Ferrous sulfate reduces thyroxine efficacy in patients with hypothyroidism

Ann Intern Med. 1992 Dec 15;117(12):1010-3. doi: 10.7326/0003-4819-117-12-1010.


Objective: To determine whether simultaneous ingestion of ferrous sulfate and thyroxine reduces the efficacy of thyroid hormone in patients with primary hypothyroidism.

Design: Uncontrolled clinical trial.

Setting: Outpatient research clinic of a tertiary care center.

Patients: Fourteen patients with established primary hypothyroidism on stable thyroxine replacement.

Intervention: All patients were instructed to ingest simultaneously, a 300-mg ferrous sulfate tablet and their usual thyroxine dose every day for 12 weeks.

Results: After 12 weeks of ferrous sulfate ingestion with thyroxine, the mean level of serum thyrotropin (thyroid stimulating hormone, TSH) rose from 1.6 +/- 0.4 to 5.4 +/- 2.8 mU/L (P < 0.01), but the free thyroxine index did not change significantly. Subjective evaluation using a clinical score showed that nine patients had an increase in symptoms and signs of hypothyroidism; the mean score for the 14 patients changed from 0 to 1.3 +/- 0.4 (P = 0.011). When iron and thyroxine were mixed together in vitro, a poorly soluble purple complex appeared that indicated the binding of iron to thyroxine.

Conclusions: Simultaneous ingestion of ferrous sulfate and thyroxine causes a variable reduction in thyroxine efficacy that is clinically significant in some patients. The interaction is probably caused by the binding of iron to thyroxine.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Female
  • Ferrous Compounds / chemistry
  • Ferrous Compounds / pharmacology*
  • Humans
  • Hypothyroidism / drug therapy*
  • Male
  • Middle Aged
  • Patient Compliance
  • Spectrophotometry
  • Thyrotropin / blood
  • Thyroxine / antagonists & inhibitors*
  • Thyroxine / blood
  • Thyroxine / chemistry


  • Ferrous Compounds
  • ferrous sulfate
  • Thyrotropin
  • Thyroxine