Affiliation:
1. Nemours Children’s Health Jacksonville , FL , USA
2. Nemours Children’s Health Wilmington , DE , USA
3. University of Chile , Santiago , Chile
Abstract
Abstract
Pubertal children with significant growth retardation represent a considerable therapeutic challenge. In growth hormone (GH) deficiency, and in those without identifiable pathologies (idiopathic short stature), the impact of using GH is significantly hindered by the relentless tempo of bone age acceleration caused by sex steroids, limiting time available for growth. Estrogen principally modulates epiphyseal fusion in females and males. GH production rates and growth velocity more than double during puberty, and high-dose GH use has shown dose-dependent increases in linear growth, but also can raise insulin-like growth factor I concentrations supraphysiologically, and increase treatment costs. Gonadotropin-releasing hormone analogs (GnRHas) suppress physiologic puberty, and when used in combination with GH can meaningfully increase height potential in males and females while rendering adolescents temporarily hypogonadal at a critical time in development. Aromatase inhibitors (AIs) block androgen to estrogen conversion, slowing down growth plate fusion, while allowing normal virilization in males and stimulating longitudinal bone growth via androgen receptor effects on the growth plate. Here, we review the physiology of pubertal growth, estrogen and androgen action on the epiphyses, and the therapeutic impact of GH, alone and in combination with GnRHa and with AIs. The pharmacology of potent oral AIs, and pivotal work on their efficacy and safety in children is also reviewed. Time-limited use of AIs is a viable alternative to promote growth in pubertal males, particularly combined with GH. Use of targeted growth-promoting therapies in adolescence must consider the impact of sex steroids on growth plate fusion, and treatment should be individualized.
Subject
Endocrinology,Endocrinology, Diabetes and Metabolism
Reference99 articles.
1. Pubertal development and regulation. Review;Abreu;Lancet Diabetes Endocrinol.,2016
2. Kisspeptin and GPR54: discovery of a novel pathway in reproduction;Seminara;J Neuroendocrinol.,2008
3. Central precocious puberty caused by mutations in the imprinted gene MKRN3;Abreu;N Engl J Med.,2013
4. Mutations in pregnancy-associated plasma protein A2 cause short stature due to low IGF-I availability;Dauber;EMBO Mol Med.,2016
5. Disorders caused by genetic defects associated with GH-dependent genes: PAPPA2 defects;Fujimoto;Mol Cell Endocrinol.,2020
Cited by
9 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献