Untreated Graves' Hyperthyroidism
Thyroid peroxidase drives excess hormone output before treatment begins.
- High: Free T4 (above normal range)
- Low: TSH (suppressed by feedback)
- 100%: TPO activity (fully active enzyme)
- Present: Symptoms (tachycardia, weight loss)
Why hormone output is high
Autoantibodies stimulate the TSH receptor, driving unchecked hormone synthesis.
Role of thyroid peroxidase
TPO iodinates thyroglobulin, the rate-limiting step of hormone production.
Thionamide Binds Thyroid Peroxidase
Methimazole or PTU molecules begin occupying the enzyme active site.
- Thionamide: Drug class (methimazole or PTU)
- TPO enzyme: Target (iodination step)
- Days: Onset (before effect seen)
- Hours: Half-life (varies by drug)
Mechanism of blockade
Drug molecules occupy TPO, preventing iodine attachment to thyroglobulin.
Methimazole vs PTU
PTU also blocks peripheral T4-to-T3 conversion, methimazole is more potent.
New Hormone Production Nearly Halted
Existing hormone stores are used up while new synthesis stays blocked.
- ~70%: TPO blockade (enzyme mostly inhibited)
- Depleting: Stored hormone (colloid reserve falling)
- Minimal: New synthesis (trickle output only)
- Weeks: Clinical lag (before levels drop)
Why effect is delayed
Stored hormone must be depleted before blood levels start falling.
Dose dependence
Higher dose deepens blockade and speeds hormone-store depletion.
T3/T4 Trending Toward Normal
Continued blockade steadily lowers circulating hormone over several weeks.
- 4–8 wks: Timeframe (typical normalization)
- Labs q4wk: Monitoring (T3, T4, TSH checked)
- Ongoing: Dose titration (adjusted to response)
- Improving: Symptom relief (as levels fall)
Tracking the curve
Hormone levels decline gradually, not immediately, over weeks of therapy.
Adjusting treatment
Dose lowered once levels approach the normal reference range.
Normalization and Agranulocytosis Vigilance
Hormones stabilize with therapy; rare severe WBC drop needs monitoring.
- ~0.3%: Agranulocytosis risk (rare but serious)
- Fever, sore throat: Warning signs (seek care immediately)
- 4500–11000: Normal WBC (cells/µL)
- Stop drug: Action if low (urgent CBC needed)
Successful outcome
T3/T4 reach normal range with continued, monitored thionamide therapy.
Agranulocytosis warning
Sudden fever or sore throat warrants immediate white cell count check.