Overview of Cadmium Thyroid Disrupting Effects and Mechanisms

Abstract

Humans are exposed to a significant number of chemicals that are suspected to produce disturbances in hormone homeostasis. Hence, in recent decades, there has been a growing interest in endocrine disruptive chemicals. One of the alleged thyroid disrupting substances is cadmium (Cd), a ubiquitous toxic metal shown to act as a thyroid disruptor and carcinogen in both animals and humans. Multiple PubMed searches with core keywords were performed to identify and evaluate appropriate studies which revealed literature suggesting evidence for the link between exposure to Cd and histological and metabolic changes in the thyroid gland. Furthermore, Cd influence on thyroid homeostasis at the peripheral level has also been hypothesized. Both in vivo and in vitro studies revealed that a Cd exposure at environmentally relevant concentrations results in biphasic Cd dose-thyroid response relationships. Development of thyroid tumors following exposure to Cd has been studied mainly using in vitro methodologies. In the thyroid, Cd has been shown to activate or stimulate the activity of various factors, leading to increased cell proliferation and a reduction in normal apoptotic activity. Evidence establishing the association between Cd and thyroid disruption remains ambiguous, with further studies needed to elucidate the issue and improve our understanding of Cd-mediated effects on the thyroid gland.

Keywords: cadmium; endocrine disruption; mechanisms; thyroid gland.

Figure 1

Schematic of Cd-mediated cellular effects. The primary pathways are to induce apoptosis when there is a cellular challenge from Cd exposure. When the ability of the cells to efficiently enter apoptosis for repair, or if apoptosis is blocked, the cell will continue to proliferate and perpetuate the genetic damage caused by oxidative stress. Damage to the mitochondrial will occur over time, membrane permeability will change and normal respiration resulting in the generation of ATP will cease. Abbreviations: ROS = Reactive Oxygen Species; FADD = Fas-Associated protein with Death Domain; ER = Endoplasmic Reticulum; AIF = Apoptosis-Inducing Factor; PI3K/Akt = Phosphoinositide 3-Kinase/Protein Kinase B.