Elizabeth A. McAninch, MD; Antonio C. Bianco, MD, PhD
Acknowledgment: The authors thank Dr. Martin Surks, Dr. Jorge Mestman, and Dr. Colum Gorman for providing additional historical insight for this project; they did not read or endorse the final text.
Disclosures: Authors have disclosed no conflicts of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M15-1799.
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that she has no financial relationships or interests to disclose. Darren B. Taichman, MD, PhD, Executive Deputy Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Deborah Cotton, MD, MPH, Deputy Editor, reports that she has no financial relationships or interest to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Catharine B. Stack, PhD, MS, Deputy Editor for Statistics, reports that she has stock holdings in Pfizer.
Requests for Single Reprints: Elizabeth A. McAninch, MD, Division of Endocrinology and Metabolism, Rush University Medical Center, 1735 West Harrison Street, Cohn Building, Room 312, Chicago, IL 60612; e-mail, Elizabeth_A_McAninch@Rush.edu.
Current Author Addresses: Dr. McAninch: Division of Endocrinology and Metabolism, Rush University Medical Center, 1735 West Harrison Street, Cohn Building, Room 312, Chicago, IL 60612.
Dr. Bianco: Division of Endocrinology and Metabolism, Rush University Medical Center, 1735 West Harrison Street, Cohn Building, Room 212, Chicago, IL 60612.
Author Contributions:Conception and design: E.A. McAninch, A.C. Bianco.
Analysis and interpretation of the data: E.A. McAninch, A.C. Bianco.
Drafting of the article: E.A. McAninch, A.C. Bianco.
Critical revision of the article for important intellectual content: E.A. McAninch, A.C. Bianco.
Final approval of the article: E.A. McAninch, A.C. Bianco.
Obtaining of funding: A.C. Bianco.
Collection and assembly of data: E.A. McAninch, A.C. Bianco.
McAninch EA, Bianco AC. The History and Future of Treatment of Hypothyroidism. Ann Intern Med. 2016;164:50-56. doi: 10.7326/M15-1799
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Published: Ann Intern Med. 2016;164(1):50-56.
This article has been corrected. The original version (PDF) is appended to this article as a Supplement.
Thyroid hormone replacement has been used for more than a century to treat hypothyroidism. Natural thyroid preparations (thyroid extract, desiccated thyroid, or thyroglobulin), which contain both thyroxine (T4) and triiodothyronine (T3), were the first pharmacologic treatments available and dominated the market for the better part of the 20th century. Dosages were adjusted to resolve symptoms and to normalize the basal metabolic rate and/or serum protein-bound iodine level, but thyrotoxic adverse effects were not uncommon. Two major developments in the 1970s led to a transition in clinical practice: 1) The development of the serum thyroid-stimulating hormone (TSH) radioimmunoassay led to the discovery that many patients were overtreated, resulting in a dramatic reduction in thyroid hormone replacement dosage, and 2) the identification of peripheral deiodinase-mediated T4-to-T3 conversion provided a physiologic means to justify l-thyroxine monotherapy, obviating concerns about inconsistencies with desiccated thyroid. Thereafter, l-thyroxine monotherapy at doses to normalize the serum TSH became the standard of care. Since then, a subgroup of thyroid hormone–treated patients with residual symptoms of hypothyroidism despite normalization of the serum TSH has been identified. This has brought into question the inability of l-thyroxine monotherapy to universally normalize serum T3 levels. New research suggests mechanisms for the inadequacies of l-thyroxine monotherapy and highlights the possible role for personalized medicine based on deiodinase polymorphisms. Understanding the historical events that affected clinical practice trends provides invaluable insight into formulation of an approach to help all patients achieve clinical and biochemical euthyroidism.
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