INSULIN, INSULIN-LIKE GROWTH FACTOR-BINDING PROTEIN-1, AND SEX HORMONE-BINDING GLOBULIN IN PATIENTS WITH TURNERS-SYNDROME - COURSE OVER AGEIN UNTREATED PATIENTS AND EFFECT OF THERAPY WITH GROWTH-HORMONE ALONEAND IN COMBINATION WITH OXANDROLONE

We have studied the course over age of fasting insulin, sex hormone-bi nding globulin (SHBG), and insulin-like growth factor (IGF)-binding pr otein-1 (IGFBP-1) in untreated children with Turner's syndrome (TS) an d 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 IGFB P-1 decreased with chronological age, and serum concentrations of thes e parameters were in the normal range. SHBG and IGFBP-1 were not coreg ulated by insulin in TS as previously reported under physiological con ditions; IGFBP-1 was inversely correlated with insulin, but SHBG was n ot, and neither parameter was correlated with the other. Twenty-eight patients were further investigated 3, 6, 9, and 12 months after the st art of GH monotherapy (12-18 IU/m(2) . week) and 3, 6, 9, and 12 month s after the addition of oxandrolone (0.0625 mg/kg . day; n = 16). Ther e was a significant increase in insulin levels during GH monotherapy a nd a further increase during combination therapy, with peak levels 3 m onths after the start of GH and combination therapy, respectively. Bot h SHBG and IGFBP-1 levels decreased significantly during GH monotherap y, with a further dramatic decrease after the addition of oxandrolone. Levels of free testosterone were unaffected by both treatment regimen s. 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 concentr ations during GH monotherapy. In conclusion, there were no abnormaliti es in serum concentrations of insulin, SHBG, and IGFBP-1 in untreated patients that could help to explain the retarded growth in patients wi th TS. All effects of combined GH and oxandrolone therapy on endocrine parameters such as insulin, SHBG, IGFBP-1 and IGF-I mimic the endocri ne pattern normally observed during the pubertal growth spurt. Our dat a 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 patie nts with TS.