PMC8578890_01
Continuous blood glucose monitoring, mean blood glucose level before and after treatment with diazoxide and enhanced abdominal computer tomography findings compatible with acute necrotizing pancreatitis on admission. Oral diazoxide improved the hypoglycemic state of the patient. The values of amylase and lipase described on day 18 are values before diazoxide treatment. The blood levels of pancreatic amylase (152  596 U/L) and lipase (97 538 U/L) increased on day 19. Arrow heads indicate treatment with 125 mg diazoxide. Red regions indicate the interval during which the sensor glucose level was less than 70mg/dl. During the tube feeding, we used Peptino (Terumo, Tokyo, Japan), which is a liquid digestive meal. We used ELNEOPA-NF No.2 injection from Otsuka Pharmaceuticals (Tokushima, Japan) for the total parental injection. (A). Enhanced computer tomography (CT) images show enlargement of the pancreas with low-density areas in the pancreatic body (B) and peripancreatic fluid collections. There is no evidence of a pancreatic tumor (C). An arterial secretagogue injection (SASI) test shows insulin hypersecretion in the whole pancreases (D).  : Splenic Artery,  : Gastroduodenal artery,  : Dorsal splenic artery,  : Superior mesenteric artery,  : Proper hepatic artery).
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The decrease in episodes of hypoglycemia and laboratory data of glycemia during childhood and monitoring of blood glucose levels (Free-style Libre Pro, Abbott Japan, Tokyo, Japan) after admission to our institution suggest that the patient was responsive to diazoxide ( Figure 1A ). Table 1  and  Figure 1A  ). There was no sign of primary hyperparathyroidism. However, after discontinuation of diazoxide, the patient had refractory hypoglycemia caused by hyperinsulinemia (  Table 1  and  Figure 1A  ). However, the blood levels of pancreatic amylase (152 596 U/L) and lipase (97 538 U/L) further increased on day 19 ( Figure 1A ). The SASI test revealed hypersecretion of insulin from the whole pancreas (  Figure 1D  ). In addition, the pathological study showed large-sized islets of Langerhans distributed in the whole pancreas, with the density of islets increasing from the body through the tail of the pancreas ( Figures 2A, B ). Importantly, in addition to the ductuloinsular complex in the pancreas ( Figure 2C ), the histopathological examination of peripancreatic lymph nodes showed the presence of nests of neuroendocrine cells ( Figure 2D  and  Supplementary Figures 1A-C ).
Hematoxylin & eosin staining of pancreas surgical specimen. Staining shows the increased density of Langerhans cells from the body through the tail of the pancreas (A, B), ductuloinsular complex (C), and lymph node metastases (D). Scale bars indicate 500 microm in (A) and 200 microm in (C, D).
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In addition, the pathological study showed large-sized islets of Langerhans distributed in the whole pancreas, with the density of islets increasing from the body through the tail of the pancreas ( Figures 2A, B ). Importantly, in addition to the ductuloinsular complex in the pancreas ( Figure 2C ), the histopathological examination of peripancreatic lymph nodes showed the presence of nests of neuroendocrine cells ( Figure 2D  and  Supplementary Figures 1A-C ).
Immunohistochemical staining of pancreas surgical specimen. Low magnification of pancreatic tail tissue stained with hematoxylin & eosin (A). Immunohistochemical staining of pancreatic tail tissue showed positivity for synaptophysin (B), neural cell adhesion molecule or CD56 (C), somatostatin receptor 2 (D), and insulin (E). Glucagon staining was negative (F). Scale bar indicates 500 microm in (A) and 200 microm in (B-F).
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Additional pathological findings were neuroendocrine cell nests larger than 1 mm with pleomorphic and enlarged nuclei, positive staining for synaptophysin and neural cell adhesion molecule (CD56), and positive staining for somatostatin receptor 2 (SSTR2a) in the pancreatic tail ( Figures 3A-D ). Immunofluorescence staining also demonstrated an increased number of insulin-producing beta-cells in the patient's pancreas ( Figures 3E, F ).