What is the appropriate management of hyperthyroidism in a non‑pregnant adult with mild‑to‑moderate disease in primary care?

Management of Hyperthyroidism in Primary Care

First-Line Treatment: Antithyroid Drugs

For non-pregnant adults with mild-to-moderate Graves' disease or toxic nodular goiter in primary care, initiate methimazole as first-line therapy while providing immediate symptomatic relief with beta-blockers. 1, 2

Initial Pharmacologic Management

Start methimazole 10-20 mg daily (depending on severity) as the preferred antithyroid drug due to superior efficacy and safety profile compared to propylthiouracil 1, 2. Propylthiouracil should be reserved only for patients intolerant to methimazole or during the first trimester of pregnancy, as it carries risk of severe hepatotoxicity including acute liver failure requiring transplantation 3.

Add beta-blocker therapy immediately for symptomatic control while awaiting thyroid hormone normalization 1:

• Atenolol 25-50 mg daily or propranolol for tachycardia, tremor, and anxiety 1
• Titrate to target heart rate <90 bpm if blood pressure tolerates 1
• Reduce beta-blocker dose once euthyroid state is achieved to avoid bradycardia 1

Monitoring Strategy During Initial Treatment

Monitor free T4 or free T3 every 2-4 weeks during the first 3 months to guide dose adjustments 1. The goal is to maintain free T4/T3 in the high-normal range using the lowest effective methimazole dose—not to normalize TSH, which may remain suppressed for months even after achieving euthyroidism 1.

Critical pitfall to avoid: Do not reduce methimazole based solely on suppressed TSH while free T4 remains elevated, as this leads to inadequate treatment and recurrent hyperthyroidism 1.

Treatment Duration and Long-Term Management

Continue methimazole for 12-18 months for Graves' disease, with the understanding that approximately 50% of patients will relapse after discontinuation 2, 4. For patients with persistently elevated TSH-receptor antibodies at 12-18 months, either continue methimazole for an additional 12 months or consider definitive therapy with radioactive iodine or thyroidectomy 2.

Long-term methimazole therapy (5-10 years) is feasible and associated with lower recurrence rates (15%) compared to short-term treatment (50%), making it a reasonable option for patients who prefer to avoid definitive therapy 4.

Critical Safety Monitoring

Agranulocytosis occurs in the first 3 months and presents with sore throat and fever 1. Instruct patients to:

• Stop methimazole immediately if fever or sore throat develops
• Obtain urgent CBC before restarting 1

Monitor for hepatotoxicity (especially with propylthiouracil): fever, nausea, vomiting, right upper quadrant pain, dark urine, jaundice—discontinue drug immediately if suspected 1.

Watch for vasculitis (life-threatening): skin changes, hematuria, respiratory symptoms 1.

Definitive Treatment Options

When to Refer for Radioactive Iodine or Surgery

Definitive treatment is recommended for patients who relapse after completing a course of antithyroid drugs 2. However, continued long-term low-dose methimazole can be considered as an alternative 2.

Radioactive iodine (I-131) ablation is increasingly used as first-line therapy and is well-tolerated, with the main long-term consequence being hypothyroidism 5, 6. It is absolutely contraindicated in pregnancy and breastfeeding, and pregnancy must be avoided for 4 months following administration 1, 5. RAI may worsen Graves' ophthalmopathy—it is contraindicated in active/severe orbitopathy, and steroid prophylaxis is warranted in mild/active orbitopathy 2.

Thyroidectomy should be performed by an experienced high-volume thyroid surgeon and is indicated when 2, 7:

• Radioactive iodine is refused or contraindicated
• Large goiter causes compressive symptoms
• Patient preference for definitive cure
• Recent evidence shows thyroidectomy is very effective and safe, and can be performed as an outpatient procedure 7

Toxic Nodular Goiter

Radioactive iodine or thyroidectomy is the treatment of choice for toxic nodular goiter, as antithyroid drugs will not cure this condition 1, 5. Radiofrequency ablation is rarely used 4.

Special Populations and Scenarios

Subclinical Hyperthyroidism

For TSH <0.1 mIU/L, treatment should be considered particularly for 1:

• Patients older than 60 years (3-fold increased risk of atrial fibrillation over 10 years) 1
• Those with cardiac disease, osteopenia, or osteoporosis risk 1
• Estrogen-deficient women (bone loss risk) 1

For TSH 0.1-0.45 mIU/L, routine treatment is not recommended due to insufficient evidence of adverse outcomes, though elderly patients with cardiovascular risk factors may warrant consideration 1.

Destructive Thyroiditis

Thyroiditis is self-limited and requires different management than Graves' disease 1:

• Beta-blockers for symptomatic relief during the hyperthyroid phase 1
• Antithyroid drugs are NOT indicated (no autonomous hormone production) 1
• Monitor with symptom evaluation and free T4 testing every 2 weeks 1
• Introduce levothyroxine if the patient becomes hypothyroid (low free T4/T3, even if TSH not yet elevated) 1

Cardiovascular Comorbidities

Beta-blockers are recommended for rate control in hyperthyroid patients with atrial fibrillation (occurs in 5-15% of hyperthyroid patients, more frequently in those over 60 years) 1. When beta-blockers cannot be used, non-dihydropyridine calcium channel antagonists (diltiazem or verapamil) are alternatives 1.

If rhythm control strategy is selected, thyroid function must be normalized prior to cardioversion to reduce risk of recurrence—antiarrhythmic drugs and cardioversion are generally unsuccessful while thyrotoxicosis persists 1.

Anticoagulation should be guided by CHA₂DS₂-VASc risk factors, not solely by presence of hyperthyroidism 1.

Diagnostic Confirmation Before Treatment

Biochemical confirmation requires low TSH with elevated free T4 or free T3 1, 6. For nosological diagnosis (determining the cause), helpful tools include 4:

• TSH-receptor antibodies (positive in Graves' disease)
• Thyroid peroxidase antibodies
• Thyroid ultrasonography
• Scintigraphy (if thyroid nodules present or etiology unclear) 6

Common Pitfalls to Avoid

• Never attempt cardioversion in thyrotoxic patients without first achieving euthyroid state 1
• Do not monitor TSH alone during initial methimazole treatment—use free T4/T3 to guide dose adjustments 1
• Do not overlook agranulocytosis risk in the first 3 months of thioamide therapy 1
• Avoid propylthiouracil except in first trimester pregnancy or methimazole intolerance due to severe hepatotoxicity risk 3
• Remember to reduce beta-blocker dose once euthyroid to avoid bradycardia 1