Hypogonadism in a patient with a mutation in the luteinizing hormone beta-subunit gene

N Engl J Med. 2004 Dec 16;351(25):2619-25. doi: 10.1056/NEJMoa040326.


A 30-year-old man who presented with delayed puberty and infertility was found to have hypogonadism associated with an absence of circulating luteinizing hormone. The patient had a homozygous missense mutation in the gene that encodes the beta subunit of luteinizing hormone (Gly36Asp), a mutation that disrupted a vital cystine knot motif and abrogated the heterodimerization and secretion of luteinizing hormone. Treatment with human chorionic gonadotropin increased circulating testosterone, promoted virilization, and was associated with the appearance of normal spermatozoa in low concentrations. This case illustrates the important physiological role that luteinizing hormone plays in male sexual maturation and fertility.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Chorionic Gonadotropin / pharmacology
  • Chorionic Gonadotropin / therapeutic use
  • Humans
  • Hypogonadism / drug therapy
  • Hypogonadism / genetics*
  • Hypogonadism / pathology
  • Infertility, Male / drug therapy
  • Infertility, Male / genetics
  • Luteinizing Hormone, beta Subunit / genetics*
  • Male
  • Mutation, Missense*
  • Puberty, Delayed / drug therapy
  • Puberty, Delayed / genetics
  • Sequence Analysis, DNA
  • Spermatogenesis / drug effects
  • Testis / pathology
  • Testosterone / blood


  • Chorionic Gonadotropin
  • Luteinizing Hormone, beta Subunit
  • Testosterone