admittomedicine

amiodarone and thyroid

3 min read

"the iodine bomb"

Amiodarone contains ~37% iodine by weight. A 200mg daily dose delivers ~6–75mg of free iodine (vs daily requirement of 0.15mg). It causes thyroid dysfunction via iodine load and direct cytotoxicity.

physiology & pharmacokinetics

  • Half-life: ~100 days. Toxicity persists months after discontinuation.
  • Intrinsic Effects:
    1. Inhibits 5’-deiodinase (Type 1 & 2): Blocks conversion of T4 T3.
    2. Wolff-Chaikoff Effect: Acute iodine load transiently inhibits organification (normal adaptation).
    3. Jod-Basedow Effect: Iodine load fuels excess synthesis in autonomous nodules (pathological).

acute phase labs (<3 months)

Initiation causes a predictable, transient physiologic pattern. Do NOT treat.

  • TSH (transient suppression of pituitary D2).
  • Total and Free T4 (blocked conversion + decreased clearance).
  • T3 (blocked production).
  • Action: Retest in 3 months. TSH should normalise; T4 may remain slightly elevated.

amiodarone-induced hypothyroidism (AIH)

  • Epidemiology: More common in iodine-sufficient areas (e.g., North America).
  • Mechanism: Failure to “escape” the Wolff-Chaikoff effect (inhibitory effect of iodine).
  • Risk Factors: Pre-existing antibodies (Anti-TPO), Hashimoto’s, female sex.
  • Management:
    • Don’t stop Amiodarone (if essential for arrhythmia).
    • Treat: replace with Levothyroxine.
    • Target: TSH may need to be higher (upper normal to slightly elevated) because Amiodarone blocks T4T3 conversion. Aggressive normalisation risks arrhythmia.

amiodarone-induced thyrotoxicosis (AIT)

Can be a medical emergency in the cardiac patient. Mortality is increased, especially if LVEF <40%.

differentiation (type 1 vs type 2)

Differentiation directs treatment, though mixed forms are common.

FeatureType 1 AIT (Synthesis)Type 2 AIT (Destructive)
PathophysiologyJod-Basedow Effect.
Iodine fuels pre-existing autonomy.		Destructive Thyroiditis.
Direct drug cytotoxicity (lysosomal activation).
Patient ProfileUnderlying MNG or latent Graves’.
Iodine-deficient areas.		Healthy thyroid gland.
Iodine-sufficient areas.
OnsetEarly (median 3 months).Late (median 30 months).
Vascularity (Doppler)Increased (“Inferno”).Absent/Low.
Radioiodine UptakeLow/Normal (detectable).Undetectable (<1%).
Sestamibi ScanIncreased uptake.Decreased uptake.

clinical pearl: doppler ultrasound

Colour Flow Doppler is the most useful rapid discriminator.

  • High Flow: Type 1 (Synthesis).
  • Low Flow: Type 2 (Destruction).

management of AIT

Discontinuation of Amiodarone is controversial (long half-life = no immediate benefit; blocks T3 receptors/beta-adrenergic conversion). Consult Cardiology.

  1. Type 1 (Synthesis):

    • Methimazole (High dose: 30–40 mg/day).
    • Note: Resistance is common due to high intrathyroidal iodine stores.
    • Potassium Perchlorate (blocks iodine uptake) is historical/rarely used due to toxicity.

  2. Type 2 (Destructive):

    • Prednisone (30–40 mg/day taper over 3 months).
    • Mechanism: Anti-inflammatory/membrane stabilising.
    • Course: Often creates a hypothyroid phase after resolution.

  3. Mixed / Uncertain (Most Common Scenario):

    • Start BOTH: High dose Methimazole + Prednisone.
    • Re-evaluate: If rapid response (<2 weeks), likely Type 2 taper MMI. If resistant, likely Type 1 taper steroids.

  4. Refractory / Unstable Cardiac Status:

    • Total Thyroidectomy: Definitive management. Do not delay if cardiac function deteriorates (mortality benefit in severe LV dysfunction).