SCFE usually occurs when there is a growth spurt during puberty, with the risk compounding in cases of obesity and abnormal anatomy of the proximal femur6. In recent years, more and more attention is being given to the role of endocrine factors in the occurrence of SCFE. Delayed closure of the epiphysis due to hormonal disorders increases the risk of SCFE. In previous reports, hypopituitarism, hypothyroidism, and hypogonadism were common endocrine causes of SCFE7-10. CAH is also an endocrine disease characterized by hormonal disorders. The main hormones involved are adrenocortical hormones and sex hormones. This is the first report of SCFE in a child who was diagnosed with CAH.
The linear growth of childhood results from endochondral ossification in the growth plate. During adolescence, endocrine levels change greatly, and disturbances in endocrine mechanisms may lead to a weak physiological function of the proximal femur. Therefore, the effects of several hormones on the epiphyseal plate should be understood. Pre-pubertal growth is mainly regulated by growth hormone-insulin-like growth factor 1 (GH-IGF-1) axis and the thyroid hormone (T3), while sex steroids are major regulators of pubertal growth. Increased sex hormones can also lead to increased GH-IGF-1 axis activity. GH can stimulate chondrocyte proliferation. IGF-1 is a key factor in ossification of the epiphyseal cartilage. Thyroid hormone promotes bone maturation and longitudinal growth, but excess thyroid hormone promotes early bone closure. A physiological dose of glucocorticoids (GC) is beneficial for normal growth, but excess GC inhibits growth by inhibiting chondrocyte proliferation and cartilage matrix synthesis11.
According to the CAH classification, the patient in this case belongs to the type that is salt-wasting, which is characterized by GC deficiency, mineralocorticoid deficiency, and accumulation of sex hormones. The excess postnatal androgen presence led the child to have premature growth of pubic hair, rapid skeletal growth, and premature epiphyseal fusion, ultimately growing to a lower height than what the parents’ target was. The patient’s bone age at the age of 5 had already reached 13 years. It can be seen from the height growth chart (Fig. 1) that at 5 years of age, the patient had a height advantage over that of his peers, but as he got older, the advantage diminished. Under the parents’ desire to improve the height of the patient, the patient has been receiving a combination of GnRH analogs and growth hormone under the guidance of an endocrinologist since the age of 5. The patient’s height increased from 118cm at the age of 5 to 150cm at the time of admission with an average increase of 5-6cm per year. Meanwhile, the growth velocity has dropped to 4cm per year in the past two years. Under the anti-androgenic effect of gonadotropin-releasing hormone analogs, the bone age of the child did not increase significantly. His parents were satisfied with his treatment, until the SCFE happened. The patient’s overall medical history led us to think about whether could be a connection between the application of GnRH analogs and SCFE. Previous studies have reported the effects of the combined application of GnRH analogs and GH, with no occurrence of SCFE described in the adverse events12. The latest CAH treatment guidelines in 2018 also clarified the effect of the combined application of GnRH analogs and GH on improving height12,13. In addition, some studies have shown that growth hormone was safe for improving height14. Nonetheless, SCFE seems to have spontaneously occurred in this patient with no clear cause. We speculate two possible reasons. First, the epiphyseal plate was not closed due to the application of GnRH analogs, which increased the risk of SCFE. And second, the long-term use of GC could have affected chondrocyte proliferation and cartilage matrix synthesis, which caused unbalanced growth of the epiphyseal plate.
After sufficient endocrine evaluation, we improved the position of the femoral head relative to the femoral neck, and fixed them using Dunn’s procedure. Unfortunately, at the 1-year follow-up, the patient suffered from right avascular necrosis of the femoral head (ANFH). A study of adolescent SCFE by Julio Javier Masquijo15 showed that the incidence of ANFH after surgery was 47.6% (10/21 hips). As we all know, GC is a common cause of ANFH. This patient recovered the use of GC after surgery due to CAH therapy. Therefore, the possibility of ANFH may be higher when GC continued to be used after surgery. For the patient in this case, the next treatment may only be waiting for total hip arthroplasty treatment. Previous study indicated that the combination of GH and GnRH analogs improved final height by about 7cm in patients with CAH12. Nevertheless, compared with the permanent loss of function of the right hip, the improvement of height may become relatively unimportant. Therefore, we should be cautious towards the occurrence of SCFE in the process of this treatment. Presently, what we can do is continue regular follow-up to prevent SCFE on the contralateral side, and wait for the opportunity to perform THA surgery on the right hip. In addition, comprehensive endocrine examination should be performed preoperatively to prevent adrenal crisis and imbalance of serum sodium and potassium, especially in children with salt-wasting type CAH.