Abstract
The pathogenesis of growth failure in Turner's syndrome is not clear but might be attributed to a decreased sensitivity to insulinlike 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 (Et) 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+E-2 treated girls, circulating IGP-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+E-2 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