Occurrence of slipped capital femoral epiphysis in children undergoing gonadotropin-releasing hormone agonist therapy for the treatment of central precocious puberty.

BACKGROUND: Obesity, age and hormone imbalances including hypothyroidism and growth hormone deficiency and therapy, but not gonadotropin-releasing hormone agonist (GnRHa) therapy, have been identified as risk factors for slipped capital femoral epiphysis (SCFE). Five of 7 reported cases describe SCFE in children shortly after GnRHa therapy cessation. METHODS: We report 3 cases of SCFE that occurred in children on GnRHa therapy for the treatment of central precocious puberty (CPP) and discuss possible promoting factors. RESULTS: An otherwise healthy 8.75-year-old girl [body mass index (BMI) Z score +1.75] developed SCFE 6.75 years into GnRHa therapy for idiopathic CPP. A second girl (with a history of acute lymphoblastic leukemia requiring total body irradiation) was 10.6 years old (BMI Z score +1.06) when she developed SCFE 3.3 years into GnRHa therapy. The third case was an 8.75-year-old female with CPP secondary to a hypothalamic hamartoma (BMI Z score +1.65) who developed bilateral SCFE 5.6 years into therapy. CONCLUSION: Increasing evidence suggests an association between GnRHa therapy for CPP and the occurrence of SCFE. We suggest that a lack of adequate sex hormone exposure at a 'critical period' of bone formation may result in a weakened epiphysis that becomes susceptible to slipping. © 2013 S. Karger AG, Basel.

Safety of growth hormone treatment of children with idiopathic short stature: the US experience.

Recombinant human growth hormone (rhGH) is approved in the United States for treatment of idiopathic short stature (ISS). The occurrence of adverse events (AEs) and the long-term safety of rhGH treatment in this patient population are reviewed. Data were analyzed from postmarketing surveillance studies that included ISS patients, prospective ISS treatment trials and studies of specific AEs in smaller groups of rhGH-treated children. Frequency rates of targeted AEs (i.e., scoliosis, slipped capital femoral epiphysis, intracranial hypertension, pancreatitis) in patients with ISS are similar to or lower than the rates observed in other rhGH-treated conditions. At dosages of 0.24-0.37 mg/kg/week, rhGH treatment in children with ISS does not adversely affect blood glucose levels. At dosages ≥ 0.3 mg/kg/week, a dose-dependent increase in mean fasting and stimulated insulin levels is observed. Current evidence derived from 'on-treatment' surveillance studies suggests that rhGH does not increase the risk for new malignancies in children with ISS.The safety profile of rhGH at doses ≤ 0.37 mg/kg/week for the treatment of children with ISS is similar to or better than the profile seen in other rhGH-treated conditions and is not associated with any predictable AEs. Due to a continuing trend toward dose escalation to achieve greater height-promoting effects and the possibility of delayed post-treatment effects of hyperinsulinemia and/or heightened GH and insulin-like growth factor I exposure on cancer risk, caution and ongoing scrutiny of risks versus benefits are warranted.