Skip to main content
SpringerLink
Log in
Book cover

Pediatric Endocrinology pp 381–394Cite as

Turner Syndrome, Kallmann Syndrome and Noonan Syndrome

  • Chapter
  • First Online:

  • 2737 Accesses

Part of the book series: Contemporary Endocrinology ((COE))

Abstract

Delayed puberty is defined as the absence of any sign of puberty in a child at a chronologic age 2 standard deviations above the mean age of pubertal development for a given population. Normal puberty is initiated by the onset of pulsatile secretion of gonadotropin-releasing hormone (GnRH) from the hypothalamus. These pulses cause release of luteinizing hormone (LH) and follicular-stimulating hormone (FSH) from the pituitary gland. These pituitary gonadotropins then circulate to the gonads and stimulate production of sex steroids. The differential diagnosis of pubertal delay is extensive but can most easily be divided into three categories: The first group represents temporary delays of puberty that are functional disorders, most commonly, constitutional delay of growth and puberty. The second is hypogonadotropic hypogonadism, in which hypothalamic or pituitary failure results in deficiency of circulating gonadotropins. Finally, hypergonadotropic hypogonadism results from primary gonadal failure, with subsequent lack of negative feedback of sex steroids at the hypothalamic and pituitary levels resulting in elevated serum gonadotropin levels.

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

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   189.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD   249.99
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

Learn about institutional subscriptions

References

  1. Marshall WA, Tanner JM. Variations in the pattern of pubertal changes in girls. Am J Dis Child. 1969;44:291–301.

    Article  CAS  Google Scholar 

  2. Marshall WA, Tanner JM. Variations in the pattern of pubertal changes in boys. Am J Dis Child. 1970;45:13–21.

    Article  CAS  Google Scholar 

  3. Argente J. Diagnosis of late puberty. Horm Res. 1999;51 Suppl 3:95–100.

    Article  CAS  PubMed  Google Scholar 

  4. Sedelmeyer I, Palmert MR. Delayed puberty: analysis of a large case series from an academic center. J Clin Endocrinol Metab. 2002;87(4):1613–20.

    Article  Google Scholar 

  5. Rosenfield RL. Clinical Review 6: diagnosis and management of delayed puberty. J Clin Endocrinol Metab. 1990;70(3):559–62.

    Article  CAS  PubMed  Google Scholar 

  6. Warren PW. Effects of undernutrition on reproductive function in the human. Endocr Rev. 1983;4:363–77.

    Article  CAS  PubMed  Google Scholar 

  7. Warren MP, Van de Wiele RL. Clinical and metabolic features of anorexia nervosa. Am J Obstet Gynecol. 1973;117:435–49.

    CAS  PubMed  Google Scholar 

  8. Hudson JL, Hudson MS. Endocrine dysfunction in anorexia nervosa and bulimia: comparison with abnormalities in other psychiatric disorders and disturbances due to metabolic factors. Psychiatr Dev. 1984;2(4):237–72.

    CAS  PubMed  Google Scholar 

  9. Weimann E, Witzel C, Schwidergall S, Bohles HJ. Prepubertal perturbations in elite gymnasts caused by sport specific training regimens and inadequate nutritional intake. Int J Sports Med. 2000;21(3):210–5.

    Article  CAS  PubMed  Google Scholar 

  10. Warren MP, Stiehl AL. Exercise and female adolescents: effects on the reproductive and skeletal systems. J Am Med Womens Assoc. 1999;54(3):115–20.

    CAS  PubMed  Google Scholar 

  11. Picardi A, Cipponeri E, Bizzarri C, Fallucca S, Guglielmi C, Possilli P. Menarche in type 1 diabetes is still delayed despite good metabolic control. Fertil Steril. 2008;90(5):1875–7.

    Article  PubMed  Google Scholar 

  12. Pallais JC, Au M, Pitteloud N, Seminara S, Crowley Jr W. Isolated gonadotropin-releasing hormone (GnRH) deficiency overview. In: Pagon RA, Bird TD, Dolan CR, Stephens K, editors. GeneReviews [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2007. May 23 [updated 2010 Oct 14].

    Google Scholar 

  13. Dwyer AA, Hayes FJ, Plummer L, Pitteloud N, Crowley Jr WF. The long-term clinical follow-up and natural history of men with adult-onset idiopathic hypogonadotropic hypogonadism. J Clin Endocrinol Metab. 2010;95(9):4235–43.

    Article  CAS  PubMed  Google Scholar 

  14. Herbison A. Genetics of puberty. Horm Res. 2007;68 Suppl 5:75–9.

    Article  PubMed  Google Scholar 

  15. Pallais JC, Au M, Pitteloud N, Seminara S, Crowley Jr W. Kallmann syndrome. In: Pagon RA, Bird TD, Dolan CR, Stephens K, editors. GeneReviews [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2007. May 23 [updated 2011 Jan 04].

    Google Scholar 

  16. Layman LC. The molecular basis of human hypogonadotropic hypogonadism. Mol Genet Metab. 1999;68:191–9.

    Article  CAS  PubMed  Google Scholar 

  17. Silveria L, Trarback E, Latronico AC. Genetic basis for GnRH-dependent pubertal disorders in humans. Mol Cell Endocrinol. 2010;324:30–8.

    Article  Google Scholar 

  18. Chan Y, de Guillebon A, Lang-Muritano M, Plummer L, Cerrato F, Tsiaris S, Gaspert A, Lavoie HB, Wu C-H, Crowley Jr WF, Amory JK, Pitteloud N, Seminara S. GNRH1 mutations in patients with idiopathic hypogonadotropic hypogonadism. Proc Natl Acad Sci U S A. 2009;106(28):11703–8.

    Article  CAS  PubMed  Google Scholar 

  19. Niakan LL, McCabe ER. DAX-1 origin, function and novel role. Mol Genet Metab. 2005;86(1–2):70–83.

    Article  CAS  PubMed  Google Scholar 

  20. Merke DP, Tajima T, Baron J, Cutler GB. Hypogonadotropic hypogonadism in a female caused by an X-linked recessive mutation in the DAX1 gene. N Engl J Med. 1999;340:1248–52.

    Article  CAS  PubMed  Google Scholar 

  21. Weiss J, Axelrod L, Whitcomb RW, Harris PE, Crowley Jr W, Jameson JL. Hypogonadism caused by a single amino acid substitution in the β subunit of luteinizing hormone. N Engl J Med. 1992;326:179–83.

    Article  CAS  PubMed  Google Scholar 

  22. Matthews CH, Borgato S, Beck-Peccoz P, Adams M, Tone Y, Gambin G, Casagrande S, Tedeschini G, Benedetti A, Chaterjee VKK. Primary amenorrhea and infertility due to mutation in the β-subunit of follicle-stimulating hormone. Nat Genet. 1993;5:83–6.

    Article  CAS  PubMed  Google Scholar 

  23. Layman LC, Lee EJ, Peak DB, Namnoum AB, Vu KK, van Lingen BL, Gray MR, McDonough PG, Reindollar RH, Jameson JL. Delayed puberty and hypogonadism caused by a mutation in the follicle stimulating hormone beta-subunit gene. N Engl J Med. 1997;337:607–11.

    Article  CAS  PubMed  Google Scholar 

  24. Cogan JD, Wu W, Phillips JAI, Arnhold IJP, Agapito A, Fofanova OV, Osorio MGF, Bircan I, Moreno A, Mendonca BB. The PROP1 2-base pair deletion is a common cause of combined pituitary hormone deficiency. J Clin Endocrinol Metab. 1998;83:3346–9.

    Article  CAS  PubMed  Google Scholar 

  25. Wu W, Cogan JD, Pfaffle RW, Dasen JS, Frisch H, O’Connell SM, Flynn SE, Brown MR, Mullis PE, Parks JS, Phillips III JA, Rosenfeld MG. Mutations in PROP1 cause familial combined pituitary hormone deficiency. Nat Genet. 1998;18:147–9.

    Article  CAS  PubMed  Google Scholar 

  26. Kelberman D, Dattani MT. Role of transcription factors in midline central nervous system and pituitary defects. Endocr Dev. 2009;14:67–82.

    Article  CAS  PubMed  Google Scholar 

  27. Dauber A, Hirschhorn JN, Picker J, Maher TA, Milunsky A. Delayed puberty due to a novel mutation in CHD7 causing CHARGE. Pediatrics. 2010;126(6):e1594–8.

    Article  PubMed  Google Scholar 

  28. Rappaport R, Brauner R. Growth and endocrine disorders secondary to cranial irradiation. Pediatr Res. 1989;25(6):561–7.

    Article  CAS  PubMed  Google Scholar 

  29. Smyth CM, Bremner WJ. Klinefelter syndrome. Arch Intern Med. 1998;158(12):1309–14.

    Article  CAS  PubMed  Google Scholar 

  30. Laue L, Wu SM, Kudo M, et al. A nonsense mutation of the human luteinizing hormone receptor gene in Leydig cell hypoplasia. Hum Mol Genet. 1995;4:1429–33.

    Article  CAS  PubMed  Google Scholar 

  31. Kremer H, Kraaij R, Toledo SP, et al. Male pseudohermaphroditism due to a homozygous missense mutation of the luteinizing hormone receptor gene. Nat Genet. 1995;9:160–4.

    Article  CAS  PubMed  Google Scholar 

  32. Latronico AC, Anasti J, Arnhold IJP, et al. Testicular and ovarian resistance to luteinizing hormone caused by inactivating mutations of the luteinizing hormone-receptor gene. N Engl J Med. 1996;334:507–12.

    Article  CAS  PubMed  Google Scholar 

  33. Gromoll J, Eiholzer U, Nieschlag E, Simoni M. Male hypogonadism caused by homozygous deletion of exon 10 of the luteinizing hormone (LH) receptor: differential action of human chorionic gonadotropin and LH. J Clin Endocrinol Metab. 2000;85(6):2281–6.

    Article  CAS  PubMed  Google Scholar 

  34. Jamieson CR, van der Burgt I, Brady AF, van Reen M, Elsawi MM, Hol F, Jeffrey S, Patton MA, Mariman E. Mapping a gene for Noonan syndrome to the long arm of chromosome 12. Nat Genet. 1994;8:357–60.

    Article  CAS  PubMed  Google Scholar 

  35. Romano AA, Allanson JE, Dahlgren J, Gelb BD, Hall B, Pierpont ME, Roberts AE, Robinson W, Takemoto CM, Noonan JA. Noonan syndrome: clinical features, diagnosis, and management guidelines. Pediatrics. 2010;126(4):746–59.

    Article  PubMed  Google Scholar 

  36. Blagovidow N, Page DC, Huff DE, et al. Ullrich Turner syndrome in a XY female fetus with deletion of the sex-determining portion of the Y chromosome. Am J Med Genet. 1989;34:159–62.

    Article  Google Scholar 

  37. Scherer G, Chempp W, Baccichetti C, et al. Duplication of an Xp segment that includes the ZFX locus causes sex inversion in man. Hum Genet. 1989;81:291–4.

    CAS  PubMed  Google Scholar 

  38. Aittomaki K, Herva R, Stenman U-H, Juntunen K, Ylostalo P, Hovatta O, de la Chapelle A. Clinical features of primary ovarian failure caused by a point mutation in the follicle-stimulating hormone receptor gene. J Clin Endocrinol Metab. 1996;81:3722–6.

    Article  CAS  PubMed  Google Scholar 

  39. Rappaport R, Maguelone GF. Disorders of sexual differentiation. In: Bertrand J, Rappaport R, Sizonenko P, editors. Pediatric endocrinology: physiology, pathophysiology, and clinical aspects. 2nd ed. London: Williams and Wilkins; 1993.

    Google Scholar 

  40. New MI. Inborn errors of adrenal steroidogenesis. Mol Cell Endocrinol. 2003;211(1–2):75–83.

    Article  CAS  PubMed  Google Scholar 

  41. Brinkmann AO. Molecular basis of androgen insensitivity. Mol Cell Endocrinol. 2001;179(1–2):105–9.

    Article  CAS  PubMed  Google Scholar 

  42. McPhaul MJ. Molecular defects of the androgen receptor. J Steroid Biochem Mol Biol. 1999;69(1–6):315–22.

    Article  CAS  PubMed  Google Scholar 

  43. Evans BAJ, Hughes IA, Bevan CL, Patterson MN, Gregory JW. Phenotypic diversity in siblings with partial androgen insensitivity syndrome. Arch Dis Child. 1997;76:529–31.

    Article  CAS  PubMed  Google Scholar 

  44. Bramswig JH, Heimes U, Heiermann E, et al. The effects of different cumulative doses of chemotherapy on testicular function. Cancer. 1990;65:1298–302.

    Article  CAS  PubMed  Google Scholar 

  45. Sanders JE. Growth and development after hematopoietic cell transplant in children. Bone Marrow Transplant. 2008;41(2):223–7.

    Article  CAS  PubMed  Google Scholar 

  46. Bayer L, Bayley N. Growth diagnosis. Chicago: University of Chicago Press; 1959.

    Google Scholar 

  47. Reynolds EL, Wines JV. Physical changes associated with adolescence in boys. Am J Dis Child. 1951;82:529–47.

    CAS  Google Scholar 

  48. Harlan W, Grillo G, Cornoni-Huntley J, Leaverton P. Sexual characteristics of boys 12 to 17 years of age: the U.S. Health Examination Survey. J Pediatr. 1979;95(2):293–7.

    Article  CAS  PubMed  Google Scholar 

  49. Harlan W, Harlan E, Grillo G. Sexual characteristics of girls 12 to 17 years of age: the U.S. Health Examination Survey. J Pediatr. 1980;96(6):1074–8.

    Article  CAS  PubMed  Google Scholar 

  50. Odink RJ, Schoemaker J, Schoute E, Herder E, Delemarre-van de Waal HA. Predictive value of serum follicular-stimulating hormone levels in the differentiation between hypogonadotropic hypogonadism and constitutional delay of puberty. Horm Res. 1998;49(6):279–87.

    Article  CAS  PubMed  Google Scholar 

  51. Grinspon RP, Ropelato MG, Gottlieb S, Keselman A, Martínez A, Ballerini MG, Domené 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(6):2811–8.

    Article  CAS  PubMed  Google Scholar 

  52. Wu FCW, Brown DC, Butler GE, Stirling HF, Kelnar CJH. Early morning plasma testosterone is an accurate predictor of imminent pubertal development in prepubertal boys. J Clin Endocrinol Metab. 1990;70:26–31.

    Google Scholar 

  53. Gambineri A, Pasquali R. Testosterone therapy in men: clinical and pharmacological perspectives. J Endocrinol Invest. 2000;23:196–214.

    CAS  PubMed  Google Scholar 

  54. Brook CGD. Treatment of late puberty. Horm Res. 1999;51 suppl 3:101–3.

    Article  CAS  PubMed  Google Scholar 

  55. Richmond EJ, Rogol AD. Male pubertal development and the role of androgen therapy. Nat Clin Pract Endocrinol Metab. 2007;3:338–44.

    Article  CAS  PubMed  Google Scholar 

  56. Bourguignon J-P. Delayed puberty and hypogonadism. In: Bertrand J, Rappaport R, Sizonenko P, editors. Pediatric endocrinology: physiology, pathophysiology, and clinical aspects. 2nd ed. London: Williams and Wilkins; 1993.

    Google Scholar 

  57. Pozo J, Argente J. Ascertainment and treatment of delayed puberty. Horm Res. 2003;60 suppl 3:35–48.

    Article  CAS  PubMed  Google Scholar 

  58. Mayo A, Macintyre H, Wallace AM, Ahmed SF. Transdermal testosterone application: pharmacokinetics and effects on pubertal status, short-term growth, and bone turnover. J Clin Endocrinol Metab. 2004;89(2):681–7.

    Article  CAS  PubMed  Google Scholar 

  59. De Sanctis V, Vullo C, Urso L, Rigolin F, Cavallini A, Caramelli K, Daugherty C, Mazer N. Clinical experience using the Androderm testosterone transdermal system in hypogonadal adolescents and young men with beta-thalassemia major. J Pediatr Endocrinol Metab. 1998;11 Suppl 3:891–900.

    PubMed  Google Scholar 

  60. Divasta AD, Gordon CM. Hormone replacement therapy and the adolescent. Curr Opin Obstet Gynecol. 2010;22:363–8.

    Article  PubMed  Google Scholar 

  61. Finkelstein JW, Susman EJ, Chinchilli VM, et al. Effects of estrogen or testosterone on self-reported sexual responses and behaviors in hypogonadal adolescents. J Clin Endocrinol Metab. 1998;83(7):2281–5.

    Article  CAS  PubMed  Google Scholar 

  62. Susman EF, Finkelstein JW, Chinchilli VM, et al. The effect of sex hormone replacement therapy on behavior problems and moods in adolescents with delayed puberty. J Pediatr. 1998;133(4):521–5.

    Article  CAS  PubMed  Google Scholar 

  63. Hoffman AR, Crowley WF. Induction of puberty in men by long-term pulsatile administration of low dose gonadotropin-releasing hormone. N Engl J Med. 1982;307:1237–41.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Endocrinology, Children’s Hospital Boston, 300 Longwood Avenue, Boston, MA, 02115, USA

    Diane E. J. Stafford M.D.

Authors
  1. Diane E. J. Stafford M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Diane E. J. Stafford M.D. .

Editor information

Editors and Affiliations

  1. School of Medicine, Department of Pediatrics, The Johns Hopkins University, 600 North Wolfe St., Baltimore, 21287, Maryland, USA

    Sally Radovick

  2. , Department of Pediatrics, Children's Hospital of Buffalo, 219 Bryant St., Buffalo, 14222, New York, USA

    Margaret H. MacGillivray

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media New York

About this chapter

Cite this chapter

Stafford, D.E.J. (2013). Turner Syndrome, Kallmann Syndrome and Noonan Syndrome. In: Radovick, S., MacGillivray, M. (eds) Pediatric Endocrinology. Contemporary Endocrinology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-395-4_22

Download citation

  • DOI: https://doi.org/10.1007/978-1-60761-395-4_22

  • Published:

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-60761-394-7

  • Online ISBN: 978-1-60761-395-4

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation