were not related to changes in body mass index. CONCLUSIONS GH treatment with 6 U/m(2)/day in combination with low dose ethinyl oestradiol in girls with Turner syndrome aged greater than or equal to 11 years did not negatively influence glucose levels, but induced higher levels of insulin indicating relative insulin resistance. These changes in insulin levels were independent of the frequency of the GH injections (once vs. twice daily). After discontinuation of GH treatment, insulin values decreased to baseline levels.