Continuing Education Activity

Radioactive iodine therapy is used in the management and treatment of hyperthyroidism. This activity describes the indications, actions, and contraindications of radioactive iodine therapy as a valuable agent in the treatment of hyperthyroidism. This activity will highlight the mechanism of action, adverse event profile, and other key factors pertinent to members of the interprofessional team in the treatment of patients with hyperthyroidism.

Objectives:

• Identify the mechanism of action of radioactive iodine therapy.
• Describe the potential adverse effects involved with radioactive iodine therapy.
• Review the appropriate monitoring for patients receiving iodine therapy.
• Outline some interprofessional team strategies for improving care coordination and communication to advance radioactive iodine therapy and improve outcomes.

Indications

Radioactive iodine (iodine-131) therapy is indicated for the management of hyperfunctioning thyroid disease and thyroid cancer.[1][2] It is classified as radioactive nuclear medicine and was first synthesized in 1941, and the FDA approved it in 1971 for its therapeutic use. Its action causes permanent destruction to the thyroid tissue by emitting radiation of two sorts, gamma and beta rays.[3][4] Gamma radiation effects are more useful for diagnostic purposes, whereas beta radiation effects are therapeutic.[4] Its action is dependant on the uptake of iodine from thyroid tissue and is ineffective in patients who have a hyperfunctioning disease without iodine uptake. It is indicated in patients with high surgical risk and decreased life expectancy or patients who have failed to obtain a euthyroid state or can not tolerate oral anti-thyroid agents. Radioactive iodine therapy may be administered as adjuvant therapy to surgery in patients with thyroid carcinoma and may be given four to six weeks of post-surgery.[5]

FDA Approved

• Graves disease
• Toxic adenoma
• Toxic multinodular goiter
• Non-toxic multinodular goiter
• Well-differentiated thyroid carcinoma

Radioactive iodine diagnostic use can differentiate between the different hyper or hypo-functioning thyroid diseases. This differentiation occurs by measuring the uptake of radioactive iodine in the thyroid after 24-hours.[6]

Increased RAIU[7]

• Graves disease
• Toxic multinodular goiter
• Thyroid adenoma 

Decreased RAIU[7]

• Subacute thyroiditis
• Painless thyroiditis
• Iodine-induced hyperthyroidism
• Factitious hyperthyroidism

Mechanism of Action

Iodine is a natural precursor for thyroid hormones triiodothyronine (T3) and thyroxine (T4) and is uptaken from the blood into the thyroid follicular cell by the sodium and iodide transporter. Similarly, radioactive iodine (RAI) exerts its effects once it is taken up by the follicular cells of the thyroid, emitting beta rays that further cause definitive local damage to the thyroid tissue.[8][9]

Administration

Iodine-131 is available as[4]:

• Oral gelatine capsules
• Oral drinking solution
• Intravenous injections

Hyperthyroid dosage

• 148 to 370 MBq

Thyroid carcinoma dosage

• 3700 to 5550 MBq

Medications contradicted before therapy:

• Antithyroid medication (propylthiouracil, methimazole)
• Amiodarone
• Contrast agents

During radioactive iodine therapy, agents containing iodine can hinder its uptake from the transporter of thyroid cells, as iodine is a natural precursor for thyroid hormones. All patients should be on an iodine-free diet for seven days and longer for patients receiving therapy for thyroid carcinoma.[8] Although contraindicated, treatment with antithyroid agent methimazole (MTZ) may be initiated before radioactive iodine therapy in select patients with severe hyperfunctioning thyroid disease or cardiac disease. Transient thyrotoxicosis may transpire shortly following radioactive iodine therapy due to the leakage of stored triiodothyronine (T3) and thyroxine (T4).[8][7] Thionomide therapy may decrease any storage of thyroid hormones and ensure a euthyroid state to prevent possible complications of thyrotoxicosis.[8] Methimazole is preferred over propylthiouracil(PTU) as it has a significant failure rate.[6] If a patient receives ethionamide, the recommendation is to discontinue it three to five days before radioactive iodine therapy.[6] 

Adverse Effects

Adverse effects range from mild to severe, depending on the dose administered.

Early Complications[2][5]

• Nausea
• Vomiting
• Chest Pain
• Pruritis
• Hives
• Anemia
• Leukopenia
• Thrombocytopenia
• Teratogenicity
• Bone marrow suppression
• Radiation thyroiditis
• Sialadenitis/xerostomia
• Gonadal damage/Infertility
• Dry eye
• Nasolacrimal duct obstruction
• Transient thyrotoxicosis
• Pulmonary fibrosis
• Brain edema

Late Complications[2]

• Bone marrow depression
• Leukemia
• Stomach Cancer
• Bladder Cancer
• Breast Cancer
• Pulmonary fibrosis
• Permanent bone marrow suppression
• Genetic effects
• Hypothyroidism

The recommendation for patients who have preexisting ophthalmopathy is to have treatment with oral prednisone therapy to prevent exacerbations. Treatment can be started a few days after RAI therapy and should continue for 1 to 3 months.[6][10] The damage to thyroid tissue during radioactive iodine therapy can release thyroid antigens, which may travel to the TSH autoantibodies located in the orbital, causing inflammatory and osmotic effects.[11] Treatment with RAI may predispose patients to permanent hypothyroidism as it causes definitive destruction of thyroid tissue. Patients may require lifelong thyroxine therapy.[7]

Contraindications

Radioactive iodine therapy (RAI) is contraindicated in the following:

• Pregnancy
• Breastfeeding
• Carcinoma with no iodine uptake
• Graves ophthalmopathy (moderate to severe)
• Severe thyrotoxicosis
• Vomiting
• Diarrhea

The radioactive substance can pass through the placenta and may cause definitive thyroid damage and irreversible mental retardation to the developing fetus. Contraceptive use is a strong recommendation to females of childbearing age who are planning radioactive iodine therapy. A negative pregnancy test should be a consideration before initiating therapy as pregnancy and breastfeeding are absolute contraindications.[7][10]

Monitoring

Monitoring and routine checkups are lifelong for patients following RAI therapy. Thyroid function tests are to be observed every 4-6 weeks for six months until the patient achieves a euthyroid or hypothyroid state. Free Thyroxine levels should be monitored routinely after treatment, as TSH levels can remain low for an extended duration despite the patient being clinically euthyroid. TFT can be monitored at six to twelve-month periods after achieving the treatment outcome. If treatment failure is suspected, and the patient is still in a hyperthyroid state six months post-therapy, the clinician may reconsider RAI retreatment.[6]

Toxicity

• Radiation-induced toxicity
• Hypersensitivity reactions
• Radiation-induced thyroiditis

Potassium iodide(KI) effectively blocks radioactive iodine uptake in the thyroid and can be helpful during toxicity.[12][13] RAI, once administered, has rapid absorption through the gastrointestinal tract and is spread to the thyroidal tissue via the bloodstream. RAI excretion is mainly within the kidneys. Patients with renal dysfunction are at risk of decreased clearance and increased levels of RAI and toxicity.[14] Precautions should be advised to patients post-RAI therapy, as radiation may be harmful around others. Clinical staff must particularly take measures to avoid contact and exposure around women during pregnancy and children.[6]

Enhancing Healthcare Team Outcomes

Radioactive iodine therapy(RAI) is a nuclear agent that is FDA-approved and indicated for hyperfunctioning thyroid disease and thyroid carcinoma. This agent's use should be under the management under the supervision of an interprofessional team, including an endocrinologist, a primary care clinician, nurses, and pharmacists. Thorough follow-up and communication between the primary care clinician and specialists are vital to monitor free T4 and TSH levels to gauge the success or complications of treatment. Providers involved in the patients' direct care, such as nurses, should be familiar with the clinical signs and symptoms of treatment complications such as thyroid storm, ophthalmopathy, and transient hypothyroidism. Consultation with an ophthalmologist may be necessary for patients suffering from thyroid-associated orbitopathy.

Counseling and discontinuation of treatment are strongly advised during pregnancy. A negative pregnancy test should be considered before therapy, as radioactive iodine can readily cross the placenta and be taken up by the fetus, further causing irreversible damage. Select patients should be educated on pre-treatment if needed, and all patients should receive counsel about iodine restriction before therapy. Patients should receive clear instructions regarding radiation toxicity and avoidance of household contacts, pregnant women, and children. The interprofessional team should also counsel patients on the adverse effects of therapy, and the early and late complications that may arise, and the severity of the complications.