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Cited by 138Thyroid Disorders and TreatmentsAdrenal Hormones and DisordersThyroid Cancer Diagnosis and Treatment

Reduction in extrathyroidal triiodothyronine production by propylthiouracil in man.

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Saberi, M, Sterling, F H, Utiger, R D·1975·Journal of Clinical Investigation
DOI 10.1172/jci107924PMC PMC301739
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Abstract

To determine if propylthiouracil (PTU) inhibited extrathyroidal thyroxine (T4) to triiodothyronine (T3) conversion in man, PTU was administered to T4-treated hypothyroid patients and serial measurements of T4, T3, and thyrotropin (TSH) carried out. All patients had proven thyroidal hypothyroidism and had been receiving 0.1 or 0.2 mg T4 daily for at least 2 mo before study. Hormone measurements were made for 5 consecutive days before and daily during a 7-day treatment period with PTU, 1,000 mg/day. In eight patients receiving 0.1 mg T4 daily, administration of PTU resulted in a prompt fall in mean serum T3 concentrations from 78 plus or minus 6 ng/100 ml (SEM) to 61 plus or minus 3 ng/100 ml after 1 day. The mean serum T3 concentrations ranged from 55 to 60 ng/100 ml during the remainder of the PTU treatment period (P less than 0.01). The mean control serum TSH concentration was 29.6 muU/ml and it increased to a peak of 40 muU/ml on the 5th and 6th days. In five patients receiving 0.2 mg T4 daily, the mean control serum T3 concentration was 84 plus or minus 7 NG/100ML. It fell to 70 plus or minus 5 ng/100 ml after 1 day and 63 plus or minus 7 ng/100 ml after 2 days of PTU administration and thereafter ranged from 6) to 69 ng/100 ml (P LESS THAN 0.01). Serum TSH concentrations did not increase. No changes in serum T4 concentrations were found in either group. In five patients who received 100 mg methimazole (MMI) daily for 7 days there were no changes in serum T4, T3, or TSH concentrations. These results indicate that PTU, but not MMI, produces a prompt and sustained, albeit modest, reduction in serum T3 concentrations in patients whose sole or major source of T3 is ingested T4. These findings most likely result from inhibition of extrathyroidal formation of T3 from T4.

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Crossref · 10.1172/jci107924

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  • In rodent models, TSH secretion is normalized before T3 levels are fully restored in plasma and other tissues, resulting in low circulating T3 levels and "tissue hypothyroidism."

    “Thus in rodent models, TSH secretion is normalized before T3 levels are fully restored in the plasma and other tissues, resulting in low circulating T3 levels and “tissue hypothyroidism.””

    From Evidence-Based Use of Levothyroxine/Liothyronine Combinations in Treating Hypothyroidism: A Consensus Document (2021) · cites this paper as [6]

    The Results (p. 220–221) report that PTU lowered serum T3 in human patients while TSH did not change significantly. The study does not show that TSH normalized before T3 was restored in rodent plasma or tissues, or establish tissue hypothyroidism. (LLM, conf=0.78)

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  • The role of D2 is to convert T4 to T3; approximately 60% of circulating T3 is estimated to originate from the D2 pathway in healthy individuals (18-20).

    “The role of D2 is to convert T4 to T3; approximately 60% of circulating T 3 is estimated to originate from the D2 pathway in healthy individuals (18-20).”

    From Guidelines for the Treatment of Hypothyroidism: Prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement (2014) · cites this paper as [19]

    The Introduction says that a large portion of serum T3 is produced by extrathyroidal conversion of T4. It does not identify D2 as the pathway or estimate that D2 produces approximately 60% of circulating T3 in healthy individuals. The indexed passages provide section labels but no page numbers. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • In LT4-treated thyroidectomized patients, achieving normal serum TSH levels, the D2 pathway contributes approximately 80% of circulating T3.

    “In LT4-treated thyroidectomized patients to achieve normal serum TSH levels, the D2 pathway contributes with ∼ 80% of the circulating T3 [6].”

    From Evidence-Based Use of Levothyroxine/Liothyronine Combinations in Treating Hypothyroidism: A Consensus Document (2021) · cites this paper as [6]

  • In rodent models, TSH secretion is normalized before T3 levels are fully restored in the plasma and other tissues, resulting in low circulating T3 levels and 'tissue hypothyroidism.'

    “Thus in rodent models, TSH secretion is normalized before T3 levels are fully restored in the plasma and other tissues, resulting in low circulating T3 levels and 'tissue hypothyroidism.'”

    From Evidence-Based Use of Levothyroxine/Liothyronine Combinations in Treating Hypothyroidism: A Consensus Document (2021) · cites this paper as [6]

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Research works printed but not linked: 1

  1. Snedecor, G. W., and W. G. Cochran. 1967. Statistical Methods. 6th edition. University of Iowa Press, Ames, Iowa. 593 pp.

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Authors
Saberi, M., Sterling, F. H., & Utiger, R. D.
Affiliations
University of Pennsylvania (US)
Venue
Journal of Clinical Investigation
Publisher
American Society for Clinical Investigation
Published
1975-02-01
Volume
55
Issue
2
Pages
218-223
ISSN
0021-9738 (ISSN-L)
DOI
10.1172/jci107924
PMC
PMC301739
OpenAlex
W2051726957
Cited by
138
References
26
Citations by year
2025: 1 · 2024: 1 · 2023: 2 · 2022: 1 · 2021: 2 · 2020: 2 · 2019: 1 · 2018: 1 · 2017: 3 · 2016: 1 · 2014: 3 · 2012: 3
FWCI
10.91
Type
journal article
Language
en
Open access
Locations
  • Journal of Clinical Investigation (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
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 › Endocrinology, Diabetes and Metabolism › Thyroid Cancer Diagnosis and Treatment
Keywords
propylthiouracil, methimazole, T4 to T3 conversion, thyroid hormone synthesis inhibition, hypothyroidism, thyroxine therapy, thyroid-stimulating hormone, serum triiodothyronine, antithyroid drugs
MeSH terms
Administration, Oral, Adult, Aged, Depression, Chemical, Female, Humans, Hypothyroidism, Male, Methimazole, Middle Aged, Propylthiouracil, Thyroid Neoplasms, Thyroidectomy, Thyroiditis, Autoimmune, Thyrotropin, Thyroxine, Triiodothyronine

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