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The radioactive iodine uptake (RAIU) test measures the overall metabolism and kinetics of iodine in the thyroid gland by quantifying how much orally ingested iodide is concentrated in the thyroid gland. Iodine-123 (I-123) is the most commonly used radioisotope for RAIU testing. Iodine is essential for metabolism, as it is required for the intrathyroidal synthesis of triiodothyronine (T3) and thyroxine (T4). Dietary iodide (I−), the ionized form of iodine, is rapidly absorbed into the plasma through the gastrointestinal tract. Dietary iodide then enters the follicular cells of the thyroid gland via the sodium-iodide symporter (NIS). NIS utilizes a gradient generated by sodium-potassium ATPase for cotransport. NIS is predominantly located in the basolateral membrane of the thyroid follicular cells, where it can increase the concentration of the iodide in the thyroid gland up to 40 times the plasma level.[1] NIS is one factor that affects the concentration of iodine within the thyroid gland, and its expression is regulated by thyroid-stimulating hormone (TSH).[2] Once in the thyroid gland, iodide undergoes organification into thyroglobulin, where it is used to produce T3 and T4.[2][3] I-123, a radioisotope of iodine, is often used for RAIU and nuclear medicine thyroid imaging, also known as a thyroid scan. I-123 is an ideal radiopharmaceutical due to its low radiation burden and optimal imaging quality compared to I-131 sodium iodide (NaI).[3] I-123 is produced in a cyclotron by bombarding xenon-124 (Xe-124) or tellurium-123 (Te-123) with protons. I-123 emits gamma radiation at 159 keV and has a half-life of 13 hours, decaying by electron capture to form Te-123.[4] I-123 sodium iodide is administered orally as a pill or liquid. The iodide is rapidly absorbed in the upper gastrointestinal tract. The radioisotope begins concentrating in the thyroid gland within 20 to 30 minutes. RAIU with I-123 is typically measured 24 hours after administration to minimize background activity, with an additional uptake measurement sometimes taken at 4 to 6 hours.

Severe complications are not associated with the I-123 examination, aside from the factors that may decrease the sensitivity of the I-123 uptake scan or the contraindications related to radiation exposure through the placenta during pregnancy or breastfeeding. As iodide freely crosses the placenta and is concentrated and excreted in breast milk, I-123 administration is relatively contraindicated in pregnant patients and nursing mothers. Additionally, for the radiotracer to be effectively administered and absorbed, the patient must be able to tolerate oral ingestion of the I-123 capsule or liquid. Routine nuclear medicine quality control of the uptake probe should be performed and documented to prevent errors, including assessments of sensitivity, energy spectrum, constancy, background, peaking, energy resolution, efficiency, and minimum detectable activity. Other potential error sources include incorrect positioning of the patient or phantom, incorrect patient background measurement (which should be mid-thigh rather than near the urinary bladder), substernal thyroid gland, phantom contamination, dose malabsorption, high background activity, recent iodinated contrast exposure, and residual radioactivity from another radiopharmaceutical. Renal failure can elevate RAIU, while conditions such as euthyroid sick syndrome can reduce it.[2][6][7]