IGF-I resistance and Turner's syndrome.
The pathogenesis of growth failure in Turner's syndrome is not clear but might be attributed to a decreased sensitivity to insulin-like growth factor-I (IGF-I) in distinct cell lines or to its reduced autocrine/paracrine action. Growth hormone (GH) therapy leads to increments in IGF-I levels and to growth acceleration. In order to evaluate the pattern of overcoming IGF-I resistance through childhood and adolescence, we measured IGF-I in 78 girls with Turner's syndrome aged 4.6-18.3 years on 160 occasions without or during GH (1 IU/kg/week [0.33 mg/kg/week]) or GH+estradiol (E2) therapy and compared them with local IGF-I standards. In untreated patients, IGF-I levels were low normal (-0.71+/-0.18 SDS, mean +/- SEM). In both GH or GH+E2 treated girls, circulating IGF-I levels were persistently supraphysiological (GH only: +3.61+/-0.23 SDS; GH + estradiol: +3.18+/-0.31 SDS). The age-dependent pattern of IGF-I secretion was conserved but the pubertal increase occurred earlier. The highest standardized IGF-I levels were observed at age 8.5-9.4 years (+6.62+/-1.00 SDS) and 9.5-10.4 years (+5.61+/-1.03 SDS). GH+E2 substitution had no additional effect on circulating IGF-I. We conclude that high IGF-I levels are needed to overcome the IGF-resistance in Turner's syndrome. They reflect the action of GH therapy but not of estrogens. The earlier pubertal increase of IGF-I might be caused by exaggerated adrenal androgens.
Lebl
J
J
Department of Pediatrics, 3rd Faculty of Medicine, Charles University, Prague, Czech Republic. lebl@fnkv.cz
Průhová
S
S
Zapletalová
J
J
Pechová
M
M
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D004351:Drug Resistance; D004958:Estradiol / Q000627:therapeutic use; D005260:Female; D006128:Growth; D019382:Human Growth Hormone / Q000627:therapeutic use; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000378:metabolism / Q000494:pharmacology*; D011627:Puberty; D014424:Turner Syndrome / Q000188:drug therapy / Q000503:physiopathology*
D019382:Human Growth Hormone; D004958:Estradiol; D007334:Insulin-Like Growth Factor I