Endocrine Abstracts

Introduction: Diabetes mellitus (DM) results from a defect in insulin secretion and/or its action. The Breast-Cancer Susceptibility Gene 2 (BRCA2), like BRCA1, is a tumour suppressor gene, and its mutation is associated with an increased risk of breast cancer and, in males, testicular cancer. In patients with the BRCA1/2 mutation, the level of Insulin-like Growth Factor (IGF)-1 and, consequently, the peripheral sensitivity to insulin are reduced, suggesting that this could be the causal relationship between insulin resistance and the development of dysglycemia in these patients.

Clinical case: Male patient, 26 years old, with normal weight, referred to the Endocrinology consultation for DM of dubious etiology diagnosed in routine analyses with his attending physician (fasting blood glucose of 103 mg/dl and blood glucose 2h post-75g of oral glucose of 334 mg/dl). He reported polyuria and polydipsia of moderate intensity and of indeterminate evolution time, without associated weight loss. He had a diagnosis of testicular teratocarcinoma in 2012, aged 16, for which he undergone left orchiectomy, followed by chemotherapy with bleomycin, etoposide and cisplatin (between 2013 and 2014) and having the genetic study revealed mutation in the BRCA2 gene. He also has atopic eczema, currently medicated with dupilumab, without glucocorticoid therapy. He have a family history of DM in the maternal grandmother. Hypoglycemic therapy was started by his primary care physician with metformin 1000 mg/day, with subsequent referral to a tertiary treatment center. No stigmata of any endocrinopathy on physical examination, namely acanthosis nigricans, was noted. Analytically, in the first consultation, he presented an occasional measurement of glucose of 188 mg/dl, with C-peptide of 6.58 pg/ml and anterior pituitary function without alterations. Anti-pancreatic islet antibodies, anti-GAD65, anti-IA2 and anti-ZnT8 were negative. Next Generation Sequencing panel for monogenic DM did not reveal any pathogenic variant. It was then added, due to insulin resistance, pioglitazone 15 mg/day and the patient manifested an excellent glycemic control (HbA1c 5.7%, TIR 90%, TBR 4%, TAR 6% and CV 29.7%), maintaining follow-up in the Endocrinology consultation.

Conclusion: We report the case of a young, normal-weight patient with DM and mutation in the BRCA2 gene whose evaluation excluded autoimmune etiology and MODY diabetes, which highlights the clinical heterogeneity associated with dysglycemia. The possible relationship between insulin resistance and mutation in the BRCA2 gene could be the etiology of DM in this context, emphasizing the importance of assessing glucose metabolism in this population subgroup.