Amiodarone and Thyroid Disorders

Amiodarone and Thyroid Disorders

1. Major Adverse Effects of Amiodarone

1. Thyroid dysfunction (hypothyroidism and thyrotoxicosis)
2. QTc prolongation (low risk of torsades compared to other class I/III drugs)
3. Bradycardia
4. Hepatic toxicity
5. Pulmonary toxicity
6. Blue-gray skin discoloration and photosensitivity
7. Corneal microdeposits
8. Neurologic adverse effects

2. Why Amiodarone Affects the Thyroid

1. Amiodarone contains ~37% iodine by weight.
2. A daily dose of 200–600 mg provides iodine far above physiological requirements.
3. Thyroid effects result from the following:
• excess iodine load
• intrinsic drug and metabolite (desethylamiodarone, DEA) effects
• inhibition of thyroid hormone metabolism and action

3. Main Mechanisms

3.1 Wolff–Chaikoff Effect

1. Excess iodine inhibits iodide organification and thyroid hormone synthesis.
2. Normally transient due to the escape phenomenon.
3. Failure to escape → hypothyroidism.

3.2 Jod-Basedow Phenomenon

1. Occurs in autonomous thyroid tissue.
2. Leads to iodine-induced increased hormone synthesis.
3. Causes type 1 thyrotoxicosis.

3.3 Deiodinase Inhibition

1. Inhibition of type 1 and type 2 5′-deiodinase.
2. ↓ T4 → T3 conversion, ↑ reverse T3.
3. Transient ↑ TSH and altered hormone profile.

4. Effects on Thyroid Function Tests

1. Early:
• ↑ TSH (transient)
• ↑ T4/FT4
• ↑ rT3
• ↓ T3
2. Chronic:
• FT4 high-normal
• T3 low-normal
• TSH normalizes

5. Amiodarone-Induced Hypothyroidism (AIH)

5.1 Epidemiology & Risk Factors

1. More common in iodine-sufficient regions
2. More common in women
3. Associated with:
• Hashimoto thyroiditis
• anti-TPO antibodies

5.2 Pathogenesis

1. Failure of Wolff–Chaikoff escape
2. Direct iodine inhibition
3. Increased susceptibility in autoimmune thyroid disease

5.3 Clinical Features

1. Develops 6–12 months after therapy
2. Typical hypothyroid symptoms

5.4 Diagnosis

1. Subclinical:
• TSH: 4.5–10 mU/L
• FT4 normal
2. Clinical:
• TSH > 10 mU/L
• FT4 low

5.5 Treatment

1. Levothyroxine
2. Amiodarone usually continued
3. Start with a low dose, titrate
4. Higher doses often required

6. Amiodarone-Induced Thyrotoxicosis (AIT)

6.1 General

1. More common in iodine-deficient areas
2. More common in men
3. Can occur during therapy or months after discontinuation

6.2 Type 1 AIT

1. Underlying thyroid disease present
2. Mechanism: increased hormone synthesis
3. Findings:
• increased vascularity
• normal/high uptake

6.3 Type 2 AIT

1. Normal thyroid initially
2. Mechanism:
• destructive thyroiditis
• release of preformed hormone
3. Findings:
• low vascularity
• low uptake
4. May progress to hypothyroidism

6.4 Mixed AIT

1. Combination of both mechanisms
2. Diagnosis often difficult

7. Clinical Features of AIT

1. Weight loss
2. Heat intolerance
3. Fatigue
4. Muscle weakness
5. Palpitations
6. Recurrence/worsening of arrhythmias

8. Diagnosis of AIT

1. ↓ TSH, ↑ FT4
2. T3 normal or elevated
3. Differentiation requires imaging and clinical context

9. Treatment of AIT

9.1 Type 1

1. Thionamides
2. ± sodium perchlorate
3. Consider stopping amiodarone
4. Definitive therapy: radioiodine or surgery

9.2 Type 2

1. Glucocorticoids
2. May resolve spontaneously
3. Surgery if severe

9.3 Mixed

1. Combination therapy

10. Monitoring

1. Before therapy:
• TSH, FT4 (± FT3)
• anti-TPO, anti-Tg antibodies
• thyroid ultrasound
2. During therapy:
• TSH and FT4 every 6 months

11. High-Yield Pearls

1. AIH → impaired synthesis (Wolff–Chaikoff failure)
2. AIT type 1 → increased synthesis
3. AIT type 2 → destructive thyroiditis
4. Treat AIH with levothyroxine
5. Treat AIT1 with thionamides
6. Treat AIT2 with glucocorticoids
7. Monitor thyroid function regularly

References

1. Medić F, Bakula M, Alfirević M, Bakula M, Mucić K, Marić N. Amiodarone and thyroid dysfunction. Acta Clin Croat. 2022;61(2):327–341.
2. Basaria S, Cooper DS. Amiodarone and the thyroid. Am J Med. 2005;118(7):706–714.
3. Cohen-Lehman J, Dahl P, Danzi S, Klein I. Effects of amiodarone therapy on thyroid function. Nat Rev Endocrinol. 2010;6(1):34–41.
4. Bogazzi F, Bartalena L, Martino E. Approach to the patient with amiodarone-induced thyrotoxicosis. J Clin Endocrinol Metab. 2010;95(6):2529–2535.
5. Ross DS. Amiodarone and thyroid dysfunction. In: UpToDate.