Cappiello E, Boldorini R, Tosoni A, Piraneo S, Bernasconi R, Raggi U
Divisione di Cardiologia, Istituto di Scienze Biomediche Luigi Sacco, Ospedale Luigi Sacco, Milano, Italy.
J Endocrinol Invest. 1995 Dec;18(11):862-8. doi: 10.1007/BF03349834.
Amiodarone-induced thyrotoxicosis occurs in 2-12.1% of patients on chronic amiodarone treatment. In most cases its pathogenesis is related to iodine overload in the presence of preexisting thyroid abnormalities, such as multinodular or diffuse goiter or autonomous nodule. A minority of patients show apparently normal glands or pictures of non-autoimmune thyroiditis. However, there is recent evidence of a direct toxic effect of amiodarone, with consequent release of iodothyronines into the circulation. We report a patient with amiodarone-induced thyrotoxicosis with toxic thyroid effects demonstrated by electron microscopy in a fine-needle aspiration biopsy. There were three main pathologic findings: multilamellar lysosomal inclusions, intramitchondrial glycogen inclusions--both ultrastructural findings indicating thyroid cell damage--and a microscopic morphological pattern of thyroid cell hyperfunction. No inflammatory changes were found. Plasma thyroglobulin levels were high. The patient proved to be a non responder to simultaneous administration of methimazole (starting dose 30 mg/day) and potassium perchlorate (1000 mg/day for 40 days), while still taking amiodarone, thus providing evidence against a possible pathogenetic role of iodine overload. Dexamethasone (starting dose 3 mg/day) was added to methimazole. After three months euthyroidism had been restored and plasma thyroglobulin level substantially decreased. Subsequent subclinical hypothyroidism developed, which persisted after stopping antithyroid treatment and required substitution treatment with levothyroxine. In view of the primary role of lysosome function in the proteolysis of thyroglobulin molecules and of the energy-requiring carrier-mediated transport of monoiodotyrosine across the lysosomal membrane for iodine salvage and reutilization, we suggest that the pathological lysosomal and mitochondrial changes observed could be an ultrastructural marker for subsequent hypothyroidism in amiodarone-induced thyrotoxicosis. Our observations suggest the usefulness of ultrastructural thyroid evaluation and serial plasma thyroglobulin determinations to thoroughly evaluate the underlying pathogenetic mechanisms in amiodarone-associated thyrotoxicosis with apparently normal thyroid glands. Moreover, more knowledge of its pathogenesis could improve both prognostic stratification and treatment guides.
在接受慢性胺碘酮治疗的患者中，胺碘酮诱发的甲状腺毒症发生率为2%至12.1%。在大多数情况下，其发病机制与存在预先存在的甲状腺异常（如多结节性或弥漫性甲状腺肿或自主性结节）时的碘过载有关。少数患者甲状腺看起来正常或表现为非自身免疫性甲状腺炎。然而，最近有证据表明胺碘酮具有直接毒性作用，从而导致碘甲状腺原氨酸释放到循环中。我们报告了一例胺碘酮诱发的甲状腺毒症患者，细针穿刺活检的电子显微镜检查显示有毒性甲状腺效应。有三个主要病理发现：多层溶酶体包涵体、线粒体内糖原包涵体——这两个超微结构发现均表明甲状腺细胞受损——以及甲状腺细胞功能亢进的微观形态模式。未发现炎症变化。血浆甲状腺球蛋白水平升高。该患者在仍服用胺碘酮的情况下，对同时给予甲巯咪唑（起始剂量30mg/天）和高氯酸钾（1000mg/天，共40天）无反应，从而提供了反对碘过载可能致病作用的证据。地塞米松（起始剂量3mg/天）被添加到甲巯咪唑中。三个月后甲状腺功能恢复正常，血浆甲状腺球蛋白水平大幅下降。随后出现亚临床甲状腺功能减退，在停止抗甲状腺治疗后仍持续存在，需要用左甲状腺素替代治疗。鉴于溶酶体功能在甲状腺球蛋白分子蛋白水解中的主要作用，以及单碘酪氨酸跨溶酶体膜进行碘 salvage和再利用所需能量的载体介导转运，我们认为观察到的病理性溶酶体和线粒体变化可能是胺碘酮诱发的甲状腺毒症后续甲状腺功能减退的超微结构标志物。我们的观察结果表明，超微结构甲状腺评估和连续血浆甲状腺球蛋白测定对于彻底评估甲状腺看似正常的胺碘酮相关性甲状腺毒症的潜在发病机制是有用的。此外，对其发病机制有更多了解可以改善预后分层和治疗指导。
