A 62-year-old woman on levothyroxine for hypothyroidism has a rise in TSH and a fall in T4 after increasing milk intake and starting an iron supplement. What is the most likely cause?

• A. Increased metabolism of the drug
• B. Decreased absorption of a drug
• C. Enhanced absorption of the drug
• D. No effect on absorption

Answer: (B)

Nutrient–drug interactions can markedly change how a drug is absorbed from the gut. Levothyroxine, used for hypothyroidism, is especially susceptible to chelation by polyvalent cations such as calcium and iron. When calcium-rich milk and an iron supplement are taken, they can bind to levothyroxine in the intestinal lumen and form insoluble complexes, which reduces the drug’s absorption into the bloodstream.

Because less levothyroxine reaches systemic circulation, thyroid hormone levels fall (lower T4) and the pituitary senses this and raises TSH to try to stimulate more hormone production. This pattern matches the scenario described after increasing milk intake and starting an iron supplement.

So the most likely cause is decreased absorption of levothyroxine due to chelation with calcium and iron in the gut. To avoid this, separate dosing: take levothyroxine on an empty stomach with water, and keep calcium- or iron-containing products at least several hours away from it.