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

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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

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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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A Radioimmunoassay for Measurement of Thyroxine in Unextracted Serum*
CHOPRA, I. J. (1972) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-34-6-938 · Cited by 539
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
Thyroid Hormone Action in Cell Culture: Demonstration of Nuclear Receptors in Intact Cells and Isolated Nuclei
Samuels, H. H., & Tsai, J. S. (1973) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.70.12.3488 · Cited by 337
An improved radioimmunoassay of triiodothyronine in serum: its application to clinical and physiological studies.
CHOPRA, I. J., HO, R. S., & LAM, R. W. (1972) · PubMed · Cited by 285
Propylthiouracil 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
Inhibition of thyrotropin response to thyrotropin-releasing hormone by small quantities of thyroid hormones
Snyder, P. J., & Utiger, R. D. (1972) · Journal of Clinical Investigation · doi:10.1172/jci107014 · Cited by 201
Triiodothyronine and Thyroxine in Hyperthyroidism COMPARISON OF THE ACUTE CHANGES DURING THERAPY WITH ANTITHYROID AGENTS
Abuid, J., & Larsen, P. R. (1974) · Journal of Clinical Investigation · doi:10.1172/jci107744 · Cited by 156
Specific Triiodothyronine Binding Sites in the Anterior Pituitary of the Rat
Schadlow, A. R., Surks, M. I., Schwartz, H. L., & Oppenheimer, J. H. (1972) · Science · doi:10.1126/science.176.4040.1252 · Cited by 101
RESPONSE TO SYNTHETIC THYROTROPIN-RELEASING HORMONE IN MAN
Hershman, J. M., & Pittman, J. A. (1970) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-31-4-457 · Cited by 90
Self-citation
Interactions of L-Thyroxine or L-Triiodothyronine and Thyrotropin- Releasing Factor on the Release and Synthesis of Thyrotropin from the Anterior Pituitary Gland of Mice
Bowers, C. Y., Schally, A. V., Reynolds, G. A., & HAWLEY, W. D. (1967) · Endocrinology · doi:10.1210/endo-81-4-741 · Cited by 83

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Research works printed but not linked: 2

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

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