Klinefelter Syndrome - More Than Simply Low T

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Klinefelter syndrome (KS) is the most frequent chromosome disorder in males (1:650 newborn males), defined by 47,XXY karyotype.
  • The classical phenotype is that of a tall male with relatively long legs, small, firm testes and gynecomastia. Azoospermia and infertility are almost inevitably present.
  • Nevertheless, a broad spectrum of phenotypes has been described and >70% of the actually existing KS men may remain undiagnosed throughout their lifespan.
  • Accordingly, hypogonadism is usually not evident until early adulthood and progresses with ageing.
    • KS patients present a series of comorbidities that increase morbidity and mortality by 40%.
    • Such disturbances are the impaired metabolic profile (obesity, dyslipidemia, insulin resistance) and a tendency to thrombosis, which all favor cardiovascular disease. They also present susceptibility for specific neoplasias (breast cancer, extragonadal germ cell tumors), autoimmune diseases as well as osteoporosis and bone fractures. Moreover, KS has been associated with verbal processing and attention deficits as well as social skill impairments, leading KS individuals to academic and professional achievements inferior to those of their peers of comparable socio-economic status.
  • Testosterone replacement therapy (TRT) is the mainstay of treatment in hypogonadal KS patients; however, randomized trials are needed to determine optimal therapeutic regimens and follow-up schedules.

"Klinefelter syndrome: more than hypogonadism," Metabolism, 2018 January 27, https://www.ncbi.nlm.nih.gov/pubmed/29382506/
 
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