SAT-148 Late Diagnosis of Klinefelter Syndrome: Overcoming Phenotypic Variability and Diagnostic Oversights

Abstract Disclosure: A. Kamran: None. C. Okigbo: None. We present a case of Klinefelter syndrome (KS) diagnosed in adulthood, highlighting the challenges in recognizing this common yet underdiagnosed condition. Early diagnosis is critical due to the association of KS with metabolic, cardiovascular and psychosocial comorbidities. This report explores factors contributing to diagnostic delays, including phenotypic variability, limited awareness and reduced emphasis on physical examination. A 27-year-old male was referred to endocrinology by his primary care physician (PCP) for low testosterone with fatigue, low libido and erectile dysfunction. Initially started on testosterone gel, he discontinued it due to concerns about transfer risk at work. He reported no testicular trauma, fractures, voice changes, or developmental delays-though he dropped out of high school. Puberty occurred at age 13, but he struggles with obesity and sparse hair growth since adolescence. He was diagnosed with HIV a year prior and is on antiretroviral therapy. Physical examination revealed gynecomastia, non-palpable testicles, micropenis and sparse facial and body hair. His height and BMI were 5’11 and 51, respectively. Early morning fasting total testosterone (42 ng/dL) and free testosterone (8.7 pg/mL) were low with elevated LH (28.4 IU/L) and FSH (13.3 IU/L). Additional test results included SHBG 10 nmol/L, prolactin 6.8 ng/mL, TSH 1.21 µIU/mL, ACTH 18 pg/mL, cortisol 11.7 µg/dL, and IGF-1 163 ng/mL (Z-score -0.2). Karyotyping confirmed a 47 XXY pattern consistent with KS. Mammogram revealed gynecomastia without malignancy. He was started on intramuscular testosterone; a DXA scan and testicular ultrasound are pending. KS, the most common chromosomal disorder in men, is underdiagnosed due to its phenotypic variability. While classic features such as a eunuchoid appearance, pubertal arrest and small testes may lead to a timely diagnosis, atypical presentations often delay recognition. In this case, the patient lacked typical KS characteristics such as excessive height and his elevated BMI masked the diagnosis. His hypogonadism was initially attributed to obesity rather than KS. Physical examination during the endocrine evaluation revealed non-palpable testes and micropenis, critical findings previously overlooked. Small testes remain the most consistent phenotypic feature of KS. This emphasizes the importance of physical examinations in prompting timely referrals to Endocrinology. KS is associated with increased risks of osteoporosis, cardiovascular disease and psychosocial challenges. Raising awareness and focusing on physical examinations can improve diagnostic timing and reduce complications. Enhanced awareness is key to preventing diagnostic delays. Presentation: Saturday, July 12, 2025