{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:09:19Z","timestamp":1792789759859,"version":"4.5.0"},"reference-count":169,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2025,6,20]],"date-time":"2025-06-20T00:00:00Z","timestamp":1750377600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Health"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Thyroid hormones (THs) play a central role in cardiovascular and metabolic regulation, influencing lipid metabolism, insulin sensitivity and resting energy expenditure. Inherited disorders of impaired sensitivity to THs\u2014including resistance to thyroid hormone alpha (RTH\u03b1) and beta (RTH\u03b2), monocarboxylate transporter 8 (MCT8) deficiency and selenoprotein deficiency\u2014lead to complex, multisystemic clinical features. Although these conditions are rare, with RTH\u03b2 being the most common and affecting about 1 in 20,000 newborns, they share clinical features with more prevalent thyroid disorders, such as hypothyroidism and hyperthyroidism, as well as neurological manifestations including muscle wasting and spasticity. These conditions present abnormal patterns of thyroid function and are associated with tissue-specific comorbidities such as arrhythmias, heart failure, dyslipidemia, hepatic steatosis, insulin resistance, and metabolic syndrome. To date, no targeted or controlled studies have evaluated the impact of lifestyle modifications in these patient populations. Therefore, this narrative review proposes plausible management strategies based on pathophysiological insights into the effects of thyroid hormones on target organs, combined with clinical reasoning and evidence extrapolated from related disorders. Physical exercise and diet may complement pharmacological treatments (e.g., levothyroxine or TRIAC) to improve cardiovascular and metabolic outcomes. In RTH\u03b2, aerobic exercise enhances cardiovascular health, while a Mediterranean diet supports lipid control and glycemic parameters. In RTH\u03b1, physical exercise may aid neuromotor development, and a fluid-rich, fiber-moderated diet can alleviate constipation. In MCT8 deficiency, physiotherapy may improve mobility and relieve contractures, while nutritional support (e.g., feeding tube, gastrostomy) can be necessary to tackle feeding difficulties and reduce pulmonary complications. In selenoprotein deficiency, low-to-moderate physical exercise and an antioxidant-rich diet may protect against oxidative stress at several tissue levels. Although quantitative evidence is limited, this narrative review synthesizes current insights, providing a meaningful basis for future validation and research.<\/jats:p>","DOI":"10.3390\/nu17132053","type":"journal-article","created":{"date-parts":[[2025,6,20]],"date-time":"2025-06-20T06:10:27Z","timestamp":1750399827000},"page":"2053","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Lifestyle Interventions to Tackle Cardiovascular Risk in Thyroid Hormone Signaling Disorders"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-5117-3825","authenticated-orcid":false,"given":"Simone","family":"Rodolfi","sequence":"first","affiliation":[{"name":"Department of Medical Biotechnology and Translational Medicine, University of Milan, 20100 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuditta","family":"Rurale","sequence":"additional","affiliation":[{"name":"IRCCS Istituto Auxologico Italiano, Department of Endocrine and Metabolic Diseases, 20100 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Marelli","sequence":"additional","affiliation":[{"name":"IRCCS Istituto Auxologico Italiano, Department of Endocrine and Metabolic Diseases, 20100 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2068-9581","authenticated-orcid":false,"given":"Luca","family":"Persani","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnology and Translational Medicine, University of Milan, 20100 Milan, Italy"},{"name":"IRCCS Istituto Auxologico Italiano, Department of Endocrine and Metabolic Diseases, 20100 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Campi","sequence":"additional","affiliation":[{"name":"IRCCS Istituto Auxologico Italiano, Department of Endocrine and Metabolic Diseases, 20100 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e240125","DOI":"10.1530\/ETJ-24-0125","article-title":"2024 European Thyroid Association Guidelines on diagnosis and management of genetic disorders of thyroid hormone transport, metabolism and action","volume":"13","author":"Persani","year":"2024","journal-title":"Eur. 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