Introduction: Klinefelter Syndrome (KS) is the most common male sex-chromosome abnorrmality, typically presenting with features of hypogonadism. The association between KS and Type 2 Diabetes is not fully understood as early treatment with testosterone does not minimise this complication. We present an unusual case of simultaneous diagnosis of T2DM and Klinefelter Syndrome in a young adult.
Case: A 17 year old Pakistani gentleman presented with a short history of osmotic symptoms, hyperglycaemia and weight gain. Medical history included beta-thalassaemia trait and family history of T2DM. Venous glucose was 17.8 mmol/l, blood ketone 2.8 mmol/l, hydrogen ion concentration 47 mmol/l and serum bicarbonate 24 mmol/l. HbA1c was 96 mmol/mol and weight 106.2 kg with BMI 34.6 kg/m2. Clinical signs of insulin resistance and hypercortisolaemia were observed; acanthosis nigricans, livid abdominal striae, proximal myopathy and gynaecomastia. Distribution of facial, axillary and pubic hair was normal and testicular volume was significantly reduced bilaterally (<5 ml). Total cholesterol was 5.4 mmol/l and LDL-C 3.5 mmol/l. Anterior pituitary profile confirmed 0900 testosterone 1.4 nmol/l, LH 13.1 U/l, FSH 23.3 U/l, TSH 1.89 mU/l, FT4 14.2 pmol/l and prolactin 1.74 mU/l. Cortisol adequately suppressed to <30 nmol/l after 1 mg dexamethasone. Glutamate decarboxylase (GAD) and islet antigen-2 (IA-2) antibodies were undetectable and c-peptide measureable (3.23 nmol/l [0.36−1.12]). Subcutaneous insulin was commenced with metformin (total daily dose 190 units). Karyotype was 47 XXY, in keeping with Klinefelter Syndrome. Bone densitometry is awaited and testosterone replacement therapy will commence after counseling.
Conclusion: The prevalence of metabolic syndrome in people with KS is 44%. The relative contribution of hypogonadism in the pathogenesis of diabetes remains unclear and both distribution and accumulation of adipose tissue may be more relevant. Testosterone replacement yields marginal cardiovascular benefit but has not been proven to attenuate diabetes risk. Acute hyperglycaemia is not a typical presenting feature of KS and current recommendations advise annual screening for T2DM following a positive diagnosis.