Vitti P, Rago T, Tonacchera M, Pinchera A
Department of Endocrinology and Metabolism, University of Pisa, Pisa, Italy.
J Endocrinol Invest. 2002;25(10 Suppl):16-8.
Toxic nodular goiter (TNG) is the most frequent cause of thyrotoxicosis in the elderly, specially in iodine deficient areas. Epidemiological studies have shown that in iodine deficient areas (Jutland) the incidence of hyperthyroidism is significantly higher with respect to areas with normal iodine intake (Iceland) and it is due to TNG. A careful epidemiological study recently carried out in Pescopagano, in southern Italy, an area characterized by a mild to moderate iodine deficiency, indicates that, in its natural history, nodular goiter contributes to the development of functional autonomy and eventually hyperthyroidism. Somatic activating mutations of the TSH receptor are involved in the pathogenesis of TNG. It is supposed that the prolonged iodine deficiency associated with chronic TSH stimulation increases the replication of follicular thyroid cells, and favor the appearance and expression of mutations of the TSH receptor gene. The clinical signs are usually more subtle than those observed in Graves' disease: a long phase of subclinical hyperthyroidism (normal circulating thyroid hormones and undetectable TSH levels) can precede the appearance of the symptoms. Cardiac symptoms are most frequent, (arrhythmia and atrial fibrillation). Thyroid scintigraphy in toxic multinodular goiter shows an uneven distribution of the radionuclide with multiple hyperfunctioning nodules and cold nodules. Thyroid US shows goiter with inhomogeneous solid nodules often with ill-defined borders. The treatment with antithyroid drug does not allow a permanent remission of hyperthyroidism, but its use is indicated to achieve euthyroidism before the definitive treatment. The definitive treatment is radioiodine or thyroidectomy.
毒性结节性甲状腺肿（TNG）是老年人甲状腺毒症最常见的病因，在碘缺乏地区尤为如此。流行病学研究表明，在碘缺乏地区（日德兰半岛），甲状腺功能亢进的发病率相对于碘摄入正常的地区（冰岛）显著更高，且这是由TNG所致。最近在意大利南部的佩斯科普加诺进行了一项细致的流行病学研究，该地区的特点是碘缺乏程度为轻度至中度，研究表明，在其自然病程中，结节性甲状腺肿会促使功能自主性的发展，并最终导致甲状腺功能亢进。促甲状腺激素（TSH）受体的体细胞激活突变参与了TNG的发病机制。据推测，与慢性TSH刺激相关的长期碘缺乏会增加甲状腺滤泡细胞的复制，并有利于TSH受体基因突变的出现和表达。其临床症状通常比格雷夫斯病更为隐匿：在症状出现之前，可能会有一个较长的亚临床甲状腺功能亢进期（循环甲状腺激素正常且TSH水平检测不到）。心脏症状最为常见（心律失常和心房颤动）。毒性多结节性甲状腺肿的甲状腺闪烁扫描显示放射性核素分布不均，有多个功能亢进结节和冷结节。甲状腺超声显示甲状腺肿伴有不均匀的实性结节，边界通常不清晰。使用抗甲状腺药物治疗不能使甲状腺功能亢进永久缓解，但在确定性治疗前使用该药有助于实现甲状腺功能正常。确定性治疗方法是放射性碘治疗或甲状腺切除术。
