[Repeated non-epileptic seizures in a previously healthy young woman - a case report].

UNLABELLED: A previously healthy 18 year old female has repeated admissions over a six week period to the emergency department because of seizures. She has no previous history of epilepsy and denies any drug use. Imaging and electroencephalogram do not indicate epilepsy. Blood sugar levels are low on two occasions, 1.3 mmol / L and 1.7mmól / L (4.0 - 6.0 mmol / L). After further investigations the suspicion of an insulin-producing tumor arises. Extensive research and imaging is conducted to look for tumor growth without any findings. Subsequently she was sent abroad for further evaluation with a 11C-5HTP-PET scan, selective angiography with celiacography and an intra-arterial calcium stimulation test. She was diagnosed with nesidioblastosis. Here we will discuss the presentation and work-up of the medical case and review this rare causative disease. KEY WORDS: repeated seizures, neuroglycopenic symptoms, noninsulinoma pancreatogenous hypoglycemia syndrome (NIPHS), endogenous hyperinsulinemic hypoglycemia, nesidioblastosis. Correspondence: Guðrun Mist Gunnarsdottir, gudrunmi@landspitali.is.

Nesidioblastosis coexisting with non-functioning islet cell tumour in an adult.

The most common cause of hyperinsulinaemic hypoglycaemia in adult is insulinoma. Although nesidioblastosis is a rare but well-recognized disorder of persistent hypoglycaemia in infants, it is extremely rare in adults.We present a case of a 59-year-old woman with small neuroendocrine tumour of the tail of the pancreas, diagnosed by CT scans and MRI, and hypoglycaemic syndrome. Laparoscopic distal pancreatectomy was performed, and pathologic examination showed a well-differentiated, non-functioning endocrine tumour of the pancreas and diffuse nesidioblastosis in the remnant gland. In the early postoperative period, recurrent hypoglycaemia occurred in spite of oral diazoxide therapy. Plasma proinsulin levels were extremely high. 18F-DOPA positron emission tomography showed a pathologic uptake of tracer in the head and the uncinate process of the pancreas. Subtotal pancreatectomy was suggested but the patient refused operation: she is taking diazoxide 100 mg three times daily. Coexistence of nesidioblastosis with a neuroendocrine tumour makes preoperative diagnosis and management of severe hypoglycaemia more difficult. Nesidioblastosis should be considered in differential diagnosis of hypoglycaemic syndrome, but histological examination is necessary for a definitive tissue diagnosis.

Adult onset nesidioblastosis treated by subtotal pancreatectomy.

CONTEXT: Nesidioblastosis is a rare cause of non insulinoma pancreatogenous hypoglycemic syndrome seen in adults. It is characterized by postprandial hypoglycemia with high insulin and C-peptide levels without any detectable pancreatic lesion. The definitive diagnosis can be made only on histopathological examination of the resected specimen. CASE REPORT: We report a case of a 50-year-old lady presenting with hypoglycemic attacks being misdiagnosed preoperatively as insulinoma and treated with enucleation leading to recurrence of symptoms after 6 months. Later medical therapy was tried which failed and patient needed subtotal pancreatectomy for resolution of symptoms. CONCLUSION: Nesidioblastosis should be suspected in patients with endogenous hyperinsulinemic hypoglycemia without any detectable pancreatic tumor on preoperative imaging.

Prolonged successful therapy for hyperinsulinaemic hypoglycaemia after gastric bypass: the pathophysiological role of GLP1 and its response to a somatostatin analogue.

BACKGROUND: Spontaneous hyperinsulinaemic hypoglycaemia following gastric bypass surgery (GBS) is increasingly recognised. However, its pathophysiology remains unclear. Some patients require pancreatectomy. Medical therapy with calcium channel blockers, acarbose and diazoxide has been reported to be beneficial but has variable adherence and response. METHOD: We demonstrate the role of GLP1, counter-regulatory hormones and the subsequent response of GLP1 to somatostatin analogue therapy in a 42-year-old woman with persistent neuroglycopaenia 6 years after GBS. Plasma GLP1, insulin and glucose were measured for 5  h on three settings: i) a 75  g oral glucose tolerance test (OGTT); ii) a standard liquid test meal (LTM); and iii) an OGTT 30  min after a s.c. injection of 100  µg octreotide. RESULTS: In comparison with obese non-diabetic controls, the patient had an elevated fasting and a markedly enhanced GLP1 response during the OGTT, followed by an exaggerated insulin response and a subsequent low glucose level. The GLP1 response to a LTM was similar but greater. Octreotide given prior to the OGTT attenuated both the GLP1 and insulin responses and abolished hypoglycaemia. Octreotide therapy significantly improved the patient's neuroglycopaenic symptoms. The hormone profile was reassessed after 6 months following the LTM preceded by octreotide injection. Peak GLP1 and insulin responses were less pronounced than pretreatment responses and without hypoglycaemia. The patient was treated with lanreotide and had remained symptom-free and euglycaemic for 4 years. CONCLUSION: An exaggerated incretin response following altered gastrointestinal anatomy was the likely cause of hypoglycaemia in our GBS patient. Somatostatin successfully suppressed this response acutely and in the long term, thereby avoiding pancreatectomy and its sequelae.

Hepatocyte nuclear factor 4α gene mutation associated with familial neonatal hyperinsulinism and maturity-onset diabetes of the young.

Neonatal macrosomia and hyperinsulinemic hypoglycemia with strong family history of diabetes may indicate monogenic diabetes. Here we report a family in which 4 individuals in 3 generations were found to have a mutation (Arg80Gln) in hepatocyte nuclear factor 4α. Genetic testing was a factor in choosing sulfonylurea therapy for diabetes.

Insulin responses to selective arterial calcium infusion under hyperinsulinemic euglycemic glucose clamps: case studies in adult nesidioblastosis and childhood insulinoma.

Selective arterial calcium stimulation and hepatic venous sampling (ASVS) for insulin secretion is used as a diagnostic procedure in patients with insulinomas or adult nesidioblastosis. In some of those patients, severe hypoglycemia requiring urgent glucose administration occurs during the procedure. Such glucose administration, however, may affect the results and damage the validity of the test. We report two cases of hyperinsulinemic hypoglycemia, in which ASVS tests were successfully performed under hyperinsulinemic euglycemic glucose clamps. A 40-year-old male with nesidioblastosis developed continual severe hypoglycemia several years after a Billroth II-Braun gastrectomy, and continuous glucose infusion could not be stopped even during ASVS tests. A 9-year-old girl with an insulinoma that showed atypical hypovascularity on imaging examinations had ASVS tests under a glucose clamp for safety. Hyperinsulinemic (approximately 100 microU/ml) euglycemic (approximately 90 mg/dl) clamps were achieved by an artificial endocrine pancreas. The insulin analogue lispro was utilized for clamps and endogenous insulin was measured with an assay that does not cross-react with the analogue. Diagnostically significant responses (more than twofold) of insulin secretion were observed under hyperinsulinemic clamps in both cases. The use of the hyperinsulinemic glucose clamp technique during the ASVS test should be considered for maintaining the safety of some hypoglycemic patients.

A rare case of adult-onset nesidioblastosis treated successfully with diazoxide.

A 54-year-old man was admitted to our hospital for evaluation of hypoglycemia. He had frequent episodes of loss of concentration before dinner. The ratio of IRI to plasma glucose (PG) was 0.8-1.0. Abdominal CT revealed no pancreatic tumor, and angiography of splenic artery showed no definite tumor stain within the pancreas. Based on the results of selective arterial calcium stimulation and hepatic venous sampling (ASVS), the provisional diagnosis was a small insulinoma in the pancreatic body. The patient underwent subtotal distal pancreatectomy. However, histopathological and immunohistochemical examinations of the resected tissue showed hypertrophy of islets of Langerhans islands and beta cells around pancreatic ducts. The final diagnosis was adult-onset nesidioblastosis. Postoperatively, the patient continued to exhibit hyperinsulinemia and nighttime hypoglycemia. Octreotide, voglibose and diet therapies failed to improve the nocturnal hypoglycemia. However, treatment with diazoxide at a starting dose of 200 mg/day resulted in immediate amelioration of nocturnal hypoglycemia. This is the first Japanese adult case of nesidioblastosis treated successfully with diazoxide. This case report suggests that diazoxide may be effective for adult-onset nesidioblastosis in a manner similar to that described for pediatric cases.

Nesidioblastosis--a rare cause of hypoglycaemia in adults.

A case of suspected clinically hormonally active insulinoma in a 48-year-old woman is presented. Despite the lack of features, which might correspond to the insulinoma in radiological examinations, the patient was qualified for a distal subtotal pancreatectomy and then, due to persistent hyperinsulinism, for total pancreatectomy. The insulinoma was found neither in a palpable examination of the pancreas nor in the intraoperative ultrasonic examination. In a histopathological examination supplemented with immunohistochemical tests, nesidioblastosis - a rare cause of hypoglycaemia in adults - was diagnosed.

Normal pregnancy in a woman with nesidioblastosis treated with somatostatin analog octreotide.

OBJECTIVE: We report the case of a 36-yr-old woman with nesidioblastosis treated throughout pregnancy with high doses of octreotide. We studied the course of blood glucose, foetal growth and development. METHODS: Blood samples were obtained every month throughout pregnancy and taken at birth from the umbilical cord. Sonography was performed repeatedly to monitor foetal growth. RESULTS: The daily dose of octreotide was adapted to blood glucose levels: a dose of 1000 microg was infused during the first part of pregnancy, then it was decreased step by step during the last trimester of gestation. An elective cesarean section was performed at 32 weeks of gestation. High octreotide concentrations were obtained during the first part of gestation (range 2888-5021 pg/ml). During the third trimester of pregnancy blood glucose increased despite high insulin levels attesting physiological insulin-resistance. Plasma levels of placental GH and IGF-1 levels were similar to those observed in a normal pregnancy. Despite the presence of octreotide in the umbilical cord, TSH, free T4, PRL and pituitary GH concentrations were normal at birth. The female newborn (weight 3520 g, length 52 cm) had no malformation, and presented with normal postnatal development. CONCLUSION: Our study demonstrates that: 1) octreotide treatment can be effective in controlling endogenous hyperinsulinism during pregnancy; 2) octreotide does not affect physiological changes during pregnancy such as insulin-resistance or placental GH level; 3) exposure of the foetus to octreotide throughout pregnancy does not induce any malformation and does not affect foetal development.