{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T19:22:17Z","timestamp":1775503337801,"version":"3.50.1"},"reference-count":40,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T00:00:00Z","timestamp":1755648000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: The therapeutic response in Graves\u2019 Disease (GD) remains largely unpredictable. Patients often experience persistent symptoms that are poorly correlated with thyroid hormone levels, an undefined treatment duration, and the need for long-term or definitive therapies. Based on the nuclear antagonistic properties of L-carnitine (LCT) on thyroid hormone action and the immunomodulatory role of selenium (Se), we aimed to assess the impact of adding a combined LCT and Se supplement to standard methimazole (MMI) therapy on the biochemical profile and quality of life (QoL) of patients with overt GD. Methods: This multicenter prospective randomized trial enrolled 60 consecutive patients with newly diagnosed overt GD. Participants were randomized to receive either standard treatment with MMI alone (Control Group) or MMI plus the combined LCT\/Se supplement (Intervention Group). TSH, fT3, fT4, and TSH\u2013receptor antibodies (TRAb) levels were evaluated every two months for up to 24 months or until spontaneous remission or definitive therapy. At each visit, patients completed a symptom questionnaire addressing the frequency of typical thyrotoxic symptoms. Results: No significant differences were observed between groups in the trend or time-to-normalization of TSH, fT3, and fT4 levels. However, the Intervention Group reached TRAb negativity significantly earlier (HR = 2.35 (1.14\u20134.81), p = 0.016), with a synergistic interaction with MMI therapy. MMI requirements were consistently lower in the Intervention Group, both in average dosage (p = 0.013) and cumulative dose (p = 0.020). The rate of spontaneous remission was significantly higher (OR = 11.22 (3.35\u201346.11), p &lt; 0.001). Overall symptom burden did not differ significantly between groups; however, the supplement exerted an independent effect in reducing the severity of tremor, irritability, mood lability, heat intolerance, and exertional dyspnea. Conclusions: Our findings suggest the clinical benefits of adding combined LCT and Se supplementation to MMI in the treatment of overt GD, including shorter disease duration, lower cumulative MMI exposure and earlier TRAb normality, that could positively influence TRAb-related prognostic outcomes.<\/jats:p>","DOI":"10.3390\/nu17162693","type":"journal-article","created":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T13:18:14Z","timestamp":1755695894000},"page":"2693","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Adding L-Carnitine and Selenium to Methimazole in Graves\u2019 Disease: A Prospective Randomized Trial on Thyroid Markers and Quality of Life"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8792-5334","authenticated-orcid":false,"given":"Mattia","family":"Rossi","sequence":"first","affiliation":[{"name":"Endocrinology, Diabetology and Metabolism, Department of Medical Sciences, University of Turin, 10128 Turin, Italy"},{"name":"Endocrinology, Diabetology and Metabolism, AO \u201cOrdine Mauriziano di Torino\u201d, 10128 Turin, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Letizia","family":"Meomartino","sequence":"additional","affiliation":[{"name":"Endocrinology, Diabetology and Metabolism, Department of Medical Sciences, University of Turin, 10128 Turin, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Zavattaro","sequence":"additional","affiliation":[{"name":"Endocrinology, Department of Translational Medicine, University of Piemonte Orientale, 13100 Novara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gloria","family":"Selvatico","sequence":"additional","affiliation":[{"name":"Endocrinology, Diabetology and Metabolism, Department of Medical Sciences, University of Turin, 10128 Turin, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruth","family":"Rossetto Giaccherino","sequence":"additional","affiliation":[{"name":"Endocrinology, Diabetology and Metabolism, Department of Medical Sciences, University of Turin, 10128 Turin, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9125-4721","authenticated-orcid":false,"given":"Loredana","family":"Pagano","sequence":"additional","affiliation":[{"name":"Endocrinology, Diabetology and Metabolism, Department of Medical Sciences, University of Turin, 10128 Turin, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,20]]},"reference":[{"key":"ref_1","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. 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