yuyun 2010-6-8 00:34
環境物質誘發自體免疫甲狀腺功能疾病
作者：Paul W. Mamula, PhD
出處：WebMD醫學新聞
May 20 2010（明尼蘇達州明尼亞波里斯）－根據專家於美國甲狀腺醫學會（ATA）2010年春季會議報告，多重基因與環境因素會誘發人類的自體免疫疾病。
洛杉磯加州大學David Geffen醫學院內科與生理學教授Gregory A. Brent醫師發表他們的發現。
他報告，基因解釋了大約70%造成自體免疫疾病風險的原因，剩下的可能與許多環境誘發因子有關。
他解釋，許多毒素會影響碘的攝取，以及甲狀腺荷爾蒙的製造、代謝、結合與作用。
他表示，最常影響甲狀腺代謝的物質是高氯酸鹽（一種礦石燃料添加物）、硫氰化物（一種在香菸裡的化合物）、以及戴奧辛（一種殺蟲劑）。他附帶表示，很少有研究評估這些物質是如何影響人類的。
Brent醫師表示，問題是，大部分甲狀腺毒性物質已經在活體以及動物模式上發現。對於人類的顯著性很難去評估。
Brent醫師報告，部分人類危險因子是醫療用放射線、環境釋放輻射線（例如車諾比核爆事件以及長島原子彈）、環境汙染物質、以及過多的碘攝取。
醫療用放射線可能誘發抗甲狀腺抗體以及自體免疫疾病。Brent醫師指出，部分接受放射線碘治療非葛瑞氏疾病甲狀腺功能亢進最終會發生葛瑞氏疾病。
根據Brent醫師表示，環境釋放是許多研究暴露與甲狀腺疾病之間關係的基礎。毒理學家想要知道接受的劑量。他附帶表示，對於這些放射線意外，我們已經有與疾病關聯性最佳的證據，因為劑量是已知的。
他報告幾個來自選定人類研究的例子，這些研究顯示核災害I131釋放以及原子彈爆炸後的效應。一項研究追蹤一群原子彈爆炸倖存者，許多人發生抗甲狀腺抗體，以及甲狀腺功能低下。這個異常以U型相關性表現，就像在車諾比核爆倖存者身上看到的一樣。
根據Brent醫師表示，飲食中加入碘也會誘發特定個體與群眾的疾病。他表示，居住在缺碘地區的人們，給予他們碘，會刺激免疫反應以及抗體生成。
Brent醫師宣稱，研究者們已經有環境毒性物質對人類影響效應的最新證據。他向與會者表示，已經發現越來越多與甲狀腺功能作用受損有關的化合物。
甲狀腺會受到毒性物質影響。研究者們對於這些物質對人類影響所知不多。這些化合物包括多氯聯苯（PCBs）、殺蟲劑、多溴聯苯醚（PBDEs）與雙酚A（BPA）。
Brent醫師表示，在實驗動物模式中，BPA已經被證實會影響甲狀腺受體與甲狀腺功能。雖然BPA目前是個擔憂，但該化合物在人類效應的證據並不多。部分證據存在於工業暴露到其他化合物情況下，但這些缺乏劑量反應數據。
Brent醫師表示，避免甲狀腺功能問題最好的方法是找出危險因子並試著避免它們。環境因子可以解釋大約30%自體免疫甲狀腺疾病的風險。容易避免的危險因子包括特定藥物、吸菸、壓力（雖然難以證實）、缺乏硒、以及被汙染的井水（高氯酸鹽）。
紐約西奈山醫學院研究副主任、同時也是ATA一位主持人的Yaron Tomer醫師向Medscape糖尿病與內分泌學表示，臨床醫師們沒有環境對人類影響很好的數據，但是Brent醫師的發表總結了目前的研究結果且沒有太大的偏見。
所有發表在這項會議的綜論將會刊登在2010年7月的甲狀腺（Thyroid）期刊上。
Brent醫師表示沒有相關資金上的往來。Tomer醫師表示接受國家衛生研究院的研究經費，但是報告沒有其他相關資金往來。
Environmental Agents Trigger Autoimmune Thyroid Disease
By Paul W. Mamula, PhD
Medscape Medical News
May 20 2010 (Minneapolis, Minnesota) — Multiple genetic and environmental risk factors can trigger autoimmune thyroid disease in humans, according to experts here at the American Thyroid Association (ATA) Spring 2010 Meeting.
Gregory A. Brent, MD, professor of medicine and physiology at the David Geffen School of Medicine at the University of California at Los Angeles, presented the findings.
He reported that "genetic background accounts for about 70% of the risk for autoimmune thyroid disease. The remainder is likely related to a range of environmental triggers."
A number of toxicants affect iodine uptake and thyroid hormone synthesis, metabolism, binding, and action, he explained.
He noted that among the more common agents that affect thyroid metabolism are perchlorates (a rocket fuel additive), thiocyanates (a compound in cigarettes), and dioxins (a class of pesticides). Few studies assess how these agents affect humans, he added.
"The problem is that most of these thyroid toxicants have been identified in?vitro and in animal models. The significance for humans is much more difficult to assess," said Dr. Brent.
Dr. Brent reported that some of the risk factors for humans are medical radiation, environmental releases of radiation (such as from the Chernobyl nuclear reactor accident and the Hiroshima atomic bomb), environmental pollutants, and excess iodine intake.
Medical radiation can trigger antithyroid antibodies and autoimmune thyroid disease. Dr. Brent pointed out that some patients treated with radioactive iodine for non-Graves' disease hyperthyroidism eventually develop Graves' disease.
Environmental releases have served as the basis for many studies of exposure and thyroid disease, according to Dr. Brent. "Toxicologists want to know the dose given. For these radiation accidents, we have the best evidence of the [disease] relationship because the dose is known," he added.
He presented examples from selected studies in humans that demonstrated the effects of I131 releases in nuclear accidents and after the atomic bomb. One study that followed a cohort of atomic bomb survivors found that many people developed antithyroid antibodies and hypothyroidism. The disorders manifested a U-shaped relationship, as did findings in studies of the Chernobyl survivors.
Iodine added to the diet can trigger disease in select individuals and populations, according to Dr. Brent. He noted that among people in iodine-deficient areas, giving them iodine can stimulate immune response and antibodies.
Researchers have the least evidence for environmental toxicant effects in humans, Dr. Brent stated.
"A whole range of compounds are being increasingly recognized that are associated with the impairment of thyroid hormone action," he told meeting attendees.
The thyroid is influenced by toxicants. Researchers know very little about their effects in humans. These compounds include polychlorinated biphenyls (PCBs), pesticides, polybrominated diphenyl ethers (PBDEs), and bisphenol?A (BPA).
In experimental animals, BPA has been shown to affect thyroid receptors and thyroid function, said Dr. Brent. Although BPA is of concern now, evidence of its effects in humans is sparse. Some evidence exists for industrial exposure to other compounds, but these lack dose-response data.
The way to avoid thyroid problems is to recognize risk factors and try to avoid them, Dr. Brent said. He noted that environmental factors account for about 30% of the risk for autoimmune thyroid disease. Risk factors that are easily avoided include certain drugs, cigarette smoke, stress (although difficult to prove), selenium deficiency, and contaminated well water (perchlorates).
Yaron Tomer, MD, vice chair of research at Mount Sinai School of Medicine in New York City, and a presenter at the ATA, told Medscape Diabetes & Endocrinology that "physicians don't have good human data for environmental insults, but Dr. Brent's presentation summarized the existing data well and without bias."
All of the reviews presented at this meeting will appear in the July?2010 issue of Thyroid.
Dr. Brent has disclosed no relevant financial relationships. Dr. Tomer reports receiving research grants from the National Institutes of Health, but reports no other relevant financial relationships.
American Thyroid Association (ATA) Spring 2010 Meeting. Presented May?15, 2010.