{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T12:53:28Z","timestamp":1791204808965,"version":"4.1.0"},"reference-count":95,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:00:00Z","timestamp":1791158400000},"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:p>\n                    Metabolic dysfunction-associated steatotic liver disease (MASLD) affects approximately 30% of adults worldwide, yet is still framed largely as a hepatological disorder despite being driven substantially by endocrine and metabolic dysfunction. This review proposes a unified endocrine framework organised around seven hormonal axes, presenting each in terms of molecular pathogenesis, clinical presentation, and therapeutic implications. Insulin resistance is the central driver, coupling chronic caloric excess to hepatic\n                    <jats:italic>de novo<\/jats:italic>\n                    lipogenesis through selective hepatic insulin resistance, although genetic variants in\n                    <jats:italic>PNPLA3<\/jats:italic>\n                    and\n                    <jats:italic>TM6SF2<\/jats:italic>\n                    can uncouple steatosis from metabolic risk. Adipose tissue dysfunction contributes through adipocyte senescence, adipokine imbalance, and inflammatory adipose\u2013liver signalling. Reduced hepatic thyroid hormone sensitivity, even in euthyroid individuals, predicts steatosis and fibrosis and underpins the first approved liver-directed therapy. Gonadal steroids exert sexually dimorphic effects, with testosterone deficiency, menopausal oestrogen loss, and polycystic ovary syndrome representing distinct risk states. Glucocorticoid dysregulation is stage-dependent, shifting from enhanced hepatic cortisol clearance in steatosis to local amplification in steatohepatitis. The gut-liver-endocrine axis, encompassing incretin, bile acid, and fibroblast growth factor signalling, has proved the most therapeutically tractable. Reduced GH\/IGF-1 signalling, whether from pituitary disease or obesity-induced functional suppression, promotes both steatosis and fibrogenesis. Biological sex and life-course influences spanning developmental programming and ageing further modify these determinants. Two agents, resmetirom and semaglutide, now have US FDA accelerated approval for noncirrhotic MASH with moderate-to-advanced fibrosis, supporting the principle that correcting axis-specific endocrine dysfunction can produce measurable hepatic benefit; however, both approvals are accelerated and await confirmatory outcome data, while others remain investigational. An endocrine framework offers both a coherent account of pathogenesis and a rational basis for biomarker-guided, phenotype-targeted therapy.\n                  <\/jats:p>","DOI":"10.3389\/fendo.2026.1967494","type":"journal-article","created":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T12:15:52Z","timestamp":1791202552000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Endocrine determinants of MASLD: mechanisms and therapeutic targets"],"prefix":"10.3389","volume":"17","author":[{"given":"Richa","family":"Chaturvedi","sequence":"first","affiliation":[{"name":"Advance Centre for Obesity, Diabetes and Endocrinology (ACODE), Indraprastha Apollo Hospital","place":["Delhi, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anu","family":"Mathew","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Fortis Hospital, Gurugram","place":["Haryana, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aprajita","family":"Pradhan","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Max Superspecialty Hospital, Dwarka","place":["Delhi, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Goyal","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Yatharth Super Speciality Hospital","place":["New Delhi, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Sharma","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Aakash Hospital, Dwarka","place":["Delhi, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Varsha","family":"Kachroo","sequence":"additional","affiliation":[{"name":"Advance Centre for Obesity, Diabetes and Endocrinology (ACODE), Indraprastha Apollo Hospital","place":["Delhi, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chhavi","family":"Agrawal","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Fortis Escorts Heart Institute","place":["Delhi, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aishwarya","family":"Krishnamurthy","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Max Super Speciality Hospital, Ghaziabad","place":["Uttar Pradesh, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Surabhi","family":"Atreja","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, UC Davis Medical Center","place":["Sacramento, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashish","family":"Atreja","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford","place":["Redwood, CA, United 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