title: Leydig cell clustering and Reinke crystal distribution in relation to hormonal function in adult patients with testicular dysgenesis syndrome (TDS) including cryptorchidism.
abstract: OBJECTIVE
  Testicular dysgenesis syndrome (TDS) comprises testicular germ cell cancer, cryptorchidism and some cases of male infertility and hypospadias, which can be linked to impairment of intrauterine gonadal development. Among histological signs of TDS, large Leydig cell (LC) clusters (micronodules) are frequently present. This study aimed to investigate possible associations of LC micronodules with the presence of Reinke crystals and hormonal function of LCs, the latter primarily reflected by serum concentrations of luteinising hormone (LH) and testosterone, in patients with TDS.
  
  
  METHODS
  A retrospective study of 101 andrological patients with TDS (infertility with and without a history of cryptorchidism or presence of germ cell neoplasia in situ) and 20 controls with normal testis histology and LC-function. Archived testicular biopsies were re-evaluated for the presence of LC micronodules and Reinke crystals and the findings were correlated with testis size and serum concentrations of LH, follicle-stimulating hormone (FSH), testosterone, inhibin B, estradiol and sex hormone binding globulin (SHBG).
  
  
  RESULTS
  TDS patients with bilateral LC micronodules had significantly lower concentrations of LH, FSH and inhibin B, a lower testosterone/LH-ratio and smaller testis sizes compared to TDS-patients lacking this feature. Presence of LC micronodules was correlated with a lower number of Reinke crystals, while cryptorchid testes had a significantly higher number of crystals than normally descended TDS testes.
  
  
  CONCLUSIONS
  LC micronodules appear to be a compensatory mechanism caused by androgenic failure and are presumably driven by high concentrations of LH. A relative paucity of Reinke crystals in LCs within micronodules in normally descended TDS testes may be a feature of recently renewed immature Leydig cells. The increased number of Reinke crystals in LCs in testes that were either undescended at birth or are persistently undescended could indicate an impairment of LC renewal in cryptorchidism.
authors.affiliation: Department of Growth and Reproduction, and International Center for Research and Research Training on Endocrine Disrupting Effects on Male Reproduction & Child Health (EDMaRC), Section 5064, Copenhagen University Hospital (Rigshospitalet), Blegdamsvej 9, 2100, Copenhagen, Denmark.|Department of Pathology, University Hospital Herlev, Herlev, Denmark.
authors.forename: Rikke R
authors.initials: RR
authors.lastname: Soerensen
authors.affiliation: Department of Growth and Reproduction, and International Center for Research and Research Training on Endocrine Disrupting Effects on Male Reproduction & Child Health (EDMaRC), Section 5064, Copenhagen University Hospital (Rigshospitalet), Blegdamsvej 9, 2100, Copenhagen, Denmark.
authors.forename: Trine H
authors.initials: TH
authors.lastname: Johannsen
authors.affiliation: Department of Growth and Reproduction, and International Center for Research and Research Training on Endocrine Disrupting Effects on Male Reproduction & Child Health (EDMaRC), Section 5064, Copenhagen University Hospital (Rigshospitalet), Blegdamsvej 9, 2100, Copenhagen, Denmark.
authors.forename: Niels E
authors.initials: NE
authors.lastname: Skakkebaek
authors.affiliation: Department of Growth and Reproduction, and International Center for Research and Research Training on Endocrine Disrupting Effects on Male Reproduction & Child Health (EDMaRC), Section 5064, Copenhagen University Hospital (Rigshospitalet), Blegdamsvej 9, 2100, Copenhagen, Denmark. erm@rh.dk.
authors.forename: Ewa
authors.initials: E
authors.lastname: Rajpert-De Meyts
mesh_terms: D000328:Adult; D003456:Cryptorchidism / Q000097:blood / Q000473:pathology; D006059:Gonadal Dysgenesis / Q000097:blood* / Q000473:pathology*; D006801:Humans; D007985:Leydig Cells / Q000473:pathology*; D008297:Male; D009373:Neoplasms, Germ Cell and Embryonal / Q000097:blood / Q000473:pathology; D013733:Testicular Diseases / Q000097:blood* / Q000473:pathology*; D013736:Testicular Neoplasms / Q000097:blood / Q000473:pathology