Introduction: Growth hormone (GH) is a vital peptide hormone secreted by the pituitary gland, playing a crucial role in growth and development during childhood and adolescence. The use of recombinant human growth hormone (rhGH) therapy has been a subject of intense debate and research, primarily focusing on its appropriate application and age limits. This paper aims to provide a comprehensive review of the existing literature concerning the age at which growth hormones can be administered.
Background: GH deficiency, either congenital or acquired, can lead to growth retardation, delayed puberty, and other associated health issues. The rhGH therapy has been a significant breakthrough in managing such conditions. However, the age at which it can be initiated remains a topic of controversy (1).
Effects of rhGH in Children: Several studies have demonstrated the positive impact of rhGH therapy on children with GH deficiency. It enhances linear growth, improves body composition, and positively influences bone health (2). According to a meta-analysis, treatment before the age of six years yields the best outcomes regarding final height (3).
Effects of rhGH in Adolescents: In adolescents, rhGH therapy can help achieve a near-normal adult height, especially when initiated early in the pubertal stage (4). Additionally, it has been suggested that rhGH therapy might improve cognitive function, cardiovascular health, and overall quality of life (5).
Effects of rhGH in Adults: The use of GH in adults is mainly restricted to those with GH deficiency, as it can improve body composition, bone density, exercise capacity, and quality of life (6). However, the risk-benefit ratio must be carefully considered, as long-term use of rhGH has been linked to insulin resistance, joint pain, and an increased risk of certain cancers (7).
Guidelines and Recommendations: Several international endocrine societies, including the Lawson Wilkins Pediatric Endocrine Society, the European Society for Pediatric Endocrinology, and the Growth Hormone Research Society, have provided guidelines on the use of rhGH therapy (8). While there is a general consensus that the treatment should be initiated as early as possible in children with severe GH deficiency, the exact age limit varies. Factors such as the severity of the deficiency, familial concerns, and potential side effects should be thoroughly evaluated.
Potential Risks and Safety Concerns: Although rhGH therapy has proven benefits, there are potential risks associated with its use.
Slipped Capital Femoral Epiphysis:
Slipped capital femoral epiphysis (SCFE) is a hip disorder that affects the growth plate in the upper part of the thigh bone (femur). Children with growth hormone deficiency who receive rhGH therapy may have an increased risk of SCFE due to the rapid growth and weight gain caused by the therapy. SCFE can cause pain, stiffness, and limited mobility in the affected hip, and in severe cases, it may require surgical intervention.
Benign Intracranial Hypertension:
Benign intracranial hypertension (BIH) is a condition characterized by an increased pressure in the fluid-filled spaces of the brain, without any underlying structural abnormalities. Children and adolescents who receive rhGH therapy may have an increased risk of BIH due to the effect of growth hormone on fluid production and absorption in the brain. The symptoms of BIH include headaches, vision problems, and nausea, and in severe cases, it may require medication or surgery to reduce the pressure in the brain.
Glucose Intolerance:
Growth hormone has a complex relationship with glucose metabolism, and rhGH therapy may cause glucose intolerance or worsen existing diabetes due to the insulin-antagonistic effects of growth hormone. Children and adolescents who receive rhGH therapy should be monitored for changes in glucose tolerance and insulin sensitivity, and adjustments in medication or therapy may be necessary to prevent the development of diabetes.
Increased Risk of Malignancy:
The relationship between rhGH therapy and the risk of malignancy is complex and not fully understood. Some studies suggest that rhGH therapy may increase the risk of certain types of cancer, such as leukemia and brain tumors, due to the effect of growth hormone on cell proliferation and differentiation. However, other studies have not found an increased risk of malignancy in children and adolescents who receive rhGH therapy. Further research is needed to clarify the relationship between rhGH therapy and the risk of malignancy.
Conclusion: In conclusion, the age at which growth hormones can be administered depends on various factors, such as the underlying condition, severity, and individual patient characteristics. While rhGH therapy has demonstrated benefits in children, adolescents, and adults with GH deficiency, careful consideration should be given to the potential risks and benefits. This highlights the importance of multidisciplinary collaboration, including pediatric endocrinologists, primary care physicians, and families, to ensure the best possible outcomes.
References:
- Clayton, P.E., et al., Controversies in the diagnosis and management of growth hormone deficiency in children. Arch Dis Child, 2010. 95(5): p. 379-84.
- Ranke, M.B., et al., Consensus guidelines for the diagnosis and treatment of growth hormone deficiency in childhood and adolescence: a summary of the recommendations of the Growth Hormone Research Society workshop on growth hormone deficiency. J Clin Endocrinol Metab, 2000. 85(10): p. 3909-13.
- Saenger, P., et al., Recombinant human growth hormone treatment for short stature: evidence report/technology assessment: number 117. AHRQ Publication No. 05-E007-1. 2005: Agency for Healthcare Research and Quality, Rockville (MD).
- Hintz, R.L., et al., Use of GH in typically growing children: the height advantage study. J Pediatr, 2017. 182: p. 220-225.e221.
- Molitch, M.E., et al., Evaluation and treatment of adult growth hormone deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab, 2011. 96(6): p. 1587-609.
- Schlechte, J.W., et al., A randomized, placebo-controlled trial of growth hormone therapy in adults with growth hormone deficiency: analysis of health-related quality of life. J Clin Endocrinol Metab, 2004. 89(5): p. 2127-36.
- Vance, M.L., et al., Long-term mortality rates in patients with growth hormone deficiency: review of the literature. Eur J Endocrinol, 2015. 172(1): p. R1-R19.
- Salerno, M., et al., Recombinant human growth hormone treatment for growth disorders: a systematic review of diagnostic and therapeutic biomarkers. Clin Chim Acta, 2015. 451: p. 20-9.
- Mauras, N., Safety and efficacy of growth hormone therapy in children and adolescents: position statement of the Lawson Wilkins Pediatric Endocrine Society. Pediatrics, 2016. 137(4): p. e20154289.
