Treatment of amiodarone-induced thyrotoxicosis type 2: a randomized clinical trial

J Clin Endocrinol Metab. 2012 Feb;97(2):499-506. doi: 10.1210/jc.2011-2390. Epub 2011 Nov 30.

Abstract

Context: Amiodarone-induced thyrotoxicosis (AIT) type 2 is self-limiting in nature, but most physicians are reluctant to continue amiodarone. When prednisone fails to restore euthyroidism, possibly due to mixed cases of AIT type 1 and 2, perchlorate (ClO(4)) might be useful because ClO(4) reduces the cytotoxic effect of amiodarone on thyrocytes.

Objectives: Our objectives were to demonstrate the feasibility of continuation of amiodarone in AIT type 2 and to evaluate the usefulness of ClO(4) (given alone or in combination with prednisone) in AIT type 2.

Design and setting: A randomized multicenter study was conducted in 10 Dutch hospitals.

Methods: Patients with AIT type 2 were randomized to receive prednisone 30 mg/d (group A, n = 12), sodium perchlorate 500 mg twice daily (group B, n = 14), or prednisone plus perchlorate (group C, n = 10); all patients continued amiodarone and were also treated with methimazole 30 mg/d. Follow-up was 2 yr.

Main outcome measures: Treatment efficacy (defined as TSH values ≥ 0.4 mU/liter under continuation of amiodarone) and recurrent thyrotoxicosis were evaluated.

Results: Initial therapy was efficacious in 100, 71, and 100% of groups A, B, and C, respectively (P = 0.03). The 29% failures in group B became euthyroid after addition of prednisone. Neither the time to reach TSH of 0.4 mU/liter or higher [8 wk (4-20), 14 wk (4-32), and 12 wk (4-28) in groups A, B, and C respectively] nor the time to reach free T(4) of 25 pmol/liter or below [4 wk (4-20), 12 wk (4-20), and 8 wk (4-20) in groups A, B, and C) were significantly different between groups (values as median with range). Recurrent thyrotoxicosis occurred in 8.3%.

Conclusion: Euthyroidism was reached despite continuation of amiodarone in all patients. Prednisone remains the preferred treatment modality of AIT type 2, because perchlorate given alone or in combination with prednisone had no better outcomes.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Amiodarone / adverse effects*
  • Anti-Arrhythmia Agents / adverse effects
  • Antithyroid Agents / adverse effects
  • Antithyroid Agents / therapeutic use
  • Endocrine Disruptors / adverse effects
  • Endocrine Disruptors / therapeutic use
  • Feasibility Studies
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Perchlorates / adverse effects
  • Perchlorates / therapeutic use*
  • Recurrence
  • Thyroid Function Tests
  • Thyrotoxicosis / chemically induced*
  • Thyrotoxicosis / classification
  • Thyrotoxicosis / therapy*
  • Treatment Outcome

Substances

  • Anti-Arrhythmia Agents
  • Antithyroid Agents
  • Endocrine Disruptors
  • Perchlorates
  • Amiodarone
  • perchlorate