Presentation at AACE 2011 focuses on understanding environmental toxins and other disrupters to the endocrine system.
One of the barriers to understanding environmental disrupters to the endocrine system is simply confusion with the definitions: many terms are similar to those in toxicology, explained Gregory Brent, MD, professor of medicine and physiology at the UCLA School of Medicine and chief, Endocrinology and Diabetes Division at the VA Greater Los Angeles Healthcare System. Brent spoke at the 20th Annual Meeting and Clinical Congress of the American Association of Clinical Endocrinologists.
He began his talk by defining toxicants, which are chemicals found in the environment that cause toxic effects and which are not made by plants or animals, and toxins, which cause toxic effects and are made by plants or animals. Endocrine disrupters include both toxicants and toxins which “interfere with hormone biosynthesis, metabolism or action, resulting in a deviation from normal homeostatic control or reproduction,” he explained. The entire endocrine system is vulnerable to these disrupters, and the agents that are best characterized are those responsible for reproduction, metabolic syndrome/obesity, increased incidence of thyroid cancer, and increased incidence of congenital hypothyroidism. Most disrupters operate through the classic nuclear receptors (AR, ER, TR, RAR), orphan receptors, enzymes in steroid synthesis pathways, adrenergic receptors, and hormone metabolism.
Brent continued by reviewing examples of endocrine disrupters. These include PCB’s, which are used in processes involving oils, lubricants, industry, and commercial products, and which cause disruptions in sperm motility, reduced serum T4, and are partial agonists for thyroid receptors. BPA’s are primarily found in plastics and epoxy can linings and are thyroid receptor antagonists, with the most susceptible population being pregnant women. TBT is found in paints, PVC pipe manufacturing, and fungicides—they are RXR and PPAR-gamma agonists and are adipogenic. DES and DDT/DDE cause disruptions in reproductive functioning among other effects.
Brent spent some time describing phytoestrogens, which are bioactive molecules present as nutritional constituents of commonly consumed vegetables (eg, soy, legumes). They bind to estrogen receptors and induce an agonist/antagonist response, with a preference for estrogen receptor beta. Phytoestrogens are TPO inhibitors and implicated in breast cancer. In a study of four-week-old mice, after one week on a soy-free diet, they were supplemented with 14 days of various doses of genistein. Results revealed that at low doses the genistein was adipogenic and at high doses it was anti-adipogenic. “This is typical of toxicology results,” he explained. One misconception about soy foods he cleared up was that there is no evidence soy isoflavones adversely affect thyroid function. The only exception is for those on thyroxin.
There is definitely an impact of external radiation on thyroid function, which is of special concern in light of recent events in Japan. In addition to increased risk for thyroid cancer, radiation may cause autoimmune disease and thyroid nodules. So how might humans absorb radiation from the environment? Brent gave an example using cows’ milk. Radioiodine in the air causes contamination in the ground, which is absorbed by cows upon grazing, and from there it goes into cows’ milk and is consumed by humans, especially children. A recent study on children exposed to radiation from the Chernobyl accident found marked increases in thyroid cancer. Whether due to milk consumption or other exposure, the study highlights the definite risks associated with radiation exposure. The question then becomes, how do we protect ourselves? In the event of nuclear disaster, potassium iodide does work to protect the thyroid, confirmed Brent.
Ultimately, in the absence of nuclear disaster, there are steps we can take to protect ourselves from environmental disrupters, said Brent. Individuals should routinely have their thyroids checked, ensure adequate iodine intake, try to avoid products containing known toxins and toxicants, and maintain a healthy diet.