Insulin, insulin-like growth factor-binding protein-1, and sex hormone-binding globulin in patients with Turner's syndrome: course over age in untreated patients and effect of therapy with growth hormone alone and in combination with oxandrolone.

Abstract

We have studied the course over age of fasting insulin, sex hormone-binding globulin (SHBG), and insulin-like growth factor (IGF)-binding protein-1 (IGFBP-1) in untreated children with Turner's syndrome (TS) and measured the course of these parameters during therapy with GH alone and in combination with oxandrolone. Forty patients with TS, aged 3.7-16.4 yr, were investigated before any therapy. Fasting insulin levels increased significantly with chronological age, whereas SHBG and IGFBP-1 decreased with chronological age, and serum concentrations of these parameters were in the normal range. SHBG and IGFBP-1 were not coregulated by insulin in TS as previously reported under physiological conditions; IGFBP-1 was inversely correlated with insulin, but SHBG was not, and neither parameter was correlated with the other. Twenty-eight patients were further investigated 3, 6, 9, and 12 months after the start of GH monotherapy (12-18 IU/m2-week) and 3, 6, 9, and 12 months after the addition of oxandrolone (0.0625 mg/kg.day; n = 16). There was a significant increase in insulin levels during GH monotherapy and a further increase during combination therapy, with peak levels 3 months after the start of GH and combination therapy, respectively. Both SHBG and IGFBP-1 levels decreased significantly during GH monotherapy, with a further dramatic decrease after the addition of oxandrolone. Levels of free testosterone were unaffected by both treatment regimens. IGFBP-1 was inversely correlated with insulin concentrations at all time points after the start of therapy. SHBG was inversely correlated with IGF-I concentrations, but showed no relation to insulin concentrations during GH monotherapy. In conclusion, there were no abnormalities in serum concentrations of insulin, SHBG, and IGFBP-1 in untreated patients that could help to explain the retarded growth in patients with TS. All effects of combined GH and oxandrolone therapy on endocrine parameters such as insulin, SHBG, IGFBP-1 and IGF-I mimic the endocrine pattern normally observed during the pubertal growth spurt. Our data confirm the importance of insulin in the regulation of IGFBP-1, but do not point to a coregulation of IGFBP-1 and SHBG by insulin in patients with TS.