Insulinoma is a tumor that affects the neuroendocrine system and leads to the overproduction of insulin, resulting in low blood sugar levels or hypoglycemia.

How Common is Insulinoma?

Insulinoma occurs roughly 1 to 4 times per million people each year.

What are signs and symptoms of Insulinoma?

The signs and symptoms of Insulinoma include: - Heart palpitations - Trembling - Excessive sweating - Hazy vision - Confusion - Seizures - Changes in behavior - Loss of memory of the event These symptoms are a result of the body's sympathetic nervous system reacting to low blood sugar. In severe cases, hypoglycemia can cause neuroglycopenic symptoms such as hazy vision, confusion, seizures, changes in behavior, and even a loss of memory of the event. In rare cases, insulinoma may also present with psychiatric symptoms, particularly panic attacks. It is important to note that weight gain is also typically observed in most patients with insulinoma.

How do you get Insulinoma?

Scientists don't completely understand why a solitary insulinoma occurs, but it may be due to a small change in the way insulin is produced. In some cases, insulinoma can be linked to the MEN1 syndrome, a genetic disorder.

What else can Insulinoma be?

Persistent Hyperinsulinemic Hypoglycemia of Infancy (PHHI), Noninsulinoma Pancreatogenous Hypoglycemia Syndrome (NIPHS), Post-Gastric Bypass Hypoglycemia, Factitious Use of Insulin, Sulfonylurea-Induced Hypoglycemia, Insulin Autoimmune Hypoglycemia, Non-Islet-Cell Tumors that Secrete Insulin-like Growth Factors (IGF), and Nesidioblastosis.

What kinds of test are needed for Insulinoma?

The types of tests needed for diagnosing and locating an insulinoma include: 1. 72-hour fasting test: This test checks for low blood sugar and measures insulin, C-peptide, proinsulin, and beta-hydroxybutyrate levels. It also checks for negative sulfonylurea levels. 2. Imaging tests: Computed tomography (CT) scans with contrast, abdominal ultrasound, magnetic resonance imaging (MRI), and GLP-1 imaging can be used to locate the tumor. 3. Invasive tests: Endoscopic ultrasonography (EUS) and selective arterial calcium stimulation test (SACST) with hepatic venous sampling may be performed if non-invasive tests fail. 4. Histology examination and immunostaining: These tests confirm the diagnosis of insulinoma by examining certain proteins. 5. Genetic testing: Young patients with insulinoma should undergo genetic testing, especially if there are personal or family histories of endocrine diseases. In addition to these tests, other factors such as tumor size, Ki67 index, blood insulin and C-peptide levels, and the presence of metastasis are considered to determine the risk of malignancy.

How is Insulinoma treated?

Insulinoma can be treated through surgery, specifically a surgical resection. This procedure involves removing the tumor, either through enucleation or partial distal pancreatectomy. Laparoscopic techniques are increasingly used, resulting in shorter hospital stays and similar positive outcomes. Medications like diazoxide or somatostatin analogs can also be given before surgery to reduce insulin release or enhance glycogen breakdown. In more severe cases, specialist cancer care and targeted therapies like everolimus may be required. In advanced cases, surgical resection may still be considered if most of the tumor can be safely operated on. Other treatments like chemotherapy and peptide receptor radionuclide therapy are being researched for potential relief and symptom control.

What are the side effects when treating Insulinoma?

The side effects when treating Insulinoma include: - Constant low blood sugar - Disruption of daily activities - Long-lasting brain damage - Potential death

Are there long term effects of Insulinoma?

The prognosis for insulinoma depends on whether the tumor is benign or malignant, as well as whether the patient has MEN1 syndrome. Here are the key points: - For patients with a benign insulinoma, the ten-year survival rate after successful surgery is 88%, and the surgery cures 87.5% of patients. - However, if the insulinoma is malignant, the ten-year survival rate after successful surgery is only 29%. - Patients with MEN1 syndrome have a higher risk of recurrence, with a recurrence rate of about 21% at both 10 and 20 years post-surgery, compared to a lower recurrence rate of 5% at ten years and 7% at 20 years for those without MEN1.

Insulinoma

What is Insulinoma?

Insulinoma is a kind of tumor affecting the neuroendocrine system, which controls the production of hormones in our bodies. This tumor tends to produce a lot of insulin, leading to low blood sugar levels, or hypoglycemia. Generally, insulinoma is a single non-cancerous tumor, but it can occasionally be linked to a condition called multiple endocrine neoplasia type 1 (MEN1), where multiple glands in the body overproduce hormones.

People with insulinoma often experience episodes of low blood sugar, typically when they haven’t eaten for a while. If a doctor suspects insulinoma, they’ll usually conduct biochemical tests to diagnose the condition. Surgery to remove the tumor is the most preferred treatment option.

It’s important to locate the tumor using imaging techniques so the surgeon can understand it better before performing the surgery. There are alternative treatment methods that a doctor may consider, based on the size and stage of the tumor.

What Causes Insulinoma?

Scientists don’t completely understand why a solitary insulinoma, a type of tumor that affects the pancreas, occurs. Normally, when the amount of sugar in your blood – also known as your plasma glucose concentration – is high, your pancreas secretes insulin, a hormone that helps regulate blood sugar levels. And when your blood sugar level drops, your pancreas stops releasing insulin. But in people with insulinoma, the body still produces insulin, even when blood sugar levels are low.

This condition, called hyperinsulinemia, might be due to the body’s insulin production process going into overdrive because of a small change in the way insulin is produced. Once the amount of insulin inside the body’s cells gets too high, the excess insulin is released into the blood.

Hyperinsulinemia can cause several issues, one of which is hypoglycemia, or low blood sugar. This is because an overproduction of insulin promotes the making of glycogen, a stored form of glucose, reduces the creation of new glucose, and slows down the breakdown of glycogen back into glucose.

MEN1 is a health condition that increases the likelihood of developing tumors on the pituitary gland (which regulates hormones in the body), parathyroid (which regulates calcium in blood), and the pancreas and intestines. If insulinomas occur with this condition, most commonly, there is a mutation in the MEN1 gene located on chromosome 11q13.

Risk Factors and Frequency for Insulinoma

Insulinoma, a type of tumor, occurs roughly 1 to 4 times per million people each year. It’s typically a single non-harmful (benign) tumor. However, it can be harmful (malignant) in about 5.8% of cases. In around 7% of cases, it can coexist with other benign tumors, while between 6% and 7.6% of the time, it’s linked with MEN1 syndrome, a genetic disorder. People are usually diagnosed with insulinoma through surgery between the ages of 47 to 50.

Signs and Symptoms of Insulinoma

Insulinoma is a health condition that often leads to hypoglycemia, or low blood sugar. It’s most commonly identified by fasting hypoglycemia, which is present in approximately 73% of patients. About 20% of patients experience hypoglycemia both when fasting and after meals. An increase in reports show that some patients only suffer from hypoglycemia after meals, and this trend is more common in men. Weight gain also typically occurs in most patients with insulinoma.

The symptoms of hypoglycemia can vary. They can include heart palpitations, trembling, and excessive sweating, which are signs of the body’s sympathetic nervous system reacting to low blood sugar. If hypoglycemia becomes severe, it can cause neuroglycopenic symptoms, which include hazy vision, confusion, seizures, changes in behavior, and even a loss of memory of the event.

Heart palpitations
Trembling
Excessive sweating
Hazy vision
Confusion
Seizures
Changes in behavior
Loss of memory of the event

When a patient shows signs of hypoglycemia, has a recorded low blood sugar level, and their symptoms get better after consuming glucose (a kind of sugar), insulinoma is usually suspected. This set of criteria is known as Whipple’s triad. In rare cases, insulinoma may also show up through psychiatric symptoms, particularly panic attacks.

Testing for Insulinoma

If your doctor suspects that you might have an insulinoma, which is a tumor that produces insulin, they will conduct two critical evaluations. The first is diagnosing the tumor, and the second is finding its location.

A 72-hour fasting test is generally the most reliable method to diagnose an insulinoma. This test becomes necessary when typical symptoms like low blood sugar, weakness, or blurry vision aren’t present, or when correct tests weren’t performed during episodes of extremely low blood sugar. The fasting test includes several checks: your blood sugar should be below 55 mg/dL, your insulin level should be at or over 3 microUnits/mL, your C-peptide level should be at or over 0.6 ng/mL, your proinsulin level should be at or over 5 pmol/L, and the beta-hydroxybutyrate level should be at or below 2.7 mmol/L. Your sulfonylurea levels (a type of medicine used to treat type 2 diabetes) should be negative. Altogether, these results suggest that your low blood sugar is caused by excessive insulin production.

The next step involves accurately locating the tumor using non-invasive techniques. Computed tomography (CT) scans with contrast, where a special dye is used to highlight the tumor, are commonly used and successfully locate the tumor about 70 to 80% of the time. On a CT, an insulinoma shows up as a small, solid mass that becomes brighter after contrast. Alternatively, an abdominal ultrasound focusing on the pancreas can be used due to its convenience and lower cost. A magnetic resonance image (MRI) can find around 85% of insulinomas and is thus highly reliable. A new test that uses Glucagon-like peptide-1 receptor (GLP-1) imaging has shown promising results in localize insulinomas with a success rate from 66 to 97% in preliminary studies.

If non-invasive methods fail, your doctor might consider invasive tests such as endoscopic ultrasonography (EUS) or a selective arterial calcium stimulation test (SACST) with hepatic venous sampling (a test that helps localize the tumor in the pancreas). EUS is more accurate than CT scans in localizing insulinomas and can also obtain a tissue sample from the tumor for further testing. SACST has a high success rate and is often performed when non-invasive tests fail, or in patients with a specific condition called MEN1 syndrome.

Afterward, a histology examination and immunostaining (a special process in the lab to detect certain proteins) for chromogranin A, synaptophysin, and insulin would be performed to confirm the diagnosis of insulinoma. The Ki67 index, a marker to determine how rapidly the cells in the tumor are dividing and growing, is also important to evaluate, especially if the patient’s disease is progressing rapidly.

In some cases, doctors might consider the tumor as potentially malignant if it’s larger than 2 cm, if Ki67 is more than 2%, or if certain genetic markers are present. Other factors such as a rapid development of hypoglycemia (in less than 8 hours), higher blood insulin level (greater than 28 microUnits/mL), higher C-peptide level (greater than 4.0 ng/mL), and larger tumor size (greater than 2.5 cm) also indicate an increased risk of malignancy. The spread of the tumor to the liver or the presence of lymph node metastasis are also crucial factors to consider.

All young patients with insulinoma should undergo genetic testing. If there are personal or family histories of endocrine diseases, they may be tested for MEN1 syndrome, a genetic disorder affecting the endocrine glands.

Treatment Options for Insulinoma

If you’re dealing with a disease like insulinoma, which is a small tumor in the pancreas that produces an excess of insulin, your doctor might recommend surgery as a treatment option. This procedure, called a surgical resection, is typically recommended for diseases that are currently local but could become more advanced. With insulinoma, successful surgery can often cure the condition.

The surgery is usually performed in one of two ways. One method involves small-scale surgery to remove the tumor, known as enucleation. The second option involves a more aggressive operation where a portion of the pancreas is removed, known as a partial distal pancreatectomy. Nowadays, surgeons are increasingly choosing to perform these procedures laparoscopically, meaning they use small incisions. This method tends to result in shorter hospital stays and similar positive results compared to older, more invasive techniques.

Sometimes, robotic techniques are employed for surgery. Also, some patients might need a slightly different approach, especially patients with a condition known as MEN1. In such cases, a larger portion of the pancreas might be removed in addition to the tumor removal.

There are treatments that can be given before surgery, too. These include medications like diazoxide or therapeutics called somatostatin analogs. In cases where surgery isn’t a good option, like when a patient is unwell or the tumor can’t be removed, these medications can be helpful, too. They work by reducing the release of insulin or enhancing the breakdown of glycogen, which is a form of sugar storage in your body. Many patients become symptom-free after starting these medications. If the medications don’t work well, adjusting the dosing or considering surgery can help.

In severe and challenging cases, where symptoms persist and the tumor continues to grow, specialist cancer care might be required. There are targeted therapies available for such circumstances. Everolimus, for example, is one of them that inhibits a protein i.e., mTOR, which plays a key role in cell proliferation.

If the illness is already quite advanced, surgical resection could still be considered if most of the tumor can be operated on safely. There are still many unanswered questions about the best treatment approaches and more research is needed. However, various treatments, like chemotherapy involving 5-FU or temozolomide, may provide potential relief in patients with severely progressed conditions. Some latest research points towards an innovative treatment named ‘peptide receptor radionuclide therapy’, which could potentially offer survival benefits and help control symptoms in unresectable or borderline resectable cases. However, this treatment needs to be researched more extensively to confirm its effectiveness and role in treating insulinomas.

The following medical conditions can cause low blood sugar:

Persistent high insulin levels in newborns (Persistent Hyperinsulinemic Hypoglycemia of Infancy or PHHI)
A rare disorder causing low blood sugar from the pancreas (Noninsulinoma Pancreatogenous Hypoglycemia Syndrome or NIPHS)
Low blood sugar following a gastric bypass surgery (Post-Gastric Bypass Hypoglycemia)
Lows blood sugar because of insulin misuse (Factitious Use of Insulin)
Hypoglycemia induced by a class of diabetic drugs (Sulfonylurea-Induced Hypoglycemia)
Low blood sugar caused by immune reaction to insulin (Insulin Autoimmune Hypoglycemia)
Cancerous and noncancerous tumors that secrete hormones similar to insulin (Non-Islet-Cell Tumors that Secrete Insulin-like Growth Factors or IGF)
A rare pancreas disorder in newborns (Nesidioblastosis)

What to expect with Insulinoma

For individuals with insulinoma, a type of tumor that produces too much insulin, the ten-year survival rate after a successful surgery is 88%. Moreover, the surgery cures 87.5% of the patients, with ‘cure’ being defined as freedom from symptoms for at least six months post-surgery.

However, the survival rates are different if the insulinoma is malignant, or cancerous. In one study, the ten-year survival rate after successful surgery was 29%, while in another, the five-year survival rate was 24%.

There’s also an increased risk of surgery not being successful or experiencing a recurrence of the disease for patients with MEN1 syndrome (a genetic condition that increases the risk of developing various types of tumors) or malignant insulinomas. Specifically, patients with MEN1 have a recurrence rate of about 21% at both 10 and 20 years post-surgery. In contrast, those without MEN1 have a lower recurrence rate of 5% at ten years and 7% at 20 years after surgery.

Possible Complications When Diagnosed with Insulinoma

Insulinoma can lead to several complications. These include constant low blood sugar which can disrupt someone’s day-to-day activities, long-lasting damage to the brain’s ability to think and understand, and in very severe cases it can even cause death.

Complications linked to Insulinoma:

Constant low blood sugar
Disruption of daily activities
Long-lasting brain damage
Potential death

Recovery from Insulinoma

Patients suffering from insulinoma, who don’t have the MEN1 condition, typically get a follow-up visit between 3 and 6 months after their tumor removal surgery. During this visit, doctors will carry out certain tests and imaging studies again to check their health progress. If the treatment has been successful, doctors will only need to see the patients again if the symptoms return.

On the other hand, if some patients continue to experience symptoms after the surgery, there could be multiple tumors or the presence of the MEN1 syndrome. In these cases, their doctors would need to do further imaging studies. If patients have multiple insulinomas or MEN1, they should have yearly check-ups, even if they seem to be cured after the tumor removal surgery.

Preventing Insulinoma

It’s important for patients and their family members to know how to spot signs related to low blood sugar, also known as hypoglycemia. Additionally, they should learn easy methods to increase blood sugar levels quickly if they become too low. Patients should continue to see doctors who specialize in hormone disorders, called endocrinologists, for checks and treatment of insulinoma, which is a tumor in the pancreas that can cause low blood sugar. In some cases, these doctors might suggest genetic testing.