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Insulinoma

Beta Cell Tumor

Insulinomas are the most common endocrine tumors of the pancreas.


Presentation

The main clinical manifestation of an insulinoma is fasting hypoglycemia. Symptoms are insidious and can mimick various central nervous system disorders, like epilepsy and psychiatric disorders [6]. The presentation is characterized by the Whipple triad in many patients which includes:

  • Presence of symptoms and signs of hypoglycemia.
  • Concomitant low blood sugar. 
  • Reversibility of symptoms by glucose administration.

Adrenergic symptoms resulting from the catecholaminergic response include weakness, anxiety, nausea, hunger, sweating, tremor, tachycardia, and palpitations. Neuroglycopenic symtoms oberserved in patients are headache, confusion, lethargy, diplopia, blurred vision, amnesia, seizures and in more severe cases unconsciousness. The symptoms can be aggravated by alcohol intake, exercise, and certain medications.

Weakness
  • Adrenergic symptoms resulting from the catecholaminergic response include weakness, anxiety, nausea, hunger, sweating, tremor, tachycardia, and palpitations.[symptoma.com]
  • 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.[hopkinsmedicine.org]
  • Symptoms of sympathetic stimulation (faintness, weakness, tremulousness, palpitation, sweating, hunger, and nervousness) are often present.[merckmanuals.com]
Weight Gain
  • The child had a favorable evolution in the clinical follow-up, presenting with weight gain and progressive remission to complete disappearance of most symptoms-except for the mental impairments.[ncbi.nlm.nih.gov]
  • The patients presented with symptoms of sweating, tremors, drowsiness, palpitations, loss of consciousness, abnormal behavior, seizures and weight gain.[ncbi.nlm.nih.gov]
  • References: [2] [3] [4] [5] [6] Clinical features Clinical features of hypoglycemia Relief of symptoms after administering glucose (See also Whipple's triad ) Weight gain Symptoms characteristic of other endocrine neoplasias may occur.[amboss.com]
  • Sudden weight gain is sometimes seen. The diagnosis of insulinoma is suspected in a patient with symptomatic fasting hypoglycemia.[en.wikipedia.org]
  • Symptoms may include: Anxiety , behavior changes, or confusion Clouded vision Loss of consciousness or coma Convulsions or tremor Dizziness or headache Hunger or weight gain Fast heart rate or palpitations Sweating Exams and Tests After fasting, your[owensborohealthse3.adam.com]
Pallor
  • This can cause symptoms such as: sweating pallor racing of the heartbeat feelings of anxiety irritability or confusion unusual behaviour blackouts or seizures.[yourhormones.info]
  • The patient reported occasional episodes of weakness, sweating, pallor, tremor, confusion, paresthesias, and visual blurring in the previous year. He denied taking any drugs. Cardiovascular, respiratory, and neurological examinations were normal.[journals.lww.com]
Fatigue
  • We ask about general symptoms (anxious mood, depressed mood, fatigue, pain, and stress) regardless of condition. Last updated: May 12, 2019[patientslikeme.com]
Malnutrition
  • We report a case of insulinoma in an 11-year-old boy with malnutrition and mild psychic retardation.[ncbi.nlm.nih.gov]
Nausea
  • Symptoms resulting from the catecholaminergic response to hypoglycemia (i.e. tremulousness, palpitations, tachycardia, sweating, hunger, anxiety, nausea) are not as common. Sudden weight gain is sometimes seen.[en.wikipedia.org]
  • Adrenergic symptoms resulting from the catecholaminergic response include weakness, anxiety, nausea, hunger, sweating, tremor, tachycardia, and palpitations.[symptoma.com]
  • Ketotic hypoglycaemia presents with symptoms of hypoglycaemia (eg sweating, irritable, confused) and also nausea and vomiting. Severe hypoglycaemia may cause fainting, seizures and loss of consciousness.[patient.info]
  • The first group includes headaches, double and/or blurred vision, confusion, dizziness, abnormal behaviour, lethargy, amnesia and, on rare occasions, convulsions and coma (2, 4-6); the autonomic symptoms include sweating, weakness, hunger, tremors, nausea[scielo.org.co]
Vomiting
  • Ketotic hypoglycaemia presents with symptoms of hypoglycaemia (eg sweating, irritable, confused) and also nausea and vomiting. Severe hypoglycaemia may cause fainting, seizures and loss of consciousness.[patient.info]
  • Additional symptoms include abdominal pain, nausea, and vomiting. Most somatostatinomas are large and have spread (metastasized) upon diagnosis.[rarediseases.org]
Abdominal Pain
  • When this occurs, you can get the following symptoms: abdominal pain back pain diarrhea jaundice, or yellowing of the skin and eyes Doctors don’t know exactly why people get insulinomas. The tumors typically show up without warning.[healthline.com]
  • The most common symptom associated with nonfunctioning pNENs is abdominal pain and, in some cases, an abdominal mass may be present.[rarediseases.org]
  • Symptoms related to the tumor and its factors may be intermittent and vague, but the most common presentation is periodic abdominal pain sometimes accompanied by malignant carcinoid syndrome, characterized by flushing of the face, severe diarrhea, and[pancreatica.org]
Palpitations
  • We present a case of a 9-year-old girl presenting with repeated loss of consciousness, concomitant with a pale face, palpitations, and convulsions, which had persisted for 2 years and had been aggravated during the previous 2 months.[ncbi.nlm.nih.gov]
  • During the clinical course of pancreatic neuroendocrine tumor, she had experienced palpitations, cold sweats and faintness between meals that indicated her tumors had attained the characteristics of an insulinoma, and her quality of life was impacted[ncbi.nlm.nih.gov]
  • The patients presented with symptoms of sweating, tremors, drowsiness, palpitations, loss of consciousness, abnormal behavior, seizures and weight gain.[ncbi.nlm.nih.gov]
  • It manifests with various autonomic and neuroglycopenic symptoms such as tremor, palpitations, weakness, diaphoresis, hyperphagia, visual disturbances, confusion, behavioral and personality changes, seizures and coma.[orpha.net]
Tachycardia
  • Symptoms resulting from the catecholaminergic response to hypoglycemia (i.e. tremulousness, palpitations, tachycardia, sweating, hunger, anxiety, nausea) are not as common. Sudden weight gain is sometimes seen.[en.wikipedia.org]
  • Adrenergic symptoms resulting from the catecholaminergic response include weakness, anxiety, nausea, hunger, sweating, tremor, tachycardia, and palpitations.[symptoma.com]
  • ., tachycardia, anxiety, palpitations, weakness, diaphoresis), which are exaggerated by fasting in 73% of cases.[cancertherapyadvisor.com]
  • Neuroglycopenia Adrenergic Diplopia (double vision) Weakness, warmth Blurred vision Sweating Confusion, Abnormal behavior Hunger Amnesia to Symptoms, Events Tremor Seizures Palpations (heart pounding) Loss of consciousness Tachycardia (heart racing) Coma[endocrinediseases.org]
Hypertension
  • The possible etiology of hypertension induced by an insulinoma is catecholamine release in response to hypoglycemia, which may cause acute hypertension through activation of the sympatho-adrenal system.[ncbi.nlm.nih.gov]
  • Multivariate analysis indicated that higher initial BMI was associated with increased weight loss (p   .001). 63.8% of patients with hypertension recovered and improved sleep quality was evident in all patients with obstructive sleep apnea syndrome within[ncbi.nlm.nih.gov]
  • She had a history of hypertension, but not diabetes (HbA1c range, 4.8%-5.6%), liver or kidney disease. Her family history was significant for diabetes in her mother. She had a prior smoking history, but no alcohol or substance use.[healio.com]
  • Affected individuals may have a round, moon-shaped face, thin, fragile skin that bruises easily, high blood pressure (hypertension), generalized muscle weakness, behavioral changes, facial flushing, and weakened bones that fracture easily (osteoporosis[rarediseases.org]
Hypotension
  • […] include PPHrPomas, which secrete parathyroid hormone-related protein and may cause hyperparathyroidism; calcitoninomas, which secrete calcitonin and can cause watery diarrhea and facial flushing; and neurotensinomas, which can cause low blood pressure (hypotension[rarediseases.org]
Blurred Vision
  • Neuroglycopenic symtoms oberserved in patients are headache, confusion, lethargy, diplopia, blurred vision, amnesia, seizures and in more severe cases unconsciousness.[symptoma.com]
  • This includes tiredness, weakness, tremors, recurrent headache, diplopia (when a single object is perceived as two images), and blurred vision.[knowcancer.com]
  • Hypoglycemia is a dangerous condition that can cause blurred vision, lightheadedness, and unconsciousness. It can also be life-threatening. An insulinoma usually needs to be surgically removed.[healthline.com]
  • Symptoms of insulinoma The symptoms of insulinoma are largely similar to the symptoms of hypoglycemia , which include: Blurred vision Anxiety Sweating Trouble concentration and Weakness These are all typically mild symptoms caused by changes in insulin[diabetes.co.uk]
  • Symptoms of insulinoma The symptoms of insulinoma are largely similar to the symptoms of hypoglycemia, which include: Blurred vision Anxiety Sweating Trouble concentration and Weakness These are all typically mild symptoms caused by changes in insulin[diabetes.co.uk]
Diplopia
  • This includes tiredness, weakness, tremors, recurrent headache, diplopia (when a single object is perceived as two images), and blurred vision.[knowcancer.com]
  • These include recurrent headache, lethargy, diplopia, and blurred vision, particularly with exercise or fasting. Severe hypoglycemia may result in seizures, coma, and permanent neurological damage.[en.wikipedia.org]
  • Neuroglycopenic symtoms oberserved in patients are headache, confusion, lethargy, diplopia, blurred vision, amnesia, seizures and in more severe cases unconsciousness.[symptoma.com]
  • Neuroglycopenia Adrenergic Diplopia (double vision) Weakness, warmth Blurred vision Sweating Confusion, Abnormal behavior Hunger Amnesia to Symptoms, Events Tremor Seizures Palpations (heart pounding) Loss of consciousness Tachycardia (heart racing) Coma[endocrinediseases.org]
  • It may also present with transient hemiplegia, hypothermia or hyperthermia, convulsions, diplopia and strabismus [ 9 ] . If untreated, it can progress to stupor, coma and, exceptionally, death.[patient.info]
Hunger
  • CASE REPORT: We report the case of sporadic insulinoma in an exceptionally very young 10-year-old boy who presented with a 1-month history of episodic tremulousness, diaphoresis, increased hunger, confusion and fainting.[ncbi.nlm.nih.gov]
  • Symptoms: sweating tremor rapid heart rate anxiety hunger dizziness headache clouding vision confusion behavioral changes convulsions loss of consciousness Signs and tests: The person's blood may be tested while fasting (not eating).[uclahealth.org]
  • Adrenergic symptoms resulting from the catecholaminergic response include weakness, anxiety, nausea, hunger, sweating, tremor, tachycardia, and palpitations.[symptoma.com]
  • 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 very rare tumors. They usually occur as single, small tumors.[owensborohealthse3.adam.com]
  • 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.[ufhealth.org]
Abnormal Behavior
  • We report a case of insulinoma in a 55 years old female who presented with episodes of abnormal behavior and altered sensorium.[ncbi.nlm.nih.gov]
  • When a patient manifests abnormal behavior during the night and early morning, glucose monitoring should be performed, especially during the night and early morning.[ncbi.nlm.nih.gov]
  • The patients presented with symptoms of sweating, tremors, drowsiness, palpitations, loss of consciousness, abnormal behavior, seizures and weight gain.[ncbi.nlm.nih.gov]
  • Neuroglycopenia Adrenergic Diplopia (double vision) Weakness, warmth Blurred vision Sweating Confusion, Abnormal behavior Hunger Amnesia to Symptoms, Events Tremor Seizures Palpations (heart pounding) Loss of consciousness Tachycardia (heart racing) Coma[endocrinediseases.org]
  • behavior Unconsciousness Amnesia Adrenergic symptoms (from hypoglycemia-related adrenalin release): Weakness, sweating, tachycardia, palpitations, and hunger Seizures See Clinical Presentation for more detail.[emedicine.com]
Seizure
  • The following case report highlights the need for careful reassessment of all seizures that are atypical and refractory to medication.[ncbi.nlm.nih.gov]
  • This case highlights the importance of considering hypoglycemia in the evaluation of night terrors and new-onset seizures.[ncbi.nlm.nih.gov]
  • Following a clinical diagnosis of insulinoma, distal pancreatectomy was performed; her seizures didn't occur again.[ncbi.nlm.nih.gov]
  • We present the case of a 70 year old man who was admitted with history of generalized tonic clonic seizures on and off since 6 years in spite of being on regular therapy with anticonvulsants.[ncbi.nlm.nih.gov]
  • A 58-year-old Chinese man presented with intermittent seizure episodes after being misdiagnosed with epilepsy for eight years. MRI revealed an abnormally strong signal in the distal pancreas.[ncbi.nlm.nih.gov]
Confusion
  • The clinical features of an insulinoma are fasting hypoglycemia with neuroglycopenic symptoms including confusion and unusual behavior, while hypertension is usually not associated with the disease.[ncbi.nlm.nih.gov]
  • Pediatricians should be aware of confusing and nonspecific symptoms, especially when children with insulinoma present mental or neurological retardation.[ncbi.nlm.nih.gov]
  • CASE REPORT: We report the case of sporadic insulinoma in an exceptionally very young 10-year-old boy who presented with a 1-month history of episodic tremulousness, diaphoresis, increased hunger, confusion and fainting.[ncbi.nlm.nih.gov]
  • MATERIALS AND METHODS: Forty patients with hypoglycemia and increased/confusing results of serum insulin and C-peptide concentration and negative/inconclusive results of other imaging examinations were enrolled in the study.[ncbi.nlm.nih.gov]
  • Neuroglycopenic symtoms oberserved in patients are headache, confusion, lethargy, diplopia, blurred vision, amnesia, seizures and in more severe cases unconsciousness.[symptoma.com]
Tremor
  • The patients presented with symptoms of sweating, tremors, drowsiness, palpitations, loss of consciousness, abnormal behavior, seizures and weight gain.[ncbi.nlm.nih.gov]
  • Adrenergic symptoms resulting from the catecholaminergic response include weakness, anxiety, nausea, hunger, sweating, tremor, tachycardia, and palpitations.[symptoma.com]
  • This includes tiredness, weakness, tremors, recurrent headache, diplopia (when a single object is perceived as two images), and blurred vision.[knowcancer.com]
  • It manifests with various autonomic and neuroglycopenic symptoms such as tremor, palpitations, weakness, diaphoresis, hyperphagia, visual disturbances, confusion, behavioral and personality changes, seizures and coma.[orpha.net]
Dizziness
  • He presented to our outpatient department with a two-week history of dizziness and morning cold sweats. A random serum glucose test revealed hypoglycaemia.[ncbi.nlm.nih.gov]
  • A 47-year-old woman with medical history of migraine, depression, hypercholesterolemia, iron deficiency anemia, and peptic ulcer disease presented with complaints of frequent episodes of dizziness, blurring of vision, and anxiety over the past 4 months[ncbi.nlm.nih.gov]
  • Approximately 3 hours later, the patient felt dizzy and lost consciousness when her plasma glucose level fell to 14 mg/dL. She also was found to have new hypokalemia of 2.6 mmol/L.[healio.com]
  • Symptoms: sweating tremor rapid heart rate anxiety hunger dizziness headache clouding vision confusion behavioral changes convulsions loss of consciousness Signs and tests: The person's blood may be tested while fasting (not eating).[uclahealth.org]
  • Symptoms may include: Anxiety , behavior changes, or confusion Clouded vision Loss of consciousness or coma Convulsions or tremor Dizziness or headache Hunger or weight gain Fast heart rate or palpitations Sweating Exams and Tests After fasting, your[owensborohealthse3.adam.com]
Headache
  • Neuroglycopenic symtoms oberserved in patients are headache, confusion, lethargy, diplopia, blurred vision, amnesia, seizures and in more severe cases unconsciousness.[symptoma.com]
  • Tabs Content Clinical Overview Diagnosis Indications for Testing Pancreatic tumor Blood glucose 40 mg/dL without other etiology Hypoglycemia symptoms without other etiology Confusion/altered consciousness Sweating/diaphoresis Headache Visual disturbance[arupconsult.com]
  • This includes tiredness, weakness, tremors, recurrent headache, diplopia (when a single object is perceived as two images), and blurred vision.[knowcancer.com]
  • Symptoms: sweating tremor rapid heart rate anxiety hunger dizziness headache clouding vision confusion behavioral changes convulsions loss of consciousness Signs and tests: The person's blood may be tested while fasting (not eating).[uclahealth.org]
  • These include recurrent headache, lethargy, diplopia, and blurred vision, particularly with exercise or fasting. Severe hypoglycemia may result in seizures, coma, and permanent neurological damage.[en.wikipedia.org]

Workup

Physiologically, the blood glucose level is maintained by a negative feedback mechanism. Decrease in blood glucose levels reduces insulin secretion. Inappropriately elevated levels of insulin in the presence of hypoglycemia and serum insulin to plasma glucose ratio > 0.3 (μU/mL)/(mg/dL) are diagnostic of insulinoma. Prolonged (ie, 48 or 72 h) supervised fast in hospitalized patients is the main test in diagnosing the condition. When symptoms of hypoglycemia appear, blood should be sampled and the biochemical diagnosis can be made, if the following parameters are found [7]:

  • Blood glucose less than 40 mg/dL 
  • C-peptide exceeding 2.5 ng/mL
  • Absence of plasma sulfonylurea
  • Increased serum insulin level of 10 µU/mL or more
  • Increased proinsulin level of ≥25% or ≥22 pmol

After the biochemical diagnosis has been established, imaging studies are used to localize the tumor which is necessary to plan the surgical approach. Helical or multislice CT scan has 82-94% sensitivity, magnetic resonance imaging (MRI) 40-70%. Transabdominal ultrasonography, 111-In-pentetreotide imaging, and fluorine-18-L-dihydroxyphenylalanine positron emission tomography (18F-DOPA PET) are other noninvasive tests. Invasive modalities help to localize the tumor when non-invasive techniques are not sufficient. Endoscopic ultrasonography has up to 90% sensitivity [8], the accuracy of selective arteriography is 82%.

Fasting Hypoglycemia
  • We report a rare case of an insulinoma diagnosed in an individual presenting exclusively with postprandial hypoglycemia without fasting hypoglycemia.[ncbi.nlm.nih.gov]
  • Most patients (n 18, 62.1%) had fasting hypoglycemia, about a third (31%) both postprandial and fasting hypoglycemia, and 6.9% postprandial hypoglycemia only.[ncbi.nlm.nih.gov]
  • The clinical features of an insulinoma are fasting hypoglycemia with neuroglycopenic symptoms including confusion and unusual behavior, while hypertension is usually not associated with the disease.[ncbi.nlm.nih.gov]
  • Flash glucose monitoring (FGM) systems revealed glucose profiles with fasting hypoglycemia, which facilitated the clinical diagnosis of insulinoma even though she was unaware of her hypoglycemia.[ncbi.nlm.nih.gov]
  • These results demonstrate that fasting hypoglycemia in the insulinoma patients is usually due to suppression of glucose production rather than to acceleration of glucose utilization, as is widely thought.[diabetes.diabetesjournals.org]
Glucose Decreased
  • Since glucose utilization exceeded glucose production to a greater extent in insulinoma patients than in normal subjects, plasma glucose decreased to 44 3 mg/dl in insulinoma patients, but only to 84 1 mg/dl in normal subjects ( P 0.001).[diabetes.diabetesjournals.org]

Treatment

Medical therapy is indicated in patients with malignant insulinomas and in those who are not surgical candidates. Diazoxide, octreotide and lanreotide (somatostatin analogues), verapamil [9] and phenytoin [10] and everolimus are used to treat insulinoma. Experiences with radiotherapy and chemotherapy are limited. Surgical excision of the insulinoma is the definitive treatment and currently the therapy of choice. Enucleation is the treatment option for all benign insulinomas, when technically feasible. For tumors that are anatomically unsuitable for enucleation or multiple tumors, a larger segmental resection of the pancreas, distal pancreatectomy or pancreaticoduodenectomy is performed.

Prognosis

The long-term survival rate of patients with benign insulinoma is normal. In patients with malignant insulinomas, survival is significantly worse. After surgical removal, the long-term risk of recurrence is high in patients with MEN-1 syndrome [4].

Etiology

Insulinomas can occur sporadically or in association with multiple endocrine neoplasia (MEN)-1 syndrome. MEN-1 syndrome is an autosomal dominant disorder characterized by development of tumors in pituitary, parathyroid gland, pancreas, and the skin. It is associated with mutations in the MEN1 gene mapped to chromosome 11q13 [2] [3] and loss of heterozygosity. Sporadic insulinomas are typically less than 2 cm in diameter and solitary. Insulinomas associated with MEN-1 syndrome develop earlier, are frequently multiple and tend to recur.

Epidemiology

The incidence is 3 to 10 cases per 1,000,000, but was reported to be higher in autopsy studies. The median age at diagnosis is approximately 47 years, with a mild female preponderance [4]. 5 to 10% are malignant and 16% of cases are associated with MEN-1 syndrome [5]. The median age at diagnosis of insulinomas in conjunction with MEN-1 syndrome is the mid 20s and malignant insulinomas are seen more frequently in this patient group. Insulinomas have been reported in all ethnic groups.

Sex distribution
Age distribution

Pathophysiology

An insulinoma is a rare pancreatic endocrine tumor, deriving mainly from islet cells, that hypersecretes insulin. Rarely other hormones such as adrenocorticotropic hormone (ACTH), glucagon, gastrin, human chorionic gonadotropin, and somatostatin are produced by the tumor. Malignant tumors are usually larger in size and liver and regional lymph nodes are the most common sites of metastatic spread.

Prevention

There are no guidelines for the prevention of insulinoma.

Summary

An insulinoma is a rare pancreatic endocrine tumor, deriving mainly from islet cells, that produces excessive amounts of insulin. 90-95% of insulinomas are benign. The incidence is 3 to 10 cases per 1,000,000 [1] and the majority of patients are between 30 and 60 years of age. The presentation is characterized by the Whipple triad in many patients which includes:

  • Presence of symptoms and signs of hypoglycemia.
  • Concomitant low blood sugar. 
  • Reversibility of symptoms by glucose administration.

Surgical removal of the tumor is currently the treatment of choice and is curative in most cases. Medical therapy is indicated in patients with malignant insulinomas and in those who are not surgical candidates.

Patient Information

An insulinoma is a rare tumor in the pancreas that secretes insulin. In the majority of cases, the tumor is not cancerous (benign). Insulinomas are rare and tend to affect women more than men. They most frequently are diagnosed in people who are between ages 30 and 60.

The pancreas is an organ located behind the stomach which produces several important hormones, including insulin, glucagon, and somatostatin that control the level of sugar in the blood. When an insulinoma developed in the pancreas, it continues to secrete insulin, even when the blood sugar is too low, a condition called hypoglycemia. Symptoms include double vision, blurred vision, headache, lethargy, confusion, weakness, sweating, hunger, tremors, tremulousness, anxiety, rapid heart rate and in severe cases, seizures and coma.

To make the diagnosis, the doctor will perform a blood test to check blood sugar, insulin levels and several other values. To determine the location and size of the insulinoma, imaging studies will be made. The most common treatment for an insulinoma is surgical removal of the tumor and there are various types of surgery available to remove the insulinoma. If surgery is not possible, medical treatment is necessary.

References

Article

  1. Dadan J, Wojskowicz P, Wojskowicz A. Neuroendocrine tumors of the pancreas. Wiad Lek. 2008. 61(1-3):43-7.
  2. Wermer P. Endocrine adenomatosis and peptic ulcer in a large kindred: inherited multiple tumors and mosaic pleiotropism in man. Am J Med. 1963;35:205–212.
  3. Larsson C, Skogseid B, Oberg K, Nakamura Y, Nordenskjöld M. Multiple endocrine neoplasia type 1 gene maps to chromosome 11 and is lost in insulinoma. Nature. 1988;332:85–87.
  4. Service FJ, McMahon MM, O’Brien PC, Ballard DJ. Functioning insulinoma: incidence, recurrence, and long-term survival of patients: a 60-year study. Mayo Clin Proc 1991 66:711–719
  5. Mukai K, Grotting JC, Greider MH, Rosai J. Retrospective study of 77 pancreatic endocrine tumors using the immunoperoxidase method. Am J Surg Pathol 1982;6:387-399
  6. Vig S, Lewis M, Foster KJ, Stacey-Clear A. Lessons to be learned: a case study approach insulinoma presenting as a change in personality. J R Soc Promot Health 2001;121:56-61
  7. Mathur A, Gorden P, Libutti SK. Insulinoma. Surg Clin North Am 2009;89:1105-21.
  8. Schumacher B, Lubke HJ, Frieling T, Strohmeyer G, Starke AA 1996 Prospective study on the detection of insulinoma by endoscopic ultrasonography. Endoscopy 28:273–276
  9. Hirshberg B, Cochran C, Skarulis MC, Libutti SK, Alexander HR, Wood BJ, Chang R, Kleiner DE, Gorden P. Malignant insulinoma: spectrum of unusual clinical features. Cancer. 2005;104(2):264.
  10. Hofeldt FD, Dippe SE, Levin SR, Karam JH, Blum MR, Forsham PH. Effects of diphenylhydantoin upon glucose-induced insulin secretion in three patients with insulinoma. Diabetes. 1974;23(3):192.

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Last updated: 2017-08-09 17:48