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

  The symptoms include faintness, weakness, trembling, awareness of the heartbeat (palpitations), sweating, nervousness, and profound hunger. [msdmanuals.com]

  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]

• 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]

• Unconsciousness

  A 53-year-old woman fell unconscious during postprandial exercises. [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]

  Many say that the ferret will begin to respond in 5 or 10 minutes, and in some instances, this is true; however I have not found this to be the case if the ferret is unconscious. Many times it has taken an hour or more before the ferret responds. [miamiferret.org]

  CASE REPORT A 75 year old woman presented, unconscious, after a collapse at home. An initial diagnosis of a cerebrovascular accident was made. However, the capillary blood glucose concentration was measured at 1.1 mmol/l. [pmj.bmj.com]

  Patient 2 A seventy-five-year-old woman who experienced an episode of unconsciousness due to hypoglycemia with a serum glucose level 34 mg/dl was referred. [pancreas.imedpub.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 • a pale appearance (pallor) • racing of the heartbeat • feelings of anxiety • irritability or confusion • double vision • unusual behaviour • blackouts or seizures These episodes can occur particularly when [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]

• 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]

• 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]

• Abdominal Pain

  The most common symptom associated with nonfunctioning pNENs is abdominal pain and, in some cases, an abdominal mass may be present. [rarediseases.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]

  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]

  pain, malabsorption, and cholelithiasis. 13 Recent studies have also focused on the antiproliferative and growth stabilization of somatostatin analogs on malignant NETs. 30, 32 Two studies, the placebo-controlled, double-blind, prospective randomized [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]

  […] with MEN1), small ( Insulinoma patients characteristically present with symptoms of recurrent hypoglycemia, especially neuroglucopenic symptoms (e.g., confusion, altered consciousness, visual changes) and symptoms due to sympathetic overdrive (e.g., tachycardia [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]

  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]

• Sweating

  Abstract A 45-year-old female who presented with loss of consciousness and a cold sweat was found to have a pancreatic tumor and multiple liver metastases. [ncbi.nlm.nih.gov]

  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]

  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]

• Blurred Vision

  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. [symptoma.com]

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

  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]

• 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

  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]

  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]

  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]

  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]

• 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

  This case highlights the importance of considering hypoglycemia in the evaluation of night terrors and new-onset seizures. [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]

  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]

  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 caused by low blood sugar (hypoglycemia) include faintness, weakness, headache, and confusion. Diagnosis includes blood and imaging tests. Treatment is surgery and sometimes chemotherapy. [msdmanuals.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

  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]

  Symptoms caused by low blood sugar (hypoglycemia) include faintness, weakness, headache, and confusion. Diagnosis includes blood and imaging tests. Treatment is surgery and sometimes chemotherapy. [msdmanuals.com]

  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]

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]

  […] patients during development of fasting hypoglycemia and in 8 normal volunteers studied over an identical interval. [diabetes.diabetesjournals.org]

• Glucose Decreased

  During a subsequent 8-h fast, glucose production and glucose utilization decreased in both groups, but more markedly in insulinoma patients. [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.

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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
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