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Where Are Insulinomas Found

Practice Essentials

Practice Essentials

Insulinomas are the most common cause of hypoglycemia resulting from endogenous hyperinsulinism. Approximately 90-95% of insulinomas are benign, and long-term cure with total resolution of preoperative symptoms is expected after complete resection. [1] See the image below. Signs and symptoms Insulinomas are characterized clinically by the Whipple triad, as follows: Presence of symptoms of hypoglycemia (about 85% of patients) Documented low blood sugar at the time of symptoms About 85% of patients with insulinoma present with one of the following symptoms of hypoglycemia: Hypoglycemia can also result in the following: Adrenergic symptoms (from hypoglycemia-related adrenalin release): Weakness, sweating, tachycardia, palpitations, and hunger See Clinical Presentation for more detail. Diagnosis Lab studies Failure of endogenous insulin secretion to be suppressed by hypoglycemia is the hallmark of an insulinoma. Thus, the finding of inappropriately elevated levels of insulin in the face of hypoglycemia is the key to diagnosis. The biochemical diagnosis of insulinoma is established in 95% of patients during prolonged fasting (up to 72 h) when the following results are found: Serum insulin levels of 10 µU/mL or more (normal < 6 µU/mL) C-peptide levels exceeding 2.5 ng/mL (normal < 2 ng/mL) Proinsulin levels greater than 25% (or up to 90%) of immunoreactive insulin levels Imaging studies Insulinomas can be located with the following imaging modalities: Real-time transabdominal high-resolution ultrasonography: 50% sensitivity Intraoperative transabdominal high-resolution ultrasonography with the transducer wrapped in a sterile rubber glove and passed over the exposed pancreatic surface: Detects more than 90% of insulinomas Computed tomography (CT) scanning: 82-94% sensitivity Continue reading >>

Insulinoma

Insulinoma

Causes, incidence, and risk factors: The pancreas is an organ in the abdomen. The pancreas makes several enzymes and hormones, including the hormone insulin. Insulin's job is to reduce the level of sugar (glucose) in the blood by helping it move into cells. Most of the time when your blood sugar level drops too low, the pancreas stops making insulin until your blood sugar returns to normal. Tumors of the pancreas that produce too much insulin are called insulinomas. Insulinomas keep making insulin, even when your blood sugar drops too low. A high blood insulin level causes a low blood sugar level (hypoglycemia ). Hypoglycemia may be mild, leading to symptoms such as anxiety and hunger. Or it can be severe, leading to seizures, coma, and even death. Insulinomas are rare tumors. They usually occur as single, small tumors in adults. These tumors are very rare in children. Most children with high blood insulin levels have many areas of overactive insulin-releasing cells in the pancreas, instead of a single tumor. More than 90% of insulinomas are non-cancerous (benign) tumors. People with the genetic syndrome called multiple endocrine neoplasia type I are at risk of insulinomas and other endocrine tumors . Symptoms: Behavior changes Clouded vision Coma Dizziness Headache Hunger Sweating Tremor Weight gain Signs and tests: After fasting, your blood may be tested for: Blood C-peptide level Blood glucose level Blood insulin level Drugs that cause the pancreas to release insulin CT or MRI scan of the abdomen , or PET scan may be done to look for a tumor in the pancreas. If the test is negative, one of the following tests may be performed: Treatment: Surgery is the recommended treatment for insulinoma. The tumor is first found by tests or surgery. Medication may be used to get pa Continue reading >>

Insulin, C-peptide And Proinsulin For The Biochemical Diagnosis Of Hypoglycaemia Related To Endogenous Hyperinsulinism

Insulin, C-peptide And Proinsulin For The Biochemical Diagnosis Of Hypoglycaemia Related To Endogenous Hyperinsulinism

Abstract Objective: We evaluated the respective value of insulin, C-peptide and proinsulin levels in 33 patients with endogenous hyperinsulinism and in 67 controls to determine the best parameters and thresholds to make or to rule out the diagnosis of endogenous hyperinsulinism. Results: When blood glucose levels were below 2.5 mmol/l, insulin was <21 pmol/l in 8–35% of the patients and in all controls; C-peptide was >0.2 nmol/l in all insulinomas but not in the nesidioblastosis or in the controls; proinsulin was >5 pmol/l in all patients but not in the controls. When fasting blood glucose levels reached 2.5–3.3 mmol/l, proinsulin was <22 pmol/l in all the controls and >22 pmol/l in 74% of the patients. Proinsulin after an overnight fast was below 22 pmol/l in all non-obese controls and above 22 pmol/l in 73% of non-obese patients. Conclusion: Proinsulin levels above 5 pmol/l with blood glucose levels below 2.5 mmol/l during a 72 h fast test represent the best criterion for the diagnosis of endogenous hyperinsulinism, reaching 100% diagnostic specificity and sensitivity. Concomitant C-peptide levels above 0.2 nmol/l also make the diagnosis of all our insulinoma patients, not the diagnosis of nesidioblastosis, while insulin levels have much less diagnostic accuracy. Whether proinsulin levels above 22 pmol/l could also make the diagnosis of endogenous hyperinsulinism in part of the patients at the time of fasting blood glucose levels between 2.5 and 3.3 mmol/l or after an overnight fast in non-obese subjects needs further study. Introduction The biological criteria for the diagnosis of fasting hypoglycaemia related to endogenous hyperinsulinism have been challenged within recent years. They were previously based on the finding of inappropriate serum levels of insulin Continue reading >>

Insulinoma

Insulinoma

The pancreas is an organ in the abdomen. The pancreas makes several enzymes and hormones, including the hormone insulin. Insulin's job is to reduce the level of sugar (glucose) in the blood by helping it move into cells. Most of the time when your blood sugar level drops too low, the pancreas stops making insulin until your blood sugar returns to normal. Tumors of the pancreas that produce too much insulin are called insulinomas. Insulinomas keep making insulin, even when your blood sugar drops too low. A high blood insulin level causes a low blood sugar level (hypoglycemia). Hypoglycemia may be mild, leading to symptoms such as anxiety and hunger. Or it can be severe, leading to seizures, coma, and even death. Insulinomas are rare tumors. They usually occur as single, small tumors. But there can also be several small tumors. Most insulinomas are non-cancerous (benign) tumors. People with certain genetic disorders such as multiple endocrine neoplasia type I are at risk for insulinomas. Continue reading >>

Insulinoma

Insulinoma

An insulinoma is a rare pancreatic beta-cell tumor that hypersecretes insulin. The main symptom is fasting hypoglycemia. Diagnosis is by a 48- or 72-h fast with measurement of glucose and insulin levels, followed by endoscopic ultrasound. Treatment is surgery when possible. Drugs that block insulin secretion (eg, diazoxide, octreotide, calcium channel blockers, beta-blockers, phenytoin) are used for patients not responding to surgery. Insulinomas are a type of pancreatic endocrine tumor that arises from islet cells. Of all insulinomas, 80% are single and may be curatively resected if identified. Only 10% of insulinomas are malignant. Insulinoma occurs in 1/250,000 at a median age of 50 yr, except in multiple endocrine neoplasia (MEN) type 1 (about 10% of insulinomas), when it occurs in the 20s. Insulinomas associated with MEN 1 are more likely to be multiple. Surreptitious administration of exogenous insulin can cause episodic hypoglycemia mimicking insulinoma. Hypoglycemia secondary to an insulinoma occurs during fasting. Symptoms of hypoglycemia due to insulinoma are insidious and may mimic various psychiatric and neurologic disorders. CNS disturbances include headache, confusion, visual disturbances, motor weakness, palsy, ataxia, marked personality changes, and possible progression to loss of consciousness, seizures, and coma. Symptoms of sympathetic stimulation (faintness, weakness, tremulousness, palpitation, sweating, hunger, and nervousness) are often present. Plasma glucose should be measured during symptoms. If hypoglycemia is present (glucose < 40 mg/dL [2.78 mmol/L]), an insulin level should be measured on a simultaneous sample. Hyperinsulinemia of > 6 μU/mL (42 pmol/L) suggests an insulin-mediated cause, as does a serum insulin to plasma glucose ratio > 0. Continue reading >>

Diagnosis And Management Of Insulinoma

Diagnosis And Management Of Insulinoma

Go to: CLINICAL SIGNS Insulinomas are the most common cause of hypoglycemia related to endogenous hyperinsulinism. The episodic nature of the hypoglycemic attack is due to the intermittent secretion of insulin by the tumor[8]. Common autonomic symptoms of an insulinoma include diaphroresis, tremor, and palpitations, whereas neuroglycopenenic symptoms include confusion, behavioral changes, personality changes, visual disturbances, seizures and coma[34,35]. Diagnosis of insulinomas can be challenging. Although it was originally considered that symptoms only became evident in the fasting state or following exercise, it is now known that patients with an insulinoma can also present with postprandial symptoms[36,37]. The classical diagnosis of insulinoma depends on satisfying the criteria of Whipple’s triad, which remains the cornerstone of the screening process: (1) hypoglycemia (plasma glucose < 50 mg/dL); (2) neuroglycopenic symptoms; and (3) prompt relief of symptoms following the administration of glucose (Table 1)[38]. In adults with symptoms of neuroglycopenia or documented low blood glucose levels, the gold standard for biochemical diagnosis remains measurement of plasma glucose, insulin, C-peptide, and proinsulin during a 72-h fast (Table 1). This prolonged fasting test can detect up to 99% of insulinomas[39]. Endogenous hypoglycemia due to insulinomas was previously based on findings of abnormal serum levels of insulin, C-peptide, and, more recently, proinsulin at the time of fasting hypoglycemia. To date, there is some general agreement regarding the diagnostic thresholds that must be reached for insulin, C-peptide, and proinsulin levels to be considered abnormal. Several years ago, ratios calculated from insulin and blood glucose levels were used, with the insu Continue reading >>

Insulinoma Diagnosis

Insulinoma Diagnosis

How do you diagnose an insulinoma? Insulinomas can be diagnosed through a simple fasting blood test. Your NET specialist will look for a certain combination of: Low blood sugar (less than 2.2 mmol/l) High insulin (6 microunits/ml or higher) High levels of C peptide (0.2nmol/l or higher), an inactive amino acid that in a healthy body will be produced in equal amounts to insulin. The doctor may also use a ‘rule of thumb’ guide called the Whipple’s Triad. Under this guide an insulinoma will be considered if you experience: Symptoms and signs of hypoglycaemia Blood sugar levels below 2.2 mmol/l Recovery from an attack after eating something sugary If you are on medication for diabetes you can still be tested for insulinomas If someone takes insulin, doctors will be looking at the levels of C peptides in the blood. Commercially used insulin does not contain C peptides, so a test will look for certain levels that might suggest a tumour is present. If someone takes sulphonylurea tablets (that lower blood glucose levels) the doctor will be looking at the level of sulphonylurea in the blood in relation to insulin, blood sugar and C peptide levels. If it is normal an insulinoma will be suspected. The long fast If further confirmation is needed you may be invited into hospital for a special fasting test that can take between 48 and 72 hours. You will not be allowed to eat or drink, apart from water, throughout this period. You will have blood tests at intervals of between three to six hours, and also whenever you show symptoms of low blood sugar, to look at the key levels of blood glucose, insulin, C peptides and sulphonylurea. This hospital fasting test will diagnose insulinomas in more than 90% of cases. The Blood Tests for an insulinoma Insulinomas can be diagnosed throug Continue reading >>

Insulinoma

Insulinoma

What is an insulinoma? The pancreas makes insulin, which helps keep your blood sugar level balanced. Tumors on your pancreas, called insulinomas, make extra insulin, more than your body can use. This causes blood sugar levels to drop too low. These tumors are rare and usually do not spread to other parts of your body. What causes an insulinoma? The cause of insulinomas is unknown. What are the risk factors for an insulinoma? There are few risk factors for insulinomas. But, women seem to be affected more often than men. Most often, it starts between ages 40 and 60. Some genetic diseases can raise your chance of getting an insulinoma. They are: Multiple endocrine neoplasia type 1, abnormal tissue growth in the endocrine system Von Hippel-Lindau syndrome, an inherited disease that causes tumors and cysts throughout your body Other genetic syndromes, such as neurofibromatosis type 1 and tuberous sclerosis What are the symptoms of an insulinoma? Insulinomas can cause these symptoms: Confusion Sweating Weakness Rapid heartbeat If your blood sugar gets too low, you can pass out and even go into a coma. How are insulinomas diagnosed? Insulinomas can be difficult to diagnose. The average time between the start of symptoms and a diagnosis is about 3 years. If your healthcare provider suspects an insulinoma, you may stay in the hospital for a few days. This is so your doctor can watch your blood sugar and other substances in your blood while you fast. You will not be able to eat or drink anything except water during this time. If you have an insulinoma, you will probably have very low blood sugar levels within 48 hours of starting this test. If your symptoms of low blood sugar have been after meals, you may also have a test of your blood sugar and insulin for several hours after a Continue reading >>

Canine Insulinoma

Canine Insulinoma

This article will address the canine insulinoma, a cancerous growth that produces an over- abundance of the blood glucose regulating hormone, insulin. Let's review some terms related to this discussion on canine insulinoma: Cancer - A general term frequently used to indicate any of various types of malignant neoplasms (see below), most of which invade surrounding tissues, may metastasize (see below) to several sites, and are likely to recur after attempted removal and to cause death of the patient unless adequately treated. Neoplasm - An abnormal tissue that grows by cellular proliferation more rapidly than normal and continues to grow after the stimuli that initiated the new growth ceases. Closely related to a tumor. Tumor - An abnormal growth of tissue resulting from uncontrolled progressive multiplication of cells and serving no physiological function. Closely related to a neoplasm. Malignant - Resistant to treatment; occurring in severe form, invades surrounding tissues and is frequently fatal. Benign - Denoting the mild character of an illness or the non-malignant character of a neoplasm. Metastatic - The shifting of a disease, from one part of the body to another. In cancer, the appearance of tumors in parts of the body remote from the origin of the primary tumor. Chemotherapy - Treatment of disease by means of chemical substances or medications. Exocrine gland - A gland that secretes a substance that ends up outside the body either directly or through a duct. Endocrine gland - A gland that secretes a substance internally as into the bloodstream. What is a canine insulinoma, where is one found and what affect does an insulinoma have on the dog? The canine insulinoma is a cancerous growth located on or within the pancreas of the dog. The pancreas is a secretory org Continue reading >>

Gastrointestinal Neuroendocrine Tumors

Gastrointestinal Neuroendocrine Tumors

Insulinoma Insulinomas are the most common type of NET. They occur more commonly in females in the fifth or sixth decade. These tumors secrete insulin or less commonly proinsulin which lead to the clinical syndrome of hypoglycemic symptoms, low blood glucose, and relief with administration of glucose, referred to as Whipple’s triad. These symptoms are often exacerbated with fasting and relieved by food consumption. Patients will have an elevated serum insulin or proinsulin level in the setting of a low or normal glucose level (ratio >0.3). A serum C-peptide level should be obtained (and >1.7 ng/ml in the case of insulinoma) to rule out exogenous insulin administration. Occasionally, patients may be admitted to the hospital for diagnosis. During this time, patients are fasted and serum insulin levels monitored for up to 72 hours. The majority of insulinomas are small (< 2cm), solitary, benign (>90%) and uniformly distributed throughout the pancreas. CT, transabdominal ultrasound, and MRI have a <50% sensitivity. Unlike other NETs, insulinomas are rarely detected with somatostatin (octreotide) radionucleotide scanning. Endoscopic ultrasound has reported sensitivities up to 80%. Arteriography with portal venous sampling has sensitivity in the 80-90% range but is an invasive procedure. The most sensitive imaging technique is intraoperative ultrasound, which localizes over 90% of insulinomas. Therefore, after the biochemical diagnosis of insulinoma is made, we usually obtain a CT scan and, if negative, an endoscopic ultrasound. Even if the lesion does not localize, we would still proceed to the operating room and perform intraoperative palpation and ultrasound for localization. The treatment of choice for insulinoma is complete resection of the tumor. Because the vast majo Continue reading >>

Preoperative Detection Of Pancreatic Insulinomas On Multiphasic Helical Ct

Preoperative Detection Of Pancreatic Insulinomas On Multiphasic Helical Ct

OBJECTIVE. The objective was to analyze enhancement characteristics of insulinomas and to determine the ability of multiphase CT to localize these tumors. MATERIALS AND METHODS. Prospective interpretations of multiphase helical CT scans were reviewed in 30 patients who had insulinomas resected over a 5-year period. CT scans were retrospectively reviewed to determine enhancement characteristics, tumor conspicuity in each phase of enhancement, and potential causes for false-negative findings. RESULTS. Sixty-three percent (19/30) of tumors were identified on CT prospectively. An additional six tumors were visualized in retrospect, allowing characterization of 25 (83%) of 30 tumors. Most tumors were hyperdense on at least one phase (n = 19), three tumors were hypoattenuating, and three were isodense and pedunculated. Insulinomas were most conspicuous on the early phase in 15 patients and in the portal venous phase in three. All tumors that underwent pancreatic phase imaging were seen (13/13), whereas three of 18 arterial and six of 25 portal venous phase findings were inconclusive for tumor. In the six examinations with false-negative findings in which the tumor could be seen in retrospect, two tumors were isodense and pedunculated, three were in close proximity to vessels, and one had a cystic appearance. CONCLUSION. Multiphasic CT has a moderate sensitivity in the detection of insulinomas. Most tumors are more conspicuous on the earlier phases of enhancement. The pancreatic phase may be more useful than the arterial phase. Potential sources of false-negative results include tumors adjacent to vessels, pedunculated morphology, or nonhyperattenuating lesions. Continue reading >>

Diagnosis Difficulties In Insulinomas

Diagnosis Difficulties In Insulinomas

AE Ranetti, A Mazilu, C Spiroiu & A Mihai We have studied 5 cases of insulinomas presented in our clinic in 2004–2005 with typical signs and symptoms of hypoglycemia correlated with high insulinemia. The medium insulin value in the morning was 57.9 mUI/ml, but we found values ranging from 10–98 mUI/ml for medium and severe hypoglycemia. There was no correlation between severity of hypoglycemia and insulin level, proven by repeated insulin dosages. The purpose of our analysis was to identify the best-suitable diagnosis imaging methods for location of insulinomas, by comparing abdominal ultrasonography, CT, MRI and echographic endoscopy. None of the cases had shown positive results on abdominal (pancreatic) ultrasound. Four of the cases had negative abdominal CT scan, in one of this cases the tumor was identified on MRI abdominal scan, with 1.2 cm diameter, but all of them were visualized using echoendoscopy. The fifth case who underwent a previous unsuccessful pancreatic resection for insulinoma had negative abdominal MRI, CT scan, echoendoscopy, with high level insulinemia and metastatic lesions in the liver found on echoendoscopy. Selective celiac artery catheterization shown tumor in second part of duodenum. All tumors were successfully operated. Conclusions: Repeated insulin dosage is necessary to confirm insulinoma as well as multiple imaging methods. Echoendoscopy is still the gold standard for insulinoma detection, CT and MRI are useful in planning the surgery by indicating the exact location regarding the adjacent structures. Background: Due to its cross-talk with estrogen receptor (ER) signalling, increased IGF-I signalling through the IGF-I receptor (IGF-IR) has been postulated as an important factor in the development of tamoxifen resistance in breast canc Continue reading >>

Pancreatic Neuroendocrine Tumors: Insulinoma

Pancreatic Neuroendocrine Tumors: Insulinoma

What is an insulinoma? An insulinoma is a tumor, usually benign (non-cancerous), made up of specialized beta islet cells (see below) that constantly secrete insulin, causing hypoglycemia (low blood glucose–sugar). Normally, as the glucose rises with eating, the pancreas responds by secreting more insulin, which in turn helps utilize or store the glucose and its blood level drops back down into a safe range. Subsequently, as the glucose level continues to fall toward the lower limit of normal (normal, 60-100mg/dL), the secretion of insulin (by the normal beta cells in the pancreas) stops, and this allows the glucose to remain in the normal range. This type of feedback regulation is the hallmark of endocrine organs (thyroid, parathyroid, endocrine part of the pancreas, pituitary, gonad, and adrenal glands that secrete specific hormones). When an insulinoma is present, insulin regulation is abnormal such that the tumor continues to secrete insulin even though the glucose level may fall to a dangerously low level. Even though insulinoma is the most common pancreatic islet cell tumor, it is very rare, occurring in only 3-4 per million people. Except in very rare familial (occurring in families, transmitted genetically from parent to child) situations, the exact cause is unknown. Figure 1: The average age to develop an insulinoma is the mid-40s (range, 10-82 years), and occurs slightly more frequently in females than males. Most are sporadic (occurring "out of the blue" with no known cause) with about 10% occurring as part of the Multiple Endocrine Neoplasia type 1 (MEN 1) syndrome. At least 90% have single, benign, small (less than 2 cm – 3/4 of an inch) tumors (Figure 1). Hypoglycemic symptoms are experienced by virtually all patients with insulinoma and can be grouped Continue reading >>

Insulinoma

Insulinoma

What is an insulinoma? Insulinoma is a tumor of the pancreas that produces excessive amounts of insulin. Insulinomas are more common in women. The tumors are usually small (less than 2cm) and more than 90% of all insulinomas are benign (non-cancerous). Insulinomas produce excessive amounts of insulin and this causes low blood sugar. The typical symptoms that patients complain about are related to the development of low bloods sugar and include tiredness, weakness, tremulous and hunger. Many patients have to eat frequently to prevent symptoms from the low blood sugar. Some patients may develop psychiatric symptoms because of the low blood sugar. How is the diagnosis is made? The diagnosis is made by simultaneous measurements of blood sugar and insulin levels in the blood. A low blood sugar with a high insulin level confirms the diagnosis. Once the diagnosis made based on the biochemical analysis then the physician will perform further studies to detect the tumor in the pancreas. Since most of these tumors are small, detection of the tumor in the pancreas may be difficult. Some of the studies that are performed to detect the tumor include a detailed CT scan, MRI, octreotide scan, and an endoscopic ultrasound. An experienced surgeon often detects these tumors even where they are not seen on radiological testing prior to surgery. Imaging the pancreas during the surgery directly with an ultrasound detects the majority of these tumors. How is insulinoma treated Insulinoma is a benign tumor of the pancreas in 90% of patients and removal of the tumor cures the patient of the symptoms. Surgical removal of the tumor is the treatment of choice. More than 90% of patients will not require any further treatment after removal of the tumor. The operations that are usually performed for Continue reading >>

Human Insulinomas Show Distinct Patterns Of Insulin Secretion In Vitro

Human Insulinomas Show Distinct Patterns Of Insulin Secretion In Vitro

Insulinomas are β-cell tumors that cause hypoglycemia through inappropriate secretion of insulin. Characterization of the in vitro dynamics of insulin secretion by perifused fragments of 10 human insulinomas permitted their subdivision into three functional groups with similar insulin content. Group A (four patients with fasting and/or postprandial hypoglycemic episodes) showed qualitatively normal responses to glucose, leucine, diazoxide, tolbutamide, and extracellular CaCl2 omission or excess. The effect of glucose was concentration dependent, but, compared with normal islets, insulin secretion was excessive in both low- and high-glucose conditions. Group B (three patients with fasting hypoglycemic episodes) was mainly characterized by large insulin responses to 1 mmol/L glucose, resulting in very high basal secretion rates that were inhibited by diazoxide and restored by tolbutamide but were not further augmented by other agents except for high levels of CaCl2. Group C (three patients with fasting hypoglycemic episodes) displayed very low rates of insulin secretion and virtually no response to stimuli (including high CaCl2 concentration) and inhibitors (CaCl2 omission being paradoxically stimulatory). In group B, the presence of low-Km hexokinase-I in insulinoma β-cells (not in adjacent islets) was revealed by immunohistochemistry. Human insulinomas thus show distinct, though not completely heterogeneous, defects in insulin secretion that are attributed to the undue expression of hexokinase-I in 3 of 10 patients. Insulinomas are uncommon, usually benign, tumors of pancreatic β-cells, which cause hyperinsulinemic hypoglycemia (1–4). Early morphological studies (5,6) have led to distinct classifications of insulinomas on the basis of their histological and structu Continue reading >>

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