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Thyroxine vs Thyroxine Plus Triiodothyronine in Treatment of Hypothyroidism After Thyroidectomy for Graves' Disease
Abstract
It was recently demonstrated that treatment with levorotatory thyroxine (T4) plus triiodothyronine (T3) compared with treatment with T4 alone improves psychologic functioning in hypothyroid patients with thyroid cancer or autoimmune thyroiditis. In the present double-blind crossover study, we again compared the effects of combined thyroid replacement vs monotherapy on psychologic function, endocrine function, cardiovascular function, and body composition. The patients were women who were hypothyroid after thyroidectomy for Graves' disease. The substitution of 10 microg of T3 for 50 microg of T4 caused a statistically significant decrease in free T4 concentration but no significant change in T3 or thyroid-stimulating hormone concentration. Symptoms of hypothyroidism and of hyperthyroidism tended to decrease on a standard symptom scale after combined treatment. With combined hormone replacement, mental state tended to improve on some mood scales but not on cognitive tests. We found alterations in left ventricular diastolic function but no change in body composition after the combined treatment regimen. These preliminary findings in a small group of patients with Graves' disease are consistent with earlier findings that thyroid replacement with T4-T3 combination improves mental functioning.
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Eleven trials were 5-16 weeks, three trials were 4-6 months, and one trial was 1 year in duration.
“Eleven trials were 5–16 weeks (23,46,49,51–53,58–60,71,79), three trials were 4–6 months (17,48,78), and one trial was 1 year in duration (47).”
From Evidence-Based Use of Levothyroxine/Liothyronine Combinations in Treating Hypothyroidism: A Consensus Document (2021) · cites this paper as [51]
Echocardiography parameters were basically unaltered in one trial that included this assessment.
“Echocardiography parameters were basically unaltered in one trial that included this assessment (51).”
From Evidence-Based Use of Levothyroxine/Liothyronine Combinations in Treating Hypothyroidism: A Consensus Document (2021) · cites this paper as [51]
In one trial, the benefit of combination therapy was observed only in thyroid cancer patients and not in patients with autoimmune thyroiditis.
“This may constitute a bias, as the benefit of combination therapy in one trial was observed only in the thyroid cancer patients and not in patients with autoimmune thyroiditis [48,49] .”
From 2012 ETA Guidelines: The Use of L-T4 + L-T3 in the Treatment of Hypothyroidism (2012) · cites this paper as [48]
Patient preference for combination therapy was associated with improvement in QoL, cognition, mood and symptoms in three trials but absent in two trials.
“Patient preference for combination therapy was associated with improvement in QoL, cognition, mood and symptoms in three trials [5,44,48] but absent in two trials [40,46] .”
From 2012 ETA Guidelines: The Use of L-T4 + L-T3 in the Treatment of Hypothyroidism (2012) · cites this paper as [48]
Some of the trials noted improvements (or trends towards improvement) in clinical parameters such as diastolic cardiac function, QoL, or lipid profiles.
“Some of these trials did note improvements (or trends towards improvement) in clinical parameters such as diastolic cardiac function 34 , QoL 36,40,50,51 , or lipid profiles 39,53 .”
From A review of the safety of triiodothyronine in combination with levothyroxine for the management of hypothyroidism (2024) · cites this paper as [50]
All but one randomized controlled studies of combined LT4/LT3 in hypothyroid subjects failed to find any differences in weight between combined LT4/LT3 and LT4 monotherapy.
“However, all but one randomized controlled studies of combined LT4/ LT3 in hypothyroid subjects failed to find any differences in weight between combined LT4/LT3 and LT4 monotherapy (31-39).”
From Effects of levothyroxine replacement or suppressive therapy on energy expenditure and body composition (2016) · cites this paper as [32]
Echocardiography parameters were basically unaltered in one trial that included this assessment.
“Echocardiography parameters were basically unaltered in one trial that included this assessment [51].”
From Evidence-Based Use of Levothyroxine/Liothyronine Combinations in Treating Hypothyroidism: A Consensus Document (2021) · cites this paper as [51]
Of the 14 combination therapy trials that have been completed, 10 employed once-daily LT3 administration, 4 employed twice-daily LT3 therapy, and none used three times a day LT3 therapy.
“Of the 14 combination therapy trials that have been completed, 10 employed once-daily LT3 administration [23, 46, 47, 49, 51, 52, 59, 71, 78, 79], 4 employed twicedaily LT3 therapy [17, 48, 53, 60], and none used three times a day LT3 therapy.”
From Evidence-Based Use of Levothyroxine/Liothyronine Combinations in Treating Hypothyroidism: A Consensus Document (2021) · cites this paper as [51]
In available crossover trials, four trials incorporating 128 patients showed a preference for combination therapy.
“In the available crossover trials, when examining the patients who completed the trials, four trials that incorporated 128 patients showed there was a preference for combination therapy [23, 46, 50, 51]”
From Evidence-Based Use of Levothyroxine/Liothyronine Combinations in Treating Hypothyroidism: A Consensus Document (2021) · cites this paper as [51]
Eleven prior combination therapy trials were 5-16 weeks, three trials were 4-6 months, and one trial was 1 year in duration.
“Eleven trials were 5-16 weeks [23, 46, 49, 51-53, 58-60, 71, 79], three trials were 4-6 months [17, 48, 78], and one trial was 1 year in duration [47].”
From Evidence-Based Use of Levothyroxine/Liothyronine Combinations in Treating Hypothyroidism: A Consensus Document (2021) · cites this paper as [51]
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Metadata
- Authors
- Bunevicius, R., Jakubonien, N., Jurkevicius, R., Cernicat, J., Lašas, L., & Prange, A. J.
- Affiliations
- Hospital of Lithuanian University of Health Sciences Kaunas Clinics (LT)
- University of North Carolina at Chapel Hill (US)
- Corresponding author
- Prange, Arthur J
- Venue
- Endocrine
- Published
- 2002
- Volume
- 18
- Issue
- 2
- Pages
- 129-134
- ISSN
- 0969-711X (ISSN-L)
- OpenAlex
- W1997047813
- Cited by
- 111
- References
- 2
- Citations by year
- 2025: 6 · 2024: 7 · 2023: 4 · 2022: 3 · 2021: 6 · 2020: 6 · 2019: 9 · 2018: 9 · 2017: 4 · 2016: 7 · 2015: 4 · 2014: 5 · 2013: 2 · 2012: 9
- FWCI
- 1.92
- Type
- journal article
- Language
- en
- Update notices
- erratum (2013-03-09)
- Open access
- closed
- Locations
- Endocrine (publishedVersion)
- PubMed (publishedVersion)
- Lithuanian University of Health Sciences (submittedVersion)
- 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
- thyroxine, triiodothyronine, hypothyroidism, Graves' disease, thyroidectomy, free thyroxine, thyroid-stimulating hormone, left ventricular diastolic function, body composition, mood, cognitive function, cardiovascular function
- MeSH terms
- Adult, Drug Therapy, Combination, Female, Graves Disease, Humans, Hypothyroidism, Middle Aged, Thyroidectomy, Thyroxine, Triiodothyronine, Patient Satisfaction, Hormone Replacement Therapy
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