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Ferrous Sulfate Reduces Thyroxine Efficacy in Patients with Hypothyroidism

Norman R. C. Campbell, MD; Brian B. Hasinoff, PhD; Helga Stalts, RN; Babu Rao, MD; and Norman C. W. Wong, MD
[+] Article and Author Information

Grant Support: By the Research and Development Committee of the Foothills Hospital, Calgary, Alberta; and by the Natural Sciences and Engineering Research Council of Canada. Boots Pharmaceuticals provided the thyroxine for the study. Dr. Campbell is supported by the Brenda Strafford Foundation.

Requests for Reprints: Norman Campbell, MD, Department of Medicine, Faculty of Medicine, The University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta, Canada T2N 4N1.

Current Author Addresses: Drs. Campbell and Wong and Ms. Stalts: Department of Medicine, Faculty of Medicine, The University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta, Canada, T2N 4N1. Dr. Hasinoff: Faculty of Pharmacy, University of Manitoba, Winnipeg, Manitoba, Canada R3T 2N2.

Dr. Rao: Somayji Gastroenterology Group, 408 Mid State Medical Center, 2010 Church Street, Nashville, TN 37203.


© 1992 American College of PhysiciansAmerican College of Physicians


Ann Intern Med. 1992;117(12):1010-1013. doi:10.7326/0003-4819-117-12-1010
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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.

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