What is the best approach to manage a patient with thyrotoxicosis?

Management of Thyrotoxicosis

Immediate Diagnostic Evaluation

The first step is to confirm thyrotoxicosis biochemically and determine its etiology, as management differs fundamentally between Graves' disease, toxic nodular disease, and thyroiditis. 1

• Measure TSH, free T4, and total T3 to confirm thyrotoxicosis (suppressed TSH with elevated thyroid hormones) 1
• Obtain TSH receptor antibodies (TRAb) or thyroid-stimulating immunoglobulin (TSI) to diagnose Graves' disease 2
• Consider radioactive iodine uptake scan (RAIUS) or Technetium-99m scan if the diagnosis remains unclear—high uptake indicates Graves' disease or toxic nodular disease, while low uptake suggests thyroiditis 2, 1
• Check thyroid peroxidase (TPO) antibodies when thyroiditis is suspected 2

Symptomatic Management for All Causes

Beta-blockers should be initiated immediately for symptomatic relief regardless of the underlying cause. 3, 1

• Non-selective beta-blockers with alpha receptor-blocking capacity are preferred for symptomatic patients 2
• Propranolol is particularly effective as it also blocks peripheral conversion of T4 to T3 3, 1
• Atenolol is an alternative for patients who cannot tolerate non-selective agents 4
• Beta-blockers control palpitations, tremor, anxiety, and heat intolerance within hours to days 3, 1

Definitive Treatment Based on Etiology

For Graves' Disease (Most Common Cause)

Antithyroid drugs, radioactive iodine, or surgery are the three definitive treatment options—the choice depends on disease severity, patient preference, and comorbidities. 5, 1

Antithyroid Drug Therapy

• Methimazole is the preferred antithyroid drug for most patients due to once-daily dosing, fewer side effects, and superior efficacy 6, 5, 1
• Start methimazole 10-30 mg daily depending on severity (higher doses for severe thyrotoxicosis) 5, 1
• Propylthiouracil should be reserved for first-trimester pregnancy, thyroid storm, or methimazole intolerance due to risk of severe hepatotoxicity 7, 5, 1
• Monitor thyroid function every 4-6 weeks initially, then every 2-3 months once euthyroid 6, 5, 1
• Treatment duration of 12-18 months is recommended before attempting discontinuation 5, 1
• Remission rates after antithyroid drug withdrawal are only 20-30% for short-term therapy and not substantially better with longer courses 8, 1
• Warn patients to report immediately any sore throat, fever, rash, or jaundice—these may indicate agranulocytosis or hepatotoxicity 6, 7

Radioactive Iodine (RAI)

• RAI is the most definitive treatment for Graves' disease and is preferred for patients who relapse after antithyroid drugs 5, 1
• RAI is contraindicated in pregnancy and breastfeeding 1
• Most patients become hypothyroid after RAI and require lifelong levothyroxine replacement 1
• Antithyroid drugs should be discontinued 3-7 days before RAI administration to allow adequate uptake 1

Surgery (Total or Near-Total Thyroidectomy)

• Surgery is preferred for patients with large goiters (>80 grams), compressive symptoms, or coexisting suspicious thyroid nodules 5, 1
• Patients must be rendered euthyroid before surgery using antithyroid drugs 5, 1
• Inorganic iodide (potassium iodide or Lugol's solution) should be added 7-10 days preoperatively to reduce thyroid vascularity 3, 1

For Thyroiditis (Including Immune Checkpoint Inhibitor-Induced)

Thyroiditis is self-limiting and requires only conservative management during the thyrotoxic phase. 2, 4

• Do not use antithyroid drugs for thyroiditis—they are ineffective because the thyroid is not actively producing excess hormone 2, 4
• Beta-blockers provide symptomatic relief during the thyrotoxic phase 2, 4
• The thyrotoxic phase typically lasts 1 month and is followed by hypothyroidism 2
• Monitor thyroid function every 2-3 weeks to detect transition to hypothyroidism 2
• Initiate levothyroxine when TSH becomes elevated and free T4 falls below normal 2
• Hypothyroidism after thyroiditis is usually permanent and requires lifelong thyroid hormone replacement 2

For Toxic Multinodular Goiter or Toxic Adenoma

Radioactive iodine or surgery are the only definitive treatments—antithyroid drugs provide only temporary control. 5, 1

• Antithyroid drugs can be used for initial stabilization but do not induce remission 5, 1
• RAI is preferred for elderly patients or those with surgical contraindications 1
• Surgery is preferred for large goiters, compressive symptoms, or when rapid definitive treatment is needed 1

Management of Thyroid Storm (Life-Threatening Emergency)

Thyroid storm requires immediate multi-drug therapy to prevent cardiovascular collapse and death. 3

• Propylthiouracil 500-1000 mg loading dose, then 250 mg every 4 hours (preferred over methimazole because it blocks peripheral T4 to T3 conversion) 3
• Inorganic iodide (potassium iodide or Lugol's solution) given 1 hour after antithyroid drug to block thyroid hormone release 3
• Propranolol 40-80 mg every 4-6 hours (or IV if patient cannot take oral medications) 3
• Hydrocortisone 100 mg IV every 8 hours to block peripheral conversion and treat potential relative adrenal insufficiency 3
• Aggressive supportive care including cooling, IV fluids, and treatment of precipitating factors 3

Special Populations

Pregnancy

• Propylthiouracil is preferred in the first trimester due to lower risk of congenital malformations compared to methimazole 7, 5, 1
• Switch to methimazole in the second and third trimesters to avoid maternal hepatotoxicity from PTU 6, 7, 1
• Use the lowest effective dose to maintain free T4 in the upper normal range 1
• RAI and surgery are contraindicated during pregnancy 1

Patients with Atrial Fibrillation

• Beta-blockers are essential for rate control in thyrotoxicosis-induced atrial fibrillation 2
• Anticoagulation should be based on CHA2DS2-VASc score, not solely on the presence of thyrotoxicosis 2
• Most patients revert to sinus rhythm once euthyroid is achieved 2

Immune Checkpoint Inhibitor Therapy

• Continue immunotherapy in most cases—thyroid dysfunction rarely requires treatment interruption 2
• Monitor TSH every 4-6 weeks for the first 3 months, then every second cycle 2
• Endocrinology consultation is recommended for all cases of thyrotoxicosis in patients on immune checkpoint inhibitors 2

Critical Pitfalls to Avoid

• Never start antithyroid drugs for thyroiditis—they are ineffective and delay recognition of the self-limiting nature of the condition 2, 4
• Never give iodide before antithyroid drugs in thyroid storm—iodide will worsen thyrotoxicosis if given first 3
• Never assume thyrotoxicosis is permanent—thyroiditis commonly transitions to hypothyroidism within weeks 2
• Never use methimazole in first-trimester pregnancy—it carries risk of congenital malformations including aplasia cutis and choanal atresia 6, 1
• Never perform surgery on an unprepared thyrotoxic patient—this can precipitate thyroid storm 5, 1
• In patients with suspected central hypothyroidism or adrenal insufficiency, always start corticosteroids before thyroid hormone to prevent adrenal crisis 2, 4

Monitoring During Treatment

• Check thyroid function (TSH, free T4, total T3) every 4-6 weeks during initial antithyroid drug therapy 6, 5, 1
• Monitor complete blood count and liver function at baseline and with any symptoms suggesting agranulocytosis or hepatotoxicity 6, 7
• Patients on antithyroid drugs must report immediately any sore throat, fever, rash, jaundice, or right upper quadrant pain 6, 7
• Once euthyroid, monitor thyroid function every 2-3 months during continued antithyroid drug therapy 5, 1