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Cited by 24Thyroid Disorders and TreatmentsThyroid and Parathyroid SurgeryThyroid Cancer Diagnosis and Treatment

Use of levothyroxine in the management of hypothyroidism: A historical perspective

Open access
Kahaly, George J., Gottwald-Hostalek, Ulrike·2022·Frontiers in Endocrinology
DOI 10.3389/fendo.2022.1054983PMC PMC9666762
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Abstract

The thyroid operates within a complex system of homeostatic regulation, where the level of thyrotropin (TSH) influences the rate of secretion of the principal thyroid hormones, thyroxine (T4) and triiodothyronine (T3). The devastating consequences of untreated thyroid dysfunction have been evident for centuries. Indeed, sources from antiquity described goitre and cretinism, two of the clinical sequelae of untreated overt thyroid disease. It was not until the first part of the 19 th century that goitre and cretinism were first associated with iodine status; however, the endocrine function of the thyroid was not clearly identified until the early part of the 20 th century. Three principal innovations in the 20 th century supported the use of levothyroxine (LT4) replacement therapy for the management of hypothyroidism: a practical technique for the synthesis of LT4 suitable to support pharmaceutical use (late 1940s), the discovery that LT4 is converted to the active thyroid hormone, T3, in the peripheral tissues (1970), and the development of robust and sensitive assay methodology for measuring thyroid hormones in the blood (1960 onwards). Synthetic LT4, titrated to bring the level of TSH within a predefined “normal” reference range, is now established as the mainstay of treatment for hypothyroidism, and provides adequate restoration of thyroid hormone function for most people with this condition. Future research will explore further the nuances of the hypothalamic-pituitary-thyroid axis, and the place, if any, for T3 within the management of thyroid dysfunction.

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Crossref · 10.3389/fendo.2022.1054983

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  • For over 50 years, LT4 has been the standard of care for the treatment of hypothyroidism.

    “For over 50 years now, LT4 has been the standard of care for the treatment of hypothyroidism (39).”

    From Emerging Therapies in Hypothyroidism (2024) · cites this paper as [39]

    The section ‘Establishment of LT4 as the standard of care for hypothyroidism’ explicitly calls LT4 the standard of care. The Conclusions say it emerged as the mainstay in the second half of the 20th century, but the paper does not establish that it had held that status for over 50 years by 2022. (LLM, conf=0.84)

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Research works printed but not linked: 8

  1. [25]Schiff M. Résumé d’une nouvelle série d’expériences sur les effets de l’ablation des corps thyroîdes. In: Revue médicale de la suisse romande (Geneve: Imprimerie Charles Schuchardt), vol. 4. (1884). p. 425–45.
  2. [29]Chatin A. Recherches sur l'iode des eaux douces) de la présence de ce corps dans les plantes at les animaux terrestes. In: Comptes rendus hebdomadaires des séances de l'Academie des sciences (Paris: Gauthier-Villars), vol. 31. (1851). p. 280–3.
  3. [43]Spencer CA. Assay of thyroid hormones and related substances. Available at: https://www.ncbi.nlm.nih.gov/books/NBK279113/ (Accessed March 2020).
  4. [47]The united states pharmacopeial convention 2009 current USP monograph of levothyroxine sodium tablets (published in revision bulletin, official February 1, 2010). Available at: https://www.uspnf.com/sites/default/files/usp_pdf/EN/USPNF/levothyroxineSodiumTablets.pdf (Accessed September 2010).
  5. [53]Wiersinga WM Duntas L Fadeyev V Nygaard B Vanderpump MP. 2012 ETA Guidelines: The use of l-T4 + l-T3 in the treatment of hypothyroidism. Eur Thyroid J (2012) 1: 55– 71. doi: 10.1159/000339444 24782999 PMC3821467 · DOI · Paper page
  6. [58]Peeters RP Visser TJ. Metabolism of thyroid hormone. Available at: https://www.ncbi.nlm.nih.gov/books/NBK285545 (Accessed February 2020).
  7. [59]Biondi B. Mechanisms in endocrinology: Heart failure and thyroid dysfunction. Eur J Endocrinol (2012) 167: 609–18. doi: 10.1210/jc.2003-031641 22956554 · DOI · Paper page
  8. [60]Hansen PS Brix TH Sørensen TI Kyvik KO Hegedüs L. Major genetic influence on the regulation of the pituitary-thyroid axis: a study of healthy Danish twins. J Clin Endocrinol Metab (2004) 89: 1181–87. doi: 10.1210/jc.2003-031641 15001606 · DOI · Paper page

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Authors
Kahaly, G. J., & Gottwald-Hostalek, U.
Affiliations
Johannes Gutenberg University Mainz (DE)
Corresponding author
Kahaly, George J.
ORCID
Kahaly, George J.
Venue
Frontiers in Endocrinology
Publisher
Frontiers Media SA
Published
2022-11-02
Volume
13
Pages
1054983-1054983
ISSN
1664-2392 (ISSN-L)
DOI
10.3389/fendo.2022.1054983
PMC
PMC9666762
OpenAlex
W4308123309
Cited by
24
References
53
Citations by year
2026: 9 · 2025: 5 · 2024: 6 · 2023: 4
FWCI
0.53
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Endocrinology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
  • Health Sciences › Medicine › Surgery › Thyroid and Parathyroid Surgery
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Cancer Diagnosis and Treatment
Keywords
levothyroxine, hypothyroidism, thyroid hormone replacement, goiter, cretinism, iodine deficiency, thyroid-stimulating hormone, triiodothyronine, thyroid hormone assay, hypothalamic-pituitary-thyroid axis, thyroid hormone synthesis
MeSH terms
Congenital Hypothyroidism, Goiter, Humans, Thyroid Hormones, Thyrotropin, Thyroxine

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