In an adult non‑pregnant patient with a suppressed TSH (<0.005 µIU/mL) and markedly elevated free T4 (>100 pmol/L), what initial medications should be started?

Immediate Antithyroid Drug Therapy Required for Severe Thyrotoxicosis

Start propylthiouracil (PTU) 200–300 mg orally every 6–8 hours immediately, or methimazole 20–30 mg orally once daily if PTU is unavailable or contraindicated. This patient presents with severe overt hyperthyroidism (TSH <0.005 µIU/mL with markedly elevated free T4 >100 pmol/L), requiring urgent antithyroid drug therapy to prevent life-threatening complications including thyroid storm, atrial fibrillation, and cardiovascular collapse 1.

Initial Medication Selection and Dosing

Propylthiouracil (Preferred for Severe Cases)

• Start PTU 200–300 mg orally every 6–8 hours (total daily dose 600–900 mg divided into 3–4 doses) for severe hyperthyroidism with very large goiters 1
• PTU has the advantage of blocking peripheral conversion of T4 to T3, providing faster symptomatic relief in severe thyrotoxicosis 2, 3
• The usual maintenance dose after initial control is 100–150 mg daily, but this patient requires maximal initial dosing 1

Methimazole (Alternative Option)

• Start methimazole 30–40 mg orally once daily if PTU is unavailable or if the patient has contraindications to PTU 2, 3
• Methimazole is generally preferred for long-term management due to once-daily dosing, lower cost, and fewer major side effects, but PTU may be superior in acute severe thyrotoxicosis 2
• Methimazole can be given as a single daily dose, improving adherence 2

Critical Safety Monitoring

Immediate Laboratory Surveillance

• Obtain baseline complete blood count (CBC) with differential, comprehensive metabolic panel including liver function tests (ALT, AST, bilirubin, alkaline phosphatase), and prothrombin time before initiating therapy 1
• Recheck thyroid function tests (TSH, free T4) every 4–6 weeks initially until biochemical control is achieved 4
• Monitor CBC weekly for the first 3 months to detect agranulocytosis, which occurs in 0.3–0.5% of patients and typically develops within the first 3 months of treatment 3, 5

Life-Threatening Adverse Effects to Monitor

Agranulocytosis (most dangerous complication):

• Occurs in 0.1–0.5% of patients, typically within the first 3 months of therapy 5
• Instruct the patient to immediately report fever, sore throat, mouth ulcers, or any signs of infection 1
• If agranulocytosis develops, immediately discontinue the antithyroid drug and initiate granulocyte colony-stimulating factor (G-CSF) 5
• Cross-reactivity between PTU and methimazole can occur, so switching may not be safe if agranulocytosis develops 3

Severe hepatotoxicity (especially with PTU):

• PTU can cause severe, even fatal hepatocellular or cholestatic liver injury 1, 3
• Instruct the patient to immediately report anorexia, pruritus, jaundice, light-colored stools, dark urine, or right upper quadrant pain 1
• Recheck liver function tests every 2–4 weeks for the first 3 months, then every 6–8 weeks 1, 3
• If ALT/AST rises >3 times the upper limit of normal or jaundice develops, immediately discontinue PTU and consider switching to methimazole (though methimazole can also rarely cause hepatotoxicity) 3

ANCA-positive vasculitis (rare but serious with PTU):

• Occurs primarily with long-term PTU exposure 3
• Instruct the patient to report new rash, hematuria, decreased urine output, dyspnea, or hemoptysis 1
• If vasculitis is suspected, immediately discontinue PTU and do not switch to methimazole 1

Adjunctive Symptomatic Management

Beta-Blocker Therapy for Cardiovascular Protection

• Start propranolol 20–40 mg orally every 6–8 hours (or atenolol 25–50 mg once daily) to control tachycardia, tremor, and anxiety while awaiting antithyroid drug effect 6
• Beta-blockers provide immediate symptomatic relief but do not treat the underlying hyperthyroidism 6
• Reduce beta-blocker dose as the patient becomes euthyroid, as hyperthyroidism increases beta-blocker clearance 1
• Contraindications include severe asthma, decompensated heart failure, and high-degree AV block 6

Additional Supportive Measures

• Ensure adequate hydration and nutritional support, as severe hyperthyroidism causes a hypermetabolic state with increased caloric requirements 6
• Consider short-term benzodiazepines (e.g., lorazepam 0.5–1 mg every 8 hours as needed) for severe anxiety or agitation 6
• Avoid iodinated contrast agents and amiodarone, which can exacerbate hyperthyroidism 4

Monitoring and Dose Adjustment Timeline

First 4–6 Weeks (Acute Phase)

• Recheck TSH and free T4 every 4–6 weeks until free T4 normalizes 4
• Continue maximal antithyroid drug dosing until free T4 falls into the normal range 1
• Monitor for clinical improvement: decreased heart rate, weight stabilization, reduced tremor, improved energy 4

After Biochemical Control (Maintenance Phase)

• Once free T4 normalizes, reduce antithyroid drug dose by 30–50% to prevent iatrogenic hypothyroidism 4, 1
• For PTU: reduce to 100–150 mg daily in divided doses 1
• For methimazole: reduce to 5–10 mg once daily 2
• Recheck TSH and free T4 every 6–8 weeks during dose titration, then every 3–6 months once stable 4
• Target TSH within the reference range (0.5–4.5 mIU/L) with normal free T4 4

Common Pitfalls to Avoid

Do not delay treatment waiting for additional testing – severe thyrotoxicosis requires immediate antithyroid drug initiation to prevent cardiovascular complications and thyroid storm 1, 6

Do not use antithyroid drugs as monotherapy indefinitely without planning definitive treatment – after 12–18 months of medical management, consider radioactive iodine ablation or thyroidectomy for definitive cure, as long-term remission with antithyroid drugs alone occurs in only 20–50% of adults 7

Do not switch from PTU to methimazole (or vice versa) if agranulocytosis develops – cross-reactivity can occur, and the patient should proceed directly to definitive therapy (radioiodine or surgery) 3, 5

Do not overlook drug interactions – antithyroid drugs potentiate warfarin (monitor INR closely), and as the patient becomes euthyroid, doses of digoxin, theophylline, and beta-blockers may need reduction due to decreased clearance 1

Do not use PTU as first-line in children or adolescents – severe hepatotoxicity is more common in pediatric patients, so methimazole is preferred except in rare circumstances 1, 3

Do not forget to counsel about pregnancy – if the patient is a woman of childbearing age, discuss contraception or pregnancy planning, as both PTU and methimazole cross the placenta (PTU is preferred in the first trimester due to lower teratogenic risk) 1, 2, 3