Back To Search Results

Sodium Iodide I 131

Editor: Craig E. Grossman Updated: 2/13/2023 7:56:37 PM


Radioactive iodine ablation (RAI), which entails the administration of radioactive iodine-131, is used to treat hyperthyroidism and in the adjuvant setting for differentiated thyroid carcinoma (DTC).[1][2]

Ninety-five percent of thyroid carcinomas derive from the thyroid hormone-producing follicular cells of the thyroid gland; DTCs, the most common subtype, include both papillary and follicular histologies.[3] DTC is often treated with radioiodine-131 in the adjuvant setting due to the cell’s specificity to uptake iodine. Undifferentiated (or anaplastic) thyroid cancer, although still derived from the thyroid hormone-producing follicular cells, typically does not respond to RAI because of the complete loss of expression of the sodium-iodine symporter (NIS) in these cancer subtypes.[3][4][5] The goal of radioiodine therapy is to ablate any residual cancer cells and kill normal thyroid cells remaining post-thyroidectomy, resulting in undetectable serum thyroglobulin levels (a biomarker of viable thyroid tissue) and consequently improve disease-free and disease-specific survival.[1][6][7][8] The American Thyroid Association (ATA) has established indications for RAI in patients with thyroid cancer, based upon the risk of recurrence post-thyroidectomy. This three-tier risk classification system is based on various pathologic features, as indicated below:

Low Risk

  • Papillary carcinoma with all the following features:
    • No distant metastases
    • No lymph node involvement
    • Gross total tumor resection
    • No tumor invasion of local/locoregional structures
    • Non-aggressive histology
    • No radioiodine uptake outside the thyroid bed on post-thyroidectomy iodine whole-body scan
    • Clinical N0 or ≤ 5 pathologic N1 micrometastases (< 0.2 cm in largest dimension)
    • No vascular invasion
  • Intrathyroidal encapsulated follicular variant of papillary thyroid carcinoma.
  • Intrathyroidal, well-differentiated follicular carcinoma with capsular invasion and no to minimal (< 4 foci) vascular invasion
  • Intrathyroidal, papillary microcarcinoma

Intermediate Risk

  • Microscopic invasion into perithyroidal tissues
  • Radioiodine uptake within the neck on a post-RAI whole body scan
  • Aggressive histology (i.e., tall cell, insular, columnar cell carcinoma, Hürthle cell carcinoma, follicular thyroid cancer, hobnail variant)
  • Papillary carcinoma with vascular invasion
  • Clinical suspicion of regional lymph node involvement (cN1), all involved lymph nodes < 3 cm in largest dimension; or > 5 regional lymph nodes containing cancer on pathologic analysis (pN1), all lymph nodes < 3 cm in the largest dimension.
  • Multifocal papillary microcarcinoma with extrathyroidal extension

High Risk

  • Gross extrathyroidal extension
  • Incomplete tumor resection
  • Distant Metastasis (either on imaging, pathology, or significantly elevated postoperative serum thyroglobulin level)
  • Pathologic regional lymph node involvement (pN1) with at least one lymph node ≥3 cm in the largest dimension
  • Follicular carcinoma with extensive (> 4 foci of) vascular invasion

In the case of patients with hyperthyroidism (which includes Grave’s disease, toxic multinodular goutier, and toxic adenoma) who are not candidates for or who fail radical or partial thyroidectomy or antithyroid drug therapy, the ATA recommends radioiodine as a first-line or alternative treatment.[2] Specifically, RAI is preferable for the elderly, medically inoperable patients due to multiple significant comorbidities, and patients with a small-sized goiter.  

Radioactive iodine isotope administration also serves a role in the diagnosis and long-term follow-up of patients with DTC and the diagnosis of hyperthyroidism.[1][2] The ATA recommends whole-body SPECT-CT scans to measure the uptake of radioiodine-131 or radioiodine-123 (another radioactive iodine isotope) for the initial evaluation of thyroid nodules, as well as both immediately and 6 to 12 months following RAI therapy in intermediate and high-risk DTC patients. Whole-body radioiodine scans are also useful in patients with iodine uptake on initial post-RAI therapy scans and in the presence of serum thyroglobulin antibodies (which can interfere with the thyroglobulin laboratory assay, thereby producing a false-negative result).[1] Radioiodine uptake of thyroidal tissue is also used to evaluate thyrotoxicosis when etiology is unable to be determined with biochemical evaluation (TSH and thyroid hormone testing) and is an option for patients with clinical signs suspicious for toxic adenoma or toxic multinodular goiter.[2]

Mechanism of Action

Register For Free And Read The Full Article
Get the answers you need instantly with the StatPearls Clinical Decision Support tool. StatPearls spent the last decade developing the largest and most updated Point-of Care resource ever developed. Earn CME/CE by searching and reading articles.
  • Dropdown arrow Search engine and full access to all medical articles
  • Dropdown arrow 10 free questions in your specialty
  • Dropdown arrow Free CME/CE Activities
  • Dropdown arrow Free daily question in your email
  • Dropdown arrow Save favorite articles to your dashboard
  • Dropdown arrow Emails offering discounts

Learn more about a Subscription to StatPearls Point-of-Care

Mechanism of Action

The efficacy of radioiodine therapy depends on the ability of thyroid cells to uptake iodine, primarily via the NIS.[5] Radioiodine-131 beta particles react with intracellular water to produce free radicals, which are cytotoxic via DNA and cellular organelle damage.[9]


Radioiodine is administered orally in pill form.[10]

In patients with low-risk or intermediate-risk DTC with low-risk features (i.e., low volume central neck metastases with no further extension or adverse features stated above), an ablative dose of 30 mCi is the recommendation from the ATA.  However, in patients with less than complete or near-complete thyroidectomy, or adverse pathologic features, the RAI administered dose should be increased accordingly, to a maximum of 150 mCi.[1]

To maximize RAI uptake into thyroid cells, thyroid-stimulating hormone (TSH) levels preferentially increase by either the injection of recombinant human TSH (rhTSH) or withdrawal of supplemental thyroid hormone (which the patient must take in the absence of a thyroid gland). rhTSH has the advantage of maintaining a euthyroid state, thereby minimizing the unwanted side-effects of hypothyroidism. Although both methods appear to have equivalent efficacy, the ATA does not recommend using rhTSH in high-risk DTC patients due to insufficient evidence. Patients typically consume a low iodine diet for approximately 1 to 2 weeks before RAI to facilitate radioiodine uptake further.[1]

The ATA recommends a single dose of 10 to 15 mCi to treat Grave’s disease and a single dose of 10 to 20 mCi for toxic multinodular goiter or toxic adenoma.[2] Before administering radioiodine in patients with hyperthyroidism, the patient should take a β-adrenergic blocker or methimazole to prevent transient thyrotoxicosis resulting from the overwhelming release of thyroid hormone from cell death. This approach should especially merit consideration in at-risk populations such as the elderly and those with cardiovascular co-morbidities.[2]

Adverse Effects

Although iodine channels express predominantly in thyroid cells, additional cell types express this receptor, including the lactating breast, gastric mucosa, and salivary and lacrimal glands, leading to dose-dependent short- and long-term side effects.[11][12] Acute sialoadenitis, the most common short-term side effect from RAI (approximately 30% incidence), can occur as early as several hours after treatment and may persist for up to one year following therapy. Xerostomia (approximately 20 to 40% incidence), a complication associated with hyposalivation, manifests weeks to months following RAI and can persist for months to years.[13][14] Repercussions of chronic hyposalivation include increased incidence of dental caries, dysgeusia (altered taste), and difficulty with mastication and deglutition.[15] Other adverse effects of RAI therapy include nausea, alopecia, conjunctivitis, and xerophthalmia (dry eyes).[13][16]

Due to insufficient evidence, the ATA does not have specific guidelines for preventing or mediating these toxicities.  However, various interventions, albeit with limited efficacy, exist, including the use of sialagogues (i.e., lemon candies, chewing gum, lemon juice), sialoendoscopic surgery, and the co-administration of certain radioprotectors such as amifostine.[1][17][18][19][20][21]


Due to the presence of iodine channels in lactating breast tissue, RAI is contraindicated in pregnancy and breastfeeding women.[22][23][24]

Radioiodine has been found in breast milk for up to one month following the administration of therapeutic radioiodine-131.[25] The ATA, therefore, recommends the usage of diagnostic radioiodine-123 or low dose radioiodine-131 scanning to assess radioiodine uptake in breast tissue before RAI therapy in women who are breastfeeding and are unable to defer therapy due to the severity of their disease.[1] 

The ATA additionally recommends all women of childbearing age undergo a pregnancy test before RAI therapy and avoid pregnancy 6 to 12 months following treatment.[1] Studies have demonstrated that there may be an increased risk of miscarriage up to one year following RAI therapy.[25]

Enhancing Healthcare Team Outcomes

Radioactive iodine is widely used in the treatment of hyperthyroidism and thyroid carcinoma. Radioiodine administration requires a specialized interprofessional team of highly trained healthcare providers, including nurses, physicians, radiotherapy-specialized pharmacists, and radiation safety. All providers involved in radioiodine administration should be aware of its indications, contraindications, and adverse effects. One contraindication all providers should be mindful of is pregnancy. Providers should collaborate and ensure proper education of women of childbearing age to prevent radioiodine administration if pregnant and/or breastfeeding due to potential teratogenic effects; health care providers should obtain a thorough sexual history and implement routine pregnancy testing in women of childbearing age.

Additional recommendations to enhance patient-centered care include establishing interprofessional collaboration and open communication among providers (i.e., tumor board discussions), quality assurance measures to identify areas for improvement of health care delivery, and finally, implementation of checklists ito ensure efficient provider-patient communication and reduce adverse clinical outcomes.[26] [Level 5]



Haugen BR,Alexander EK,Bible KC,Doherty GM,Mandel SJ,Nikiforov YE,Pacini F,Randolph GW,Sawka AM,Schlumberger M,Schuff KG,Sherman SI,Sosa JA,Steward DL,Tuttle RM,Wartofsky L, 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid : official journal of the American Thyroid Association. 2016 Jan;     [PubMed PMID: 26462967]


Ross DS,Burch HB,Cooper DS,Greenlee MC,Laurberg P,Maia AL,Rivkees SA,Samuels M,Sosa JA,Stan MN,Walter MA, 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis. Thyroid : official journal of the American Thyroid Association. 2016 Oct;     [PubMed PMID: 27521067]


Kondo T,Ezzat S,Asa SL, Pathogenetic mechanisms in thyroid follicular-cell neoplasia. Nature reviews. Cancer. 2006 Apr;     [PubMed PMID: 16557281]

Level 3 (low-level) evidence


Smallridge RC,Ain KB,Asa SL,Bible KC,Brierley JD,Burman KD,Kebebew E,Lee NY,Nikiforov YE,Rosenthal MS,Shah MH,Shaha AR,Tuttle RM, American Thyroid Association guidelines for management of patients with anaplastic thyroid cancer. Thyroid : official journal of the American Thyroid Association. 2012 Nov;     [PubMed PMID: 23130564]


Spitzweg C,Harrington KJ,Pinke LA,Vile RG,Morris JC, Clinical review 132: The sodium iodide symporter and its potential role in cancer therapy. The Journal of clinical endocrinology and metabolism. 2001 Jul;     [PubMed PMID: 11443208]

Level 3 (low-level) evidence


Jonklaas J,Sarlis NJ,Litofsky D,Ain KB,Bigos ST,Brierley JD,Cooper DS,Haugen BR,Ladenson PW,Magner J,Robbins J,Ross DS,Skarulis M,Maxon HR,Sherman SI, Outcomes of patients with differentiated thyroid carcinoma following initial therapy. Thyroid : official journal of the American Thyroid Association. 2006 Dec;     [PubMed PMID: 17199433]

Level 2 (mid-level) evidence


Kazaure HS,Roman SA,Sosa JA, Aggressive variants of papillary thyroid cancer: incidence, characteristics and predictors of survival among 43,738 patients. Annals of surgical oncology. 2012 Jun;     [PubMed PMID: 22065195]


Chow SM,Yau S,Kwan CK,Poon PC,Law SC, Local and regional control in patients with papillary thyroid carcinoma: specific indications of external radiotherapy and radioactive iodine according to T and N categories in AJCC 6th edition. Endocrine-related cancer. 2006 Dec;     [PubMed PMID: 17158761]

Level 2 (mid-level) evidence


Jeon J, Review of Therapeutic Applications of Radiolabeled Functional Nanomaterials. International journal of molecular sciences. 2019 May 10;     [PubMed PMID: 31083402]


Esposito G, Initial radioiodine administration: when to use it and how to select the dose. Endocrinology and metabolism clinics of North America. 2014 Jun;     [PubMed PMID: 24891168]


Dohán O,De la Vieja A,Paroder V,Riedel C,Artani M,Reed M,Ginter CS,Carrasco N, The sodium/iodide Symporter (NIS): characterization, regulation, and medical significance. Endocrine reviews. 2003 Feb;     [PubMed PMID: 12588808]


Andresen NS,Buatti JM,Tewfik HH,Pagedar NA,Anderson CM,Watkins JM, Radioiodine Ablation following Thyroidectomy for Differentiated Thyroid Cancer: Literature Review of Utility, Dose, and Toxicity. European thyroid journal. 2017 Jul;     [PubMed PMID: 28868259]


Alexander C,Bader JB,Schaefer A,Finke C,Kirsch CM, Intermediate and long-term side effects of high-dose radioiodine therapy for thyroid carcinoma. Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 1998 Sep;     [PubMed PMID: 9744341]

Level 2 (mid-level) evidence


Hyer S,Kong A,Pratt B,Harmer C, Salivary gland toxicity after radioiodine therapy for thyroid cancer. Clinical oncology (Royal College of Radiologists (Great Britain)). 2007 Feb;     [PubMed PMID: 17305259]

Level 2 (mid-level) evidence


Jensen SB,Vissink A, Salivary gland dysfunction and xerostomia in Sjögren's syndrome. Oral and maxillofacial surgery clinics of North America. 2014 Feb;     [PubMed PMID: 24287192]


Fard-Esfahani A,Emami-Ardekani A,Fallahi B,Fard-Esfahani P,Beiki D,Hassanzadeh-Rad A,Eftekhari M, Adverse effects of radioactive iodine-131 treatment for differentiated thyroid carcinoma. Nuclear medicine communications. 2014 Aug;     [PubMed PMID: 24751702]


Nakada K,Ishibashi T,Takei T,Hirata K,Shinohara K,Katoh S,Zhao S,Tamaki N,Noguchi Y,Noguchi S, Does lemon candy decrease salivary gland damage after radioiodine therapy for thyroid cancer? Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2005 Feb;     [PubMed PMID: 15695785]

Level 1 (high-level) evidence


Van Nostrand D,Atkins F,Bandaru VV,Chennupati SP,Moreau S,Burman K,Wartofsky L, Salivary gland protection with sialagogues: a case study. Thyroid : official journal of the American Thyroid Association. 2009 Sep;     [PubMed PMID: 19500022]

Level 3 (low-level) evidence


Meng Q,Fang W,Long X,Deng M,Li J,Ke J, Sialoendoscopy combined with an internal stent and postoperative massage as a comprehensive treatment of delayed I{sup}131{/sup}-induced parotitis. The British journal of oral     [PubMed PMID: 28697989]


Bohuslavizki KH,Klutmann S,Jenicke L,Brenner W,Feyerabend B,Henze E,Clausen M, Radioprotection of salivary glands by S-2-(3-aminopropylamino)-ethylphosphorothioic (amifostine) obtained in a rabbit animal model. International journal of radiation oncology, biology, physics. 1999 Aug 1;     [PubMed PMID: 10477022]

Level 3 (low-level) evidence


Bohuslavizki KH,Klutmann S,Brenner W,Kröger S,Buchert R,Bleckmann C,Mester J,Henze E,Clausen M, Radioprotection of salivary glands by amifostine in high-dose radioiodine treatment. Results of a double-blinded, placebo-controlled study in patients with differentiated thyroid cancer. Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al]. 1999 Nov;     [PubMed PMID: 10584133]

Level 1 (high-level) evidence


Sisson JC,Freitas J,McDougall IR,Dauer LT,Hurley JR,Brierley JD,Edinboro CH,Rosenthal D,Thomas MJ,Wexler JA,Asamoah E,Avram AM,Milas M,Greenlee C, Radiation safety in the treatment of patients with thyroid diseases by radioiodine 131I : practice recommendations of the American Thyroid Association. Thyroid : official journal of the American Thyroid Association. 2011 Apr;     [PubMed PMID: 21417738]


Cho JY,Léveillé R,Kao R,Rousset B,Parlow AF,Burak WE Jr,Mazzaferri EL,Jhiang SM, Hormonal regulation of radioiodide uptake activity and Na /I- symporter expression in mammary glands. The Journal of clinical endocrinology and metabolism. 2000 Aug;     [PubMed PMID: 10946907]

Level 3 (low-level) evidence


Tazebay UH,Wapnir IL,Levy O,Dohan O,Zuckier LS,Zhao QH,Deng HF,Amenta PS,Fineberg S,Pestell RG,Carrasco N, The mammary gland iodide transporter is expressed during lactation and in breast cancer. Nature medicine. 2000 Aug;     [PubMed PMID: 10932223]

Level 3 (low-level) evidence


Gorman CA, Radioiodine and pregnancy. Thyroid : official journal of the American Thyroid Association. 1999 Jul;     [PubMed PMID: 10447020]


Moncayo VM,Applegate KE,Duszak R Jr,Barron BJ,Fitz J,Halkar RK,Lee DJ,Schuster DM, The nuclear medicine therapy care coordination service: a model for radiologist-driven patient-centered care. Academic radiology. 2015 Jun;     [PubMed PMID: 25766086]