Page 75 - Slipped Capital Femoral Epiphysis Pathogenetic and Clinical aspects

anterior pituitary gland and thyroid-releasing hormone (TRH) by the hypothalamus. Thyroid hormones are essential for longitudinal growth and normal skeletal maturation [12].
Circulating active thyroid hormone, T3, is formed by deionisation of T4 in the liver and kidney. T4 is derived from the thyroid gland [33].
T3 is essential for resting zone cells differentiation and hypertrophic chondrocyte differentiation during bone formation. T3 has an indirect role on growth by influencing GH secretion and a direct role which has been shown by the presence of thyroid receptor α1 (TRα1) and thyroid receptor β (TRβ) presence in proliferating chondrocytes in the physis. T3 also regulates osteoblast activity, bone turnover and vascular invasion [14, 17, 18, 32, 33].
Tightly controlled concentrations are essential [14, 33]: childhood hypothyroidism 4 causes growth failure, whereas thyrotoxicosis causes accelerated growth and
slightly advanced bone age, which may lead to a moderately decreased final height.
The negative feedback loop of an important regulator of chondrocyte differentiation, Indian hedgehog–parathyroid hormone-related hormone (IHH–
PTHrH), can be altered by the thyroid status. IHH belongs to a family of hedgehog proteins which plays a crucial role in embryonic development. IHH is secreted by pre-hypertrophic chondrocytes and is mainly a regulator of the pace of chondrocyte differentiation. It stimulates the local production of PTHrP. PTHrP acts on PTHrP receptor expressing pre-hypertrophic chondrocytes to maintain cell proliferation, reduce IHH production and complete a feedback loop in which PTHrP exerts a negative signal that inhibits hypertrophic differentiation [18, 33, 34]. The levels of expression in early hypertrophic chondrocytes of IHH and PTHrP are higher during early puberty than at later stages. It has been suggested that these proteins might be involved in the regulation of pubertal growth because a reduced expression of IHH–PTHrH is found during the progress of pubertal development [35]. The IHH–PTHrH feedback loop does not only regulate chondrocyte proliferation and differentiation but also osteoblast differentiation, thereby, coupling chondrogenesis to osteogenesis [18, 36].
In conclusion, thyroid hormone exerts direct and indirect effects on the physis and facilitates physis closure at the end of puberty via signaling of the IHH–PTHrH pathway. As SCFE occurs at the end of puberty, where the closure of the physis is delayed, it could be possible that changes in thyroid hormones disturb the closure of the physis. Although there are hardly data available to determine the exact role of abnormalities in this axis in SCFE, Wells et al. [37] found that this was the most
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