Delayed Diagnosis of 48, XXYY Syndrome in an Adult Male Presenting with Severe Insulin Resistance and Hypergonadotropic Hypogonadism: A Case Report
- 1Postgraduate Student, Department of General Medicine, Sree Balaji Medical College and Hospital, Chennai, Tamil Nadu, India.
- 2Professor, Department of General Medicine, Sree Balaji Medical College and Hospital, Chennai, Tamil Nadu, India.
- 3Assistant Professor, Department of General Medicine, Sree Balaji Medical College and Hospital, Chennai, Tamil Nadu, India.
Abstract
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, long-standing 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.
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BibTeX
@article{krishna2026delayed,
title = {{Delayed Diagnosis of 48, XXYY Syndrome in an Adult Male Presenting with Severe Insulin Resistance and Hypergonadotropic Hypogonadism: A Case Report}},
author = {Buddha Sai Krishna and K Arun and V Jayakaran and Abinaya Venkateshan and Mathisha Ebby Perrin},
journal = {Journal of Clinical and Diagnostic Research},
year = {2026},
month = nov,
doi = {10.7860/jcdr/2026/88722.24689},
url = {https://doi.org/10.7860/jcdr/2026/88722.24689},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Delayed Diagnosis of 48, XXYY Syndrome in an Adult Male Presenting with Severe Insulin Resistance and Hypergonadotropic Hypogonadism: A Case Report
AU - Buddha Sai Krishna
AU - K Arun
AU - V Jayakaran
AU - Abinaya Venkateshan
AU - Mathisha Ebby Perrin
PY - 2026
DA - 2026/11/04
JO - Journal of Clinical and Diagnostic Research
DO - 10.7860/jcdr/2026/88722.24689
UR - https://doi.org/10.7860/jcdr/2026/88722.24689
AB - 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, long-standing 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.
SN - 2249-782X
SN - 0973-709X
ER -