Hill R N, Erdreich L S, Paynter O E, Roberts P A, Rosenthal S L, Wilkinson C F
Office of Pesticides and Toxic Substances, U.S. Environmental Protection Agency, Washington, D.C. 20460.
Fundam Appl Toxicol. 1989 May;12(4):629-97.
Ample information in experimental animals indicates a relationship between inhibition of thyroid-pituitary homeostasis and the developmental thyroid follicular cell neoplasms. This is generally the case when there are long-term reductions in circulating thyroid hormones which have triggered increases in circulating thyroid stimulating hormone. Such hormonal derangements leading to neoplasms have been produced by different regimens, including dietary iodide deficiency, subtotal thyroidectomy, and administration of natural and xenobiotic chemical substances. The carcinogenic process proceeds through a number of stages, including follicular cell hypertrophy, hyperplasia, and benign and sometimes malignant neoplasms. Given the interrelationship between the thyroid and pituitary glands, conditions that result in stimulation of the thyroid can also result in stimulation of the pituitary, with the development of hyperplastic and neoplastic changes. The progression of events leading to thyroid (and pituitary) neoplasms can be reversed under certain circumstances be reestablishing thyroid-pituitary homeostasis. Most chemicals that have induced follicular cell tumors seem to operate through inhibition of the synthesis of thyroid hormone or an increase in their degradation and removal. For some of these compounds, it appears that genotoxic reactions may not be playing a dominant role in the carcinogenic process. A seemingly small group of thyroid carcinogens seems to lack influence on thyroid-pituitary status and may in part be operating via their genotoxic potential. In contrast with the well-established relationship between thyroid-pituitary derangement and follicular cell neoplasms in animals, the state of information in humans is much less certain. At this time, ionizing radiation is the only acknowledged human thyroid carcinogen, a finding well established in experimental systems as well. Although humans respond to goitrogenic stimuli as do animals, with the development of cellular hypertrophy, hyperplasia, and under certain circumstances nodular lesions, disagreement exists as to whether malignant transformation occurs in any predictable manner. It would seem that if humans develop thyroid tumors following long-term derangement in thyroid-pituitary status, they may be less sensitive than the commonly used animal models.
实验动物的大量信息表明，甲状腺 - 垂体稳态的抑制与甲状腺滤泡细胞发育性肿瘤之间存在关联。当循环甲状腺激素长期减少，从而引发循环促甲状腺激素增加时，通常会出现这种情况。不同的方案，包括饮食碘缺乏、甲状腺次全切除术以及天然和外源性化学物质的给药，都已导致这种导致肿瘤的激素紊乱。致癌过程会经历多个阶段，包括滤泡细胞肥大、增生以及良性甚至有时是恶性肿瘤。鉴于甲状腺和垂体之间的相互关系，导致甲状腺受到刺激的情况也可能导致垂体受到刺激，并出现增生性和肿瘤性变化。在某些情况下，通过重新建立甲状腺 - 垂体稳态，导致甲状腺（和垂体）肿瘤的事件进展可以逆转。大多数诱发滤泡细胞肿瘤的化学物质似乎是通过抑制甲状腺激素的合成或增加其降解和清除来起作用的。对于其中一些化合物，遗传毒性反应似乎在致癌过程中并不起主导作用。一小部分甲状腺致癌物似乎对甲状腺 - 垂体状态没有影响，可能部分是通过其遗传毒性潜力起作用的。与动物中甲状腺 - 垂体紊乱与滤泡细胞肿瘤之间已明确的关系形成对比的是，人类的相关信息状况要不确定得多。目前，电离辐射是唯一被认可的人类甲状腺致癌物，这一发现在实验系统中也已得到充分证实。尽管人类与动物一样对致甲状腺肿刺激有反应，会出现细胞肥大、增生，在某些情况下还会出现结节性病变，但对于是否会以任何可预测的方式发生恶性转化仍存在分歧。似乎如果人类在甲状腺 - 垂体状态长期紊乱后发生甲状腺肿瘤，他们可能比常用的动物模型更不敏感。
