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Klinefelter syndrome

Last reviewed: 6 Aug 2025
Last updated: 04 Jun 2024

Summary

Definition

History and exam

Key diagnostic factors

  • infertility
  • failure to complete pubertal maturation
  • small testes
  • expressive speech delay in early childhood
  • micropenis
  • cryptorchidism
Full details

Other diagnostic factors

  • developmental delay
  • behavioral problems in childhood
  • tall stature
  • lack of facial and pubic hair
  • gynecomastia
  • sexual dysfunction/reduced libido
  • high fat-to-muscle ratio/abdominal obesity
  • social/ psychological issues
  • fatigue
Full details

Risk factors

  • increased maternal age
Full details

Diagnostic tests

1st tests to order

  • chromosomal karyotype
  • serum total testosterone
  • serum LH/FSH
Full details

Tests to consider

  • inhibin B
Full details

Treatment algorithm

ONGOING

children

adolescents

adults

Contributors

Authors

​Alan D. Rogol, MD, PhD

Professor Emeritus

Departments of Pediatrics and Pharmacology

University of Virginia

Charlottesville

VA

Disclosures

ADR declares consultation for Antares Pharma (androgen therapy for adolescents), Ascendis Pharma (long-acting growth hormone therapy), BioMarin Pharmaceuticals (therapy for growth plate disorders), Pfizer Pharmaceuticals (long-acting growth hormone), Tolmar Pharmaceuticals (androgen therapy for adolescents), the US Anti-Doping Agency (testosterone and growth hormone in US elite athletes), and the World Anti-doping Agency (testosterone and growth hormone in International elite athletes); he is the Chair DSMB for oral growth hormone secretagogue for Lumos Pharma.

Gary E. Butler, ​MD, FRCPCH

Consultant in Paediatric and Adolescent Endocrinology

University College London Hospital

Clinical Professor of Child and Adolescent Health

UCL Great Ormond Street Institute of Child Health

London

UK

Disclosures

GEB declares that he has no competing interests.

Claus Højbjerg Gravholt, MD, PhD

Professor and Consultant

Department of Endocrinology and Internal Medicine

Department of Molecular Medicine

Aarhus University Hospital

Aarhus University

Aarhus

Denmark

Declarações

CHV has received honorariums within the last 3 years from Novo Nordisk, Merck, and Astra Zeneca for talks on Turner syndrome and endocrine side effects of protein kinase inhibitors.

Revisores

Shanlee Davis, ​MD, PhD

​Associate Professor

Pediatrics-Endocrinology

University of Colorado

Aurora

CO

Declarações

SD serves as a site investigator for Ascendis Pharma on a long-acting growth hormone study. SD serves as a medical advisor for the nonprofit organization Living with XXY. SD has received research funding from the NIH, the Boettcher Foundation, the Pediatric Endocrine Society, AXYS, Living with XXY, and the Turner Syndrome Global Alliance.

Tet Yap, ​MB BChir, MD, MA, FRCS(Urol), FEBU

Consultant Andrological Surgeon

Guy's and St Thomas' Hospital NHS Foundation Trust

London

UK

Declarações

TY declares that he has no competing interests.

Peer reviewer acknowledgements

BMJ Best Practice topics are updated on a rolling basis in line with developments in evidence and guidance. The peer reviewers listed here have reviewed the content at least once during the history of the topic.

Disclosures

Peer reviewer affiliations and disclosures pertain to the time of the review.

Referências

Nossas equipes internas de editoria e de evidências trabalham em conjunto com colaboradores internacionais especializados e pares revisores para garantir que forneçamos acesso às informações o mais clinicamente relevantes possível.

Principais artigos

Butler G, Srirangalingam U, Faithfull J, et al. Klinefelter syndrome: going beyond the diagnosis. Arch Dis Child. 2023 Mar;108(3):166-71. Resumo

Zitzmann M, Aksglaede L, Corona G, et al. European Academy of Andrology guidelines on Klinefelter syndrome. Endorsing organization: European Society of Endocrinology. Andrology. 2021 Jan;9(1):145-67.Texto completo  Resumo

Gravholt CH, Chang S, Wallentin M, et al. Klinefelter syndrome: integrating genetics, neuropsychology, and endocrinology. Endocr Rev. 2018 Aug 1;39(4):389-423.Texto completo  Resumo

Jayasena CN, Anderson RA, Llahana S, et al. Society for Endocrinology guidelines for testosterone replacement therapy in male hypogonadism. Clin Endocrinol (Oxf). 2022 Feb;96(2):200-19.Texto completo  Resumo

Bhasin S, Brito JP, Cunningham GR, et al. Testosterone therapy in men with hypogonadism: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2018 May 1;103(5):1715-44.Texto completo  Resumo

Artigos de referência

Uma lista completa das fontes referenciadas neste tópico está disponível para os usuários com acesso total ao BMJ Best Practice.
  • Klinefelter syndrome images
  • Diagnósticos diferenciais

    • Other male sex chromosome aneuploidies
    • Other causes of developmental delay
    • Central (secondary) hypogonadism
    Mais Diagnósticos diferenciais
  • Diretrizes

    • European Academy of Andrology guidelines on Klinefelter syndrome​
    • Testosterone therapy in men with hypogonadism
    Mais Diretrizes
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