The emergence of levothyroxine as a treatment for hypothyroidism

Hennessey, James V.

doi:10.1007/s12020-016-1199-8

Cited by 66Thyroid Disorders and TreatmentsThyroid and Parathyroid SurgeryThyroid Cancer Diagnosis and Treatment

The emergence of levothyroxine as a treatment for hypothyroidism

Hennessey, James V.·2017·Endocrine

DOI 10.1007/s12020-016-1199-8

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Abstract

Objective To describe the historical refinements, understanding of physiology and clinical outcomes observed with thyroid hormone replacement strategies.Methods A Medline search was initiated using the search terms, levothyroxine, thyroid hormone history, levothyroxine mono therapy, thyroid hormone replacement, combination LT4 therapy, levothyroxine Bioequivalence. Pertinent articles of interest were identified by title and where available abstract for further review. Additional references were identified in the course of review of the literature identified.Results Physicians have intervened in cases of thyroid dysfunction for more than two millennia. Ingestion of animal thyroid derived preparations has been long described but only scientifically documented for the last 130 years. Refinements in hormone preparation, pharmaceutical production and regulation continue to this day. The literature provides documentation of physiologic, pathologic and clinical outcomes which have been reported and continuously updated. Recommendations for effective and safe use of these hormones for reversal of patho-physiology associated with hypothyroidism and the relief of symptoms of hypothyroidism has documented a progressive refinement in our understanding of thyroid hormone use. Studies of thyroid hormone metabolism, action and pharmacokinetics have allowed evermore focused recommendations for use in clinical practice. Levothyroxine mono-therapy has emerged as the therapy of choice of all recent major guidelines.Conclusions The evolution of thyroid hormone therapies has been significant over an extended period of time. Thyroid hormone replacement is very useful in the treatment of those with hypothyroidism. All of the most recent guidelines of major endocrine societies recommend levothyroxine mono-therapy for first line use in hypothyroidism.

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Adherence to a LT4 preparation results in significantly reduced hypothyroidism-related non-drug medical costs and hypothyroidism-related total medical costs.
“Moreover, adherence to a LT4 preparation results in significantly reduced hypothyroidism-related non-drug medical costs and hypothyroidism-related total medical costs (28, 40).”
From ETA guidelines for the use of levothyroxine sodium preparations in monotherapy to optimize the treatment of hypothyroidism (2025) · cites this paper as [40]
Owing to uncertainties regarding levothyroxine bioequivalence of certain generics to branded compounds, some variation in patients' TSH levels was observed.
“Owing to some uncertainties regarding the levothyroxine bioequivalence of certain generics to that of branded compounds, some variation in patients’ TSH levels were observed (28, 39, 40).”
From ETA guidelines for the use of levothyroxine sodium preparations in monotherapy to optimize the treatment of hypothyroidism (2025) · cites this paper as [40]
LT4 is a safe, effective hormone replacement therapy for hypothyroidism caused by autoimmune thyroiditis, partial or total thyroidectomy, radioiodine treatment, or drug side effects.
“The drug levothyroxine (LT4) constitutes a safe, effective hormone replacement therapy for hypothyroidism caused by autoimmune thyroiditis, partial or total thyroidectomy, radioiodine treatment, or drug side effects [ 1 – 5 ].”
From Factors influencing the levothyroxine dose in the hormone replacement therapy of primary hypothyroidism in adults (2022) · cites this paper as [1]

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Gastrointestinal malabsorption of thyroxine
Virili, C., Antonelli, A., Santaguida, M. G., Benvenga, S., & Centanni, M. (2019) · Endocrine Reviews · doi:10.1210/er.2018-00168 · Cited by 164 · see citing works
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ETA guidelines for the use of levothyroxine sodium preparations in monotherapy to optimize the treatment of hypothyroidism
Centanni, M., Duntas, L., Feldt-Rasmussen, U., Koehrle, J., Peeters, R. P., Razvi, S., Trimboli, P., & Virili, C. (2025) · European Thyroid Journal · doi:10.1530/etj-25-0123 · Cited by 38 · see citing works
“Switching among generics is not associated with clinically signi ﬁ cant changes in TSH level for Brito et al. in a study encompassing some 16,000 patients (38) but not for others (28, 37, 39, 40).”
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Authors: Hennessey, J. V.
Affiliations: Beth Israel Deaconess Medical Center (US)
Corresponding author: Hennessey, James V.
ORCID: Hennessey, James V.
Venue: Endocrine
Publisher: Springer Science and Business Media LLC
Published: 2016-12-16
Volume: 55
Issue: 1
Pages: 6-18
ISSN: 0969-711X (ISSN-L)
1355-008X
1559-0100
DOI: 10.1007/s12020-016-1199-8
OpenAlex: W2566552250
Cited by: 66
References: 121
Citations by year: 2026: 3 · 2025: 8 · 2024: 3 · 2023: 9 · 2022: 9 · 2021: 8 · 2020: 8 · 2019: 8 · 2018: 6 · 2017: 4
FWCI: 0.88
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (unspecified)
Locations: Endocrine (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 › Endocrinology, Diabetes and Metabolism › Thyroid Cancer Diagnosis and Treatment
Keywords: levothyroxine, hypothyroidism, thyroid hormone replacement, levothyroxine monotherapy, bioequivalence, thyroid hormone metabolism, thyroid hormone action, thyroid hormone regulation, treatment guidelines
MeSH terms: Animals, Drug Compounding, Drug Interactions, Drug Therapy, Combination, Endocrinology, Humans, Hypothyroidism, Societies, Scientific, Therapeutic Equivalency, Thyroid (USP), Thyroxine, United States, Practice Guidelines as Topic, Evidence-Based Medicine, Hormone Replacement Therapy, History, 20th Century, History, 21st Century, Precision Medicine

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The emergence of levothyroxine as a treatment for hypothyroidism

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