Efficacy of methimazole before the administration of radioactive iodine in the management of Graves’ disease: a systematic review and meta-analysis

Bolakale-Rufai, Ikeoluwapo Kendra; Abioro, Imodoye; Ngene, Samuel Osobuchi; Woldeamanuel, Yohannes

doi:10.1590/1516-3180.2022.0225.R1.19102022

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Sao Paulo Medical Journal

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ORIGINAL ARTICLE • Sao Paulo Med. J. 141 (5) • 2023 • https://doi.org/10.1590/1516-3180.2022.0225.R1.19102022 copy

Efficacy of methimazole before the administration of radioactive iodine in the management of Graves’ disease: a systematic review and meta-analysis

Authorship SCIMAGO INSTITUTIONS RANKINGS

ABSTRACT

BACKGROUND:

The efficacy of anti-thyroid drugs in conjunction with radioactive iodine therapy in the management of Graves’ disease is still controversial.

OBJECTIVE:

To compare the efficacy of pretreatment with methimazole before the administration of radioactive iodine for the treatment of Graves’ disease.

DESIGN AND SETTING:

A systematic review and meta-analysis was conducted at a teaching/tertiary hospital in Ibadan, Nigeria.

METHODS:

A systematic search of the PubMed, Embase, Cochrane Library, and Web of Science databases was performed from inception to December, 2021.

RESULTS:

Five studies with 297 participants were included. There was no difference in the risk of persistent hyperthyroidism when radioactive iodine was used in conjunction with methimazole compared with when radioactive iodine was used alone (relative risk: 1.02, 95% confidence interval, CI: 0.62–1.66; P = 0.95, I² = 0%). Subgroup analysis based on the duration between discontinuation of methimazole and the administration of radioactive iodine showed a lower risk of persistent hyperthyroidism when methimazole was discontinued within 7 days before radioactive iodine use, although this did not reach statistical significance (risk ratio: 0.85, CI: 0.28–2.58).

CONCLUSIONS:

The use of methimazole before radioactive iodine administration was not associated with an increased risk of persistent hyperthyroidism. Concerns about medication toxicity and adverse effects should be considered when clinicians make decisions on combination therapies for the treatment of Graves’ disease.

PROSPERO REGISTRATION:

CRD42020150013, https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=150013.

KEY WORDS (MeSH terms):
Methimazole; Graves disease; Elements, radioactive; Hyperthyroidism

AUTHORS’ KEY WORDS:
Anti-thyroid drugs; Radioactive iodine; Hyperthyroidism secondary

Study	Country	AgeRAI+MMZ	AgeRAI	SexRAI+MMZ(M/F)	SexRAI(M/F)	No. assigned to RAI+MMZ	No. assigned to R AI	Duration of MMZ discontinuation (days)	FT4 RAI+MMZ(pmol/L)	FT4RAI(pmol/L)	Follow up(months)
Andrade et al.²⁰20. Andrade VA, Gross JL, Maia AL. Effect of methimazole pretreatment on serum thyroid hormone levels after radioactive treatment in Graves’ hyperthyroidism. J Clin Endocrinol Metab. 1999;84(11):4012-6. PMID:11502768; https://doi.org/10.1210/jcem.86.8.7707. https://doi.org/https://doi.org/10.1210/...	Brazil	37.6	34.5	2/25	4/24	23	28	4	61.78 ± 5.15	59.20 ± 5.92	1
Andrade et al.²²22. Andrade VA, Gross JL, Maia AL. The effect of methimazole pretreatment on the efficacy of radioactive iodine therapy in Graves’ hyperthyroidism: one-year follow-up of a prospective, randomized study. J Clin Endocrinol Metab. 2001;86(8):3488-93. PMID: 11502768; https://doi.org/10.1210/jcem.86.8.7707. https://doi.org/https://doi.org/10.1210/...	Brazil	37.4	35.1	2/27	4/28	29	32	4	59.20 ± 27.00	57.90 ± 21.90	12
Braga et al.²¹21. Braga M, Walpert N, Burch HB, Solomon BL, Cooper DS. The effect of methimazole on cure rates after radioiodine treatment for Graves’ hyperthyroidism: a randomized clinical trial. Thyroid. 2002;12(2):135-9. PMID: 11916282; https://doi.org/10.1089/105072502753522365. https://doi.org/https://doi.org/10.1089/...	United States	43.0	35.0	6/10	0/18	16	18	6	44.30 ± 21.00	66.80 ± 35.70	8
Burch et al.²³23. Burch HB, Solomon BL, Cooper DS, et al. The effect of antithyroid drug pretreatment on acute changes in thyroid hormone levels after (131)I ablation for Graves’ disease. J Clin Endocrinol Metab. 2001;86(7):3016-21. PMID: 11443161; https://doi.org/10.1210/jcem.86.7.7639. https://doi.org/https://doi.org/10.1210/...	United States	42.0	36.0	7/14	2/19	21	21	6	80.00 ± 45.00	52.00 ± 40.00	0.5
Pirnat et al.²⁴24. Pirnat E, Zaletel K, Gaberšček S, Hojker S. The outcome of 131I treatment in Graves’ patients pretreated or not with methimazole. Hell J Nucl Med. 2011;14(1):25-9. PMID: 21512661.	Slovenia	43.5	46.8	8/42	8/51	50	59	7	20.40 ± 9.10	38.00 ± 17.80	1,3,6,&12

Unique ID	Experimental	Comparator	Randomization process	Deviations from intended interventions	Missing outcome data	Measurement of the outcome	Selection of the reported result	Overall
Andrade et al.²²22. Andrade VA, Gross JL, Maia AL. The effect of methimazole pretreatment on the efficacy of radioactive iodine therapy in Graves’ hyperthyroidism: one-year follow-up of a prospective, randomized study. J Clin Endocrinol Metab. 2001;86(8):3488-93. PMID: 11502768; https://doi.org/10.1210/jcem.86.8.7707. https://doi.org/https://doi.org/10.1210/...	RAI+MMZ	RAI	+	+	+	+	?	+
Braga et al.²¹21. Braga M, Walpert N, Burch HB, Solomon BL, Cooper DS. The effect of methimazole on cure rates after radioiodine treatment for Graves’ hyperthyroidism: a randomized clinical trial. Thyroid. 2002;12(2):135-9. PMID: 11916282; https://doi.org/10.1089/105072502753522365. https://doi.org/https://doi.org/10.1089/...	RAI+MMZ	RAI	?	+	+	?	?	?
Andrade et al.²⁰20. Andrade VA, Gross JL, Maia AL. Effect of methimazole pretreatment on serum thyroid hormone levels after radioactive treatment in Graves’ hyperthyroidism. J Clin Endocrinol Metab. 1999;84(11):4012-6. PMID:11502768; https://doi.org/10.1210/jcem.86.8.7707. https://doi.org/https://doi.org/10.1210/...	RAI+MMZ	RAI	+	+	+	+	?	?
Burch et al.²³23. Burch HB, Solomon BL, Cooper DS, et al. The effect of antithyroid drug pretreatment on acute changes in thyroid hormone levels after (131)I ablation for Graves’ disease. J Clin Endocrinol Metab. 2001;86(7):3016-21. PMID: 11443161; https://doi.org/10.1210/jcem.86.7.7639. https://doi.org/https://doi.org/10.1210/...	RAI+MMZ	RAI	+	?	+	+	+	?
Pirnat et al.²⁴24. Pirnat E, Zaletel K, Gaberšček S, Hojker S. The outcome of 131I treatment in Graves’ patients pretreated or not with methimazole. Hell J Nucl Med. 2011;14(1):25-9. PMID: 21512661.	RAI+MMZ	RAI	?	?	+	?	?	?

	Study name/Subgroup name	Risk ratio	CI lower limit	CI upper limit	Weight	Q	p_Q	I²
1	Andrade et al.²²22. Andrade VA, Gross JL, Maia AL. The effect of methimazole pretreatment on the efficacy of radioactive iodine therapy in Graves’ hyperthyroidism: one-year follow-up of a prospective, randomized study. J Clin Endocrinol Metab. 2001;86(8):3488-93. PMID: 11502768; https://doi.org/10.1210/jcem.86.8.7707. https://doi.org/https://doi.org/10.1210/...	1.38	0.40	4.77	66.25%
2	Andrade et al.²⁰20. Andrade VA, Gross JL, Maia AL. Effect of methimazole pretreatment on serum thyroid hormone levels after radioactive treatment in Graves’ hyperthyroidism. J Clin Endocrinol Metab. 1999;84(11):4012-6. PMID:11502768; https://doi.org/10.1210/jcem.86.8.7707. https://doi.org/https://doi.org/10.1210/...	1.83	0.32	10.45	33.75%
3	4 days	1.52	0.28	8.18	45.01%	0.07	0.793	0.00%
4	Braga et al.²¹21. Braga M, Walpert N, Burch HB, Solomon BL, Cooper DS. The effect of methimazole on cure rates after radioiodine treatment for Graves’ hyperthyroidism: a randomized clinical trial. Thyroid. 2002;12(2):135-9. PMID: 11916282; https://doi.org/10.1089/105072502753522365. https://doi.org/https://doi.org/10.1089/...	1.13	0.07	18.34	28.17%
5	Burch et al.²³23. Burch HB, Solomon BL, Cooper DS, et al. The effect of antithyroid drug pretreatment on acute changes in thyroid hormone levels after (131)I ablation for Graves’ disease. J Clin Endocrinol Metab. 2001;86(7):3016-21. PMID: 11443161; https://doi.org/10.1210/jcem.86.7.7639. https://doi.org/https://doi.org/10.1210/...	1.50	0.26	8.50	71.83%
6	6 days	1.38	0.27	7.16	46.69%	0.03	0.859	0.00%
7	Pirnat et al.²⁴24. Pirnat E, Zaletel K, Gaberšček S, Hojker S. The outcome of 131I treatment in Graves’ patients pretreated or not with methimazole. Hell J Nucl Med. 2011;14(1):25-9. PMID: 21512661. (12 months)	1.18	0.17	8.25	11.87%
8	Pirnat et al.²⁴24. Pirnat E, Zaletel K, Gaberšček S, Hojker S. The outcome of 131I treatment in Graves’ patients pretreated or not with methimazole. Hell J Nucl Med. 2011;14(1):25-9. PMID: 21512661. (6 months)	2.36	0.61	9.09	22.70%
9	Pirnat et al.²⁴24. Pirnat E, Zaletel K, Gaberšček S, Hojker S. The outcome of 131I treatment in Graves’ patients pretreated or not with methimazole. Hell J Nucl Med. 2011;14(1):25-9. PMID: 21512661. (3 months)	0.51	0.14	1.88	23.73%
10	Pirnat et al.²⁴24. Pirnat E, Zaletel K, Gaberšček S, Hojker S. The outcome of 131I treatment in Graves’ patients pretreated or not with methimazole. Hell J Nucl Med. 2011;14(1):25-9. PMID: 21512661. (1 month)	0.59	0.24	1.47	41.71%
11	7 days	0.85	0.28	2.58	8.30%	3.59	0.309	16.46%
12	Combined effect size	1.38	1.07	1.79		4.96	0.665	0.00%

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