How to Adjust Methimazole (MMI) Dose in Hyperthyroidism: A Step-by-Step Lab-Based Guide

🎯 1. Goal of Therapy

• Normalize Free T4 (FT4) and Free T3 (FT3) levels.

• TSH is not reliable early — it remains suppressed for weeks to months even after hormones normalize.

• The primary lab for dose adjustment = FT4 (± FT3).

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🧪 2. Monitoring Schedule

Time after starting MMI	Lab to Check	Why
Baseline	TSH, FT4, FT3, CBC, LFT	Starting point & safety
4–6 weeks after starting	FT4 ± FT3 (ignore TSH)	Adjust dose
Every 4–6 weeks thereafter	FT4 ± FT3	Continue titration
Once euthyroid	Every 2–3 months	Maintenance phase
After 12–18 months	TRAb + TFT	Consider stopping drug

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📊 3. How to Adjust MMI Dose — Step by Step

Lab Pattern	Interpretation	Action / Adjustment
FT4 & FT3 high  TSH suppressed	Inadequate control (still hyperthyroid)	🔺 Increase MMI by 5–10 mg/day e.g. from 15 → 20–25 mg/day
FT4 & FT3 slightly above normal	Partial control	Continue same dose and recheck in 4 weeks
FT4 normal, FT3 normal, TSH low	Improving (normal thyroid hormones)	Maintain current MMI dose — do not increase (TSH recovery is slow)
FT4 & FT3 low, TSH still low	Over-treatment (now hypothyroid)	🔻 Decrease MMI by 5–10 mg/day or temporarily stop for 1 week
FT4 low, TSH high	Overt hypothyroidism	Stop MMI and start levothyroxine 25–50 µg/day (block–replace regimen if long-term)
Normal TFT x 2 visits, 4–6 wks apart	Euthyroid achieved	Taper MMI to 5–10 mg/day maintenance
Relapse after withdrawal (TSH low, FT4 high)	Recurrence	Restart MMI or consider RAI / surgery

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💡 4. Clinical Pearls for Dose Adjustment

1. Base dose adjustment on FT4 trend, not TSH early on.→ TSH may stay suppressed even after normalization of T4.

2. Don’t change dose more often than every 4 weeks.→ MMI has a long half-life; thyroid stores take time to respond.

3. Use the smallest dose that maintains an euthyroid state.→ Avoid overtreatment → iatrogenic hypothyroidism.

4. When in doubt:→ Repeat labs in 2–4 weeks instead of making drastic changes.

5. CBC and LFT:→ Only repeat if the patient develops fever, sore throat, or jaundice (suspect agranulocytosis or hepatotoxicity).
   

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⚙️ 5. Example Case-Based Adjustment

Patient: Started MMI 15 mg/dayAfter 6 weeks:

• FT4 = 1.9 ng/dL (↑, still high)

• FT3 = 6.8 pg/mL (↑)

• TSH = <0.01

➡️ Interpretation: Still hyperthyroid → increase MMI to 20–25 mg/day.Recheck FT4, FT3 in 4–6 weeks.

Next visit:

• FT4 = 1.1 ng/dL (normal)

• FT3 = 4.0 pg/mL (normal)

• TSH = 0.02 (still low)

➡️ Keep current MMI dose (20 mg/day).Recheck in 6 weeks.

Later visit (after 3 months):

• FT4 = 0.7 ng/dL (low)

• TSH = 5.0 (↑)

➡️ Over-suppression → reduce MMI to 10 mg/day.

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📋 6. Typical Methimazole Dosing Table (Guideline Reference: ATA 2016, Thai CPG 2021)

Severity (based on FT4 level)	FT4 (ng/dL)	MMI Starting Dose	Adjustment Range
Mild (FT4 < 2.5)	1.6–2.5	10 mg/day	5–15 mg/day
Moderate (FT4 2.5–4.0)	2.5–4.0	20 mg/day	10–30 mg/day
Severe (FT4 > 4.0)	>4.0	30–40 mg/day	20–40 mg/day
Maintenance (once euthyroid)	FT4 normal	5–10 mg/day	5–10 mg/day

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🔁 7. When to Stop Methimazole

After 12–18 months of stable euthyroidism:

• Check TRAb:

  • Negative TRAb: can stop drug (low relapse risk)

  • Positive TRAb: continue for another 6 months or switch to RAI

Recheck TFT every 1–3 months for relapse during first year post-withdrawal.

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📚 8. Key Guidelines

• American Thyroid Association (ATA) 2016: Hyperthyroidism and Other Causes of Thyrotoxicosis

• Thai Endocrine Society CPG (2021): Clinical Practice Guideline for Thyrotoxicosis

• Endocrine Society, 2022: Management of Graves’ Disease and Thyrotoxicosis
  

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🩺 Take-Home Summary

Parameter	Main Lab for Adjustment	TSH use	Check Interval
Mild/Moderate cases	FT4 ± FT3	Ignore early (lags behind)	q4–6 weeks
Dose adjustment	Based on FT4 trend	Only use TSH once euthyroid	—
Target	Normal FT4 & FT3	TSH eventually normalizes	—

Mnemonic to remember:🧩 “4-6-4 Rule”

• Check labs every 4–6 weeks

• Adjust based on FT4

• Maintain for 4–6 months after normalization before considering taper