Introduction

An iodine-131 (I-131) scan is a noninvasive radionuclide imaging procedure used to visualize the functionality of thyroid tissue, detect metastatic thyroid cancer, and assess the remaining thyroid tissue after thyroidectomy. The thyroid gland plays a vital role in producing essential thyroid hormones necessary for survival and regulating energy metabolism. The ingested iodine, critical for thyroid hormone production, is selectively absorbed by thyroid follicular cells and facilitated by sodium iodide symporters (NIS).[1] 

Thyroid-stimulating hormone (TSH) controls the function of the NIS, allowing the body to absorb the circulating iodine in the form of iodide salt. When iodide enters follicular cells, it undergoes oxidation by the thyroid peroxidase enzyme to convert iodide into iodine. Organification is the subsequent biochemical reaction that integrates iodine into thyroglobulin, thereby synthesizing the thyroid hormones thyroxine (T4) and triiodothyronine (T3).

Iodine molecules can be labeled with radiotracers and utilized for both diagnostic and therapeutic applications in diverse thyroid conditions, including Graves disease, toxic multinodular goiter, and thyroid cancer. The 2 most frequently used radiotracers for thyroid tissue scans are I-123 and I-131.

The primary differences between the 2 radiotracers are:

• I-123 has a half-life of approximately 13 hours, decays by gamma emission, and delivers superior image quality. I-123 is expensive and less readily available, and it is primarily used for imaging of the thyroid gland in cases of benign thyroid disease, such as thyroid nodules and multinodular goiter. Although I-123 can be used for imaging and monitoring thyroid cancer, its reduced sensitivity in detecting pulmonary metastases, cost considerations, and limited availability make I-131 the preferred choice.[2]

• I-131 has a half-life of approximately 8.2 days, decays through beta emission, and is more cost-effective and widely accessible.[2] 1-131 is primarily utilized for imaging in cases of thyroid cancer.

I-131 is utilized to treat differentiated thyroid cancer after thyroidectomy, toxic adenoma, toxic multinodular goiter, and Graves disease. The ingestion of radioiodine induces thyroid cell death through the emission of beta particles. The use of I-131 in both the treatment and diagnosis of thyroid cancer exemplifies theranostics, which is a concept that integrates diagnostic imaging and therapeutic intervention for a particular condition by using the same radiolabeled molecule, either in a modified form or with varying radiolabeled agent doses.[2][3] 

A whole-body pre-radioiodine assessment, post-radioiodine treatment evaluation, and ongoing surveillance for thyroid cancer are all valid applications for an I-131 scan. Pre-radioiodine treatment scans are conducted less frequently. After a thyroidectomy, most patients usually retain some remnant thyroid tissue in their bodies. They may then be given a therapeutic dose of I-131 and undergo a post-radioiodine scan. Pretreatment I-131 scans should be considered when surgical procedures and neck ultrasonography fail to assess the extent of residual disease clearly. In addition, the scans may be warranted when residual disease may influence the decision regarding the dose or necessity of radioiodine treatment.

Procedures

Preparation

Pregnancy and breastfeeding are contraindications, as a developing fetus can start absorbing radioactive iodine at approximately 10 weeks of gestation. Patients are advised to follow a low-iodine diet for approximately 7 to 14 days before the procedure. This dietary regimen excludes iodized salt, dairy products, egg yolks, and seafood while emphasizing the consumption of fresh vegetables, fruits, meats, and noniodized or kosher salt. The dietary restrictions are intended to improve the efficacy of I-131 therapy and the accuracy of pre- and post-therapy scans using I-131. Nevertheless, a recent comparative study did not reveal any significant difference in the response to radioactive iodine therapy for Graves disease between patients who adhered to a low-iodine diet and those who did not.[2]

Patients undergoing treatment with antithyroid medications for hyperthyroidism are advised to discontinue these medications for 5 to 7 days to enhance iodine uptake. However, in severe hyperthyroidism, where discontinuing the medications could be detrimental, the discontinuation period may be reduced to 3 days.

Elevating TSH levels enhances iodine uptake and optimizes imaging. The optimal TSH level for the test or potential treatment is 30 mIU/L or higher.[2] 

There are 2 ways to achieve elevated TSH levels, as mentioned below.

1. Withdrawal of thyroid hormone: Thyroid hormone withdrawal is recommended for patients with advanced and high-risk thyroid cancer. Patients who have undergone total or near-total thyroidectomy should discontinue thyroid replacement therapy for a period of 4 to 6 weeks before the procedure to induce pituitary TSH secretion. This recommendation is relevant for patients receiving thyroid hormones either as replacement therapy or suppressive doses. Due to its shorter half-life, reducing the discontinuation period to 2 weeks when using triiodothyronine may be feasible.[2]
2. Preparation with thyrotropin alfa: Thyrotropin alfa, a recombinant TSH (rhTSH) molecule, increases TSH levels without discontinuing thyroid hormone replacement, thus preventing hypothyroidism symptoms.[2] The dosing regimen involves 2 subcutaneous injections of 0.9 mg each, administered to patients 24 hours apart. The American Thyroid Association (ATA) approves this method for remnant ablation after total thyroidectomy in patients with differentiated thyroid cancer who do not exhibit distant metastasis.[2] 

Procedures

In a pre-ablation or surveillance I-131 scan, patients ingest a small dose of radioactive iodine in the form of capsules or liquid, and the scan is typically performed 24 to 72 hours later. Patients undergo post-therapy I-131 scans 3 to 7 days after an I-131 ablation or adjuvant therapy dose.

The imaging procedure for I-131 involves specific patient preparations and positioning to ensure accurate results, as mentioned below. 

• The patient must fast or abstain from eating for at least 4 hours before and up to 1 hour after taking the iodine dose.

• The patient must recline in a supine position on a movable examination table to conduct this procedure. Before each series of images, they are instructed to consume a substantial amount of water to eliminate any potential physiological activity in the pharynx or esophagus.

• A high-energy collimator γ-camera equipped with I-131 sodium iodide is used to capture both anterior and posterior planar images, as well as spot images of the nasopharynx, thyroid bed, or chest.

• A medium-energy collimator can be chosen instead of a low-energy collimator while using I-123, as it can improve image quality. The scanning procedure is typically conducted at the 18- to 24-hour intervals.

• A single-photon emission computed tomography (SPECT) scan can examine the area from the skull base to the diaphragm and focus on any specific concerns found during the whole-body I-131 scan. This enhances the ability to detect both regional and distant metastasis.

• Serum thyroglobulin and anti-thyroglobulin antibody assays are obtained simultaneously.[4]

Indications

An I-131 scan serves as a valuable diagnostic tool for examining various thyroid disorders, with primary applications including:

• Distinguishing hyperthyroidism from other types of thyrotoxicosis, although I-123 is more frequently utilized.
• Visualizing ectopic thyroid tissue.
• Visualizing remnants of normal or cancerous thyroid tissue and detecting thyroid cancer recurrence or distant metastasis.
• Restaging thyroid cancer typically occurs 6 to 12 months after thyroidectomy and radioactive iodine ablation therapy.
• Assisting in the calculation of the appropriate I-131 therapy dosage. 
• Determining the safest dosage of I-131 therapy for vital organs, particularly in cases where patients have undergone multiple prior treatments. This process is known as dosimetry.
• Determining the functionality of thyroid nodules.
• Evaluating congenital thyroid abnormalities, with the preference for I-123 due to its lower radiation exposure.[5]

Potential Diagnosis

The potential diagnoses associated with thyroid-related conditions are as follows:

• Graves disease
• Thyrotoxicosis due to Hashimoto disease
• Thyroiditis
• Presence of remnant thyroid tissue in the thyroid bed after total thyroidectomy
• Recurrence of differentiated thyroid cancer
• Metastasis of differentiated thyroid cancer
• Toxic multinodular goiter
• Toxic adenoma
• Ectopic thyroid tissue
• Excess exogenous thyroid hormone replacement

Normal and Critical Findings

Physiological Uptake

Thyroid tissue exhibits a significant affinity for iodine uptake. Extra-thyroidal tissues such as the stomach, salivary glands, breast (particularly during lactation), and the urinary tract also contain NIS, resulting in physiological iodine uptake.[6] As radioiodine is metabolized in the liver and subsequently excreted through the urinary tract, it is common to observe visualization of the liver, gallbladder, kidneys, bladder, and ureters during imaging. 

Infected and inflamed tissues, cystic lesions, and ectopic thyroid tissue can also take up and trap I-131. Ectopic thyroid tissue, visualized on an I-131 scan, results from embryological remnants or malformations during the development of the thyroid gland. Typical examples include a lingual or sublingual thyroid, a thyroglossal duct, or a mediastinal thyroid gland.[6][7][8]

Pathological Uptake

After a thyroidectomy, any radioiodine uptake that deviates from the anticipated physiological distribution observed on a post-therapy I-131 scan is indicative of either remnant thyroid tissue or metastatic disease. Conducting a whole-body scan after therapy is crucial to influence the treatment plan based on the results.[9]

Increased blood flow and the presence of NIS in tumors enable iodine uptake in conditions such as breast cancer, gastric adenocarcinoma, or bronchial adenocarcinoma.[6] External contamination by body fluids or, in rare cases, iodine ingestion can mimic metastatic involvement. Typically, this pattern is readily recognized by experienced healthcare professionals and is correlated clinically with the patient's medical history and laboratory results.[10] These observations typically involve superficial areas, and acquiring lateral and oblique images helps to identify the lesion. Furthermore, using SPECT can provide valuable information regarding the anatomical location of the uptake for further assessment.

Patients with hyperthyroidism with elevated or normal radioiodine uptake indicate Graves disease or thyrotoxicosis due to Hashimoto disease. Individuals exhibiting nearly absent radioiodine uptake may have thyroiditis, an excessive or intentional thyroid replacement, or ectopic hyperthyroidism, such as metastatic follicular thyroid cancer or struma ovarii.

Interfering Factors

Thyroid stunning refers to inhibiting the uptake or retention of I-131 after administering a diagnostic dose. Stunning is a transient phenomenon and occurs less frequently with I-123. Therefore, I-123 is the preferred radiotracer for imaging benign thyroid conditions. Stunning occurs due to the reduction in the number of functioning thyroid cells caused by radiation emitted during the test.[11] 

When a small dose of I-131 is administered before a larger treatment dose, it may lead to a phenomenon called "stunning" of thyroid cells, potentially diminishing the treatment's efficacy. Radioactive iodine therapy is approved and deemed safe for both adults and children.[12]

Certain medications can disrupt iodine uptake in the thyroid. To prepare for scanning, the use of the following medications for the specified duration should be discontinued before the procedure:

• Methimazole for 3 to 5 days
• Propylthiouracil for 3 to 5 days
• Bromides for 1 week
• Mercurials for 1 week
• Nitrates for 1 week
• Perchlorate for 1 week
• Salicylates, in large doses, for 1 week
• Sulfonamides for 1 week
• Thiocyanate for 1 week
• Iodine-containing cough medicines and vitamins for 2 weeks
• Iodine solution (Lugol) for 2 to 3 weeks
• Iodine-containing topical agents for 2 to 3 weeks
• Kelp for 2 to 3 weeks
• T3 for 2 to 3 weeks
• Levothyroxine (T4) for 4 to 6 weeks 
• Thyroid extracts or desiccated thyroid extracts for 4 weeks
• Intravenous iodinated contrast materials for 4 to 6 weeks
• Oil-based iodinated contrast materials for 3 to 6 months
• Amiodarone for 3 to 6 months

Complications

Numerous complications associated with an I-131 scan stem from either the preparatory steps preceding the scan or prior treatment with I-131 before post-ablative scans. Some complications include:

• Hypothyroidism-associated symptoms include fatigue, depression, weight gain, constipation, muscle aches, and decreased concentration.

• Rapid growth of persistent or metastatic thyroid cancer with elevated TSH levels, potentially leading to airway obstruction or bone pain after rhTSH administration, in rare cases.

• Secondary malignancies due to I-131 treatment.

• Transient oligospermia and decreases in ovarian function as a result of I-131 treatment.

• Nausea, salivary gland inflammation, or dry mouth due to the therapy with I-131.[13]

• Bone marrow suppression with higher accumulated doses of iodine.[14] 

• Mild anemia, low white blood count, or thrombocytopenia that is not typically clinically significant.

• Mild, transient hyponatremia and hypokalemia due to the induced hypothyroid state.[15] 

• Increased risk of thyroid cancer and increased mortality from breast cancer after iodine therapy for Graves disease.[16][17][18] 

• Moderate-to-severe thyroid eye disease that can worsen with I-131 treatment and is a relative contraindication.

• Stunning of the normal thyroid tissue that can diminish the effectiveness of therapeutic I-131 doses.

Patient Safety and Education

In the interest of patient safety and education, adhering to specific guidelines following I-131 ablation or adjuvant therapy is crucial, some of which are mentioned below.

• Patients should practice self-isolation following I-131 ablation or adjuvant therapy, considering their dose and patient-specific characteristics, according to nuclear medicine recommendations.

• Patients intending to travel by air should be aware that they may trigger radiation detectors for approximately 2 to 3 months and should carry an official letter confirming this.

• Patients are advised to refrain from becoming pregnant for 6 months following radioactive iodine treatment.

• Patients should cease breastfeeding for at least 6 weeks before undergoing the test or treatment to prevent increased uptake and radiation absorption in breast tissue.

• Patients are recommended to discontinue breastfeeding following I-131 administration. Subsequent pregnancies may allow for the resumption of breastfeeding. However, after I-123 administration, breastfeeding can safely resume after a waiting period of 72 hours.

Clinical Significance

An I-131 scan is an important imaging tool for diagnosing and treating thyroid disorders. Performing pre- and post-therapy scans in patients with differentiated thyroid cancer enables disease surveillance and assists clinicians in determining the most suitable treatment approach. Furthermore, it is essential to identify potentially false-positive and false-negative imaging findings during interpretation and correlate them with the patient's characteristics.