The DOI matches its Crossref record; 26 of the 26 references it cites were found in a registry or an index.
Reduction in extrathyroidal triiodothyronine production by propylthiouracil in man.
Open accessAbstract
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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“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]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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]
Experimental — accuracy not yet measuredIn the citing paper
“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 the citing paper
“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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Citations
Cites
Conversion of Thyroxine (T4) to triiodothyronine (T3) in athyreotic human subjects
Braverman, L. E., Ingbar, S. H., & Sterling, K. (1970) · Journal of Clinical Investigation · doi:10.1172/jci106304 · Cited by 485
Studies of Thyrotropin Physiology by Means of Radioimmunoassay
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Self-citationPropylthiouracil inhibits the conversion of l-thyroxine to l-triiodothyronine
Oppenheimer, J. H., Schwartz, H. L., & Surks, M. I. (1972) · Journal of Clinical Investigation · doi:10.1172/jci107063 · Cited by 258
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The extrathyroidal conversion rate of thyroxine to triiodothyronine in normal man
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Triiodothyronine Radioimmunoassay
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Self-citationPlacental Transport of Thyroxine
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Triiodothyronine in cord serum
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Self-citationTriiodothyronine Concentration in Cord and Maternal Sera at Term
Eastman, C. J., Corcoran, J. M., Jequier, A. M., Ekins, R. P., & Williams, E. S. (1973) · Clinical Science · doi:10.1042/cs0450251 · Cited by 21
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Flagged first, then by citations
Research works printed but not linked: 1
- Snedecor, G. W., and W. G. Cochran. 1967. Statistical Methods. 6th edition. University of Iowa Press, Ames, Iowa. 593 pp.
Cited by
Sorted by citations
Jonklaas, J., Bianco, A. C., Bauer, A. J., Burman, K. D., Cappola, A. R., Celi, F. S., Cooper, D. S., Kim, B. W., Peeters, R. P., Rosenthal, M. S., et al. (2014) · Thyroid® · doi:10.1089/thy.2014.0028 · Cited by 1,928
“Presumably this reduction is due to inhibition of the PTU-susceptible D1, illustrating both that D1 contributes in part to maintenance of serum T3 and that D2 contributes importantly to maintenance of serum T3 levels (19).”
Bianco, A. C., Salvatore, D., Gereben, B., Berry, M. J., & Larsen, P. R. (2002) · Endocrine Reviews · doi:10.1210/edrv.23.1.0455 · Cited by 1,853
Cellular and Molecular Basis of Deiodinase-Regulated Thyroid Hormone Signaling1
Gereben, B., Zavacki, A. M., Ribich, S., Kim, B. W., Huang, S. A., Simonides, W. S., Zeöld, A., & Bianco, A. C. (2008) · Endocrine Reviews · doi:10.1210/er.2008-0019 · Cited by 891
Deiodinases: implications of the local control of thyroid hormone action
Bianco, A. C., & Kim, B. W. (2006) · Journal of Clinical Investigation · doi:10.1172/jci29812 · Cited by 845
Larsen, P. R., Silva, J. E., & Kaplan, M. M. (1981) · Endocrine Reviews · doi:10.1210/edrv-2-1-87 · Cited by 546
Metadata
- Authors
- Saberi, M., Sterling, F. H., & Utiger, R. D.
- Affiliations
- University of Pennsylvania (US)
- Venue
- Journal of Clinical Investigation
- Published
- 1975-02-01
- Volume
- 55
- Issue
- 2
- Pages
- 218-223
- ISSN
- 0021-9738 (ISSN-L)
- 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
- bronze
- doi.org
- 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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