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.

doi:10.1046/j.1365-2265.1996.00800.x

Cited by 41Thyroid Disorders and TreatmentsThyroid and Parathyroid SurgeryOphthalmology and Eye Disorders

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

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Abstract

OBJECTIVE The optimal dosage regimen for carbimazole (CBZ) in the treatment of hyperthyroidism remains uncertain, despite clinical use of the drug for approximately fifty years. We have compared the early clinical and biochemical responses to 20 or 40 mg/day of CBZ given as initial treatment for hyperthyroidism. DESIGN Prospective open multicentre trial. PATIENTS Sixty‐three patients presenting with hyperthyroidism. MEASUREMENTS Serum total and free thyroid hormones, serum TSH and SHBG were measured at baseline and at 4 and 10 weeks after start of therapy. Weight, pulse and a symptom questionnaire were also monitored at 6 and 12 weeks. RESULTS Patients randomized to a starting dose of 40 mg/day CBZ had lower total (98 ± 10 it 158 ± 11 nmol/l, P < 0.001) and free T4 (19.4 ± 2.6 vs 35.2 ± 3.7 pmol/l, P < 0.001) and total (2.6 ± 0.3 vs 4.3 ± 0.4 nmol/l, P < 0.001 and free T3 (8.3 ± 1.0 vs 13.7 ± 1.2 pmol/l, P < 0.01) at 4 weeks than those receiving 20 mg/day. Clinical responses at 6 and 12 weeks (weight, pulse, symptom score) and SHBG concentrations were similar. Drug‐related hypothyroidism was less likely to occur at 4 and 10 weeks in those patient who initially received 20 mg CBZ/day, but this dose was less effective at controlling hyperthyroidism in those with more severe hyperthyroidism with baseline TT4 > 260 nmol/l. CONCLUSIONS In treating hyperthyroidism, 20 mg/day carbimazole is effective, convenient and has a lower risk than 40 mg/day of iatrogenic hypothyroidism in patients with mild or moderate hyperthyroidism. Higher doses are required for those with severe hyperthyroidism.

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The MMI dose should be targeted to the degree of thyroid dysfunction because too low a dose will not restore a euthyroid state in severe disease and an excessive dose can cause iatrogenic hypothyroidism in mild disease.
“The dose of MMI should be targeted to the degree of thyroid dysfunction because too low a dose will not restore a euthyroid state in patients with severe disease (115) and an excessive dose can cause iatrogenic hypothyroidism in patients with mild disease (116).”
From 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis (2016) · cites this paper as [116]

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2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis
Ross, D. S., Burch, H. B., Cooper, D. S., Greenlee, M. C., Laurberg, P., Maia, A. L., Rivkees, S. A., Samuels, M., Sosa, J. A., Stan, M. N., et al. (2016) · Thyroid® · doi:10.1089/thy.2016.0229 · Cited by 2,938 · see citing works
“The dose of MMI should be targeted to the degree of thyroid dysfunction because too low a dose will not restore a euthyroid state in patients with severe disease (115) and an excessive dose can cause iatrogenic hypothyroidism in patients with mild disease (116).”
Background
Antithyroid Drugs
Cooper, D. S. (2005) · New England Journal of Medicine · doi:10.1056/nejmra042972 · Cited by 1,008 · see citing works
Hyperthyroidism
Cooper, D. S. (2003) · The Lancet · doi:10.1016/s0140-6736(03)14073-1 · Cited by 377 · see citing works
Comparison of Methimazole and Propylthiouracil in Patients with Hyperthyroidism Caused by Graves’ Disease
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 · see citing works
“There has been only one study reporting such an analysis (12), which observed that 20 mg/d carbimazole, a precursor of MMI, was too low for severe Graves’ patients (initial T4 20 g/dl) but adequate for less severely hyperthyroid patients.”
Background
Antithyroid drug regimen for treating Graves’ hyperthyroidism
Abraham, P., Avenell, A., McGeoch, S. C., Clark, L. F., & Bevan, J. S. (2010) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd003420.pub4 · Cited by 249 · see citing works
Antithyroid drugs in the management of patients with Graves' disease: an evidence-based approach to therapeutic controversies.
Cooper, D. (2003) · Journal of Clinical Endocrinology and Metabolism · doi:10.1210/jc.2003-030185 · Cited by 142 · see citing works
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 · see citing works
“The optimal starting dose has been a matter of some debate (Page et al., 1996).”
Background
ANTITHYROID DRUGS FOR THE TREATMENT OF HYPERTHYROIDISM CAUSED BY GRAVES' DISEASE
Cooper, D. S. (1998) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/s0889-8529(05)70308-x · Cited by 101 · see citing works
Predictors of long-term remission in patients with Graves’ disease: a single center experience
Anagnostis, P. G., Adamidou, F., Pοlyzos, S. A., Katergari, S., Karathanasi, E. M., Zouli, C., Panagiotou, A., & Kita, M. D. (2013) · Endocrine · doi:10.1007/s12020-013-9895-0 · Cited by 74 · see citing works
Comparison of Efficacy and Adverse Effects Between Methimazole 15 mg+Inorganic Iodine 38 mg/Day and Methimazole 30 mg/Day as Initial Therapy for Graves' Disease Patients with Moderate to Severe Hyperthyroidism
Sato, S., Noh, J. Y., Sato, S., Suzuki, M., Yasuda, S., Matsumoto, M., Kunii, Y., Mukasa, K., Sugino, K., Ito, K., et al. (2015) · Thyroid · doi:10.1089/thy.2014.0084 · Cited by 67 · see citing works
“There is also a report describing a similar high dose of the MMI pro-drug carbimazole as being necessary for severe hyperthyroidism (2).”
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 · see citing works
“These findings have been recently confirmed in a study comparing 20 mg and 40 mg of carbimazole for the initiation of treatment of Graves’ disease (Page et al., 1996).”
Background
The safety and efficacy of antithyroid drugs
Azizi, F. (2005) · Expert Opinion on Drug Safety · doi:10.1517/14740338.5.1.107 · Cited by 50 · see citing works
“On the other hand, over aggressive thionamide dosing [32] or use of thionamides in iodine deficient patients [33] may cause iatrogenic hypothyroidism; however, in some resistant cases with severe thyrotoxicosis, higher doses of thionamides are required.”
Background
Antithyroid drug regimen for treating Graves' hyperthyroidism
Abraham, P., Avenell, A., Watson, W. A., Park, C. M., & Bevan, J. S. (2005) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd003420.pub3 · Cited by 50 · see citing works
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 · see citing works
“A number of studies have consistently shown that treatment of hyperthyroidism with single daily dose of 15±60 mg of MMI is effective in the induction of euthyroidism in 80%2100% of the patients in one to seven months (Greer et al., 1977; Macfarlane et al., 1983; Morgan et al., 1984; Shiroozu et al., 1986; Arntzenius e…”
Background
Treatment of adult Graves’ disease
Corvilain, B., Hamy, A., Brunaud, L., Borson‐Chazot, F., Orgiazzi, J., Hachmi, L. B. S., Semrouni, M., Rodien, P., & Lussey‐Lepoutre, C. (2018) · Annales d Endocrinologie · doi:10.1016/j.ando.2018.08.003 · Cited by 35 · see citing works
Comparison of methimazole and propylthiouracil in the management of children and adolescents with Graves’ disease: efficacy and adverse reactions during initial treatment and long-term outcome
Sato, H., Minagawa, M., Sasaki, N., Sugihara, S., Kazukawa, I., Minamitani, K., Wataki, K., Konda, S., Inomata, H., Sanayama, K., et al. (2011) · Journal of Pediatric Endocrinology and Metabolism · doi:10.1515/jpem.2011.194 · Cited by 33 · see citing works
Pharmacodynamic Response to Anti-thyroid Drugs in Graves' Hyperthyroidism
Abbara, A., Clarke, S. A., Brewster, R., Simonnard, A., Eng, P. C., Phylactou, M., Papadopoulou, D., Izzi‐Engbeaya, C. N., Sam, A. H., Wernig, F., et al. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.00286 · Cited by 27 · see citing works
Low failure rate of fixed administered activity of 400 MBq 131I with pre-treatment with carbimazole for thyrotoxicosis: the Gateshead Protocol
Razvi, S., Basu, A., McIntyre, E. A., Wahid, S. T., Bartholomew, P. H., & Weaver, J. U. (2004) · Nuclear Medicine Communications · doi:10.1097/01.mnm.0000130242.29692.b2 · Cited by 19 · see citing works
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 · see citing works
“, [48], observed that 20 mg per day of CBZ was too low in the more severely hyperthyroid patients, with the majority still hyperthyroid at 4 wk.”
Background
An update on the pharmacological management of hyperthyroidism due to Graves’ disease
Bartalena, L., Tanda, M. L., Bogazzi, F., Piantanida, E., Lai, A., & Martino, E. (2005) · Expert Opinion on Pharmacotherapy · doi:10.1517/14656566.6.6.851 · Cited by 17 · see citing works
“(2005) 6(6) 855 hyperthyroidism may lead to hypothyroidism [20].”
Background
Hypothyroidism During Antithyroid Drug Treatment with Methimazole is a Favorable Prognostic Indicator in Patients with Graves' Disease
Choo, Y. K., Yoo, W. S., Kim, D. W., & Chung, H.-K. (2010) · Thyroid · doi:10.1089/thy.2009.0126 · Cited by 16 · see citing works
“ATD-associated hypothyroidism is thought to result from overly aggressive dosing in mild hyperthyroidism or failure to adjust the ATD dosage (10).”
Outcome of treatment of hyperthyroidism
Bringmann, I. M., van Leeuwen, B. L., Hennemann, G., et al. (1999) · Journal of Endocrinological Investigation · doi:10.1007/bf03343552 · Cited by 12 · see citing works
Novel spiroimidazopyridine derivative SAK3 improves methimazole-induced cognitive deficits in mice
Husain, N., Yabuki, Y., & Fukunaga, K. (2017) · Neurochemistry International · doi:10.1016/j.neuint.2017.03.001 · Cited by 11 · see citing works
“However, several reports indicate that hypothyroidism occurs following chronic MMI treatment due to improper monitoring of drug dosage (Page et al., 1996; CakicMilosevic et al., 2004).”
BackgroundInfluential
Free Thyroxine, Anti-Thyroid Stimulating Hormone Receptor Antibody Titers, and Absence of Goiter Were Associated with Responsiveness to Methimazole in Patients with New Onset Graves' Disease
Choi, H. S., & Yoo, W. S. (2017) · Endocrinology and Metabolism · doi:10.3803/enm.2017.32.2.281 · Cited by 10 · see citing works
Audit of long‐term treatment outcomes of thyrotoxicosis in a single‐centre virtual clinic: The utility of long‐term antithyroid drugs
Levy, M. J., Reddy, N. L., Price, D. E., Bhake, R. C., Bremner, E., Barrowcliffe, M., Kieffer, V., Robinson, C., Zaccardi, F., & Howlett, T. A. (2022) · Clinical Endocrinology · doi:10.1111/cen.14721 · Cited by 9 · see citing works
“When commencing ATD for newly diagnosed thyrotoxicosis, we have typically recommended CBZ 40mg once daily for 4 weeks and then reduced it to 20mg once daily, based on the results of an earlier collaborative study.(7) Patients are frequently referred to the clinic having already started other dose regimes in primary ca…”
Method
Comparison of methimazole/hydrocortisone ointment with oral methimazole in patients with graves disease: A prospective, randomized, open-label, parallel-group, 18-month study
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 · see citing works
The American Thyroid Association and American Association of Clinical Endocrinologists Guidelines for Hyperthyroidism and Other Causes of Thyrotoxicosis: An Appraisal
Daniels, G. H. (2011) · Endocrine Practice · doi:10.4158/ep11120.ed · Cited by 8 · see citing works
Effect of low and high doses of carbimazole in the treatment of Grave’s thyrotoxicosis: A prospective, open-label, and observational study
Singh, S. K., Singh, R., Bedi, S., Singh, V., Tiwari, A., & Kumar, P. (2025) · Thyroid Research and Practice · doi:10.4103/trp.trp_6_25 · Cited by 2 · see citing works
Effects of Dose Level of Anti-thyroid Drug Carbimazole on Thermoregulation and Blood Constituents in Male Rabbits(Oryctolagus cuniculus)
Saeed, I. H. (2014) · Advances in Research · doi:10.9734/air/2014/7802 · Cited by 2 · see citing works
“As the optimal dose regimen for CBZ in the treatment of hyperthyroidism remains uncertain [22], it was intended to establish a suitable effective dose of CBZ to induce experimental hypothyroidism in rabbits.”
Background
Hypothyroidism
McDermott, M., & Ridgway, E. C. (2009) · CRC Press eBooks · doi:10.3109/9781420070651-5 · Cited by 2 · see citing works
Treatment Options for Primary Thyroid Disease in Patients with Heart Failure
Toft, A. D., & Gaskell, K. M. (2009) · Springer eBooks · doi:10.1007/978-88-470-1143-4_19 · Cited by 2 · see citing works
Graves’ disease in India: epidemiological, clinical, and genetic differences from Caucasians
Singh, S. K., Singh, R., Pandey, A. K., Singh, V., Tiwari, A., & Rai, P. K. (2025) · Postgraduate Medical Journal · doi:10.1093/postmj/qgaf204 · Cited by 1 · see citing works
Graves’ Disease
Hollander, J. M., & Davies, T. F. (2009) · Elsevier eBooks · doi:10.1016/b978-1-4160-4745-2.00012-2 · Cited by 1 · see citing works
Hyperthyroidism Due to Graves’ Disease, Toxic Nodules and Toxic Multinodular Goiter
Burman, K. D. (2009) · CRC Press eBooks · doi:10.3109/9781420070651-3 · Cited by 1 · see citing works
Tormenta tiroidea
Crespo-Morfin, P. B., Guerrero-Gutiérrez, M. A., Damus-Ligonio, S. I., Guízar-Enríquez, K. O., Phinder-Puente, M. E., & Pérez‐Nieto, O. R. (2024) · Medicina Crítica · doi:10.35366/116322 · Cited by 2 · see citing works
Criterios de utilización de los antitiroideos en el tratamiento del hipertiroidismo
Navarro, E., & Astorga, R. (2000) · Revista Clínica Española · doi:10.1016/s0014-2565(00)70648-5 · Cited by 1 · see citing works
Antithyroid Drugs
Toft, A. D. (2004) · Elsevier eBooks · doi:10.1016/b0-12-475570-4/00139-6 · Cited by 1 · see citing works
Management of Graves' Disease in Children and Adolescents: Should Radioiodine Treatment Be Given?
Huen, K. (2004)
Evidence Based Medicine in Endocrinology
Rhee, S. Y., & Kim, Y. S. (2008) · Journal of Korean Endocrine Society · doi:10.3803/jkes.2008.23.6.379
Antithyroid drug therapy for Graves’ disease
Shin, S. M., & Yi, K. H. (2021) · Journal of Korean Medical Association · doi:10.5124/jkma.2021.64.10.690
“치료 전 유리T4 (free T4, FT4)치에 따라 치료에 필요 한 항갑상선제 용량이 차이가 있는지 비교한 연구에서 FT4 치가 7 ng/dL를 넘는 중증 갑상선기능항진증의 경우에는 MMI의 경우 30 mg (15 mg과 비교)[19], CBZ은 40 mg (20 mg과 비교)[20]의 고용량을 사용하여야 갑상선기능이 호전 되었다.”
Antithyroid drug treatment for thyrotoxicosis
Toft, A. D. (2011) · doi:10.1093/med/9780199235292.003.3189

Authors: Page, S. R., Sheard, C. E., Herbert, M., Hopton, M., & Jeffcoate, W. J.
Affiliations: Nottingham City Hospital (GB)
Queen's Medical Centre (GB)
Royal Derby Hospital (GB)
Corresponding author: Page, S. R.
ORCID: Jeffcoate, W. J.
Venue: Clinical Endocrinology
Publisher: Wiley
Published: 1996-11
Volume: 45
Issue: 5
Pages: 511-515
ISSN: 0300-0664 (ISSN-L)
1365-2265
DOI: 10.1046/j.1365-2265.1996.00800.x
OpenAlex: W2078591199
Cited by: 41
References: 0
Citations by year: 2025: 2 · 2024: 1 · 2022: 1 · 2021: 1 · 2020: 1 · 2018: 1 · 2017: 2 · 2016: 1 · 2014: 2 · 2013: 1
FWCI: 1.07
Type: journal article
Language: en
Open access: closed
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor, 2553 d)
Locations: Clinical Endocrinology (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
Health Sciences › Medicine › Surgery › Thyroid and Parathyroid Surgery
Health Sciences › Medicine › Pathology and Forensic Medicine › Ophthalmology and Eye Disorders
Keywords: carbimazole, hyperthyroidism, initial treatment, dose comparison, drug-induced hypothyroidism, free thyroxine, free triiodothyronine, serum TSH, sex hormone-binding globulin, symptom scores, pulse rate, weight
MeSH terms: Adolescent, Adult, Aged, Carbimazole, Drug Administration Schedule, Humans, Hyperthyroidism, Hypothyroidism, Middle Aged, Prospective Studies, Antithyroid Agents, Thyroxine, Triiodothyronine

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A comparison of 20 or 40 mg per day of carbimazole in the initial treatment of hyperthyroidism

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