Cardiometabolic Profiles of Boys With Klinefelter Syndrome

Cardiometabolic Profiles of Pubertal Boys With Klinefelter Syndrome With or Without One Year of Exogenous Testosterone Treatment

This study plans to learn more about how to measure the way the the body's energy system works in boys with Klinefelter syndrome, including the heart, lungs, muscles, and liver. This is important to know so that investigators understand how hormones and an extra X chromosome relate to diseases such as diabetes, extra weight gain, heart disease and liver diseases.

Klinefelter syndrome (KS) is the most common chromosomal abnormality in males and is associated with primary gonadal failure in adolescence and a high morbidity and mortality from cardiovascular-related diseases (CVD) in adulthood. Recent studies in children and adolescent boys with KS have found a high prevalence of CVD risk markers, however the underlying mechanisms have not been explored. Our central hypothesis is that pubertal boys with KS have relative testosterone deficiency resulting in abnormal energy metabolism that predisposes them to later CVD, and that exogenous testosterone will modify these abnormalities.

In this study, investigators will measure markers of cardiometabolic risk in pubertal boys with KS.

Inclusion Criteria:

• Male, 47,XXY karyotype (non-mosaic)
• Age 12-17 years
• Tanner stage 3-5 pubic hair
• T naïve group only: No exogenous androgen exposure within the past 5 years
• T exposed group only: currently on topical testosterone, with duration of treatment between 1-2 years.

Exclusion Criteria:

• Cognitive, psychiatric, or physical impairment resulting in inability to tolerate the study procedures
• MRI incompatible metal
• Diagnosis of type 1 or type 2 diabetes
• Hypertension greater than 140/90 mm/Hg at rest (would make exercise studies unsafe)
• Weight > 300 lbs (limit for DEXA)
• Testosterone treatment for <1 year or >2 years