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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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“The optimum duration of ATD treatment is 12 - 18 months, while short (6 months) treatment courses are associated with a high recurrence rate (22, 49); the underlying mechanisms for remission induced by ATDs are still uncertain.”
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“08), it is also associated with a higher frequency of adverse events [19].”
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Thyroid disorders in elderly: A comprehensive review
Thiruvengadam, S., & Luthra, P. (2021) · Disease-a-Month · doi:10.1016/j.disamonth.2021.101223 · Cited by 20
Risk of Diabetes in Patients with Long-Standing Graves’ Disease: A Longitudinal Study
Song, E., Koo, M. J., Noh, E., Hwang, S. Y., Park, M., Kim, J. A., Roh, E., Choi, K. M., Baik, S. H., Cho, G. J., et al. (2021) · Endocrinology and Metabolism · doi:10.3803/enm.2021.1251 · Cited by 18
“Block-and-replace” treatment in Graves’ disease: experience in a cohort of pediatric patients
Vigone, M. C., Peroni, E., Frenna, M. D., Mora, S., Barera, G., & Weber, G. (2019) · Journal of Endocrinological Investigation · doi:10.1007/s40618-019-01144-0 · Cited by 18
Resistant Thyrotoxicosis in a Patient with Graves Disease: A Case Report
Saleem, T., Sheikh, A., & Masood, Q. (2011) · Journal of Thyroid Research · doi:10.4061/2011/649084 · Cited by 18
Treatment options in the young patient with Graves' disease
Cheetham, T. D., & Bliss, R. (2015) · Clinical Endocrinology · doi:10.1111/cen.12871 · Cited by 17
Treatment of Graves Hyperthyroidism with Thionamides-Derived Drugs: Review
García-Mayor, R. V., & Larrañaga, A. (2010) · Medicinal Chemistry · doi:10.2174/1573406411006040239 · Cited by 18
“With respect to breast feeding, MMI appears more than PTU in breast milk [61] but in low concentrations.”
BackgroundŽarković, M., Wiersinga, W. M., Perros, P., Bartalena, L., Donati, S., Okosieme, O. E., Morris, D. S., Fichter, N., Lareida, J., Daumerie, C., et al. (2020) · Journal of Endocrinological Investigation · doi:10.1007/s40618-020-01320-7 · Cited by 17
A survey of the young person’s experience of Graves’ disease and its management
Lane, L. C., Rankin, J. M., & Cheetham, T. D. (2020) · Clinical Endocrinology · doi:10.1111/cen.14359 · Cited by 17
Lee, J.-E., Lee, D. H., Oh, T. J., Kim, K. M., Choi, S. H., Lim, S. K., Park, Y. J., Park, D. J., Jang, H. C., & Moon, J. H. (2018) · JMIR Research Protocols · doi:10.2196/resprot.8119 · Cited by 19
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Lane, L. C., Kuś, A., Bednarczuk, T., Bossowski, A. T., Daroszewski, J., Jurecka‐Lubieniecka, B., Cordell, H. J., Pearce, S. H. S., Cheetham, T. D., & Mitchell, A. L. (2020) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgaa347 · Cited by 16
“Genotype frequency CC 16 (13) 23 (7) CT 67 (57) 158 (45) TT 35 (30) 170 (48) P value 0.”
BackgroundLong-term management of Graves disease: a narrative review
Kim, H. (2022) · Journal of Yeungnam Medical Science · doi:10.12701/jyms.2022.00444 · Cited by 17
Kazakou, P., Tzanetakos, D., Vakrakou, A. G., Tzartos, J. S., Evangelopoulos, Μ.-E., Anagnostouli, M. C., Stathopoulos, P., Kassi, G., Stefanis, L., Kilidireas, C., et al. (2023) · Clinical and Experimental Medicine · doi:10.1007/s10238-022-00981-3 · Cited by 17
“…indicating that GD after ALZ treatment seems to have a more unpredictable course compared to conventional GD, requiring long-term ATD therapy or possible radical treatment (radioactive iodine or surgery); it should be noted here that “conventional” GD has a remission rate of 50% [7, 12, 14, 34].”
BackgroundPeng, R., Xie, P., Zhou, J., Zhou, W., Wang, Y., Chen, X., Yin, Q., Shen, L., Meng, L., Ye, L., et al. (2024) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgae892 · Cited by 15
Song, E., Kim, M., Park, S., Park, M., Kim, J. A., Roh, E., Yu, J. H., Kim, N. H., Seo, J. A., Kim, S. G., et al. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.761782 · Cited by 15
Interventions for preventing and treating hyperthyroidism in pregnancy
Earl, R., Crowther, C. A., & Middleton, P. (2010) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd008633.pub2 · Cited by 15
A Study on Nonthermal Irreversible Electroporation of the Thyroid
Lv, Y., Zhang, Y., Huang, J., Wang, Y., & Rubinsky, B. (2019) · Technology in Cancer Research & Treatment · doi:10.1177/1533033819876307 · Cited by 14
Karmisholt, J., Andersen, S. L., Bulow-Pedersen, I., Krejbjerg, A., Nygaard, B., & Carlé, A. (2022) · European Thyroid Journal · doi:10.1530/etj-22-0031 · Cited by 14
Is beta-carotene consumption associated with thyroid hormone levels?
Far, B. F., Lomer, N. B., Gharedaghi, H., Sahrai, H., Mahmoudvand, G., & Rouzbahani, A. K. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1089315 · Cited by 17
“The management pathway for hyperthyroidism produced by an excess of thyroid hormones is determined by the patient’s age, symptoms, comorbidities, and individual preferences (60).”
BackgroundHookham, J., Truran, P., Allahabadia, A., & Balasubramanian, S. P. (2016) · Postgraduate Medical Journal · doi:10.1136/postgradmedj-2015-133756 · Cited by 13
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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