Treatment for Toxic Multinodular Goiter
For toxic multinodular goiter, radioactive iodine (RAI) therapy or thyroidectomy are the definitive treatment options, with antithyroid drugs (methimazole or propylthiouracil) serving only as temporary measures to control hyperthyroidism before definitive therapy or in patients who cannot tolerate other treatments. 1, 2
Treatment Algorithm
First-Line Definitive Therapy
Choose between RAI and surgery based on these specific criteria:
Surgery is preferred when: 3, 4
- Compressive symptoms are present (dyspnea, dysphagia, dysphonia, orthopnea)
- Thyroid volume exceeds 100-130 grams
- Substernal extension exists (RAI is less effective in this setting)
- Patient desires immediate, permanent cure with no recurrence risk
- Suspicious nodules require evaluation (occult malignancy found in 2-3% of specimens)
RAI therapy is preferred when: 4, 5
- No compressive symptoms exist
- Patient has significant surgical comorbidities
- Thyroid volume is moderate (<100 grams)
- Patient refuses surgery
RAI Therapy Specifics
- Administer 200 μCi per gram of thyroid tissue (corrected to 100% 24-hour uptake)
- Single dose cures 78-92% of patients
- Typical doses range 25-30 mCi for moderate goiters, 50-100 mCi for larger glands
- Median thyroid volume reduction of 43% occurs by 24 months post-treatment
- 92% cure rate achieved with 1-2 treatments
Important RAI considerations: 5
- Hypothyroidism develops in 14% within 5 years (6% without antithyroid pretreatment, 20% with pretreatment)
- Antithyroid drug pretreatment increases hypothyroidism risk and should be avoided when possible
- For large goiters (>100g), multiple doses are often required
Surgical Approach
- Total thyroidectomy now preferred over subtotal thyroidectomy
- Provides immediate, permanent cure with zero recurrence
- Permanent hypocalcemia occurs in 1.1-3% of patients
- Complication rates are volume-dependent: 4.3% with high-volume surgeons (>100 cases/year) vs 4-fold higher with low-volume surgeons (<10 cases/year)
- Refer to high-volume thyroid surgeons
Antithyroid Drug Therapy
Methimazole or propylthiouracil are FDA-approved but only for specific situations: 1, 2, 7
Indications for antithyroid drugs:
- Temporary control before definitive therapy (surgery or RAI)
- Patients intolerant of both surgery and RAI
- Patient refusal of definitive therapy
Do NOT use antithyroid drugs expecting remission 8—toxic multinodular goiter represents autonomous function, not autoimmune disease like Graves', so remission does not occur
Long-term methimazole data: 7
- 96.2% remained euthyroid on 4.1-6.3 mg daily for 60-100 months
- Adverse effects occurred only in first 3 months (elevated liver enzymes, skin reactions)
- Not inferior to RAI in maintaining euthyroidism, but does not cure the underlying disease
Propylthiouracil warnings: 2
- Reserved for methimazole-intolerant patients only
- Black box warning for severe liver problems, liver failure, and death
- Can cause serious risks during pregnancy including fetal harm and maternal/infant death
- Low white blood cell counts can be life-threatening
- Risk of vasculitis affecting skin, kidneys, or lungs
Alternative Therapies
Laser ablation followed by RAI: 9
- Consider for patients refusing surgery with very large nodules
- Laser ablation shrinks nodules first, then lower RAI dose completes treatment
- Level III evidence supports ethanol ablation for patients unfit for surgery 4
Common Pitfalls to Avoid
- Never use prolonged antithyroid drugs as definitive therapy 8—this is not Graves' disease and will not remit
- Do not assume "hot" nodules are benign 8—always evaluate suspicious ultrasound features with FNA regardless of functional status
- Avoid antithyroid drug pretreatment before RAI when possible 5—it increases hypothyroidism risk from 6% to 20%
- Do not use RAI as first-line for large goiters with compressive symptoms 3, 4—surgery provides superior symptom relief and definitive decompression