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: The purpose of this study was to determine the prevalence of thyroid carcinoma in patients who underwent ultrasound-guided fine needle aspiration biopsy (USgFNA) of thyroid nodules in the island of Cyprus. Ultrasound features as well as the presence of autoimmune thyroid disease were evaluated as risk factors for malignancy. Methods: 322 consecutively examined patients (272 females/50 males, age 13-81) underwent USgFNA of thyroid nodules in a referral endocrine clinic between July 2007 and July 2009. The ultrasonographic characteristics examined were: echogenicity, margin irregularity, composition, calcifications, presence of increased vasculature and nodule size. The presence or absence of autoimmune thyroid disease was recorded. Results: From the 548 nodules examined, 74 (13.6%) were classified as THY3, 4 or 5. 75 patients (123 nodules) underwent surgical resection. 46 patients (64 nodules) proved to have thyroid carcinoma by histology. There was a significant correlation of suspicious/malignant cytology with solid composition, hypoechogenicity, irregular margins and the presence of calcifications. A significant association was also noted between the presence of positive antithyroglobulin antibodies (p < 0.05) and Graves' disease (p = 0.01) with suspicious/malignant cytology. Conclusion: The overall prevalence of thyroid cancer was 14.3%. Ultrasound characteristics were highly predictive of thyroid malignancy. Thyroid autoimmunity should be considered as a risk factor.

Objective. To determine the prevalence of lymph node (LN) metastasis and extrathyroidal extension (ETE) in patients with papillary thyroid microcarcinoma (PTMC) in Cyprus and to evaluate the role of preoperative ultrasound (U/S) examination. Methods. A retrospective study of 102 patients who underwent thyroidectomy for PTMC in a 2-year period. Preoperatively, all patients had a thyroid and neck U/S examination with LN mapping. Tumor size according to the largest diameter, number of foci, LN metastasis, and ETE data was collected from the histopathological report and was compared to the preoperative U/S reports. Results. LN metastasis was present in 23.5% of patients. 15.7% had central, 3.9% had lateral, and 3.9% had both central and lateral LN metastasis. ETE was present in 27.5% of patients. 21.6% had multifocal disease, and in this group, 40.9% had LN metastasis and 36.4% had ETE. Multifocality (p=0.03), size of tumor (p=0.05), and ETE (p≤0.001) were significantly associated with LN metastasis. The prevalence of LN metastasis in multifocal PTMC ≤5 mm was the same with multifocal PTMC >5 mm. The preoperative U/S sensitivity for the suspicious lateral neck and central LN was 100%, and the specificity was 100%. The preoperative U/S sensitivity for nodules suspicious for ETE was 53.6%, and the specificity was 100%. Conclusion. The presence of LN metastasis and ETE in our PTMC patients in Cyprus is frequent. Neck U/S mapping is a highly reliable and accurate tool in identifying metastatic nodes. LN metastasis is associated with ETE and multifocality. Suspicious subcentimeter nodules should undergo FNA irrespective of size when multifocality is suspected.

Objective: Hyperthyroidism is characterized by weight fluctuations and overshoot of weight regain following treatment. We aimed to identify parameters predicting peak percentage weight gain (PWG) in the post-treatment period. Methods: We included 110 patients (73 (66.4%) women) with hyperthyroidism 6–36 months after treatment initiation. The primary outcome was PWG of ≥10% (group A) or <10% (group B). We performed adjusted analyses by logistic regression with age, sex, disease-related weight loss, hypothyroidism occurrence, free T4 at diagnosis (fT4-t0) and disease duration as independent variables. Results: Post-treatment mean (SD) weight gain was 7.4 (5.22) kg, whereas disease-related weight loss was 5.3 (5.15) kg. Group A (52.7% participants) compared to group B had significantly higher median (IQR) fT4-t0 at 47.4 (36.2, 97.2) vs 29.3 (22.8, 40.4) ng/dL (P < 0.001) and disease-related weight loss at 6.8 (3, 10) vs 2.5 (0, 4.8) kg (P < 0.001) and non-significantly higher presentation free triiodothyronine at 19.6 (10.4, 44.1) vs 11.8 (8.7, 22.9) pg/mL (P = 0.078) and TRAb at 6.3 (3, 16.1) vs 4.2 (2.4, 8.7) IU/L (P = 0.093), respectively. Significant predictor variables of post-treatment PWG in logistic regression were disease-related weight loss (OR = 1.23, P = 0.002) and fT4-t0 (OR = 1.04, P = 0.008). Conclusion: More than half the patients with hyperthyroidism had ≥10% PWG post-treatment. Indicators of disease severity, namely disease-related weight loss and baseline thyroid hormones, were predictive of excessive weight gain post-treatment and could be utilized for risk stratification and early intervention.

Background: Adiposity may be associated with thyroid nodularity. However, its impact on the number of nodules and the risk of malignancy is unclear. Aim: To evaluate the impact of adiposity on thyroid nodules using body mass index (BMI), ultrasonographic (US) data and cytological data. Methods: A retrospective cohort study of 310 patients with thyroid nodules was performed. Patients were categorized based on their BMI, and grayscale US data and fine-needle aspiration cytology results were evaluated. Results: Patients with BMI ≥ 25 kg/m2 were found to have a higher number of thyroid nodules compared to those with BMI < 25 kg/m2 (4.25 ± 2.42 vs 3.66 ± 1.93) (P value = 0.05). Patients with BMI ≥ 25 kg/m2 had more suspicious and malignant cytology than those with BMI < 25 kg/m2 (P value = 0.029). Patients with BMI ≥ 25 kg/m2 had more nodules with intermediate and high suspicion sonographic patterns. However, this did not reach statistical significance. Conclusion: Overweight and obese patients have a trend for more thyroid nodules and have a higher risk of being diagnosed with thyroid malignancy.