Hyperinsulinoma Conditions
The most common but not the only etiology of recurrent severe hypoglycemia in an adult is an insulinoma. Less common is nesidioblastosis and neoplasms producing insulin-like growth factor. Thus an occasional patient with a hemangiopericytoma presents with hypoglycemia; a history of a hemangiopericytoma resected previously is not uncommon. Generally not
appreciated is that a large nonpancreatic leiomyosarcoma may mimic clinical findings of an insulinoma, including severe hypoglycemia. Even a bowel adenocarcinoma with liver metastases can have hypoglycemia induced by tumor insulin-like growth factor production. Occasionally encountered is hypoglycemia developing in a patient with renal failure or fulminant hepatic failure.
Insulinoma
The most common islet cell endocrine tumor is an insulinoma. A Japanese literature search of over 1000 patients with insulinoma or hypoglycemic syndrome revealed that 81% of these tumors were 20 mm or smaller. About 90% are benign and most tend to be solitary, solid, and homogeneous.Multiple insulinomas should suggest MEN-I syndrome. Primary extrapancreatic insulinomas are rare. Cystic insulinomas are uncommon. Histologically, an insulinoma mimics normal islet cells. It is difficult to tell with some whether indeed it is a neoplasm or simply represents hyperplasia. Autonomous insulin synthesis and secretion are the hallmark of an insulinoma even in a setting of low blood glucose levels, leading to further hypoglycemia and resultant clinical findings.
Most insulinomas are small and are difficult to detect with imaging. Conventional CT, grayscale US, and MRI are of limited value. In one study, combined dual-phase thin-section multidetector CT and endoscopic US achieved a diagnostic sensitivity of 100% in detecting these tumors. Endoscopic US appears to be somewhat more sensitive in detecting insulinomas in the pancreatic head and less sensitive in the pancreatic tail. Nevertheless, some tumors are found only by the surgeon or by intraoperative
US; some surgeons opine that detection of an insulinoma does not require extensive preoperative localization.
A rare insulinoma is hyperdense to normal pancreatic parenchyma on precontrast CT. An early arterial phase and pancreatic phase appears best in detecting these tumors. Postcontrast CT ring-like enhancement progressing into homogeneous tumor enhancement is seen in about half of these tumors. The uncommon malignant insulinoma is a highly vascular tumor in the pancreatic tail often detected from liver metastases; liver venous sampling after arterial stimulation with calcium confirms insulin secretion. In some, serum levels of a-fetoprotein and trypsin are markedly elevated. Intraoperative US is very helpful in localizing these tumors and in defining adjacent structures.
Magnetic resonance imaging localizes some pancreatic insulinomas. They are hypointense on T1- and hyperintense on T2-weighted sequences and are homogeneously hyperintense on postcontrast images. While not usually performed, indium- 111–octreotide scintigraphy does, at times, localize an insulinoma. Insulin venous sampling is useful in detecting insulinomas not detected by other imaging modalities. Calcium gluconate is injected directly into the gastroduodenal, splenic, and superior mesenteric arteries, followed by venous sampling. Injection into an artery supplying an insulinoma results in a marked increase in the draining vein insulin level. An insulin increase post–calcium infusion of at least 100% above basal levels is considered abnormal. Such an approach obviates the need for transhepatic portal venous sampling and is simpler. This test is also useful for suspected hepatic metastases; no increase in insulin concentration in hepatic venous blood after intraarterial calcium stimulation makes insulinoma liver metastases unlikely. Nevertheless, this test should be interpreted with caution, because an injection into an artery not supplying a tumor may also increase venous insulin levels, possibly by the influx ofcalcium into a tumor via intrapancreatic
anastomoses.
Nesidioblastosis
Nesidioblastosis, also called noninsulinoma pancreatogenous hypoglycemic syndrome and other similar names, is a rare condition consisting of islet hyperplasia and b-cell hyperfunction. This is a nonneoplastic condition but is discussed here because it is in the differential of a suspected insulinoma. Also, occasionally nesidioblastosis coexists with an insulinoma. Nesidioblastosis is a well-recognized entity in neonates but also occasionally develops in adults. It may be part of MEN-I syndrome. Familial nesidioblastosis occurs in neonates. These patients present with hyperinsulinemic hypoglycemia, but a prolonged fast tends to be normal. An insulinoma is usually suspected, but preoperative localization, operative exploration, and intraoperative US do not detect a tumor. At times a blind distal pancreatectomy is performed. The diagnosis is made by the pathologist finding nesidioblasts and islet cell hyperplasia in a resected specimen. Also, the islets are structurally abnormal. A defect in insulin gene regulation appears involved in these patients.
Portal venous sampling in some of these patients shows a gradient in insulin concentration, and a misdiagnosis of insulinoma is thus made. These patients have a positive selective arterial calcium stimulation test indicative of pancreatic b-cell hyperfunction (there is an increase in plasma insulin level when calcium is injected into the arteries supplying the pancreas). In neonates, a >95% pancreatectomy is performed for persistent hyperinsulinemic hypoglycemia due to nesidioblastosis and failed medical management. At times only that portion of the gland lying between the common bile duct and duodenum and a small rim of pancreas along the duodenal sweep are not resected; still, in about one third of children with such a resection, hyperinsulinemia and hypoglycemia recur and a near-total pancreatic resection is then necessary. Of interest is that partial pancreatic regrowth develops in some of these ueouates. On a long-term basis, over two
thirds of these children with a 95% pancreatectomy develop diabetes.
appreciated is that a large nonpancreatic leiomyosarcoma may mimic clinical findings of an insulinoma, including severe hypoglycemia. Even a bowel adenocarcinoma with liver metastases can have hypoglycemia induced by tumor insulin-like growth factor production. Occasionally encountered is hypoglycemia developing in a patient with renal failure or fulminant hepatic failure.
Insulinoma
The most common islet cell endocrine tumor is an insulinoma. A Japanese literature search of over 1000 patients with insulinoma or hypoglycemic syndrome revealed that 81% of these tumors were 20 mm or smaller. About 90% are benign and most tend to be solitary, solid, and homogeneous.Multiple insulinomas should suggest MEN-I syndrome. Primary extrapancreatic insulinomas are rare. Cystic insulinomas are uncommon. Histologically, an insulinoma mimics normal islet cells. It is difficult to tell with some whether indeed it is a neoplasm or simply represents hyperplasia. Autonomous insulin synthesis and secretion are the hallmark of an insulinoma even in a setting of low blood glucose levels, leading to further hypoglycemia and resultant clinical findings.
Most insulinomas are small and are difficult to detect with imaging. Conventional CT, grayscale US, and MRI are of limited value. In one study, combined dual-phase thin-section multidetector CT and endoscopic US achieved a diagnostic sensitivity of 100% in detecting these tumors. Endoscopic US appears to be somewhat more sensitive in detecting insulinomas in the pancreatic head and less sensitive in the pancreatic tail. Nevertheless, some tumors are found only by the surgeon or by intraoperative
US; some surgeons opine that detection of an insulinoma does not require extensive preoperative localization.
A rare insulinoma is hyperdense to normal pancreatic parenchyma on precontrast CT. An early arterial phase and pancreatic phase appears best in detecting these tumors. Postcontrast CT ring-like enhancement progressing into homogeneous tumor enhancement is seen in about half of these tumors. The uncommon malignant insulinoma is a highly vascular tumor in the pancreatic tail often detected from liver metastases; liver venous sampling after arterial stimulation with calcium confirms insulin secretion. In some, serum levels of a-fetoprotein and trypsin are markedly elevated. Intraoperative US is very helpful in localizing these tumors and in defining adjacent structures.
Magnetic resonance imaging localizes some pancreatic insulinomas. They are hypointense on T1- and hyperintense on T2-weighted sequences and are homogeneously hyperintense on postcontrast images. While not usually performed, indium- 111–octreotide scintigraphy does, at times, localize an insulinoma. Insulin venous sampling is useful in detecting insulinomas not detected by other imaging modalities. Calcium gluconate is injected directly into the gastroduodenal, splenic, and superior mesenteric arteries, followed by venous sampling. Injection into an artery supplying an insulinoma results in a marked increase in the draining vein insulin level. An insulin increase post–calcium infusion of at least 100% above basal levels is considered abnormal. Such an approach obviates the need for transhepatic portal venous sampling and is simpler. This test is also useful for suspected hepatic metastases; no increase in insulin concentration in hepatic venous blood after intraarterial calcium stimulation makes insulinoma liver metastases unlikely. Nevertheless, this test should be interpreted with caution, because an injection into an artery not supplying a tumor may also increase venous insulin levels, possibly by the influx ofcalcium into a tumor via intrapancreatic
anastomoses.
Nesidioblastosis
Nesidioblastosis, also called noninsulinoma pancreatogenous hypoglycemic syndrome and other similar names, is a rare condition consisting of islet hyperplasia and b-cell hyperfunction. This is a nonneoplastic condition but is discussed here because it is in the differential of a suspected insulinoma. Also, occasionally nesidioblastosis coexists with an insulinoma. Nesidioblastosis is a well-recognized entity in neonates but also occasionally develops in adults. It may be part of MEN-I syndrome. Familial nesidioblastosis occurs in neonates. These patients present with hyperinsulinemic hypoglycemia, but a prolonged fast tends to be normal. An insulinoma is usually suspected, but preoperative localization, operative exploration, and intraoperative US do not detect a tumor. At times a blind distal pancreatectomy is performed. The diagnosis is made by the pathologist finding nesidioblasts and islet cell hyperplasia in a resected specimen. Also, the islets are structurally abnormal. A defect in insulin gene regulation appears involved in these patients.
Portal venous sampling in some of these patients shows a gradient in insulin concentration, and a misdiagnosis of insulinoma is thus made. These patients have a positive selective arterial calcium stimulation test indicative of pancreatic b-cell hyperfunction (there is an increase in plasma insulin level when calcium is injected into the arteries supplying the pancreas). In neonates, a >95% pancreatectomy is performed for persistent hyperinsulinemic hypoglycemia due to nesidioblastosis and failed medical management. At times only that portion of the gland lying between the common bile duct and duodenum and a small rim of pancreas along the duodenal sweep are not resected; still, in about one third of children with such a resection, hyperinsulinemia and hypoglycemia recur and a near-total pancreatic resection is then necessary. Of interest is that partial pancreatic regrowth develops in some of these ueouates. On a long-term basis, over two
thirds of these children with a 95% pancreatectomy develop diabetes.
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