Efficacy and Safety of Once Weekly Thyroxine as Compared to Daily Thyroxine in Managing Primary Hypothyroidism: A Systematic Review and Meta-Analysis
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Aims: No meta-analysis is available which has holistically analyzed efficacy and safety of once weekly thyroxine (OWT) vs. standard daily therapy (SDT) with regards to managing primary hypothyroidism. We undertook this meta-analysis to address this knowledge gap. Methods: Electronic databases were searched for clinical trials involving hypothyroid patients receiving OWT in intervention arm, and SDT in control arm. Primary outcome was to evaluate changes in serum thyroid stimulating hormone. Secondary outcomes were to evaluate alterations in total tetra-iodothyronine (TT4), total tri-iodothyronine (TT3), free T4 (FT4), free T3 (FT4), heart rate (HR), cardiac function, symptomatology, and adverse events. Results: From initially screened 159 studies, data from four trials involving 294 patients were analyzed. Patients of OWT had significantly higher thyroid stimulating hormone (TSH) [mean difference (MD) +1.85 mU/L (95% confidence interval, CI: 0.95–2.75); P < 0.01; I 2 = 63%], comparable TT4 [MD -0.87 mcg/dl (95% CI: -2.98–1.24); P = 0.42; I 2 = 65%], and significantly lower TT3 [MD -15.7 ng/dl (95% CI: -29.9–1.51); P = 0.03; I 2 = 90%], following 6-weeks therapy. TT4 [MD 3.05 mcg/dl (95% CI: 1.44–4.66); P < 0.01], and FT4 [MD 0.56 ng/dl (95% CI: 0.04–1.08); P = 0.03; I 2 = 66%] were significantly higher 2 h after thyroxine intake, in people on OWT compared to SDT. TT4 levels were significantly higher 4 h after thyroxine intake in OWT as compared to SDT [MD 0.70 ng/dl (95% CI: 0.52–0.88); P < 0.01]. Following 4–8 h of intake of thyroxine, isovolumetric contraction time [MD 3.62 ms (95% CI: 1.93–5.31); P < 0.01; I 2 = 0%] and aortic ejection time/pre-ejection period ratio [MD 0.01 (95% CI: 0.00–0.02); P = 0.02; I 2 = 0%], were significantly higher in people on OWT as compared to SDT. Conclusion: OWT is associated with less efficient control of hypothyroidism at 6 weeks and may be associated with supraphysiologic elevation of thyroid hormone levels along with transient echocardiographic changes in some patients following 2-4 h of thyroxine intake.
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In the short term, weekly oral LT4 treatment produces higher total T4 and free T4 levels, echocardiographic changes, tachycardia, and palpitations, but these do not persist long term.
“In the short term, higher total T4 and free T4 levels are observed, as well as echocardiographic changes, tachycardia, and palpitations, but these symptoms do not persist in the long term.”
From Refractory hypothyroidism: unraveling the complexities of diagnosis and management (2023) · cites this paper as [94]
Weekly oral LT4 treatment gives slightly less effective control of hypothyroidism, with higher TSH and lower total T3 levels.
“Weekly oral treatment shows slightly less effective control of hypothyroidism, with higher TSH levels and lower total T3 levels.”
From Refractory hypothyroidism: unraveling the complexities of diagnosis and management (2023) · cites this paper as [94]
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GRADE: an emerging consensus on rating quality of evidence and strength of recommendations
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BackgroundMethodInfluentialAssessing the Quality of Randomized Trials
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Treatment of Hypothyroidism with Once Weekly Thyroxine1
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Twice-weekly dosing for thyroxine replacement in elderly patients with primary hypothyroidism
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Abstract #1076: Hypothyroidism - Once a Week Treatment Option in Young and Middle Aged Adults.
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Refractory hypothyroidism: unraveling the complexities of diagnosis and management
Quiroz-Aldave, J. E., Concepción-Zavaleta, M. J., Durand-Vásquez, M. D. C., Concepción-Urteaga, L. A., Gamarra-Osorio, E. R., Suárez-Rojas, J., Rafael-Robles, L. D. P., Paz-Ibarra, J., & Román-González, A. (2023) · Endocrine Practice · doi:10.1016/j.eprac.2023.09.003 · Cited by 14 · see citing works
- Authors
- Dutta, D., Jindal, R., Kumar, M., Mehta, D., Dhall, A., & Sharma, M.
- Affiliations
- Safdarjang Hospital (IN)
- Corresponding author
- Dutta, Deep
- Venue
- Indian Journal of Endocrinology and Metabolism
- Published
- 2021-03
- Volume
- 25
- Issue
- 2
- Pages
- 76-85
- ISSN
- 2230-8210 (ISSN-L)
- 2230-9500
- PMC
- PMC8477739
- OpenAlex
- W3196738394
- Cited by
- 10
- References
- 19
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 3 · 2023: 1 · 2022: 2
- FWCI
- 1.12
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Licence
- cc-by-nc-sa
- Locations
- Indian Journal of Endocrinology and Metabolism (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- 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
- primary hypothyroidism, thyroid-stimulating hormone, total thyroxine, total triiodothyronine, free thyroxine, free triiodothyronine, heart rate, adverse events, drug safety and efficacy, peak and trough drug levels, cardiac function, symptomatology
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