SUN-132 - Klinefelter Syndrome Presenting with a Fragility Fracture and Cardiovascular Complications in an Adult Male

Introduction: Klinefelter syndrome (KS) is a common chromosomal disorder characterized by primary hypogonadism, typically resulting from a 47,XXY karyotype. While reproductive and endocrine manifestations are well described, less recognized complications include decreased bone mineral density with increased risk of fracture and cardiovascular abnormalities, including left ventricular hypertrophy (LVH), mitral valve issues, and early atherosclerotic disease. Early identification is critical to mitigate long-term morbidity and mortality.

Clinical

Case: The patient is a 33-year-old obese male who presented to the emergency room following a ground-level fall and was found to have a complex left acetabular two column fracture extending into the iliac wing, raising concern for underlying bone fragility. Bone density scan revealed bone mineral density (BMD) was lower than expected for age, particularly at the lumbar spine with BMD of 0.699 g/cm2 and Z-score of -3.6. Evaluation for secondary causes of osteoporosis revealed severely low morning serum testosterone levels with total testosterone of 44 ng/dL (n 300-1,080 ng/dL), free testosterone 8.7 pg/mL (n 47-244 pg/mL), and elevated LH and FSH levels consistent with primary hypogonadism. Chromosomal analysis revealed karyotype 47, XXY consistent with a diagnosis of KS. On further history, the patient indicated that he and his wife were having difficulty conceiving a baby. He was also experiencing issues with decreased libido, erectile dysfunction, and loss of facial hair. He reported right orchiectomy 8 years prior for a benign testicular lesion. Mild gynecomastia was noted on physical exam. After discussion of risks and benefits, the patient was initiated on testosterone replacement therapy.

On subsequent visits, the patient reported chest pain. Nuclear Medicine PET Cardiac Stress test revealed left ventricular hypertrophy with suspected microvascular disease. No valvular or other cardiac abnormalities were seen on echocardiogram. There was no prior personal or family history of cardiovascular disease. Given the association between KS and increased risk of cardiovascular abnormalities, these findings were attributed to underlying syndrome-related pathology.

Conclusion: This case highlights the importance of recognizing non-reproductive manifestations of Klinefelter syndrome, particularly skeletal and cardiovascular complications. It is thought that the cardiovascular complications are likely due to the effects of the extra X chromosome. While reduced bone density and increased fracture risk are likely due to combination of testosterone deficiency and genetic factors. Early diagnosis and management, including hormone replacement and appropriate screening, are essential to reduce long-term complications. Increased awareness of these associations can improve multidisciplinary care and patient outcomes.

*Unless otherwise noted, all abstracts presented at ENDO must not be released to the press or the public until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.*