A widely discussed topic in the pathophysiology of thyroid nodules is the role of obesity, a state that leads to increased systemic inflammatory markers. Leptin plays a vital role in forming thyroid nodules and cancer through several mechanisms. Together with chronic inflammation, there is an augmentation in the secretion of tumor necrosis factor (TNF) and the cytokine interleukin 6 (IL-6), which contributed to cancer development, progression and metastasis. In addition, leptin exerts a modulatory action in the growth, proliferation and invasion of thyroid carcinoma cell lines via activating various signal pathways, such as Janus kinase/signal transducer and activator of transcription, mitogen-activated protein kinase (MAPK) and/or phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt). Through several proposed mechanisms, aberrant endogenous estrogen levels have been suggested to play a vital role in the development of both benign and malignant nodules. Metabolic syndrome triggers the development of thyroid nodules by stimulating thyroid proliferation and angiogenesis due to hyperinsulinemia, hyperglycemia and dyslipidemia. Insulin resistance influences the distribution and structure of the thyroid blood vessels. Insulin growth factor 1 (IGF-1) and insulin affect the regulation of the expression of thyroid genes and the proliferation and differentiation of thyroid cells. TSH can promote the differentiation of pre-adipocytes to mature adipocytes but also, in the presence of insulin, TSH possesses mitogenic properties. This review aims to summarize the underlying mechanisms explaining the role of obesity in the pathophysiology of thyroid nodules and discuss potential clinical implications.

Background/Objectives: Both adiposity and Hashimoto’s thyroiditis (HT) are states of chronic inflammation. Adiposity may increase the risk of thyroid nodules and thyroid carcinoma. However, its role in patients with HT remains unclear. The connections among thyroid nodularity, adiposity, and HT have not been explored. Aim: To investigate the impact of adiposity on thyroid nodularity in patients with HΤ and to determine whether there are any differences in the risk for thyroid cancer. Methods: This retrospective cohort study included 294 consecutive patients with HT who were categorized according to their body mass index (BMI). Grayscale ultrasound (US) and fine-needle aspiration (FNA) cytology results were evaluated in association with clinicopathological characteristics. Results: After controlling for age and gender, nodules from patients with a BMI ≥ 25 kg/m² showed significantly more suspicious or malignant cytology (Thy 4–5) compared to patients with a BMI < 25 kg/m² (27.03% vs. 18.18%; p < 0.01). Although not statistically significant after adjustments, patients with BMI ≥ 25 kg/m² demonstrated a higher proportion of nodules classified as highly suspicious on ultrasound (28.20% vs. 22.46%). Additionally, overweight and obese patients tended to have more thyroid nodules (mean ± SD: 2.91 ± 2.11) than normal-weight patients (2.36 ± 1.79), a difference approaching marginal significance (p = 0.06). Conclusions: Adiposity is associated with more suspicious and malignant cytology in patients with HT. Overweight and obese patients with HT tended to have more thyroid nodules. Further studies are needed to investigate the mechanisms linking obesity, thyroid nodules, and HT.

Background: Obesity has been implicated in the pathogenesis and progression of several malignancies, including papillary thyroid carcinoma (PTC), but its role in tumor aggressiveness remains controversial. This study aimed to investigate the association between adiposity, as measured by body mass index (BMI), and histopathological features of aggressiveness in patients with PTC. Methods: This single-center retrospective study included 298 consecutive adult patients diagnosed with PTC between 2016 and 2021 at an endocrine referral center. Patients were stratified based on BMI into normal weight (<25 kg/m²) and overweight/obese (≥25 kg/m²) groups. Clinical, metabolic, and histopathological data were compared between the two groups. Results: Overweight/obese patients had significantly higher rates of hypertension, type 2 diabetes, fasting glucose, and triglycerides, as well as lower high-density lipoprotein cholesterol (all p < 0.01). Tumor size was similar between groups, with over 85% of tumors measuring ≤ 1 cm (microcarcinomas) and no significant difference in the proportion of tumors > 1 cm (p = 0.582). There were no significant differences in multifocality (p = 0.269) or extrathyroidal extension (ETE) (p = 0.826). Lymph node metastases occurred in 34% of normal weight and 28% of overweight/obese patients, without a statistically significant difference (p = 0.402). Lymph node compartment involvement did not significantly differ between groups (p = 0.160). Conclusions: Despite being associated with adverse metabolic profiles, higher BMI was not linked to tumor aggressiveness in patients with predominantly early-stage PTC. As the incidence of obesity and PTC continues to rise, these findings highlight the need for further research into early-stage PTC biology and more precise risk measures of adiposity beyond BMI alone.