Cited by 25Thyroid Disorders and TreatmentsAdrenal Hormones and DisordersThyroid and Parathyroid Surgery

Increased requirement of replacement doses of levothyroxine caused by liver cirrhosis.

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Benvenga, Salvatore, Capodicasa, Giovanni, Perelli, Sarah, Ferrari, Silvia Martina, Fallahi, Poupak, Antonelli, Alessandro·2018·Frontiers in Endocrinology

Abstract

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).”
  • 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).”
  • 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).”
  • 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).”

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References 65 · Cited by 25

Research works printed but not linked: 1

  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
Published
2018-04-18
Volume
9
Pages
150-150
ISSN
1664-2392 (ISSN-L)
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
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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