{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T20:04:37Z","timestamp":1791489877319,"version":"4.3.4"},"reference-count":16,"publisher":"Bioscientifica","issue":"2","license":[{"start":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T00:00:00Z","timestamp":1771286400000},"content-version":"vor","delay-in-days":322,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["journals.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,4,1]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>The optimal treatment with antithyroid drugs (ATDs) for a first episode of Graves\u2019 disease (GD) remains controversial.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Retrospective, two academic centres study of newly diagnosed GD between 1990 and 2022, treated with ATD in block-and-replace (B+R) regimen for at least 12 months and followed up for at least 1 year after ATD discontinuation or until disease relapse. Sixty patients received high-dose B+R (HD) with fixed ATD dose maintained during the study, and 60 patients received low-dose B+R (LD) with lower ATD dose adjusted during the study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Baseline characteristics were similar in both groups. The point-prevalence of euthyroidism was not different between HD and LD (38 vs 47%, P = 0.460 at 6 months, 69 vs 82%, P = 0.194 at 12 months, 70 vs 78%, P = 0.370 at 18 months, respectively). At 18 months, 27% HD vs 38% LD (P = 0.242) had thyroid eye disease. There were no differences in the number or type of ATD-related adverse events (AE) (no AE 73 vs 78%, P = 0.707). LD received mean lower ATD dose (15.3 \u00b1 4.2 vs 30.0 \u00b1 0.0 mg\/day, P &amp;lt; 0.001) and lower levothyroxine dose (72.6 \u00b1 16.7 vs 100.6 \u00b1 24.5 \u03bcg\/day, P &amp;lt; 0.001). After a first course of ATD, 63% of HD patients and 60% of LD patients relapsed (P = 0.707) after a median time (interquartile range) of 11.0 (18) vs 7.0 (19) months (P = 0.109).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>We observed similar relapse rates in patients with a first episode of GD receiving up to 50% less ATD and 30% less levothyroxine dose than high-dose B+R regimen.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1530\/etj-25-0039","type":"journal-article","created":{"date-parts":[[2025,4,2]],"date-time":"2025-04-02T09:47:29Z","timestamp":1743587249000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-17","source":"Crossref","is-referenced-by-count":2,"title":["High-dose versus low-dose block-and-replace treatment for a first episode of Graves\u2019 disease"],"prefix":"10.1530","volume":"14","author":[{"given":"Arnaud","family":"Smolders","sequence":"first","affiliation":[{"name":"Department of Endocrinology and Nutrition, Cliniques Universitaires Saint-Luc, Universit\u00e9 Catholique de Louvain 1 , ,","place":["Brussels, Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aglaia","family":"Kyrilli","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Hopital Erasme, Universit\u00e9 Libre de Bruxelles 2 , ,","place":["Brussels, Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2665-9455","authenticated-orcid":true,"given":"Stefan Matei","family":"Constantinescu","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Nutrition, Cliniques Universitaires Saint-Luc, Universit\u00e9 Catholique de Louvain 1 , ,","place":["Brussels, Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard","family":"Corvilain","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Hopital Erasme, Universit\u00e9 Libre de Bruxelles 2 , ,","place":["Brussels, Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chantal","family":"Daumerie","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Nutrition, Cliniques Universitaires Saint-Luc, Universit\u00e9 Catholique de Louvain 1 , ,","place":["Brussels, Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8437-3933","authenticated-orcid":true,"given":"Maria-Cristina","family":"Burlacu","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Nutrition, Cliniques Universitaires Saint-Luc, Universit\u00e9 Catholique de Louvain 1 , ,","place":["Brussels, Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","published-online":{"date-parts":[[2025,4,2]]},"reference":[{"key":"2026070712525649300_bib1","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1159\/000490384","article-title":"2018 European Thyroid Association guideline for the management of graves\u2019 hyperthyroidism","volume":"7","author":"Kahaly","year":"2018","journal-title":"Eur Thyroid J"},{"key":"2026070712525649300_bib2","doi-asserted-by":"crossref","first-page":"2956","DOI":"10.1210\/clinem\/dgae222","article-title":"A 2023 International Survey of clinical practice patterns in the management of graves disease: a decade of change","volume":"109","author":"Villagelin","year":"2024","journal-title":"J Clin Endocrinol Metab"},{"key":"2026070712525649300_bib3","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1136\/bmj.4.5885.143","article-title":"Single dose, \u201cblock-replace\u201d drug therapy in hyperthyroidism","volume":"4","author":"Wise","year":"1973","journal-title":"Br Med J"},{"key":"2026070712525649300_bib4","article-title":"Antithyroid drug regimen for treating Graves' hyperthyroidism","volume":"2010","author":"Abraham","year":"2010","journal-title":"Cochrane Database Syst Rev"},{"key":"2026070712525649300_bib5","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1111\/cen.12478","article-title":"Block & replace regime versus titration regime of antithyroid drugs for the treatment of Graves' disease: a retrospective observational study","volume":"81","author":"Vaidya","year":"2014","journal-title":"Clin Endocrinol"},{"key":"2026070712525649300_bib6","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1007\/s40618-020-01320-7","article-title":"Antithyroid drugs in Graves' hyperthyroidism: differences between \u201cblock and replace\u201d and \u201ctitration\u201d regimes in frequency of euthyroidism and Graves' orbitopathy during treatment","volume":"44","author":"\u017darkovi\u0107","year":"2021","journal-title":"J Endocrinol Invest"},{"key":"2026070712525649300_bib7","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1046\/j.1365-2265.1998.00446.x","article-title":"A randomized trial of short-term treatment of Graves' disease with high-dose carbimazole plus thyroxine versus low-dose carbimazole","volume":"48","author":"Grebe","year":"1998","journal-title":"Clin Endocrinol"},{"key":"2026070712525649300_bib8","doi-asserted-by":"crossref","first-page":"1337","DOI":"10.1007\/s40618-020-01431-1","article-title":"Block-and-replace vs. titration antithyroid drug regimen for Graves' hyperthyroidism: two is not always better than one","volume":"44","author":"Duntas","year":"2021","journal-title":"J Endocrinol Invest"},{"key":"2026070712525649300_bib9","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1089\/thy.2016.0229","article-title":"2016 American Thyroid Association Guidelines for diagnosis and management of hyperthyroidism and other causes of thyrotoxicosis","volume":"26","author":"Ross","year":"2016","journal-title":"Thyroid"},{"key":"2026070712525649300_bib10","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1089\/thy.2011.0039","article-title":"Sustained control of Graves' hyperthyroidism during long-term low-dose antithyroid drug therapy of patients with severe Graves' orbitopathy","volume":"21","author":"Laurberg","year":"2011","journal-title":"Thyroid"},{"key":"2026070712525649300_bib11","first-page":"1516","article-title":"A prospective randomized trial of antithyroid drug dose in Graves' disease therapy. European Multicenter Study Group on antithyroid drug treatment","volume":"76","author":"Reinwein","year":"1993","journal-title":"J Clin Endocrinol Metab"},{"key":"2026070712525649300_bib12","doi-asserted-by":"crossref","first-page":"1707","DOI":"10.1007\/s40618-020-01479-z","article-title":"Change in newly diagnosed Graves' disease phenotype between the twentieth and the twenty-first centuries: meta-analysis and meta-regression","volume":"44","author":"Ippolito","year":"2021","journal-title":"J Endocrinol Invest"},{"key":"2026070712525649300_bib13","first-page":"2470","article-title":"Methimazole has no dose-related effect on the intensity of the intrathyroidal autoimmune process in relapsing Graves' disease","volume":"80","author":"Paschke","year":"1995","journal-title":"J Clin Endocrinol Metab"},{"key":"2026070712525649300_bib14","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1089\/thy.2014.0084","article-title":"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","volume":"25","author":"Sato","year":"2015","journal-title":"Thyroid"},{"key":"2026070712525649300_bib15","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1530\/eje.1.02295","article-title":"Remission of Graves' disease during anti-thyroid drug therapy. Time to reconsider the mechanism?","volume":"155","author":"Laurberg","year":"2006","journal-title":"Eur J Endocrinol"},{"key":"2026070712525649300_bib16","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1038\/s41430-020-00766-5","article-title":"Urinary sodium and iodine concentrations among Belgian adults: results from the first national Health Examination Survey","volume":"75","author":"Vandevijvere","year":"2021","journal-title":"Eur J Clin Nutr"}],"container-title":["European Thyroid Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/etj.bioscientifica.com\/view\/journals\/etj\/14\/2\/ETJ-25-0039.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/etj.bioscientifica.com\/downloadpdf\/journals\/etj\/14\/2\/ETJ-25-0039.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/journals.bioscientifica.com\/etj\/article-pdf\/doi\/10.1530\/ETJ-25-0039\/36918\/etj-25-0039.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/journals.bioscientifica.com\/etj\/article-pdf\/doi\/10.1530\/ETJ-25-0039\/36918\/etj-25-0039.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T17:21:40Z","timestamp":1783444900000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.bioscientifica.com\/etj\/article\/14\/2\/e250039\/4363\/High-dose-versus-low-dose-block-and-replace"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,1]]},"references-count":16,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,4,1]]}},"URL":"https:\/\/doi.org\/10.1530\/etj-25-0039","relation":{},"ISSN":["2235-0802","2235-0640"],"issn-type":[{"value":"2235-0802","type":"electronic"},{"value":"2235-0640","type":"print"}],"subject":[],"published":{"date-parts":[[2025,4,1]]},"article-number":"e250039"}}