The DOI matches its Crossref record; 25 of the 25 references it cites were found in a registry or an index.
Controlled Clinical Trial of Combined Triiodothyronine and Thyroxine in the Treatment of Hypothyroidism
Open accessAbstract
A -double-blind crossover trial of a combined preparation of triiodothyronine and thyroxine (1:4 ratio) compared with thyroxine alone was conducted with 99 patients previously stabilized on. thyroxine as treatment for hypothyroidism. Four patients were excluded during the trial and eight afterwards owing to gross deficiencies in taking the tablets. Of the remaining 87 patients 42 (48%) had no -preference for either medication, 29 (33%) preferred thyroxine alone, and 16 (18%) the combination. A high incidence of unpleasant symptoms was experienced during the two months' treatment with the combined preparation. The serum protein-bound iodine levels were lowered (mean reduction 1.8 mug./100 ml.) on the combination, but the labelled T(3)-resin sponge uptake values were not altered and remained in the normal range. on both treatments.
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“Earlier studies in the 1960s suggested that LT3 was associated with an excess risk of thyrotoxicosis and its cardiovascular complications (69).”
From Risk of Death and Adverse Effects in Patients on Liothyronine: A Multisource Systematic Review and Meta-analysis (2025) · cites this paper as [69]
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 daily L-T3 dose was administered as a single dose in all trials except four, in which it was divided in two doses [37,40,42,43] .”
From 2012 ETA Guidelines: The Use of L-T4 + L-T3 in the Treatment of Hypothyroidism (2012) · cites this paper as [37]
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In the citing paper
“The L-T3 dose administered during combination therapy varied between 5 and 25 g daily, with the exception of the oldest study in which 40-60 g L-T3 was given [37] .”
From 2012 ETA Guidelines: The Use of L-T4 + L-T3 in the Treatment of Hypothyroidism (2012) · cites this paper as [37]
The cited source says what the claim attributes to it.
In the citing paper
“The earliest study from 1970 [37] and the most recent one from 2009 [5] are not included in the meta-analysis, but all other studies (performed between 1999 and 2005) are included in the meta-analysis [34] .”
From 2012 ETA Guidelines: The Use of L-T4 + L-T3 in the Treatment of Hypothyroidism (2012) · cites this paper as [37]
In the citing paper
“The second of these studies involved administration of high doses of thyroid hormones, including doses of T3 of up to 60 mg/day 52 .”
From A review of the safety of triiodothyronine in combination with levothyroxine for the management of hypothyroidism (2024) · cites this paper as [52]
In the citing paper
“There were few suggestions of AE consistent with iatrogenic thyrotoxicosis due to over treatment with T3, and these (biochemical evidence of increased bone resorption or palpitations) arose in studies where the LT4:T3 ratio of treatment was particularly low (4:1) 39,52 .”
From A review of the safety of triiodothyronine in combination with levothyroxine for the management of hypothyroidism (2024) · cites this paper as [52]
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Citations
Cites
JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM
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Drug Defaulting in a General Practice
Porter, A. M. W. (1969) · BMJ · doi:10.1136/bmj.1.5638.218 · Cited by 258
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Mitchell, M. L., HARDEN, A. B., & O’ROURKE, M. E. (1960) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-20-11-1474 · Cited by 105
Surgical Treatment of Thyrotoxicosis
Hedley, A. J., Flemming, C. J., CHESTERS, M. I., Michie, W., & Crooks, J. (1970) · BMJ · doi:10.1136/bmj.1.5695.519 · Cited by 83
THYROID STATUS IN PREGNANCY AND IN WOMEN TAKING ORAL CONTRACEPTIVES
Goolden, A. W. G., GARTSIDE, J. M., & Sanderson, C. (1967) · The Lancet · doi:10.1016/s0140-6736(67)92420-8 · Cited by 69
Combined Thyroxine and Triiodothyronine for Thyroid Replacement Therapy
Taylor, S., Kapur, M., & Adie, R. (1970) · BMJ · doi:10.1136/bmj.2.5704.270 · Cited by 44
Self-citation
Research works printed but not linked: 10
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- Devlin, W. F., and Stephenson, N. R. (1962). journal of Pharmacy and Pharmacology, 14, 597.
- Devlin, W. F., and Watanabe, H. (1966). Journal of Pharmaceutical Sciences, 55, 390.
- Lavietes, P. H., and Epstein, F. H. (1964). Annals of Internal Medicine, 60, 79.
- Lemieux, R., and Talmage, J. M. (1966). Journal of Pharmacy and Pharma- cology, 18, 94.
- Pileggi, V. J., Golub, 0. J., and Lee, N. D. (1965). Journal of Clinical Endocrinology and Metabolism, 25, 949.
- Porter, A. M. W. (1969). British Medical Journal, 1, 218.
- Sachs, B. A., Wolfman, L., and Murthy, G. (1968). Amcrican Journal of the Medical Sciences, 256, 232.
- Selenkow, H. A., and Wool, M. S. (1967). Annals of Internal Medicine, 67, 90.
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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
“(528) in 1970, since the dosages of LT4 that were used were higher than those typically used in current clinical practice and the study predated utilization of TSH measurements, both of which may have contributed to TH overreplacement in the study.”
Bunevičius, R., Kažanavičius, G., Žalinkevičius, R., & Prange, A. J. (1999) · New England Journal of Medicine · doi:10.1056/nejm199902113400603 · Cited by 482
2012 ETA Guidelines: The Use of L-T4 + L-T3 in the Treatment of Hypothyroidism
Wiersinga, W. M., Duntas, L., Fadeyev, V., Nygaard, B., & Vanderpump, M. P. J. (2012) · European Thyroid Journal · doi:10.1159/000339444 · Cited by 427
Grozinsky-Glasberg, S., Fraser, A., Nahshoni, E., Weizman, A., & Leibovici, L. (2006) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2006-0448 · Cited by 296
Treatment with thyroid hormone
Biondi, B., & Wartofsky, L. (2014) · Endocrine Reviews · doi:10.1210/er.2013-1083 · Cited by 259
“In 1970, Smith et al (128) published the first double-blind crossover study to assess the effects of combination therapy with T3 and T4 in patients with hypothyroidism.”
Background
Metadata
- Authors
- Smith, R. N., Taylor, S. A., & Massey, J. C.
- Affiliations
- Sheffield Children's Hospital (GB)
- ORCID
- Taylor, S. A.
- Venue
- BMJ
- Publisher
- BMJ
- Published
- 1970-10-17
- Volume
- 4
- Issue
- 5728
- Pages
- 145-148
- ISSN
- 0007-1447 (ISSN-L)
- 0959-8138
- 1468-5833
- PMC
- PMC1819870
- OpenAlex
- W2054161925
- Cited by
- 106
- References
- 25
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 2 · 2023: 5 · 2022: 1 · 2021: 5 · 2020: 2 · 2019: 5 · 2018: 7 · 2016: 6 · 2015: 3 · 2014: 4 · 2013: 3 · 2012: 4
- FWCI
- 2.77
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- BMJ (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Abbott Laboratories
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Surgery › Thyroid and Parathyroid Surgery
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Cancer Diagnosis and Treatment
- Keywords
- hypothyroidism, triiodothyronine, thyroxine, drug preference, adverse drug reactions, serum protein-bound iodine, thyroid hormone replacement
- MeSH terms
- Adult, Aged, Clinical Trials as Topic, Drug Synergism, Female, Humans, Hypothyroidism, Male, Middle Aged, Thyroid Function Tests, Thyroxine, Tremor, Triiodothyronine
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