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Hypogonadotroper Hypogonadismus aufgrund eines IHH oder Kallmann-Syndroms beim Mann

Hypogonadotropic hypogonadism due to IHH or Kallmann syndrome in males

Zusammenfassung

Beim männlichen Geschlecht wird die Prävalenz des isolierten hypogonadatropen Hypogonadismus (IHH)/Kallmann-Syndroms auf etwa 1:10.000 geschätzt. Leitsymptom für den IHH ist die ausbleibende Pubertätsentwicklung in Kombination mit erniedrigten Gonadotropinen und einer verminderten Testosteronkonzentration. Wenn zusätzlich eine Anosmie/Hyposmie (in etwa 60% der Fälle) vorliegt, spricht man von einem Kallmann-Syndrom. IHH/Kallmann-Syndrom sind klinisch und genetisch sehr heterogene Krankheitsbilder. Die genetische Diagnostik und therapeutischen Möglichkeiten werden diskutiert.

Abstract

The prevalence of isolated hypogonadotropic hypogonadism (IHH)/Kallmann syndrome in males is about 1:10,000. IHH is characterized by absent sexual development and low levels of gonadotropins and testosterone. Kallmann syndrome is characterized by the association of HH and total or partial loss of olfaction (in 60%). IHH/Kallmann syndrome are very heterogeneous disorders. Clinical and genetic diagnosis as well as therapy will be discussed.

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Literatur

  1. 1.

    Behre HM, Nieschlag E, Partsch CJ et al (2009) Störungen im Bereich des Hypothalamus und der Hypophyse. In: Nieschlag E, Behre HM, Nieschlag S (Hrsg) Andrologie – Grundlagen und Klinik der reproduktiven Gesundheit des Mannes. Springer, Berlin, S 175–198

  2. 2.

    Beranova M, Oliveira LM, Bedecarrats GY et al (2001) Prevalence, phenotypic spectrum and modes of inheritance of gonadotropin-releasing hormone receptor mutations in idiopathic hypogonadotropic hypogonadism. J Clin Endocrinol Metab 86:1580–1588

    PubMed  Article  CAS  Google Scholar 

  3. 3.

    Bianco S, Kaiser UB (2009) The genetic and molecular basis of idiopathic hypogonadotropic hypogonadism. Nat Rev Endocrinol 5:569–576

    PubMed  Article  CAS  Google Scholar 

  4. 4.

    Bouloux P, Warne DW, Loumaye E; FSH Study Group in Men’s Infertility (2002) Efficacy and safety of recombinant human follicle-stimulating hormone in men with isolated hypogonadotropic hypogonadism. Fertil Steril 77:270–273

    PubMed  Article  Google Scholar 

  5. 5.

    Büchter D, Behre HM, Kliesch S, Nieschlag E (1998) Pulsatile GnRH or human chorionic gonadotropin/human menopausal gonadotropin as effective treatment for men with hypogonadotropic hypogonadism: a review of 42 cases. Eur J Endocrinol 139:298–303

    PubMed  Article  Google Scholar 

  6. 6.

    Caron P, Chauvin S, Christin-Maitre S et al (1999) Resistance of hypogonadic patients with mutated GnRH receptor genes to pulsatile GnRH administration. J Clin Endocrinol Metab 84:990–996

    PubMed  Article  CAS  Google Scholar 

  7. 7.

    Caronia LM, Martin C, Welt CK et al (2011) A genetic basis for functional hypothalamic amenorrhea. N Engl J Med. 364:215–225

    Google Scholar 

  8. 8.

    Chan YM, Guillebon A de, Lang-Muritano M et al (2009) GNRH1 mutations in patients with idiopathic hypogonadotropic hypogonadism. PNAS 106:11703–11709

    PubMed  Article  CAS  Google Scholar 

  9. 9.

    Cooper TG, Noonan E, Eckardstein S von et al (2010) World Health Organization reference values for human semen characteristics. Hum Reprod Update 16:231–245

    PubMed  Article  Google Scholar 

  10. 10.

    Coutant R, Biette-Demeneix E, Bouvattier C et al (2010) Baseline inhibin B and anti-Mullerian hormone measurements for diagnosis of hypogonadotropic hypogonadism (HH) in boys with delayed puberty. J Clin Endocrinol Metab 95:5225–5232

    PubMed  Article  CAS  Google Scholar 

  11. 11.

    Dode C, Texeira L, Levilliers J et al (2006) Kallmann syndrome: mutations in the genes encoding prokineticin-2 and prokineticin receptor-2. PLoS Genet 2(19):e175. Epub

    PubMed  Article  Google Scholar 

  12. 12.

    Dwyer AA, Hayes FJ, Plummer L et al (2010) The long-term clinical follow-up and natural history of men with adult-onset idiopathic hypogonadotropic hypogonadism. J Clin Endocrinol Metab 95:4235–4243

    PubMed  Article  CAS  Google Scholar 

  13. 13.

    Falardeau J, Chung WC, Beenken A et al (2008) Decreased FGF8 signaling causes deficiency of gonadotropin-releasing hormone in humans and mice. J Clin Invest 118:2822–2831

    PubMed  Article  CAS  Google Scholar 

  14. 14.

    Han TS, Bouloux PM (2010) What is the optimal therapy for young males with hypogonadotropic hypogonadism? Clin Endocrinol (Oxf) 72:731–737

    Google Scholar 

  15. 15.

    Kaplan JD, Bernstein JA, Kwan A, Hudgins L (2010) Clues to an early diagnosis of Kallmann syndrome. Am J Med Genet A 152A:2796–2801

    PubMed  Article  Google Scholar 

  16. 16.

    Kim HG, Kurth I, Lan F et al (2008) Mutations in CHD7, encoding a chromatin-remodeling protein, cause idiopathic hypogonadotropic hypogonadism and Kallmann syndrome. Am J Hum Genet 83:511–519

    PubMed  Article  CAS  Google Scholar 

  17. 17.

    Kim HG, Ahn JW, Ullmann R et al (2010) WDR11, a WD protein that interacts with transcription factor EMX1, is mutated in idiopathic hypogonadotropic hypogonadism and Kallmann syndrome. Am J Hum Genet 87:465–479

    PubMed  Article  CAS  Google Scholar 

  18. 18.

    Lanfranco F, Gromoll J, Eckardstein S von et al (2005) Role of sequence variations of the GnRH receptor and G protein-coupled receptor 54 gene in male idiopathic hypogonadotropic hypogonadism. Eur J Endocrinol 153:845–852

    PubMed  Article  CAS  Google Scholar 

  19. 19.

    Liu PY, Baker HW, Jayadev V et al (2009) Induction of spermatogenesis and fertility during gonadotropin treatment of gonadotropin-deficient infertile men: predictors of fertility outcome. J Clin Endocrinol Metab 94:801–808

    PubMed  Article  CAS  Google Scholar 

  20. 20.

    Miura K, Acierno JS, Seminara SB (2004) Characterization of the human nasal embryonic LHRH factor gene, NELF, and a mutation screening among 65 patients with idiopathic hypogonadotropic hypogonadism (IHH). J Hum Genet 49:265–268

    PubMed  Article  CAS  Google Scholar 

  21. 21.

    Montague CT, Farooqi S, Whitehead FP et al (1997) Congenital leptin deficiency is associated with severe early-onset obesity in humans. Nature 387:903–908

    PubMed  Article  CAS  Google Scholar 

  22. 22.

    Pallais JC, Au M, Pitteloud N et al (2011) Kallmann Syndrome. In: Pagon RA, Bird TD, Dolan CR, Stephens K (Hrsg) GeneReviews [Internet]. University of Washington, Seattle/WA, updated 04 Jan 2011

  23. 23.

    Raivio T, Falardeau J, Dwyer A et al (2007) Reversal of idiopathic hypogonadotropic hypogonadism. N Engl J Med 357:863–873

    PubMed  Article  CAS  Google Scholar 

  24. 24.

    Schwanzel-Fukuda M, Bick D, Pfaff DW (1989) Luteinizing hormone-releasing hormone (LHRH)-expressing cells do not migrate normally in an inherited hypogonadal (Kallmann) syndrome. Mol Brain Res 6:311–326

    PubMed  Article  CAS  Google Scholar 

  25. 25.

    Seminara SB, Hayes FJ, Crowley WF Jr (1998) Gonadotropin-releasing hormone deficiency in the human (idiopathic hypogonadotropic hypogonadism and Kallmann’s syndrome): pathophysiological and genetic considerations. Endocr Rev 19(5):521–539

    PubMed  Article  CAS  Google Scholar 

  26. 26.

    Spratt DI, Carr DB, Merriam GR et al (1987) The spectrum of abnormal patterns of gonadotropin-releasing hormone secretion in men with idiopathic hypogonadotropic hypogonadism: clinical and laboratory correlations. J Clin Endocrinol Metab 64:283–291

    PubMed  Article  CAS  Google Scholar 

  27. 27.

    Sykiotis GP, Plummer L, Hughes VA et al (2010) Oligogenic basis of isolated gonadotropin-releasing hormone deficiency. PNAS 107:15140–15144

    PubMed  Article  CAS  Google Scholar 

  28. 28.

    Sykiotis GP, Hoang XH, Avbelj M et al (2010) Congenital idiopathic hypogonadotrophic hypogonadism: evidence of defects in the hypothalamus, pituitary, and testes. J Clin Endocrinol Metab. 95:3019–3027

    Google Scholar 

  29. 29.

    Warne DW, Decosterd G, Okada H et al (2009) A combined analysis of data to identify predictive factors for spermatogenesis in men with hypogonadotropic hypogonadism treated with recombinant human follicle-stimulating hormone and human chorionic gonadotropin. Fertil Steril 92:594–604

    PubMed  Article  CAS  Google Scholar 

  30. 30.

    Young J, Bouligand J, Francou B et al (2010) TAC3 and TACR3 defects cause hypothalamic congenital hypogonadotropic hypogonadism in humans. J Clin Endocrinol Metab 95:2287–2295

    PubMed  Article  CAS  Google Scholar 

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Correspondence to H.M. Behre.

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Behre, H., Tüttelmann, F., Ledig, S. et al. Hypogonadotroper Hypogonadismus aufgrund eines IHH oder Kallmann-Syndroms beim Mann. medgen 23, 254–258 (2011). https://doi.org/10.1007/s11825-011-0278-8

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Schlüsselwörter

  • Hypogonadotroper Hypogonadismus
  • Kallmann-Syndrom
  • Gonadotropine
  • Leydig-Zellen
  • Riechstörungen

Keywords

  • Hypogonadotropic hypogonadism
  • Kallmann syndrome
  • Gonadotropins
  • Leydig cells
  • Olfaction disorders