Physiology · Endocrine Physiology (Pituitary, Thyroid, Adrenal, Pancreas)

Wolff-Chaikoff effect describes a transient inhibition of thyroid hormone synthesis that occurs with large iodine loads. The molecular mechanism underlying iodine-mediated inhibition of organification involves:

  • A Excess iodide activates TSH receptor downregulation, reducing cAMP signaling and thyroid peroxidase gene transcription
  • B Iodide activates a chloride channel (pendrin) that diverts iodide away from the follicular lumen back into the bloodstream
  • C High intracellular inorganic iodide inhibits thyroid peroxidase (TPO)-mediated iodination of tyrosine residues on thyroglobulin via an allosteric or oxidative inhibitory mechanism
  • D High iodide concentrations activate the sodium-iodide symporter in reverse, pumping iodide out of thyrocytes
Correct answer: C. High intracellular inorganic iodide inhibits thyroid peroxidase (TPO)-mediated iodination of tyrosine residues on thyroglobulin via an allosteric or oxidative inhibitory mechanism

Explanation

The Wolff-Chaikoff effect is the acute inhibition of thyroid organification (iodination of thyroglobulin tyrosines) when intracellular iodide exceeds a threshold concentration. Excess iodide generates iodolactones and possibly other oxidized iodine species that directly inhibit thyroid peroxidase (TPO) activity. This is transient because the thyroid escapes the Wolff-Chaikoff effect within 1–2 weeks by downregulating the sodium-iodide symporter (NIS), reducing iodide uptake and restoring organification. This escape mechanism explains why chronic iodine supplementation does not cause permanent hypothyroidism in most people; it also forms the basis for using potassium iodide preoperatively (to reduce vascularity via Plummer effect) before thyroid surgery.

Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.

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