Radioactive Iodine Treatment (RAI)
Radioactive Iodine treatment (RAI) is a unique form of treatment for the differentiated forms of thyroid cancer (papillary & follicular). It is not often used in patients who are at low risk for recurrence. Generally speaking, low risk patients are those who had a singular cancerous nodule without 'aggressive features', are less than 45 years old, and have no family history of thyroid cancer. These patients may be defined as having Stage I thyroid cancer.
For a quick view of the American Thyroid Association TNM staging system see their summary here.
For a full explanation of the ‘staging’ for thyroid cancer see the American Thyroid Association’s Revised American Thyroid Association Management Guidelines for Patients with Thyroid Nodules and Differentiated Thyroid Cancer (Table 4)
To calculate your own "MACIS scoring", that is, to use their criteria to evaluate your risk of recurrence (using the above defintions) see the ATA "Thyroid Cancer Staging Calculator".
For those who are at higher risk of recurrence, the option to have RAI treatment is available and may be recommended by the treating physician.
The following information applies to those who have been advised to have RAI treatment by their doctor.
RAI treatment has two primary purposes:
- The treatment destroys any remaining thyroid cells (both normal and cancerous) and minimizes the risk of recurrence. This is also known as ablation therapy.
- Destroying any remaining normal or cancerous thyroid tissue left behind after the thyroidectomy surgery facilitates the use of a unique protein marker called Thyroglobulin (Tg) in the future. Tg is measured in blood tests.
In years past, a treatment dose of RAI was usually in the range of 3.7-5.5 GBq (100 or 150mCi). It can vary based on the size or number of initial tumours, aggressive features of the pathology, and other risk factors. More recent research indicates that a lower dose, of 1.1 GBq (30mCi) may be as effective, with fewer potential after-effects. If you require RAI, ask your doctor to discuss the dosage with you.
The initial RAI treatment may be given anytime, but is usually used sometime within six weeks to six months post-surgery.
Some specialists reverse the protocol. That is, they closely follow patients in the post-surgery months using ultrasound and blood tests (such as measuring Tg) and keep the radioactive iodine treatment an option if the test results indicate its necessity.
Approximately one week after having the RAI treatment, a nuclear scan known as a Whole Body Scan (WBS) is normally given. The scan will indicate how much remnant tissue remains in the neck area following the surgery, and may indicate any metastases (spread) of the cancer to other parts of the body.
One of the ways to maximize the uptake of the radioactive iodine is by stimulating the thyroid cells to take up the radioactive iodine by raising the TSH level. There are 2 ways of achieving a high TSH level. They include being withdrawn from hormone replacement (“going hypo”) or using Thyrogen®, a medication given by injection (see section below). Another part of the preparation is to go on a Low Iodine Diet.
The following is a list of suggested items for patients to take to the hospital with them, if they will have a period of time in a hospital isolation room, following their RAI treatment (inquire if you will have hospital isolation or home-based isolation):
The following resources are provided for those with questions about how to prepare themselves for precautions that should be taken in the days following, once RAI treatment has been given.
Our bodies require thyroid hormone (T4); a hormone taken in synthetic form (by a daily pill) once the thyroid has been removed. The body also requires T3 which it converts from T4. Without thyroid hormone, the body produces an increasing amount of thyroid stimulating hormone (TSH). An elevated TSH of at least 30 mIU/L is needed for the RAI treatment to be effective. To achieve this rise in TSH, patients may be instructed to stop taking their thyroid hormone replacement pills.
Becoming hypothyroid by hormone withdrawal, involves stopping levothyroxine (L-T4; the drug’s brand names in Canada are Synthroid and Eltroxin) for approximately 4-6 weeks prior to RAI treatment. During the time that levothyroxine is not taken, Cytomel (L-T3) may be prescribed. Cytomel is a fast-acting (and fast dissipating) form of thyroid hormone used to minimize the symptoms of hypothyroidism during hormone withdrawal. Cytomel is stopped approximately 2 weeks prior to RAI treatment.
‘Going hypo’ is a gradual process with symptoms (if any) increasing slowly over the six week period. The longer the patient is off of thyroid hormone, especially during the last two weeks prior to RAI treatment when no thyroid hormone is taken, the more likely the patient will experience symptoms of hypothyroidism.
Some Symptoms Associated with Hypothyroidism:
- Tiredness, loss of energy, weakness
- Trouble sleeping, nightmares or excess sleep
- Puffiness especially in the face and bloating
- Loss of ability to concentrate, memory loss, absentmindedness
- Weight gain
- Anxiety, panic attacks, irritability, mood swings
- Dry eyes, skin and hair; hair loss
- Change in menstrual cycle
- Joint pains and stiffness, muscle cramps
- Intolerance to cold
- Constipation and/or nausea
- Tingling or numbness in fingers or toes
- Ringing in ears
- Slight changes in eyesight
As an alternative to a patient ‘going hypo’, doctors have the option of effectively raising the TSH level by giving the patient TSH in the form of Thyrogen® (rhTSH) to prepare patients for RAI treatment. In that case, the patient does not withdraw from their thyroid hormone but continues taking their daily dose of L-T4 each day. They do not become ‘hypo’ or have associated symptoms. This form of preparation for RAI treatment is known as ‘TSH stimulated’. When taking Thyrogen® in preparation for RAI treatment it is not necessary to have a measured TSH of at least 30 mIU/L as it is during the hypo or ‘withdrawal preparation’.
Thyrogen® is fast-acting and fast-dissipating and requires two visits to a doctor (or other clinician) as it is given by injections. Most patients have mild (if any) side effects from Thyrogen® and avoid hypothyroid symptoms described above. If Thyrogen® is selected, patients will need to get the injections on the 2 days just prior to the RAI treatment.
For detailed product information about Thyrogen® including side effects and reactions, contra-indications, special information regarding the dosage (such as those for pregnant women or children), click here.
To view the typical schedule for injections of Thyrogen®, click here.
In some Canadian provinces, the cost of Thyrogen® is not covered by the provincial medical/drug programs, nor by local hospital formulary programs. In other provinces, the cost of Thyrogen® is covered. Where the costs are not covered, patients must pay for it themselves or apply to their private health insurance for full or partial coverage.
Some provinces also have drug programs available which are related to income level needs. For those who pay out of pocket, the current cost for the two injections of Thyrogen® that come within one kit, is approximately $1,800 or more.
Patients should be aware that the Thyrogen® kit does not include sterile water, which is a necessary component of the injection. Patients should be sure to pick up sterile water at the pharmacy with their prescription of Thyrogen®. Pharmacies charge up to $10 for the water.
Click here to view information about provincial coverage of the costs of Thyrogen® (note: enter drug “Thyrogen” and DIN # 02246016)
Genzyme (the manufacturer of Thyrogen®) offers assistance and further information at: 1-800-745-4447 (options #2) or email@example.com
Low Iodine Diet
To ensure that absorption of the radioactive iodine is maximized, patients should reduce the dietary intake of iodine prior to the use of RAI. This can be achieved through a Low Iodine Diet (LID). To view information about the Low Iodine Diet, click here.
View Studies For More Details Regarding the Above
Are you a Candidate for RAI?
Intermediate risk patients improved overall survival with RAI http://www.thyroidcancercanada.org/userfiles/files/Ruel_Improved_Survival_with_RAI.pdf
(Sawka et al) Decision Aid for RAI study results 2012 http://www.thyroidcancercanada.org/userfiles/files/Decision_Aid_Sawka_July_2012.pdf
(Sawka et al) Decision Aid for RAI, description (2010) http://www.thyroidcancercanada.org/userfiles/files/Sawka_Decision_Aid_Study_Trials_Journal.pdf
Haymart et al: Disease Severity and Radioactive Iodine Use for Thyroid Cancer,J Clin Endocrin Metab, 2013 doi:10.1210/jc.2012-3160 http://www.thyroidcancercanada.org/userfiles/files/Regional_use_of_RAI_Haymart.pdf
Regional Differences in the Use of RAI in Canada, Sawka et al http://www.thyroidcancercanada.org/userfiles/files/RAI_Regional_Sawka.pdf
Clinicians' area of specialty effects their use of RAI http://www.thyroidcancercanada.org/userfiles/files/Clinicians_specialty_determines_RAI_Haymart.pdf
Haymart et al: Use of Radioactive Iodine for Thyroid Cancer, JAMA. 2011;306(7):721-728 Rise in the use of RAI in 1990-2008. http://www.thyroidcancercanada.org/userfiles/files/Haymart_Use_of_RAI_mid_1990s.pdf
Ma C. Tang L et al: rhTSH-aided low-activity versus high-activity regimens of radioiodine in residual ablation for differentiated thyroid cancer: a meta-analysis. Nuclear Medicine Communications. 34(12):1150-6, 2013 Dec. Small dose RAI leads to less negative after-effects than large dose RAI. http://www.ncbi.nlm.nih.gov/pubmed/24025918
Small treatment dose of RAI (30mci) is as effective as a large dose (100mci) and prep with Thyrogen is as effective as prep with withdrawal http://www.endocrinetoday.com/view.aspx?rid=89048
Less TC patients require RAI treatment http://www.thyroid.org/patients/ct/volume4/issue10/ct_patients_v410_8_9.html
Literature review of effectiveness of RAI (1966-2008) http://online.liebertpub.com/doi/pdfplus/10.1089/thy.2009.0455
The use of Dosimetry of RAI (testing which RAI dosage is required per patient in advance of the main treatment) may be very effective in selecting a high dose of treatment for those with distant metastases. http://www.thyroid.org/professionals/publications/clinthy/volume23/issue12/clinthy_v2312_6_7.pdf
Rate of TC patients receiving RAI went up form 1990-2008, and centres vary a great deal in their use of it http://www.thyroid.org/professionals/publications/clinthy/volume24/issue1/clinthy_v241_18_19.pdf
Use of RAI in Patients who had a Partial Thyroidectomy
Kiernan et al: Use of Radioiodine after Thyroid Lobectomy in Patients with Differentiated Thyroid
Cancer: Does It Change Outcomes? Journal of the American College of Surgeons (2015), doi: 10.1016/j.jamcollsurg.2014.12.014. link
Sabra et al, Higher Administered Activities of Radioactive Iodine Are Associated with Less Structural Persistent Response in Older, but Not Younger, Papillary Thyroid Cancer Patients with Lateral Neck Lymph Node Metastases, THYROID,Volume 24, Number 7, 2014 http://www.thyroidcancercanada.org/userfiles/files/Sabra_high_dose_RAI.pdf
Mallick et al: Ablation with Low-Dose Radioiodine and Thyrotropin Alfa in Thyroid Cancer, N Engl J Med 2012;366:1674-85. UK study indicates low dose of RAI is as effective in ablation as high dose http://www.thyroidcancercanada.org/userfiles/files/NEJM_HiLo_RAI_dose_study.pdf
Schlumberger et al: Strategies of Radioiodine Ablation in Patients with Low-Risk Thyroid Cancer, The New England Journal of Medicine, May 3, 2012 Vol. 366 no. 18 French study indicates 2 low doses of RAI as effective as a large dose http://www.thyroidcancercanada.org/userfiles/files/Schlumberger_NEJM_RAI.pdf
Editorial Opinion about the French study (Schlumberger et al), and UK study (Mallick et al.) http://www.thyroidcancercanada.org/userfiles/files/Low_Dose_RAI_Editorial_NEJM.pdf
Medical Post article about the above articles http://www.thyroidcancercanada.org/userfiles/files/Medical_Post_article_re_RAI_high_low.pdf
Clerc et al: Outpatient thyroid remnant ablation using repeated low I-131 iodine activites in patients with low-risk differentiated thyroid cancer. J Clin Endocrinol Metab 2012 http://www.thyroidcancercanada.org/userfiles/files/Low_Dose_RAI.pdf
Medication that improves uptake of RAI in patients who are RAI non-avid, and/or have aggressive disease http://www.healio.com/endocrinology/thyroid/news/online/%7B85D98828-EF5A-4632-A57D-766C76F8489D%7D/Selumetinib-increased-radioiodine-uptake-in-thyroid-cancer
Ho et al: Selumetinib-enhanced radioiodine uptake in advanced thyroid cancer. N Engl J Med 2013;368:623-32. doi: 10.1056/NEJMoa1209288 Selumetnib enhances the uptake of RAI in RAI non-avid patients, by re-differentiating the cancer. http://www.thyroidcancercanada.org/userfiles/files/Selumetinib_study.pdf
Smith et al: Reversible Cognitive, Motor, and Driving Impairments in Severe Hypothyroidism, Thyroid, Vol. 25, No. 1, January 2015: 28-36 link
Tu et al: Recombinant human thyrotropin-aided versus thyroid hormone withdrawal-aided radioiodine treatment for differentiated thyroid cancer after total thyroidectomy: A meta-analysis Radiotherapy & Oncology - January 2014 (Vol. 110, Issue 1, Pages 25-30) http://www.thegreenjournal.com/article/S0167-8140%2814%2900006-1/abstract
Valle et al: In thyroidectomized patients with thyroid cancer, a serum thyrotropin of 30 μU/mL after thyroxine withdrawal is not always adequate for detecting an elevated stimulated serum thyroglobulin. A hypothyroid prep that raises the TSH to 30 μU/mL (tested at less than 4 wks of withdrawal) may not be adequate to get the full level of stimulated Tg. The actual Tg level was more revealed at 80 μU/mL (more than 4 weeks of withdrawal). http://www.thyroidcancercanada.org/userfiles/files/Valle_30_TSH_not_always_enough.pdf
Zagar et al: Recombinant Human Thyrotropin-Aided Radioiodine Therapy in Patients with Metastatic Differentiated Thyroid Carcinoma, Journal of Thyroid Research, Volume 2012, Article ID 670180. Use of Thyrogen in patients with agressive disease. http://www.thyroidcancercanada.org/userfiles/files/Zagar_use_of_Thyrogen_late_stage_disease.pdf
Luster et al: rhTSH-aided radioiodine ablation and treatment of differentiated thyroid carcinoma: a comprehensive review, Endocrine-Related Cancer (2005) 12 49–64 http:www.thyroidcancercanada.org/userfiles/files/Luster_Thyrogen_study_2005.pdf
Klubo-Gwiezdzinska et al: Potential use of recombinant human thyrotropin in the treatment of distant metastases in patients with differentiated thyroid cancer. Study indicates Thyrogen as effective as hormone withdrawal for patients with distant metastases http://www.thyroidcancercanada.org/userfiles/files/Thyrogen_in_distant_mets.pdf
Withdrawal from L-T4 vs Thyrogen as a preparation for a scanning dose of RAI: http://www.thyroidcancercanada.org/userfiles/files/Withdrawal_vs_Thyrogen_Van_Nostrand.pdf
Prep with Thyrogen as effective as withdrawal (hypothyroid) prep for RAI, French study: http://www.thyroidcancercanada.org/userfiles/files/Schlumberger_NEJM_RAI.pdf
Low Dose RAI as effective as higher dose, UK study: http://www.thyroidcancercanada/userfiles/files/NEJM_HiLo_RAI_dose_study.pdf
Alexander & Larsen, EDITORIAL, Radioiodine for Thyroid Cancer - Is Less More? N ENGL J MED 366;18 NEJM.ORG MAY 3, 2012 Editorial comment regarding the above French & UK studies
Emmanouilidis et al: Long-Term Results after Treatment of Very Low-, Low-, and High-Risk Thyroid Cancers in a Combined Setting of Thyroidectomy and Radio Ablation Therapy in Euthyroidism, International Journal of Endocrinology, Volume 2013, Article ID 769473 A study indicating Thyrogen as effective as hypo prep, as finanical viable. http://www.thyroidcancercanada.org/userfiles/files/thyrogen_vs_hypo_study_2013.pdf
Prep with Thyrogen as effective as withdrawal (hypothyroid) prep for RAI, USA study: http://www.thyroidcancercanada.org/userfiles/files/Withdrawal_vs_Thyrogen_Tuttle.pdf
Withdrawal from L-T4 for a hypothyroid preparation for RAI is associated with clinical depression http://www.nytimes.com/2011/11/22/health/for-some-psychiatric-troubles-may-begin-with-the-thyroid.html?_r=2&emc=eta1
Yoo, J et al: Recombinant Humanized Thyroid Stimulating Hormone (rhTSH) Preparation Prior To Radioiodine Ablation in Patients Who Have Undergone Thyroidectomy for Papillary or Follicular Thyroid Cancer, A Quality Initiative of the Program in Evidence-Based Care (PEBC), Cancer Care Ontario (CCO), Report Date: May 14, 2007 Cancer Care Ontario study of Thyrogen (2007) http://www.thyroidcancercanada.org/userfiles/files/Thyrogen_CCO_2007.pdf
International Study of Thyrogen (2006) http://www.thyroidcancercanada.org/userfiles/files/Thyrogen_Pacini.pdf
Quality of Life Study, Hypo vs. Thyrogen prep http://www.ncbi.nlm.nih.gov/pubmed/19856258
Ain, Kenneth: Quantified Cognitive, Motor and Driving Impairments in Hypothyroidism and Their Reversibility, abstract given at ENDO June 2014 http://www.thyroidcancercanada.org/userfiles/files/Ain_Driving_ENDO.pdf
Watch short video describing Kenneth Ain study, above
Review 1 of Kenneth Ain study, above
Review 2 of Kenneth Ain study, above
Mernagh et al, Cost-Effectiveness of Using Recombinant Human Thyroid-Stimulating Hormone before Radioiodine Ablation for Thyroid Cancer: The Canadian Perspective 2009. Using Canadian data, study indicates with taking almost all into consideration (eg. loss of work time, etc.), cost of Thyrogen is $87 per kit. http://www.thyroidcancercanada.org/userfiles/files/Cost_Utility_Analysis_of_Thyrogen_vs__withdrawal_Canada.pdf
Wang et al, To Stimulate or Withdraw? A Cost-Utility Analysis of Recombinant Human Thyrotropin Versus Thyroid Withdrawal for Radioiodine Ablation in Patients with Low-Risk Differentiated Thyroid Cancer in the United States. Using American data, study looks at cost of Thyrogen with all taken into consideration (eg. loss of work time, etc.). http://www.thyroidcancercanada.org/userfiles/files/Cost_Utility_Analysis_of_Thyrogen_vs__withdrawal_USA.pdf
Mernagh et al, Cost-Effectiveness of Using Recombinant Human TSH prior to Radioiodine Ablation for Thyroid Cancer, Compared to Treating Patients in a Hypothyroid State: The German Perspective. Using German data, study indicates with taking almost all into consideration (eg. loss of work time, etc.), cost of Thyrogen is €47 per kit. http://www.thyroidcancercanada.org/userfiles/files/Cost_Utility_Analysis_of_Thyrogen_vs__withdrawal_Germany.pdf
Radiation Safety in the Treatment of Patients with Thyroid Diseases by Radioiodine 131I: Practice Recommendations of the American Thyroid Association The American Thyroid Association Taskforce on Radioiodine Safety. ATA Guidelines for post-RAI http://www.thyroidcancercanada.org/userfiles/files/ATA_Guidelines_RAI_safety.pdf
s it okay to use a hotel room for RAI isolation period? http://www.thyroidcancercanada.org/userfiles/files/RAI_release_guidance_NRC.pdf
ATA Radiation Safety Guidelines http://www.thyroidcancercanada.org/userfiles/files/ATA_Radiation_Safety_Guidelines.pdf
Possible salivary gland damage after-effect http://www.thyroidcancercanada.org/userfiles/files/RAI_salivary_gland_damage.pdf
Nasolacrimal Drainage System Obstruction http://www.thyroidcancercanada.org/userfiles/files/RAI_Tear_Duct_Kloss.pdf
RAI & Salivary Glands http://www.thyroidcancercanada.org/userfiles/files/RAI_SalivaryGlands_Mandel.pdf