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Cited by 192Thyroid Disorders and TreatmentsThyroid Cancer Diagnosis and TreatmentAdrenal Hormones and Disorders

Propylthiouracil blocks extrathyroidal conversion of thyroxine to triiodothyronine and augments thyrotropin secretion in man.

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Geffner, D L, Azukizawa, M, Hershman, J M·1975·Journal of Clinical Investigation
DOI 10.1172/jci107925PMC PMC301740
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Abstract

Propylthiouracil (PTU) inhibits peripheral deiodination of thyroxine (T4) and triiodothyronine (T3) and decreases the metabolic effectiveness of T4 in animals. To assess the effect of PTU on extrathyroidal conversion of T4 to T3 in man, 15 studies were performed in athyreotic patients treated with 100 or 200 mug of L-T4 daily for 1 mo before the addition of PTU, 250 mg every 6 h for 8 days. serum T3, T4, and thyrotropin (TSH) were measured daily by radioimmunoassay; serum TSH response to 500-mug thyrotropin-releasing hormone (TRH) was measured before and on the last day of giving PTU. On the 100-mug LT4 dose, serum T3 fell from 120 plus or minus 5 (SE) to 83 plus or minus 6 ng/dl (P less than 0.005) with return to 113 plus or minus 5 ng/dl after stopping PTU; serum T4 (4.5 plus or minus 0.3 mug/dl) did not change. Similar results were seen in patients taking 200 mug of L-T4 daily. On the 100-mug dose of L-T4 the fall in T3 was accompanied by a reciprocal rise in serum TSH to 195 plus or minus 33% of initial concentration (P less than 0.01) with return to 104 plus or minus 8% after PTU. The serum TSH response to TRH (DELTAMUU/ml over base line) was greater during PTU therapy than during the control period. On 100-mug L-T4 DELTA TSH rose from 64 plus or minus 19 to 101 plus or minus 23 muU/ml (P less than 0.005). Expressed as percent of base-line TSH concentration, TSH rose from 140 plus or minus 52 to 280 plus or minus 44% (control vs. PTU) at 15 min, 265 plus or minus 72 to 367 plus or minus 63% at 30 min, 223 plus or minus 54 to 313 plus or minus 54% at 45 min, 187 plus or minus 45 to 287 plus or minus 51% at 60 min, and 145 plus or minus 22 to 210 plus or minus 28% at 120 min after TRH. The data suggest that PTU blocks extrathyroidal conversion of T4 to T3, thus increasing pituitary TSH secretion and augmenting the TSH response to TRH.

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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 [18]

    The Discussion reports that serum T3 fell in athyreotic patients receiving T4 during PTU treatment, consistent with conversion of T4 to T3. It does not identify D2 as the pathway or estimate that D2 produces approximately 60% of circulating T3 in healthy individuals. The indexed passages do not provide a page number for the Discussion. (LLM, conf=0.86)

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Research works printed but not linked: 2

  1. Hershman, J. M., J. G. Kenimer, A. Kojima, and R. L. Saunders. 1974. Assay of thyroid stimulating hor- mone. In Hormones in Human Plasma. H. Antoniades editor. Excerpta Medica Foundation, Publishers, Am- sterdam. 2nd edition. In press.
  2. Snedecor, G. W., and W. G. Cochran. 1967. Statistical Methods. The Iowa State University Press, Ames. 6th edition. 91.

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Authors
Geffner, D. L., Azukizawa, M., & Hershman, J. M.
Affiliations
United States Department of Veterans Affairs (US)
Venue
Journal of Clinical Investigation
Publisher
American Society for Clinical Investigation
Published
1975-02-01
Volume
55
Issue
2
Pages
224-229
ISSN
0021-9738 (ISSN-L)
DOI
10.1172/jci107925
PMC
PMC301740
OpenAlex
W2142623819
Cited by
192
References
37
Citations by year
2025: 6 · 2024: 3 · 2023: 5 · 2022: 5 · 2021: 3 · 2020: 1 · 2019: 4 · 2018: 1 · 2017: 5 · 2016: 2 · 2015: 2 · 2014: 3 · 2013: 1 · 2012: 7
FWCI
14.73
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 › Thyroid Cancer Diagnosis and Treatment
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
Keywords
propylthiouracil, thyroxine to triiodothyronine conversion, thyrotropin secretion, levothyroxine, thyroid hormone metabolism, antithyroid drugs
MeSH terms
Depression, Chemical, Humans, Injections, Intravenous, Male, Myxedema, Parkinson Disease, Propylthiouracil, Thyroid Diseases, Thyroidectomy, Thyrotropin, Thyrotropin-Releasing Hormone, Thyroxine, Triiodothyronine

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