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.

Over the last few decades, thyroid cancer incidence has had a significant increase. Despite well-known genetic and epigenetic factors (radiation, overdiagnosis, already existing benign thyroid tumors), the effect of air pollution on its incidence and mortality has not yet been fully elucidated. In this study, air pollution data from 27 EU member states is used in order to analyze its association with thyroid cancer incidence, and mortality and socioeconomic factors are examined as confounders. This ecological study used age standardized thyroid cancer incidence and mortality rates per 100,000 people for the year 2012 from 27 EU member states, collected from the International Agency for Research on Cancer, World Health Organization and European Cancer. Data regarding mean air pollutant mass concentrations for 1992, 2002 and 2012 was collected from the European Environment Agency. Data analysis was carried out using Prism 5.0 and SPSS v.20. Multiple regression analysis showed a statistically significant positive association between thyroid cancer incidence in men and the environmental 2012 masse of Benzo (k) Fluoranthene (r² = 0.2142, p = 0.042) and HexaChlorocycloHexane (r² = 0.9993, p = 0.0166). Additionally, a statistically significant positive association was observed between the thyroid cancer mortality rate in men and the 1992 environmental concentrations of Hg (r² = 0.1704, p = 0.043). Data indicates that some air pollutants may have an effect on increased thyroid cancer incidence and mortality, at least in men. However, causal relationships cannot be fully supported via ecological studies, and this article only focuses on the EU and uses only three distinct time periods.

Multiple endocrine neoplasia type 2 (MEN2) is an autosomal dominant (AD) condition with very high penetrance and expressivity. It is characterized into three clinical entities recognized as MEN2A, MEN2B, and familial medullary thyroid carcinoma (FMTC). In both MEN2A and MEN2B, there is a manifestation of multicentric tumor formation in the major organs such as the thyroid, parathyroid, and adrenal glands where the RET proto-oncogene is expressed. The FMTC form differs from MEN2A and MEN2B, since medullary thyroid carcinoma (MTC) is the only feature observed. In this present brief report, we demonstrate a collection of RET proto-oncogene genotype data from countries around the Mediterranean Basin with variable characteristics. As expected, a great extent of the Mediterranean RET proto-oncogene genotype data resemble the data reported globally. Most interestingly, higher frequencies are observed in the Mediterranean region for specific pathogenic RET variants as a result of local prevalence. The latter can be explained by founder effect phenomena. The Mediterranean epidemiological data that are presented herein are very important for domestic patients, their family members’ evaluation, and ultimately their treatment.