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Antithyroid drug regimen for treating Graves’ hyperthyroidism
Open accessAbstract
BACKGROUND: Antithyroid drugs are widely used in the therapy of hyperthyroidism. There are wide variations in the dose, regimen or duration of treatment used by health professionals. OBJECTIVES: To assess the effects of dose, regimen and duration of antithyroid drug therapy for Graves' hyperthyroidism. SEARCH STRATEGY: We searched seven databases and reference lists. SELECTION CRITERIA: Randomised and quasi-randomised trials of antithyroid medication for Graves' hyperthyroidism. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data and assessed risk of bias. Pooling of data for primary outcomes, and select exploratory analyses were undertaken. MAIN RESULTS: Twenty-six randomised trials involving 3388 participants were included. Overall the quality of trials, as reported, was poor. None of the studies investigated incidence of hypothyroidism, changes in weight, health-related quality of life, ophthalmopathy progression or economic outcomes. Four trials examined the effect of duration of therapy on relapse rates, and when using the titration regimen 12 months was superior to six months, but there was no benefit in extending treatment beyond 18 months. Twelve trials examined the effect of block-replace versus titration block-regimens. The relapse rates were similar in both groups at 51% in the block-replace group and 54% in the titration block-group (OR 0.86, 95% confidence interval (CI) 0.68 to1.08) though adverse effects (rashes (10% versus 6%) and withdrawing due to side effects (16% versus 9%)) were significantly higher in the block-replace group. Three studies considered the addition of thyroxine with continued low dose antithyroid therapy after initial therapy with antithyroid drugs. There was significant heterogeneity between the studies and the difference between the two groups was not significant (OR 0.58, 95% CI 0.05 to 6.21). Four studies considered the addition of thyroxine alone after initial therapy with antithyroid drugs. There was no significant difference in the relapse rates between the groups after 12 months follow-up (OR 1.15, 95% CI 0.79 to 1.67). Two studies considered the addition of immunosuppressive agents. The results which were in favour of the interventions would need to be validated in other populations. AUTHORS' CONCLUSIONS: The evidence suggests that the optimal duration of antithyroid drug therapy for the titration regimen is 12 to 18 months. The titration (low dose) regimen had fewer adverse effects than the block-replace (high dose) regimen and was no less effective. Continued thyroxine treatment following initial antithyroid therapy does not appear to provide any benefit in terms of recurrence of hyperthyroidism. Immunosuppressive therapies need further evaluation.
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“Pariani et al. [12] reported a high requirement (64%) for long-term ATD, RAI or surgery, compared with approximately 50% in conventional GD [80].”
From 2019 European Thyroid Association Guidelines on the Management of Thyroid Dysfunction following Immune Reconstitution Therapy (2019) · cites this paper as [80]
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Rajaii, F., Gupta, S., & Douglas, R. S. (2014) · Taiwan Journal of Ophthalmology · doi:10.1016/j.tjo.2014.03.001 · Cited by 1
Tran, H. A., & Reeves, G. E. M. (2011) · Journal of Endocrinology and Metabolism · doi:10.4021/jem.v1i1.10 · Cited by 1
“This is contrary to patients with spontaneous GD where conventional treatment is 12 18 months in total [20].”
ResultDisorders of the Thyroid in Childhood and Adolescence
Uday, S., Davies, C., & Gleeson, H. K. (2019) · Springer eBooks · doi:10.1007/978-3-319-99817-6_32 · Cited by 1
Surgical Management of Hyperthyroidism
Orloff, L. A., & Shindo, M. L. (2020) · Elsevier eBooks · doi:10.1016/b978-0-323-66127-0.00008-9 · Cited by 2
Hyperthyreose – Fokus Immunthyreopathie Basedow
Theiler‐Schwetz, V., Trummer, C., & Pilz, S. (2020) · Journal für Klinische Endokrinologie und Stoffwechsel · doi:10.1007/s41969-020-00112-x · Cited by 1
Vanderpump, M. P. J. (2021) · Oxford University Press eBooks · doi:10.1093/med/9780198851899.003.0001 · Cited by 1
Weetman, A. P. (2013) · Medicine · doi:10.1016/j.mpmed.2013.06.012 · Cited by 1
Thyroid peroxidase antibodies and their role in predicting outcomes in Graves’ disease treatment
Gewert, K., Topi, G., Planck, T., & Calissendorff, J. (2025) · Frontiers in Endocrinology · doi:10.3389/fendo.2025.1517283 · Cited by 2
“Interestingly, while a Cochrane review from 2010 did not fi nd any bene fi t from prolonged treatment (18), another systematic review and meta-analysis found that prolonged use of ATD increased remission rates (10).”
Kim, K. J., Song, E., Kim, M., Kwon, H., Ku, E. J., Kwon, H. W., Yoon, J. H., Lee, E. K., Lee, W. W., Park, Y. J., et al. (2025) · International Journal of Thyroidology · doi:10.11106/ijt.2025.18.1.65 · Cited by 1
Dual Thyroid Ectopia with Graves’ Disease: a Case Report and a Review of the Literature
Tan, T. H., Lee, B. N., Hassan, S. Z. A., Ch’ng, E. S., & Hussein, Z. B. (2012) · Nuclear Medicine and Molecular Imaging · doi:10.1007/s13139-012-0160-x · Cited by 1
“Whereas the duration of remission in medically treated Graves’ disease is usually longer, about 12–18 months [17].”
BackgroundThe adverse effects of hypothyroidism and hyperthyroidism during pregnancy
Rezazadeh, M. B. (2015) · DOAJ (DOAJ: Directory of Open Access Journals) · doi:10.17463/rcm.2015.03.009 · Cited by 1
Five cases of childhood-onset Graves’ disease treated with either surgery or radio-iodine therapy
Tomari, K., Goto, M., Shimada, A., Yagi, H., Nagashima, Y., & Hasegawa, Y. (2017) · Clinical Pediatric Endocrinology · doi:10.1297/cpe.26.265 · Cited by 1
Cardiovascular risk factors, autoimmunity and insulin resistance in Graves' disease
Ferreira, C., Neves, C., Neves, J. S., Oliveira, S. C., Sokhatska, O., Pereira, M. F., Oliveira, A., Medina, J. L., Delgado, L., & Carvalho, D. M. (2020) · Revista Portuguesa de Endocrinologia Diabetes e Metabolismo · doi:10.26497/ao190010 · Cited by 1
The Management of Thyroid Disease in COVID-19 Pandemic
Yoo, W. S., & Chung, H.-K. (2020) · International Journal of Thyroidology · doi:10.11106/ijt.2020.13.2.65 · Cited by 1
Thyroid Dermopathy Treatment of the Foot in the Setting of Graves Hyperthyroidism
Mateen, S., & Pontious, J. (2021) · The Journal of Foot & Ankle Surgery · doi:10.1053/j.jfas.2020.12.002 · Cited by 1
Updates in the Management of Graves Disease in Children
Lee, Y. J. (2023) · Ewha Medical Journal · doi:10.12771/emj.2023.e31 · Cited by 1
Metadata
- Authors
- Abraham, P., Avenell, A., McGeoch, S. C., Clark, L. F., & Bevan, J. S.
- Affiliations
- Aberdeen Royal Infirmary (GB)
- University of Aberdeen (GB)
- NHS Grampian (GB)
- Venue
- Cochrane Database of Systematic Reviews
- Publisher
- Wiley
- Published
- 2010-01-20
- Volume
- 2010
- Issue
- 1
- Pages
- CD003420-CD003420
- ISSN
- 1361-6137 (ISSN-L)
- 1465-1858
- PMC
- PMC6599817
- OpenAlex
- W2167716419
- Cited by
- 249
- References
- 66
- Citations by year
- 2026: 6 · 2025: 10 · 2024: 14 · 2023: 16 · 2022: 12 · 2021: 30 · 2020: 28 · 2019: 29 · 2018: 10 · 2017: 16 · 2016: 12 · 2015: 9 · 2014: 11 · 2013: 6 · 2012: 7
- FWCI
- 1.27
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cochrane Database of Systematic Reviews (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Ophthalmology › Ophthalmology and Eye Disorders
- Health Sciences › Medicine › Surgery › Thyroid and Parathyroid Surgery
- Keywords
- Graves' disease, Graves' hyperthyroidism, antithyroid drugs, treatment duration, relapse rate, immunosuppressants, adverse drug reactions, hypothyroidism, ophthalmopathy, health-related quality of life, economic outcomes
- MeSH terms
- Drug Administration Schedule, Female, Graves Disease, Humans, Hyperthyroidism, Male, Antithyroid Agents, Thyroxine, Randomized Controlled Trials as Topic
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