In a 36‑year‑old non‑pregnant woman with overt hyperthyroidism (T3 ≈ 400 pg/mL, free T4 ≈ 16 µg/dL, TSH < 0.005 mIU/L), what is the appropriate initial carbimazole dose and follow‑up plan?

Initial Carbimazole Dosing and Management for Severe Overt Hyperthyroidism

For this patient with severe overt hyperthyroidism (T3 ≈400 pg/mL, free T4 ≈16 µg/dL, TSH <0.005 mIU/L), start carbimazole 40 mg daily as a single dose, then reduce to 20 mg daily once thyroid hormones normalize (typically within 4-10 weeks), with TSH and free T4 monitoring every 4-6 weeks until biochemical euthyroidism is achieved. 1

Rationale for High-Dose Initiation

• Patients with severe hyperthyroidism (baseline T4 >260 nmol/L or approximately >3.4 µg/dL) require higher initial carbimazole doses to achieve adequate control, as 20 mg daily is less effective in this population 1
• Your patient's free T4 of approximately 16 µg/dL (assuming this is total T4 in nmol/L conversion ≈206 nmol/L) represents moderate-to-severe disease requiring the higher dose
• 40 mg daily achieves significantly lower T4 (98 vs 158 nmol/L) and T3 (2.6 vs 4.3 nmol/l) at 4 weeks compared to 20 mg daily 1

Dosing Algorithm

Initial Phase (Weeks 0-4)

• Start carbimazole 40 mg once daily (can be taken as single morning dose for convenience) 1, 2
• Consider adding propranolol 40-80 mg daily for the first 3 weeks to control adrenergic symptoms 2
• Recheck TSH, free T4, and T3 at 4 weeks to assess response 1

Titration Phase (Weeks 4-10)

• If free T4 has normalized or dropped to low-normal range at 4 weeks, reduce carbimazole to 20 mg daily to prevent iatrogenic hypothyroidism 1
• If free T4 remains elevated at 4 weeks, continue 40 mg daily and recheck at 6 weeks
• Monitor for iatrogenic hypothyroidism, which occurs more frequently with 40 mg daily (especially after 4-10 weeks of treatment) 1
• Recheck thyroid function every 4-6 weeks during this phase 1

Maintenance Phase (After Week 10)

• Once biochemical euthyroidism is achieved (normal T3, T4 in low-normal range, TSH beginning to rise), reduce to maintenance dose of 5-15 mg daily 2
• Most patients achieve clinical euthyroidism within 1-3 months, though those with larger goiters may take longer 2
• Continue treatment for median 18 weeks (range 9-41 weeks) until TSH response to TRH normalizes 2

Critical Monitoring Parameters

Biochemical Targets

• Target free T4 and T3 in the low-normal range before stopping treatment 2
• Wait for positive TSH response to develop (TSH begins rising toward normal) before considering treatment cessation 2
• Stopping treatment when T3/T4 are low-normal (usually 2-4 months after clinical euthyroidism) improves remission rates 2

Follow-Up Schedule

• Week 4: TSH, free T4, free T3, clinical assessment 1
• Week 6-10: Repeat thyroid function tests every 4-6 weeks 1
• After biochemical euthyroidism: Monitor every 6-8 weeks until treatment completion 2
• Post-treatment: Follow for at least 12 months to assess for relapse 2

Special Considerations for Dose-Sensitive Patients

• Patients with small thyroid glands and markedly elevated TSI may be "ATD dose-sensitive" and experience rapid drops in free T4 on conventional doses 3
• If your patient has a small goiter (thyroid volume <15 mL by ultrasound), consider starting at 30 mg daily instead of 40 mg 3
• Watch for discordant thyroid function (low-normal free T4 with inappropriately low TSH despite normal T3), which may require finer dose titration 3
• In dose-sensitive patients, free T4 can fall to hypothyroid levels within 3.6-9.3 weeks on doses as low as 5-15 mg daily 3

Common Pitfalls to Avoid

• Do not continue 40 mg daily beyond 4-10 weeks if free T4 has normalized, as this significantly increases risk of iatrogenic hypothyroidism 1
• Do not stop treatment as soon as T3/T4 normalize—wait until they are in the low-normal range and TSH begins to rise 2
• Do not use 20 mg daily as initial dose in severe hyperthyroidism (baseline T4 >260 nmol/L), as it is less effective 1
• Monitor for drug-related side effects including urticaria, which may necessitate switching to alternative therapy 4
• Avoid stopping treatment prematurely—median treatment duration is 18 weeks, with 39% achieving prolonged remission when treatment is appropriately timed 2

Expected Outcomes

• Clinical euthyroidism typically achieved within 1-3 months 2
• Biochemical normalization (T3, T4 in low-normal range) usually occurs 2-4 months after clinical improvement 2
• 39% of patients achieve prolonged remission (>1 year) when treatment is stopped at appropriate time (median 77 weeks remission) 2
• Weight gain, pulse normalization, and symptom improvement occur similarly with both 20 mg and 40 mg initial doses by 6-12 weeks 1