Klinefelter Syndrome

Discussion in 'Men's Health Forum' started by Michael Scally MD, Mar 5, 2017.

  1. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Calogero AE, Giagulli VA, Mongioi LM, et al. Klinefelter syndrome: cardiovascular abnormalities and metabolic disorders. J Endocrinol Invest. https://link.springer.com/article/10.1007%2Fs40618-017-0619-9

    Klinefelter syndrome (KS) is one of the most common genetic causes of male infertility. This condition is associated with much comorbidity and with a lower life expectancy. The aim of this review is to explore more in depth cardiovascular and metabolic disorders associated to KS.

    KS patients have an increased risk of cerebrovascular disease (standardized mortality ratio, SMR, 2.2; 95% confidence interval, CI, 1.6-3.0), but it is not clear whether the cause of the death is of thrombotic or hemorrhagic nature.

    Cardiovascular congenital anomalies (SMR, 7.3; 95% CI, 2.4-17.1) and the development of thrombosis or leg ulcers (SMR, 7.9; 95% CI, 2.9-17.2) are also more frequent in these subjects.

    Moreover, cardiovascular abnormalities may be at least partially reversed by testosterone replacement therapy (TRT).

    KS patients have also an increased probability of endocrine and/or metabolic disease, especially obesity, metabolic syndrome and type 2 diabetes mellitus. The effects of TRT on these abnormalities are not entirely clear.
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  2. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    [OA] Portal Vein Thrombosis Due to an Increase in Dose of testosterone in a Young Man with Klinefelter Syndrome

    Klinefelter syndrome (KS) is associated with increased incidence of thrombotic events. Hypofibrinolysis is associated with increased risk of thromboembolism. Although testosterone replacement therapy (TRT) inhibits the hypofibrinolysis, it can still cause thrombosis paradoxically due to increased dose and duration of use.

    Herein, we present a case of a young male diagnosed with KS who was taking testosterone. The dose was increased to boost the energy levels, and the patient presented with abdominal pain. Computed tomography (CT) of the abdomen showed extensive portal vein thrombosis. He was started on enoxaparin followed by apixaban. Studies need to be done regarding the need for thromboembolism prophylaxis in patients on TRT.

    Amjad W, Khatoon S, Tarasaria T, Sharifova G. Portal Vein Thrombosis Due to an Increase in Dose of Testosterone in a Young Man with Klinefelter Syndrome. Cureus 2017;9:e1823. Portal Vein Thrombosis Due to an Increase in Dose of Testosterone in a Young Man with Klinefelter Syndrome
  3. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    [OA] Klinefelter Syndrome: More Than Hypogonadism

    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, but may be overcome by TESE and ICSI. 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. Nevertheless, the majority fall within the average range regarding their intellectual abilities and adaptive functioning.

    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.

    Kanakis GA, Nieschlag E. Klinefelter syndrome: more than hypogonadism. Metabolism: clinical and experimental 2018. Klinefelter syndrome: more than hypogonadism. - PubMed - NCBI
  4. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Management of Cardiovascular Complications in Klinefelter Syndrome Patients

    INTRODUCTION: Klinefelter syndrome (KS), also known as 47, XXY, shows increased mortality when compared with mortality rates among the general population. Cardiovascular, hemostatic, metabolic diseases are implicated. Moreover, cardiac congenital anomalies in KS can contribute to the increase in mortality.

    AREAS COVERED: In this study, we have systematically reviewed the relationships between KS and the cardiovascular system and the management of cardiovascular complication. In summary, patients with KS display increased cardiovascular risk profile, characterized by increased prevalence of metabolic alterations including dyslipidemia, diabetes mellitus (DM), and abnormalities in biomarkers of cardiovascular disease.

    KS subjects are characterized by subclinical abnormalities in endothelial function and in left ventricular (LV) systolic and diastolic function, which - when associated with chronotropic incompetence - may negatively influence cardiopulmonary performance.

    Moreover, KS patients appear to be at a higher risk for cardiovascular disease, due to thromboembolic events with high prevalence of recurrent venous ulcers, venous insufficiency, recurrent venous and arterial thromboembolism leading to deep venous thrombosis or pulmonary embolism.

    EXPERT OPINION: Considering the unequivocal finding of increased mortality of KS patients, we suggest a periodic cardiovascular follow up in specialized centers with multidisciplinary care teams that comprise endocrinologists and cardiologists dedicated to KS syndrome.

    Accardo G, Amoresano Paglionico V, Di Fraia R, et al. Management of cardiovascular complications in Klinefelter syndrome patients. Expert review of endocrinology & metabolism 2019:1-8. https://www.tandfonline.com/doi/abs/10.1080/17446651.2019.1584036?journalCode=iere20
  5. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Klinefelter Syndrome and Diabetes

    Purpose of Review - Klinefelter syndrome (KS) is associated with increased insulin resistance and high rates of type 2 diabetes (T2DM). Our aim was to review what is known about the prevalence of diabetes in men with KS, potential mechanisms underlying the observed metabolic phenotype, and the data that are available to guide treatment decisions.

    Recent Findings - The increased prevalence of T2DM seen in men with KS appears to be the result of multiple mechanisms including increased truncal adiposity and socioeconomic disadvantages, but it is likely not a direct consequence of hypogonadism alone.

    No randomized trials have been conducted to evaluate the impact of testosterone replacement therapy on T2DM in men with KS, but observational data suggest that testosterone replacement is not associated with lower rates of diabetes or improved glycemic control.

    Summary - Metabolic derangements are common in KS, but treatment strategies specific to this population are lacking. Early lifestyle and dietary interventions are likely important. Additional research is needed to dissect the complex interaction between genotype and metabolic phenotype.

    Collaboration between academic centers caring for men with KS is needed to facilitate the development of evidence-based clinical practice guidelines, which would inform optimal screening and treatment strategies for this patient population.

    O’Connor MJ, Snyder EA, Hayes FJ. Klinefelter Syndrome and Diabetes. Current Diabetes Reports 2019;19:71. Klinefelter Syndrome and Diabetes