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]

  Symptoms of sympathetic stimulation (faintness, weakness, tremulousness, palpitation, sweating, hunger, and nervousness) are often present. [merckmanuals.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]

  This includes tiredness, weakness, tremors, recurrent headache, diplopia (when a single object is perceived as two images), and blurred vision. [knowcancer.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]

  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]

  Some patients (18%) experience weight gain. [clinicaladvisor.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]

  Case Presentation In this report, we present a 15-year-old female who visited her primary care provider complaining of intermittent episodes of altered mental status including fatigue, irritability, and poor concentration. [ijpeonline.biomedcentral.com]

  History revealed that she did, indeed, have severe fatigue. She did not complain of syncope, palpitations, or diaphoresis. [clinical.diabetesjournals.org]

  […] level in blood, such as sweating, dizziness/confusion, blurring of vision, and even loss of consciousness Nausea and vomiting Abdominal pain, back pain Loss of appetite, weight loss Diarrhea, indigestion Yellowing of skin (jaundice) Dark-colored urine Fatigue [dovemed.com]

  The most frequent side effects of sunitinib observed were diarrhea, nausea, vomiting, asthenia, and fatigue. 35 Conclusion Insulinoma is a very rare neuroendocrine tumor that has a unique presentation at the time of diagnosis. [dovepress.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]

• Positive Whipple Triad

  We present a 47-year-old woman who had recurrent neuroglycopenic symptoms and positive Whipple triad for 28 months. [ncbi.nlm.nih.gov]

• Nausea

  They produce the typical symptoms of low blood glucose levels: Excessive hunger Shaking Sweating Palpitations Ventricular tachycardia Nausea Dizziness The typical symptoms correspond to the so-called Whipple triad. [flexikon.doccheck.com]

  Adrenergic symptoms resulting from the catecholaminergic response include weakness, anxiety, nausea, hunger, sweating, tremor, tachycardia, and palpitations. [symptoma.com]

  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]

  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]

  Nausea, ptyalism, vomiting or gagging, or pawing at the mouth may also be described. [mspca.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 signs and symptoms may include the following: Symptoms of low glucose level in blood, such as sweating, dizziness/confusion, blurring of vision, and even loss of consciousness Nausea and vomiting Abdominal pain, back pain Loss of appetite, weight [dovemed.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]

  None of the patients had abdominal pain or jaundice. Unintentional weight gain was found in 95 cases (48%). None of the patients in this cohort had previous negative laparotomies for insulinomas. [jamanetwork.com]

• 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]

  Nausea, ptyalism, vomiting or gagging, or pawing at the mouth may also be described. [mspca.org]

  The signs and symptoms may include the following: Symptoms of low glucose level in blood, such as sweating, dizziness/confusion, blurring of vision, and even loss of consciousness Nausea and vomiting Abdominal pain, back pain Loss of appetite, weight [dovemed.com]

  The most frequent side effects of sunitinib observed were diarrhea, nausea, vomiting, asthenia, and fatigue. 35 Conclusion Insulinoma is a very rare neuroendocrine tumor that has a unique presentation at the time of diagnosis. [dovepress.com]

• Increased Appetite

  She denied having seizures and diabetes but he noticed increased appetite over the past year. She had no family history of diabetes, thyroid or pituitary disease. [oatext.com]

• Palpitations

  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]

  They produce the typical symptoms of low blood glucose levels: Excessive hunger Shaking Sweating Palpitations Ventricular tachycardia Nausea Dizziness The typical symptoms correspond to the so-called Whipple triad. [flexikon.doccheck.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]

• Tachycardia

  They produce the typical symptoms of low blood glucose levels: Excessive hunger Shaking Sweating Palpitations Ventricular tachycardia Nausea Dizziness The typical symptoms correspond to the so-called Whipple triad. [flexikon.doccheck.com]

  Adrenergic symptoms resulting from the catecholaminergic response include weakness, anxiety, nausea, hunger, sweating, tremor, tachycardia, and palpitations. [symptoma.com]

  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]

  tachycardia, anxiety, palpitations, weakness, diaphoresis), which are exaggerated by fasting in 73% of cases. [clinicaladvisor.com]

• 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]

  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]

  She was also a known hypertensive on regular medications. Her vital signs were within normal limits. Auscultation of the chest revealed bilateral crepitations. Rest of the systemic examination was normal. [apicareonline.com]

  Diazoxide was primarily introduced in the 1950s for the treatment of hypertension; however, its side effects of hyperglycemia has made the drug applicable for the management of insulinoma. 28 Diazoxide inhibits insulin release from β cells via stimulation [dovepress.com]

• 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]

  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]

  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]

  Neuroglycopenic symtoms oberserved in patients are headache, confusion, lethargy, diplopia, blurred vision, amnesia, seizures and in more severe cases unconsciousness. [symptoma.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]

  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]

  Adrenergic symptoms resulting from the catecholaminergic response include weakness, anxiety, nausea, hunger, sweating, tremor, tachycardia, and palpitations. [symptoma.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]

  They produce the typical symptoms of low blood glucose levels: Excessive hunger Shaking Sweating Palpitations Ventricular tachycardia Nausea Dizziness The typical symptoms correspond to the so-called Whipple triad. [flexikon.doccheck.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]

  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]

  Case presentation: A 35-year-old male had history of night time seizures with hallucinations, delirium and spasms, lasting from 10 minutes to 1.5 hours for about 2 years. These seizures were always resolving spontaneously. [endocrine-abstracts.org]

• 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]

  Neuroglycopenic symtoms oberserved in patients are headache, confusion, lethargy, diplopia, blurred vision, amnesia, seizures and in more severe cases unconsciousness. [symptoma.com]

• Tremor

  Adrenergic symptoms resulting from the catecholaminergic response include weakness, anxiety, nausea, hunger, sweating, tremor, tachycardia, and palpitations. [symptoma.com]

  The patients presented with symptoms of sweating, tremors, drowsiness, palpitations, loss of consciousness, abnormal behavior, seizures and weight gain. [ncbi.nlm.nih.gov]

  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]

  They produce the typical symptoms of low blood glucose levels: Excessive hunger Shaking Sweating Palpitations Ventricular tachycardia Nausea Dizziness The typical symptoms correspond to the so-called Whipple triad. [flexikon.doccheck.com]

  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]

• 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]

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]

  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]

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.

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].

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.

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.

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.

There are no guidelines for the prevention of insulinoma.

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.

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.

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.