What is the recommended starting dose, titration schedule, and treatment duration of carbimazole for adults (and children) with newly diagnosed Graves’ disease, and how should it be monitored and adjusted?

Carbimazole Dosing for Hyperthyroidism

For adults with newly diagnosed Graves' disease, start carbimazole at 15 mg daily rather than 30 mg daily, as the lower starting dose significantly reduces the risk of agranulocytosis while maintaining therapeutic efficacy.

Starting Dose

Adults

• Initial dose: 15 mg daily is recommended over the traditional 30 mg daily starting dose 1
• The 15 mg daily starting dose reduces agranulocytosis risk from 0.814% to 0.219% compared to 30 mg daily (p < 0.01) 1
• Combined agranulocytosis plus neutropenia rates are also significantly lower with 15 mg daily (0.474% vs 1.581%, p < 0.001) 1
• Single daily dosing is convenient and effective 2

Special Populations

• Patients with small thyroid glands (<15 mL) and markedly elevated TSI titers may be "ATD dose-sensitive" and require even lower starting doses (5-10 mg daily) with closer monitoring 3
• These patients can achieve biochemical euthyroidism with maintenance doses as low as 0.7-3.2 mg daily 3

Pregnancy

• Use the lowest possible dose to maintain free T4 in the high-normal range 4
• Monitor every 2-4 weeks during pregnancy 4

Titration and Monitoring

Initial Phase

• Clinical euthyroidism typically occurs within 1-3 months of starting therapy 2
• Patients with larger goiters and elevated alkaline phosphatase may take longer to respond 2
• Monitor thyroid function tests every 2-4 weeks initially 4

Dose-Sensitive Patients

• For patients with small glands and very high TSI (>1487%), serum free T4 can fall to low-normal or hypothyroid levels within 3.6-9.3 weeks on conventional doses 3
• These patients require finer dose titration at closer follow-up intervals (every 2-3 weeks) 3
• Watch for discordant thyroid function patterns (low/low-normal free T4 with inappropriately low/mid-normal TSH despite normal free T3) 3

Maintenance Phase

• Adjust dose to maintain serum T3 and T4 in the low-normal range 2
• Continue monitoring every 4-8 weeks once stable

Treatment Duration

• Median treatment duration: 18 weeks (range 9-41 weeks) before attempting withdrawal 2
• Stop carbimazole when:
  • Serum T3 and T4 are in the low-normal range 2
  • Positive TSH response to TRH develops 2
  • This typically occurs 2-4 months after clinical euthyroidism is achieved 2

Important Caveats

Radioiodine Therapy Interactions

• Discontinue carbimazole before radioiodine therapy rather than increasing radioiodine dose 5
• Simultaneous carbimazole reduces radioiodine success rates across all target dose ranges in both Graves' disease and toxic nodular goiter 5
• If dose escalation is necessary for high-dose radioiodine therapy, target dose amplification factors are 5.5 for Graves' disease and 3.0 for toxic nodular goiter 5

Adjunctive Thyroxine

• Do not add thyroxine to carbimazole therapy 6
• Combined carbimazole-thyroxine therapy does not reduce recurrence rates compared to carbimazole alone (recurrence at 6±4 months vs 7±4 months, no significant difference) 6

Remission Rates

• Approximately 39% of patients achieve prolonged remission (>1 year) after short-term carbimazole therapy when stopped at appropriate biochemical targets 2

Monitoring for Agranulocytosis

• Highest risk occurs with higher starting doses 1
• Monitor complete blood count if fever, sore throat, or other signs of infection develop
• The dose-dependent nature of agranulocytosis makes the 15 mg starting dose particularly important for safety 1