Abstract Introduction Klinefelter Syndrome (KS) is the most common cause of primary hypogonadism in males. Large registry-based studies show a 40% increase in mortality, especially cardiovascular mortality, among KS patients. Research has demonstrated an increased prevalence of metabolic syndrome, and small case-series have shown a high prevalence of chronotropic incompetence (CI) and sedentary lifestyle among adolescents and young adults with KS. Case A 52-year-old male with KS and obesity presented to Pulmonology clinic with four years of dyspnea on exertion. The patient was taking a prolonged steroid taper for secondary adrenal insufficiency from iatrogenic corticosteroid administration for a prior pituitary adenoma. Pulmonary function tests (PFTs) revealed a forced expiratory volume in one second to forced vital capacity (FEV1/FVC) ratio of 0.77, normal lung volumes and diffusing capacity for carbon monoxide, and a 10% FEV1 bronchodilator response. Asthma therapy was initiated without improvement. Evaluations for other causes of dyspnea, including echocardiogram, thoracic imaging, and nuclear stress testing, were negative. A cardiopulmonary exercise test demonstrated a low peak oxygen consumption (V˙O2) of 0.98 liters per minute (L/min) (36% predicted), indicative of severely reduced exercise capacity. His significantly reduced peak heart rate (90 beats per minute, 54% predicted) and shallow heart rate rise relative to V˙O2 were consistent with severe chronotropic insufficiency. The patient also had a concomitant mechanical ventilatory limitation signified by a maximum exercise minute ventilation (MV) of 40 L/min, which was 80% of his pretest MVV (49 L/min). Positional PFTs showed preserved FEV1 and FVC between supine and seated positions, reassuring against diaphragmatic weakness. Overall, the findings raised concern for global muscular weakness driving the ventilatory limitation. Discussion CI resulting in impaired exercise performance is an emerging characteristic being described in KS patients. A case series of 69 young-adult KS patients (mean age 30) revealed CI in 51% of patients, with a mean maximal heart rate of 147, corroborating findings seen in a case series of 19 adolescents. The severity of CI in this case along with the patient’s age greater than 40 are previously undescribed findings that demonstrate the potential for CI to persist or worsen into adulthood. Additionally, the patient’s ventilatory limitation secondary to overall muscular weakness demonstrates the adverse effects that can be seen in chronic glucocorticoid treatment and sedentary lifestyle in a patient already at risk of an unfavorable metabolic profile from underlying KS. These findings prompted a recommendation to resume testosterone therapy to address sarcopenia. This abstract is funded by: None
Gay et al. (Fri,) studied this question.