Abdominal Radiology

, Volume 41, Issue 8, pp 1596–1603 | Cite as

Testis ultrasound in Klinefelter syndrome infertile men: making the diagnosis and avoiding inappropriate management

  • Laurence RocherEmail author
  • Loris Moya
  • Jean Michel Correas
  • Pierre Mutuon
  • Sophie Ferlicot
  • Jacques Young
  • Vincent Izard
  • Gérard Benoit
  • Sylvie Brailly-Tabard
  • Marie France Bellin



To compare the testicular Color Doppler ultrasound (US), hormone levels, and histological results from 67 infertile men with Klinefelter syndrome (KS), vs. 66 non-KS non-obstructive azoospermic men.


Scrotal US images were collected from 67 infertile KS and 66 non-obstructive, non-KS azoospermic men. The testis volume, echotexture, vascularity, and microliths were evaluated and graded. We defined the following echo pattern alteration groups: normal, striated, coarse, and measurable nodules. The vascularization was classified as low, normal, moderate, or strong. Testosterone, follicle-stimulating hormone, luteinizing hormone, and inhibin B levels were determined. Large testicular nodules were removed. A testicular biopsy and sperm extraction was performed in 18 of the KS, and all of the 66 non-KS men.


The mean testis volume was low in the KS, compared to the non-KS patients: i.e., 2 vs. 8 mL (P < 0.0001). The distributions in the echotexture groups differed markedly, with coarse or nodular patterns in the KS men, and normal/striated patterns in the control patients (P < 0.0001). The vascularization and microlithiasis grades were higher in the KS patients than the control men (P < 0.0001 and P < 0.001, respectively). All of the nodules removed from the KS patients were benign Leydig cell tumors, and all of the biopsies showed marked Leydig cell hyperplasia, with spermatogenesis in only two patients. The non-KS biopsies were predominantly Sertoli cell-only syndrome.


Small testes, with a coarse or nodular echotexture, hypervascularization, and microlithiasis are associated with KS. The KS nodules were benign Leydig cell tumors/hyperplasias.


Male infertility Testis tumors Klinefelter syndrome Color Doppler ultrasound Leydig cell tumors Hypogonadism 



We thank Valentine Sallerin, Florian Maxwell and Sophie Domingues for language editing of the paper, Beatrice Ducot for statistical analysis advices. We thank Bénédicte Renoir, Guillaume Cluzel, Ludivine Glas, and Amel Fékir for their daily work with infertile men. We thank Thomas Bessede for his advices.

Compliance with ethical standards

Conflict of interest

Nothing to disclose.

Human and Animal Rights Statement

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

For this type of study formal consent is not required.

Supplementary material

Video 1 Color Doppler KS patient testis findings: hypoechoic nodules and hypervascularization (AVI 3279 kb)

Video 2 Example of a nodular hyperechoic hilum (KS patient) (AVI 2811 kb)


  1. 1.
    Klinefelter H, Rifenstein E, Albright F (1942) Syndrome characterized by gynecomastia, aspermatogenesis without A leydigism and excretion of follicle stimulating hormone. J Clin Endocrinol Metab 2:615–627CrossRefGoogle Scholar
  2. 2.
    Lanfranco F, Kamischke A, Zitzmann M, Nieschlag E (2004) Klinefelter’s syndrome. Lancet 364:273–283. doi: 10.1016/S0140-6736(04)16678-6 CrossRefPubMedGoogle Scholar
  3. 3.
    Aksglaede L, Juul A (2013) Testicular function and fertility in men with Klinefelter syndrome: a review. Eur J Endocrinol 168:R67–R76. doi: 10.1530/EJE-12-0934 CrossRefPubMedGoogle Scholar
  4. 4.
    Ekerhovd E, Westlander G (2002) Testicular sonography in men with Klinefelter syndrome shows irregular echogenicity and blood flow of high resistance. J Assist Reprod Genet 19:517–522CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Westlander G, Ekerhovd E, Granberg S, et al. (2001) Testicular ultrasonography and extended chromosome analysis in men with nonmosaic Klinefelter syndrome: a prospective study of possible predictive factors for successful sperm recovery. Fertil Steril 75:1102–1105CrossRefPubMedGoogle Scholar
  6. 6.
    Rock A, Marcelli F, Robin G, et al. (2014) Clinical and paraclinical features of Klinefelter syndrome consulting for male infertility. Progres Urol. 24:757–763. doi: 10.1016/j.purol.2014.08.003 CrossRefGoogle Scholar
  7. 7.
    Accardo G, Vallone G, Esposito D, et al. (2015) Testicular parenchymal abnormalities in Klinefelter syndrome: a question of cancer? Examination of 40 consecutive patients. Asian J Androl 17:154–158. doi: 10.4103/1008-682X.128514 CrossRefPubMedGoogle Scholar
  8. 8.
    Richenberg J, Brejt N (2012) Testicular microlithiasis: is there a need for surveillance in the absence of other risk factors? Eur Radiol 22:2540–2546. doi: 10.1007/s00330-012-2520-4 CrossRefPubMedGoogle Scholar
  9. 9.
    Krausz C (2011) Male infertility: pathogenesis and clinical diagnosis. Best Pract Res Clin Endocrinol Metab 25:271–285. doi: 10.1016/j.beem.2010.08.006 CrossRefPubMedGoogle Scholar
  10. 10.
    Lotti F, Maggi M (2015) Ultrasound of the male genital tract in relation to male reproductive health. Hum Reprod Update 21:56–83. doi: 10.1093/humupd/dmu042 CrossRefPubMedGoogle Scholar
  11. 11.
    Jungwirth A, Diemer T, Dohle G.R, et al. (2014) Guidelines on male infertility.
  12. 12.
    Eifler JB Jr, King P, Schlegel PN (2008) Incidental testicular lesions found during infertility evaluation are usually benign and may be managed conservatively. J Urol 180:261–264 (discussion 265). doi: 10.1016/j.juro.2008.03.021 CrossRefPubMedGoogle Scholar
  13. 13.
    Toren PJ, Roberts M, Lecker I, et al. (2010) Small incidentally discovered testicular masses in infertile men–is active surveillance the new standard of care? J Urol 183:1373–1377. doi: 10.1016/j.juro.2009.12.012 CrossRefPubMedGoogle Scholar
  14. 14.
    Carmignani L, Gadda F, Gazzano G, et al. (2003) High incidence of benign testicular neoplasms diagnosed by ultrasound. J Urol 170:1783–1786. doi: 10.1097/01.ju.0000092066.01699.90 CrossRefPubMedGoogle Scholar
  15. 15.
    Dohle GR, Elzanaty S, van Casteren NJ (2012) Testicular biopsy: clinical practice and interpretation. Asian J Androl 14:88–93. doi: 10.1038/aja.2011.57 CrossRefPubMedGoogle Scholar
  16. 16.
    Sterbis J, Toritsetimiyin E (2015) Leydig cell hyperplasia in the setting of Klinefelter syndrome. BMJ Case Rep. doi: 10.1136/bcr-2015-209805 PubMedGoogle Scholar
  17. 17.
    Lahlou N, Fennoy I, Ross JL, et al. (2011) Clinical and hormonal status of infants with nonmosaic XXY karyotype. Acta Paediatr Oslo Nor 1992 100:824–829. doi: 10.1111/j.1651-2227.2011.02280.x Google Scholar
  18. 18.
    Wikström AM, Dunkel L (2008) Testicular function in Klinefelter syndrome. Horm Res 69:317–326. doi: 10.1159/000117387 CrossRefPubMedGoogle Scholar
  19. 19.
    Aksglaede L, Skakkebaek NE, Almstrup K, Juul A (2011) Clinical and biological parameters in 166 boys, adolescents and adults with nonmosaic Klinefelter syndrome: a Copenhagen experience. Acta Paediatr Oslo Nor 1992 100:793–806. doi: 10.1111/j.1651-2227.2011.02246.x Google Scholar
  20. 20.
    Holm M, Rajpert-De Meyts E, Andersson A-M, Skakkebaek NE (2003) Leydig cell micronodules are a common finding in testicular biopsies from men with impaired spermatogenesis and are associated with decreased testosterone/LH ratio. J Pathol 199:378–386. doi: 10.1002/path.1309 CrossRefPubMedGoogle Scholar
  21. 21.
    Lottrup G, Nielsen JE, Maroun LL, et al. (2014) Expression patterns of DLK1 and INSL3 identify stages of Leydig cell differentiation during normal development and in testicular pathologies, including testicular cancer and Klinefelter syndrome. Hum Reprod Oxf Engl 29:1637–1650. doi: 10.1093/humrep/deu124 CrossRefGoogle Scholar
  22. 22.
    Nieschlag E, Werler S, Wistuba J, Zitzmann M (2014) New approaches to the Klinefelter syndrome. Ann Endocrinol 75:88–97. doi: 10.1016/j.ando.2014.03.007 CrossRefGoogle Scholar
  23. 23.
    Abramsky L, Chapple J (1997) 47, XXY (Klinefelter syndrome) and 47, XYY: estimated rates of and indication for postnatal diagnosis with implications for prenatal counselling. Prenat Diagn 17:363–368CrossRefPubMedGoogle Scholar
  24. 24.
    Butruille C, Marcelli F, Ghoneim T, et al. (2012) Management of testicular lesions in a population of infertile patients. Prog En Urol J Assoc Fr Urol Société Fr Urol 22:45–52. doi: 10.1016/j.purol.2011.08.030 CrossRefGoogle Scholar
  25. 25.
    Leonhartsberger N, Ramoner R, Aigner F, et al. (2011) Increased incidence of Leydig cell tumours of the testis in the era of improved imaging techniques. BJU Int 108:1603–1607. doi: 10.1111/j.1464-410X.2011.10177.x CrossRefPubMedGoogle Scholar
  26. 26.
    Samplaski MK, Lo KC, Grober ED, et al. (2014) Phenotypic differences in mosaic Klinefelter patients as compared with non-mosaic Klinefelter patients. Fertil Steril 101:950–955. doi: 10.1016/j.fertnstert.2013.12.051 CrossRefPubMedGoogle Scholar
  27. 27.
    De Sanctis V, Fiscina B, Soliman A, et al. (2013) Klinefelter syndrome and cancer: from childhood to adulthood. Pediatr Endocrinol Rev 11:44–50PubMedGoogle Scholar
  28. 28.
    Tada M, Takimoto Y, Kishimoto T (1990) Immature teratoma of the testis associated with Klinefelter’s syndrome: a case report. Hinyokika Kiyo 36:1471–1474PubMedGoogle Scholar
  29. 29.
    Yoshida T, Takao T, Tsujimura A, et al. (2006) Testicular epidermoid cyst in Klinefelter’s syndrome. Int J Urol 13:478–480. doi: 10.1111/j.1442-2042.2006.01331.x CrossRefPubMedGoogle Scholar
  30. 30.
    Reddy SR, Svec F, Richardson P (1991) Seminoma of the testis in a patient with 48, XXYY variant of Klinefelter’s syndrome. South Med J 84:773–775CrossRefPubMedGoogle Scholar
  31. 31.
    Hasle H, Mellemgaard A, Nielsen J, Hansen J (1995) Cancer incidence in men with Klinefelter syndrome. Br J Cancer 71:416–420CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Soria JC, Durdux C, Chrétien Y, et al. (1999) Malignant Leydig cell tumor of the testis associated with Klinefelter’s syndrome. Anticancer Res 19:4491–4494PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Laurence Rocher
    • 1
    • 7
    • 9
    Email author
  • Loris Moya
    • 1
  • Jean Michel Correas
    • 8
    • 9
  • Pierre Mutuon
    • 2
  • Sophie Ferlicot
    • 3
    • 7
  • Jacques Young
    • 4
    • 7
  • Vincent Izard
    • 5
  • Gérard Benoit
    • 7
  • Sylvie Brailly-Tabard
    • 6
    • 7
  • Marie France Bellin
    • 1
    • 7
  1. 1.Service de Radiologie diagnostique et interventionelleHôpitaux Paris Sud, Site BicêtreLe Kremlin Bicêtre CedexFrance
  2. 2.Service de Santé publique et d’épidémiologieHôpitaux Paris SudLe Kremlin Bicêtre CedexFrance
  3. 3.Service d’anatomo-pathologieHôpitaux Paris SudLe Kremlin Bicêtre CedexFrance
  4. 4.Service d’endocrinologieHôpitaux Paris SudLe Kremlin Bicêtre CedexFrance
  5. 5.Service d’UrologieHôpitaux Paris SudLe Kremlin Bicêtre CedexFrance
  6. 6.Service de Biologie HormonaleHôpitaux Paris SudLe Kremlin Bicêtre CedexFrance
  7. 7.Faculté Paris SudLe Kremlin BicêtreFrance
  8. 8.Hopital Necker, Faculté Paris 5Service de RadiologieParisFrance
  9. 9.Institut LangevinParisFrance

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