Delayed Puberty

  • Caroline Colvin
  • Gayathri Devineni
  • Ambika P. Ashraf


Puberty is an indelible period of metamorphosis of the human life cycle, which culminates in sexual maturation and reproductive capability. The failure to develop in a normal and timely fashion can, therefore, cause profound anxiety in individuals and families. Furthermore, awareness that pubertal delay can indicate significant underlying pathology compels physicians to investigate any perceived deviation from a rigidly defined acceptable pattern of development. The ability to distinguish between various causes of delay and to differentiate significant underlying pathology from common benign delay can be daunting often requiring prudent investigation. Depending on the ultimate diagnosis, treatment options vary, but most patients can ultimately expect to achieve pubertal maturation and fertility.

Puberty is initiated when the hypothalamic gonadotropin-releasing hormone (GnRH) pulse generator begins secreting brief nocturnal pulses of GnRH from the hypothalamic arcuate nucleus that subsequently stimulate the pituitary to release luteinizing hormone (LH) and follicle-stimulating hormone (FSH) (Palmert and Dunkel, N Engl J Med 366:443–453, 2012). A recently discovered hormone, kisspeptin, acts on the hypothalamic GnRH neurons, stimulating GnRH secretion (Seminara and Crowley, J Neuroendocrinol 20:727–731, 2008). The gonadotropins (LH and FSH) promote gonadal maturation and gonads synthesize sex steroids, including testosterone and estrogen, and other proteins. LH acts on theca cells and interstitial cells to produce progestins and androgens which diffuse into adjacent granulosa cells. FSH acts on granulosa cells to stimulate aromatization of these androgens to estrogen. Estrogen and testosterone then promote pubertal changes throughout the body and provide negative feedback effect on the GnRH and gonadotropins (Fig. 17.1). The first physical signs of puberty are typically breast development in girls and testicular enlargement in boys (testicular volume >3 ml/≥2.5 cm in length). Some children, especially girls, have the appearance of pubic hair prior to the initiation of breast development, but in the absence of other puberty signs this usually represents adrenarche [adrenal source of androgens, independent of hypothalamic–pituitary–gonadal (HPG) axis maturation] and not true puberty. The trigger(s) for reactivation of the HPG axis is not completely understood; but, modifying factors include general health, nutrition, genetic determinants, and pubertal timing among primary relatives. Elevated body mass index is associated with delayed puberty in boys (Lee et al., Arch Pediatr Adolesc Med 164:139–144, 2010; Nathan et al., J Pediatr Endocrinol Metab 19:971–977, 2006). Many of the genes involved in the HPG axis maturation are still unknown. Kisspeptin-1 and its cognate receptor (GPR54, a G-protein-coupled receptor) are integral to the normal function of HPG axis and play a critical role in the physiologic regulation of puberty (Seminara and Crowley, J Neuroendocrinol 20:727–731, 2008; Messager et al., Proc Natl Acad Sci U S A 102:1761–1766, 2005). Kisspeptin is co-expressed with neurokinin B and dynorphin and hence these signaling pathways are also important in physiologic regulation of puberty (Silveira et al., J Clin Endocrinol Metab 95:2276–2280, 2010). There is evidence that leptin, a 16 kDa hormone product of the Ob gene, synthesized by adipocytes, plays a permissive role (Gueorguiev et al., Pituitary 4:79–86, 2001; Farooqi et al., N Engl J Med 341:879–884, 1999).

Although the lower limit of normal for the onset of puberty is contestible, the average age for this process is generally accepted to be 9–10 years for girls and 10–11 years for boys (Palmert and Dunkel, N Engl J Med 366:443–453, 2012; Parent et al., Endocr Rev 24:668–693, 2003). Delayed puberty can be defined as failure to demonstrate signs of pubertal maturation by an age that is ≥2 standard deviations above the population mean (Palmert and Dunkel, N Engl J Med 366:443–453, 2012). Lack of testicular enlargement by age 14 in males, lack of breast development by age 13 in females, absence of menarche by age 16 in girls, or absence of menarche within 5 years of pubertal onset (Delemarre et al., Eur J Endocrinol 159(Suppl 1):S9–15, 2008; Fenichel, Endocr Dev 22:138–159, 2012). Interestingly, males present far more often for evaluation of delayed puberty, but it has been suggested that this is in part due to a referral bias (Sedlmeyer and Palmert, J Clin Endocrinol Metab 87:1613–1620, 2002; Rosenfield, J Clin Endocrinol Metab 70:559–562, 1990).


Luteinizing Hormone Pubertal Timing Hypogonadotropic Hypogonadism Gonadal Dysgenesis Primary Amenorrhea 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Sedlmeyer IL, Palmert MR. Delayed puberty: analysis of a large case series from an academic center. J Clin Endocrinol Metab. 2002;87:1613–20.PubMedCrossRefGoogle Scholar
  2. 2.
    Palmert MR, Dunkel L. Clinical practice. Delayed puberty. N Engl J Med. 2012;366:443–53.PubMedCrossRefGoogle Scholar
  3. 3.
    Seminara SB, Crowley Jr WF. Kisspeptin and GPR54: discovery of a novel pathway in reproduction. J Neuroendocrinol. 2008;20:727–31.PubMedCrossRefGoogle Scholar
  4. 4.
    Lee JM, Kaciroti N, Appugliese D, Corwyn RF, Bradley RH, Lumeng JC. Body mass index and timing of pubertal initiation in boys. Arch Pediatr Adolesc Med. 2010;164:139–44.PubMedCrossRefGoogle Scholar
  5. 5.
    Nathan BM, Sedlmeyer IL, Palmert MR. Impact of body mass index on growth in boys with delayed puberty. J Pediatr Endocrinol Metab. 2006;19:971–7.PubMedCrossRefGoogle Scholar
  6. 6.
    Messager S, Chatzidaki EE, Ma D, Hendrick AG, Zahn D, Dixon J, Thresher RR, Malinge I, Lomet D, Carlton MB, Colledge WH, Caraty A, Aparicio SA. Kisspeptin directly stimulates gonadotropin-releasing hormone release via G protein-coupled receptor 54. Proc Natl Acad Sci U S A. 2005;102:1761–6.PubMedCrossRefGoogle Scholar
  7. 7.
    Silveira LG, Noel SD, Silveira-Neto AP, Abreu AP, Brito VN, Santos MG, Bianco SD, Kuohung W, Xu S, Gryngarten M, Escobar ME, Arnhold IJ, Mendonca BB, Kaiser UB, Latronico AC. Mutations of the KISS1 gene in disorders of puberty. J Clin Endocrinol Metab. 2010;95:2276–80.PubMedCrossRefGoogle Scholar
  8. 8.
    Gueorguiev M, Goth ML, Korbonits M. Leptin and puberty: a review. Pituitary. 2001;4:79–86.PubMedCrossRefGoogle Scholar
  9. 9.
    Farooqi IS, Jebb SA, Langmack G, Lawrence E, Cheetham CH, Prentice AM, Hughes IA, McCamish MA, O’Rahilly S. Effects of recombinant leptin therapy in a child with congenital leptin deficiency. N Engl J Med. 1999;341:879–84.PubMedCrossRefGoogle Scholar
  10. 10.
    Parent AS, Teilmann G, Juul A, Skakkebaek NE, Toppari J, Bourguignon JP. The timing of normal puberty and the age limits of sexual precocity: variations around the world, secular trends, andchanges after migration. Endocr Rev. 2003;24:668–93.PubMedCrossRefGoogle Scholar
  11. 11.
    Delemarre EM, Felius B, Delemarre-van de Waal HA. Inducing puberty. Eur J Endocrinol. 2008;159 Suppl 1:S9–15.PubMedCrossRefGoogle Scholar
  12. 12.
    Fenichel P. Delayed puberty. Endocr Dev. 2012;22:138–59.PubMedCrossRefGoogle Scholar
  13. 13.
    Rosenfield RL. Clinical review 6: diagnosis and management of delayed puberty. J Clin Endocrinol Metab. 1990;70:559–62.PubMedCrossRefGoogle Scholar
  14. 14.
    Wehkalampi K, Widen E, Laine T, Palotie A, Dunkel L. Association of the timing of puberty with a chromosome 2 locus. J Clin Endocrinol Metab. 2008;93:4833–9.PubMedCrossRefGoogle Scholar
  15. 15.
    Albanese A, Stanhope R. Predictive factors in the determination of final height in boys with constitutional delay of growth and puberty. J Pediatr. 1995;126:545–50.PubMedCrossRefGoogle Scholar
  16. 16.
    Counts DR, Pescovitz OH, Barnes KM, Hench KD, Chrousos GP, Sherins RJ, Comite F, Loriaux DL, Cutler Jr GB. Dissociation of adrenarche and gonadarche in precocious puberty and in isolated hypogonadotropic hypogonadism. J Clin Endocrinol Metab. 1987;64:1174–8.PubMedCrossRefGoogle Scholar
  17. 17.
    Kelch RP, Hopwood NJ, Marshall JC. Diagnosis of gonadotropin deficiency in adolescents: limited usefulness of a standard gonadotropin-releasing hormone test in obese boys. J Pediatr. 1980;97:820–4.PubMedCrossRefGoogle Scholar
  18. 18.
    Wu FC, Brown DC, Butler GE, Stirling HF, Kelnar CJ. Early morning plasma testosterone is an accurate predictor of imminent pubertal development in prepubertal boys. J Clin Endocrinol Metab. 1993;76:26–31.PubMedCrossRefGoogle Scholar
  19. 19.
    Grinspon RP, Ropelato MG, Gottlieb S, Keselman A, Martinez A, Ballerini MG, Domene HM, Rey RA. Basal follicle-stimulating hormone and peak gonadotropin levels after gonadotropin-releasing hormone infusion show high diagnostic accuracy in boys with suspicion of hypogonadotropic hypogonadism. J Clin Endocrinol Metab. 2010;95:2811–8.PubMedCrossRefGoogle Scholar
  20. 20.
    Resende EA, Lara BH, Reis JD, Ferreira BP, Pereira GA, Borges MF. Assessment of basal and gonadotropin-releasing hormone-stimulated gonadotropins by immunochemiluminometric and immunofluorometric assays in normal children. J Clin Endocrinol Metab. 2007;92:1424–9.PubMedCrossRefGoogle Scholar
  21. 21.
    Coutant R, Biette-Demeneix E, Bouvattier C, Bouhours-Nouet N, Gatelais F, Dufresne S, Rouleau S, Lahlou N. Baseline inhibin B and anti-Mullerian hormone measurements for diagnosis of hypogonadotropic hypogonadism (HH) in boys with delayed puberty. J Clin Endocrinol Metab. 2010;95:5225–32.PubMedCrossRefGoogle Scholar
  22. 22.
    Simon D. Puberty in chronically diseased patients. Horm Res. 2002;57 Suppl 2:53–6.PubMedCrossRefGoogle Scholar
  23. 23.
    Buchacz K, Rogol AD, Lindsey JC, Wilson CM, Hughes MD, Seage 3rd GR, Oleske JM, Rogers AS. Delayed onset of pubertal development in children and adolescents with perinatally acquired HIV infection. J Acquir Immune Defic Syndr. 2003;33:56–65.PubMedCrossRefGoogle Scholar
  24. 24.
    Caronia LM, Martin C, Welt CK, Sykiotis GP, Quinton R, Thambundit A, Avbelj M, Dhruvakumar S, Plummer L, Hughes VA, Seminara SB, Boepple PA, Sidis Y, Crowley Jr WF, Martin KA, Hall JE, Pitteloud N. A genetic basis for functional hypothalamic amenorrhea. N Engl J Med. 2011;364:215–25.PubMedCrossRefGoogle Scholar
  25. 25.
    Kaplowitz P. Clinical characteristics of 104 children referred for evaluation of precocious puberty. J Clin Endocrinol Metab. 2004;89:3644–50.PubMedCrossRefGoogle Scholar
  26. 26.
    Wyshak G, Frisch RE. Evidence for a secular trend in age of menarche. N Engl J Med. 1982;306:1033–5.PubMedCrossRefGoogle Scholar
  27. 27.
    de Roux N, Genin E, Carel JC, Matsuda F, Chaussain JL, Milgrom E. Hypogonadotropic hypogonadism due to loss of function of the KiSS1-derived peptide receptor GPR54. Proc Natl Acad Sci U S A. 2003;100:10972–6.PubMedCrossRefGoogle Scholar
  28. 28.
    Semple RK, Topaloglu AK. The recent genetics of hypogonadotrophic hypogonadism—novel insights and new questions. Clin Endocrinol (Oxf). 2010;72:427–35.CrossRefGoogle Scholar
  29. 29.
    Shaw ND, Seminara SB, Welt CK, Au MG, Plummer L, Hughes VA, Dwyer AA, Martin KA, Quinton R, Mericq V, Merino PM, Gusella JF, Crowley Jr WF, Pitteloud N, Hall JE. Expanding the phenotype and genotype of female GnRH deficiency. J Clin Endocrinol Metab. 2011;96:E566–76.PubMedCrossRefGoogle Scholar
  30. 30.
    Raivio T, Falardeau J, Dwyer A, Quinton R, Hayes FJ, Hughes VA, Cole LW, Pearce SH, Lee H, Boepple P, Crowley Jr WF, Pitteloud N. Reversal of idiopathic hypogonadotropic hypogonadism. N Engl J Med. 2007;357:863–73.PubMedCrossRefGoogle Scholar
  31. 31.
    Halac I, Zimmerman D. Endocrine manifestations of craniopharyngioma. Childs Nerv Syst. 2005;21:640–8.PubMedCrossRefGoogle Scholar
  32. 32.
    Darzy KH, Shalet SM. Pathophysiology of radiation-induced growth hormone deficiency: efficacy and safety of GH replacement. Growth Horm IGF Res. 2006;16(Suppl A):S30–40.PubMedCrossRefGoogle Scholar
  33. 33.
    Dattani MT, Martinez-Barbera JP, Thomas PQ, Brickman JM, Gupta R, Martensson IL, Toresson H, Fox M, Wales JK, Hindmarsh PC, Krauss S, Beddington RS, Robinson IC. Mutations in the homeobox gene HESX1/Hesx1 associated with septo-optic dysplasia in human and mouse. Nat Genet. 1998;19:125–33.PubMedCrossRefGoogle Scholar
  34. 34.
    Reynaud R, Gueydan M, Saveanu A, Vallette-Kasic S, Enjalbert A, Brue T, Barlier A. Genetic screening of combined pituitary hormone deficiency: experience in 195 patients. J Clin Endocrinol Metab. 2006;91:3329–36.PubMedCrossRefGoogle Scholar
  35. 35.
    Zentner GE, Layman WS, Martin DM, Scacheri PC. Molecular and phenotypic aspects of CHD7 mutation in CHARGE syndrome. Am J Med Genet A. 2010;152A:674–86.PubMedCrossRefGoogle Scholar
  36. 36.
    Pinto G, Abadie V, Mesnage R, Blustajn J, Cabrol S, Amiel J, Hertz-Pannier L, Bertrand AM, Lyonnet S, Rappaport R, Netchine I. CHARGE syndrome includes hypogonadotropic hypogonadism and abnormal olfactory bulb development. J Clin Endocrinol Metab. 2005;90:5621–6.PubMedCrossRefGoogle Scholar
  37. 37.
    Goldstone AP, Holland AJ, Hauffa BP, Hokken-Koelega AC, Tauber M. Recommendations for the diagnosis and management of Prader-Willi syndrome. J Clin Endocrinol Metab. 2008;93:4183–97.PubMedCrossRefGoogle Scholar
  38. 38.
    Beales PL, Elcioglu N, Woolf AS, Parker D, Flinter FA. New criteria for improved diagnosis of Bardet-Biedl syndrome: results of a population survey. J Med Genet. 1999;36:437–46.PubMedGoogle Scholar
  39. 39.
    Pasquino AM, Passeri F, Pucarelli I, Segni M, Municchi G. Spontaneous pubertal development in Turner’s syndrome. Italian Study Group for Turner’s Syndrome. J Clin Endocrinol Metab. 1997;82:1810–3.PubMedCrossRefGoogle Scholar
  40. 40.
    Latronico AC, Arnhold IJ. Inactivating mutations of LH and FSH receptors—from genotype to phenotype. Pediatr Endocrinol Rev. 2006;4:28–31.PubMedGoogle Scholar
  41. 41.
    Beranova M, Oliveira LM, Bedecarrats GY, Schipani E, Vallejo M, Ammini AC, Quintos JB, Hall JE, Martin KA, Hayes FJ, Pitteloud N, Kaiser UB, Crowley Jr WF, Seminara SB. Prevalence, phenotypic spectrum, and modes of inheritance of gonadotropin-releasing hormone receptor mutations in idiopathic hypogonadotropic hypogonadism. J Clin Endocrinol Metab. 2001;86:1580–8.PubMedCrossRefGoogle Scholar
  42. 42.
    Layman LC. Mutations in the follicle-stimulating hormone-beta (FSH beta) and FSH receptor genes in mice and humans. Semin Reprod Med. 2000;18:5–10.PubMedCrossRefGoogle Scholar
  43. 43.
    Layman LC, Lee EJ, Peak DB, Namnoum AB, Vu KV, van Lingen BL, Gray MR, McDonough PG, Reindollar RH, Jameson JL. Delayed puberty and hypogonadism caused by mutations in the follicle-stimulating hormone beta-subunit gene. N Engl J Med. 1997;337:607–11.PubMedCrossRefGoogle Scholar
  44. 44.
    Howell SJ, Shalet SM. Spermatogenesis after cancer treatment: damage and recovery. J Natl Cancer Inst Monogr 2005:12–7Google Scholar
  45. 45.
    Myhre AG, Halonen M, Eskelin P, Ekwall O, Hedstrand H, Rorsman F, Kampe O, Husebye ES. Autoimmune polyendocrine syndrome type 1 (APS I) in Norway. Clin Endocrinol (Oxf). 2001;54:211–7.CrossRefGoogle Scholar
  46. 46.
    Kaufman FR, Kogut MD, Donnell GN, Goebelsmann U, March C, Koch R. Hypergonadotropic hypogonadism in female patients with galactosemia. N Engl J Med. 1981;304:994–8.PubMedCrossRefGoogle Scholar
  47. 47.
    Lee PA, Houk CP, Ahmed SF, Hughes IA. Consensus statement on management of intersex disorders. International Consensus Conference on Intersex. Pediatrics. 2006;118:e488–500.PubMedCrossRefGoogle Scholar
  48. 48.
    Arici A, Matalliotakis IM, Koumantakis GE, Goumenou AG, Neonaki MA, Koumantakis EE. Diagnostic role of inhibin B in resistant ovary syndrome associated with secondary amenorrhea. Fertil Steril. 2002;78:1324–6.PubMedCrossRefGoogle Scholar
  49. 49.
    Mueller A, Berkholz A, Dittrich R, Wildt L. Spontaneous normalization of ovarian function and pregnancy in a patient with resistant ovary syndrome. Eur J Obstet Gynecol Reprod Biol. 2003;111:210–3.PubMedCrossRefGoogle Scholar
  50. 50.
    ACOG Committee on Adolescent Health Care. ACOG Committee Opinion No. 355: Vaginal agenesis: diagnosis, management, and routine care. Obstet Gynecol. 2006;108:1605–9.CrossRefGoogle Scholar
  51. 51.
    Wit JM, Rekers-Mombarg LT. Final height gain by GH therapy in children with idiopathic short stature is dose dependent. J Clin Endocrinol Metab. 2002;87:604–11.PubMedCrossRefGoogle Scholar
  52. 52.
    Ibanez L, Potau N, Zampolli M, Virdis R, Gussinye M, Carrascosa A, Saenger P, Vicens-Calvet E. Use of leuprolide acetate response patterns in the early diagnosis of pubertal disorders: comparison with the gonadotropin-releasing hormone test. J Clin Endocrinol Metab. 1994;78:30–5.PubMedCrossRefGoogle Scholar
  53. 53.
    Lanes R. A GnRH analog test in diagnosing gonadotropin deficiency in males with delayed puberty. J Pediatr. 2006;149:731; author reply 731–2.PubMedCrossRefGoogle Scholar
  54. 54.
    Wilson DA, Hofman PL, Miles HL, Unwin KE, McGrail CE, Cutfield WS. Evaluation of the buserelin stimulation test in diagnosing gonadotropin deficiency in males with delayed puberty. J Pediatr. 2006;148:89–94.PubMedCrossRefGoogle Scholar
  55. 55.
    Zamboni G, Antoniazzi F, Tato L. Use of the gonadotropin-releasing hormone agonist triptorelin in the diagnosis of delayed puberty in boys. J Pediatr. 1995;126:756–8.PubMedCrossRefGoogle Scholar
  56. 56.
    Segal TY, Mehta A, Anazodo A, Hindmarsh PC, Dattani MT. Role of gonadotropin-releasing hormone and human chorionic gonadotropin stimulation tests in differentiating patients with hypogonadotropic hypogonadism from those with constitutional delay of growth and puberty. J Clin Endocrinol Metab. 2009;94:780–5.PubMedCrossRefGoogle Scholar
  57. 57.
    Dunkel L, Perheentupa J, Virtanen M, Maenpaa J. Gonadotropin-releasing hormone test and human chorionic gonadotropin test in the diagnosis of gonadotropin deficiency in prepubertal boys. J Pediatr. 1985;107:388–92.PubMedCrossRefGoogle Scholar
  58. 58.
    Dunkel L, Perheentupa J, Virtanen M, Maenpaa J. GnRH and HCG tests are both necessary in differential diagnosis of male delayed puberty. Am J Dis Child. 1985;139:494–8.PubMedGoogle Scholar
  59. 59.
    Degros V, Cortet-Rudelli C, Soudan B, Dewailly D. The human chorionic gonadotropin test is more powerful than the gonadotropin-releasing hormone agonist test to discriminate male isolated hypogonadotropic hypogonadism from constitutional delayed puberty. Eur J Endocrinol. 2003;149:23–9.PubMedCrossRefGoogle Scholar
  60. 60.
    Kauschansky A, Dickerman Z, Phillip M, Weintrob N, Strich D. Use of GnRH agonist and human chorionic gonadotrophin tests for differentiating constitutional delayed puberty from gonadotrophin deficiency in boys. Clin Endocrinol (Oxf). 2002;56:603–7.CrossRefGoogle Scholar
  61. 61.
    Arrigo T, Cisternino M, De Luca F, Saggese G, Messina MF, Pasquino AM, De Sanctis V. Final height outcome in both untreated and testosterone-treated boys with constitutional delay of growth and puberty. J Pediatr Endocrinol Metab. 1996;9:511–7.PubMedCrossRefGoogle Scholar
  62. 62.
    Buyukgebiz A. Treatment of constitutional delayed puberty with a combination of testosterone esters. Horm Res. 1995;44 Suppl 3:32–4.PubMedGoogle Scholar
  63. 63.
    Soliman AT, Khadir MM, Asfour M. Testosterone treatment in adolescent boys with constitutional delay of growth and development. Metabolism. 1995;44:1013–5.PubMedCrossRefGoogle Scholar
  64. 64.
    Ankarberg-Lindgren C, Elfving M, Wikland KA, Norjavaara E. Nocturnal application of transdermal estradiol patches produces levels of estradiol that mimic those seen at the onset of spontaneous puberty in girls. J Clin Endocrinol Metab. 2001;86:3039–44.PubMedCrossRefGoogle Scholar
  65. 65.
    Brook CG. Management of delayed puberty. Br Med J (Clin Res Ed). 1985;290:657–8.CrossRefGoogle Scholar
  66. 66.
    Bondy CA. Care of girls and women with Turner syndrome: a guideline of the Turner Syndrome Study Group. J Clin Endocrinol Metab. 2007;92:10–25.PubMedCrossRefGoogle Scholar
  67. 67.
    Achermann JC, Jameson JL. Advances in the molecular genetics of hypogonadotropic hypogonadism. J Pediatr Endocrinol Metab. 2001;14:3–15.PubMedCrossRefGoogle Scholar
  68. 68.
    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;357:1743–8.PubMedCrossRefGoogle Scholar
  69. 69.
    Poirot C, Vacher-Lavenu MC, Helardot P, Guibert J, Brugieres L, Jouannet P. Human ovarian tissue cryopreservation: indications and feasibility. Hum Reprod. 2002;17:1447–52.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Caroline Colvin
    • 1
  • Gayathri Devineni
    • 2
  • Ambika P. Ashraf
    • 1
  1. 1.Division of Pediatric Endocrinology and Metabolism, Department of PediatricsChildren’s of Alabama, University of Alabama at BirminghamBirminghamUSA
  2. 2.Pediatric EndocrinologyChildren’s Hospital of AtlantaAtlantaUSA

Personalised recommendations