I-123 Uptake

Procedures

RAIU preparation begins with restricting the patient's iodine intake and discontinuing interfering medications to maximize I-123 uptake by thyroid tissue.[5] For RAIU alone, 3.7 MBq (100 µCi) of sodium iodide I-123 is administered orally. An uptake probe (2-inch diameter) equipped with a nonradioactive thallium-activated sodium iodide (NaI [Tl]) crystal (approximately 2 inches thick), a flat field collimator, a photomultiplier tube detector, and a multichannel analyzer is used to measure the 159 keV gamma peak. If rapid iodine turnover is suspected in hyperthyroidism, an additional RAIU measurement may be performed at 4 to 6 hours along with the routine 24-hour assessment.

The radioactive dose is initially placed in a Lucite neck phantom with the same geometry as the patient's neck and counted before administration. A second nearly identical standard dose, which is not administered to the patient, may also be used in the phantom for subsequent neck counts. The patient is positioned either sitting or supine with the neck extended, while the probe is maintained at a fixed distance of 20 to 30 cm. Additional counts are taken from the room background and the patient's mid-thigh, away from the urinary bladder, to assess background activity.

• If a second standard dose is not used, the decay-corrected 24-hour RAIU is calculated as follows:

RAIU (in %) = (24 h Neck−24 h Thigh) / ([Initial dose in phantom counts−Initial room background] × [I-123 decay correction factor for 24h]) x 100%

• If a second nearly identical standard dose is used, the 24-hour RAIU is calculated by incorporating the standard dose as follows:

RAIU (in %) = (24 h Neck−24 h Thigh) / (|Correction factor to adjust for the difference in activity between initial patient dose and initial standard dose| × [24 h standard in phantom−24 h room background]) x 100%

If an uptake probe is unavailable, a nuclear scintillation gamma camera with a low-energy parallel-hole collimator may be used, provided it has been validated against a reliable standard.[6][7] RAIU is measured both before and after perchlorate administration for the perchlorate discharge test in neonatal hypothyroidism.[8]

An oral dose of 7.4 to 14.8 MBq (200-400 µCi) of I-123 is administered for combined thyroid RAIU and imaging. RAIU is performed as described earlier, while thyroid imaging is conducted 24 hours after administration using a conventional or small-field gamma camera with a pinhole or parallel-hole collimator centered at 159 keV. Imaging is captured with the patient in a supine position with the neck extended.

Thyroid radioactive uptake can also be measured using intravenous technetium-99m (Tc-99m) pertechnetate. However, unlike iodine, Tc-99m pertechnetate is trapped but not organified, which may limit its ability to accurately reflect overall thyroid function. RAIU can also be assessed using I-131 sodium iodide, which, similar to I-123, undergoes both trapping and organification. I-131 has a half-life of 8 days and emits beta particles along with a primary 364 keV gamma photon, resulting in significantly higher ionizing radiation exposure for the patient. When available, RAIU with I-123 sodium iodide is preferred in the United States due to its lower radiation burden.[7][6] However, globally, Tc-99m pertechnetate is widely utilized due to its lower costs, lower radiation dose, and availability from a Mo-99/Tc-99m generator.

Indications

Hyperthyroidism is a common condition worldwide. In populations with adequate iodine intake, the etiology of hyperthyroidism is autoimmune hyperthyroidism, which accounts for approximately 80% of cases. In iodine-deficient populations, the most common cause is toxic multinodular goiter, which is a nonimmune condition.[9]

RAIU with I-123 measures overall thyroid function in hyperthyroidism and aids in differentiating among differential causes, including productive, destructive, and factitious thyrotoxicosis. This can also be used to calculate the appropriate dose for I-131 therapy, enabling pretreatment radiation dosimetry to be tailored to the specific needs of individual patients.[10] I-123 RAIU and scan may help evaluate thyroid nodules, particularly when TSH levels are subnormal or low. Although the value of I-123 RAIU in evaluating hypothyroidism is limited, it can be useful as part of the perchlorate discharge test to identify an iodine organification defect in neonatal hypothyroidism.[11][12][13][8]

Potential Diagnosis

The RAIU I-123 test can help diagnose normal, increased, or decreased thyroid metabolism.

Normal and Critical Findings

The normal reference range for RAIU can vary depending on laboratory technique and local geographic dietary iodine intake. Sample normal RAIU ranges might be 3% to 16% at 6 hours and 8% to 25% at 24 hours. Please see StatPearls' companion resource, "Thyroid Uptake and Scan," for more information.

Thyrotoxicosis is a clinical condition characterized by inappropriately elevated levels of circulating thyroid hormones. The etiology of thyrotoxicosis can be categorized into endogenous and exogenous sources of TSH. Increased endogenous TSH secretion may occur in various conditions, including Graves disease, toxic autonomous nodules, and toxic multinodular goiter. Increased exogenous thyroid hormone secretion can occur in cases of factitious hyperthyroidism or excessive levothyroxine (LT4) replacement therapy. Please see StatPearls' companion resource, "Thyrotoxicosis," for more information.

Thyroid scintigraphy provides a map of thyroid parenchyma, highlighting both hypo-functioning and autonomously functioning nodules.[14] Hyperfunctioning nodules, or those with increased radiotracer uptake, are rarely malignant; therefore, in many cases, cytologic evaluation is not required.[14]

Graves Disease

Graves disease classically presents as hyperthyroidism with a suppressed TSH. Graves disease is an autoimmune disease caused by an antibody targeted at the TSH receptor. This antibody mimics TSH and leads to excessive stimulation of the thyroid gland. The I-123 examination in Graves disease would demonstrate a diffusely enlarged thyroid gland with increased RAIU.[13] The pyramidal lobe, which is often not visualized, may be seen just superior to the isthmus due to the diffuse increased radiotracer uptake in the thyroid.

Occasionally, the 24-hour radiotracer uptake of the thyroid gland will be normal in a patient with Graves disease. This finding is due to the rapid turnover of TSH, which depletes the radiotracer that the thyroid gland has taken up. However, RAIU at 4 to 6 hours will typically show increased radiotracer uptake, which can aid in diagnosing Graves disease in cases with rapid iodine turnover.[15]

A variant of Graves disease, known as Marine-Lenhart syndrome, occurs when cold thyroid nodules are present alongside Graves disease.[15][16] This presentation can also be described as Graves disease with a multinodular goiter, where cold nodular areas appear within a thyroid gland that has overall increased radiotracer uptake. RAIU is elevated in both Graves disease and Marine-Lenhart syndrome.

Toxic Autonomous Nodule

A thyroid nodule may function independently of TSH, continually secreting thyroid hormone. This nodule will show increased radiotracer uptake, while the remaining thyroid tissue may exhibit normal or decreased radiotracer uptake, depending on the extent of secretion from the toxic autonomous nodule. These toxic nodules are typically histologically adenomas and often demonstrate mutated TSH receptors that are perpetually activated.[15] The toxic autonomous nodule is also known as Plummer disease. Overall, thyroid gland RAIU may be mildly decreased, normal, or mildly elevated in cases of a toxic autonomous nodule.[10]

Toxic Multinodular Goiter

Multinodular goiter is typically first identified through physical examination or ultrasound, revealing an enlarged thyroid with multiple nodules. These nodules can eventually progress to hyperplasia and possibly become autonomous. Patients often present with low or subnormal TSH levels. The radiotracer uptake is heterogeneous, with areas of increased uptake corresponding to hot nodules and areas of decreased uptake corresponding to cold nodules. The severity of thyrotoxicosis is generally milder compared to Graves disease. Overall, thyroid gland RAIU may be mildly decreased, normal, or mildly elevated in toxic multinodular goiter.[15][16]

Iodine-induced Hyperthyroidism

The body's natural defense against excess thyroid hormone production is the Wolff-Chaikoff effect, which inhibits the organification of thyroglobulin into T3 or T4. This effect regulates thyroid hormone production in response to excessive iodine intake. This effect can be triggered by iodine-containing medications (most commonly amiodarone), the administration of iodine-based contrast agents, or excessive dietary iodine intake, particularly in regions with iodine deficiency. Occasionally, the thyroid may develop autonomous nodules that bypass the Wolff-Chaikoff effect, leading to hyperthyroidism in the setting of iodine repletion. This effect, known as the Jod-Basedow effect, is more commonly observed in areas with iodine deficiency. I-123 scans usually demonstrate uniformly low radiotracer uptake, with a corresponding decrease in RAIU.[15]

Subacute Thyroiditis

Subacute thyroiditis, also known as giant cell thyroiditis or "de Quervain thyroiditis," is typically characterized by thyrotoxicosis accompanied by neck pain and fever, often following a viral upper respiratory infection. The post-infectious inflammatory response triggers giant cell invasion of the thyroid tissue, causing disruption and leakage of thyroid hormone. As a result, RAIU is diminished because thyroid hormone is no longer concentrated within the thyroid tissue. Clinically, patients usually present with a suppressed TSH.[16]

Silent Thyroiditis

Silent thyroiditis, an autoimmune condition, is characterized by lymphocytic infiltration of the thyroid gland, leading to disruption of the gland and the subsequent release of thyroid hormone. Thyroid peroxidase levels are typically elevated in silent thyroiditis. Unlike subacute thyroiditis, silent thyroiditis is painless. Silent thyroiditis can also occur postpartum, with symptoms typically appearing 2 to 6 months after delivery and usually being self-limiting, lasting 2 to 6 weeks. The elevated thyroid hormone levels lead to a low TSH. The thyroid gland shows reduced RAIU, similar to subacute thyroiditis.[16][17][15]

Hashimoto Thyroiditis

Hashimoto thyroiditis is an autoimmune disease characterized by lymphocytic infiltration of the thyroid tissue and autoimmunity to thyroid antigens. Common antibodies involved include antithyroglobulin (present in 55%-90% of cases) and antibodies to thyroid peroxidase (present in 90%-95% of cases). The infiltration by lymphocytes and plasma cells eventually causes the destruction of thyroid follicles, followed by fibrosis. As fibrosis progresses, the thyroid gland enlarges. As the disease progresses, more thyroid tissue is replaced with fibrosis, leading to depressed thyroid hormone production and a hypothyroid state.

Radiotracer uptake varies depending on the phase of the disease. In the early stages, thyroid hormones are released due to the destruction of thyroid follicles, resulting in increased RAIU. As the disease progresses, the body eventually becomes hypothyroid, with consistent scintigraphy findings of decreased RAIU and an elevated TSH. The decreased radiotracer uptake is nonuniform, as areas of fibrosis do not take up radiotracer.[17]

Thyrotoxicosis of Extrathyroidal Origin

Extrathyroidal sources of thyroid hormone include exogenous thyroid hormone ingestion, as seen in factitious hyperthyroidism, as well as thyroid hormone–producing metastatic thyroid cancer and struma ovarii—a teratomatous ovarian mass containing functional thyroid tissue. Another extrathyroidal cause of thyrotoxicosis is TSH-induced thyrotoxicosis, which results from an autonomous TSH-secreting pituitary adenoma, and it is the only extrathyroidal cause linked to an elevated RAIU. Clinically, patients may present with varying levels of thyrotoxicosis, depending on the amount of thyroid hormone released by the exogenous source. Factitious hyperthyroidism can often be challenging to diagnose, as patients often do not disclose exogenous thyroid hormone ingestion. In most cases, the ingested hormone is T4, which leads to a higher-than-normal T4 to T3 ratio.

Thyroid hormone production from metastatic thyroid malignancy is uncommon, as it requires a well-differentiated metastatic tumor, which is typically less efficient at producing and secreting thyroid hormone. These metastases are usually detected in the setting of known thyroid cancer on I-131 imaging. Similar to metastatic thyroid malignancy, struma ovarii does not efficiently secrete thyroid hormone and rarely produces clinically significant amounts. Struma ovarii is often an incidental finding when pathological evaluation of an ovarian mass reveals thyroid tissue. While overall thyroid gland RAIU in the neck is decreased, the lesion itself may demonstrate elevated RAIU.[15]

Neonatal Hypothyroidism

An iodine organification defect is identified as the cause of neonatal hypothyroidism if RAIU is reduced by at least 10% following the administration of sodium perchlorate.[8]

Interfering Factors

Iodine intake should be limited before an I-123 RAIU or RAIU uptake and scan. If a patient is exposed to too much iodine before the scanning, it can reduce the thyroid gland's ability to absorb iodine, which lowers the sensitivity of the RAIU and scan. Potential sources of excess iodine include thyroid-related medications, such as antithyroid drugs, and various iodinated substances like amiodarone and intravenous contrast agents. An iodine-rich diet, including foods like kelp and seaweed, can also decrease the sensitivity of the RAIU and scan.[2][10]

Intravenous contrast agents should be avoided for 2 to 4 weeks before an I-123 uptake scan.[10] Notably, iodinated contrast material reduces radiotracer uptake by decreasing the number of NIS, independent of its free iodine content.[5] Amiodarone should be discontinued for 3 to 6 months before an I-123 RAIU or uptake scan.[2][10] Kelp and seaweed consumption should also be avoided for 2 to 4 weeks before the scan.[10] Additional medications that should be held include antithyroid drugs such as methimazole, carbimazole, and propylthiouracil, as well as thyroid hormone replacements such as levothyroxine (LT4) and liothyronine (LT3).

Complications

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]

Patient Safety and Education

Patient Safety

I-123 is relatively safe as a gamma emitter, except for pregnant patients and nursing mothers. The estimated effective dose equivalent for a 3.7 MBq (100 µCi) I-123 RAIU is 0.74 mSv (74 mrem).[2][18][19] The dosing of I-123 in children should be adjusted based on patient weight, ensuring it is as low as reasonably achievable while maintaining test accuracy.

Patient Education

I-123 is a radioisotope of iodine used in thyroid uptake scans to assess thyroid function. By measuring radiotracer uptake, the RAIU study evaluates overall thyroid activity. When combined with clinical symptoms, blood tests, and other imaging modalities such as ultrasound, I-123 RAIU, or a combined RAIU and thyroid scan, provides a comprehensive assessment of thyroid pathology, aiding in diagnosis.

Clinical Significance

RAIU with I-123 scintigraphy is a valuable test that provides functional information about the thyroid gland, including its activity. In combination with laboratory findings such as thyroid hormone and TSH levels, physical examination, and other imaging tests, I-123 RAIU can assist in diagnosing the causes of thyrotoxicosis, calculating I-131 therapy doses, and detecting iodine organification defects in neonatal hypothyroidism.