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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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Cites
Measuring inconsistency in meta-analyses
Higgins, J. P. T., Thompson, S. G., Deeks, J. J., & Altman, D. G. (2003) · BMJ · doi:10.1136/bmj.327.7414.557 · Cited by 63,139
A Coefficient of Agreement for Nominal Scales
Cohen, J. (1960) · Educational and Psychological Measurement · doi:10.1177/001316446002000104 · Cited by 42,398
Systematic Reviews: Identifying relevant studies for systematic reviews
Dickersin, K., Scherer, R. W., & Lefebvre, C. (1994) · BMJ · doi:10.1136/bmj.309.6964.1286 · Cited by 2,255
Cooper, D. S. (2005) · New England Journal of Medicine · doi:10.1056/nejmra042972 · Cited by 1,008
The Management of Hyperthyroidism
Wood, A. J. J., & Franklyn, J. A. (1994) · New England Journal of Medicine · doi:10.1056/nejm199406163302407 · Cited by 302
Nakamura, H., Noh, J. Y., Itoh, K., Fukata, S., Miyauchi, A., Hamada, N., & Working Group of the Japan Thyroid Association for the Guideline of the Treatment of Graves’ Disease (2007) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2006-2135 · Cited by 277
Salvi, M., Vannucchi, G. M., Campi, I., Currò, N., Dazzi, D., Simonetta, S., Bonara, P., Rossi, S., Sina, C., Guastella, C., et al. (2007) · European Journal of Endocrinology · doi:10.1530/eje.1.02325 · Cited by 261
Administration of Thyroxine in Treated Graves' Disease
Hashizume, K., Ichikawa, K., Sakurai, A., Suzuki, S., Takeda, T., Kobayashi, M., Miyamoto, T., Arai, M., & Nagasawa, T. (1991) · New England Journal of Medicine · doi:10.1056/nejm199104043241403 · Cited by 214
A systematic review of drug therapy for Graves’ hyperthyroidism
Abraham, P., Avenell, A., Park, C. M., Watson, W. A., & Bevan, J. S. (2005) · European Journal of Endocrinology · doi:10.1530/eje.1.01993 · Cited by 211
Allannic, H., Fauchet, R., Orgiazzi, J., Orgiazzi, A., GENETET, B., LORCY, Y., GUERRIER, A. M. L., Delambre, C., & Derennes, V. (1990) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-70-3-675 · Cited by 192
REINWEIN, D., Benker, G., Lazarus, J. H., & Alexander, W. D. (1993) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.76.6.8501160 · Cited by 181
Romaldini, J. H., Bromberg, N., Werner, R. S., TANAKA, L. M., Rodrigues, H. F., WERNER, M. C., TANAKA, L. M., Rodrigues, H. F., WERNER, M. C., Farah, C. S., et al. (1983) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-57-3-563 · Cited by 162
Fassi, D. E., Nielsen, C. H., Bonnema, S. J., Hasselbalch, H. C., & Hegedűs, L. D. (2007) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2006-2388 · Cited by 160
McIver, B., Rae, P., Beckett, G. J., Wilkinson, E., Gold, A., & Toft, A. D. (1996) · New England Journal of Medicine · doi:10.1056/nejm199601253340403 · Cited by 135
Nedrebo, B., Holm, P., Uhlving, S., Sorheim, J., Skeie, S., Eide, G., Husebye, E., Lien, E., & Aanderud, S. (2002) · European Journal of Endocrinology · doi:10.1530/eje.0.1470583 · Cited by 132
Antithyroid drugs and Graves' disease — prospective randomized assessment of long‐term treatment
Maugendre, D., Gatel, A., Campion, L., Massart, C., Guilhem, I., LORCY, Y., Lescouarc’h, J., Herry, J. Y., & Allannic, H. (1999) · Clinical Endocrinology · doi:10.1046/j.1365-2265.1999.00629.x · Cited by 116
Glinoer, D., Nayer, P. D., & Bex, M. (2001) · European Journal of Endocrinology · doi:10.1530/eje.0.1440475 · Cited by 111
Benker, G., REINWEIN, D., Kahaly, G., Tegler, L., Alexander, W. D., Faßbinder, J., & Hirche, H. (1998) · Clinical Endocrinology · doi:10.1046/j.1365-2265.1998.00554.x · Cited by 108
Rituximab in relapsing Graves' disease, a phase II study
Heemstra, K. A., Toes, R. E. M., Sepers, J. M., Pereira, A. M., Corssmit, E. P. M., Huizinga, T. W. J., Romijn, J. A., & Smit, J. W. A. (2008) · European Journal of Endocrinology · doi:10.1530/eje-08-0084 · Cited by 105
Vrca, V. B., Škreb, F., Čepelak, I., Romić, Ž., & Mayer, L. (2004) · Clinica Chimica Acta · doi:10.1016/j.cccn.2003.10.028 · Cited by 98
Tsai, W., Pei, D., Wang, T., Wu, D., Li, J., Wei, C. L., Lee, C., Chen, S., & Kuo, S. (2005) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2005.02249.x · Cited by 83
García-Mayor, R. V., Páramo, C., Cano, R. L., Méndez, L. F. P., Galofré, J. C., & Andrade, A. (1992) · Journal of Endocrinological Investigation · doi:10.1007/bf03348811 · Cited by 69
LITHIUM CARBONATE IN THE TREATMENT OF THYROTOXICOSIS
Kristensen, O., Andersen, H. H., & Pallisgaard, G. (1976) · The Lancet · doi:10.1016/s0140-6736(76)90414-1 · Cited by 68
NICHOLAS, W. C., FISCHER, R. G., STEVENSON, R. A., & BASS, J. D. (1995) · Southern Medical Journal · doi:10.1097/00007611-199509000-00018 · Cited by 64
Weetman, A. P., Pickerill, A. P., Watson, P. H., Chatterjee, K., & Edwards, O. M. (1994) · QJM · doi:10.1093/oxfordjournals.qjmed.a068938 · Cited by 62
Medical Therapy of Graves' Disease: Does Thyroxine Prevent Recurrence of Hyperthyroidism?
Lucas, A., Salinas, I., Rius, F., Pizarro, E., Granada, M., Foz, M., & Sanmartı́, A. (1997) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.82.8.4118 · Cited by 61
Prediction of Outcome in Graves' Disease after Carbimazole Treatment
Weetman, A. P., Ratanachaiyavong, S., MIDDLETON, G. W., LOVE, W., John, R. M., OWEN, G. M., Darke, C., Lazarus, J. H., HALL, R., & McGregor, A. (1986) · QJM · doi:10.1093/oxfordjournals.qjmed.a067969 · Cited by 55
Controversies in the management of Graves' disease
Leech, N. J., & Dayan, C. M. (1998) · Clinical Endocrinology · doi:10.1046/j.1365-2265.1998.00558.x · Cited by 55
Tamai, H., Hayaki, I., Kawai, K., Komaki, G., Matsubayashi, S., Kuma, K., Kumagai, L. F., & Nagataki, S. (1995) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.80.5.7744989 · Cited by 52
Cho, B. Y., Shong, M. H., Yl, K. H., Lee, H. K., Koh, C., & Mln, H. K. (1992) · Clinical Endocrinology · doi:10.1111/j.1365-2265.1992.tb02269.x · Cited by 51
Effect of Methimazole, with or without l -Thyroxine, on Remission Rates in Graves’ Disease1
Rittmaster, R. S., Abbott, E. C., Douglas, R., Givner, M. L., Lehmann, L., Reddy, S. S. K., Salisbury, S. R., Shlossberg, A. H., Tan, M. H., & York, S. E. (1998) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.83.3.4613 · Cited by 50
Efficacy of single daily dosage of methimazole vs. propylthiouracil in the induction of euthyroidism
Homsanit, M., Sriussadaporn, S., Vannasaeng, S., Peerapatdit, T., Nitiyanant, W., & Vichayanrat, A. (2001) · Clinical Endocrinology · doi:10.1046/j.1365-2265.2001.01239.x · Cited by 48
He, C.-T., Hsieh, A.-T., Pei, D., Hung, Y.-J., Wu, L.-Y., Yang, T., Lian, W., Huang, W.-S., & Kuo, S.-W. (2004) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2004.02032.x · Cited by 47
Hoermann, R., Quadbeck, B., Roggenbuck, U., Szabolcs, I., Pfeilschifter, J., Meng, W., Reschke, K., Hackenberg, K., Dettmann, J., Prehn, B., et al. (2002) · Thyroid · doi:10.1089/105072502321085225 · Cited by 43
A comparison of 20 or 40 mg per day of carbimazole in the initial treatment of hyperthyroidism
Page, S. R., Sheard, C. E., Herbert, M., Hopton, M., & Jeffcoate, W. J. (1996) · Clinical Endocrinology · doi:10.1046/j.1365-2265.1996.00800.x · Cited by 41
KALLNER, G., Vitols, S., & Ljunggren, J. ‐. (1996) · Journal of Internal Medicine · doi:10.1046/j.1365-2796.1996.489827000.x · Cited by 38
Short‐term treatment of Graves' disease with methimazole in high versus low doses
Jorde, R., Ytre-Arne, K., Störmer, J., & Sundsfjord, J. (1995) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.1995.tb00914.x · Cited by 35
Grebe, S. K. G., Feek, C. M., Ford, H. C., Fagerström, J. N., Cordwell, D. P., DeLaHunt, J., & Toomath, R. J. (1998) · Clinical Endocrinology · doi:10.1046/j.1365-2265.1998.00446.x · Cited by 35
Prospective Randomized Comparison of Propylthiouracil
Gwinup, G. (1978) · JAMA · doi:10.1001/jama.1978.03280500053019 · Cited by 34
Treatment of Graves' disease by carbimazole: high dose with thyroxine compared to titration dose
Edmonds, C., & TELLEZ, M. U. (1994) · European Journal of Endocrinology · doi:10.1530/eje.0.1310120 · Cited by 34
Treatment of hyperthyroidism with a small single daily dose of methimazole
Mashio, Y., Beniko, M., Ikota, A., Mizumoto, H., & KUNITA, H. (1988) · European Journal of Endocrinology · doi:10.1530/acta.0.1190139 · Cited by 33
Kubota, S., Ohye, H., Nishihara, E., Kudo, T., Ito, M., Fukata, S., Amino, N., Kuma, K., & Miyauchi, A. (2005) · Endocrine Journal · doi:10.1507/endocrj.52.735 · Cited by 31
Raber, W., Kmen, E., Waldhäusl, W., & Vierhapper, H. (2000) · European Journal of Endocrinology · doi:10.1530/eje.0.1420117 · Cited by 31
Effect of Methimazole, with or without L-Thyroxine, on Remission Rates in Graves' Disease
Rittmaster, R. S. (1998) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.83.3.814 · Cited by 31
Escobar-Morreale, H. F., Gotarredona, J. S., Villar, L. M., García‐Robles, R., González‐Porqué, P., SANCHO, J. M., & Varela, C. (1996) · Thyroid · doi:10.1089/thy.1996.6.29 · Cited by 30
Pfeilschifter, J., & Ziegler, R. (1997) · European Journal of Endocrinology · doi:10.1530/eje.0.1360081 · Cited by 27
Do higher doses of carbimazole improve remission in Graves' disease?
Wilson, R., Buchanan, L., Fraser, W. D., McKillop, J. H., & Thomson, J. A. (1996) · QJM · doi:10.1093/qjmed/89.5.381 · Cited by 21
Role of colestipol in the treatment of hyperthyroidism
Hagag, P., Nissenbaum, H., & Weiss, M. (1998) · Journal of Endocrinological Investigation · doi:10.1007/bf03348036 · Cited by 16
Messina, M., Milani, P., Gentile, L., monaco, A. G. D., Brossa, C., Porta, M., & Camanni, F. (1987) · Journal of Endocrinological Investigation · doi:10.1007/bf03348132 · Cited by 16
TSH suppression combined with carbimazole for Graves' disease: effect on remission and relapse rates
Pujol, P., Osman, A., Grabar, S., Daurès, J., Galtier, F., Boegner, C., Baldet, L., Raye, R., Bringer, J., & Jaffiol, C. (1998) · Clinical Endocrinology · doi:10.1046/j.1365-2265.1998.00466.x · Cited by 15
Bromberg, N., Romaldini, J. H., Werner, R. S., Sgarbi, J. A., & WERNER, M. C. (1992) · Journal of Endocrinological Investigation · doi:10.1007/bf03348703 · Cited by 13
Meng, W., Meng, S., Männchen, E., Hampel, R., Kirsch, G., Dannenberg, J., & Krabbe, S. (2009) · Experimental and Clinical Endocrinology & Diabetes · doi:10.1055/s-0029-1211074 · Cited by 13
Mastorakos, G. P., Doufas, A. G., Mantzos, E., Mantzos, J. D., & Koutras, D. A. (2003) · Journal of Endocrinological Investigation · doi:10.1007/bf03348195 · Cited by 13
Medikamentöse Behandlung der Immunhyperthyreose (Typ Morbus Basedow)
Quadbeck, B., Hörmann, R., Janssen, O. E., & Mann, K. (2003) · Der Internist · doi:10.1007/s00108-003-0876-x · Cited by 10
HIGHER THAN CONVENTIONAL DOSES OF CARBIMAZOLE IN THE TREATMENT OF THYROTOXICOSIS
O'Malley, B. P., Rosenthal, F. D., Northover, B. J., Jennings, P. E., & WOODS, K. L. (1988) · Clinical Endocrinology · doi:10.1111/j.1365-2265.1988.tb01226.x · Cited by 9
Chen, L., Wang, H., Gao, Y., Liang, J., Men, W., Bai, J., Qi, W.-B., Zhang, J.-S., Zhang, J., Ren, J.-Q., et al. (2008) · Current Therapeutic Research · doi:10.1016/j.curtheres.2008.08.004 · Cited by 8
[Synthetic antithyroid drugs and Basedow's disease or the choice of a therapeutic strategy].
Allannic, H., LORCY, Y., Am, L., Delambre, C., Stetieh, H., Am, M., & Orgiazzi, J. (1991) · PubMed · Cited by 7
Leclere, J.-C. (1994) · PubMed · Cited by 7
[Recurrence of Graves-Basedow disease: the influence of treatment schedule].
Iriarte, M. J. G., Llenas, L. F., Beroiz, A. I., Apiñániz, E. A., Erdozain, R. R., & Torre, E. L. M. (1995) · PubMed · Cited by 6
[Improvement of the prognosis of Basedow's disease by using high doses of carbimazole].
Duprey, J., Louis, M.-F., Ducornet, B., Lifchitz, E., Mosse, A., Sultan, M., & Izembart, M. (1988) · PubMed · Cited by 6
Huszno, B., Trofimiuk, M., Gołkowski, F., Plinta, T., & Szybiński, Z. (2004) · PubMed · Cited by 4
Thyroxine suppression therapy in Graves' disease
Toft, A. D. (1997) · Baillière s Clinical Endocrinology and Metabolism · doi:10.1016/s0950-351x(97)80753-7 · Cited by 4
Soltani, A., Moayyeri, A., & Azizi, F. (2007) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2007.01.001 · Cited by 4
Antithyroid Drugs for the Treatment of Graves Disease
Peixoto, M. C., Buescu, A., alves, M. R. B. G., Albernaz, M. D. S., Coeli, C. M., & Vaisman, M. (2006) · The Endocrinologist · doi:10.1097/01.ten.0000249137.35809.b3 · Cited by 4
[Clinical epidemiology of Basedow's disease in Belgium].
Glinoer, D. (2000) · PubMed · Cited by 3
Research works printed but not linked: 2
- Reinwein, 1993, A prospective randomized trial of antithyroid drug dose in Graves' disease therap, Journal of Clinical Endocrinology and Metabolism, 76, 1516
- Tuncel, 2000, Effects of antithyroid drugs alone and plus L-thyroxine on the relapse of Graves disease, Journal of Endocrinological Investigation, 23, A71
Cited by
Sorted by citations
Bahn, R. S., Burch, H. B., Cooper, D. S., Garber, J. R., Greenlee, M. C., Klein, I., Laurberg, P., McDougall, I. R., Montori, V. M., Rivkees, S. A., et al. (2011) · Endocrine Practice · doi:10.4158/ep.17.3.456 · Cited by 1,098
2018 European Thyroid Association Guideline for the Management of Graves’ Hyperthyroidism
Kahaly, G. J., Bartalena, L., Hegedüs, L., Leenhardt, L., Poppe, K. G., & Pearce, S. H. S. (2018) · European Thyroid Journal · doi:10.1159/000490384 · Cited by 1,025
De Leo, S., Lee, S. Y., & Braverman, L. E. (2016) · The Lancet · doi:10.1016/s0140-6736(16)00278-6 · Cited by 883
Diagnosis and management of Graves disease: a global overview
Bartalena, L. (2013) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2013.193 · Cited by 311
Hyperthyroidism: aetiology, pathogenesis, diagnosis, management, complications, and prognosis
Wiersinga, W. M., Poppe, K. G., & Effraimidis, G. (2023) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(23)00005-0 · Cited by 254
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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