{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T18:33:13Z","timestamp":1789842793801,"version":"4.0.1"},"reference-count":28,"publisher":"The Endocrine Society","issue":"1","license":[{"start":{"date-parts":[[2025,1,9]],"date-time":"2025-01-09T00:00:00Z","timestamp":1736380800000},"content-version":"vor","delay-in-days":28,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,12,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>A 75-year-old female presented with fasting hypoglycemic episodes. A supervised fast ended at 72\u2005hours fulfilling Whipple triad, with suppressed insulin and C-peptide levels, but discordantly suppressed serum \u03b2-hydroxybutyrate levels. After 21 months of recurring symptoms, a repeat fast ended at 48\u2005hours with Whipple triad, suppressed serum \u03b2-hydroxybutyrate level, and borderline nonsuppressed C-peptide level, suggesting endogenous hyperinsulinism. Serum insulin levels were discordantly suppressed. Computed tomography (CT) of the abdomen demonstrated an enhancing 1.36 \u00d7 0.93-cm nodule in the head of the pancreas. Endoscopic ultrasound (EUS)-guided fine-needle aspirate of the lesion derived cytology consistent with a neuroendocrine tumor, but fine-needle core biopsy returned normal pancreatic tissue. Because the results were equivocal, functional imaging with 68Gallium-DOTA-exendin-4 positron emission tomography CT was performed, which confirmed the diagnosis of a single head-of-pancreas insulinoma. The patient declined surgical resection. Oral diazoxide therapy resulted in significant peripheral edema. Hence, EUS-guided radiofrequency ablation of the lesion was performed, and the patient remains symptom free 10 months postprocedure. This case illustrates that (1) exendin-4\u2013based positron emission tomography may help one confidently diagnose and localize insulinoma when prior biochemical or endoscopic biopsy results are ambiguous; and (2) EUS-guided radiofrequency ablation is an efficacious alternative option to surgical resection in the frail, elderly patient with insulinoma.<\/jats:p>","DOI":"10.1210\/jcemcr\/luae232","type":"journal-article","created":{"date-parts":[[2024,11,30]],"date-time":"2024-11-30T12:16:55Z","timestamp":1732969015000},"source":"Crossref","is-referenced-by-count":1,"title":["Insulinoma With Ambiguous Biochemistry, Positive 68Ga-DOTA-Exendin-4 PET-CT, and Effective Endoscopic Ablation"],"prefix":"10.1210","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-5336-4016","authenticated-orcid":false,"given":"Fernando Jia Jing","family":"Loo","sequence":"first","affiliation":[{"name":"Department of Endocrinology, Tan Tock Seng Hospital , 308433","place":["Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melvin Kok Seng","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Woodlands Health Campus , 737628","place":["Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hian Liang","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine and Molecular Imaging, Singapore General Hospital , 169608","place":["Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles Kien Fong","family":"Vu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Tan Tock Seng Hospital , 308433","place":["Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9693-2587","authenticated-orcid":false,"given":"Yin Chian","family":"Kon","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Tan Tock Seng Hospital , 308433","place":["Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2025,1,9]]},"reference":[{"issue":"3","key":"2025011704225932100_luae232-B1","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1210\/jc.2008-1410","article-title":"Evaluation and management of adult hypoglycemic disorders: an Endocrine Society clinical practice guideline","volume":"94","author":"Cryer","year":"2009","journal-title":"J Clin Endocrinol Metab"},{"issue":"6","key":"2025011704225932100_luae232-B2","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1097\/MPA.0b013e3181ebaffd","article-title":"NANETS consensus guidelines for the diagnosis of neuroendocrine tumor","volume":"39","author":"Vinik","year":"2010","journal-title":"Pancreas"},{"issue":"2","key":"2025011704225932100_luae232-B3","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1159\/000335591","article-title":"ENETS consensus guidelines for the management of patients with digestive neuroendocrine neoplasms: functional pancreatic endocrine tumor syndromes","volume":"95","author":"Jensen","year":"2012","journal-title":"Neuroendocrinology"},{"issue":"1-2","key":"2025011704225932100_luae232-B4","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/j.cccn.2003.12.023","article-title":"Assessment of hyperinsulinaemia at the termination of the prolonged fast","volume":"342","author":"Wiesli","year":"2004","journal-title":"Clinica Chimica Acta"},{"issue":"5","key":"2025011704225932100_luae232-B5","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1530\/eje.0.1490413","article-title":"Insulin levels measured with an insulin-specific assay in patients with fasting hypoglycaemia related to endogenous hyperinsulinism","volume":"149","author":"Vezzosi","year":"2003","journal-title":"Eur J Endocrinol"},{"issue":"2","key":"2025011704225932100_luae232-B6","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1111\/cen.14406","article-title":"Exendin-4-based imaging in insulinoma localization: systematic review and meta-analysis","volume":"95","author":"Shah","year":"2021","journal-title":"Clin Endocrinol"},{"issue":"6","key":"2025011704225932100_luae232-B7","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1046\/j.1365-2796.2002.01060.x","article-title":"A plasma glucose concentration below 2.5\u2005mmol L\u2212 1 is not an appropriate criterion to end the 72-h fast","volume":"252","author":"Wiesli","year":"2002","journal-title":"J Intern Med"},{"issue":"5","key":"2025011704225932100_luae232-B8","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1210\/jcem-37-5-698","article-title":"Homeostasis during fasting. Hormone substrate differences between men and women","volume":"37","author":"Merimee","year":"1973","journal-title":"J Clin Endocrinol Metab"},{"key":"2025011704225932100_luae232-B9","doi-asserted-by":"crossref","first-page":"994707","DOI":"10.3389\/fendo.2022.994707","article-title":"The optimal diagnostic criteria of endogenous hyperinsulinemic hypoglycemia based on a large cohort of Chinese patients","volume":"13","author":"Yu","year":"2022","journal-title":"Front Endocrinol"},{"issue":"1","key":"2025011704225932100_luae232-B10","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1530\/EJE-07-0109","article-title":"Insulin, C-peptide and proinsulin for the biochemical diagnosis of hypoglycaemia related to endogenous hyperinsulinism","volume":"157","author":"Vezzosi","year":"2007","journal-title":"Eur J Endocrinol"},{"issue":"4","key":"2025011704225932100_luae232-B11","doi-asserted-by":"crossref","first-page":"498","DOI":"10.3803\/EnM.2014.29.4.498","article-title":"Clinical implications of various criteria for the biochemical diagnosis of insulinoma","volume":"29","author":"Ahn","year":"2014","journal-title":"Endocrinol Metab"},{"issue":"11","key":"2025011704225932100_luae232-B12","doi-asserted-by":"crossref","first-page":"767","DOI":"10.7326\/0003-4819-157-11-201212040-00004","article-title":"Diagnostic accuracy of an \u201camended\u201d insulin\u2013glucose ratio for the biochemical diagnosis of insulinomas","volume":"157","author":"Nauck","year":"2012","journal-title":"Ann Intern Med"},{"issue":"4","key":"2025011704225932100_luae232-B13","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1210\/jc.2008-2031","article-title":"Secular trends in the presentation and management of functioning insulinoma at the Mayo Clinic, 1987\u20132007","volume":"94","author":"Placzkowski","year":"2009","journal-title":"J Clin Endocrinol Metab"},{"issue":"6","key":"2025011704225932100_luae232-B14","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1530\/EJE-18-0879","article-title":"Comparison of the diagnostic accuracy of the current guidelines for detecting insulinoma","volume":"180","author":"Dauben","year":"2019","journal-title":"Eur J Endocrinol"},{"issue":"2","key":"2025011704225932100_luae232-B15","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/0168-8227(94)90153-8","article-title":"Assessment of immunoassays for insulin in diagnostic tests for insulinoma","volume":"26","author":"Shimizu","year":"1994","journal-title":"Diabetes Res Clin Pract"},{"issue":"2","key":"2025011704225932100_luae232-B16","first-page":"448","article-title":"Insulin surrogates in insulinoma","volume":"77","author":"O\u2019Brien","year":"1993","journal-title":"J Clin Endocrinol Metab"},{"issue":"8","key":"2025011704225932100_luae232-B17","doi-asserted-by":"crossref","first-page":"4555","DOI":"10.1210\/jc.2005-0033","article-title":"Increasing serum betahydroxybutyrate concentrations during the 72-hour fast: evidence against hyperinsulinemic hypoglycemia","volume":"90","author":"Service","year":"2005","journal-title":"J Clin Endocrinol Metab"},{"issue":"11","key":"2025011704225932100_luae232-B18","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1038\/nrendo.2009.198","article-title":"Diagnosis of insulinoma in a patient with hypoglycemia without obvious hyperinsulinemia","volume":"5","author":"Coelho","year":"2009","journal-title":"Nat Rev Endocrinol"},{"issue":"6","key":"2025011704225932100_luae232-B19","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1258\/000456303770367315","article-title":"Insulinoma: how reliable is the biochemical evidence?","volume":"40","author":"Chammas","year":"2003","journal-title":"Ann Clin Biochem"},{"issue":"4","key":"2025011704225932100_luae232-B20","doi-asserted-by":"crossref","first-page":"1464","DOI":"10.1210\/jc.2002-021543","article-title":"The diagnosis of fasting hypoglycemia due to an islet-cell tumour obscured by a highly specific insulin assay","volume":"88","author":"Chia","year":"2003","journal-title":"J Clin Endocrinol Metab"},{"issue":"4","key":"2025011704225932100_luae232-B21","doi-asserted-by":"crossref","first-page":"660","DOI":"10.4158\/EP10016.CR","article-title":"Beta-cell adenomas without hyperinsulinemia with use of highly specific insulin radioimmunoassays: case report and review of literature","volume":"16","author":"G\u00f3mez-P\u00e9rez","year":"2010","journal-title":"Endocr Pract"},{"issue":"12","key":"2025011704225932100_luae232-B22","doi-asserted-by":"crossref","first-page":"4752","DOI":"10.1210\/jc.2013-2182","article-title":"The role of proinsulin and insulin in the diagnosis of insulinoma: a critical evaluation of the Endocrine Society clinical practice guideline","volume":"98","author":"Guettier","year":"2013","journal-title":"J Clin Endocrinol Metab"},{"issue":"10","key":"2025011704225932100_luae232-B23","doi-asserted-by":"crossref","first-page":"1861","DOI":"10.1001\/archinte.1985.00360100127021","article-title":"Anomalous glucose and insulin responses in patients with insulinoma: caveats for diagnosis","volume":"145","author":"Dons","year":"1985","journal-title":"Arch Intern Med"},{"issue":"8","key":"2025011704225932100_luae232-B24","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1056\/NEJM198702193160805","article-title":"The effects of biosynthetic human proinsulin on carbohydrate metabolism in non-insulin-dependent diabetes mellitus","volume":"316","author":"Glauber","year":"1987","journal-title":"N Engl J Med"},{"issue":"10","key":"2025011704225932100_luae232-B25","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1002\/jlcr.3750","article-title":"Exendin-4 analogs in insulinoma theranostics","volume":"62","author":"Jansen","year":"2019","journal-title":"J Labelled Com Radiopharm"},{"issue":"10","key":"2025011704225932100_luae232-B26","doi-asserted-by":"crossref","first-page":"1332","DOI":"10.1007\/s00595-011-4547-6","article-title":"Surgical management of pancreatic neuroendocrine tumors","volume":"41","author":"Kimura","year":"2011","journal-title":"Surg Today"},{"issue":"11","key":"2025011704225932100_luae232-B27","doi-asserted-by":"crossref","first-page":"2834","DOI":"10.1016\/j.cgh.2023.02.022","article-title":"Endoscopic ultrasound-guided radiofrequency ablation versus surgical resection for treatment of pancreatic insulinoma","volume":"21","author":"Crin\u00f2","year":"2023","journal-title":"Clin Gastroenterol Hepatol"},{"key":"2025011704225932100_luae232-B28","doi-asserted-by":"crossref","first-page":"17562848211042171","DOI":"10.1177\/17562848211042171","article-title":"Endoscopic ultrasound-guided ethanol and radiofrequency ablation of pancreatic insulinomas: a systematic literature review","volume":"14","author":"El Sayed","year":"2021","journal-title":"Ther Adv Gastroenterol"}],"container-title":["JCEM Case Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jcemcr\/article-pdf\/3\/1\/luae232\/61383079\/luae232.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcemcr\/article-pdf\/3\/1\/luae232\/61383079\/luae232.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,17]],"date-time":"2025-01-17T04:23:22Z","timestamp":1737087802000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcemcr\/article\/doi\/10.1210\/jcemcr\/luae232\/7945881"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,12]]},"references-count":28,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2024,12,12]]}},"URL":"https:\/\/doi.org\/10.1210\/jcemcr\/luae232","relation":{},"ISSN":["2755-1520"],"issn-type":[{"value":"2755-1520","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,1]]},"published":{"date-parts":[[2024,12,12]]},"article-number":"luae232"}}