Abstract Recombinant human growth hormone (rhGH) is an effective therapeutic drug for improving short stature. Currently, rhGH can be used for various causes of short stature, including growth hormone deficiency, and the expansion of its clinical application has raised concerns about its safety. Based on existing evidence, when rhGH is used in a standardized manner for physiological replacement therapy, its safety profile is favorable. In clinical practice, attention should be focused on short-term safety during rhGH treatment, with the combination of literature evidence and clinical experience. There is still no definitive conclusion on the long-term safety due to insufficient duration of rhGH treatment. This paper reviews the possible adverse events that may occur during rhGH treatment and their risk control measures, aiming to help clinical physicians understand the overall safety of rhGH treatment and improve its clinical standardization.
Grimberg A, DiVall SA, Polychronakos C, et al. Guidelines for growth hormone and insulin-like growth factor-I treatment in children and adolescents: growth hormone deficiency, idiopathic short stature, and primary insulin-like growth factor-I deficiency[J]. Horm Res Paediatr, 2016, 86(6): 361-397. PMID: 27884013. DOI: 10.1159/000452150.
Yuen KCJ, Biller BMK, Radovick S, et al. American Association of Clinical Endocrinologists and American College of Endocrinology guidelines for management of growth hormone deficiency in adults and patients transitioning from pediatric to adult care[J]. Endocr Pract, 2019, 25(11): 1191-1232. PMID: 31760824. DOI: 10.4158/GL-2019-0405.
Bamba V, Kanakatti Shankar R. Approach to the patient: safety of growth hormone replacement in children and adolescents[J]. J Clin Endocrinol Metab, 2022, 107(3): 847-861. PMID: 34636896. DOI: 10.1210/clinem/dgab746.
Darendeliler F, Karagiannis G, Wilton P. Headache, idiopathic intracranial hypertension and slipped capital femoral epiphysis during growth hormone treatment: a safety update from the KIGS database [J]. Horm Res, 2007, 68(Suppl 5): 41-47. PMID: 18174706. DOI: 10.1159/000110474.
Child CJ, Zimmermann AG, Chrousos GP, et al. Safety outcomes during pediatric GH therapy: final results from the prospective GeNeSIS observational program[J]. J Clin Endocrinol Metab, 2019, 104(2): 379-389. PMID: 30219920. PMCID: PMC6300411. DOI: 10.1210/jc.2018-01189.
Iughetti L, Vivi G, Balsamo A, et al. Thyroid function in patients with Prader-Willi syndrome: an Italian multicenter study of 339 patients[J]. J Pediatr Endocrinol Metab, 2019, 32(2): 159-165. PMID: 30703060. DOI: 10.1515/jpem-2018-0388.
S?vendahl L, Polak M, Backeljauw P, et al. Long-term safety of growth hormone treatment in childhood: two large observational studies: NordiNet IOS and ANSWER[J]. J Clin Endocrinol Metab, 2021, 106(6): 1728-1741. PMID: 33571362. PMCID: PMC8118578. DOI: 10.1210/clinem/dgab080.
Mostoufi-Moab S, Isaacoff EJ, Spiegel D, et al. Childhood cancer survivors exposed to total body irradiation are at significant risk for slipped capital femoral epiphysis during recombinant growth hormone therapy[J]. Pediatr Blood Cancer, 2013, 60(11): 1766-1771. PMID: 23818448. PMCID: PMC4564250. DOI: 10.1002/pbc.24667.
Witbreuk M, van Kemenade FJ, van der Sluijs JA, et al. Slipped capital femoral epiphysis and its association with endocrine, metabolic and chronic diseases: a systematic review of the literature[J]. J Child Orthop, 2013, 7(3): 213-223. PMID: 24432080. PMCID: PMC3672463. DOI: 10.1007/s11832-013-0493-8.
Witkowska-Sedek E, Labochka D, Stelmaszczyk-Emmel A, et al. Evaluation of glucose metabolism in children with growth hormone deficiency during long-term growth hormone treatment[J]. J Physiol Pharmacol, 2018, 69(2): 219-230. PMID: 29980142. DOI: 10.26402/jpp.2018.2.08.
Pellegrin MC, Michelon D, Faleschini E, et al. Glucose metabolism evaluated by glycated hemoglobin and insulin sensitivity indices in children treated with recombinant human growth hormone[J]. J Clin Res Pediatr Endocrinol, 2019, 11(4): 350-357. PMID: 30819016. PMCID: PMC6878334. DOI: 10.4274/jcrpe.galenos.2019.2019.0281.
23 U.S. Food and Drug Administration. SKYTROFA? prescribing information[EB/OL]. [2022-02-01]. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761177s001lbl.pdf.
Stagi S, Ferrari V, Ferrari M, et al. Inside the Noonan "universe": literature review on growth, GH/IGF axis and rhGH treatment: Facts and concerns[J]. Front Endocrinol (Lausanne), 2022, 13: 951331. PMID: 36060964. PMCID: PMC9434367. DOI: 10.3389/fendo.2022.951331.
S?vendahl L, Cooke R, Tidblad A, et al. Long-term mortality after childhood growth hormone treatment: the SAGhE cohort study[J]. Lancet Diabetes Endocrinol, 2020, 8(8): 683-692. PMID: 32707116. DOI: 10.1016/S2213-8587(20)30163-7.
Barake M, Arabi A, Nakhoul N, et al. Effects of growth hormone therapy on bone density and fracture risk in age-related osteoporosis in the absence of growth hormone deficiency: a systematic review and meta-analysis[J]. Endocrine, 2018, 59(1): 39-49. PMID: 29030774. DOI: 10.1007/s12020-017-1440-0.