Turner Syndrome, Insulin Sensitivity and Growth Hormone Treatment

Abstract

Mild insulin resistance appears to be an early metabolic defect in girls with Turner syndrome (TS). Impaired glucose tolerance has been reported in 10–34% of patients with TS, and type 2 diabetes mellitus is 2–4 times more common and occurs at a younger age in girls with TS than in the general population. In a mixed longitudinal and cross-sectional study, we analysed carbohydrate tolerance and insulin sensitivity in 46 children and adolescents with TS who reached their final height after long-term treatment (mean 6.3 ± 2.5 years) with growth hormone (GH: 0.33 mg/kg/week [0.05 mg/kg/day]), and in 36 of these patients who were followed-up after the cessation of GH therapy (mean follow-up, 2.6 ± 2.5 years; range, 1–9.5 years). Patients with TS were compared with an age-matched female control group. Insulin sensitivity appeared to be lower in patients with TS than in controls, even before the start of GH therapy. As in controls, insulin sensitivity decreased with age in patients with TS, and levels were lower in those aged >12 years than in those aged <12 years. GH therapy resulted in good catch-up growth in patients with TS, with final height significantly higher than projected height evaluated before the initiation of GH therapy. Insulin sensitivity increased after 7–8 years of therapy and, on the cessation of GH therapy, returned to pre-treatment levels. The increase in insulin sensitivity seen on the cessation of GH therapy appeared to be influenced negatively by body mass index and triglyceride levels, and correlated positively with the number of years since cessation of GH therapy. As in the general population, excess weight and an abnormal lipid profile, in particular excess triglyceride levels, worsened insulin sensitivity. In conclusion, our study confirms that GH therapy reduces insulin sensitivity, but at its cessation there is a return to pre-therapy values. We therefore report a progressive improvement in carbohydrate tolerance and insulin function in patients with TS, despite an increase in age.

Effect of Oxandrolone on Glucose Metabolism in Growth Hormone-Treated Girls with Turner Syndrome

“…In accordance with our findings, several other studies found that insulin sensitivity decreased during GH therapy [6,9,26,27,28]. These studies showed that after discontinuing GH therapy, insulin sensitivity indices either returned to pre-treatment levels [27], or decreased to values just above baseline but comparable with those of healthy post-pubertal girls [29]. In our study, the indices returned to pretreatment levels, confirming the reversibility of the effect of GH on insulin sensitivity.…”

TRANSITION IN ENDOCRINOLOGY: Treatment of Turner's syndrome during transition

“…During the last decade many studies showed growth hormone (GH) treatment as safe and effective for growth promotion in TS. Table 2 presents the results of growth therapy and indicates positive, negative and neutral determinants of therapy effectiveness as well as consequences and side effects of hormonal therapy in the analysed articles (4,5,7,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50).…”

“…Elevated levels of IGF1 should be avoided in view of the potential long-term adverse effects. Also careful monitoring for benign intracranial hypertension, scoliosis, slipped capital femoral epiphysis, body proportion, abnormal glucose tolerance and reduced insulin sensitivity is recommended (41,43,50,107).…”

Insulin resistance in adolescents with Turner syndrome is comparable to obese peers, but the overall metabolic risk is lower due to unknown mechanism

“…However, there is a worth mentioning aspect of the present study's design. Previous studies showed increased metabolic risk in TS girls/woman in comparison to the healthy, normal-weight patients [3,[17][18][19][20]. The present study is the first to date comparing markers of the metabolic risk in patients with TS on growth hormone treatment and obese peers.…”