Effect of Growth Hormone and Oxandrolone Treatment on Glucose Metabolism in Turner Syndrome

Abstract

In 18 girls with Turner syndrome, glucose tolerance was studied before treatment and after 6 and 24 months of growth-promoting treatment with recombinant human growth hormone (24 IU/m²/week; 8 mg/m²/week) and oxandrolone (0.06 mg/kg/day), as well as after termination of the treatment. One girl developed an overt non-ketotic diabetes mellitus 50 months after termination of treatment. The results of the remaining 17 girls in whom the effect of treatment on glucose metabolism was reversible are presented as a group. Their median age at the beginning of the treatment was 10.4 years (range 6.9–15.9), and 15.0 years (range 12.1–19.9) at the final assessment. There was a moderate, but not significant rise in fasting glucose throughout the course of the longitudinal study. At oral glucose tolerance testing (oGTT), the area under the curve for glucose rose significantly (p = 0.013) during the period of treatment and returned to the basic value thereafter. Fasting insulin and especially the integrated insulin values (AUCi; area under the curve for insulin) during oGTT increased continuously during treatment, declined after termination of treatment but were still significantly (p = 0.04) higher than before treatment. Considering the fact that in untreated girls with Turner syndrome the fasting insulin and the AUCi increase with age, one can conclude that the insulinaemia returned to age-specific norm after termination of treatment. Thus the effect of a combined growth hormone and oxandrolone growth-promoting treatment on glucose metabolism was fully reversible in these 17 girls with Turner syndrome.

Effect of Discontinuation of Long-Term Growth Hormone Treatment on Carbohydrate Metabolism and Risk Factors for Cardiovascular Disease in Girls with Turner Syndrome

“…Furthermore, after ending GH treatment, insulin levels and the indices for relative insulin resistance (30Ј and 120Ј ratios for insulin/glucose) fell but only to a point above pretreatment levels. Similar results have been found previously in children with idiopathic short stature and in girls with TS after discontinuation of GH treatment (18,19). Moreover, we show that stimulated insulin levels after discontinuation were comparable with normal postpubertal girls.…”

Diabetes and lipid disorders

“…Fasting glucose levels have been found unchanged during GH treatment in most studies [21][22][23][24][25][26], but increased in others [27], while a dose response study only found increased fasting glucose in the group that received the highest GH doses [25]. The values returned to baseline values after termination of GH [25].…”

“…One explanation could be reduced insulin sensitivity. The insulin levels decrease after termination of GH, but do not return to levels as low as before treatment [21,25,28]. This could be an irreversible effect of GH, but could also be due to the fact that both fasting insulin and area under the curve for insulin (AUC I ) increases with age, particularly during adolescence [31].…”

“…Most studies find a significant increase of glucose levels (OGTT) during GH treatment [21,[27][28][29]. Other studies find similar glucose levels despite decreased insulin sensitivity (ISI comp ) before and after GH [23][24][25], with a return to pre-treatment levels 6 months after GH discontinuation [28].…”

“…There have been reports of girls developing diabetes during GH treatment [32] or 50 months after termination of GH and Oxandrolon treatment [21].…”