Skip to main content

Update in Pediatric Endocrinology

  • Chapter
  • First Online:
Update in Pediatrics
  • 238 Accesses

Abstract

Endocrine disorders refer to disease states affecting the glands that produce hormones regulating metabolism, growth, development, reproduction and other bodily functions. Disorders of the adrenal glands, growth, puberty, and the thyroid are cornerstones of pediatric endocrinology. While the endocrine care of children has much overlap with the endocrine care of adults, there are many unique aspects of pediatric endocrinology including the physiologic process of growth and puberty. Thyroid and adrenal disorders in children have similarities to these disorders in adults but there are some important differences and nuances in the management of these disorders in children. The purpose of this chapter is not to provide an exhaustive review but rather to highlight some concepts unique to pediatric endocrine care including some recent updates.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Abawi O, et al. Impact of body mass index on growth hormone stimulation tests in children and adolescents: a systematic review and meta-analysis. Crit Rev Clin Lab Sci. 2021;58(8):576–95.

    Article  CAS  PubMed  Google Scholar 

  • Abraham P, et al. Antithyroid drug regimen for treating Graves’ hyperthyroidism. Cochrane Database Syst Rev. 2010;2010((1):CD003420.

    PubMed  Google Scholar 

  • Abreu AP, Dauber A, Macedo DB, Noel SD, Brito VN, Gill JC, et al. Central precocious puberty caused by mutations in the imprinted gene MKRN3. N Engl J Med. 2013;368(26):2467–75.

    Article  CAS  PubMed  Google Scholar 

  • Acharya SV, Gopal RA, et al. Utility of single luteinizing hormone determination 3 h after depot leuprolide in monitoring therapy of gonadotropin-dependent precocious puberty. Pituitary. 2009;12(4):335–8.

    Article  CAS  PubMed  Google Scholar 

  • Addison T. On the constitutional and local effects of disease of the supra-renal capsules (Special edition). Birmingham: ALA; 1980.

    Google Scholar 

  • Aguire RS, Rugster EA. Central precocious puberty: from genetics to treatment. Best Pract Res Clin Endocrinol Metab. 2018;32(4):343–54.

    Article  Google Scholar 

  • Alatzoglou KS, et al. Expanding the spectrum of mutations in GH1 and GHRHR: genetic screening in a large cohort of patients with congenital isolated growth hormone deficiency. J Clin Endo Metab. 2009;94(9):3191–9.

    Article  CAS  Google Scholar 

  • Albanese A, Kewley GD, Long A, Pearl KN, Robins DG, Stanhope R. Oral treatment for constitutional delay of growth and puberty in boys: a randomised trial of an anabolic steroid or testosterone undecanoate. Arch Dis Child. 1994;71(4):315–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Albertsson-Wikland K. Mortality is not increased in recombinant human growth hormone-treated patients when adjusting for birth characteristics. J Clin Endocrinol Metab. 2016;101(5):2149–59.

    Article  CAS  PubMed  Google Scholar 

  • Albertsson-Wikland K, et al. Dose-dependent effect of growth hormone on final height in children with short stature without growth hormone deficiency. J Clin Endocrinol Metab. 2008;93(11):4342–50.

    Article  CAS  PubMed  Google Scholar 

  • Bang P, et al. Identification and management of poor response to growth-promoting therapy in children with short stature. Clin Endocrinol (Oxf). 2012;77(2):169–81.

    Article  CAS  PubMed  Google Scholar 

  • Bauer AJ, Wassner AJ. Thyroid hormone therapy in congenital hypothyroidism and pediatric hypothyroidism. Endocrine. 2019;66:51–62.

    Article  CAS  PubMed  Google Scholar 

  • Bellone J, Valetto MR, Aimaretti G, Segni M, Volta C, Cardimale G, et al. Effects of phenylalanine, histidine, and leucine on basal and GHRH-stimulated GH secretion and on PRL, insulin, and glucose levels in short children. Comparison with the effects of arginine. J Pediatr Endocrinol Metab. 1996;9(5):523–31.

    Article  CAS  PubMed  Google Scholar 

  • Berglund A, Gravholt CH, Olsen MS, Christiansen JS, Stochholm K. Growth hormone replacement does not increase mortality in patients with childhood-onset growth hormone deficiency. Clin Endocrinol (Oxf). 2015;83(5):677–83.

    Article  CAS  PubMed  Google Scholar 

  • Bigambo FM, Sun H, et al. Association between phenols exposure and earlier puberty in children: a systematic review and meta-analysis. Environ Res. 2020;190:110056.

    Article  CAS  PubMed  Google Scholar 

  • Binder G, Schweizer R, Haber P, Blumenstock G, Braun R. Accuracy of endocrine tests for detecting hypogonadotropic hypogonadism in girls. J Pediatr. 2015;167(3):674–8e1.

    Article  CAS  PubMed  Google Scholar 

  • Binder G, et al. GHD diagnostics in Europe and the US: an audit of national guidelines and practice. Horm Res Paediatr. 2019;92(3):150–6.

    Article  CAS  PubMed  Google Scholar 

  • Biro FM, Galvez MP, Greenspan LC, Succop PA, Vangeepuram N, Pinney SM, et al. Pubertal assessment method and baseline characteristics in a mixed longitudinal study of girls. Pediatrics. 2010;126(3):e583–90.

    Article  PubMed  Google Scholar 

  • Boguszewski M, et al. Safety of growth hormone replacement in survivors of cancer and intracranial and pituitary tumours: a consensus statement. Eur J Endocrinol. 2022;186(6):P35–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bornstein SR, Allolio B, Arlt W, Barthel A, Don-Wauchope A, Hammer GD, et al. Diagnosis and treatment of primary adrenal insufficiency: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2016;101(2):364–89.

    Article  CAS  PubMed  Google Scholar 

  • Bradely SH, et al. Precocious puberty. BMJ. 2020;368:l6597. https://doi.org/10.1136/bmj.l6597.

    Article  Google Scholar 

  • Butler GE, Sellar RE, et al. Oral testosterone undecanoate in the management of delayed puberty in boys: pharmacokinetics and effects on sexual maturation and growth. J Clin Endo Metab. 1992;75(1):37–44.

    CAS  Google Scholar 

  • Butler MG, Lee J, Manzardo AM, Gold JA, Miller JL, Kimonis V, et al. Growth charts for non-growth hormone treated Prader-Willi syndrome. Pediatrics. 2015;135(1):e126–35.

    Article  PubMed  PubMed Central  Google Scholar 

  • Cantas-Orsdemir S, et al. Prevalence of cranial MRI findings in girls with central precocious puberty: a systematic review and meta-analysis. J Pediatr Endocrinol Metab. 2018;31(7):701–10.

    Article  PubMed  Google Scholar 

  • Canton APM, Seraphim CE. Pioneering studies on monogenic central precocious puberty. Arch Endocrinol Metab. 2019;63(4):438–44.

    Article  PubMed  PubMed Central  Google Scholar 

  • Carel JC, Tresca JP, Letrait M, Chaussain JL, Lebouc Y, Job JC, et al. Growth hormone testing for the diagnosis of growth hormone deficiency in childhood: a population register-based study. J Clin Endocrinol Metab. 1997;82(7):2117–21.

    Article  CAS  PubMed  Google Scholar 

  • Carel JC, Ecosse E, Landier F, Meguellati-Hakkas D, Kaguelidou F, Rey G, et al. Long-term mortality after recombinant growth hormone treatment for isolated growth hormone deficiency or childhood short stature: preliminary report of the French SAGhE study. J Clin Endocrinol Metab. 2012;97(2):416–25.

    Article  CAS  PubMed  Google Scholar 

  • Chan YM, Lippincott MF, et al. Divergent responses to kisspeptin in children with delayed puberty. JCI Insight. 2018;3(8):e99109.

    Article  PubMed  PubMed Central  Google Scholar 

  • Chan YM, Lippincott MF, et al. Using Kisspeptin to predict pubertal outcomes for youth with pubertal delay. J Clin Endocrinol Metab. 2020;105(8):e2717–25.

    Article  PubMed  PubMed Central  Google Scholar 

  • Chaudhary S, Walia R, et al. FSH-stimulated Inhibin B (FSH-iB): a novel marker for the accurate prediction of pubertal outcome in delayed puberty. J Clin Endocrinol Metab. 2021;106(9):e3495–505.

    Article  PubMed  Google Scholar 

  • Chen M, Eugster EA. Central precocious puberty: update on diagnosis and treatment. Paediatr Drugs. 2015;17(4):273–81.

    Article  PubMed  PubMed Central  Google Scholar 

  • Chi CH, Durham E, Neely EK. Pharmacodynamics of aqueous leuprolide acetate stimulation testing in girls: correlation between clinical diagnosis and time of peak luteinizing hormone level. J Pediatr. 2012;161(4):757–9. e1

    Article  CAS  PubMed  Google Scholar 

  • Chioma L, Papucci G, et al. Use of testosterone gel compared to intramuscular formulation for puberty induction in males with constitutional delay of growth and puberty: a preliminary study. J Endocrinol Invest. 2018;41(2):259–63.

    Article  CAS  PubMed  Google Scholar 

  • Cohen LE. Idiopathic short stature: a clinical review. JAMA. 2014;311(17):1787–96.

    Article  PubMed  Google Scholar 

  • Cohen P, Rogol AD, Deal CL, Saenger P, Reiter EO, Ross JL, et al. Consensus statement on the diagnosis and treatment of children with idiopathic short stature: a summary of the Growth Hormone Research Society, the Lawson Wilkins Pediatric Endocrine Society, and the European Society for Paediatric Endocrinology Workshop. J Clin Endocrinol Metab. 2008;93(11):4210–7.

    Article  CAS  PubMed  Google Scholar 

  • Collett-Solberg P, et al. Diagnosis, genetics, and therapy of short stature in children: A Growth Hormone Research Society International Perspective. Horm Res Paediatr. 2019;92(1):1–14.

    Article  CAS  PubMed  Google Scholar 

  • Coope H, et al. Expert Opin Orphan Drugs. 2021;9(3):67–76. https://doi.org/10.1080/21678707.2021.1903871.

    Article  CAS  Google Scholar 

  • Coutant R, de Casson FB, Rouleau S, Douay O, Mathieu E, Gatelais F, et al. Divergent effect of endogenous and exogenous sex steroids on the insulin-like growth factor I response to growth hormone in short normal adolescents. J Clin Endocrinol Metab. 2004;89(12):6185–92.

    Article  CAS  PubMed  Google Scholar 

  • Darendeliler F, et al. Headache, idiopathic intracranial hypertension and slipped capital femoral epiphysis during growth hormone treatment: a safety update from the KIGS database. Horm Res. 2007;68(Suppl 5):41–7.

    PubMed  Google Scholar 

  • Deal C, et al. Efficacy and safety of weekly somatrogon vs daily somatropin in children with growth hormone deficiency: A Phase 3 Study. J Clin Endocrinol Metab. 2022;107(7):e2717–28.

    Article  PubMed  PubMed Central  Google Scholar 

  • DeBoer MD, Denson LA. Delays in puberty, growth, and accrual of bone mineral density in pediatric Crohn’s disease: despite temporal changes in disease severity, the need for monitoring remains. J Pediatr. 2013;163(1):17–22.

    Article  PubMed  PubMed Central  Google Scholar 

  • Deladoey J, et al. Is the incidence of congenital hypothyroidism really increasing? A 20-year retrospective population-based study in Québec. J Clin Endocrinol Metab. 2011;96(8):2422–9.

    Article  CAS  PubMed  Google Scholar 

  • Demirbilek H, et al. Assessment of gonadotrophin suppression in girls treated with GnRH analogue for central precocious puberty; validity of single luteinizing hormone measurement after leuprolide acetate injection. Clin Endocrinol (Oxf). 2012;76(1):126–30.

    Article  CAS  PubMed  Google Scholar 

  • Dunkel L. Treatment of idiopathic short stature: effects of gonadotropin-releasing hormone analogs, aromatase inhibitors and anabolic steroids. Horm Res Paediatr. 2011;76(Suppl 3):27–9.

    Article  CAS  PubMed  Google Scholar 

  • Yang Y, Bai X, Yuan X, Zhang Y, Shen S, Yang H, Du H, Zhu H, Pan H. Endocrine. Efficacy and safety of long-acting growth hormone in children with short stature: a systematic review and metaanalysis. 2019;65(1):25–34. PMID 31119649

    Google Scholar 

  • Eugster EA, et al. Tamoxifen treatment for precocious puberty in McCune-Albright syndrome: a multicenter trial. J Pediatr. 2003;143:60–6.

    Article  CAS  PubMed  Google Scholar 

  • Federici S, Goggi G, et al. New and consolidated therapeutic options for pubertal induction in hypogonadism: in-depth review of the literature. Endocr Rev. 2022;43(5):824–51.

    Article  PubMed  Google Scholar 

  • Ferguson KK, Peterson KE, Lee JM, Mercado-Garcia A, Blank-Goldenberg C, Tellez-Rojo MM, et al. Prenatal and peripubertal phthalates and bisphenol A in relation to sex hormones and puberty in boys. Reprod Toxicol. 2014;47:70–6.

    Article  CAS  PubMed  Google Scholar 

  • Franzini IA, et al. GnRH analog is ineffective in increasing adult height in girls with puberty onset after 7 years of age: a systematic review and meta-analysis. Eur J Endocrinol. 2018;179(6):381–90.

    Article  CAS  PubMed  Google Scholar 

  • Freriks K, Sas TC, Traas MA, Netea-Maier RT, den Heijer M, Hermus AR, et al. Long-term effects of previous oxandrolone treatment in adult women with Turner syndrome. Eur J Endocrinol. 2013;168(1):91–9.

    Article  CAS  PubMed  Google Scholar 

  • Giustina A, Scalvini T, Tassi C, Desenzani P, Poiesi C, Wehrenberg WB, et al. Maturation of the regulation of growth hormone secretion in young males with hypogonadotropic hypogonadism pharmacologically exposed to progressive increments in serum testosterone. J Clin Endocrinol Metab. 1997;82(4):1210–9.

    CAS  PubMed  Google Scholar 

  • Gohil A, et al. Delayed and precocious puberty: genetic underpinnings and treatments. Endocrinol Metab Clin North Am. 2020;49(4):741–57.

    Article  PubMed  PubMed Central  Google Scholar 

  • Grassi G, et al. Minding the gap between cortisol levels measured with second-generation assays and current diagnostic thresholds for the diagnosis of adrenal insufficiency: a single-center experience. Hormones (Athens). 2020;19(3):425–31.

    Article  CAS  PubMed  Google Scholar 

  • Grimberg A, 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. Horm Res Paediatr. 2016;86(6):361–97.

    Article  CAS  PubMed  Google Scholar 

  • Growth Hormone Research Society. Consensus guidelines for the diagnosis and treatment of growth hormone (GH) deficiency in childhood and adolescence: summary statement of the GH Research Society. GH Research Society. J Clin Endocrinol and Met. 2000;85(11):3990–3.

    Google Scholar 

  • Hage C, et al. Advances in differential diagnosis and management of growth hormone deficiency in children. Nat Rev Endocrinol. 2021;17(10):608–24.

    Article  PubMed  Google Scholar 

  • Hanley P, et al. Thyroid disorders in children and adolescents: a review. JAMA Pediatr. 2016;170(10):1008–19.

    Article  PubMed  Google Scholar 

  • Harrington J, Palmert MR. Clinical review: distinguishing constitutional delay of growth and puberty from isolated hypogonadotropic hypogonadism: critical appraisal of available diagnostic tests. J Clin Endocrinol Metab. 2012;97(9):3056–67.

    Article  CAS  PubMed  Google Scholar 

  • Hawkins J, et al. Prevalence of endocrine disorders among children exposed to lavender essential oil and tea tree essential oils. Int J Pediatr Adolesc Med. 2022;9(2):117–24.

    Article  PubMed  Google Scholar 

  • Herman-Giddens ME, Steffes J, Harris D, Slora E, Hussey M, Dowshen SA, et al. Secondary sexual characteristics in boys: data from the Pediatric Research in Office Settings Network. Pediatrics. 2012;130(5):e1058–68.

    Article  PubMed  Google Scholar 

  • Hilczer M, Smyczynska J, Lewinski A. Limitations of clinical utility of growth hormone stimulating tests in diagnosing children with short stature. Endocr Regul. 2006;40(3):69–75.

    CAS  PubMed  Google Scholar 

  • Howard SR, Dunkel L, et al. Delayed puberty-phenotypic diversity, molecular genetic mechanisms, and recent discoveries. Endocr Rev. 2019;87(4):1613–20.

    Google Scholar 

  • Ibba A, et al. IGF1 for the diagnosis of growth hormone deficiency in children and adolescents: a reappraisal. Endocr Connect. 2020;9(11):1095–102.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Javaid MK, et al. Best practice management guidelines for fibrous dysplasia/McCune-Albright syndrome: a consensus statement from the FD/MAS international consortium. Orphanet J Rare Dis. 2019;64(2):121–7.

    Google Scholar 

  • Joint LWPES/ESPE CAH Working Group. Consensus statement on 21-hydroxylase deficiency from the Lawson Wilkins Pediatric Endocrine Society and the European Society for Paediatric Endocrinology. J Clin Endocrinol Metab. 2002;87(9):4048–53.

    Article  Google Scholar 

  • Jonklaas J, Bianco AC, Bauer AJ, Burman KD, Cappola AR, Celi FS, et al. Guidelines for the treatment of hypothyroidism: prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement. Thyroid. 2014;24(12):1670–751.

    Article  PubMed  PubMed Central  Google Scholar 

  • Kamath C, Adlan MA, Premawardhana LD. The role of thyrotrophin receptor antibody assays in Graves’ disease. J Thyroid Res. 2012;2012:525936.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kapadia CR, Nebesio TD, Myers SE, Willi S, Miller BS, Allen DB, et al. Endocrine effects of inhaled corticosteroids in children. JAMA Pediatr. 2016;170(2):163–70.

    Article  PubMed  Google Scholar 

  • Karras S, Memi E, Kintiraki E, Krassas GE. Pathogenesis of propylthiouracil-related hepatotoxicity in children: present concepts. J Pediatr Endocrinol Metab. 2012;25(7-8):623–30.

    Article  CAS  PubMed  Google Scholar 

  • Koch HM, Wittassek M, Bruning T, Angerer J, Heudorf U. Exposure to phthalates in 5-6 years old primary school starters in Germany—a human biomonitoring study and a cumulative risk assessment. Int J Hyg Environ Health. 2011;214(3):188–95.

    Article  CAS  PubMed  Google Scholar 

  • Krishna K, Fuqua J, et al. Use of gonadotropin-releasing hormone analogs in children: Update by an International Consortium. Horm Res Paediatr. 2019;91(6):357–72.

    Article  Google Scholar 

  • Kuczmarski RJ, Ogden CL, Guo SS, Grummer-Strawn LM, Flegal KM, Mei Z, et al. CDC growth charts for the United States: methods and development. Vital Health Stat 11. 2000;2002(246):1–190.

    Google Scholar 

  • Lafranchi S. Thyroiditis and acquired hypothyroidism. Pediatr Ann. 1992;21(1):29, 32-9

    Article  CAS  PubMed  Google Scholar 

  • Lawrence S, Cummings E, Chanoine JP, Metzger DL, Palmert M, Sharma A, et al. Canadian Pediatric Endocrine Group extension to WHO growth charts: Why bother? Paediatr Child Health. 2013;18(6):295–7.

    Article  PubMed  PubMed Central  Google Scholar 

  • Lawrence S, Cummings E, Chanoine JP, Metzger D, Palmert M, Sharma A, et al. Use of growth charts in Canada: A National Canadian Paediatric Surveillance Program survey. Paediatr Child Health. 2015;20(4):185–8.

    Article  PubMed  PubMed Central  Google Scholar 

  • Lazar L, Frumkin RB, Battat E, Lebenthal Y, Phillip M, Meyerovitch J. Natural history of thyroid function tests over 5 years in a large pediatric cohort. J Clin Endocrinol Metab. 2009;94(5):1678–82.

    Article  CAS  PubMed  Google Scholar 

  • Lee HS, Hwang JS. The treatment of Graves’ disease in children and adolescents. Ann Pediatr Endocrinol Metab. 2014;19(3):122–6.

    Article  PubMed  PubMed Central  Google Scholar 

  • Lee DS, Ryoo NY, et al. Basal luteinizing hormone and follicular stimulating hormone: is it sufficient for the diagnosis of precocious puberty in girls? Ann Pediatr Endocrinol Metab. 2013;18(4):196–201.

    Article  PubMed  PubMed Central  Google Scholar 

  • Leger J, Gelwane G, Kaguelidou F, Benmerad M, Alberti C. Positive impact of long-term antithyroid drug treatment on the outcome of children with Graves’ disease: National Long-term Cohort Study. J Clin Endocrinol Metab. 2012;97(1):110–9.

    Article  CAS  PubMed  Google Scholar 

  • Leger J, et al. European Society for Paediatric Endocrinology consensus guidelines on screening, diagnosis, and management of congenital hypothyroidism. Horm Res Paediatr. 2014;81:80–103.

    Article  CAS  PubMed  Google Scholar 

  • Lem AJ, et al. Adult height in short children born SGA treated with growth hormone and gonadotropin releasing hormone analog: results of a randomized, dose-response GH trial. J Clin Endocrinol Metab. 2012;97(11):4096–105.

    Article  CAS  PubMed  Google Scholar 

  • Leschek EW, Flor AC, et al. Effect of antiandrogen, aromatase inhibitor, and gonadotropin-releasing hormone analog on adult height in familial male precocious puberty. J Pediatr. 2017;190:229–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lewis KA, Goldyn AK, West KW, Eugster EA. A single histrelin implant is effective for 2 years for treatment of central precocious puberty. J Pediatr. 2013;163(4):1214–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Loche S, et al. Effect of body mass index on the growth hormone response to clonidine stimulation testing in children with short stature. Clin Endocrinol (Oxf). 2011;74(6):726–31.

    Article  CAS  PubMed  Google Scholar 

  • Loftus J, et al. Association of daily growth hormone injection adherence and height among children with growth hormone deficiency. Endocr Pract. 2022;28(6):565–71.

    Article  PubMed  Google Scholar 

  • Lomniczi A, Wright H, Castellano JM, Sonmez K, Ojeda SR. A system biology approach to identify regulatory pathways underlying the neuroendocrine control of female puberty in rats and nonhuman primates. Horm Behav. 2013;64(2):175–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Marin G, Domene HM, Barnes KM, Blackwell BJ, Cassorla FG, Cutler GB Jr. The effects of estrogen priming and puberty on the growth hormone response to standardized treadmill exercise and arginine-insulin in normal girls and boys. J Clin Endocrinol Metab. 1994;79(2):537–41.

    CAS  PubMed  Google Scholar 

  • Martin DD, Wit JM, Hochberg Z, Savendahl L, van Rijn RR, Fricke O, et al. The use of bone age in clinical practice—Part 1. Horm Res Paediatr. 2011a;76(1):1–9.

    Article  CAS  PubMed  Google Scholar 

  • Martin DD, Wit JM, Hochberg Z, van Rijn RR, Fricke O, Werther G, et al. The use of bone age in clinical practice—Part 2. Horm Res Paediatr. 2011b;76(1):10–6.

    Article  CAS  PubMed  Google Scholar 

  • Mauras N, Ross JL. Randomized trial of aromatase inhibitors, growth hormone, or combination in pubertal boys with idiopathic, short stature. J Clin Endocrinol Metab. 2016;101(12):4984–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mauras N, Gonzalez de Pijem L, Hsiang HY, Desrosiers P, Rapaport R, Schwartz ID, et al. Anastrozole increases predicted adult height of short adolescent males treated with growth hormone: a randomized, placebo-controlled, multicenter trial for one to three years. J Clin Endocrinol Metab. 2008;93(3):823–31.

    Article  CAS  PubMed  Google Scholar 

  • Mauras N, Ross J, et al. Management of growth disorders in puberty: GH, GnRHa, and aromatase inhibitors: a clinical review. Endocr Rev. 2023;44(1):1–13.

    Article  PubMed  Google Scholar 

  • Mericq MV, Eggers M, Avila A, Cutler GB Jr, Cassorla F. Near final height in pubertal growth hormone (GH)-deficient patients treated with GH alone or in combination with luteinizing hormone-releasing hormone analog: results of a prospective, randomized trial. J Clin Endocrinol Metab. 2000;85(2):569–73.

    CAS  PubMed  Google Scholar 

  • Midyett LK, Moore WV, Jacobson JD. Are pubertal changes in girls before age 8 benign? Pediatrics. 2003;111(1):47–51.

    Article  PubMed  Google Scholar 

  • Miller BS, et al. Emergency management of adrenal insufficiency in children: advocating for treatment options in outpatient and field settings. J Invest Med. 2020;68(1):16–25.

    Article  Google Scholar 

  • Morishima A, Grumbach MM, Simpson ER, Fisher C, Qin K. Aromatase deficiency in male and female siblings caused by a novel mutation and the physiological role of estrogens. J Clin Endocrinol Metab. 1995;80(12):3689–98.

    CAS  PubMed  Google Scholar 

  • Mul D, Wit JM, Oostdijk W, Van den Broeck J. The effect of pubertal delay by GnRH agonist in GH-deficient children on final height. J Clin Endocrinol Metab. 2001;86(10):4655–6.

    Article  CAS  PubMed  Google Scholar 

  • Murray PG, Dattani MT, Clayton PE. Controversies in the diagnosis and management of growth hormone deficiency in childhood and adolescence. Arch Dis Child. 2016;101(1):96–100.

    Article  CAS  PubMed  Google Scholar 

  • Natale V, Rajagopalan A. Worldwide variation in human growth and the World Health Organization growth standards: a systematic review. BMJ Open. 2014;4(1):e003735.

    Article  PubMed  PubMed Central  Google Scholar 

  • National Institute for Health and Care Excellence [NICE]. Guidelines on the use of growth hormone. NICE; 2010.

    Google Scholar 

  • Nejedly N, et al. Normal and abnormal growth in the pediatric patient. Curr Probl Pediatr Adolesc Health Care. 2020;50(3):100771.

    Article  PubMed  Google Scholar 

  • Neumann U, et al. A prospective study of children aged 0-8 years with CAH and adrenal insufficiency treated with hydrocortisone granules. J Clin Endocrinol Metab. 2021;106(3):e1433–40. https://doi.org/10.1210/clinem/dgaa626.

    Article  PubMed  Google Scholar 

  • Oliveri A, et al. Congenital hypothyroidism due to defects of thyroid development and mild increase of TSH at screening: data from the Italian National Registry of infants with congenital hypothyroidism. J Clin Endocrinol Metab. 2013;98:1403–8.

    Article  Google Scholar 

  • Owen BM, Bookout AL, Ding X, Lin VY, Atkin SD, Gautron L, et al. FGF21 contributes to neuroendocrine control of female reproduction. Nat Med. 2013;19(9):1153–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Palmert MR, Dunkel L. Clinical practice. Delayed puberty. N Engl J Med. 2012;366(5):443–53.

    Article  CAS  PubMed  Google Scholar 

  • Palmert MR, et al. Clinical practice. Delayed puberty. N Engl J Med. 2012;366(5):443–53.

    Article  CAS  PubMed  Google Scholar 

  • Parent A-S, et al. The timing of normal puberty and the age limits of sexual precocity: variations around the world, secular trends, and changes after migration. Endocr Rev. 2003;24(5):668–93.

    Article  PubMed  Google Scholar 

  • Perry R, Kecha O, Paquette J, Huot C, Van Vliet G, Deal C. Primary adrenal insufficiency in children: twenty years experience at the Sainte-Justine Hospital, Montreal. J Clin Endocrinol Metab. 2005;90(6):3243–50.

    Article  CAS  PubMed  Google Scholar 

  • Phelan N, Conway SH, Llahana S, Conway GS. Quantification of the adverse effect of ethinylestradiol containing oral contraceptive pills when used in conjunction with growth hormone replacement in routine practice. Clin Endocrinol (Oxf). 2012;76(5):729–33.

    Article  CAS  PubMed  Google Scholar 

  • Porter J, et al. Immediate-release granule formulation of hydrocortisone, Alkindi®, for treatment of paediatric adrenal insufficiency (Infacort development programme). Expert Rev Endocrinol Metab. 2018;13(3):119–24.

    Article  CAS  PubMed  Google Scholar 

  • Punthakee Z, Legault L, Polychronakos C. Prednisolone in the treatment of adrenal insufficiency: a re-evaluation of relative potency. J Pediatr. 2003;143(3):402–5.

    Article  CAS  PubMed  Google Scholar 

  • Quigley CA, Wan X, Garg S, Kowal K, Cutler GB Jr, Ross JL. Effects of low-dose estrogen replacement during childhood on pubertal development and gonadotropin concentrations in patients with Turner syndrome: results of a randomized, double-blind, placebo-controlled clinical trial. J Clin Endocrinol Metab. 2014;99(9):E1754–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rabbiosi S, et al. Congenital hypothyroidism with eutopic thyroid gland: analysis of clinical and biochemical features at diagnosis and after re-evaluation. J Clin Endocrinol Metabol. 2013;98(4):1395–402.

    Article  CAS  Google Scholar 

  • Radetti G, Maselli M, Buzi F, Corrias A, Mussa A, Cambiaso P, et al. The natural history of the normal/mild elevated TSH serum levels in children and adolescents with Hashimoto’s thyroiditis and isolated hyperthyrotropinaemia: a 3-year follow-up. Clin Endocrinol (Oxf). 2012;76(3):394–8.

    Article  CAS  PubMed  Google Scholar 

  • Ramsey J, et al. Lavender products associated with premature Thelarche and prepubertal gynecomastia: case reports and endocrine-disrupting chemical activities. J Clin Endocrinol Metab. 2019;104(11):5393–405.

    Article  PubMed  PubMed Central  Google Scholar 

  • Ranke M, et al. Relevance of IGF-I, IGFBP-3, and IGFBP-2 measurements during GH treatment of GH-deficient and non-GH-deficient children and adolescents. Horm Res. 2001;55(3):115–24.

    CAS  PubMed  Google Scholar 

  • Ranke M, et al. Treatment of children and adolescents with idiopathic short stature. Nat Rev Endocrinol. 2013;9(6):325–34.

    Article  CAS  PubMed  Google Scholar 

  • Resende EAMR, Lara BHJ, et al. Assessment of basal and gonadotropin-releasing hormone-stimulated gonadotropins by immunochemiluminometric and immunofluorometric assays in normal children. J Clin Endo Metab. 2007;92(4):1424–9.

    Article  CAS  Google Scholar 

  • Rivkees SA. Pediatric Graves’ disease: management in the post-propylthiouracil era. Int J Pediatr Endocrinol. 2014;2014(1):10.

    Article  PubMed  PubMed Central  Google Scholar 

  • Rivkees SA, Szarfman A. Dissimilar hepatotoxicity profiles of propylthiouracil and methimazole in children. J Clin Endocrinol Metab. 2010;95(7):3260–7.

    Article  CAS  PubMed  Google Scholar 

  • Rivkees SA, Sklar C, Freemark M. Clinical review 99: the management of Graves’ disease in children, with special emphasis on radioiodine treatment. J Clin Endocrinol Metab. 1998;83(11):3767–76.

    CAS  PubMed  Google Scholar 

  • Rodd C, Metzger DL, Sharma A. Extending World Health Organization weight-for-age reference curves to older children. BMC Pediatr. 2014;14:32.

    Article  PubMed  PubMed Central  Google Scholar 

  • Rogol AJ, et al. Etiologies and early diagnosis of short stature and growth failure in children and adolescents. J Pediatr. 2014;164(5 Suppl):S1–14.e6. https://doi.org/10.1016/j.jpeds.2014.02.027.

    Article  PubMed  Google Scholar 

  • Rose SR, Vogiatzi MG, Copeland KC. A general pediatric approach to evaluating a short child. Pediatr Rev. 2005;26(11):410–20.

    Article  PubMed  Google Scholar 

  • Rose SR, Brown RS, Foley T, Kaplowitz PB, Kaye CI, Sundararajan S, et al. Update of newborn screening and therapy for congenital hypothyroidism. Pediatrics. 2006;117(6):2290–303.

    Article  PubMed  Google Scholar 

  • Ross DS, et al. American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis. Thyroid. 2016;26(10):1343–421.

    Article  PubMed  Google Scholar 

  • Rothenbuhler A, Linglart A, et al. A randomized pilot trial of growth hormone with anastrozole versus growth hormone alone, starting at the very end of puberty in adolescents with idiopathic short stature. Int J Pediatr Endocrinol. 2015b;2015(1):4.

    Article  PubMed  PubMed Central  Google Scholar 

  • Saggese G, Federico G, Barsanti S, Fiore L. The effect of administering gonadotropin-releasing hormone agonist with recombinant-human growth hormone (GH) on the final height of girls with isolated GH deficiency: results from a controlled study. J Clin Endocrinol Metab. 2001;86(5):1900–4.

    Article  CAS  PubMed  Google Scholar 

  • Sas TC, Gault EJ, Bardsley MZ, Menke LA, Freriks K, Perry RJ, et al. Safety and efficacy of oxandrolone in growth hormone-treated girls with Turner syndrome: evidence from recent studies and recommendations for use. Horm Res Paediatr. 2014;81(5):289–97.

    Article  CAS  PubMed  Google Scholar 

  • Savendahl L, et al. Long-term mortality after childhood growth hormone treatment: the SAGhE cohort study. Lancet. 2020;8(8):683–92.

    Google Scholar 

  • Savendahl L, et al. Effective GH replacement with once-weekly somapacitan vs daily gh in children with GHD: 3-year results from REAL 3. J Clin Endocrinol Metabol. 2021;107(5):1357–67.

    Article  Google Scholar 

  • Scalco RC, et al. Effectiveness of the combined recombinant human growth hormone and gonadotropin-releasing hormone analog therapy in pubertal patients with short stature due to SHOX deficiency. J Clin Endocrinol Metab. 2010;95(1):328–32.

    Article  CAS  PubMed  Google Scholar 

  • Schmidt H, Knorr D, et al. Oral testosterone undecanoate for the induction of puberty in anorchid boys. Arch Dis Child. 1998;78(4):397.

    Article  CAS  PubMed  Google Scholar 

  • Schroor EJ, van Weissenbruch MM, Knibbe P, de Waal HA D-v. The effect of prolonged administration of an anabolic steroid (oxandrolone) on growth in boys with constitutionally delayed growth and puberty. Eur J Pediatr. 1995;154(12):953–7.

    Article  CAS  PubMed  Google Scholar 

  • Sedlmeyer IL, Palmert MR, et al. Delayed puberty: analysis of a large case series from an academic center. J Clin Endocrinol Metab. 2002;87(4):1613.

    Article  CAS  PubMed  Google Scholar 

  • Selva KA, Mandel SH, Rien L, Sesser D, Miyahira R, Skeels M, et al. Initial treatment dose of L-thyroxine in congenital hypothyroidism. J Pediatr. 2002;141(6):786–92.

    Article  CAS  PubMed  Google Scholar 

  • Selva KA, Harper A, Downs A, Blasco PA, Lafranchi SH. Neurodevelopmental outcomes in congenital hypothyroidism: comparison of initial T4 dose and time to reach target T4 and TSH. J Pediatr. 2005;147(6):775–80.

    Article  CAS  PubMed  Google Scholar 

  • Seminara SB. Kisspeptin in reproduction. Semin Reprod Med. 2007;25(5):337–43.

    Article  CAS  PubMed  Google Scholar 

  • Seminara SB, Messager S, Chatzidaki EE, Thresher RR, Acierno JS Jr, Shagoury JK, et al. The GPR54 gene as a regulator of puberty. N Engl J Med. 2003;349(17):1614–27.

    Article  CAS  PubMed  Google Scholar 

  • Shulman DI, Palmert MR, Kemp SF. Adrenal insufficiency: still a cause of morbidity and death in childhood. Pediatrics. 2007;119(2):e484–94.

    Article  PubMed  Google Scholar 

  • Silverman LA, Neely EK, Kletter GB, Lewis K, Chitra S, Terleckyj O, et al. Long-term continuous suppression with once-yearly histrelin subcutaneous implants for the treatment of central precocious puberty: A Final Report of a Phase 3 Multicenter Trial. J Clin Endocrinol Metab. 2015;100(6):2354–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Smith DW, Truog W, Rogers JE, Greitzer LJ, Skinner AL, McCann JJ, et al. Shifting linear growth during infancy: illustration of genetic factors in growth from fetal life through infancy. J Pediatr. 1976;89(2):225–30.

    Article  CAS  PubMed  Google Scholar 

  • Smith EP, Boyd J, Frank GR, Takahashi H, Cohen RM, Specker B, et al. Estrogen resistance caused by a mutation in the estrogen-receptor gene in a man. N Engl J Med. 1994;331(16):1056–61.

    Article  CAS  PubMed  Google Scholar 

  • Speiser PW, et al. Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2018;103:4043–88.

    Article  PubMed  PubMed Central  Google Scholar 

  • Stephen MD, et al. Gonadotropin-dependent precocious puberty: neoplastic causes and endocrine considerations. Int J Pediatr Endocrinol. 2011;2011(1):184502.

    Article  PubMed  PubMed Central  Google Scholar 

  • Swerdlow AJ, Higgins CD, Adlard P, Preece MA. Risk of cancer in patients treated with human pituitary growth hormone in the UK, 1959-85: a cohort study. Lancet. 2002;360(9329):273–7.

    Google Scholar 

  • Tamhane S, et al. GH Therapy in childhood cancer survivors: a systematic review and meta-analysis. J Clin Endo Metab. 2018;103(8):2794–801.

    Article  Google Scholar 

  • Tarquinio DC, Jones MC, Jones KL, Bird LM. Growth charts for 22q11 deletion syndrome. Am J Med Genet A. 2012;158A(11):2672–81.

    Article  PubMed  Google Scholar 

  • Thornton P, et al. Weekly lonapegsomatropin in treatment-naïve children with growth hormone deficiency: The Phase 3 heiGHt Trial. J Clin Endocrinol Metab. 2021;106(11):3184–95.

    Article  PubMed  PubMed Central  Google Scholar 

  • Touwslager RN, Gielen M, Derom C, Mulder AL, Gerver WJ, Zimmermann LJ, et al. Determinants of infant growth in four age windows: a twin study. J Pediatr. 2011a;158(4):566–72e2.

    Article  PubMed  Google Scholar 

  • Touwslager RN, Gielen M, Mulder AL, Gerver WJ, Zimmermann LJ, Fowler T, et al. Changes in genetic and environmental effects on growth during infancy. Am J Clin Nutr. 2011b;94(6):1568–74.

    Article  CAS  PubMed  Google Scholar 

  • van Gool SA, Kamp GA, Visser-van Balen H, Mul D, Waelkens JJ, Jansen M, et al. Final height outcome after three years of growth hormone and gonadotropin-releasing hormone agonist treatment in short adolescents with relatively early puberty. J Clin Endocrinol Metab. 2007;92(4):1402–8.

    Article  PubMed  Google Scholar 

  • Varimo T, Huopio H, et al. Letrozole versus testosterone for promotion of endogenous puberty in boys with constitutional delay of growth and puberty: a randomised controlled phase 3 trial. Lancet Child Adolesc Health. 2019;3(2):109–20.

    Article  PubMed  Google Scholar 

  • Weise M, Drinkard B, Mehlinger SL, Holzer SM, Eisenhofer G, Charmandari E, et al. Stress dose of hydrocortisone is not beneficial in patients with classic congenital adrenal hyperplasia undergoing short-term, high-intensity exercise. J Clin Endocrinol Metab. 2004;89(8):3679–84.

    Article  CAS  PubMed  Google Scholar 

  • WHO Multicentre Growth Reference Study Group. Assessment of differences in linear growth among populations in the WHO Multicentre Growth Reference Study. Acta Paediatr Suppl. 2006;450:56–65.

    Article  Google Scholar 

  • Wickman S, Sipila I, Ankarberg-Lindgren C, Norjavaara E, Dunkel L. A specific aromatase inhibitor and potential increase in adult height in boys with delayed puberty: a randomised controlled trial. Lancet. 2001;357(9270):1743–8.

    Article  CAS  PubMed  Google Scholar 

  • Wit JM, Oostdijk W. Novel approaches to short stature therapy. Best Pract Res Clin Endocrinol Metab. 2015;29(3):353–66.

    Article  CAS  PubMed  Google Scholar 

  • Wit JM, Hero M, Nunez SB. Aromatase inhibitors in pediatrics. Nat Rev Endocrinol. 2012;8(3):135–47.

    Article  CAS  Google Scholar 

  • Wittassek M, Koch HM, Angerer J, Bruning T. Assessing exposure to phthalates - the human biomonitoring approach. Mol Nutr Food Res. 2011;55(1):7–31.

    Article  CAS  PubMed  Google Scholar 

  • Wittneben JG, et al. Esthetic and clinical performance of implant-supported all-ceramic crowns made with prefabricated or CAD/CAM Zirconia abutments: a randomized, multicenter clinical trial. Hum Reprod. 2017;96(2):163–70.

    CAS  Google Scholar 

  • Xie C, Zhao Y, Gao L, Chen J, Cai D, Zhang Y. Elevated phthalates’ exposure in children with constitutional delay of growth and puberty. Mol Cell Endocrinol. 2015;407:67–73.

    Article  CAS  PubMed  Google Scholar 

  • Xie C, Epstein LH, Eiden RD, Shenassa ED, Li X, Liao Y, et al. Stunting at 5 years among SGA newborns. Pediatrics. 2016;137(2):e20152636.

    Article  PubMed  Google Scholar 

  • Yanovski JA, Rose SR, Municchi G, Pescovitz OH, Hill SC, Cassorla FG, et al. Treatment with a luteinizing hormone-releasing hormone agonist in adolescents with short stature. N Engl J Med. 2003;348(10):908–17.

    Article  CAS  PubMed  Google Scholar 

  • Yazdani P, Lin Y, Raman V, Haymond M. A single sample GnRHa stimulation test in the diagnosis of precocious puberty. Int J Pediatr Endocrinol. 2012;2012(1):23.

    Article  PubMed  PubMed Central  Google Scholar 

  • Yuce O, Bideci A, et al. Diagnostic value of urinary luteinizing hormone levels in the monitoring of precocious puberty treatment. Arch Endocrinol Metab. 2020;64(2):121–7.

    PubMed  PubMed Central  Google Scholar 

  • Zemel BS, Pipan M, Stallings VA, Hall W, Schadt K, Freedman DS, et al. Growth charts for children with Down syndrome in the United States. Pediatrics. 2015;136(5):e1204–11.

    Article  PubMed  Google Scholar 

  • Zhou B, et al. A meta-analysis of combination therapy with gonadotrophin-releasing hormone agonist and growth hormone for children with idiopathic short stature and normal timed puberty. Endocrine. 2022;75(3):698–708.

    Article  CAS  PubMed  Google Scholar 

  • Zhu J, et al. A shared genetic basis for self-limited delayed puberty and idiopathic hypogonadotropic hypogonadism. J Clin Endocrinol Metab. 2015;100(4):E646–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Seth D. Marks .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2023 The Author(s), under exclusive license to Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Marks, S.D., Wicklow, B.A. (2023). Update in Pediatric Endocrinology. In: Beckwith, S. (eds) Update in Pediatrics. Springer, Cham. https://doi.org/10.1007/978-3-031-41542-5_14

Download citation

  • DOI: https://doi.org/10.1007/978-3-031-41542-5_14

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-031-41541-8

  • Online ISBN: 978-3-031-41542-5

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics