{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T23:41:25Z","timestamp":1792194085103,"version":"4.4.0"},"reference-count":36,"publisher":"Georg Thieme Verlag KG","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Horm Metab Res"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Thyroidectomy and radioactive iodine therapy are definitive treatments for\n                    Graves\u2019 disease, toxic nodular disease, and differentiated thyroid cancer. With\n                    improving survival rates and expanding indications for definitive therapy, a\n                    growing population is living for decades in a state of athyreosis requiring\n                    lifelong thyroid hormone replacement. Current management strategies largely\n                    emphasize serum thyroid-stimulating hormone targets and oncological\n                    surveillance, yet the long-term metabolic and physiological implications of\n                    chronic athyreosis remain incompletely explored. The potential longevity\n                    implications of long-term athyreosis are examined through a system-based\n                    framework integrating hormonal balance, mitochondrial regulation, metabolic\n                    adaptation, skeletal and cardiovascular health, and inflammatory signaling. This\n                    narrative review synthesizes evidence from endocrinology, metabolism, oncology,\n                    and aging research to evaluate physiological differences between endogenous\n                    thyroid hormone secretion and pharmacological replacement in athyreotic\n                    patients. Particular attention is given to tissue-level triiodothyronine\n                    availability, deiodinase activity, and downstream bioenergetic effects.\n                    Athyreotic patients lack intrinsic thyroidal triiodothyronine secretion and\n                    depend entirely on the peripheral conversion of levothyroxine to generate\n                    circulating and intracellular triiodothyronine. Emerging evidence suggests that\n                    levothyroxine monotherapy may not fully replicate physiological thyroid hormone\n                    dynamics in all individuals, potentially influencing mitochondrial biogenesis,\n                    resting energy expenditure, body composition, bone turnover, and cardiovascular\n                    remodeling. In thyroid cancer survivors, chronic thyroid-stimulating hormone\n                    suppression introduces additional considerations for skeletal and cardiac\n                    outcomes. Patients treated for autoimmune thyroid disease may also exhibit\n                    persistent immune dysregulation despite gland ablation. Athyreosis represents a\n                    distinct and permanent endocrine state with implications extending beyond\n                    biochemical euthyroidism. A system-based perspective that considers\n                    mitochondrial resilience, cardiometabolic integrity, skeletal preservation, and\n                    inflammatory tone may enhance long-term management strategies for this expanding\n                    survivorship population. Prospective studies are needed to clarify the impact of\n                    various thyroid hormone replacement paradigms on functional aging and longevity\n                    outcomes.<\/jats:p>","DOI":"10.1055\/a-2969-5828","type":"journal-article","created":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T22:53:02Z","timestamp":1792191182000},"source":"Crossref","is-referenced-by-count":0,"title":["Athyreosis and Thyroid Hormone Signaling: A System-Based Framework\n                    for Long-Term Endocrine Health"],"prefix":"10.1055","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-1064-2257","authenticated-orcid":false,"given":"Angela D.","family":"Mazza","sequence":"additional","affiliation":[{"name":"Metabolic Center for Wellness, Florida, United States","place":["Oviedo"],"department":["Endocrinology"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2026,10,16]]},"reference":[{"issue":"12","key":"ref1","doi-asserted-by":"crossref","first-page":"3844","DOI":"10.1245\/s10434-014-3846-8","article-title":"Total thyroidectomy is associated with increased risk of complications for low-\n                    and high-volume surgeons","volume":"21","author":"A Hauch","year":"2014","journal-title":"Ann Surg Oncol"},{"issue":"03","key":"ref2","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1002\/cncr.30360","article-title":"2015 American Thyroid Association management guidelines for adult patients with\n                    thyroid nodules and differentiated thyroid cancer: what is new and what has\n                    changed?","volume":"123","author":"B R 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Morton","year":"2018","journal-title":"Br J Sports Med"},{"issue":"11","key":"ref36","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1038\/s41577-019-0190-z","article-title":"Sleep and inflammation: partners in sickness and in health","volume":"19","author":"M R Irwin","year":"2019","journal-title":"Nat Rev Immunol"}],"container-title":["Hormone and Metabolic 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