Page 70 - Slipped Capital Femoral Epiphysis Pathogenetic and Clinical aspects

Chapter 4
Since obesity and pubertal growth spurt seem to be the main risk factors for SCFE, we will start by explaining the influence of (1) the GH-IGF-1 axis, (2) sex steroids and (3) leptin. Their influence on the physis is complex. Subsequently, we will discuss thyroid hormone, glucocorticoids, vitamin D, chronic disease and diagnostic endocrine measurements in SCFE.
Obesity and SCFE
GH-IGF-1 axis and SCFE Growth hormone (GH) is a peptide hormone that stimulates growth, cell reproduction and regeneration in humans and other animals. GH is normally produced in an abundant quantity by the pituitary somatotroph cells. It is secreted in a pulsatile manner stimulated by hypothalamic GH-releasing hormone (GHrH), inhibited by somatostatin (growth hormone-inhibiting hormone) and under negative feedback of the peripheral effectors GH, IGF-1 and insulin-like growth factor binding protein (IGFBP) [15-18]. During pubertal development, the basal secretion and pulse amplitude of GH increases two-fold to three-fold as a result of increasing levels of sex hormones [12].
According to the dual effector theory, GH can act directly as well as indirectly, via IGF-1, on the physis. Directly, GH acts on the resting zone and is responsible for local IGF-1 production, which stimulates clonal expansion of proliferative chondrocytes in an autocrine/paracrine manner. Indirectly, GH stimulates IGF-1 synthesis in the liver, which, in turn, activates chondrocyte proliferation in the physis [12, 18-23]. IGF-1 is a peptide hormone and a major metabolic regulator in the body. Most circulating IGF-1 is synthesized by the liver. It has anabolic effects on muscle and bone and catabolic effects on fat [16]. Recent studies indicate that locally acting IGF-1 is a key determinant of endochondral ossification and that GH, glucocorticoids (GC) and T3 regulate the expression of IGF-1 and its receptor in the physis directly [14, 22]. Insulin like growth factor 1 (IGF-1) gives thanks to its name from the similarity of insulin. It also explains the ability of IGF-1 to bind to insulin receptors and insulin’s ability to bind to the IGF-1 receptor [17, 18].
Hepatic IGF-1 is almost entirely bound to IGFBPs. There is a family of six, of which IGFBP3 is the most important. Acid labile subunit (ALS), also synthesized by the liver, acts as a stabilizer for the ternary complex with IGF-1 and IGFBP3. Only 1 % of plasma IGF-1 occurs in free bioactive form [13, 15, 17, 24]. Circulatory IGF is detected by the hypothalamus and pituitary gland to inhibit GH secretion, completing the feedback loop [16].
68