Precocious Puberty

Chapter

Abstract

Puberty is the stage of development leading to sexual maturation and reproductive potential. Normal puberty is regulated by the hypothalamic–pituitary–gonadal (HPG) axis which is activated at the onset of puberty from the quiescent prepubertal state. Precocious puberty is the onset of pubertal changes at an earlier age than is expected for the population. Precocious pubertal development may occur by either premature activation of the HPG axis (central precocious puberty) or exposure to endogenous or exogenous sex steroids independent of HPG axis activation (peripheral precocious puberty). Although some children evaluated for precocious puberty will have variants of normal development such as premature thelarche (breast development), pathologic causes will need to be ruled out in others (Kaplowitz, J Clin Endocrinol Metab 89(8):3644–3650, 2004).

Keywords

Testosterone Androgen Estradiol Tempo Acne 

References

  1. 1.
    Kaplowitz P. Clinical characteristics of 104 children referred for evaluation of precocious puberty. J Clin Endocrinol Metab. 2004;89(8):3644–50.PubMedCrossRefGoogle Scholar
  2. 2.
    Kaplan SL, Grumbach MM. Clinical review 14: pathophysiology and treatment of sexual precocity. J Clin Endocrinol Metab. 1990;71(4):785–9.PubMedCrossRefGoogle Scholar
  3. 3.
    de Kretser DM, Hedger MP, Loveland KL, Phillips DJ. Inhibins, activins and follistatin in reproduction. Hum Reprod Update. 2002;8(6):529–41.PubMedCrossRefGoogle Scholar
  4. 4.
    Apter D, Butzow TL, Laughlin GA, Yen SS. Gonadotropin-releasing hormone pulse generator activity during pubertal transition in girls: pulsatile and diurnal patterns of circulating gonadotropins. J Clin Endocrinol Metab. 1993;76(4):940–9.PubMedCrossRefGoogle Scholar
  5. 5.
    Sisk CL, Foster DL. The neural basis of puberty and adolescence. Nat Neurosci. 2004;7(10):1040–7.PubMedCrossRefGoogle Scholar
  6. 6.
    Penny R, Olambiwonnu NO, Frasier SD. Serum gonadotropin concentrations during the first four years of life. J Clin Endocrinol Metab. 1974;38(2):320–1.PubMedCrossRefGoogle Scholar
  7. 7.
    Schmidt H, Schwarz HP. Serum concentrations of LH and FSH in the healthy newborn. Eur J Endocrinol. 2000;143(2):213–5.PubMedCrossRefGoogle Scholar
  8. 8.
    Parent AS, Matagne V, Bourguignon JP. Control of puberty by excitatory amino acid neurotransmitters and its clinical implications. Endocrine. 2005;28(3):281–6.PubMedCrossRefGoogle Scholar
  9. 9.
    Marshall WA, Tanner JM. Variations in pattern of pubertal changes in girls. Arch Dis Child. 1969;44(235):291–303.PubMedCrossRefGoogle Scholar
  10. 10.
    Marshall WA, Tanner JM. Variations in the pattern of pubertal changes in boys. Arch Dis Child. 1970;45(239):13–23.PubMedCrossRefGoogle Scholar
  11. 11.
    Sun SS, Schubert CM, Chumlea WC, et al. National estimates of the timing of sexual maturation and racial differences among US children. Pediatrics. 2002;110(5):911–9.PubMedCrossRefGoogle Scholar
  12. 12.
    Sun SS, Schubert CM, Liang R, et al. Is sexual maturity occurring earlier among U.S. children? J Adolesc Health. 2005;37(5):345–55.PubMedCrossRefGoogle Scholar
  13. 13.
    Chumlea WC, Schubert CM, Roche AF, et al. Age at menarche and racial comparisons in US girls. Pediatrics. 2003;111(1):110–3.PubMedCrossRefGoogle Scholar
  14. 14.
    Freedman DS, Khan LK, Serdula MK, Dietz WH, Srinivasan SR, Berenson GS. Relation of age at menarche to race, time period, and anthropometric dimensions: the Bogalusa Heart Study. Pediatrics. 2002;110(4):e43.PubMedCrossRefGoogle Scholar
  15. 15.
    Kaplowitz PB, Slora EJ, Wasserman RC, Pedlow SE, Herman-Giddens ME. Earlier onset of puberty in girls: relation to increased body mass index and race. Pediatrics. 2001;108(2):347–53.PubMedCrossRefGoogle Scholar
  16. 16.
    Lee PA, Kulin HE, Guo SS. Age of puberty among girls and the diagnosis of precocious puberty. Pediatrics. 2001;107(6):1493.PubMedCrossRefGoogle Scholar
  17. 17.
    Weise M, De-Levi S, Barnes KM, Gafni RI, Abad V, Baron J. Effects of estrogen on growth plate senescence and epiphyseal fusion. Proc Natl Acad Sci U S A. 2001;98(12):6871–6.PubMedCrossRefGoogle Scholar
  18. 18.
    Herman-Giddens ME, Wang L, Koch G. Secondary sexual characteristics in boys: estimates from the national health and nutrition examination survey III, 1988–1994. Arch Pediatr Adolesc Med. 2001;155(9):1022–8.PubMedCrossRefGoogle Scholar
  19. 19.
    Tinggaard J, Mieritz MG, Sorensen K, et al. The physiology and timing of male puberty. Curr Opin Endocrinol Diabetes Obes. 2012;19(3):197–203.PubMedCrossRefGoogle Scholar
  20. 20.
    Blizzard RM, Martha PM, Kerrigan JR, Mauras N, Rogol AD. Changes in growth hormone (GH) secretion and in growth during puberty. J Endocrinol Invest. 1989;12(8 Suppl 3):65–8.PubMedGoogle Scholar
  21. 21.
    Midyett LK, Moore WV, Jacobson JD. Are pubertal changes in girls before age 8 benign? Pediatrics. 2003;111(1):47–51.PubMedCrossRefGoogle Scholar
  22. 22.
    Kaplowitz PB, Oberfield SE. Reexamination of the age limit for defining when puberty is precocious in girls in the United States: implications for evaluation and treatment. Drug and Therapeutics and Executive Committees of the Lawson Wilkins Pediatric Endocrine Society. Pediatrics. 1999;104(4 Pt 1):936–41.PubMedCrossRefGoogle Scholar
  23. 23.
    Palmert MR, Malin HV, Boepple PA. Unsustained or slowly progressive puberty in young girls: initial presentation and long-term follow-up of 20 untreated patients. J Clin Endocrinol Metab. 1999;84(2):415–23.PubMedCrossRefGoogle Scholar
  24. 24.
    Pasquino AM, Pucarelli I, Passeri F, Segni M, Mancini MA, Municchi G. Progression of premature thelarche to central precocious puberty. J Pediatr. 1995;126(1):11–4.PubMedCrossRefGoogle Scholar
  25. 25.
    Pescovitz OH, Hench KD, Barnes KM, Loriaux DL, Cutler Jr GB. Premature thelarche and central precocious puberty: the relationship between clinical presentation and the gonadotropin response to luteinizing hormone-releasing hormone. J Clin Endocrinol Metab. 1988;67(3):474–9.PubMedCrossRefGoogle Scholar
  26. 26.
    Salardi S, Cacciari E, Mainetti B, Mazzanti L, Pirazzoli P. Outcome of premature thelarche: relation to puberty and final height. Arch Dis Child. 1998;79(2):173–4.PubMedCrossRefGoogle Scholar
  27. 27.
    Ghizzoni L, Milani S. The natural history of premature adrenarche. J Pediatr Endocrinol Metab. 2000;13 Suppl 5:1247–51.PubMedGoogle Scholar
  28. 28.
    Ibanez L, Dimartino-Nardi J, Potau N, Saenger P. Premature adrenarche—normal variant or forerunner of adult disease? Endocr Rev. 2000;21(6):671–96.PubMedCrossRefGoogle Scholar
  29. 29.
    Ibanez L, Virdis R, Potau N, et al. Natural history of premature pubarche: an auxological study. J Clin Endocrinol Metab. 1992;74(2):254–7.PubMedCrossRefGoogle Scholar
  30. 30.
    Ibanez L, Potau N, Virdis R, et al. Postpubertal outcome in girls diagnosed of premature pubarche during childhood: increased frequency of functional ovarian hyperandrogenism. J Clin Endocrinol Metab. 1993;76(6):1599–603.PubMedCrossRefGoogle Scholar
  31. 31.
    Rosenfield RL. Normal and almost normal precocious variations in pubertal development premature pubarche and premature thelarche revisited. Horm Res. 1994;41 Suppl 2:7–13.PubMedCrossRefGoogle Scholar
  32. 32.
    Baranowski E, Hogler W. An unusual presentation of acquired hypothyroidism: the Van Wyk-Grumbach syndrome. Eur J Endocrinol. 2012;166(3):537–42.PubMedCrossRefGoogle Scholar
  33. 33.
    Jaruratanasirikul S, Patarapinyokul S, Mitranun W. Androgen-producing adrenocortical carcinoma: report of 3 cases with different clinical presentations. J Med Assoc Thai. 2012;95(6):816–20.PubMedGoogle Scholar
  34. 34.
    Kunz GJ, Klein KO, Clemons RD, Gottschalk ME, Jones KL. Virilization of young children after topical androgen use by their parents. Pediatrics. 2004;114(1):282–4.PubMedCrossRefGoogle Scholar
  35. 35.
    Durbin KL, Diaz-Montes T, Loveless MB. Van wyk and grumbach syndrome: an unusual case and review of the literature. J Pediatr Adolesc Gynecol. 2011;24(4):e93–6.PubMedCrossRefGoogle Scholar
  36. 36.
    Barnes ND, Hayles AB, Ryan RJ. Sexual maturation in juvenile hypothyroidism. Mayo Clin Proc. 1973;48(12):849–56.PubMedGoogle Scholar
  37. 37.
    Li ST, Lozano P, Grossman DC, Graham E. Hormone-containing hair product use in prepubertal children. Arch Pediatr Adolesc Med. 2002;156(1):85–6.PubMedCrossRefGoogle Scholar
  38. 38.
    Yu YM, Punyasavatsu N, Elder D, D’Ercole AJ. Sexual development in a two-year-old boy induced by topical exposure to testosterone. Pediatrics. 1999;104(2):e23.PubMedCrossRefGoogle Scholar
  39. 39.
    Buzi F, Pilotta A, Dordoni D, Lombardi A, Zaglio S, Adlard P. Pelvic ultrasonography in normal girls and in girls with pubertal precocity. Acta Paediatr. 1998;87(11):1138–45.PubMedCrossRefGoogle Scholar
  40. 40.
    De Sanctis V, Corrias A, Rizzo V, et al. Etiology of central precocious puberty in males: the results of the Italian Study Group for Physiopathology of Puberty. J Pediatr Endocrinol Metab. 2000;13 Suppl 1:687–93.PubMedGoogle Scholar
  41. 41.
    Faizah M, Zuhanis A, Rahmah R, et al. Precocious puberty in children: a review of imaging findings. Biomed Imaging Interv J. 2012;8(1):e6.PubMedGoogle Scholar
  42. 42.
    Mogensen SS, Aksglaede L, Mouritsen A, et al. Pathological and incidental findings on brain MRI in a single-center study of 229 consecutive girls with early or precocious puberty. PLoS One. 2012;7(1):e29829.PubMedCrossRefGoogle Scholar
  43. 43.
    Neely EK, Wilson DM, Lee PA, Stene M, Hintz RL. Spontaneous serum gonadotropin concentrations in the evaluation of precocious puberty. J Pediatr. 1995;127(1):47–52.PubMedCrossRefGoogle Scholar
  44. 44.
    Brito VN, Batista MC, Borges MF, et al. Diagnostic value of fluorometric assays in the evaluation of precocious puberty. J Clin Endocrinol Metab. 1999;84(10):3539–44.PubMedCrossRefGoogle Scholar
  45. 45.
    Carel JC, Leger J. Clinical practice. Precocious puberty. N Engl J Med. 2008;358(22):2366–77.PubMedCrossRefGoogle Scholar
  46. 46.
    Chemaitilly W, Trivin C, Adan L, Gall V, Sainte-Rose C, Brauner R. Central precocious puberty: clinical and laboratory features. Clin Endocrinol (Oxf). 2001;54(3):289–94.CrossRefGoogle Scholar
  47. 47.
    Iughetti L, Predieri B, Ferrari M, et al. Diagnosis of central precocious puberty: endocrine assessment. J Pediatr Endocrinol Metab. 2000;13 Suppl 1:709–15.PubMedGoogle Scholar
  48. 48.
    de Brito VN, Latronico AC, Arnhold IJ, et al. Treatment of gonadotropin dependent precocious puberty due to hypothalamic hamartoma with gonadotropin releasing hormone agonist depot. Arch Dis Child. 1999;80(3):231–4.PubMedCrossRefGoogle Scholar
  49. 49.
    Kim EY, Lee MI. Psychosocial aspects in girls with idiopathic precocious puberty. Psychiatry Investig. 2012;9(1):25–8.PubMedCrossRefGoogle Scholar
  50. 50.
    Crowley Jr WF, Comite F, Vale W, Rivier J, Loriaux DL, Cutler Jr GB. Therapeutic use of pituitary desensitization with a long-acting lhrh agonist: a potential new treatment for idiopathic precocious puberty. J Clin Endocrinol Metab. 1981;52(2):370–2.PubMedCrossRefGoogle Scholar
  51. 51.
    Rosenfield RL. Selection of children with precocious puberty for treatment with gonadotropin releasing hormone analogs. J Pediatr. 1994;124(6):989–91.PubMedCrossRefGoogle Scholar
  52. 52.
    Mul D, Bertelloni S, Carel JC, Saggese G, Chaussain JL, Oostdijk W. Effect of gonadotropin-releasing hormone agonist treatment in boys with central precocious puberty: final height results. Horm Res. 2002;58(1):1–7.PubMedCrossRefGoogle Scholar
  53. 53.
    Klein KO, Barnes KM, Jones JV, Feuillan PP, Cutler Jr GB. Increased final height in precocious puberty after long-term treatment with LHRH agonists: the National Institutes of Health experience. J Clin Endocrinol Metab. 2001;86(10):4711–6.PubMedCrossRefGoogle Scholar
  54. 54.
    Bar A, Linder B, Sobel EH, Saenger P, DiMartino-Nardi J. Bayley-Pinneau method of height prediction in girls with central precocious puberty: correlation with adult height. J Pediatr. 1995;126(6):955–8.PubMedCrossRefGoogle Scholar
  55. 55.
    Comite F, Cassorla F, Barnes KM, et al. Luteinizing hormone releasing hormone analogue therapy for central precocious puberty. Long-term effect on somatic growth, bone maturation, and predicted height. JAMA. 1986;255(19):2613–6.PubMedCrossRefGoogle Scholar
  56. 56.
    Kletter GB, Kelch RP. Clinical review 60: effects of gonadotropin-releasing hormone analog therapy on adult stature in precocious puberty. J Clin Endocrinol Metab. 1994;79(2):331–4.PubMedCrossRefGoogle Scholar
  57. 57.
    Weise M, Flor A, Barnes KM, Cutler Jr GB, Baron J. Determinants of growth during gonadotropin-releasing hormone analog therapy for precocious puberty. J Clin Endocrinol Metab. 2004;89(1):103–7.PubMedCrossRefGoogle Scholar
  58. 58.
    Badaru A, Wilson DM, Bachrach LK, et al. Sequential comparisons of one-month and three-month depot leuprolide regimens in central precocious puberty. J Clin Endocrinol Metab. 2006;91(5):1862–7.PubMedCrossRefGoogle Scholar
  59. 59.
    Eugster EA, Clarke W, Kletter GB, et al. Efficacy and safety of histrelin subdermal implant in children with central precocious puberty: a multicenter trial. J Clin Endocrinol Metab. 2007;92(5):1697–704.PubMedCrossRefGoogle Scholar
  60. 60.
    Fuld K, Chi C, Neely EK. A randomized trial of 1- and 3-month depot leuprolide doses in the treatment of central precocious puberty. J Pediatr. 2011;159(6):982–987 e981.PubMedCrossRefGoogle Scholar
  61. 61.
    Bhatia S, Neely EK, Wilson DM. Serum luteinizing hormone rises within minutes after depot leuprolide injection: implications for monitoring therapy. Pediatrics. 2002;109(2):E30.PubMedCrossRefGoogle Scholar
  62. 62.
    Kunz GJ, Sherman TI, Klein KO. Luteinizing hormone (LH) and estradiol suppression and growth in girls with central precocious puberty: is more suppression better? Are pre-injection LH levels useful in monitoring treatment? J Pediatr Endocrinol Metab. 2007;20(11):1189–98.PubMedCrossRefGoogle Scholar
  63. 63.
    Cassio A, Bal MO, Orsini LF, et al. Reproductive outcome in patients treated and not treated for idiopathic early puberty: long-term results of a randomized trial in adults. J Pediatr. 2006;149(4):532–6.PubMedCrossRefGoogle Scholar
  64. 64.
    Antoniazzi F, Zamboni G, Bertoldo F, et al. Bone mass at final height in precocious puberty after gonadotropin-releasing hormone agonist with and without calcium supplementation. J Clin Endocrinol Metab. 2003;88(3):1096–101.PubMedCrossRefGoogle Scholar
  65. 65.
    Unal O, Berberoglu M, Evliyaoglu O, Adiyaman P, Aycan Z, Ocal G. Effects on bone mineral density of gonadotropin releasing hormone analogs used in the treatment of central precocious puberty. J Pediatr Endocrinol Metab. 2003;16(3):407–11.PubMedCrossRefGoogle Scholar
  66. 66.
    Carel JC, Eugster EA, Rogol A, et al. Consensus statement on the use of gonadotropin-releasing hormone analogs in children. Pediatrics. 2009;123(4):e752–62.PubMedCrossRefGoogle Scholar
  67. 67.
    Arrigo T, Cisternino M, Galluzzi F, et al. Analysis of the factors affecting auxological response to GnRH agonist treatment and final height outcome in girls with idiopathic central precocious puberty. Eur J Endocrinol. 1999;141(2):140–4.PubMedCrossRefGoogle Scholar
  68. 68.
    Lee PA. Central precocious puberty. An overview of diagnosis, treatment, and outcome. Endocrinol Metab Clin North Am. 1999;28(4):901–18.PubMedCrossRefGoogle Scholar
  69. 69.
    Tanaka T, Niimi H, Matsuo N, et al. Results of long-term follow-up after treatment of central precocious puberty with leuprorelin acetate: evaluation of effectiveness of treatment and recovery of gonadal function. The TAP-144-SR Japanese Study Group on Central Precocious Puberty. J Clin Endocrinol Metab. 2005;90(3):1371–6.PubMedCrossRefGoogle Scholar
  70. 70.
    Eugster EA, Rubin SD, Reiter EO, Plourde P, Jou HC, Pescovitz OH. Tamoxifen treatment for precocious puberty in McCune-Albright syndrome: a multicenter trial. J Pediatr. 2003;143(1):60–6.PubMedCrossRefGoogle Scholar
  71. 71.
    Feuillan P, Calis K, Hill S, Shawker T, Robey PG, Collins MT. Letrozole treatment of precocious puberty in girls with the McCune-Albright syndrome: a pilot study. J Clin Endocrinol Metab. 2007;92(6):2100–6.PubMedCrossRefGoogle Scholar
  72. 72.
    Mieszczak J, Lowe ES, Plourde P, Eugster EA. The aromatase inhibitor anastrozole is ineffective in the treatment of precocious puberty in girls with McCune-Albright syndrome. J Clin Endocrinol Metab. 2008;93(7):2751–4.PubMedCrossRefGoogle Scholar
  73. 73.
    Reiter EO, Norjavaara E. Testotoxicosis: current viewpoint. Pediatr Endocrinol Rev. 2005;3(2):77–86.PubMedGoogle Scholar
  74. 74.
    Haddad N, Eugster E. An update on the treatment of precocious puberty in McCune-Albright syndrome and testotoxicosis. J Pediatr Endocrinol Metab. 2007;20(6):653–61.PubMedCrossRefGoogle Scholar
  75. 75.
    Bertelloni S, Baroncelli GI, Lala R, et al. Long-term outcome of male-limited gonadotropin-independent precocious puberty. Horm Res. 1997;48(5):235–9.PubMedCrossRefGoogle Scholar
  76. 76.
    Kreher NC, Pescovitz OH, Delameter P, Tiulpakov A, Hochberg Z. Treatment of familial male-limited precocious puberty with bicalutamide and anastrozole. J Pediatr. 2006;149(3):416–20.PubMedCrossRefGoogle Scholar
  77. 77.
    Leschek EW, Jones J, Barnes KM, Hill SC, Cutler Jr GB. Six-year results of spironolactone and testolactone treatment of familial male-limited precocious puberty with addition of deslorelin after central puberty onset. J Clin Endocrinol Metab. 1999;84(1):175–8.PubMedCrossRefGoogle Scholar
  78. 78.
    Reiter EO, Mauras N, McCormick K, et al. Bicalutamide plus anastrozole for the treatment of gonadotropin-independent precocious puberty in boys with testotoxicosis: a phase II, open-label pilot study (BATT). J Pediatr Endocrinol Metab. 2010;23(10):999–1009.PubMedCrossRefGoogle Scholar
  79. 79.
    Soriano-Guillen L, Lahlou N, Chauvet G, Roger M, Chaussain JL, Carel JC. Adult height after ketoconazole treatment in patients with familial male-limited precocious puberty. J Clin Endocrinol Metab. 2005;90(1):147–51.PubMedCrossRefGoogle Scholar
  80. 80.
    Almeida MQ, Brito VN, Lins TS, et al. Long-term treatment of familial male-limited precocious puberty (testotoxicosis) with cyproterone acetate or ketoconazole. Clin Endocrinol (Oxf). 2008;69(1):93–8.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Pediatric EndocrinologyUniversity of FloridaGainsvilleUSA

Personalised recommendations