Advertisement

Precocious Puberty

  • Madhusmita Misra
  • Sally Radovick
Chapter

Abstract

Precocious puberty has been a focus of interest for both the pediatric endocrinologist and the primary pediatrician for many years. The development and application of GnRH agonist (GnRHa) therapy to treat central precocious puberty in the 1980s significantly changed our approach to this disorder. More recently, application of molecular biological techniques has provided us with a better understanding of the intricacies of the regulation of gonadotropin and sex-steroid production characteristic of normal pubertal development and provided us with the tools to elucidate the etiologies of previously uncharacterized disorders of precocious puberty.

Keywords

Precocious puberty Gonadotropin-releasing hormone (GnRH) GnRH agonist (GnRHa) Follicle-stimulating hormone (FSH) Luteinizing hormone (LH) Androgen Estrogen Central precocious puberty (CPP) Peripheral precocious puberty Gonadotropin-independent precocious puberty 

Notes

Acknowledgment

The editors wish to thank Henry Rodriguez MD and Grace C. Dougan MD for their contributions to this chapter in the prior edition.

References

  1. 1.
    Grumbach MM, Kaplan SL. Recent advances in the diagnosis and management of sexual precocity. Acta Paediatr Jpn. 1988;30(Suppl):155–75.PubMedGoogle Scholar
  2. 2.
    Schwanzel-Fukuda M, et al. Migration of luteinizing hormone-releasing hormone (LHRH) neurons in early human embryos. J Comp Neurol. 1996;366:547–57.PubMedCrossRefGoogle Scholar
  3. 3.
    Plant TM, et al. The arcuate nucleus and the control of gonadotropin and prolactin secretion in the female rhesus monkey (Macaca mulatta). Endocrinology. 1978;102(1):52–62.PubMedCrossRefGoogle Scholar
  4. 4.
    Mueller PL, et al. Hormone ontogeny in the ovine fetus. IX. Luteinizing hormone and follicle-stimulating hormone response to luteinizing hormone-releasing factor in mid-and late gestation and in the neonate. Endocrinology. 1981;108(3):881–6.PubMedCrossRefGoogle Scholar
  5. 5.
    Sklar CA, et al. Hormone ontogeny in the ovine fetus. VII. Circulating luteinizing hormone and follicle-stimulating hormone in mid-and late gestation. Endocrinology. 1981;108(3):874–80.PubMedCrossRefGoogle Scholar
  6. 6.
    Winter JS, et al. Gonadotrophins and steroid hormones in the blood and urine of prepubertal girls and other primates. Clin Endocrinol Metab. 1978;7(3):513–30.PubMedCrossRefGoogle Scholar
  7. 7.
    Zsarmovsky AH, Garcia-Segura TL, Horvath LM, Naftolin BF. Plasticity of the hypothalamic GABA system and their relationship with GnRH neurons during positive gonadotropin feedback in non-human primates in 82nd Annual Meeting of the Endocrine Society; 2000; Toronto, ON, Canada.Google Scholar
  8. 8.
    Zhang SJ, Jackson MB. GABA-activated chloride channels in secretory nerve endings. Science. 1993;259:531–4.PubMedCrossRefGoogle Scholar
  9. 9.
    Terasawa EF, Fernandez DL. Neurobiological mechanisms of the onset of puberty in primates. Endocr Rev. 2001;22(1):111–51.PubMedGoogle Scholar
  10. 10.
    Dhom G. The prepubertal and pubertal growth of the adrenal (adrenarche). Beitr Pathol. 1973;150(4):357–77.PubMedCrossRefGoogle Scholar
  11. 11.
    Sklar CA, Kaplan SL, Grumbach MM. Evidence for dissociation between adrenarche and gonadarche: studies in patients with idiopathic precocious puberty, gonadal dysgenesis, isolated gonadotropin deficiency, and constitutionally delayed growth and adolescence. J Clin Endocrinol Metab. 1980;51(3):548–56.PubMedCrossRefGoogle Scholar
  12. 12.
    James VHT. The endocrine function of the human adrenal cortex. Proceedings of the Serono Symposia, Vol. 18. London/New York: Academic; 1978. p. ix, 628.Google Scholar
  13. 13.
    Zhang LH, et al. Serine phosphorylation of human P450c 17 increases 17,20-lyase activity: implications for adrenarche and the polycystic ovary syndrome. Proc Natl Acad Sci U S A. 1995;92(23):10,619–23.CrossRefGoogle Scholar
  14. 14.
    Miller WL, Auchus RJ, Geller DH. The regulation of 17,20 lyase activity. Steroids. 1997;62(1):133–42.PubMedCrossRefGoogle Scholar
  15. 15.
    Braunstein GD. Gynecomastia. N Engl J Med. 1993;328(7):490–5.PubMedCrossRefGoogle Scholar
  16. 16.
    Herman-Giddens ME, et al. Secondary sexual characteristics and menses in young girls seen in office practice: a study from the Pediatric Research in Office Settings network. Pediatrics. 1997;99(4):505–12.PubMedCrossRefGoogle Scholar
  17. 17.
    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;108:347–53.PubMedCrossRefGoogle Scholar
  18. 18.
    Biro FM, McMahon RP, Striegel-Moore R, Crawford PB, Obarzanek E, Morrison JA, Barton BA, Falkner F. Impact of timing of pubertal maturation on growth in black and white female adolescents: the National Heart, Lung, and Blood Institute Growth and Health Study. J Pediatr. 2001;138:636–43.PubMedCrossRefGoogle Scholar
  19. 19.
    Kaplowitz PR, 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
  20. 20.
    Rosenfield RL, Lipton RB, Drum ML. Thelarche, pubarche and menarche attainment in children with normal and elevated body mass index. Pediatrics. 2009;123:84–8.PubMedCrossRefGoogle Scholar
  21. 21.
    Biro FM, Galvez MP, Greenspan LC, Succop PA, et al. Pubertal assessment method and baseline characteristics in a mixed longitudinal study of girls. Pediatrics. 2010;126:e583–90.PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Susman EJ, Houts RM, Steinberg L, Belsky J, et al. Longitudinal development of secondary sexual characteristics in girls and boys between ages 9 ½ and 15 ½ years. Arch Pediatr Adolesc Med. 2010;164:166–73.PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    Fuqua J. Treatment and outcomes of precocious puberty: an update. J Clin Endocrinol Metab. 2013;98(6):2198–207.PubMedCrossRefGoogle Scholar
  24. 24.
    Rosenfield RL, et al. Current age of onset of puberty [letter]. Pediatrics. 2000;106(3):622–3.PubMedCrossRefGoogle Scholar
  25. 25.
    Kaplowitz P, Bloch C. Section on endocrinology, American Academy of Pediatrics. Evaluation and referral of children with signs of early puberty. Pediatrics. 2016;137(1):e20153732.CrossRefGoogle Scholar
  26. 26.
    Ibanez L, 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.PubMedGoogle Scholar
  27. 27.
    Ibanez L, et al. Girls diagnosed with premature pubarche show an exaggerated ovarian androgen synthesis from the early stages of puberty: evidence from gonadotropin-releasing hormone agonist testing. Fertil Steril. 1997;67(5):849–55.PubMedCrossRefGoogle Scholar
  28. 28.
    Ibanez L, de Zegher F, Potau N. Premature pubarche, ovarian hyperandrogenism, hyperinsulinism and the polycystic ovary syndrome: from a complex constellation to a simple sequence of prenatal onset. J Endocrinol Invest. 1998;21(9):558–66.PubMedCrossRefGoogle Scholar
  29. 29.
    Ibanez L, et al. Hyperinsulinaemia, dyslipaemia and cardiovascular risk in girls with a history of premature pubarche. Diabetologia. 1998;41(9):1057–63.PubMedCrossRefGoogle Scholar
  30. 30.
    Ibanez L, Potau N, De Zegher F. Endocrinology and metabolism after premature pubarche in girls. Acta Paediatr Suppl. 1999;88(33):73–7.PubMedGoogle Scholar
  31. 31.
    Ibanez L, Potau N, de Zegher P. Recognition of a new association: reduced fetal growth, precocious pubarche, hyperinsulinism and ovarian dysfunction. Ann Endocrinol (Paris). 2000;61(2):141–2.Google Scholar
  32. 32.
    Volta C, et al. Isolated premature thelarche and thelarche variant clinical and auxological follow-up of 119 girls. J Endocrinol Invest. 1998;21(3):180–3.PubMedCrossRefGoogle Scholar
  33. 33.
    Ilicki A, et al. Premature thelarche—natural history and sex hormone secretion in 68 girls. Acta Paediatr Scand. 1984;73(6):756–62.PubMedCrossRefGoogle Scholar
  34. 34.
    Pasquino AM, et al. Progression of premature thelarche to central precocious puberty. J Pediatr. 1995;126(1):11–4.PubMedCrossRefGoogle Scholar
  35. 35.
    Mills JL, et al. Premature thelarche. Natural history and etiologic investigation. Am J Dis Child. 1981;135(8):743–5.PubMedCrossRefGoogle Scholar
  36. 36.
    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
  37. 37.
    Jenner MR, et al. Hormonal changes in puberty. IV. Plasma estradiol, LH, and FSH in prepubertal children, pubertal females, and in precocious puberty, premature thelarche, hypogonadism, and in a child with a feminizing ovarian tumor. J Clin Endocrinol Metab. 1972;34(3):521–30.PubMedCrossRefGoogle Scholar
  38. 38.
    Escobar ME, Rivarola MA, Bergada C. Plasma concentration of oestradiol-17beta in premature thelarche and in different types of sexual precocity. Acta Endocrinol. 1976;81(2):351–61.PubMedGoogle Scholar
  39. 39.
    Colon I, et al. Identification of phthalate esters in the serum of young Puerto Rican girls with premature breast development [in process citation]. Environ Health Perspect. 2000;108(9):895–900.PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Belgorosky A, Chaler E, Rivarola MA. High serum sex hormone-binding globulin (SHBG) in premature thelarche. Clin Endocrinol (Oxf). 1992;37(3):203–6.CrossRefGoogle Scholar
  41. 41.
    Pescovitz OH, et al. Premature thelarche and central precocious puberty: the relationship between clinical presentation and the gonadotropin response 10 luteinizing hormone-releasing hormone. J Clin Endocrinol Metab. 1988;67(3):474–9.PubMedCrossRefGoogle Scholar
  42. 42.
    Wang C, et al. Serum bioactive follicle-stimulating hormone levels in girls with precocious sexual development. J Clin Endocrinol Metab. 1990;70(3):615–9.PubMedCrossRefGoogle Scholar
  43. 43.
    Verrotti A, et al. Premature thelarche: a long-term follow-up. Gynecol Endocrinol. 1996;10(4):241–7.PubMedCrossRefGoogle Scholar
  44. 44.
    Aritaki S, et al. A comparison of patients with premature thelarche and idiopathic true precocious puberty in the initial stage of illness. Acta Paediatr Jpn. 1997;39(1):21–7.PubMedCrossRefGoogle Scholar
  45. 45.
    Orley JN, Goblyos P. Modern imaging methods in paediatric breast examination. Ceska Gynekol. 1995;60(3):153–7.PubMedGoogle Scholar
  46. 46.
    Salardi S, et al. Outcome of premature thelarche: relation to puberty and final height. Arch Dis Child. 1998;79(2):173–4.PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    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.PubMedGoogle Scholar
  48. 48.
    Ibanez L, et al. Precocious pubarche, hyperinsulinism, and ovarian hyperandrogenism in girls: relation to reduced fetal growth. J Clin Endocrinol Metab. 1998;83(10):3558–62.PubMedCrossRefGoogle Scholar
  49. 49.
    Francois I, de Zegher F. Adrenarche and fetal growth. Pediatr Res. 1997;41:440–2.PubMedCrossRefGoogle Scholar
  50. 50.
    Ibanez L, Potau N, de Zegher F. Precocious pubarche, dyslipidemia, and low IGF binding protein-1 in girls: relation to reduced prenatal growth. Pediatr Res. 1999;46(3):320–2.PubMedCrossRefGoogle Scholar
  51. 51.
    Barker DJ, Hales CN, Fall CH, et al. Type 2 (non-insulin-dependent) diabetes mellitus, hypertension and hyperlipidemia (syndrome X): relation to reduced fetal growth. Diabetologia. 1993;36:62–7.PubMedCrossRefGoogle Scholar
  52. 52.
    Hawkins LA, Chasalow FL, Blethen SL. The role of adrenocorticotropin testing in evaluating girls with premature adrenarche and hirsutism/oligomenorrhea. J Clin Endocrinol Metab. 1992;74:248–53.PubMedGoogle Scholar
  53. 53.
    Speiser PW, Dupont B, Rubenstein P, Piazza A, Kastelan A, New MI. High frequency of nonclassical steroid 21-hydroxylase deficiency. Am J Hum Genet. 1985;37:650–67.PubMedPubMedCentralGoogle Scholar
  54. 54.
    Likitmaskul SC, Cowell CT, Donaghue K, et al. Exaggerated adrenarche in children presenting with premature adrenarche. Clin Endocrinol (Oxf). 1995;42:265–72.CrossRefGoogle Scholar
  55. 55.
    Temeck JW, et al. Genetic defects of steroidogenesis in premature pubarche. J Clin Endocrinol Metab. 1987;64(3):609–17.PubMedCrossRefGoogle Scholar
  56. 56.
    Sizonenko PC, Paunier L. Hormonal changes in puberty III: correlation of plasma dehydroepiandrosterone, testosterone, FSI-I, and LH with stages of puberty and bone age in normal boys and girls and in patients with Addison’s disease or hypogonadism or with premature or late adrenarche. J Clin Endocrinol Metab. 1975;41(5):894–904.PubMedCrossRefGoogle Scholar
  57. 57.
    Nestler JE, Jakubowicz DJ. Decreases in ovarian cytochrome P450c17 alpha activity and serum free testosterone after reduction of insulin secretion in polycystic ovary syndrome. N Engl J Med. 1996;29:617–23.CrossRefGoogle Scholar
  58. 58.
    Moghetti P, Castello R, Negri C, et al. Metformin effects on clinical features, endocrine and metabolic profiles, and insulin sensitivity in polycystic ovary syndrome: a randomized, double-blind, placebo-controlled 6-month trial, followed by open, long-term clinical evaluation. J Clin Endocrinol Metab. 2000;85:139–46.PubMedGoogle Scholar
  59. 59.
    Ibanez L, Valls C, Potua N, Marcos MV, de Zegher F. Sensitization to insulin in adolescent girls to normalize hirsutism, hyperandrogenism, oligomenorrhea, dyslipidemia, and hyperinsulinism after precocious pubarche. J Clin Endocrinol Metab. 2000;85:3526–30.PubMedGoogle Scholar
  60. 60.
    Geller DH, Pacaud D, Gordon CM, Misra M, of the Drug and Therapeutics Committee of the Pediatric Endocrine Society. State of the art review: emerging therapies: the use of insulin sensitizers in the treatment of adolescents with polycystic ovary syndrome (PCOS). Int J Pediatri Endocrinol. 2011;2011:9.CrossRefGoogle Scholar
  61. 61.
    Pescovitz OH, et al. The NIH experience with precocious puberty: diagnostic subgroups and response to short-term luteinizing hormone releasing hormone analogue therapy. J Pediatr. 1986;108(1):47–54.PubMedCrossRefGoogle Scholar
  62. 62.
    Robben SG, et al. Idiopathic isosexual central precocious puberty: magnetic resonance findings in 30 patients. Br J Radiol. 1995;68(805):34–8.PubMedCrossRefGoogle Scholar
  63. 63.
    Bessa DS, Macedo DB, Brito VN, França MM, et al. High frequency of MKRN3 mutations in male central precocious puberty previously classified as idiopathic. Neuroendocrinology. 2017;105(1):17–25.PubMedCrossRefGoogle Scholar
  64. 64.
    Dimitrova-Mladenova MS, Stefanova EM, Glushkova M, Todorova AP, Todorov T, Konstantinova MM, Kazakova K, Tincheva RS. Males with paternally inherited MKRN3 mutations may be asymptomatic. J Pediatr. 2016;179:263–5.PubMedCrossRefGoogle Scholar
  65. 65.
    Dauber A, Cunha-Silva M, Macedo DB, Brito VN, et al. Paternally inherited DLK1 deletion associated with familial central precocious puberty. J Clin Endocrinol Metab. 2017 May 1;102(5):1557–67.PubMedCrossRefGoogle Scholar
  66. 66.
    Mahachoklertwattana P, Kaplan SL, Grumbach MM. The luteinizing hormone-releasing hormone-secreting hypothalamic hamartoma is a congenital malformation: natural history. J Clin Endocrinol Metab. 1993;77(1):118–24.PubMedGoogle Scholar
  67. 67.
    Stewart L, Steinbok P, Daaboul J. Role of surgical resection in the treatment of hypothalamic hamartomas causing precocious puberty. Report of six cases. J Neurosurg. 1998;88(2):340–5.PubMedCrossRefGoogle Scholar
  68. 68.
    Habiby R, et al. Precocious puberty in children with neurofibromatosis type 1. J Pediatr. 1995;126(3):364–7.PubMedCrossRefGoogle Scholar
  69. 69.
    Oberfield SE, et al. Endocrine late effects of childhood cancers. J Pediatr. 1997;131(1 Pt 2):S37–41.PubMedCrossRefGoogle Scholar
  70. 70.
    Pescovitz OH, et al. True precocious puberty complicating congenital adrenal hyperplasia: treatment with a luteinizing hormone-releasing hormone analog. J Clin Endocrinol Metab. 1984;58(5):857–61.PubMedCrossRefGoogle Scholar
  71. 71.
    Soliman AT, et al. Congenital adrenal hyperplasia complicated by central precocious puberty: linear growth during infancy and treatment with gonadotropin-releasing hormone analog. Metabolism. 1997;46(5):513–7.PubMedCrossRefGoogle Scholar
  72. 72.
    Foster CM, et al. Variable response to a long-acting agonist of luteinizing hormone-releasing hormone in girls with McCune-Albright syndrome. J Clin Endocrinol Metab. 1984;59(4):801–5.PubMedCrossRefGoogle Scholar
  73. 73.
    Holland FJ, Kirsch SE, Selby S. Gonadotropin-independent precocious puberty (“testotoxicosis”); influence of maturational status on response to ketoconazole. J Clin Endocrinol Metab. 1987;64(2):328–33.PubMedCrossRefGoogle Scholar
  74. 74.
    Eckert KL, et al. A single-sample, subcutaneous gonadotropin-releasing hormone test for central precocious puberty. Pediatrics. 1996;97(4):517–9.PubMedGoogle Scholar
  75. 75.
    Rosenfield RL, et al. The rapid ovarian secretory response to pituitary stimulation by the -gonadotropin-releasing hormone agonist nafarelin in sexual precocity. J Clin Endocrinol Metab. 1986;63(6):1386–9.PubMedCrossRefGoogle Scholar
  76. 76.
    Ibanez L, et al. 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(1):30–5.PubMedGoogle Scholar
  77. 77.
    Rosenfield RL, et al. Acute hormonal responses to the gonadotropin releasing hormone agonist leuprolide: dose-response studies and comparison to nafarelin—a clinical research center study. J Clin Endocrinol Metab. 1996;81(9):3408–11.PubMedGoogle Scholar
  78. 78.
    Boyar RM, et al. Twenty-four hour patterns of plasma luteinizing hormone and follicle-stimulating hormone in sexual precocity. N Engl J Med. 1973;289(6):282–6.PubMedCrossRefGoogle Scholar
  79. 79.
    Jakacki RK, Sauder RP, Lloyd SE, et al. Pulsatile secretion of luteinizing hormone in children. J Clin Endocrinol Metab. 1982;55:453–8.PubMedCrossRefGoogle Scholar
  80. 80.
    Manasco PU, Muly DM, Godwin SM, et al. Ontogeny of gonadotrophin and inhibin secretion in normal girls through puberty based on overnight serial sampling, and comparison with normal boys. Hum Reprod. 1997;12:2108–14.PubMedCrossRefGoogle Scholar
  81. 81.
    Mitamura R, Yano K, Suzuki N, Ito Y, Makita Y, Okuno A. Diurnal rhythms of luteinizing hormone, follicle-stimulating hormone, and testosterone secretion before the onset of male puberty. J Clin Endocrinol Metab. 1999;84:29–37.PubMedGoogle Scholar
  82. 82.
    FB W, Kelnar GE, Stirling CJH, Huhtaniemi HF. Patterns of pulsatile luteinizing and follicle-stimulating hormone secretion in prepubertal (midchildhood) boys and girls and patients with idiopathic hypogonadotropic hypogonadism (Kallmann’s syndrome): a study using an ultrasensitive time-resolved immunofluorometric assay. J Clin Endocrinol Metab. 1991;72:1229–37.CrossRefGoogle Scholar
  83. 83.
    Hall DA, et al. Sonographic monitoring of LHRH analogue therapy in idiopathic precocious puberty in young girls. J Clin Ultrasound. 1986;14(5):331–8.PubMedCrossRefGoogle Scholar
  84. 84.
    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;159:982–987.e1.PubMedCrossRefGoogle Scholar
  85. 85.
    Lee PA, Klein K, Mauras N, Neely EK, Bloch CA, Larsen L, Mattia-Goldberg C, Chwalisz K. Efficacy and safety of leuprolide acetate 3-month depot 11.25 milligrams or 30 milligrams for the treatment of central precocious puberty. J Clin Endocrinol Metab. 2012;97:1572–80.PubMedCrossRefGoogle Scholar
  86. 86.
    Mericq V, Lammoglia JJ, Unanue N, Villaroel C, Hernández MI, Avila A, Iñiguez G, Klein KO. Comparison of three doses of leuprolide acetate in the treatment of central precocious puberty: preliminary results. Clin Endocrinol (Oxf). 2009;71:686–90.CrossRefGoogle Scholar
  87. 87.
    Rahhal S, Clarke WL, Kletter GB, Lee PA, Neely EK, Reiter EO, Saenger P, Shulman D, Silverman L, Eugster EA. Results of a second year of therapy with the 12-month histrelin implant for the treatment of central precocious puberty. Int J Pediatr Endocrinol. 2009;2009:812517.PubMedPubMedCentralCrossRefGoogle Scholar
  88. 88.
    Lewis KA, Eugster EA. Continual suppression by the histrelin implant for the treatment of central precocious puberty when left in place for two years. In: Proceedings from the Annual Meeting of the Pediatric Academic Societies and Asian Society for Pediatric Research; May 2, 2011; Denver, CO; Abstract 3285.1.Google Scholar
  89. 89.
    Cavallo A, et al. A simplified gonadotrophin-releasing hormone test for precocious puberty. Clin Endocrinol (Oxf). 1995;42(6):641–6.CrossRefGoogle Scholar
  90. 90.
    Oerter KE, et al. Effects of luteinizing hormone-releasing hormone agonists on final height in luteinizing hormone-releasing hormone-dependent precocious puberty. Acta Paediatr Suppl. 1993;388:62–8. discussion 69PubMedGoogle Scholar
  91. 91.
    Oostdijk W, et al. Final height in central precocious: puberty after long term treatment with a slow release GnRH agonist. Arch Dis Child. 1996;75(4):292–7.PubMedPubMedCentralCrossRefGoogle Scholar
  92. 92.
    Oerter KE, et al. Adult height in precocious puberty after long-term treatment with deslorelin. J Clin Endocrinol Metab. 1991;73(6):1235–40.PubMedCrossRefGoogle Scholar
  93. 93.
    Bar A, et al. 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
  94. 94.
    Pasquino AM, et al. Combined treatment with gonadotropin-releasing hormone analog and growth hormone in central precocious puberty. J Clin Endocrinol Metab. 1996;81(3):948–51.PubMedGoogle Scholar
  95. 95.
    Saggese G, et al. Effect of combined treatment with gonadotropin releasing hormone analogue and growth hormone in patients with central precocious puberty who had subnormal growth velocity and impaired height prognosis. Acta Paediatr. 1995;84(3):299–304.PubMedCrossRefGoogle Scholar
  96. 96.
    Walvoord EC, Pescovitz OH. Combined use of growth hormone and gonadotropin-releasing hormone analogues in precocious puberty: theoretic and practical considerations. Pediatrics. 1999;104(4 Pt 2):1010–4.PubMedGoogle Scholar
  97. 97.
    Pasquino AM, Pucarelli I, Segni M, Matrunola M, Cerroni F. Adult height in girls with central precocious puberty treated with gonadotropin-releasing hormone, analogues and growth hormone. J Clin Endocrinol Metab. 1999;84:449–52.PubMedCrossRefGoogle Scholar
  98. 98.
    Neely EK, et al. Bone mineral density during treatment of central precocious puberty. J Pediatr. 1995;127(5):819–22.PubMedCrossRefGoogle Scholar
  99. 99.
    Bertelloni S, et al. Effect of central precocious puberty and gonadotropin-releasing hormone analogue treatment on peak bone mass and final height in females. Eur J Pediatr. 1998;157(5):363–7.PubMedCrossRefGoogle Scholar
  100. 100.
    Lazar L, et al. Early polycystic ovary-like syndrome in girls with central precocious puberty and exaggerated adrenal response. Eur J Endocrinol. 1995;133(4):403–6.PubMedCrossRefGoogle Scholar
  101. 101.
    Jay N, et al. Ovulation and menstrual function of adolescent girls with central precocious puberty after therapy with gonadotropin-releasing hormone agonists. J Clin Endocrinol Metab. 1992;75(3):890–4.PubMedGoogle Scholar
  102. 102.
    Saenz CA, et al. Premature thelarche and ovarian cyst probably secondary to estrogen contamination. Bol Asoc Med P R. 1982;74(2):16–9.PubMedGoogle Scholar
  103. 103.
    Saenz de Rodriguez CA, Toro-Sola MA. Anabolic steroids in meat and rema premature thelarche. Lancet. 1982;1(8284):1300.PubMedCrossRefGoogle Scholar
  104. 104.
    Saenz de Rodriguez CA, Bongiovanni AM, Conde de Borrego L. An epidemic of precocious development in Puerto Rican children. J Pediatr. 1985;107(3):393–6.PubMedCrossRefGoogle Scholar
  105. 105.
    Cohen HE, Eisenberg P, Mandel F, Haller JO. Ovarian cysts are common in premenarchal girls: a sonographic study of 101 children 2–12 yr old. AJR Am J Roentgenol. 1992;159(1):89.PubMedCrossRefGoogle Scholar
  106. 106.
    Albright FB, Hampton AM. Syndrome characterized by osteitis fibrosa disseminata, areas of depigmentation and endocrine dysfunction, with precocious puberty in females. N Engl J Med. 1937;216:727.CrossRefGoogle Scholar
  107. 107.
    Weinstein LS, et al. Activating mutations of the stimulatory G protein in the McCune-Albright syndrome. N Engl J Med. 1991;325(24):1688–95.PubMedCrossRefGoogle Scholar
  108. 108.
    Shenker A, et al. An activating Gs alpha mutation is present in fibrous dysplasia of bone in the McCune-Albright syndrome. J Clin Endocrinol Metab. 1994;79(3):750–5.PubMedGoogle Scholar
  109. 109.
    Shenker A, et al. Severe endocrine and nonendocrine manifestations of the McCune-Albright syndrome associated with activating mutations of stimulatory G protein GS. J Pediatr. 1993;123(4):509–18.PubMedCrossRefGoogle Scholar
  110. 110.
    Pienkowski C, et al. Recurrent ovarian cyst and mutation of the Gs alpha gene in ovarian cyst fluid cells: what is the link with McCune-Albright syndrome? Acta Paediatr. 1997;86(9):1019–21.PubMedCrossRefGoogle Scholar
  111. 111.
    DiMeglio LA, Pescovitz OH. Disorders of puberty: inactivating and activating molecular mutations. J Pediatr. 1997;131(1 Pt 2):S8–12.PubMedGoogle Scholar
  112. 112.
    Mastorakos G, et al. Hyperthyroidism in McCune-Albright syndrome with a review of thyroid abnormalities sixty yr after the first report. Thyroid. 1997;7(3):433–9.PubMedCrossRefGoogle Scholar
  113. 113.
    Cavanah SF, Dons RF. McCune-Albright syndrome: how many endocrinopathies can one patient have? South Med J. 1993;86(3):34–7.CrossRefGoogle Scholar
  114. 114.
    Lee PA, Van Dop C, Migeon CJ. McCune-Albright syndrome. Long-term follow-up. JAMA. 1986;256(21):2980–4.PubMedCrossRefGoogle Scholar
  115. 115.
    Holland FJ. Gonadotropin-independent precocious puberty. Endocrinol Metab Clin North Am. 1991;20(1):191–210.PubMedGoogle Scholar
  116. 116.
    Benedict PH. Sex precocity and polyostotic fibrous dysplasia. Report of a case in a boy with testicular biopsy. Am J Dis Child. 1966;111(4):426–9.PubMedCrossRefGoogle Scholar
  117. 117.
    Foster CM, et al. Ovarian function in girls with McCune-Albright syndrome. Pediatr Res. 1986;20(9):859–63.PubMedCrossRefGoogle Scholar
  118. 118.
    Schmidt H, Kiess W. Secondary central precocious puberty in a girl with McCune-Albright syndrome responds to treatment with GnRH analogue. J Pediatr Endocrinol Metab. 1998;11(1):77–81.PubMedCrossRefGoogle Scholar
  119. 119.
    Sorgo W, et al. The effects of cyproterone acetate on statural growth in children with precocious puberty. Acta Endocrinol. 1987;115(1):44–56.PubMedGoogle Scholar
  120. 120.
    Feuillan PP, et al. Treatment of precocious puberty in the McCune-Albright syndrome with the aromatase inhibitor testolactone. N Engl J Med. 1986;315(18):1115–9.PubMedCrossRefGoogle Scholar
  121. 121.
    Feuillan PP, Jones J, Cutler GB Jr. Long-term testolactone therapy for precocious puberty in girls with the McCune-Albright, syndrome. J Clin Endocrinol Metab. 1993;77(3):647–51.PubMedGoogle Scholar
  122. 122.
    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;92:2100–6.PubMedCrossRefGoogle Scholar
  123. 123.
    Eugster EA, et al. Tamoxifen treatment of progressive precocious puberty in a patient with McCune-Albright, syndrome. J Pediatr Endocrinol Metab. 1999;12(5):681–6.PubMedCrossRefGoogle Scholar
  124. 124.
    Sims EK, Garnett S, Guzman F, Paris F, Sultan C, Eugster EA, Fulvestrant McCune-Albright study group. Fulvestrant treatment of precocious puberty in girls with McCune-Albright syndrome. Int J Pediatr Endocrinol. 2012;2012:26.PubMedPubMedCentralCrossRefGoogle Scholar
  125. 125.
    Lala R, Andreo M, Pucci A, Matarazzo P. Persistent hyperestrogenism after precocious puberty in young females with McCune-Albright syndrome. Pediatr Endocrinol Rev. 2007;4(Suppl 4):423–8.PubMedGoogle Scholar
  126. 126.
    Shenker A, et al. A constitutively activating mutation of the luteinizing hormone receptor in familial male precocious puberty [see comments]. Nature. 1993;365(6447):652–4.PubMedCrossRefGoogle Scholar
  127. 127.
    Kremer H, et al. Cosegregation of missense mutations of the luteinizing hormone receptor gene with familial male-limited precocious puberty. Hum Mol Genet. 1993;2(11):1779–83.PubMedCrossRefGoogle Scholar
  128. 128.
    Kraaij R, et al. A missense mutation in the second transmembrane segment of the luteinizing hormone receptor causes familial male-limited precocious puberty. J Clin Endocrinol Metab. 1995;80(11):3168–72.PubMedGoogle Scholar
  129. 129.
    Gromoll J, et al. A mutation in the first transmembrane domain of the lutropin receptor causes male precocious puberty. J Clin Endocrinol Metab. 1998;83(2):476–80.PubMedCrossRefGoogle Scholar
  130. 130.
    Laue L, et al. Genetic heterogeneity of constitutively activating mutations of the human luteinizing hormone receptor in familial male-limited precocious puberty. Proc Natl Acad Sci U S A. 1995;92(6):1906–10.PubMedPubMedCentralCrossRefGoogle Scholar
  131. 131.
    Latronico AC, et al. A unique constitutively activating mutation in third transmembrane helix of luteinizing hormone receptor causes sporadic male gonadotropin-independent precocious puberty. J Clin Endocrinol Metab. 1998;83(7):2435–40.PubMedGoogle Scholar
  132. 132.
    Schedewie HK, et al. Testicular leydig cell hyperplasia as a cause of familial sexual precocity. J Clin Endocrinol Metab. 1981;52(2):271–8.PubMedCrossRefGoogle Scholar
  133. 133.
    Clark PA, Clarke WL. Testotoxicosis. An unusual presentation and novel gene mutation. Clin Pediatr (Phila). 1995;34(5):271–4.CrossRefGoogle Scholar
  134. 134.
    Reiter EO, et al. Male-limited familial precocious puberty in three generations. Apparent Leydig-cell autonomy and elevated glycoprotein hormone alpha subunit. N Engl J Med. 1984;311(8):515–9.PubMedCrossRefGoogle Scholar
  135. 135.
    Egli CA, et al. Pituitary gonadotropin-independent male-limited autosomal dominant sexual precocity in nine generations: familial testotoxicosis. J Pediatr. 1985;106(1):33–40.PubMedCrossRefGoogle Scholar
  136. 136.
    Kawate N. Identification of constitutively activating mutation of the luteinising hormone receptor in a family with male limited gonadotrophin independent precocious puberty (testotoxicosis). J Med Genet. 1995;32(7):553–4.PubMedPubMedCentralCrossRefGoogle Scholar
  137. 137.
    Rosenthal SM, Grumbach MM, Kaplan SL. Gonadotropin-independent familial sexual precocity with premature Leydig and germinal cell maturation (familial testotoxicosis): effects of a potent luteinizing hormone-releasing factor agonist and medroxyprogesterone acetate therapy in four cases. J Clin Endocrinol Metab. 1983;57(3):571–9. 119PubMedCrossRefGoogle Scholar
  138. 138.
    Holland FJ, et al. Ketoconazole in the management of precocious puberty not responsive to LHRH-analogue therapy. N Engl J Med. 1985;312(16):1023–8.PubMedCrossRefGoogle Scholar
  139. 139.
    Laue L, et al. Treatment of familial male precocious puberty with spironolactone and testolactone. N Engl J Med. 1989;320(8):496–502.PubMedCrossRefGoogle Scholar
  140. 140.
    Babovic-Vuksanovic D, et al. Hazards of ketoconazole therapy in testotoxicosis. Acta Paediatr. 1994;83(9):994–7.PubMedCrossRefGoogle Scholar
  141. 141.
    Reiter EO, Mauras N, McCormick K, Kulshreshtha B, 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;23:999–1009.PubMedCrossRefGoogle Scholar
  142. 142.
    Lenz AM, Shulman D, Eugster EA, Rahhal S, Fuqua JS, Pescovitz OH, Lewis KA. Bicalutamide and third-generation aromatase inhibitors in testotoxicosis. Pediatrics. 2010;126:e728–33.PubMedPubMedCentralCrossRefGoogle Scholar
  143. 143.
    Laue L, et al. Treatment of familial male precocious puberty with spironolactone, testolactone, and deslorelin. J Clin Endocrinol Metab. 1993;76(1):151–5.PubMedGoogle Scholar
  144. 144.
    Skinner MA, et al. Ovarian neoplasms in children. Arch Surg. 1993;128(8):849–53. discussion 853–4PubMedCrossRefGoogle Scholar
  145. 145.
    Bouffet E, et al. Juvenile granulosa cell tumor of the ovary in infants: a clinicopathologic study of three cases and review of the literature. J Pediatr Surg. 1997;32(5):762–5.PubMedCrossRefGoogle Scholar
  146. 146.
    Nakashima N, Young RH, Scully RE. Androgenic granulosa cell tumors of the ovary. A clinicopathologic analysis of 17 cases and review of the literature. Arch Pathol Lab Med. 1984;108(10):786–91.PubMedGoogle Scholar
  147. 147.
    Cronje HS, et al. Granulosa and theca cell tumors in children: a report of 17 cases and literature review. Obstet Gynecol Surv. 1998;53(4):240–7.PubMedCrossRefGoogle Scholar
  148. 148.
    Bas F, Pescovitz OH, Steinmetz R. No activating mutations of FSH receptor in four children with ovarian juvenile granulosa cell tumors and the association of these tumors with central precocious puberty. J Pediatr Adolesc Gynecol. 2009;22(3):173–9.PubMedCrossRefGoogle Scholar
  149. 149.
    Masur Y, et al. Leydig cell tumors of the testis—clinical and morphologic aspects. Urologe A. 1996;35(6):468–71.PubMedCrossRefGoogle Scholar
  150. 150.
    Diamond FB Jr, et al. Hetero- and isosexual pseudoprecocity associated with testicular sex-cord tumors in an 8 year-old male. J Pediatr Endocrinol Metab. 1996;9(3):407–14.PubMedCrossRefGoogle Scholar
  151. 151.
    Kim I, Young RH, Scully RE. Leydig cell tumors of the testis. A clinicopathological analysis of 40 cases and review of the literature. Am J Surg Pathol. 1985;9(3):177–92.PubMedCrossRefGoogle Scholar
  152. 152.
    Comite F, et al. Isosexual precocious pseudopuberty secondary to a feminizing adrenal tumor. J Clin Endocrinol Metab. 1984;58(3):435–40.PubMedCrossRefGoogle Scholar
  153. 153.
    Heimann A, et al. Hepatoblastoma presenting as isosexual precocity. The clinical importance of histologic and serologic parameters. J Clin Gastroenterol. 1987;9(1):105–10.PubMedCrossRefGoogle Scholar
  154. 154.
    Otsuka T, et al. Primary pulmonary choriocarcinoma in a four month old boy complicated with precocious puberty. Acta Paediatr Jpn. 1994;36(4):404–7.PubMedCrossRefGoogle Scholar
  155. 155.
    Derenoncount AN, Castro-Magana M, Jones KL. Mediastinal teratoma and precocious puberty in a boy with mosaic Klinefelter syndrome. Am J Med Genet. 1995;55(1):38–42. 135CrossRefGoogle Scholar
  156. 156.
    Cohen AR, Wilson JA, Sadeghi-Nejad A. Gonadotropin-secreting pineal teratoma causing precocious puberty. Neurosurgery. 1991;28(4):597–602. discussion 602–3, 136.PubMedCrossRefGoogle Scholar
  157. 157.
    Tamaki N, et al. Germ cell tumors of the thalamus and the basal ganglia. Childs Nerv Syst. 1990;6(1):3–7. 137PubMedCrossRefGoogle Scholar
  158. 158.
    Kukuvitis A, Matte C, Polychronakos C. Central precocious puberty following feminizing right ovarian granulosa cell tumor. Horm Res. 1995;44(6):268–70.PubMedCrossRefGoogle Scholar
  159. 159.
    Leschek EW, et al. Localization by venous sampling of occult chorionic gonadotropin-secreting tumor in a boy with mosaic Klinefelter’s syndrome and precocious puberty. J Clin Endocrinol Metab. 1996;81(11):3825–8.PubMedGoogle Scholar
  160. 160.
    Englund AT, et al. Pediatric germ cell and human chorionic gonadotropin-producing tumors. Clinical and laboratory features. Am J Dis Child. 1991;145(11):1294–7.PubMedCrossRefGoogle Scholar
  161. 161.
    Hasle H, et al. Mediastinal germ cell tumour associated with Klinefelter syndrome. A report of case and review of the literature. Eur J Pediatr. 1992;151(10):735–9.PubMedCrossRefGoogle Scholar
  162. 162.
    Van Wyk JG. Syndrome of precocious menstruation and galactorrhea in juvenile hypothyroidism: an example of hormonal overlap in pituitary feedback. J Pediatr. 1960;57:416.CrossRefGoogle Scholar
  163. 163.
    Lindsay AV, MacGillivray ML. Multicystic ovaries detected by sonography. Am J Dis Child. 1980;134:588–92.PubMedGoogle Scholar
  164. 164.
    Bruder JS, Bremner MH, Ridgway WJ, Wierman EC. Hypothyroidism-induced macroorchidism: use of a gonadotropin-releasing agonist to understand its mechanism and augment adult stature. J Clin Endocrinol Metab. 1995;80:11–6.PubMedGoogle Scholar
  165. 165.
    Anasti JN, et al. A potential novel mechanism for precocious puberty in juvenile hypothyroidism. J Clin Endocrinol Metab. 1995;80(1):276–9.PubMedGoogle Scholar
  166. 166.
    Desforges J. Gynecomastia. N Engl J Med. 1993;328(7):490.CrossRefGoogle Scholar
  167. 167.
    Coen P. An aromatase-producing sex-cord tumor resulting in prepubertal gynecomastia. N Engl J Med. 1991;324(5):317.PubMedCrossRefGoogle Scholar
  168. 168.
    Halperin DS, Sizonenko PC. Prepubertal gynecomastia following topical inunction of estrogen containing ointment. Helv Paediatr Acta. 1983;38(4):361–6.PubMedGoogle Scholar
  169. 169.
    Edidin DL. Prepubertal gynecomastia associated with estrogen-containing hair cream. Am J Dis Child. 1982;136(7):587.PubMedGoogle Scholar
  170. 170.
    Latorre HK. Idiopathic gynecomastia in seven preadolescent boys. Am J Dis Child. 1973;126:771.PubMedCrossRefGoogle Scholar
  171. 171.
    Stratakis CA, et al. The aromatase excess syndrome is associated with feminization of both sexes and autosomal dominant transmission of aberrant P450 aromatase gene transcription. J Clin Endocrinol Metab. 1998;83(4):1348–57.PubMedGoogle Scholar
  172. 172.
    Fontoura M, et al. Precocious puberty in girls: early diagnosis of a slowly progressing variant. Arch Dis Child. 1989;64(8):1170–6.PubMedPubMedCentralCrossRefGoogle Scholar
  173. 173.
    Kreiter M, et al. Preserving adult height potential in girls with idiopathic true precocious puberty. J Pediatr. 1990;117(3):364–70.PubMedCrossRefGoogle Scholar
  174. 174.
    Bassi F, et al. Precocious puberty: auxological criteria discriminating different forms. J Endocrinol Invest. 1994;17(10):793–7.PubMedCrossRefGoogle Scholar
  175. 175.
    Leger J, Reynaud R, Czernichow P. Do all girls with apparent idiopathic precocious puberty require gonadotropin-releasing hormone agonist treatment? J Pediatr. 2000;137(6):819–25.PubMedCrossRefGoogle Scholar
  176. 176.
    Brauner R, et al. Adult height in girls with idiopathic true precocious puberty. J Clin Endocrinol Metab. 1994;9(2):415–20.Google Scholar
  177. 177.
    Ghirri P, et al. Final height in girls with slowly progressive untreated central precocious puberty. Gynecol Endocrinol. 1997;11(5):301–5.PubMedCrossRefGoogle Scholar
  178. 178.
    Brito VN, Batista MC, Borges MF, Latronico AC, Kohek MB, Thirone AC, Jorge BH, Arnhold IJ, Mendonca BB. Diagnostic value of fluorometric assays in the evaluation of precocious puberty. J Clin Endocrinol Metab. 1999;84(10):3539–44.PubMedGoogle Scholar
  179. 179.
    Tanner JM. Growth at adolescence. Oxford: Blackwell Scientific Publications; 1962. p. 30–6.Google Scholar
  180. 180.
    Ferriman D, Gallwey JD. Clinical assessment of body hair growth in women. J Clin Endocrinol Metab. 1961;21:1440.PubMedCrossRefGoogle Scholar
  181. 181.
    Eugster EA, Pescovitz OH. Precocious puberty. In: DeGroot LJ, editor. Endocrinology. 4th ed: Elsevier Health Science Books. Philadelphia: PA; 2001. p. 2011–21.Google Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Pediatric EndocrinologyMassachusetts General Hospital for ChildrenBostonUSA
  2. 2.Pediatrics, Rutgers-Robert Wood Johnson Medical SchoolNew BrunswickUSA

Personalised recommendations