{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,21]],"date-time":"2026-06-21T01:25:38Z","timestamp":1782005138364,"version":"3.54.5"},"reference-count":35,"publisher":"The Endocrine Society","issue":"1","license":[{"start":{"date-parts":[[2020,11,22]],"date-time":"2020-11-22T00:00:00Z","timestamp":1606003200000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Spontaneous hypoglycemia in nondiabetic patients poses a diagnostic challenge. Hypoglycemia in malignancy has several etiologies; an extremely rare mechanism is the Warburg effect causing excess lactate production and avid glucose consumption. We describe the clinical course of a 52-year-old man admitted for chest wall mass and severe but asymptomatic hypoglycemia. Laboratory workup was obtained for insulin vs noninsulin-mediated hypoglycemia, and biopsy of the chest wall mass and 18F-fluorodeoxyglucose positron emission tomography\/computed tomography (18F-FDG-PET\/CT) scan were performed. D10 infusion and intravenous\/oral steroids started for severe hypoglycemia. Chemotherapy was initiated after biopsy, and blood glucose (BG) and lactate levels followed with clinical response in tumor size and changes in PET\/CT. Investigations were significant for venous BG in the 40s (Ademolus Classification of Hypoglycemia grade 2 hypoglycemia), plasma insulin of less than 2 \u00b5U\/mL (2-20 \u00b5U\/mL), C-peptide of 0.2 ng\/mL (0.8-6.0 ng\/mL), insulin-like growth factor 2 (IGF-2) of 113 ng\/mL (333-967 ng\/mL), serum lactate of 16 mmol\/L (0.5-2 mmol\/L), and albumin of 2.3 g\/dL (3.4-5.4 g\/dL). Biopsy showed diffuse large B-cell lymphoma, and PET revealed highly FDG-avid disease in the chest, abdomen, and pelvis, but no FDG uptake was seen in the brain. Hypoglycemia and lactic acidosis improved remarkably after chemotherapy. PET\/CT at 4 weeks showed complete metabolic response with reappearance of physiological FDG uptake in the brain. Noninsulin-mediated hypoglycemia was likely due to the combination of profound malnutrition and rapid glucose use by cancer cells. The patient presented with exaggerated Warburg effect (hyper-Warburgism), evident by extreme glucose consumption, severe lactic acidosis, and large tumor burden on PET\/CT. Absence of cognitive symptoms was probably due to use of lactate by the brain. Chemotherapy corrected these abnormalities rapidly, and must be instituted in a timely manner.<\/jats:p>","DOI":"10.1210\/jendso\/bvaa182","type":"journal-article","created":{"date-parts":[[2020,11,22]],"date-time":"2020-11-22T02:56:30Z","timestamp":1606013790000},"source":"Crossref","is-referenced-by-count":6,"title":["Confirmed Hypoglycemia Without Whipple Triad: A Rare Case of Hyper-Warburgism"],"prefix":"10.1210","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7044-7372","authenticated-orcid":false,"given":"Itivrita","family":"Goyal","sequence":"first","affiliation":[{"name":"Division of Endocrinology, Department of Internal Medicine, University at Buffalo, Buffalo, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Ogbuah","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, University at Buffalo, Buffalo, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ajay","family":"Chaudhuri","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Department of Internal Medicine, University at Buffalo, Buffalo, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy","family":"Quinn","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, University at Buffalo and Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1342-7153","authenticated-orcid":false,"given":"Rajeev","family":"Sharma","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Department of Internal Medicine, University at Buffalo and Roswell Park Comprehensive Cancer Center, Buffalo, New York, 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acidosis and hypoglycemia in a patient with high-grade non-Hodgkin\u2019s lymphoma and elevated circulating TNF-\u03b1","volume":"72","author":"Durig","year":"1996","journal-title":"Ann Hematol."},{"key":"2021121112523356600_CIT0022","doi-asserted-by":"crossref","first-page":"1316","DOI":"10.1100\/tsw.2011.125","article-title":"Type B lactic acidosis secondary to malignancy: case report, review of published cases, insights into pathogenesis, and prospects for therapy","volume":"11","author":"Ruiz","year":"2011","journal-title":"ScientificWorldJournal."},{"issue":"3","key":"2021121112523356600_CIT0023","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.tibs.2015.12.001","article-title":"The Warburg effect: how does it benefit cancer cells?","volume":"41","author":"Liberti","year":"2016","journal-title":"Trends Biochem Sci."},{"issue":"1","key":"2021121112523356600_CIT0024","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1158\/jcr.1925.148","article-title":"The 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