Reversal of idiopathic hypogonadotropic hypogonadism

New England Journal of Medicine

Volumn 357, Issue 9, 2007, Pages 863-873

  Raivio, Taneli ^a   Falardeau, John ^a   Dwyer, Andrew ^a   Quinton, Richard ^b   Hayes, Frances J ^a   Hughes, Virginia A ^a   Cole, Lindsay W ^a   Pearce, Simon H ^b   Lee, Hang ^a   Boepple, Paul ^a   Crowley Jr , William F ^a   Pitteloud, Nelly ^a  

^a MASSACHUSETTS GENERAL HOSPITAL   (United States)

^b NEWCASTLE UNIVERSITY   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ANDROGEN; CHORIONIC GONADOTROPIN; GONADORELIN; LUTEINIZING HORMONE; TESTOSTERONE;

ADULT; ANOSMIA; ARTICLE; CLINICAL ARTICLE; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; FRAMESHIFT MUTATION; GENETIC SCREENING; HUMAN; HYPOGONADOTROPIC HYPOGONADISM; IDIOPATHIC DISEASE; KALLMANN SYNDROME; MALE; NUCLEOTIDE SEQUENCE; PRIORITY JOURNAL; TREATMENT OUTCOME;

EID: 34548331152     PISSN: 00284793     EISSN: 15334406     Source Type: Journal    
DOI: 10.1056/NEJMoa066494     Document Type: Article

References (41)

1. Hoffman AR, Crowley WF Jr. Induction of puberty in men by long-term pulsatile administration of low-dose gonadotropin-releasing hormone. N Engl J Med 1982;307:1237-41.
2. Seminara SB, Hayes FJ, Crowley WF Jr. Gonadotropin-releasing hormone deficiency in the human (idiopathic hypogonadotropic hypogonadism and Kallmann's syndrome): pathophysiological and genetic considerations. Endocr Rev 1998;19:521-39.
3. Quinton R, Duke VM, Robertson A, et al. Idiopathic gonadotrophin deficiency: genetic questions addressed through phenotypic characterization. Clin Endocrinol (Oxf) 2001;55:163-74.
4. Franco B, Guioli S, Pragliola A, et al. A gene deleted in Kallmann's syndrome shares homology with neural cell adhesion and axonal path-finding molecules. Nature 1991;353:529-36.
5. Legouis R, Hardelin JP, Levilliers J, et al. The candidate gene for the X-linked Kallmann syndrome encodes a protein related to adhesion molecules. Cell 1991;67:423-35.
6. Dodé C, Levilliers J, Dupont JM, et al. Loss-of-function mutations in FGFR1 cause autosomal dominant Kallmann syndrome. Nat Genet 2003;33:463-5.
7. de Roux N, Young J, Misrahi M, et al. A family with hypogonadotropic hypogonadism and mutations in the gonadotropin-releasing hormone receptor. N Engl J Med 1997;337:1597-602.
8. Layman LC, Cohen DP, Jin M, et al. Mutations in gonadotropin-releasing hormone receptor gene cause hypogonadotropic hypogonadism. Nat Genet 1998;18:14-5.
9. Miura K, Acierno JS Jr, Seminara SB. 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 2004;49:265-8.
10. 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.
11. Seminara SB, Messager S, Chatzidaki EE, et al. The GPR54 gene as a regulator of puberty. N Engl J Med 2003;349:1614-27.
12. Pitteloud N, Quinton R, Pearce S, et al. Digenic mutations account for variable phenotypes in idiopathic hypogonadotropic hypogonadism. J Clin Invest 2007;117:457-63.
13. Bauman A. Markedly delayed puberty or Kallmann's syndrome variant. J Androl 1986;7:224-7.
14. Kadva A, Di WL, Djahanbakhch O, Monson J, Silman R. Evidence for the Bauman variant in Kallmann's syndrome. Clin Endocrinol (Oxf) 1996;44:103-10.
15. Quinton R, Cheow HK, Tymms DJ, Bouloux PM, Wu FC, Jacobs HS. Kallmann's syndrome: is it always for life? Clin Endocrinol (Oxf) 1999;50:481-5.
16. Pitteloud N, Boepple PA, DeCruz S, Valkenburgh SB, Crowley WF Jr, Hayes FJ. The fertile eunuch variant of idiopathic hypogonadotropic hypogonadism: spontaneous reversal associated with a homozygous mutation in the gonadotropin-releasing hormone receptor. J Clin Endocrinol Metab 2001;86:2470-5.
17. Pitteloud N, Acierno JS Jr, Meysing AU, Dwyer AA, Hayes FJ, Crowley WF Jr. Reversible Kallmann syndrome, delayed puberty, and isolated anosmia occurring in a single family with a mutation in the fibroblast growth factor receptor 1 gene. J Clin Endocrinol Metab 2005;90:1317-22.
18. Ribeiro RS, Vieira TC, Abucham J. Reversible Kallmann syndrome: report of the first case with a KAL1 mutation and literature review. Eur J Endocrinol 2007;156:285-90.
19. Pitteloud N, Hayes FJ, Boepple PA, et al. The role of prior pubertal development, biochemical markers of testicular maturation, and genetics in elucidating the phenotypic heterogeneity of idiopathic hypogonadotropic hypogonadism. J Clin Endocrinol Metab 2002;87:152-60.
20. Doty RL, Applebaum S, Zusho H, Settle RG. Sex differences in odor identification ability: a cross-cultural analysis. Neuropsychologia 1985;23:667-72.
21. Pitteloud N, Meysing A, Quinton R, et al. Mutations in fibroblast growth factor receptor 1 cause Kallmann syndrome with a wide spectrum of reproductive phenotypes. Mol Cell Endocrinol 2006;254-255:60-9.
22. World Health Organization. WHO laboratory manual for the examination of human semen and sperm-cervical mucus interaction. London: Cambridge University Press, 1999.
23. Pitteloud N, Mootha VK, Dwyer AA, et al. Relationship between testosterone levels, insulin sensitivity, and mitochondrial function in men. Diabetes Care 2005;28:1636-42.
24. Hayes FJ, McNicholl DJ, Schoenfeld D, Marsh EE, Hall JE. Free alpha-subunit is superior to luteinizing hormone as a marker of gonadotropin-releasing hormone despite desensitization at fast pulse frequencies. J Clin Endocrinol Metab 1999;84:1028-36.
25. Santen RJ, Leonard JM, Sherins RJ, Gandy HM, Paulsen CA. Short- and longterm effects of clomiphene citrate on the pituitary-testicular axis. J Clin Endocrinol Metab 1971;33:970-9.
26. Oliveira LM, Seminara SB, Beranova M, et al. The importance of autosomal genes in Kallmann syndrome: genotype-phenotype correlations and neuroendocrine characteristics. J Clin Endocrinol Metab 2001;86:1532-8.
27. McCullagh EP, Beck JC, Schaffenburg CA. A syndrome of eunuchoidism with spermatogenesis, normal urinary FSH and low or normal ICSH: "fertile eunuchs." J Clin Endocrinol Metab 1953;13:489-509.
28. Sharpe RM, McKinnell C, Kivlin C, Fisher JS. Proliferation and functional maturation of Sertoli cells, and their relevance to disorders of testis function in adulthood. Reproduction 2003;125:769-84.
29. Grumbach MM. A window of opportunity: the diagnosis of gonadotropin deficiency in the male infant. J Clin Endocrinol Metab 2005;90:3122-7.
30. Burris AS, Rodbard HW, Winters SJ, Sherins RJ. Gonadotropin therapy in men with isolated hypogonadotropic hypogonadism: the response to human chorionic gonadotropin is predicted by initial testicular size. J Clin Endocrinol Metab 1988;66:1144-51.
31. Waldstreicher J, Seminara SB, Jameson JL, et al. The genetic and clinical heterogeneity of gonadotropin-releasing hormone deficiency in the human. J Clin Endocrinol Metab 1996;81:4388-95.
32. Pitteloud N, Acierno JS Jr, Meysing A, et al. Mutations in fibroblast growth factor receptor 1 cause both Kallmann syndrome and normosmic idiopathic hypogonadotropic hypogonadism. Proc Natl Acad Sci U S A 2006;103:6281-6.
33. Wray S. Development of gonadotropin-releasing hormone-1 neurons. Front Neuroendocrinol 2002;23:292-316.
34. Hébert JM, Lin M, Partanen J, Rossant J, McConnell SK. FGF signaling through FGFR1 is required for olfactory bulb morphogenesis. Development 2003;130:1101-11.
35. Tsai PS, Moenter SM, Postigo HR, et al. Targeted expression of a dominant-negative fibroblast growth factor (FGF) receptor in gonadotropin-releasing hormone (GnRH) neurons reduces FGF responsiveness and the size of GnRH neuronal population. Mol Endocrinol 2005;19:225-36.
36. Moore IT, Wingfield JC, Brenowitz EA. Plasticity of the avian song control system in response to localized environmental cues in an equatorial songbird. J Neurosci 2004;24:10182-5.
37. Nunes MC, Roy NS, Keyoung HM, et al. Identification and isolation of multipotential neural progenitor cells from the subcortical white matter of the adult human brain. Nat Med 2003;9:439-47.
38. Altman J. Autoradiographic and histological studies of postnatal neurogenesis. IV. Cell proliferation and migration in the anterior forebrain, with special reference to persisting neurogenesis in the olfactory bulb. J Comp Neurol 1969;137:433-57.
39. Gage FH. Mammalian neural stem cells. Science 2000;287:1433-8.
40. Quinton R, Hasan W, Grant W, et al. Gonadotropin-releasing hormone immunoreactivity in the nasal epithelia of adults with Kallmann's syndrome and isolated hypogonadotropic hypogonadism and in the early midtrimester human fetus. J Clin Endocrinol Metab 1997;82:309-14.
41. MacLusky NJ, Hajszan T, Prange-Kiel J, Leranth C. Androgen modulation of hippocampal synaptic plasticity. Neuroscience 2006;138:957-65.