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PubMed This is a summary of 22 peer-reviewed journal articles Updated
Nuclear Medicine · Papillary Thyroid Carcinoma

Radioactive Iodine (RAI) Therapy: Benefits and Risks

At a Glance

Radioactive iodine (RAI) is not automatically needed after papillary thyroid cancer surgery. It is chosen according to recurrence risk and can destroy iodine-absorbing cancer cells, but side effects include salivary gland problems, fertility effects, and rare second cancers.

Radioactive Iodine (RAI) therapy, also known as I-131, has been a cornerstone of thyroid cancer treatment for decades. However, our understanding of its benefits and risks has evolved significantly. Today, RAI is no longer an automatic next step after surgery. Instead, it is used as a selective therapy, reserved for situations where the potential benefit of reducing cancer recurrence outweighs the known risks of the radiation itself [1][2].

How RAI Works

The thyroid gland strongly concentrates iodine, though it is not the only tissue to do so (salivary glands, stomach, and lactating breast tissue also absorb it). RAI takes advantage of this by using a radioactive form of iodine that iodine-avid thyroid cells—including most Papillary Thyroid Carcinoma (PTC) cells—will pull inside themselves [1]. Once inside, the radiation destroys the cell from within, while leaving most other tissues in the body largely unaffected. (Note that some PTC cells lose their ability to absorb iodine, meaning RAI will not be effective for them).

A Selective Approach

Current medical guidelines (ATA and NCCN) emphasize that RAI should be “risk-adapted.” This means your care team evaluates whether you need it based on your ATA Risk Category [3][4]:

  • Low Risk: For many low-risk patients, RAI is generally not recommended. Studies have shown that for small tumors (≤1 cm) without high-risk features, RAI does not significantly reduce the risk of the cancer coming back [3][5].
  • Intermediate Risk: RAI is a “consideration.” Your doctor will look at specific factors like the number of lymph nodes involved or the presence of aggressive variants to decide if the benefit is worth the risks [3][6].
  • High Risk: RAI is strongly recommended to treat any remaining cancer cells and improve overall survival [7][8].

Safety, Isolation, and Preparation

RAI requires strict safety protocols that must be followed closely:

  • Pregnancy and Breastfeeding: RAI is absolutely contraindicated during pregnancy. A pregnancy test is mandatory before treatment. Breastfeeding must be stopped completely prior to treatment and must not be resumed for your current infant.
  • Radiation Isolation: After taking the pill, you will emit radiation for several days. You must follow mandatory, individualized isolation rules provided by your nuclear medicine team to protect family members, children, pregnant women, and pets.
  • Preparation: You will undergo a low-iodine diet and your TSH will be elevated (via hormone withdrawal or recombinant TSH injections) to “starve” the cells of iodine so they absorb the RAI.

Potential Harms and Side Effects

Because RAI can affect tissues that naturally concentrate iodine—like salivary glands and tear ducts—it can cause dose-dependent side effects.

Salivary Gland Dysfunction

The salivary glands are the most common site of side effects. RAI can cause sialadenitis (painful swelling of the glands) and xerostomia (chronic dry mouth) [9][10].

  • Frequency: Between 16% and 54% of patients report some level of salivary dysfunction [9].
  • Dose Relationship: The risk increases with higher doses. One study found that salivary gland damage was almost nonexistent at doses below 100 mCi but affected 77% of patients receiving 200 mCi or more [11].
  • Long-term Impact: While many symptoms improve within the first year, some patients experience permanent dry mouth, which can lead to increased dental cavities and difficulty swallowing [12][13].

Eye and Tear Duct Issues

RAI can also affect the nasolacrimal ducts (the tubes that drain tears from your eyes).

  • Obstruction: About 7% of patients may develop an obstruction in these ducts, leading to persistent “tearing” or watery eyes [14].
  • Risk Factors: This is more common in patients over 45 and those receiving higher cumulative doses of radiation [15].

Fertility and Reproductive Health

RAI can have temporary effects on reproductive organs.

  • Men: Transient (temporary) reduction in sperm count is common, affecting 35% to 100% of men shortly after treatment, though it usually recovers [9].
  • Women: RAI can affect ovarian reserve (the number of eggs), particularly after repeated treatments [16][17]. While most women successfully have children after RAI, doctors typically recommend waiting 6 to 12 months after treatment before trying to conceive to ensure the radiation has fully cleared the body [18][19].

Second Primary Malignancies

There is a small but documented risk that exposure to RAI may slightly increase the lifetime risk of developing a second, unrelated cancer, such as leukemia or breast cancer [20][21]. This risk is cumulative, meaning it increases each time you receive a dose of RAI. For example, the risk of leukemia has been shown to be dose-dependent and cumulative over a patient’s lifetime dose [20].

Why Less is Often More

Because of these potential long-term impacts on your quality of life, the modern trend is to use the lowest effective dose possible—or to skip RAI entirely for low-risk disease [5][22]. If RAI is recommended for you, it is because your medical team believes the risk of the thyroid cancer returning is higher than the risks of the treatment itself.

Common questions in this guide

Do all people with papillary thyroid cancer need radioactive iodine?
No. RAI is chosen according to the risk that cancer will remain or return and the expected benefit of treatment. Many people with small, low-risk tumors and no high-risk features may not need it, while it is more strongly recommended for high-risk disease.
How does radioactive iodine destroy papillary thyroid cancer cells?
I-131 is absorbed by thyroid cells that still take up iodine, including many papillary thyroid cancer cells. The radiation then damages those cells from inside the cell. RAI will not work well against tumor cells that no longer absorb iodine.
What preparation and safety steps are required for RAI treatment?
Preparation usually includes a low-iodine diet and raising TSH by temporarily stopping thyroid hormone or using recombinant TSH. A pregnancy test is required, and RAI must not be given during pregnancy; breastfeeding must be stopped and not resumed for the current infant. After treatment, individualized radiation-isolation instructions help protect family members, children, pregnant people, and pets.
What side effects can radioactive iodine cause?
The most common problems involve the salivary glands, including painful swelling and persistent dry mouth. Some people develop watery eyes from tear-duct blockage, and higher doses increase the risk of these effects. Dry mouth can contribute to cavities and difficulty swallowing.
Can RAI affect fertility or future pregnancy?
RAI can temporarily lower sperm counts in men and may reduce ovarian reserve, particularly after repeated treatments. Most women can become pregnant after RAI, but clinicians commonly recommend waiting 6 to 12 months before trying to conceive. Discuss fertility preservation and timing with the treating team, and never receive RAI during pregnancy.
How is the safest RAI dose chosen?
The treating team uses your cancer risk category, pathology, treatment goal, and expected benefit to choose a dose. Current practice favors the lowest effective dose because salivary-gland and tear-duct problems, reproductive effects, and the small risk of a second cancer can increase with higher or repeated doses. Some low-risk patients may avoid RAI entirely.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.Based on my ATA risk category and pathology, what is the specific goal of RAI for me: remnant ablation, adjuvant therapy, or treating known disease?
  2. 2.What is the lowest effective dose of RAI for my situation, and how does that dose affect my risk of long-term side effects?
  3. 3.What are your recommendations for protecting my salivary glands during and after treatment (e.g., hydration, sour candies, or timing of sialagogues)?
  4. 4.Should I see an ophthalmologist before treatment if I have a history of dry eyes or tear duct issues?
  5. 5.If fertility is a concern, how long should we wait after RAI before trying to conceive, and should we consider sperm or egg banking?
  6. 6.How will we monitor the effectiveness of the RAI treatment over the next year?

Questions For You

Tap a prompt to share your answer — we'll use it plus this page's context to start a tailored conversation.

References

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This page discusses radioactive iodine therapy for papillary thyroid cancer for informational purposes only and does not constitute medical advice. Your thyroid cancer and nuclear medicine teams should decide whether RAI is appropriate and how to manage its risks in your situation.

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