What is the treatment approach for a patient with hyperthyroidism, characterized by low Thyroid-Stimulating Hormone (TSH) and high free Thyroxine (T4) levels?

Treatment of Hyperthyroidism (Low TSH, High Free T4)

For patients with biochemically confirmed hyperthyroidism (suppressed TSH with elevated free T4), treatment should be initiated with antithyroid drugs as first-line therapy, specifically methimazole in most cases, while simultaneously determining the underlying etiology through TSH-receptor antibodies and thyroid imaging to guide definitive management. 1, 2

Immediate Diagnostic Confirmation and Etiology

• Confirm hyperthyroidism biochemically with suppressed TSH (<0.1 mIU/L) and elevated free T4 and/or T3 levels before initiating treatment 1, 2
• Measure TSH-receptor antibodies (TRAb) to identify Graves' disease, which accounts for 70% of hyperthyroidism cases 1
• Obtain thyroid ultrasonography to evaluate for toxic nodular disease (16% of cases) or thyroiditis (3% of cases) 1
• Perform thyroid scintigraphy if nodules are present or the etiology remains unclear after initial testing 2
• Review medication history for drug-induced causes including amiodarone, tyrosine kinase inhibitors, and immune checkpoint inhibitors (9% of cases) 1

First-Line Medical Management

Antithyroid Drugs (Preferred Initial Treatment)

• Initiate methimazole as the preferred antithyroid drug for most patients with Graves' disease or toxic nodular disease 1, 2
• Start propylthiouracil only in specific circumstances: first trimester of pregnancy, methimazole allergy, or thyroid storm 3
• For propylthiouracil dosing: initiate 300 mg daily in divided doses every 8 hours for adults; increase to 400 mg daily for severe hyperthyroidism or very large goiters 3
• Maintenance dose of propylthiouracil is typically 100-150 mg daily once euthyroid state is achieved 3

Beta-Adrenergic Blockade for Symptom Control

• Add beta-blockers for symptomatic relief of palpitations, tremor, anxiety, and tachycardia regardless of underlying etiology 1, 4
• Note that beta-blocker dose may need reduction as the patient becomes euthyroid due to decreased clearance 3

Monitoring During Antithyroid Drug Therapy

• Monitor thyroid function tests periodically during treatment to assess response 3
• Once clinical hyperthyroidism resolves and TSH becomes elevated, reduce the antithyroid drug dose to prevent iatrogenic hypothyroidism 3
• Obtain white blood cell count with differential if patient develops sore throat, fever, skin eruptions, or general malaise to detect agranulocytosis 3
• Monitor liver function tests (bilirubin, alkaline phosphatase, ALT/AST) if symptoms of hepatic dysfunction develop, particularly within the first 6 months 3
• Check prothrombin time before surgical procedures due to potential vitamin K inhibition by propylthiouracil 3

Definitive Treatment Options Based on Etiology

Graves' Disease

• Continue antithyroid drugs for 12-18 months as initial course, though recurrence occurs in approximately 50% of patients 1
• Consider long-term antithyroid drug therapy (5-10 years) which reduces recurrence to 15% compared to 50% with short-term treatment 1
• Identify high-risk patients for recurrence: age <40 years, FT4 ≥40 pmol/L, TSH-binding inhibitory immunoglobulins >6 U/L, or goiter size ≥WHO grade 2 1
• Offer radioactive iodine (¹³¹I) ablation or thyroidectomy for patients with recurrent disease or those preferring definitive treatment 1, 2

Toxic Nodular Goitre

• Treat with radioactive iodine (¹³¹I) or thyroidectomy as primary definitive therapy 1, 4
• Surgery is the preferred treatment for toxic adenoma and toxic multinodular goitre 4
• Radiofrequency ablation may be considered in select cases 1

Destructive Thyrotoxicosis (Thyroiditis)

• Observe with supportive care only, as this condition is usually mild and transient 1, 2
• Reserve corticosteroids for severe cases only 1
• Do not use antithyroid drugs, as there is no increased hormone synthesis—only hormone leakage 4

Critical Safety Considerations and Pitfalls

• Never use propylthiouracil as first-line in pediatric patients due to severe hepatotoxicity risk including hepatic failure requiring transplantation or resulting in death 3
• Propylthiouracil may be preferred during first trimester of pregnancy due to methimazole's association with rare fetal abnormalities, but switch to methimazole for second and third trimesters given maternal hepatotoxicity risk 3
• Monitor for vasculitis symptoms (new rash, hematuria, decreased urine output, dyspnea, hemoptysis) as severe complications and death have occurred with propylthiouracil 3
• Adjust doses of concurrent medications as patient becomes euthyroid: reduce beta-blockers, digitalis glycosides, and theophylline due to altered clearance 3
• Increase monitoring of oral anticoagulants (warfarin) due to potential enhanced anticoagulant effect from vitamin K inhibition 3

Treatment for Subclinical Hyperthyroidism

• Treat patients at highest risk: those >65 years old or with persistent TSH <0.1 mIU/L due to increased risk of osteoporosis and cardiovascular disease 2
• Treatment is typically not recommended for TSH levels between 0.1-0.45 mIU/L unless thyroiditis is excluded as the cause 5
• Treatment is generally recommended for undetectable TSH or TSH <0.1 mIU/L, particularly with overt Graves' disease or nodular thyroid disease 5

Prognosis and Long-Term Outcomes

• Untreated hyperthyroidism is associated with increased mortality, cardiac arrhythmias, heart failure, osteoporosis, and adverse pregnancy outcomes 2
• Prognosis improves with rapid and sustained control of hyperthyroidism 1
• Treatment choices should be individualized based on etiology, patient age, pregnancy status, comorbidities, and patient preference for definitive versus medical management 2