Insulinoma is a rare type of tumor in the pancreas that grows at the expense of insulin-secreting cells. Its presence is the cause of sometimes severe hypoglycemia attacks. Most often benign and small in size, the tumor is not always easy to locate. The success rate of surgical removal is high.

Definition

An insulinoma is a tumor of the pancreas, called endocrine because it causes excessive insulin secretion. This hypoglycemic hormone is normally produced in a regulated way by a class of cells in the pancreas, beta cells, to lower blood glucose levels when they rise too high. But the secretion of insulin by the tumor is uncontrolled, which leads to episodes of so-called “functional” hypoglycemia in healthy, non-diabetic adults.

About 90% of insulinomas are isolated benign tumors. A small proportion corresponds to multiple and / or malignant tumors – the latter are distinguished by the occurrence of metastases.

These tumors are generally small: nine out of ten do not exceed 2 cm, and three in ten are less than 1 cm.

Causes

The vast majority of insulinomas appear sporadically, with no identified cause. In rare cases, hereditary factors are involved.

Diagnostic

The presence of an insulinoma should be considered when a non-diabetic subject presents symptoms of recurrent episodes of hypoglycemia without any other obvious cause (alcoholism, renal, hepatic or adrenal insufficiency, drugs, etc.).

Insulinoma is manifested by very low blood glucose levels combined with abnormally high insulin levels. To demonstrate this, we practice a fasting test lasting a maximum of 72 hours under medical supervision. The diagnosis is based on blood tests taken when symptoms of hypoglycemia occur. The test is stopped as soon as the blood glucose level drops too much.

Imaging exams are then done to locate the insulinoma. The reference examination is echo-endoscopy, which allows a precise study of the pancreas using a flexible tube fitted with a camera and a miniature ultrasound probe, introduced into the digestive system through the mouth. Other tests such as an angio-scanner can also be helpful.

Despite advances in imaging, locating small tumors remains difficult. It is sometimes done after exploratory surgery thanks to palpation combined with an intraoperative ultrasound, using a specific ultrasound probe.

The people concerned

Although being the most frequent cause of tumor hypoglycaemia in adults, insulinoma remains a very rare tumor, affecting 1 to 2 people per million inhabitants (50 to 100 new cases each year in France).

The diagnosis is often made around the age of 50. Some authors note a slight female predominance.

Risk factors

Rarely, insulinoma is associated with type 1 multiple endocrine neoplasia, a rare inherited syndrome manifested by the presence of tumors in several endocrine glands. A quarter of these insulinomas are malignant. The risk of developing insulinoma would also be associated to a lesser extent with other hereditary diseases (von Hippel Lindau disease, Recklinghausen neurofibromatosis and Bourneville tuberous sclerosis).

Episodes of profound hypoglycemia most often appear – but not systematically – in the morning on an empty stomach or after exercise.

Effect on the nervous system of glucose deficiency 

Symptoms include feeling weak and unwell with or without unconsciousness, headache, visual disturbances, sensitivity, motor skills or coordination, sudden hunger … Some symptoms such as confusion or disturbances in concentration, personality or behavior can simulate psychiatric or neurological pathology, which complicates the diagnosis.

Eat hypoglycemic

In the most severe cases, hypoglycemia causes a sudden onset coma, more or less deep and often accompanied by profuse sweating.

Other symptoms

These symptoms are often associated with signs of a autonomic reaction to hypoglycemia:

• anxiety, tremors
• nausea,
• feeling of heat and sweating,
• pallor,
• tachychardie…

   

Repeated episodes of hypoglycemia can lead to weight gain.

Surgical removal of insulinoma gives very good results (cure rate around 90%).

When the tumor is single and well localized, the intervention can be very targeted (enucleation) and a minimally invasive surgery is sometimes sufficient. If the location is imprecise or in the event of multiple tumors, it is also possible to perform a partial removal of the pancreas (pancreatectomy).

Blood sugar control

While waiting for surgery or if symptoms persist after surgery, medicines such as diazoxide or somatostatin analogues can help prevent blood sugar from dropping too much.

Faced with an inoperable, symptomatic or progressive malignant insulinoma, various anti-cancer treatments can be implemented:

• Chemotherapy should be considered to reduce a large tumor mass.
• Everolimus, an immunosuppressive antitumor agent, may be helpful if hypoglycaemia persists.
• Metabolic radiotherapy uses radioactive substances administered by venous or oral route, which preferentially bind to cancer cells to destroy them. It is reserved for tumors showing few bone metastases and / or developing slowly.