Effect of carbamazepine, phenytoin and phenobarbitone on serum levels of thyroid hormones and thyrotropin in humans
Abstract
Patients on long-term treatment with either of the stereochemically related antiepileptic drugs phenytoin (DPH) or carbamazepine (CBZ) had similar changes in serum thyroid hormone concentrations. T4, FT4, FT4 index, T3, FT3, FT3 index and rT3 were reduced, whereas T3U and TSH were not significantly different from the reference group levels. Long-term phenobarbitone treatment had no convincing effect on the investigated parameters when used alone, but possibly potentiated the effect of CBZ. In patients starting on CBZ, T4 fell to a stable 70% of the basal level after 1--2 weeks. T3 decreased transitorily to 85% of the basal level. TSH showed a complementary but somewhat delayed transitory increase. T3U and TBG did not change significantly. The effect of CBZ and DPH can be explained by interference with thyroid hormone binding to TBG combined with enzyme-induced increased metabolic clearance rate of thyroid hormones without homeostatic maintenance of premedication levels of FT4 and FT3. We suggest that the regulated factor maintaining euthyroidism in these patients is the total quantity of thyroid hormones being degraded in the tissues per unit time. We conclude that serum concentrations of FT4 and FT3 do not reflect thyroid status adequately under all circumstances.
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Often patients or healthy volunteers taking phenytoin remain euthyroid.
“Often patients or healthy volunteers taking phenytoin remain euthyroid (176,177).”
From Guidelines for the Treatment of Hypothyroidism: Prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement (2014) · cites this paper as [176]
Decreased T4 and T3 concentrations without an alteration in TSH were reported in 13 patients without pre-existing hypothyroidism and nine hypothyroid patients after initiation of carbamazepine therapy.
“Decreased T4 and T3 concentrations without an alteration in TSH were reported in 13 patients without pre-existing hypothyroidism (176) and nine hypothyroid patients (181) after initiation of carbamazepine therapy.”
From Guidelines for the Treatment of Hypothyroidism: Prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement (2014) · cites this paper as [176]
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References 18 · Cited by 103
- Authors
- Rootwelt, K., Ganes, T., & Johannessen, S. I.
- Affiliations
- Department of Clinical Chemistry, Ullevål sykehus, Rikshospitalet, Sandvika, Norway
- Department of Neurology, Ullevål sykehus, Sandvika, Norway
- Sandvik (Norway) (NO)
- ORCID
- Johannessen, S. I.
- Venue
- Scandinavian Journal of Clinical and Laboratory Investigation
- Publisher
- Informa UK Limited
- Published
- 1978-12
- Volume
- 38
- Issue
- 8
- Pages
- 731-736
- ISSN
- 0036-5513 (ISSN-L)
- 1502-7686
- OpenAlex
- W2101727684
- Cited by
- 103
- References
- 18
- Citations by year
- 2025: 2 · 2023: 1 · 2022: 1 · 2021: 2 · 2019: 2 · 2018: 2 · 2017: 2 · 2016: 2 · 2015: 2 · 2014: 1 · 2013: 3
- FWCI
- 1.86
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Scandinavian Journal of Clinical and Laboratory Investigation (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmacological Effects and Toxicity Studies
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Keywords
- carbamazepine, phenytoin, phenobarbital, antiepileptic drugs, thyroid hormones, free thyroxine, free triiodothyronine, thyroid-stimulating hormone, thyroxine-binding globulin, thyroid hormone binding, enzyme induction, thyroid hormone metabolism, euthyroidism, drug-induced thyroid dysfunction
- MeSH terms
- Adult, Carbamazepine, Epilepsy, Humans, Phenobarbital, Phenytoin, Radioimmunoassay, Thyroid Hormones, Thyrotropin, Thyroxine, Thyroxine-Binding Proteins, Time Factors, Triiodothyronine, Triiodothyronine, Reverse
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