Exaggerated levothyroxine malabsorption due to calcium carbonate supplementation in gastrointestinal disorders
Abstract
OBJECTIVE: To describe a patient with primary hypothyroidism in whom ingestion of levothyroxine with calcium carbonate led to markedly elevated serum thyrotropin concentrations. CASE SUMMARY: A 61-year-old white woman with primary hypothyroidism, systemic lupus erythematosus, celiac disease, and history of Whipple resection for pancreatic cancer was euthyroid with levothyroxine 175-188 micrograms/d. After taking a high dose of calcium carbonate (1250 mg three times daily) with levothyroxine, she developed biochemical evidence of hypothyroidism (thyrotropin up to 41.4 mU/L) while remaining clinically euthyroid. Delaying calcium carbonate administration by four hours returned her serum thyrotropin to a borderline high concentration (5.7 mU/L) within a month. Serum concentrations of unbound and total thyroxine and triiodothyronine tended to decrease, but remained borderline low to normal while the patient concomitantly received levothyroxine and calcium carbonate. DISCUSSION: Concomitant administration of levothyroxine and calcium carbonate often results in levothyroxine malabsorption. While in most patients the clinical consequences of this interaction, even with prolonged exposure, are relatively small, overt hypothyrodism may develop in patients with preexisting malabsorption disorders. However, as the current case illustrates, the clinical manifestations of the initial levothyroxine deficit may not always be apparent and, of all usual laboratory thyroid function tests, only thyrotropin measurement will reliably uncover the exaggerated levothyroxine malabsorption. CONCLUSIONS: Decreased absorption of levothyroxine when given with calcium carbonate may be particularly pronounced in patients with preexisting malabsorption disorders. Once recognized, a change in drug administration schedule usually minimizes or eliminates this interaction.
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Dramatic increases in serum TSH appear to be possible in patients with more than one factor contributing to impaired LT4 absorption, as occurred in a patient with both celiac disease and calcium carbonate use (162).
“However, dramatic increases in serum TSH appear to be possible in patients with more than one factor contributing to impaired LT4 absorption, as occurred in a patient with both celiac disease and calcium carbonate use (162).”
From Guidelines for the Treatment of Hypothyroidism: Prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement (2014) · cites this paper as [162]
A retrospective study of elderly nursing home residents showed serum TSH values were unaffected when LT4 timing changed from 9 am to midnight.
“In contrast, a retrospective study of elderly nursing home residents showed that serum TSH values were unaffected when the timing of LT4 administration was changed from 9 am (1-2 hours after breakfast) compared with midnight (3 hours after a snack) (130).”
From Guidelines for the Treatment of Hypothyroidism: Prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement (2014) · cites this paper as [130]
Four of six studies examining timing of LT4 administration showed that timing influences serum TSH values in hypothyroid patients receiving treatment.
“Four studies (121,126,128,129), out of the six studies examining this issue (121,128-131), have shown that the timing of LT4 administration influences the serum TSH values of hypothyroid patients receiving treatment.”
From Guidelines for the Treatment of Hypothyroidism: Prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement (2014) · cites this paper as [130]
Biological hypothyroidism is easily corrected a few days after withdrawal of drugs reducing intestinal absorption, while a longer time (weeks to months) is needed for drugs affecting in vivo metabolism.
“Biological hypothyroidism is easily corrected a few days after withdrawal of drugs reducing intestinal absorption, while a longer time (weeks to months) is needed for drugs affecting in vivo metabolism (87, 94).”
From Levothyroxine: conventional and novel drug delivery formulations. (2023) · cites this paper as [94]
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References 26 · Cited by 40
- Authors
- Csako, G., McGriff, N. J., Rotman-Pikielny, P., Sarlis, N. J., & Pucino, F.
- Affiliations
- Gyorgy Csako MD, Assistant Chief of Clinical Chemistry, Department of Laboratory Medicine, Warren G Magnuson Clinical Center, National Institutes of Health, Bethesda, MD
- Nayahmka J McGriff PharmD, at time of writing, Primary Care Resident, Pharmacy Department, Warren G Magnuson Clinical Center; now, Assistant Professor, Department of Pharmacy Practice and Administration, University of the Sciences, Philadelphia, PA
- Pnina Rotman-Pikielny MD, Clinical Fellow, Clinical Endocrinology Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health
- National Institutes of Health (US)
- Venue
- Annals of Pharmacotherapy
- Publisher
- SAGE Publications
- Published
- 2001-12
- Volume
- 35
- Issue
- 12
- Pages
- 1578-1583
- ISSN
- 0012-6578 (ISSN-L)
- 1060-0280
- 1542-6270
- OpenAlex
- W2120448580
- Cited by
- 40
- References
- 26
- Citations by year
- 2026: 1 · 2023: 2 · 2022: 1 · 2021: 3 · 2019: 1 · 2018: 1 · 2016: 1 · 2015: 2 · 2014: 1 · 2013: 1
- FWCI
- 1.84
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annals of Pharmacotherapy (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 › Gastroenterology › Celiac Disease Research and Management
- Keywords
- calcium carbonate, drug interactions, primary hypothyroidism, thyroid-stimulating hormone, timing of drug administration, celiac disease, systemic lupus erythematosus, Whipple resection, pancreatic cancer, gastrointestinal diseases, thyroid hormone absorption
- MeSH terms
- Antacids, Calcium Carbonate, Celiac Disease, Female, Humans, Hypothyroidism, Intestinal Absorption, Lupus Erythematosus, Systemic, Malabsorption Syndromes, Middle Aged, Thyrotropin, Thyroxine
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