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Cited by 231Thyroid Disorders and TreatmentsThyroid and Parathyroid SurgeryIron Metabolism and Disorders

Ferrous sulfate reduces thyroxine efficacy in patients with hypothyroidism

Campbell, Norman R. C., Hasinoff, Brian B., Stalts, Helga, Rao, Babu, Wong, Norman C. W.·1992·Annals of Internal Medicine
DOI 10.7326/0003-4819-117-12-1010
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Abstract

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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Crossref · 10.7326/0003-4819-117-12-1010

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15 of 15 references verified0 citation errors · 0 not checkable

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  • Only two of the medications that alter LT4 absorption have been studied in a cross-over study design of chronic therapy, with two other studies also conducted prospectively.

    “Only two of these medications have been studied in a cross-over study design of chronic therapy (132,145), with two other studies also conducted prospectively (140,143).”

    From Guidelines for the Treatment of Hypothyroidism: Prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement (2014) · cites this paper as [140]

  • During a trial, TSH values of 14 hypothyroid patients increased from a mean of 1.6 mIU/L to a mean of 5.4 mIU/L with simultaneous ingestion of ferrous sulfate and LT4.

    “During the trial, the TSH values of 14 hypothyroid patients increased from a mean of 1.6 mIU/L to a mean of 5.4 mIU/L with simultaneous ingestion of ferrous sulfate and LT4.”

    From Guidelines for the Treatment of Hypothyroidism: Prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement (2014) · cites this paper as [140]

  • A simple in vitro binding experiment can quantify the binding ability of interfering agents.

    “A simple in vitro binding experiment can quantify the binding ability of interfering agents (72, 78).”

    From Levothyroxine: conventional and novel drug delivery formulations. (2023) · cites this paper as [72]

  • Direct complexation and chelation play important roles in the malabsorption of LT4 induced by the intake of many drugs, including calcium and iron supplements, aluminum-containing antacids, bile acid sequestrants, and some foods (eg, fiber-rich foods, coffee, and milk).

    “It is widely acknowledged that direct complexation and chelation play important roles in the malabsorption of LT4 induced by the intake of many drugs, including calcium and iron supplements (72, 73), aluminum-containing antacids (74), bile acid sequestrants (75, 76), and some foods (eg, fiber-rich foods, coffee, and milk) (22, 77, 78).”

    From Levothyroxine: conventional and novel drug delivery formulations. (2023) · cites this paper as [72]

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Authors
Campbell, N. R. C., Hasinoff, B. B., Stalts, H., Rao, B., & Wong, N. C. W.
ORCID
Hasinoff, Brian B.
Venue
Annals of Internal Medicine
Publisher
American College of Physicians
Published
1992-12-15
Volume
117
Issue
12
Pages
1010-1013
ISSN
  • 0003-4819 (ISSN-L)
  • 1539-3704
DOI
10.7326/0003-4819-117-12-1010
OpenAlex
W1994530252
Cited by
231
References
15
Citations by year
2026: 3 · 2025: 3 · 2024: 4 · 2023: 6 · 2022: 5 · 2021: 5 · 2020: 7 · 2019: 8 · 2018: 5 · 2017: 8 · 2016: 4 · 2015: 9 · 2014: 8 · 2013: 6 · 2012: 12
FWCI
3.50
Type
journal article
Language
en
Open access
closed
Locations
  • Annals of Internal Medicine (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
  • Health Sciences › Medicine › Surgery › Thyroid and Parathyroid Surgery
  • Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
Keywords
ferrous sulfate, thyroxine, primary hypothyroidism, drug interactions, iron supplementation, thyroid hormone absorption, serum thyrotropin, free thyroxine index, hypothyroidism symptoms
MeSH terms
Adult, Aged, Female, Ferrous Compounds, Humans, Hypothyroidism, Male, Middle Aged, Patient Compliance, Spectrophotometry, Thyrotropin, Thyroxine

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