Radioiodine, (I-131) first discovered in 1938, is a nuclear fission by-product of uranium. In the early 1940’s, radioiodine was used to study thyroid physiology, and by the late 1940’s, it was used to treat hyperthyroidism and thyroid cancer, so, remarkably, I-131 has been used clinically for the past 70 years. Iodine is actively transported and incorporated into thyroglobulin, a precursor to thyroid hormone, thus trapping the iodine in the gland. With the exception of the salivary glands, very little iodine is absorbed elsewhere in the body, and unincorporated iodine is quickly excreted in the urine, with much smaller amounts excreted in stool, saliva, and perspiration. Two radioisotopes of iodine are used clinically: I-131 (half-life 8.02 days) which used mostly for therapy, and I-123 (half-life 13 hours), which is a very low-energy gamma-emitter useful for diagnostic and imaging studies.
A radioiodine uptake (RAIU) measurement determines how much iodine the thyroid gland absorbs over a several hour period. It is useful to determine the underlying cause of thyroid dysfunction, and can be used to guide therapeutic management decisions based on the result. The procedure is straightforward: the patient ingests a known amount of radioiodine and then returns 24 hours later to have their neck measured with a device similar to a Geiger counter; the amount of radiation in the thyroid is then divided by the known starting amount of radioiodine, giving the % uptake. A normal adult thyroid RAIU is between 10-30% at 24 hrs. Patients with Graves’ disease often have a markedly elevated RAIU, wherease patients with thyroiditis typically have extremely low RAIU measurements (due to lack of iodine uptake in injured thyroid tissue). RAIU can be influenced by dietary iodine intake (e.g. vitamins, fish oil capsules, iodinated CT contrast dye), and anti-thyroid medications, so it is necessary to perform RAIU measurements several days (sometimes weeks) after these factors are discontinued or avoided. RAIU measurements are inexpensive and can be performed in the office setting.
A radioiodine thyroid scan generates an image of the iodine that is actively trapped in the thyroid, revealing areas of increased or decreased absorption. In the past, thyroid scans were sometimes performed to determine whether a thyroid nodule was “hot” a nodule that absorbed a lot of radioiodine) or “cold” (a nodule that did not absorb any radioiodine). Nearly all hot nodules are benign, but “cold” nodules carry ~20% risk of malignancy, and should be further evaluated. The advent of ultrasound and fine needle aspiration (FNA) biopsy has obviated the need for some thyroid scans, except in the diagnosis of toxic multinodular goiter or toxic adenoma. Another type of imaging study is a “whole body scan” which is obtained before or after I-131 therapy in patients who have undergone total thyroidectomy for thyroid cancer. Other nuclear medicine scans also employ I-131 in imaging other tissues (e.g. MIBG; iodine-131-meta-iodobenzylguanidine, an agent that is concentrated into adrenal medullary [chromaffin] tissue, to identify pheochromocytomas).
Radioiodine has been extensively studied under a variety of different thyroid disease, situations, doses, and ages, studies that extend back to the 1950’s. For “low” doses of radioiodine used to treat hyperthyroidism (e.g. 10-30 mCi), the risk of malignancies appears negligible in most studies and meta-analyses. However, there is heightened concern about the routine use of radioiodine in pre-adolescents, so caution is advised with radioiodine use in the pediatric population, and never used in pregnancy. I-131 therapy is usually outpatient, and recipients are instructed to follow some basic hygiene and safety precautions for varying lengths of time following therapy. The side effects of low-dose radioiodine are minimal: some patients experience minor thyroid pain which usually responds to analgesics. Rates of post-procedural hypothyroidism vary in terms of their onset, depending on the dose of radioiodine given and the underlying cause of hyperthyroidism: the majority of patients with Graves’ disease develop hypothyroidism within several months, whereas a smaller percentage of patients with toxic multinodular or toxic adenomas develop hypothyroidism (10-25%), over a longer period of time. Once the hypothyroidism develops, it usually requires life-long thyroid hormone replacement therapy.
Higher doses of radioiodine (30-200 mCi) are often used to treat high-risk papillary or follicular thyroid cancer; there is no evidence that radioiodine treatment will decrease the risk of recurrence or improve longevity in low-risk patients. Radioiodine therapy is administered to outpatients when TSH (thyroid stimulating hormone) levels are elevated (either using recombinant human TSH or thyroid hormone withdrawal). In the past decade, there has been a remarkable reduction in the doses of radioiodine used to treat thyroid cancer, with fewer side effects, but no apparent outcome differences. There are more side effects with higher doses of radioiodine therapy, including nausea, vomiting. and sialoadenitis (swelling of the salivary glands) which can lead to pain and dry mouth (xerostomia), as well as alterations in test sensation, and excessive tearing (epiphora). At high doses of radioiodine, there is an increased risk of secondary malignancies, including salivary gland, stomach, bladder, and hematologic malignancies, though these are very uncommon.
References: Sisson, J.C., et al Radiation Safety in the Treatment of Patients with Thyroid Diseases by Radioiodine 131I: Practice Recommendations of the American Thyroid Association. Thyroid 21(4):335-346, 2011