, Volume 61, Issue 2, pp 194–203 | Cite as

Klinefelter syndrome, insulin resistance, metabolic syndrome, and diabetes: review of literature and clinical perspectives

  • Andrea Salzano
  • Roberta D’Assante
  • Liam M. Heaney
  • Federica Monaco
  • Giuseppe Rengo
  • Pietro Valente
  • Daniela Pasquali
  • Eduardo Bossone
  • Daniele Gianfrilli
  • Andrea Lenzi
  • Antonio Cittadini
  • Alberto M. Marra
  • Raffaele Napoli
Mini Review



Klinefelter syndrome (KS), the most frequent chromosomic abnormality in males, is associated with hypergonadotropic hypogonadism and an increased risk of cardiovascular diseases (CVD). The mechanisms involved in increasing risk of cardiovascular morbidity and mortality are not completely understood. This review summarises the current understandings of the complex relationship between KS, metabolic syndrome and cardiovascular risk in order to plan future studies and improve current strategies to reduce mortality in this high-risk population.


We searched PubMed, Web of Science, and Scopus for manuscripts published prior to November 2017 using key words "Klinefelter syndrome" AND "insulin resistance" OR "metabolic syndrome" OR "diabetes mellitus" OR "cardiovascular disease" OR "testosterone". Manuscripts were collated, studied and carried forward for discussion where appropriate.


Insulin resistance, metabolic syndrome, and type 2 diabetes are more frequently diagnosed in KS than in the general population; however, the contribution of hypogonadism to metabolic derangement is highly controversial. Whether this dangerous combination of risk factors fully explains the CVD burden of KS patients remains unclear. In addition, testosterone replacement therapy only exerts a marginal action on the CVD system.


Since fat accumulation and distribution seem to play a relevant role in triggering metabolic abnormalities, an early diagnosis and a tailored intervention strategy with drugs aimed at targeting excessive visceral fat deposition appear necessary in patients with KS.


Klinefelter syndrome Diabetes mellitus Metabolic syndrome Insulin resistance Testosterone therapy Cardiovascular diseases 


Compliance with ethical standards

Conflict of interest

Dr. A.S. receives research grant support from Cardiopath. The remaining authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Andrea Salzano
    • 1
    • 2
  • Roberta D’Assante
    • 3
  • Liam M. Heaney
    • 2
  • Federica Monaco
    • 1
  • Giuseppe Rengo
    • 1
  • Pietro Valente
    • 1
  • Daniela Pasquali
    • 4
  • Eduardo Bossone
    • 5
  • Daniele Gianfrilli
    • 6
  • Andrea Lenzi
    • 6
  • Antonio Cittadini
    • 1
  • Alberto M. Marra
    • 3
  • Raffaele Napoli
    • 1
  1. 1.Department of Translational Medical SciencesFederico II University School of MedicineNaplesItaly
  2. 2.Department of Cardiovascular Sciences and NIHR Leicester Biomedical Research CentreUniversity of Leicester, Glenfield HospitalLeicesterUK
  3. 3.IRCCS S.D.N., Via Gianturco 113NaplesItaly
  4. 4.Department of Neurological, Metabolic, and Geriatric Science, Endocrinology UnitUniversity of Campania “Luigi Vanvitelli”CasertaItaly
  5. 5.Department of Cardiology and Cardiac SurgeryUniversity Hospital “Scuola Medica Salernitana”SalernoItaly
  6. 6.Department of Experimental MedicineSapienza University of RomeRomeItaly

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