title: Infertility and hypergonadotropic hypogonadism as first evidence of hereditary apolipoprotein A-I amyloidosis.
abstract: OBJECTIVE
  We report that primary infertility and hypergonadotropic hypogonadism in young patients may be caused by testicular amyloidosis and it is associated with the presence of a mutation in the apoA-I gene, resulting in the replacement of proline for leucine at residue 75 of the protein.
  
  
  METHODS
  Ten patients presenting with infertility, gynecomastia, decreased libido, erectile dysfunction or a family history of amyloidosis underwent clinical evaluation, hormone assays, semen analysis, ultrasonographic investigation of the testicles, testicular biopsy and DNA sequencing of the apoA-I gene.
  
  
  RESULTS
  All patients showed azoospermia and 9 had increased testicular volume. Massive amyloid deposition was observed in all testicular biopsies and the apoA-I mutation of replacement of proline for leucine at residue 75 of the protein was noted. Five patients showed hypergonadotropic hypogonadism and 5 had normal testosterone values with high gonadotropin levels.
  
  
  CONCLUSIONS
  Nonobstructive azoospermia and macro-orchidism with or without hypogonadism may be caused by hereditary apoA-I amyloidosis in young patients. Testicular amyloidosis can be the first manifestation of this systemic disease. Specific staining for amyloid deposits and genetic analysis of apoA-I mutations are recommended in young, infertile patients with macro-orchidism. Finally, surveillance in asymptomatic mutation carriers is suggested to evaluate the opportunity to implement sperm retrieval and start androgen replacement therapy when necessary.
authors.affiliation: Department of Endocrinology and Andrology, Spedali Civili, Brescia, Italy.
authors.forename: Tiziano
authors.initials: T
authors.lastname: Scalvini
authors.forename: Paola Rossana
authors.initials: PR
authors.lastname: Martini
authors.forename: Laura
authors.initials: L
authors.lastname: Obici
authors.forename: Regina
authors.initials: R
authors.lastname: Tardanico
authors.forename: Luciano
authors.initials: L
authors.lastname: Biasi
authors.forename: Gina
authors.initials: G
authors.lastname: Gregorini
authors.forename: Francesco
authors.initials: F
authors.lastname: Scolari
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Merlini
mesh_terms: D000328:Adult; D028226:Amyloidosis, Familial / Q000150:complications* / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D016632:Apolipoprotein A-I / Q000235:genetics*; D053713:Azoospermia / Q000209:etiology; D006801:Humans; D007006:Hypogonadism / Q000209:etiology* / Q000473:pathology; D007248:Infertility, Male / Q000209:etiology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D013733:Testicular Diseases / Q000209:etiology* / Q000473:pathology; D013737:Testis / Q000473:pathology
chemical_list: D016632:Apolipoprotein A-I