{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T01:31:07Z","timestamp":1791077467060,"version":"4.1.0"},"reference-count":32,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":4170,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2004,4]]},"abstract":"<jats:sec>\n            <jats:title\/>\n            <jats:p>Patients with hypopituitarism develop a phenotype similar to metabolic syndrome with central obesity and diabetes. Similarly, patients with hypothalamic damage may develop central obesity, insulin resistance, and hyperphagia. We sought to examine the clinical associations between hypopituitarism, hypothalamic dysfunction, and nonalcoholic fatty liver disease (NAFLD). A case series of patients seen at our institution with diagnoses of hypopituitarism, hypothalamic obesity, or craniopharyngioma and NAFLD was undertaken. Clinical, laboratory, and liver biopsy features were reviewed. Twenty-one patients were identified. NAFLD was diagnosed 6.4 \u00b1 7.5 years (median 3 years) after the diagnosis of hypothalamic\/pituitary dysfunction. Mean gain in body mass index (BMI) between diagnoses of hypothalamic\/pituitary disease and NAFLD was 11.3 \u00b1 8.9 kg\/m<jats:sup>2<\/jats:sup> at an average yearly rate of 2.2 \u00b1 2.2 kg\/m<jats:sup>2<\/jats:sup>. The majority of patients developed elevated glucose levels and dyslipidemia by time of diagnosis of NAFLD. Of the 10 patients biopsied, six were cirrhotic, two had nonalcoholic steatohepatitis (NASH) with fibrosis, and two had simple steatosis. Long-term follow-up of 66 \u00b1 33 months (range 12-120) was available for 18 patients. Two required liver transplantation. Six patients died, two from liver related causes. In conclusion, patients with hypothalamic and\/or pituitary disease are at risk of excessive weight gain, impaired glucose tolerance, and dyslipidemia with subsequent development of NAFLD. This group has a high prevalence of cirrhosis placing them at risk for liver-related death. The novel evidence that hypothalamic\/pituitary dysfunction may be accompanied by progressive NAFLD has important implications for the work-up and management of patients with hypothalamic\/pituitary disease. (Hepatology 2004;39:909-914.)<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.20140","type":"journal-article","created":{"date-parts":[[2004,3,26]],"date-time":"2004-03-26T08:01:41Z","timestamp":1080288101000},"page":"909-914","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":226,"title":["Nonalcoholic fatty liver disease among patients with hypothalamic and pituitary dysfunction"],"prefix":"10.1097","volume":"39","author":[{"given":"Leon A.","family":"Adams","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ariel","family":"Feldstein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith D.","family":"Lindor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Angulo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"R1-8-20241201","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1152\/physrev.1946.26.4.541","article-title":"Mechanism of the development of obesity in animals with hypothalamic lesions.","volume":"26","author":"Brobeck","year":"1946","journal-title":"Physiol Rev"},{"key":"R2-8-20241201","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1097\/00019616-200205000-00008","article-title":"Hypothalamic obesity: the sixth cranial endocrinopathy.","volume":"12","author":"Lustig","year":"2002","journal-title":"Endocrinologist"},{"key":"R3-8-20241201","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1530\/eje.0.1380089","article-title":"Hyperphagia in children with craniopharyngioma is associated with hyperleptinaemia and a failure in the downregulation of appetite.","volume":"138","author":"Roth","year":"1998","journal-title":"Eur J Endocrinol"},{"key":"R4-8-20241201","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1055\/s-2001-12932","article-title":"Animal models of steatosis.","volume":"21","author":"Koteish","year":"2001","journal-title":"Semin Liver Dis"},{"key":"R5-8-20241201","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1056\/NEJMra011775","article-title":"Nonalcoholic fatty liver disease.","volume":"346","author":"Angulo","year":"2002","journal-title":"N Engl J Med"},{"key":"R6-8-20241201","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1053\/jhep.2002.30690","article-title":"Nonalcoholic steatohepatitis, insulin resistance, and metabolic syndrome: further evidence for an etiologic association.","volume":"35","author":"Pagano","year":"2002","journal-title":"HEPATOLOGY"},{"key":"R7-8-20241201","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1053\/jhep.2002.30692","article-title":"NASH and insulin resistance: Insulin hypersecretion and specific association with the insulin resistance syndrome.","volume":"35","author":"Chitturi","year":"2002","journal-title":"HEPATOLOGY"},{"key":"R8-8-20241201","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1046\/j.1365-2265.2003.01675.x","article-title":"Comparisons of leptin, incretins and body composition in obese and lean patients with hypopituitarism and healthy individuals.","volume":"58","author":"Mersebach","year":"2003","journal-title":"Clin Endocrinol (Oxf)"},{"key":"R9-8-20241201","first-page":"1057","article-title":"Cirrhotic outcome in patients with craniopharyngioma.","volume":"15","author":"Altuntas","year":"2002","journal-title":"J Pediatr Endocrinol Metab"},{"key":"R10-8-20241201","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1055\/s-2008-1046584","article-title":"Development of complete liver cirrhosis in hyperphagia-induced fatty liver. in German.","volume":"206","author":"Basenau","year":"1994","journal-title":"Klin Padiatr"},{"key":"R11-8-20241201","doi-asserted-by":"crossref","first-page":"2467","DOI":"10.1111\/j.1572-0241.1999.01377.x","article-title":"Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions.","volume":"94","author":"Brunt","year":"1999","journal-title":"Am J Gastroenterol"},{"key":"R12-8-20241201","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1001\/archinte.1952.00240080007002","article-title":"The liver in obesity.","volume":"90","author":"Zelman","year":"1952","journal-title":"Arch Intern Med"},{"key":"R13-8-20241201","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1053\/jhep.2003.50193","article-title":"Nonalcoholic steatohepatitis: summary of an AASLD Single Topic Conference.","volume":"37","author":"Neuschwander-Tetri","year":"2003","journal-title":"HEPATOLOGY"},{"key":"R14-8-20241201","doi-asserted-by":"crossref","first-page":"199","DOI":"10.2165\/00002018-200225030-00005","article-title":"Growth hormone therapy and its relationship to insulin resistance, glucose intolerance and diabetes mellitus: a review of recent evidence.","volume":"25","author":"Jeffcoate","year":"2002","journal-title":"Drug Saf"},{"key":"R15-8-20241201","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1046\/j.1464-5491.2003.00827.x","article-title":"The role of the growth hormone-insulin-like growth factor axis in glucose homeostasis.","volume":"20","author":"Holt","year":"2003","journal-title":"Diabet Med"},{"key":"R16-8-20241201","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1136\/gut.52.6.914","article-title":"Non-alcoholic steatohepatitis and hepatic steatosis in patients with adult onset growth hormone deficiency.","volume":"52","author":"Ichikawa","year":"2003","journal-title":"Gut"},{"key":"R17-8-20241201","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1111\/j.1572-0241.2002.05641.x","article-title":"Growth hormone plasma levels in nonalcoholic fatty liver disease.","volume":"97","author":"Lonardo","year":"2002","journal-title":"Am J Gastroenterol"},{"key":"R18-8-20241201","first-page":"E824","article-title":"Influence of obesity and body fat distribution on growth hormone kinetics in humans.","volume":"277","author":"Langendonk","year":"1999","journal-title":"Am J Physiol"},{"key":"R19-8-20241201","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1046\/j.1365-2265.1999.00682.x","article-title":"Cardiovascular disease and risk factors in adults with hypopituitarism.","volume":"50","author":"Beshyah","year":"1999","journal-title":"Clin Endocrinol (Oxf)"},{"key":"R20-8-20241201","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1038\/sj.ijo.0801206","article-title":"Serum lipid and leptin concentrations in hypopituitary patients with growth hormone deficiency.","volume":"24","author":"Ozbey","year":"2000","journal-title":"Int J Obes Relat Metab Disord"},{"key":"R21-8-20241201","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1111\/j.1464-5491.1994.tb00369.x","article-title":"Obesity associated insulin resistance occurs in hypopituitary subjects.","volume":"11","author":"Page","year":"1994","journal-title":"Diabet Med"},{"key":"R22-8-20241201","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/S0950-351X(95)80338-6","article-title":"Clinical features and differential diagnosis of pituitary tumours with emphasis on acromegaly.","volume":"9","author":"Hennessey","year":"1995","journal-title":"Baillieres Clin Endocrinol Metab"},{"key":"R23-8-20241201","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1210\/jc.2003-030218","article-title":"Growth hormone replacement therapy and insulin sensitivity.","volume":"88","author":"Svensson","year":"2003","journal-title":"J Clin Endocrinol Metab"},{"key":"R24-8-20241201","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1046\/j.1365-2265.1997.2131054.x","article-title":"Elevated leptin concentrations in growth hormone-deficient hypopituitary adults.","volume":"47","author":"al-Shoumer KA, Anyaoku","year":"1997","journal-title":"Clin Endocrinol (Oxf)"},{"key":"R25-8-20241201","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1053\/beem.2002.0230","article-title":"Hypothalamic regulation of energy homeostasis.","volume":"16","author":"Sainsbury","year":"2002","journal-title":"Best Pract Res Clin Endocrinol Metab"},{"key":"R26-8-20241201","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1046\/j.1467-789X.2002.00052.x","article-title":"Hypothalamic obesity in humans: what do we know and what can be done?","volume":"3","author":"Pinkney","year":"2002","journal-title":"Obes Rev"},{"key":"R27-8-20241201","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1096\/fsb2fasebj.12.1.57","article-title":"Leptin regulates proinflammatory immune responses.","volume":"12","author":"Loffreda","year":"1998","journal-title":"FASEB J"},{"key":"R28-8-20241201","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1038\/oby.2003.74","article-title":"Systemic inflammation, adipose tissue tumor necrosis factor, and leptin expression.","volume":"11","author":"Bullo","year":"2003","journal-title":"Obes Res"},{"key":"R29-8-20241201","doi-asserted-by":"crossref","first-page":"1399","DOI":"10.1053\/gast.2002.32995","article-title":"Leptin receptor-mediated signaling regulates hepatic fibrogenesis and remodeling of extracellular matrix in the rat.","volume":"122","author":"Ikejima","year":"2002","journal-title":"Gastroenterology"},{"key":"R30-8-20241201","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1053\/jhep.2002.32029","article-title":"Leptin in hepatic fibrosis: evidence for increased collagen production in stellate cells and lean littermates of obob mice.","volume":"35","author":"Saxena","year":"2002","journal-title":"HEPATOLOGY"},{"key":"R31-8-20241201","first-page":"296A","article-title":"Leptin is an independent marker of liver fibrosis in humans with nonalcoholic fatty liver disease. abstract.","volume":"36","author":"Alba","year":"2002","journal-title":"HEPATOLOGY"},{"key":"R32-8-20241201","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1111\/j.1572-0241.2002.05644.x","article-title":"Acute severe steatohepatitis related to prednisolone therapy.","volume":"97","author":"Dourakis","year":"2002","journal-title":"Am J Gastroenterol"}],"container-title":["Hepatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fhep.20140","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.lww.com\/01515467-200404000-00008","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,1]],"date-time":"2024-12-01T12:02:07Z","timestamp":1733054527000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/01515467-200404000-00008"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,4]]},"references-count":32,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2004]]}},"URL":"https:\/\/doi.org\/10.1002\/hep.20140","relation":{},"ISSN":["0270-9139"],"issn-type":[{"value":"0270-9139","type":"print"}],"subject":[],"published":{"date-parts":[[2004,4]]}}}