Adverse events of replacement therapy in children with growth hormone deficiency

Abstract

Background. The purpose was to analyze and summarize the accumulated short-term and long-term safety data in children with growth hormone deficiency (GHD) treated using recombіnant human growth hormone (rhGH) based on the results of a physical examination, assessment of vital signs, laboratory parameters, and follow-up. Materials and methods. The study was conducted at the Odesa Regional Children’s Clinical Hospital from 2012 to 2022, with 92 children treated for GHD using rhGH at an average dose of 0.033 mg/kg/day. The evaluation of the safety of this therapy was based on assessing the incidence of adverse events (AEs) as a negative consequence of medical care. We analyzed both short-term and long-term outcomes. Results. When studying the short-term safety of rhGH therapy according to physical examination data, AEs were found in 18 (19.57 %) children, including intracranial hypertension (1), arthralgia (1), prepubertal gynecomastia (1), anemia (3), manifestation of latent adrenal insufficiency (3), latent thyroid insufficiency (2), impaired glucose tolerance (7). 20.6 (7.0 ÷ 34.2) % of patients with unacceptable adherence to rhGH therapy reported painful injections compared to 4.3 (–1.6 ÷ 10.2) % of children with acceptable compliance (χ2 = 5.15; р = 0.02). None of the children experienced serious adverse events such as scoliosis progression, slipped capital femoral epiphysis, edema, and impaired vital functions. AEs in terms of hematological and biochemical parameters were usually transient, often in combination with intercurrent diseases, and were not associated with rhGH. In long-term safety, there was no association between rhGH therapy and the risk of cancer, cardiac, and cerebrovascular diseases. Still, three children (3.26 %) had type 2 diabetes, with overweight in one case and obesity in two. Conclusions. In general, in the short-term context, rhGH therapy for children with GHD is safe. The pain at the injection site is a clinically significant AE as a cognitive emotional barrier to the adherence to rhGH therapy. From the point of view of the long-term safety of rhGH therapy, the fact that type 2 diabetes was detected in 3 (3.26 %) children with increased body weight and obesity is essential.