The Role of Adiposity in Papillary Thyroid Cancer Diagnosis and Aggressiveness

Abstract

1. Introduction This PhD dissertation investigates the relationship between adiposity and papillary thyroid carcinoma (PTC)—the most common subtype of thyroid cancer—in the context of rising global obesity rates and increasing incidence of thyroid cancer. The impact of excess body weight on thyroid nodules, malignancy risk, and tumor aggressiveness is comprehensively examined by integrating findings from a systematic review and meta-analysis, two retrospective cohort studies, and a mechanistic review. 2. Methods This dissertation includes four studies: a mechanistic review on the biological association between obesity and thyroid cancer, a systematic review and meta-analysis of the association between BMI and aggressive features of papillary thyroid carcinoma (PTC), and two retrospective clinical studies assessing BMI’s impact on thyroid nodularity in patients with and without Hashimoto’s thyroiditis. 3. Results The literature review highlighted several obesity-related biological pathways and underlying mechanisms that may drive thyroid tumorigenesis and progression, including chronic inflammation, insulin resistance, and altered adipokine signaling. The systematic review and meta-analysis had shown that elevated BMI was significantly associated with extrathyroidal extension (OR 1.26, 95% CI: 1.09–1.44 in overweight; OR 1.45, 95% CI: 1.26–1.64 in obese), multifocality (OR 1.17, 95% CI: 1.10–1.24 in overweight; OR 1.45, 95% CI: 1.29–1.62 in obese), larger tumor size (OR 1.77, 95% CI: 1.52–2.03), lymph node metastasis (OR 1.28, 95% CI: 1.12–1.44), and advanced TNM stage (OR 1.55, 95% CI: 1.27–1.83 in overweight). In a retrospective study of 310 patients with thyroid nodules, individuals with BMI ≥25 kg/m² had a higher number of nodules (mean 4.25 ± 2.42 vs 3.66 ± 1.93; p = 0.05) and a significantly greater likelihood of suspicious or malignant cytology (Thy4–Thy5: 13.64% vs 1.63%; p = 0.04, adjusted p = 0.029). A second retrospective study of 294 patients with Hashimoto’s thyroiditis (HT) found similar trends, with overweight and obese patients having more nodules (mean 2.91 ± 2.11 vs 2.36 ± 1.79; p = 0.02), and a significantly higher proportion of Thy4–Thy5 cytology results (27.03% vs 18.18%; adjusted p < 0.01). Together, these studies demonstrated that increased adiposity is not only associated with a higher burden of thyroid nodules but also with more aggressive pathological features in thyroid cancer. 4. Conclusions Overall, these findings support the role of adiposity as a modifiable risk factor for PTC diagnosis and aggressiveness. The results emphasize the importance of incorporating BMI into thyroid cancer risk stratification and surveillance protocols. This study also further strengthens the rationale for integrating obesity prevention and management into public health strategies targeting endocrine malignancies.