What is the recommended initial management of toxic multinodular goitre?

Management of Toxic Multinodular Goitre

Initiate methimazole immediately to control hyperthyroidism while preparing for definitive therapy with either radioactive iodine or total thyroidectomy, as medical management alone is not curative and serves only as bridge therapy. 1, 2

Initial Medical Stabilization

• Start methimazole as first-line antithyroid drug to achieve euthyroid state before definitive treatment, monitoring complete blood count in the first 3 months for agranulocytosis 1, 2
• Measure free T3 and free T4 to determine hyperthyroidism severity, as toxic multinodular goiter may present with T3 thyrotoxicosis even when T4 is normal 1
• Avoid propylthiouracil unless methimazole is contraindicated, as methimazole has superior safety profile and once-daily dosing 2
• In elderly patients, prioritize rapid control of hyperthyroidism to prevent cardiac complications, particularly atrial fibrillation 1

Diagnostic Workup Before Definitive Treatment

• Obtain radionuclide uptake scan using I-123 (preferred over I-131) to confirm multiple hyperfunctioning nodules and verify the entire goiter consists of thyroid tissue 3, 1
• Perform high-resolution ultrasound to document nodule characteristics and compare with radionuclide scan to identify any hypofunctioning or isofunctioning nodules requiring fine-needle aspiration biopsy 3, 1
• If compressive symptoms are present (dyspnea, dysphagia, dysphonia), obtain CT neck without contrast to evaluate substernal extension and quantify tracheal compression 3, 1
• Do not use Doppler ultrasound alone to differentiate thyrotoxicosis causes—radionuclide uptake study directly measures thyroid activity rather than inferring it from blood flow 3

Definitive Treatment Selection Algorithm

Choose surgery (total or near-total thyroidectomy) if:

• Large goiter with compressive symptoms documented on CT scan 1, 4, 5
• Substernal extension confirmed on imaging 3, 1
• Suspicious nodules on ultrasound requiring histological evaluation 1, 6
• Young patient with long life expectancy who desires rapid, definitive cure 1, 4
• Previous neck surgery or radiation making future intervention risky 1
• Patient preference to avoid radioactive iodine 5

Choose radioactive iodine (I-131) if:

• Elderly patient or significant surgical comorbidities precluding safe anesthesia 1, 4, 5
• Smaller goiter without significant compressive symptoms 1, 7
• Patient refusal of surgery 7, 8
• Recurrent hyperthyroidism following previous thyroid surgery 4

Critical caveat: Avoid iodinated contrast agents before radioactive iodine therapy, as they interfere with iodine uptake and reduce treatment efficacy 1

Comparative Effectiveness of Definitive Therapies

• Surgery achieves prompt control of hyperthyroidism and removes the goiter in a single intervention, with complications (laryngeal nerve palsy, hypoparathyroidism) occurring in <1-2% when performed by expert surgeons 1, 4, 5
• Radioactive iodine requires 3-6 months to achieve euthyroid state and may necessitate multiple doses for large goiters, but avoids surgical risks 4, 7, 5
• Large goiters with autonomously functioning nodules become euthyroid more quickly following surgery compared to radioactive iodine 5

Alternative Therapy for Select Patients

• Consider thermal ablation (radiofrequency or laser) followed by radioactive iodine for patients who refuse surgery but have large nodules that would require prohibitively high I-131 doses 8
• This combined approach (laser ablation to shrink nodules, then I-131 to ablate residual tissue) represents a valid alternative when surgery is declined, even for large coexistent hot nodules 8
• Percutaneous ethanol injection is effective for selected toxic autonomously functioning adenomas but less applicable to multinodular disease 7

Post-Treatment Management

After radioactive iodine:

• Monitor thyroid function tests every 4-6 weeks initially, then every 3-6 months 1
• Initiate levothyroxine replacement when hypothyroidism develops, which occurs in the majority of patients 1, 7
• Continue methimazole for 3-6 months post-I-131 if hyperthyroidism persists 7

After total thyroidectomy:

• Initiate levothyroxine replacement immediately postoperatively at full replacement dose (1.6 mcg/kg/day) 1
• Monitor serum calcium levels for 48-72 hours to detect hypoparathyroidism 1
• Check TSH at 6-8 weeks to adjust levothyroxine dose to maintain TSH in normal range (not suppressed, as C cells lack TSH receptors) 3, 1

Critical Pitfalls to Avoid

• Do not delay definitive treatment in elderly patients—cardiac complications from prolonged hyperthyroidism carry significant morbidity and mortality 1, 6
• Do not use levothyroxine suppression therapy in toxic multinodular goiter, as these patients already have suppressed TSH and exogenous thyroid hormone worsens thyrotoxicosis 6, 5
• Do not rely on long-term antithyroid drug therapy as definitive treatment, as it rarely controls toxic multinodular goiter permanently and requires indefinite medication with monitoring 4, 7
• Do not administer radioactive iodine without first achieving euthyroid state with methimazole, as acute thyroid hormone release can precipitate thyroid storm 7