{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T22:01:09Z","timestamp":1783807269014,"version":"3.55.0"},"reference-count":73,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2006,8,4]],"date-time":"2006-08-04T00:00:00Z","timestamp":1154649600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Endocrinology"],"published-print":{"date-parts":[[2006,11]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p><jats:bold>Objective\u2002<\/jats:bold> Noninsulinoma pancreatogenous hypoglycaemia syndrome (NIPHS), characterized by postprandial neuroglycopaenia, negative prolonged fasts and negative perioperative localization studies for insulinoma, but positive selective arterial calcium stimulation tests and nesidioblastosis in the gradient\u2010guided resected pancreas, is a rare hypoglycaemic disorder of undetermined aetiology. We analysed the clinical, morphological and immunohistological features to further clarify the aetiology and pathogenesis of this rare disease.<\/jats:p><jats:p><jats:bold>Patients\u2002<\/jats:bold> Ten consecutive patients with NIPHS (nine men and one woman, aged 29\u201378\u00a0years) were included in the study. Six of the 10 received a gradient\u2010guided subtotal (70%) or distal (50%) pancreatectomy. In the remaining four patients, diazoxide treatment was initiated and the precise mechanism of its action was assessed by meal tests.<\/jats:p><jats:p><jats:bold>Results\u2002<\/jats:bold> All of the patients showed a combination of postprandial neuroglycopaenia, negative prolonged fasts (except one patient) and negative localization studies for insulinoma, but positive calcium stimulation tests and nesidioblastosis in the gradient\u2010guided resected pancreas. Immunohistological studies of the resected pancreatic tissues revealed neither an increased rate of proliferation of \u03b2\u2010cells nor an abnormal synthesis and\/or processing of either proinsulin or amylin. Evidence of overexpression of the two pancreatic differentiation factors, PDX\u20101 and Nkx\u20106\u00b71, as well as the calcium sensing receptor (CaSR) was absent. Nevertheless, abnormal expression of islet neogenesis\u2010associated protein (INGAP), a human cytokine expressed only in the presence of islet neogenesis, in ducts and\/or islets, was identified in three of the five patients studied. All of the six patients who received a surgical operation were relieved of further neuroglycopaenic attacks, but one patient who received a subtotal pancreatectomy developed diabetes. In the remaining four patients who received diazoxide treatment, hypoglycaemic episodes were satisfactorily controlled with an attenuated response of \u03b2\u2010cell peptides to meal stimulation.<\/jats:p><jats:p><jats:bold>Conclusions\u2002<\/jats:bold> Our results strengthen the existence of this unique clinical hypoglycaemic syndrome from \u03b2\u2010cell hyperfunction as well as the value of the selective arterial calcium stimulation test in its correct diagnosis and localization. The mechanisms underlying \u03b2\u2010cell hyperfunction and release of insulin to calcium, however, remain poorly characterized. Nevertheless, in a subset of patients with NIPHS, there exists some, as yet undefined, pancreatic humoral\/paracrine factor(s) other than proinsulin, amylin, PDX\u20101, Nkx\u20106\u00b71 and possibly glucagon\u2010like peptide\u20101 (GLP\u20101) that are capable of inducing the INGAP gene and, if activated, will initiate ductal proliferation and islet neogenesis. As for the treatment, we recommend that diazoxide be tried first in each patient and, should it fail, a gradient\u2010guided subtotal or distal pancreatectomy be attempted.<\/jats:p>","DOI":"10.1111\/j.1365-2265.2006.02629.x","type":"journal-article","created":{"date-parts":[[2006,8,4]],"date-time":"2006-08-04T21:46:51Z","timestamp":1154728011000},"page":"566-578","source":"Crossref","is-referenced-by-count":72,"title":["Clinical features and morphological characterization of 10 patients with noninsulinoma pancreatogenous hypoglycaemia syndrome (NIPHS)"],"prefix":"10.1111","volume":"65","author":[{"given":"Justin G. 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