Amiodarone thyroid gland

The Class III effects of amiodarone develop over several weeks. This time-course is similar to that seen in thyroid gland ablation [25]. It is well known that patients with hypothyroidism have long QT intervals which are indicative of prolonged action potentials. Amiodarone has been shown to inhibit the conversion of thyroxine (T4) to triiodothyronine (T3) both in human subjects [26] and in vitro [27]. It has been argued that the Class III effects of amiodarone are due to its effects on thyroid hormones [28]. Others, however, argue that there is no relationship between prolongation of ventricular refractory period by amiodarone and thyroid state [29]. 

Clinical use of amiodarone is limited because of its high toxicity, which consists of cardiac block, bradycardia, cardiac insufficiency, damaged thyroid gland function, neuropathology, and increased sensitivity to light, all of which significantly limit use of amiodarona, and it is only used in therapy for extremely serious tachyarrhythmias such as reoccurring ventricular fibrillation and hemodynamic unstable ventricular tachycardia, and only under supervision of a physician in a clinical situation. Synonyms of amiodarone are cordarone, rythmarone, and others. 

Chronic oral therapy with amiodarone is associated with several side effects, including pulmonary toxicity (fibrosis and probably immunologically mediated pneumonitis), hepatotoxicity, thyroid gland dysfunction, corneal microdeposits, blue-grey skin discoloration and neurological disturbances. 

Jonckheer MH. Amiodarone and the thyroid gland. A review. Acta Cardiol 1981 36(3) 199-205. 

Despite the fact that she was clinically euthyroid, the authors suggested that this patient had amiodarone-induced hyperthyroidism. However, amiodarone inhibits the peripheral conversion of thyroxine to triiodothyronine it can therefore increase the serum thyroxine and suppress the serum TSH, as in this case. On the other hand, the reduced uptake by the thyroid gland is consistent with type 2 amiodarone-induced hyperthyroidism. The authors did not report the serum concentrations of free thyroxine and triiodothyronine. 

Cholestyramine, calcium carbonate, sucralfate, aluminum hydroxide, ferrous sulfate, soybean formula, and dietary fiber supplements may impair the absorption of levothyroxine from the G1 tract. Drugs that increase nondeiodinative T4 clearance include rifampin, carbamazepine, and possibly phenytoin. Amiodarone may block the conversion of T4 to T3. Thyroid, USP (or desiccated thyroid) is derived from hog, beef, or sheep thyroid gland. It may he antigenic in allergic or sensitive patients. Inexpensive generic brands may not be bioequivalent. 

The effects of amiodarone on thyroid function tests and in causing thyroid disease, both hyperthyroidism and hypothyroidism, have been reviewed in the context of the use of perchlorate, which acts by inhibiting iodine uptake by the thyroid gland (125), and there have been several other reviews (126-130). 

Broussolle C, Ducottet X, Martin C, Barbier Y, Bornet H, Noel G, Orgiazzi J. Rapid effectiveness of prednisone and thionamides combined therapy in severe amiodarone iodine-induced thyrotoxicosis. Comparison of two groups of patients with apparently normal thyroid glands. J Endocrinol Invest 1989 12(1) 37 2. 

Amiodarone is mostly given in a daily dose of 200 mg. This dose contains about 7 mg iodine which amounts to 35-times the daily recommended dietary iodine supply. A healthy thyroid gland compensates this overdose of iodine (Wolff—Chaikoff effect). However, patients with (subclinical) thyroid autonomy (in a euthyroid goiter in an iodine-deficient region) or subclinical thyroid autoimmune disease are very susceptible to IIH because this autoregula-tory mechanism is disturbed. 

Amiodarone induces specific ultrastructural changes of the thyroid gland in rats, including marked distortion... 

Endocrine In patients receiving the minimum dose of amiodarone, thyroid abnormalities were observed at a rate between 14% and 18%. The effects on the thyroid gland are variable. Amiodarone may cause abnormal thyroid function detected only by laboratory test as well as clinically manifested thyroid dysfunction. The mechanism of this adverse effect is complex. Amiodarone inhibits the action of deiodinase and decreases peripheral conversion of thyroid hormones. Moreover, it decreases their renal elimination and inhibits their entry to peripheral tissues. The level of T4 increases by 40% within 1-4 months of amiodarone therapy. The deiodinase activity inhibition can be noticed after 3 months of treatment. It leads to an increase in the level of thyroid stimulating hormones. Amiodarone and its metabolite have a direct cytotoxic effect on thyroid follicular cells, which results in destructive thyroiditis. Amiodarone-induced thyroid damage can lead either to hypo- or hyperthyroidism. The latter can be of two types. Type 1 usually occurs in patients with prior thyroid damage. In this type, iodine excess causes excessive synthesis of thyroid hormones whereas in type 2 the inflammatory process is followed by destruction. A destructive thyroiditis leads to the release of hormones from damaged thyroid follicular cells. This mechanism occurs in patients with no history of thyroid disorders [15]. 

Jonckheer M.H. 1981. Amiodarone and the Thyroid Gland. A Review. Acta Cardiol. 36 199-205. 

Amiodarone causes two different varieties of hyperthyroidism (SEDA-23, 199), one by the effects of excess iodine in those with latent disease (so-called type 1 hyperthyroidism), the other through a destructive thyroiditis in a previously normal gland (so-called type 2 hyperthyroidism). The two varieties can be distinguished... 

Figure 72.4 Typical thyroid pertechnetate nuclear uptake in type II amiodarone-induced TTX. Typically, there is no uptake due to the acute inflammatory process, which discharges all the THs, resulting in an absent uptake. The white arrows point to the salivary glands for comparison of uptake.

Withdrawal of amiodarone is more often considered unnecessary by North American thyroidologists in type 1 amiodarone-induced thyrotoxicosis (which occurs in patients with latent disease, due to the iodine contained in amiodarone) than in type 2 amiodarone-induced thyrotoxicosis (which is due to destructive thyroiditis in a previously normal gland) 21% versus 10% in Europe in type 1 34% versus 20% in type 2. In type 1 thyrotoxicosis thionamides represent the treatment of choice in North America and Europe, but as monotherapy in 65% compared with 51% European thyroidologists more often consider potassium perchlorate as a useful addition (31% versus 15%). Glucocorticoids are the selected treatment for type 2 thyrotoxicosis, either alone (62% V5. 46% in Europe) or in association with thionamides (16% versus 25%). After restoration of euthyroidism, thyroid ablation in the absence of recurrent thyrotoxicosis is recommended in type 1 less often in North America. If amiodarone needs to be restarted, prophylactic thyroid ablation is advised by 76% in type 1 thyrotoxicosis, while a wait-and-see strategy is adopted by 61% in type 2, as in Europe. This survey shows differences in therapeutic attitudes, which reflect the frequent uncertainty of the underlying mechanism that leads to amiodarone-induced thyrotoxicosis. 

Amiodarone, an anti-arythmic drug containing 37.2 % of organic iodine, may induce hypothyroidism and hyperthyroidism. Dysthyroidism can occur during treatment, but also many months after its discontinuation in patients with underlying thyroid disorders, as well as in subjects with apparently normal glands. We report the case of a patient who developed hypothyroidism followed by hyperthyroidism, related to amiodarone therapy. 

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