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J Endocrinol Invest. 2019 Nov;42(11):1273-1283. doi: 10.1007/s40618-019-01054-1. Epub 2019 May 27.

Safety of long-term antithyroid drug treatment? A systematic review.

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Internal Medicine and Endocrinology, Endocrine Research Center of Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, P.O. Box: 19395-4763, Tehran, Islamic Republic of Iran.
Internal Medicine and Endocrinology, Endocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, Tehran, Islamic Republic of Iran.


Continued low-dose MMI treatment for longer than 12-18 months may be considered in patients not in remission. However, ATDs are not free from adverse effects. We undertook a systematic review to clarify safety of long-term ATD treatment. Medline and the Cochrane Library for trials published between 1950 and Nov 2018 were systematically searched. We included original studies containing data for long-term (> 18 months) ATD treatment. Two reviewers independently extracted data from included trials and any disagreement was adjudicated by consensus. Of 615 related articles found, 12 fulfilled the criteria. Six articles had data for adults, five for non-adults and one article had data for both groups. The sample sizes ranged between 20 and 249 individuals, and the mean duration of ATD treatment ranged between 2.1 and 14.2 years. Considering all data from 1660 patients treated with ATD for a mean duration of 5.8 years (around 10,000 patient-years), major complications occurred only in 14 patients: 7 severe agranulocytosis, 5 severe liver damage, one ANCA-associated glomerulonephritis and one vasculitis with small cutaneous ulcerations. Minor complications rates were between 2 and 36%, while more complications were in higher doses and in the children. The most reported AE was cutaneous reaction; the other adverse events were elevated liver enzymes, leukocytopenia, arthritis, arthralgia, myalgia, thrombocytopenia, fever, nausea and oral aphthous. Long-term ATD treatment is safe, especially in low dose and in adults, indicating that it should be considered as an earnest alternative treatment for GD.


Antithyroid drugs; Continuous therapy; Graves’ disease; Long-term therapy; Methimazole; Propylthiouracil


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