Iodine-131 Uptake Study


I-131 scan is a non-invasive radionucleotide scan used for imaging of functional thyroid tissue and thyroid cancer remnant/metastasis. Theranostics in nuclear medicine described as combining diagnostic imaging and treatment for a specific disorder by using the same molecule either radiolabeled in a different form or same radiolabeled agent in different doses.[1] The visualization of the target allows for precision therapy. Iodine molecules can be labeled by radiotracers and used for diagnostic and treatment purposes in thyroid disorders.

The thyroid gland produces thyroid hormones, which are essential to survive and modulate energy metabolism. Iodine is required for thyroid hormone production. Ingested iodine is selectively taken up by thyroid follicular cells with the help of sodium-iodine symporters (NIS) to be processed.[2] NIS is regulated by TSH (thyroid-stimulating hormone). A circulating form of iodine is called iodide, and once it enters follicular cells, it is oxidized by thyroid peroxidase (TPO) enzyme to form iodine. Organification is the next biochemical reaction of the integration of iodine into the thyroglobulin to generate thyroid hormones, mainly thyroxine (T4) and triiodothyronine (T3).

Thyroid stunning can occur during a radionucleotide scan. It is defined as a suppression of iodine production from thyroid, which is temporary. It occurs due to radiation given off the scan from I-131, thus trapping function of the thyrocytes and thyroid cancer cells. It is a radiological phenomenon that a clinician needs to be aware of when administering radioactive iodine.[3] When a small dose of I-131 radioactive iodine given prior to a large dose for treatment, there could be a “stunning” of thyroid cells, which may decrease the effectiveness of treatment.

The two most common radiotracers used in thyroid scans are I-123 and I-131. The differences between these two isotopes are as follows:[1]

  • I-123 has a short half-life (approximately 13 hours), decays by gamma emission, has better imaging quality, less stunning effect, expensive, and less readily available. 
  • I-131 has a longer half-life (approximately 8.2 days), decays by beta emission, is cheaper, readily available, but may have a potential stunning effect due to higher energy capture, allows delayed imaging.



  • Approximately 7-14 days of low-iodine diet is recommended prior to the procedure. Since iodine is selectively taken up by thyroid tissue, a low-iodine diet increases the effectiveness of the I-131 therapy as well as the accuracy of I-131 pre-and post-therapy scans.
  • Thyroid cells have TSH receptors, and high TSH improves iodine intake and optimizes the imaging. High TSH levels can be achieved by two different methods:
    • Patients who are status post total thyroidectomy or near-total thyroidectomy placed on thyroid hormone either in replacement doses or suppressive doses depending on thyroid cancer risk category. The thyroid hormone is withdrawn 4-6 weeks before the procedure to stimulate pituitary TSH secretion. While this method is preferred in advanced and high-risk thyroid cancer, severe hypothyroidism can be dangerous in the elderly and in patients with certain medical problems like congestive cardiac failure, seizure, or some mental disorders.
    • Preparation with Thyrogen: it is a recombinant-TSH (rhTSH) molecule to increase TSH levels without holding thyroid hormone replacement hence avoiding hypothyroidism symptoms. Preparation includes 2 doses of Thyrogen 0.9 mg subcutaneous injections 24 hours apart from each other, and this method has been approved by the American Thyroid Association (ATA) for remnant ablation after total thyroidectomy in differentiated thyroid cancer patients without evidence of distant metastasis.[4] A TSH level of 30 mIU/L or more is preferred.[5]


  • The patient is instructed to be NPO (nothing by mouth) at least 4 hours prior to iodine dose and one hour after.
  • Diagnostic I-131 scan: A small dose of radioactive Iodine given orally as capsules or liquid form and scan is performed 4-48 hours later.
  • Post-therapy I-131 scan is performed 3-7 days after an I-131 ablation/adjuvant therapy dose is given.
  • The patient lies supine on a movable exam table, and images are obtained for planar images and also for single-photon emission computerized tomography with integrated computed tomography (SPECT-CT).
  • Planar images: A gamma emission collector camera captures whole body images on one plane.
  • SPECT-CT: Combined with a radioactive iodine scan, it helps to accurately localize and differentiate physiologic uptake from metastatic lesions. It improves the detection of smaller lesions by providing a cross-sectional three-dimensional view.[6] 
  • Serum thyroglobulin and anti-thyroglobulin antibody assays should be obtained simultaneously.


I-131 scan is a powerful tool to investigate several thyroid disorders[7] but is mainly used to:

  • To characterize thyroid function in the case of hyperthyroidism, subclinical hyperthyroidism, multinodular goiter, toxic nodule, thyroiditis, congenital hypothyroidism.
  • To visualize ectopic thyroid tissue.
  • To visualize normal or/cancerous thyroid tissue remnant, thyroid cancer recurrence or distant metastasis
  • To re-stage thyroid cancer 6-12 months after thyroidectomy and radioactive iodine ablation therapy.
  • To help with the decision of I-131 therapy dose (diagnostic pre-treatment whole-body scan)
  • To identify the I-131 therapy dose that is safe for vital organs (in a patient who has been treated multiple times before). This procedure called dosimetry.

Potential Diagnosis

  • Hyperthyroidism
  • Thyroiditis
  • Remnant thyroid tissue in the thyroid bed (after total thyroidectomy)
  • Recurrence of differentiated thyroid cancer
  • Metastasis of differentiated thyroid cancer
  • Multinodular goiter
  • Ectopic thyroid tissue

Normal and Critical Findings

Accurate interpretation of the I-131 scan is essential to identify the correct clinical course of action.

  • Physiological Uptake

I-131 whole body scan counts on the fact that thyroid tissue has a high affinity to uptake and trap the Iodine, which is performed by NIS. Some extra-thyroidal tissues like stomach, salivary glands, breast (especially if lactating), and urinary tract also express NIS and show physiologic uptake. Similarly, as absorbed radioiodine is metabolized in the liver and excreted in the urinary tract, visualization of the liver, gall bladder, kidney, bladder, and ureters is common.

Ectopic thyroid tissue may be an embryological remnant or malformation during the development that can be captured with an I-131 scan. Common examples are lingual or sublingual thyroid, thyroglossal duct, or a mediastinal thyroid gland. Ectopic thyroid tissue in ovaries is called struma ovarii.[8][9] 

  • Pathologic Uptake

In a patient who has undergone thyroidectomy, any uptake apart from physiologic distribution on a post-therapy I-131 scan may be considered as a remnant (if localized in the thyroid bed after the first I-131 ablation/therapy) or metastasis (out of the thyroid bed). Post-therapy whole-body scan is very valuable and may change the plan of care with additional information.[10]

False-positive Lesions:[11] Inflammatory, cystic, non-thyroid neoplastic disorders, for example, pleural or pericardial effusions; aspergilloma, arthritis; ovarian or breast cysts. NIS expression of the tumor and increased blood flow resulting in iodine uptake of some malignancies has been reported as in breast cancer, gastric adenocarcinoma, or bronchial adenocarcinoma. External contamination by body fluids or rarely during the intake of the Iodine may imitate metastatic involvement. Usually, the pattern is recognized easily by experienced specialists, and repeat imaging after decontamination clarifies the case.[12] They are almost always superficial, and obtaining lateral and/or oblique images helps to identify the lesion. In addition, utilizing SPECT-CT offers very valuable input about the anatomical location of the uptake for further evaluation. This is why it is important for the surgeon to remove all of the thyroid tissue at surgery, as even a little bit of thyroid tissue left will render the test and treatment inaccurate. 

Interfering Factors

  • Assess for possible iodine excess (including intravenous iodinated contrast study, medications containing iodine) before the procedure, and instruct a low iodine diet at least for 2 weeks. Some cases may need urine iodine testing to ensure optimum iodine level for I-131 scan and therapy.
  • Discontinue certain medications (like amiodarone, thyroid hormones, thioamides) in a timely manner prior to the scan.
  • Always interpret the scan results in correlation with patient clinical history, physical exam, and other biochemical findings.


  • The patient should be educated about what to expect from the procedure, including the preparation period, expected symptoms if the thyroid hormone withdrawal method is used. The effect of potential results on the treatment plan, and precautions in certain situations should be discussed.
  • If the patient is pregnant or has an allergy to iodine I-131, the scan is contraindicated.
  • Although there are no significant side effects of this procedure, if it is a post-therapy scan, there could be some nausea, salivary gland inflammation, dry mouth due to the therapy dose of I-131.
  • If the patient has moderate to severe thyroid eye disease, I-131 treatment is relatively contraindicated as it may worsen the eye symptoms.

Patient Safety and Education

  • Patients recommended avoiding breastfeeding after this test as I-131 can be secreted in breast milk.
  • If I-131 ablation or adjuvant therapy is performed, self-isolation rules apply as per the nuclear medicine recommendations depending on individual dose and patient-specific characteristics.
  • If patients are planning on going to air travel, they will set off the radiation detectors for approximately 2-3 months. They should be provided a letter explaining the reason.

Clinical Significance

  • I-131 scan is an important imaging tool to aid the diagnosis and treatment of multiple thyroid disorders. Particularly pre-therapy and post-therapy scan in differentiated thyroid cancer patients allows surveillance of the disease and guide the clinician for the treatment plan.
  • It is important to recognize potentially false positive and false negative imaging findings during interpretation and correlate with the patient's individual characteristics.
  • It is important for the surgeon to remove all thyroid tissue for thyroid cancer as leaving even a little bit of tissue will render the iodine treatment ineffective as it will all be taken up by the remnant thyroid tissue. 

Article Details

Article Author

Sahzene Yavuz

Article Editor:

Yana Puckett


5/8/2022 2:20:24 AM



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