ABSTRACT
Amiodarone is a potent antiarrhythmic drug used for treatment of many types of cardiac arrhythmias. Its structural formula contains a high dose of iodine with a considerable potential to cause thyroid gland dysfunction. The aim of the present work was to study the possible histological changes in the follicular cells of the thyroid gland in male albino rats after long-term administration of amiodarone. Reversibility of these changes was also investigated. The study was confirmed by hormonal assay, to evaluate the thyroid gland endocrine function. The present study was carried out on 40 adult male albino rats, which were divided into 3 study groups; group I, considered as control, group II [the amiodarone- treated group] received amiodarone orally in a daily dose of 30 mg/kg for 12weeks and group III [the withdrawal group] that received the same dose of amiodarone for 12 weeks and were sacrificed 6 weeks after withdrawal of the drug. Rats were sacrificed after ether anesthesia and blood samples were subjected to hormonal assay of TSH, T[4] and T[3] levels. The thyroid gland tissue samples were removed and prepared for light microscopic examination of H and E stain and toluidine blue- stained semithin sections. Electron microscopic examination was also done. Histological examination of thyroid gland in amiodarone treated- rats [group II] revealed different light microscopic and ultrastructural changes. Some follicular cells showed signs of degeneration in the form of irregular dilation of the rough endoplasmic reticulum, vacuolation of the cytoplasm and increased number of lysosomes with irregular nuclei. These changes might be due to direct cytotoxic effect of the high iodine-containing amiodarone on the follicular cells. Other follicles showed signs of hyperactivity manifested by vacuolated colloid with scalloped appearance of its edges and papillary projections of the follicular cells with epithelial stratification. The manifestations of hyperactivity appeared to be compensatory to the direct effect of the drug. Alterations of thyroid function in group II, was further confirmed by results of hormonal assay, which revealed significant increase in serum levels of both TSH and T[3] with significant decrease in the level of T[3]. In group HI, after withdrawal of the drug, many follicles exhibited histological reversibility to almost normal pattern. Manifestations of sustained activity were still depicted in few follicles with focal areas of stratification and dilation of the rough endoplasmic reticulum. Hormonal assay showed that TSH and T[3] returned to nearly normal values while T[4] remained higher than the control level. From the present study, it could be concluded that prolonged amiodarone administration caused manifest histological and biochemical changes in the follicular cells of the thyroid gland. The obtained structural and hormonal changes were almost reversible after stoppage of the drug administration. Baseline and repeated levels of thyroid hormones should be monitored in every patient on amiodarone therapy