Radioactive Iodine

Radioactive iodine (iodine-131) is an oral radiopharmaceutical that destroys thyroid tissue. It is a main definitive therapy for Graves' disease and toxic nodular goitre where surgery is unsuitable or refused, and it ablates thyroid remnants and treats metastatic disease after thyroidectomy for differentiated thyroid cancer. Hypothyroidism is the usual outcome in Graves' disease and needs lifelong levothyroxine. It requires radiation safety facilities and specialist nuclear medicine supervision.

Classification. Radioactive iodine isotope (I-131); beta and gamma emitter. Oral capsules or solution, activity measured in megabecquerels (MBq) or millicuries (mCi); 37 MBq equals 1 mCi.

Mechanism. Taken up by thyroid follicular cells through the sodium iodide symporter, where beta emission (range about 2 mm) destroys follicular cells over weeks to months while sparing surrounding tissue.

Pharmacodynamics. Thyroid hormone levels begin to fall at 2 to 4 weeks; hyperthyroidism resolves over 1 to 3 months; hypothyroidism develops at 2 to 6 months in most patients with Graves' disease.

Pharmacokinetics. Absorbed within an hour; concentrated in the thyroid (uptake 10 to 80%); effective half-life in the body about 5 to 6 days in hyperthyroidism and about 8 days physical half-life. The remainder is excreted in urine, with smaller amounts in saliva, sweat, faeces and breast milk.

Graves' disease and toxic nodular goitre (adults).

• A fixed activity of about 370 to 555 MBq (10 to 15 mCi), or a calculated activity aiming for 100 to 150 microcuries/g of thyroid tissue corrected for uptake (usual range 185 to 740 MBq). Toxic nodular disease and larger goitres need higher activities (about 555 to 1110 MBq).
• Before treatment, give a thionamide to reach a euthyroid state in the elderly, in cardiac disease and in severe thyrotoxicosis; stop the thionamide 5 to 7 days beforehand and restart 3 to 7 days after, stopping again when free T4 is normal. Give a beta-blocker for symptom control.
• Repeat after 6 months if hyperthyroidism persists.

Differentiated thyroid cancer, remnant ablation (specialist).

• 1110 to 3700 MBq (30 to 100 mCi) after thyroidectomy, with TSH raised either by 4 to 6 weeks of levothyroxine withdrawal or by recombinant human TSH; higher activity for metastatic disease, 3700 to 7400 MBq (100 to 200 mCi) in repeated courses. A low-iodine diet for 1 to 2 weeks before treatment.

Children.

• Used rarely and only by specialist teams; avoid in those under 5 years because of higher cancer risk.

Adjustments.

• Kidney: delayed clearance in severe impairment; adjust activity and arrange dialysis timing with the specialist team.
• Liver: no change.
• Older adults: higher risk of cardiac events; make euthyroid first.
• Weight: activity is based on thyroid size and uptake rather than weight.

Contraindications. Pregnancy (confirmed or possible); breastfeeding (unless stopped at least 6 weeks before treatment and not resumed for that child); inability to follow radiation safety instructions; severe active thyroid eye disease (relative, steroid cover advised).

Serious adverse effects.

• Hypothyroidism, common in Graves' disease and the aim of treatment.
• Worsening of thyroid eye disease (new or worse in about 15% of smokers); prednisolone 0.3 to 0.5 mg/kg daily from 1 to 3 days after treatment, tapered over 3 months, is given to those at risk.
• Radiation thyroiditis with pain and a transient rise in hormone, risking thyroid storm in severe disease.
• Sialadenitis with dry mouth and loss of taste after high activities; nausea; rare second cancers and bone marrow suppression at cumulative high doses.
• Transient fertility effects: advise pregnancy avoidance for 6 to 12 months and avoidance of conception by male patients for 4 to 6 months.

Major interactions.

• Iodine-containing contrast, amiodarone, potassium iodide and kelp preparations: reduce uptake; avoid for weeks.
• Thionamides: reduce efficacy if continued; stop 5 to 7 days beforehand.
• Levothyroxine and liothyronine: withdrawn before cancer ablation to raise TSH.

Special groups.

• Pregnancy: absolute contraindication; test for pregnancy within 72 hours before the dose.
• Breastfeeding: stop at least 6 weeks before, and do not resume for that child after treatment.
• Children: avoid in the very young; specialist only.
• Older adults: pretreat with a thionamide; monitor for arrhythmia.
• Kidney impairment: delayed excretion; liver impairment: no change.
• East Africa: access is limited to a few nuclear medicine centres, and waiting lists are long; surgery and long-term thionamides are common alternatives. Written radiation safety advice must be given in the patient's language.

Formulation and administration. One oral dose swallowed with water in a nuclear medicine unit. Fast for 2 to 4 hours before and 1 to 2 hours after.

Radiation safety advice for 1 to 3 weeks after:

• keep an arm's length from others;
• avoid close contact with children and pregnant women for 5 to 21 days (longer after higher activity);
• sleep apart from partners and use separate utensils;
• flush the toilet twice and wash hands;
• drink fluids and suck sour sweets to protect salivary glands.

Baseline. Free T4, TSH, thyroid uptake and scan, pregnancy test, full blood count, kidney function, eye assessment.

Monitoring.

• Free T4 and TSH at 4 to 6 weeks, then every 4 to 8 weeks until stable.
• Start levothyroxine at hypothyroidism, not before; check TSH 6 to 8 weeks after each change, then annually for life.
• After cancer ablation: whole-body scan at 3 to 7 days after treatment, thyroglobulin and neck ultrasound at 6 to 12 months.

Dose reduction and stopping. A single treatment. Repeat treatment is directed by the specialist, with total cumulative activity tracked.

Referral and escalation. All treatment is specialist. Refer urgently for worsening thyroid eye disease, thyroid storm symptoms, or neck swelling with airway compromise after treatment.