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Cited by 485Thyroid Disorders and TreatmentsThyroid Cancer Diagnosis and TreatmentThyroid and Parathyroid Surgery

Conversion of Thyroxine (T4) to triiodothyronine (T3) in athyreotic human subjects

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Braverman, Lewis E., Ingbar, Sidney H., Sterling, Kenneth·1970·Journal of Clinical Investigation
DOI 10.1172/jci106304PMC PMC535757
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Abstract

Studies of the possibility that thyroxine (T4) is converted to 3.5,3'-triiodo-L-thyronine (T3) in the extrathyroidal tissues in man have been conducted in 13 patients, all but two of whom were athyreotic or hypothyroid, and all of whom were receiving at least physiological replacement doses of synthetic sodium-L-thyroxine.T3 was found in the sera of all patients, in concentrations ranging between 243 and 680 ng/100 ml (normal range 170-270 ng/100 ml). These concentrations were far in excess of those which would have been expected on the basis of the T3 contamination of the administered T4, as measured by the same technique employed in the analysis of serum. When oral medication was enriched with (125)I-labeled T4 for 8 or more days, labeled T3 and tetraiodothyroacetic acid (Tetrac or TA(4)) were found in the serum to the extent of approximately 2-5% of total radioactivity, as assessed by unidimensional paper chromatography. The same results were obtained with a specially purified lot of radioactive T4 containing less than 0.1% T3 as a contaminant. The identities of the (125)I-labeled T3 and TA(4) were verified by two-dimensional chromatography as well as by specific patterns of binding in serum. The labeled T3 isolated was bound by albumin and by T4-binding globulin (TBG), but not by T4-binding prealbumin (TBPA): in contrast the labeled TA(4) was bound by albumin and TBPA, but not by TBG. To exclude the possibility that the conversion of T4 to T3 was a peculiarity of the oral route of administration, the sera of two additional patients were obtained 48 hr after 7-day courses of daily intravenous injections of a mixture of stable and (125)I-labeled T4. Both stable and labeled T3 were likewise found in these sera. In contrast to earlier experiments in humans in which (131)I-labeled T3 was not definitively demonstrated in serum after a single intravenous injection of (131)I-labeled T4, the present findings are taken to provide conclusive evidence of the extrathyroidal conversion of T4 to T3 in man. These results raise once again the question of the extent to which the metabolic effect of T4 is mediated through the peripheral generation of T3.

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  • The rationale for the therapeutic use of LT4 in the treatment of hypothyroidism lies in the peripheral conversion of the exogenously administered pro-hormone thyroxine (T4) into its active metabolite T3.

    “The rationale for the therapeutic use of LT4 in the treatment of hypothyroidism lies in the peripheral conversion of the exogenously administered pro-hormone thyroxine (T4) into its active metabolite T 3 (10).”

    From Guidelines for the Treatment of Hypothyroidism: Prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement (2014) · cites this paper as [10]

    The Discussion reports peripheral conversion of administered T4 to T3 in patients lacking thyroid function, supporting the proposed rationale for LT4 treatment. It also leaves open whether T4 has a primary action of its own, so describing T4 simply as a pro-hormone overstates what the paper establishes. The supplied copy gives section labels but no page numbers. (LLM, conf=0.84)

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  • Biologically active T3 is generated from T4 in humans.

    “third, the demonstration that the biologically active T3 was generated from T4 in humans (10).”

    From Guidelines for the Treatment of Hypothyroidism: Prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement (2014) · cites this paper as [10]

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Research works printed but not linked: 1

  1. Gross, J., and C. P. Leblond. 1951. Metabolites of thy- roxine. Proc. Soc. Exp. Biol. Med. 76: 686.

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Authors
Braverman, L. E., Ingbar, S. H., & Sterling, K.
Affiliations
United States Department of Veterans Affairs (US)
ORCID
Braverman, Lewis E.
Venue
Journal of Clinical Investigation
Publisher
American Society for Clinical Investigation
Published
1970-05-01
Volume
49
Issue
5
Pages
855-864
ISSN
0021-9738 (ISSN-L)
DOI
10.1172/jci106304
PMC
PMC535757
OpenAlex
W2135957727
Cited by
485
References
34
Citations by year
2026: 1 · 2025: 6 · 2024: 6 · 2023: 9 · 2022: 13 · 2021: 7 · 2020: 10 · 2019: 11 · 2018: 7 · 2017: 6 · 2016: 14 · 2015: 6 · 2014: 8 · 2013: 11 · 2012: 8
FWCI
38.80
Type
journal article
Language
en
Open access
Locations
  • Journal of Clinical Investigation (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
Abbott Laboratories
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Cancer Diagnosis and Treatment
  • Health Sciences › Medicine › Surgery › Thyroid and Parathyroid Surgery
Keywords
thyroxine to triiodothyronine conversion, athyreosis, hypothyroidism, tetraiodothyroacetic acid, thyroxine-binding globulin, thyroxine-binding prealbumin, thyroid hormone metabolism
MeSH terms
Administration, Oral, Adult, Chromatography, Paper, Female, Humans, Hypothyroidism, Injections, Intravenous, Iodine Radioisotopes, Male, Middle Aged, Myxedema, Thyroid Neoplasms, Thyroidectomy, Thyroxine, Thyroxine-Binding Proteins, Triiodothyronine

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