{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T03:09:01Z","timestamp":1785380941335,"version":"3.55.0"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T00:00:00Z","timestamp":1749168000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Aim<\/jats:title><jats:p>To evaluate the effectiveness and treatment compliance of Xiakucao Oral Liquid (XKC) combined with methimazole (MMI) on the early recovery of thyroid function in Graves\u2019 disease (GD) patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this retrospective cohort study, GD patients receiving initial treatment at Jieyang People\u2019s Hospital from January 2019 to December 2023 were included and divided into XKC+MMI group and MMI group based on the treatment regimen. The association between XKC+MMI and early thyroid function recovery was analyzed using multiple linear regression in the subgroup of patients with post-treatment data available at 3 months.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 441 patients were enrolled, among whom 113 (25.6%) patients received XKC+MMI. The proportion of patients receiving XKC+MMI was significantly higher with an initial MMI dose \u226520 mg\/day than &amp;lt;20 mg\/day (37.1% <jats:italic>vs<\/jats:italic>. 15.2%, P=0.006). In XKC+MMI group, 15 (13.3%) patients underwent continuous treatment with XKC for three months. Subgroup analysis (n=121) showed the increase of sensitive thyroid-stimulating hormone (sTSH) in XKC+MMI group was higher than that in MMI group (4.86 \u00b1 11.7 <jats:italic>vs<\/jats:italic> 1.15 \u00b1 5.16). Multivariate linear regression analysis indicated that compared with MMI alone, XKC+MMI was independently associated with the increase of sTSH (\u03b2=3.346, 95%CI: 0.353-6.339, P=0.031), and the continuous 3-month treatment of XKC+MMI was also independently associated with the increase of sTSH at 3 months (\u03b2=4.062, 95%CI: 0.516-7.608, P=0.027).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>XKC combination MMI treatment might promote early recovery of thyroid function. However, adherence to and persistence with XKC treatment still need to be improved.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2025.1560262","type":"journal-article","created":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T04:10:30Z","timestamp":1749183030000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Effectiveness of Xiakucao Oral Liquid combined with methimazole on early thyroid function recovery and treatment compliance in Graves\u2019 disease: a real-world retrospective cohort study"],"prefix":"10.3389","volume":"16","author":[{"given":"Dong","family":"Lin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lina","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jialu","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Houcheng","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bichai","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,6,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.7661\/j.cjim.20220610.079","article-title":"Clinical application guidelines for the adjuvant treatment of Graves\u2019 disease with Chinese patent medicine (2021)","volume":"42","year":"2022","journal-title":"Chin J Integrated Traditional Western Medicine"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3760\/cma.j.cn311282-20220624-00404-1","article-title":"Guidelines for diagnosis and management of hyperthyroidism and other causes of thyrotoxicosis","volume":"42","year":"2022","journal-title":"Int J Endocrinol Metab"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.794912","article-title":"Genetics, epigenetics, cellular immunology, and gut microbiota: emerging links with graves\u2019 Disease","volume":"9","author":"Zhou","year":"2021","journal-title":"Front Cell Dev Biol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2005.15.718","article-title":"Thyroid disease and increased cardiovascular risk","volume":"15","author":"Nyirenda","year":"2005","journal-title":"Thyroid"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2012-2268","article-title":"Excess mortality in hyperthyroidism: the influence of preexisting comorbidity and genetic confounding: a danish nationwide register-based cohort study of twins and singletons","volume":"97","author":"Brandt","year":"2012","journal-title":"J\u00a0Clin Endocrinol Metab"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2017-00166","article-title":"Excess mortality in treated and untreated hyperthyroidism is related to cumulative periods of low serum TSH","volume":"102","author":"Lillevang-Johansen","year":"2017","journal-title":"J Clin Endocrinol Metab"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1136\/heartjnl-2021-319752","article-title":"Incidence, risk factors, natural history and outcomes of heart failure in patients with Graves\u2019 disease","volume":"108","author":"Naser","year":"2022","journal-title":"Heart"},{"key":"B8","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1530\/eje-16-0576","article-title":"Acute cardiovascular events and all-cause mortality in patients with hyperthyroidism: a population-based cohort study","volume":"176","author":"Dekkers","year":"2017","journal-title":"Eur J Endocrinol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2019.0672","article-title":"Graves\u2019 Disease and toxic nodular goiter, aggravated by duration of hyperthyroidism, are associated with alzheimer\u2019s and vascular dementia: A registry-based long-term follow-up of two large cohorts","volume":"30","author":"Folkestad","year":"2020","journal-title":"Thyroid"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2018.0320","article-title":"Duration of hyperthyroidism and lack of sufficient treatment are associated with increased cardiovascular risk","volume":"29","author":"Lillevang-Johansen","year":"2019","journal-title":"Thyroid"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/s2213-8587(19)30059-2","article-title":"Primary therapy of Graves\u2019 disease and cardiovascular morbidity and mortality: a linked-record cohort study","volume":"7","author":"Okosieme","year":"2019","journal-title":"Lancet Diabetes Endocrinol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1007\/s12020-021-02952-2","article-title":"Increased risk of Graves ophthalmopathy in patients with increasing TRAb after radioiodine treatment and the impact of CTLA4 on TRAb titres","volume":"75","author":"Shahida","year":"2022","journal-title":"Endocrine"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1055\/s-0033-1363193","article-title":"Increased TRAb and\/or low anti-TPO titers at diagnosis of graves\u2019 disease are associated with an increased risk of developing ophthalmopathy after onset","volume":"122","author":"Lantz","year":"2014","journal-title":"Exp Clin Endocrinol Diabetes"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1507\/endocrj.k10e-123","article-title":"Persistent high TRAb values during pregnancy predict increased risk of neonatal hyperthyroidism following radioiodine therapy for refractory hyperthyroidism","volume":"58","author":"Hamada","year":"2011","journal-title":"Endocr J"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1007\/s12020-023-03569-3","article-title":"Third-Generation Thyrotropin Receptor Antibody (TRAb) assay for predicting neonatal thyroid dysfunction in pregnant women with Graves\u2019 disease","volume":"84","author":"Priyanka","year":"2024","journal-title":"Endocrine"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.3275\/8188","article-title":"Short-term effects of combined treatment with potassium bromide and methimazole in patients with Graves\u2019 disease","volume":"35","author":"Li","year":"2012","journal-title":"J Endocrinol Invest"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2265.1995.tb02030.x","article-title":"Response to methimazole in Graves\u2019 disease. The European Multicenter Study Group","volume":"43","author":"Benker","year":"1995","journal-title":"Clin Endocrinol (Oxf)"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2006-2135","article-title":"Comparison of methimazole and propylthiouracil in patients with hyperthyroidism caused by Graves\u2019 disease","volume":"92","author":"Nakamura","year":"2007","journal-title":"J Clin Endocrinol Metab"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2023.19052","article-title":"Hyperthyroidism: A review","volume":"330","author":"Lee","year":"2023","journal-title":"Jama"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2019.0085","article-title":"The long-term outcome of treatment for graves\u2019 Hyperthyroidism","volume":"29","author":"Sj\u00f6lin","year":"2019","journal-title":"Thyroid"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2019.0180","article-title":"Increased remission rates after long-term methimazole therapy in patients with graves\u2019 Disease: results of a randomized clinical trial","volume":"29","author":"Azizi","year":"2019","journal-title":"Thyroid"},{"key":"B22","doi-asserted-by":"publisher","first-page":"2","DOI":"10.3969\/j.issn.1002-0179.2006.03.012","article-title":"To observe the prognosis of ATD on graves syndrome and the relationship with TSH in the serum","volume":"21","author":"Zhang","year":"2006","journal-title":"West China Med J"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.13286\/j.1001-5213.2020.11.15","article-title":"Clinical observation of Prunella vulgaris oral liquid combined with metimidazole in the treatment of syndrome of hyperactivity of heart and liver fire of Graves\u2019 disease","volume":"40","author":"Chai","year":"2020","journal-title":"Chin J Hosp Pharmacy"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.3969\/j.issn.1001-1528.2012.01.004","article-title":"Clinical effect of Xiakucao Oral Liquid on the Graves disease","volume":"34","author":"Wu","year":"2012","journal-title":"Chin Traditional Patent Medicine"},{"key":"B25","first-page":"39","article-title":"Efficacy of Yikang powder combined with tapazol in the patients with Graves disease","volume":"19","author":"Qin","year":"2010","journal-title":"Chin J New Drugs"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.13192\/j.issn.1000-1719.2015.04.033","article-title":"Clinical observation of sanjie jiaxiao prescription and small dose of thyrozol in treatment of 60 cases of graves disease","volume":"42","author":"Li","year":"2015","journal-title":"Liaoning J Traditional Chin Medicine"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.13417\/j.gab.036.0003635","article-title":"Effect of xiakucao granules combined with thiamazole on the autoantibody and cytokines in patients with graves disease","volume":"36","author":"Wang","year":"2017","journal-title":"Genomics Appl Biol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.826067","article-title":"The potential prebiotic berberine combined with methimazole improved the therapeutic effect of graves\u2019 Disease patients through regulating the intestinal microbiome","volume":"12","author":"Han","year":"2021","journal-title":"Front Immunol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.13820\/j.cnki.gdyx.2015.02.029","article-title":"Effects of Xiakucao oral liquid on thyroid size and thyroid stimulating receptor antibody in patients with Graves\u2019 disease","volume":"36","author":"Xie","year":"2015","journal-title":"Guangdong Med J"},{"key":"B30","article-title":"Clinical observation on the treatment of toxic diffuse goiter disease with Xiakucao oral liquid combined with methimazole tablets","volume":"39","author":"Chen","year":"2023","journal-title":"J Pract Traditional Chin Medicine"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.3760\/cma.j.issn.1671-7368.2019.12.002","article-title":"Expert group for the development of guidelines for primary diagnosis and treatment of endocrine diseases. Guideline for primary care of hyperthyroidism (2019)","volume":"18","year":"2019","journal-title":"Chin J Gen Practitioners"},{"key":"B32","article-title":"Effect of Xiakucao oral liquid on STAT3 and NF-KB signal transduction pathway","volume":"21","author":"Li","year":"2019","journal-title":"Zhejiang Clin Med J"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.11675\/j.issn.0253-4304.2020.14.19","article-title":"Improvement effect and its mechanism of Prunella vulgaris polysaccharides on Graves\u2019disease mice","volume":"42","author":"Xiang","year":"2020","journal-title":"Guangxi Med J"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.7501\/j.issn.1674-6376.2021.08.031","article-title":"Systemic review of Prunella vulgaris Oral Liquid in treatment of hyperthyroidism","volume":"44","author":"Zhu","year":"2021","journal-title":"Drug Eval Res"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.4236\/jbm.2022.109013","article-title":"Summary of experience in treating hyperthyroidism with TCM syndrome differentiation","volume":"10","author":"Chen","year":"2022","journal-title":"JBM"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.16808\/j.cnki.issn1003-7705.2012.02.051","article-title":"Pathogenesis and treatment of hyperthyroidism","volume":"28","author":"Chen","year":"2012","journal-title":"Hunan J Traditional Chin Medicine"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2265.2012.04365.x","article-title":"Hepatotoxicity and cutaneous reactions after antithyroid drug administration","volume":"77","author":"Otsuka","year":"2012","journal-title":"Clin Endocrinol (Oxf)"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2008.0364","article-title":"Methimazole-induced agranulocytosis in patients with Graves\u2019 disease is more frequent with an initial dose of 30 mg daily than with 15 mg daily","volume":"19","author":"Takata","year":"2009","journal-title":"Thyroid"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1093\/qjmed\/94.8.423","article-title":"Haematopoietic growth factor in antithyroid-drug-induced agranulocytosis","volume":"94","author":"Andres","year":"2001","journal-title":"QJM"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.12336","article-title":"Antithyroid drug-related hepatotoxicity in hyperthyroidism patients: a population-based cohort study","volume":"78","author":"Wang","year":"2014","journal-title":"Br J Clin Pharmacol"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.3969\/j.issn.1008-8849.2016.24.033","article-title":"Effect of Xiukucao oral liquid on thyroid size and thyrotropin receptor\u00a0antibody in patients with Graves\u2019 disease","volume":"25","author":"Zou","year":"2016","journal-title":"Modern J Integrated Traditional Chin Western Medicine"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2025.1560262\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,23]],"date-time":"2025-06-23T13:15:01Z","timestamp":1750684501000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2025.1560262\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,6]]},"references-count":41,"alternative-id":["10.3389\/fendo.2025.1560262"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2025.1560262","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,6]]},"article-number":"1560262"}}