title: 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.
authors.affiliation: Pediatric Department, University of Vienna, Austria.
authors.forename: G
authors.initials: G
authors.lastname: Haeusler
authors.forename: K
authors.initials: K
authors.lastname: Schmitt
authors.forename: P
authors.initials: P
authors.lastname: Blümel
authors.forename: E
authors.initials: E
authors.lastname: Plöchl
authors.forename: T
authors.initials: T
authors.lastname: Waldhör
authors.forename: H
authors.initials: H
authors.lastname: Frisch
mesh_terms: D000293:Adolescent; D000375:Aging; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D005260:Female; D013006:Growth Hormone / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007328:Insulin / Q000097:blood*; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000378:metabolism*; D010074:Oxandrolone / Q000008:administration & dosage / Q000627:therapeutic use*; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism*; D013739:Testosterone / Q000097:blood; D014424:Turner Syndrome / Q000097:blood / Q000188:drug therapy*
chemical_list: D007328:Insulin; D018970:Insulin-Like Growth Factor Binding Protein 1; D012738:Sex Hormone-Binding Globulin; D013739:Testosterone; D010074:Oxandrolone; D013006:Growth Hormone