What is the Wolff-Chaikoff effect?

The Wolff-Chaikoff Effect

The Wolff-Chaikoff effect is an acute protective physiologic response of the thyroid gland that temporarily inhibits thyroid hormone synthesis when exposed to high levels of iodine, preventing thyrotoxicosis. 1

Mechanism

The Wolff-Chaikoff effect involves several key processes:

• Initial response: When the thyroid is exposed to excessive iodine, it acutely inhibits the organification of iodine (incorporation of iodine into thyroglobulin) within 24-48 hours 1, 2
• Proposed mechanism: Formation of iodopeptides that temporarily inhibit thyroid peroxidase (TPO) mRNA and protein synthesis, thereby reducing thyroglobulin iodination 1
• Protective function: This prevents the thyroid from synthesizing excessive amounts of thyroid hormones in response to iodine overload 1, 3

Escape Phenomenon

Under normal circumstances, the Wolff-Chaikoff effect is transient:

• After a few days, the thyroid "escapes" from this inhibitory effect 1
• Escape occurs through downregulation of the sodium-iodide symporter (NIS), which decreases intrathyroidal iodine concentration 1, 4
• This reduction in intracellular iodide allows the TPO-H2O2 system to resume normal activity and restore thyroid hormone synthesis 1, 4

Failure to Escape

In certain individuals, the escape phenomenon fails to occur, leading to iodine-induced hypothyroidism:

• Susceptible populations:

  • Fetuses and newborns
  • Elderly individuals
  • Patients with underlying autoimmune thyroiditis
  • Patients previously treated for Graves' disease (with RAI, surgery, or antithyroid drugs)
  • Patients with history of postpartum or subacute thyroiditis
  • Patients treated with interferon-alpha who developed transient thyroid dysfunction 1, 5

• Clinical course: The resulting hypothyroidism is typically transient, with thyroid function returning to normal within 2-3 weeks after iodide withdrawal 1

• Long-term implications: Patients who develop transient iodine-induced hypothyroidism should be monitored long-term, as many will eventually develop permanent primary hypothyroidism 1

Clinical Relevance

The Wolff-Chaikoff effect has important clinical implications:

• Iatrogenic causes: Common sources of excessive iodine exposure include:

  • Iodinated contrast media used in radiologic studies
  • Amiodarone (anti-arrhythmic medication with high iodine content)
  • Ethiodized oil (Lipiodol) used in medical procedures 2, 3

• Monitoring: Thyroid function should be monitored when using iodinated contrast media in patients with risk factors for thyroid dysfunction 2

• Treatment: Some patients may require transient thyroid hormone replacement therapy until the effect resolves 1, 5

Practical Considerations

Healthcare providers should be aware that:

• The thyroid gland normally has protective mechanisms to maintain normal function despite wide fluctuations in daily iodine intake 3
• In susceptible individuals, these protective mechanisms may fail, leading to either hypothyroidism or hyperthyroidism 3, 4
• Chronic high iodine intake may promote thyroid autoimmunity in predisposed individuals 4

Understanding the Wolff-Chaikoff effect is essential for recognizing and managing iodine-induced thyroid dysfunction, particularly in at-risk populations.