Increased requirement of replacement doses of levothyroxine caused by liver cirrhosis.
Open accessAbstract
BACKGROUND: Since hypothyroidism is a fairly common dysfunction, levothyroxine (L-T4) is one of the most prescribed medications. Approximately 70% of the administered L-T4 dose is absorbed. The absorption process takes place in the small intestine. Some disorders of the digestive system and some medicines, supplements, and drinks cause L-T4 malabsorption, resulting in failure of serum TSH to be normal. Only rarely liver cirrhosis is mentioned as causing L-T4 malabsorption. CASE REPORT: In this study, we report increased requirement of daily doses of l-thyroxine in two patients with the atrophic variant of Hashimoto's thyroiditis and liver cirrhosis. In one patient, this increased requirement could have been contributed by the increased serum levels of the estrogen-dependent thyroxine-binding globulin (TBG), which is the major plasma carrier of thyroid hormones. In the other patient, we switched from tablet L-T4 to liquid L-T4 at the same daily dose. Normalization of TSH levels was achieved, but TSH increased again when she returned to tablet L-T4. CONCLUSION: Liver cirrhosis can cause increased L-T4 requirements. In addition to impaired bile secretion, the mechanism could be increased serum TBG. A similar increased requirement of L-T4 is observed in other situations characterized by elevation of serum TBG. Because of better intestinal absorption, L-T4 oral liquid formulation is able to circumvent the increased need of L-T4 in these patients.
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A defective bile production and secretion has been proposed as one of the mechanisms leading to increased need for LT4 in patients with liver cirrhosis.
“A defective bile production and secretion has been proposed as one of the mechanisms leading to increased need for LT4 in patients with liver cirrhosis (117).”
From ETA guidelines for the use of levothyroxine sodium preparations in monotherapy to optimize the treatment of hypothyroidism (2025) · cites this paper as [117]
Conditions that interfere with bile secretion, such as obstructive disease and cirrhosis, may impair the reabsorption of T4.
“Conditions that interfere with bile secretion, such as obstructive disease and cirrhosis, may impair the reabsorption of T4 (32).”
From Levothyroxine: conventional and novel drug delivery formulations. (2023) · cites this paper as [32]
Liver cirrhosis and obstructive liver disease, which can inhibit enterohepatic circulation, were reported to increase the daily doses of LT4 required.
“In addition, liver cirrhosis and obstructive liver disease, which can inhibit enterohepatic circulation, were reported to increase the daily doses of LT4 required (32).”
From Levothyroxine: conventional and novel drug delivery formulations. (2023) · cites this paper as [32]
A switch from LT4 tablets to liquid preparations can restore thyroid function in patients with gastrointestinal dysfunction.
“In addition, a switch from LT4 tablets to liquid preparations can restore thyroid function in patients with gastrointestinal dysfunction (Fig. 3) (32, 49, 50, 60, 65, 66).”
From Levothyroxine: conventional and novel drug delivery formulations. (2023) · cites this paper as [32]
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References 65 · Cited by 25
Research works printed but not linked: 1
- [28]Benvenga S Thyroid hormone transport proteins and the physiology of hormone binding. 10th ed In: Braverman LE Cooper DS, editors. Werner and Ingbar’s The Thyroid: A Clinical and Fundamental Text. Philadelphia: Wolters Kluwer, Lippincott Williams & Wilkins (2013). p. 93– 103.
- Authors
- Benvenga, S., Capodicasa, G., Perelli, S., Ferrari, S. M., Fallahi, P., & Antonelli, A.
- Affiliations
- University of Messina (IT)
- University of Pisa (IT)
- Corresponding author
- Capodicasa, Giovanni
- Venue
- Frontiers in Endocrinology
- Publisher
- Frontiers Media SA
- Published
- 2018-04-18
- Volume
- 9
- Pages
- 150-150
- ISSN
- 1664-2392 (ISSN-L)
- PMC
- PMC5915540
- OpenAlex
- W2800186788
- Cited by
- 25
- References
- 65
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 1 · 2023: 4 · 2022: 2 · 2021: 1 · 2020: 3 · 2019: 4 · 2018: 2
- FWCI
- 1.99
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Frontiers in Endocrinology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- CINECA IRIS Institutial research information system (University of Pisa) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Health Sciences › Medicine › Surgery › Thyroid and Parathyroid Surgery
- Keywords
- levothyroxine, liver cirrhosis, hypothyroidism, thyroxine-binding globulin, estrogen, Hashimoto's thyroiditis, atrophic thyroiditis, thyroid-stimulating hormone, dose requirement
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