Delayed Diagnosis of 48, XXYY Syndrome in an Adult Male Presenting with Severe Insulin Resistance and Hypergonadotropic Hypogonadism: A Case Report

A 48,XXYY syndrome is a rare sex chromosome aneuploidy affecting 1 in 18,000 to 50,000 male births. While metabolic dysfunction is a recognised feature, most adult cases are identified during evaluations for cognitive difficulties, delayed puberty, or infertility. Initial adult presentation through extreme insulin resistance and striking dermatological markers remains highly unusual. We report a 34-year-old male presenting with a one-year history of poorly controlled diabetes and progressive hyperpigmented, scaly skin lesions. Physical examination revealed a body mass index of 28.4 kg/m2 , a waist circumference of 101 cm, sparse body hair, longstanding grade III gynaecomastia, and small bilateral testes. Dermatological assessment confirmed extensive acanthosis nigricans across the neck and axillae, paired with widespread dermatomycosis. Despite a high-dose basal-bolus insulin regimen of 90 units daily combined with four oral antidiabetic agents, severe hyperglycaemia persisted (HbA1c: 10.2%, fasting blood glucose: 320 mg/dL). Endocrine evaluation indicated primary hypergonadotropic hypogonadism, marked by low total testosterone (150 ng/dL) alongside elevated follicle-stimulating hormone (42.77 mIU/mL) and luteinising hormone (43.91 mIU/mL). A C-peptide level of 2.1 ng/mL verified preserved beta-cell function. Subsequent peripheral blood cytogenetic analysis confirmed a 48,XXYY karyotype. The patient was referred for testosterone replacement therapy, bone density monitoring, and fertility counselling. This case underscores the necessity of considering underlying sex chromosome aneuploidies in adult males who exhibit unexplained primary hypogonadism alongside highly refractory metabolic disease, ensuring timely access to essential multidisciplinary interventions.