Differentiated Thyroid Cancer in Severe Insulin Resistance

Background/Objective: Hyperinsulinemia and insulin resistance (IR) are associated with increased cancer risk. Patients with severe IR due to lipodystrophy or mutations of the insulin receptor have increased thyroid nodule prevalence at young ages, and papillary thyroid cancer (PTC) has occurred. We describe thyroid cancer cases in severe IR and analyze prevalence and clinical and pathologic features of PTC in cohorts with severe IR, mild IR, and euglycemic controls. Methods: PTC prevalence in severe IR was compared with SEER database population data. Cross-sectional comparison was performed in 70 patients with PTC (6 severe IR, 13 type 2 diabetes, and 51 controls). Main outcome measure(s) were PTC prevalence, tumor characteristics, and immunohistochemistry. Results: PTC prevalence in severe IR was 2.2% versus 0.29% based on SEER data for the US population (P < .0001). PTC patients with severe IR, mild IR, and euglycemic controls had ages 26 ± 9, 53 ± 10, and 35 ± 7 years, respectively (P < .0001). HbA1c was 8.5 ± 2.1%, 7.1 ± 1.2%, and 5.2 ± 0.2% (P < .0001). There were no between-group differences for tumor size or proportions with classical PTC, multiple tumors, regional lymph node involvement, vascular/lymphatic invasion, extrathyroidal extension, or distant metastases. There was no difference between groups in tumor insulin-like growth factor-1 receptors or smooth muscle actin expression, or BRAF mutation status. Conclusion: This study suggests that severe IR syndromes are associated with increased PTC risk. However, there were no differences in PTC characteristics between groups with varying degrees of IR. Mechanisms linking severe IR with PTC development require further investigation.