Insulinoma

Insulinoma is a tumor located in the pancreas that derives from beta cells and is characterized by excessively and uncontrolled insulin production.

How is it produced?

The pancreas is an organ made up of different types of cells; Each of these cells manufactures a type of substances known as hormones, which are released into the blood to perform different functions in the body. One of these cells is the beta cell, which makes insulin.

Under normal conditions, the beta cells of the pancreas make insulin when blood sugar levels rise, for example when we eat, and they are inhibited (they do not make insulin) when the figures are normal or low, for example fasting or exercising. But for unknown reasons, the beta cells of the pancreas can begin to manufacture insulin in excess and without that control exerted by the level of sugar in our blood.

The beta cell tumor is arranged as a mass made up of beta cells. If we analyze all the tumors of the pancreas that produce insulin under the microscope, we find a wide range of lesions: 70% are solitary benign tumors (adenomas), 10% are multiple adenomas, 10% are malignant tumors (carcinomas), and a 10% are benign lesions characterized by a greater number of uncontrolled beta cells but that do not form a mass but are diffusely distributed throughout the pancreas and that we call diffuse beta cell hyperplasia.

Insulinomas are usually small (less than 2 cm in size) and unique (90% of cases), although there are tumors so small that they are even difficult to see on the operating room table and that they make a diagnosis very difficult.

The average age at which insulinomas (adenomas and carcinomas) develop is 40 to 50 years of age. In contrast, diffuse beta cell hyperplasia is seen mostly in newborns of diabetic mothers; These children are exposed to high blood sugar levels from the mother during pregnancy and respond by increasing beta cells in size and number.

The vast majority of insulinomas are located in the pancreas, although there are tumors outside the pancreas that also make insulin; They are called extrapancreatic tumors.

On the other hand, some of these insulinomas are associated with the presence of other tumors in other organs such as the parathyroid glands, the pituitary gland or the thyroid gland, this association constituting the so-called Multiple Endocrine Neoplasia type I.

Symptoms

Increased and uncontrolled insulin secretion is what produces the symptoms and will make us suspect the presence of this tumor. Only in a late stage of evolution, the tumor also produces symptoms of its own, such as abdominal pain.

Typical symptoms include clumsiness, confusion, headache, visual difficulties, incoherent and unusual behavior, irritation for no apparent reason, and disorientation, and can lead to seizures and coma. These symptoms are due to the effect of hypoglycemia on the brain and are known as neuroglycemic symptoms. It is characteristic that these symptoms are observed especially in fasting situations (for example, when getting up in the morning, or just before lunch or dinner) or when practicing some physical activity (not necessarily intense), because in those moments the sugar (or glucose) figure in the blood is markedly lower. These crises are alleviated quickly after the administration of a food or drink that contains sugar. In addition, during hypoglycemia some patients may have symptoms secondary to an excess release of adrenaline and norepinephrine, including sweating, trembling, and palpitations.

Diagnosis

Although it may seem very easy to reach the diagnosis of an insulinoma, this is not the case. At first, the individual will have the symptoms referred to above and this will correspond to the presence of a very small or undetectable tumor with the imaging techniques that we usually use, such as abdominal ultrasound or computed tomography (CT). It can take a long time between the onset of these symptoms and the diagnosis, even years.

The diagnosis of insulinoma begins with the demonstration of high blood insulin levels at the time of hypoglycemia. As mentioned before, under normal conditions the pancreas stops making insulin if there is a decrease in blood sugar levels. In the case of an insulinoma, the pancreas continues to make insulin, even if the sugar levels are low or very low. This has made it possible to develop a test to diagnose insulinoma, which consists of producing a fast of up to 72 hours with the individual admitted to the hospital, and making determinations in blood of glucose, insulin and C-peptide (or proinsulin) from time to time. If at any time the patient has symptoms or their blood glucose levels are persistently below 40 mg / dL (= 2.2 mmol / L), the test will be terminated.

The C-peptide determination is made to rule out hypoglycemia caused by the individual himself, whether with the use, inadvertent or not, of insulin or oral hypoglycemic agents. Insulin is a protein that is made as a large protein (proinsulin), which has two chains connected by a very small chain (C-peptide). In insulinomas, in addition to plasma insulin levels, plasma proinsulin and C-peptide levels are elevated, which is not the case with exogenous administration of insulin or oral antidiabetic drugs.

When this fasting test is successful and positive, it is usually sufficient for diagnosis. But then the tumor must be located using imaging techniques: ultrasound, computed tomography (CT) and magnetic resonance imaging of the abdomen. Endoscopic ultrasound can sometimes be used to locate very small tumors. If these imaging techniques do not detect the tumor or when the tumor is suspected to be outside the pancreas, that is, metastasis, scintigraphy with somatostatin analogs (octreotide or pentreotide) can be used; although it is important to know that with this technique only less than half of insulinomas are detected.

Treatment

Treatment requires two different strategies. On the one hand, the treatment of the symptoms produced by hormonal excess (hypoglycemia). And, on the other, the treatment of the tumor itself.

The treatment of choice for insulinoma is surgical and consists of the removal of the tumor. The surgeon will decide what type of surgery is appropriate in each case. Up to 75-95% of patients are cured by surgery. Whether the surgery is effective is demonstrated by the immediate recovery of blood glucose to normal values ​​and the disappearance of neuroglycemic symptoms. In addition, the removal of the tumor allows us to study it and know if it is benign or malignant.

In cases where the tumor cannot be operated on (because there is metastasis), or if the tumor reappears after surgery, non-surgical measures will be considered. These measures include controlling hypoglycemia through small, frequent meals, and the use of drugs such as diazoxide, verapamil, phenytoin, and octreotide. These non-surgical measures are also used before carrying out the surgery to avoid possible hypoglycemia during the surgical act. In inoperable or metastatic tumors, chemotherapy can be used, the most useful drugs being doxorubicin and streptozocin.

Precautionary measures

There are no preventive treatments to prevent this tumor from appearing. The best preventive measure is to have a high index of suspicion in the individual. Insulinoma will be suspected in all patients with repeated hypoglycemia, especially in fasting or exercise situations, and in people with a family history of type 1 multiple endocrine neoplasia.

Conclusions.

Insulinoma is a very rare tumor that is generally difficult to diagnose and difficult to locate. The most effective treatment is surgical and its removal can cure the disease.