Page 72 - Slipped Capital Femoral Epiphysis Pathogenetic and Clinical aspects

Chapter 4
In the largest US registry, the National Cooperative Growth Study (NCGS), the use of recombinant human growth hormone (rhGH) treatment in children with short stature did not appear to measurably increase the risk for SCFE [25]. There are hardly any data to determine the role of abnormalities in this axis in SCFE.
In conclusion, the GH-IGF-1 axis is a major growth regulator throughout childhood and adolescence, has direct and indirect influence on the physis and is regulated by different hormones and growth factors itself.
Sex steroids in puberty and SCFE The androgen testosterone and the oestrogen estradiol are the main steroid hormones that are produced by the testes and ovaries, respectively. Androgens can be converted to oestrogens in other tissues such as liver, fat or muscle, which is especially important in overweight boys and men. In addition to the gonads, the adrenal glands produce androgens that have a low androgen activity compared to testosterone.
Androgens and oestrogens are responsible for the pubertal growth spurt. The subsequent closure of physis is dependent on oestrogens in females as well as in males [14, 20]. The onset of the adolescent growth spurt is 2 years earlier in girls than in boys. A longer period of prepubertal growth as well as a higher growth spurt account for the greater adult height of males compared to females [17]. Not surprisingly, SCFE also occurs in an earlier phase in girls, with an average age of 12.0 years, than in boys, with an average age of 13.5 years [1].
Androgens and oestrogens have a direct growth-stimulating effect on the physis, as well as an indirect effect through the enhancement of GH secretion from the pituitary gland mediated by estrogen receptor (ER-α). Thus, androgens can only influence the GH-IGF-1 axis after aromatisation into oestrogens [12, 13, 18, 26, 27]. Boys have aromatase activity in numerous tissues, including adipose tissue and muscle. Boys with idiopathic gynaecomastia are generally characterized by relative obesity, resulting in increased conversion of androgens to oestrogens [20]. Boys with the rare condition of aromatase excess syndrome have increased conversion of testosterone to estradiol and, typically, develop gynaecomastia as well as increased longitudinal growth. In contrast, delayed skeletal maturation and low bone mineral density are observed in patients with aromatase deficiency and oestrogen receptor resistance [28], underlining the importance of oestrogen action in skeletal maturation, epiphyseal closure and bone mass accrual. Oestrogens are, thus, important in the regulation of linear growth of both sexes. In addition, oestrogens have a direct and an indirect role on the physis. Directly,
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