Source – http://emedicine.medscape.com/article/129033-overview#a5
Amiodarone causes a wide spectrum of effects on the thyroid.
- Amiodarone inhibits type 1 5′-deiodinase enzyme activity, thereby decreasing the peripheral conversion of T4 to triiodothyronine (T3) and reducing the clearance of both T4 and reverse T3 (rT3). Consequently, the serum levels of T4 and rT3 increase and the serum levels of T3 decrease by 20-25%.
- Amiodarone inhibits entry of T4 and T3 into the peripheral tissue. Serum T4 levels increase by an average of 40% above pretreatment levels after 1-4 months of treatment with amiodarone. This, in itself, does not constitute evidence of hyperthyroidism (thyrotoxicosis).
- Inhibition of type 2 5′-deiodinase enzyme activity in the pituitary due to feedback regulation is seen in the first 1-3 months and leads to an increase in thyroid-stimulating hormone (TSH) levels. This is not an indication for T4 replacement in these patients. Serum TSH levels return to normal in 2-3 months as T4 concentrations rise sufficiently to overcome the partial block in T3 production. The response of TSH to thyroid-releasing hormone (TRH) may be reduced.
- Amiodarone and its metabolites may have a direct cytotoxic effect on the thyroid follicular cells, which causes a destructive thyroiditis.
- Amiodarone and its metabolite desethylamiodarone can act as a competitive antagonist of T3 at the cardiac cellular level.
In summary, serum T4 levels rise by 20-40% during the first month of therapy and then gradually fall toward high normal. Serum T3 levels decrease by up to 30% within the first few weeks of therapy and remain slightly decreased or low normal. Serum rT3 levels increase by 20% soon afterward and remain increased. Serum thyrotropin (TSH) levels usually rise after the start of therapy but return to normal in 2-3 months.
Two forms of AIT have been described. Type 1 usually affects patients with latent or preexisting thyroid disorders and is more common in areas of low iodine intake. Type 1 is caused by iodine-induced excess thyroid hormone synthesis and release (Jod-Basedow phenomenon). Type 2 occurs in patients with a previously normal thyroid gland and is caused by a destructive thyroiditis that leads to the release of preformed thyroid hormones from the damaged thyroid follicular cells. However, mixed forms of AIT may occur in an abnormal thyroid gland, with features of destructive processes and iodine excess.
The most likely mechanisms of AIH are an enhanced susceptibility to the inhibitory effect of iodine on thyroid hormone synthesis and the inability of the thyroid gland to escape from the Wolff-Chaikoff effect after an iodine load in patients with preexisting Hashimoto thyroiditis. In addition, iodine-induced damage to the thyroid follicles may accelerate the natural trend of Hashimoto thyroiditis toward hypothyroidism. Patients without underlying thyroid abnormalities are postulated to have subtle defects in iodine organification that lead to decreased thyroid hormone synthesis, peripheral down regulation of thyroid hormone receptors, and subsequent hypothyroidism.
The Wolff–Chaikoff effect is an autoregulatory phenomenon that inhibits organification in the thyroid gland, the formation of thyroid hormones inside the thyroid follicle, and the release of thyroid hormones into the bloodstream. This becomes evident secondary to elevated levels of circulating iodide. The Wolff–Chaikoff effect is an effective means of rejecting a large quantity of imbibed iodide, and therefore preventing the thyroid from synthesizing large quantities of thyroid hormone. Excess iodide transiently inhibits thyroid iodide organification.
In individuals with a normal thyroid, the gland eventually escapes from this inhibitory effect and iodide organification resumes; however, in patients with underlying autoimmune thyroid disease, the suppressive action of high iodide may persist.
The Wolff–Chaikoff effect lasts several days (around 10 days), after which it is followed by an “escape phenomenon,” which is described by resumption of normal organification of iodine and normal thyroid peroxidase function. “Escape phenomenon” is believed to occur because of decreased inorganic iodine concentration secondary to down-regulation of sodium-iodide symporter (NIS) on the basolateral membrane of the thyroid follicular cell.
The Wolff–Chaikoff effect can be used as a treatment principle against hyperthyroidism (especially thyroid storm) by infusion of a large amount of iodine to suppress the thyroid gland. Iodide was used to treat hyperthyroidism before antithyroid drugs such as propylthiouracil and methimazole were developed. Hyperthyroid subjects given iodide may experience a decrease in basal metabolic rate that is comparable to that seen after thyroidectomy.
The Jod-Basedow effect is hyperthyroidism following administration of iodine or iodide, either as a dietary supplement or as contrast medium.
This phenomenon is thus iodine-induced hyperthyroidism, typically presenting in a patient with endemic goiter (due to iodine deficiency), who relocate to an iodine-abundant geographical area. People who have Graves disease, toxic multinodular goiter, or various types of thyroid adenoma are also at risk of Jod-Basedow effect when they ingest extra iodine. The Jod-Basedow effect also been seen as a side effect of administration of the iodine-containing contrast agents, or amiodarone, an antiarrhythmic drug.
The Jod-Basedow effect does not occur in persons with normal thyroid glands who ingest extra iodine in any form.
The Jod-Basedow effect typically occurs with comparatively small increases in iodine intake, in people who have thyroid abnormalities that cause the gland to function without the control of the pituitary (i.e., a thyroid gland that is not normally suppressed by thyroid hormone driven loss of TSH secretion from the pituitary). In some ways the Jod-Basedow phenomenon is the opposite of the Wolff-Chaikoff effect.
However, (unlike the Wolff-Chaikoff effect), the Jod-Basedow effect does not occur in persons with normal thyroid glands, as thyroid hormone synthesis and release in normal persons is controlled by pituitary TSH secretion, (which does not allow hyperthyroidism when extra iodine is ingested).