Amiodarone is an antiarrhythmic drug used for arrhythmias. It delivers about 30-100 times the normal daily physiological requirement of iodine, and that matters because the thyroid handles iodine as the raw material of its hormone. Amiodarone also builds up in the thyroid and other tissues, so the load is large and does not clear at once.
A gland that is handed this much iodine can go wrong in two opposite ways. A different problem sits beside them: sometimes the excess hormone does not come from the gland at all.
Iodine as a trigger
The iodine load from amiodarone can disturb thyroid function in two opposite directions. Amiodarone-induced thyroid dysfunction therefore has two major forms, and one of them is an iodine-induced hyperthyroidism.
To see how iodine can push the gland either way, start with where it acts. A large amount of iodine reaching the gland inhibits organification. Organification is the attachment of iodine to thyroglobulin, the protein in which hormone is made, by thyroid peroxidase.
The gland shuts down, then escapes
This block has a name. The Wolff-Chaikoff effect is the temporary shutdown of hormone production when the gland is flooded with iodine. Amiodarone-induced hypothyroidism comes from this effect.
Why would a gland switch itself off? The shutdown is an acute response to high iodine, and the gland does it to prevent thyrotoxicosis. Because hormone synthesis falls, the shutdown protects the body from a surge of hormone.
The shutdown is meant to be short. Normally the gland escapes this block after a few days and resumes work. The escape comes with a fall in the iodide pump, so the gland takes up less iodide and output returns.
When escape fails
In amiodarone-induced hypothyroidism the escape fails and the block persists, so hormone production stays shut down.
Who is most at risk? Patients whose gland has already lost follicular tissue to a thyroiditis such as Hashimoto thyroiditis have less reserve. Earlier thyroid disease makes this hypothyroidism more likely, so these patients are more likely to develop amiodarone-induced hypothyroidism. They usually remain permanently hypothyroid.
Iodine-poor glands and amiodarone
Amiodarone-induced hyperthyroidism occurs in the opposite setting: populations with a low iodine supply.
The reason lies in what a low iodine supply does to the gland, which the note on severity and iodine explains. In these populations the gland forms goiter and sometimes autonomous nodules. Autonomous nodules produce hormone in the absence of TSH. When amiodarone delivers its iodine load to such a gland, that tissue overproduces hormone.
This gives hyperthyroidism rather than hypothyroidism. So the same iodine load can leave one gland underactive and another overactive. Both amiodarone effects arise from iodine acting on the gland.
Factitious thyrotoxicosis
Factitious thyrotoxicosis is different: the excess hormone does not come from the gland at all.
Some people take levothyroxine to lose weight. Levothyroxine does promote weight loss, but it is not indicated for weight loss, and it is often obtained without a prescription. Excess levothyroxine produces hyperthyroidism and even thyrotoxicosis. The effect of excess hormone on the tissues is the one described in the note on severity and iodine.
The low-thyroglobulin pattern
Thyrotoxicosis is characterised by a low level of TSH. A low TSH with thyrotoxicosis has a broad differential, from Graves disease to adenomatous nodules of the thyroid gland. So how is the factitious cause picked out?
The pattern that identifies factitious thyrotoxicosis is a very low level of thyroglobulin together with a normal thyroid gland on ultrasound and on scintigraphy. Low thyroglobulin is the clue because the hormone comes from the tablet, so the gland’s own synthesis and thyroglobulin production are suppressed.
This pattern is seen in patients who are often suffering from psychiatric conditions and who deny using levothyroxine.