Insulinoma is a hormone–active tumor of the beta cells of the pancreatic islets, secreting insulin in excess and leading to the development of hypoglycemia. Hypoglycemic attacks with insulinoma are accompanied by trembling, cold sweat, hunger and fear, tachycardia, paresthesia, speech, visual and behavioral disorders; in severe cases – convulsions and coma. Diagnosis of insulinoma is carried out using functional tests, determination of the level of insulin, C-peptide, proinsulin and blood glucose, pancreatic ultrasound, selective angiography. With insulinoma, surgical treatment is indicated – tumor enucleation, pancreatic resection, pancreatoduodenal resection or total pancreatectomy.
Meaning
Insulinoma is a benign (in 85-90% of cases) or malignant (in 10-15% of cases) tumor originating from the beta cells of the islets of Langerhans, possessing autonomous hormonal activity and leading to hyperinsulinism. Uncontrolled insulin secretion is accompanied by the development of hypoglycemic syndrome – a complex of adrenergic and neuroglycopenic manifestations.
Among the hormone-active tumors of the pancreas, insulinomas account for 70-75%; in about 10% of cases, they are a component of multiple endocrine adenomatosis type I (along with gastrinoma, pituitary tumors, parathyroid adenoma, etc.). Insulinomas are more often detected in people aged 40-60 years, in children they are rare. Insulinoma can be located in any part of the pancreas (head, body, tail); in isolated cases, it is localized extrapancreatically – in the wall of the stomach or duodenum, omentum, spleen gate, liver, and other areas. Usually the size of an insulinoma is 1.5 – 2 cm .
Pathogenesis
The development of hypoglycemia in insulinoma is caused by excessive, uncontrolled secretion of insulin by tumor b cells. Normally, when the blood glucose level drops, there is a decrease in insulin production and its entry into the bloodstream. In tumor cells, the mechanism of regulation of insulin production is disrupted: with a decrease in glucose levels, its secretion is not suppressed, which creates conditions for the development of hypoglycemic syndrome.
The most sensitive to hypoglycemia are brain cells, for which glucose serves as the main energy substrate. In this regard, with insulinoma, the phenomena of neuroglycopenia are noted, and with prolonged hypoglycemia, dystrophic changes in the central nervous system develop. Hypoglycemic state stimulates the release of contrinsular hormones into the blood (norepinephrine, glucagon, cortisol, somatotropin), which cause adrenergic symptoms.
Symptoms
During insulinoma, phases of relative well-being are distinguished, which are periodically replaced by clinically pronounced manifestations of hypoglycemia and reactive hyperadrenalinemia. In the latent period, the only manifestations of insulinoma may be obesity and increased appetite.
Acute hypoglycemic attack is the result of disruption of the adaptive mechanisms of the central nervous system and counterinsular factors. The attack develops on an empty stomach, after a long break in eating, more often in the morning. During an attack, there is a drop in blood glucose below 2.5 mmol /l.
Neuroglycopenic symptoms of insulinoma may resemble various neurological and psychiatric disorders. Patients may experience headache, muscle weakness, ataxia, confusion. In some cases, a hypoglycemic attack in patients with insulinoma is accompanied by a state of psychomotor agitation: hallucinations, incoherent cries, motor anxiety, unmotivated aggression, euphoria.
The reaction of the sympathetic-adrenal system to a sharp hypoglycemia is the appearance of tremor, cold sweat, tachycardia, fear, paresthesia. With the progression of the attack, an epileptic seizure, loss of consciousness and coma may develop. Usually the attack is stopped by intravenous infusion of glucose; however, after recovering, patients do not remember what happened. During a hypoglycemic attack, myocardial infarction may develop due to acute malnutrition of the heart muscle, signs of local damage to the nervous system (hemiplegia, aphasia), which may be mistaken for ACVA.
With chronic hypoglycemia in patients with insulinoma, the functioning of the central and peripheral nervous system is disrupted, which affects the course of the relative well-being phase. In the intercrime period, transient neurological symptoms, visual disturbances, myalgia, decreased memory and mental abilities, apathy occur. Even after the removal of the insulinoma, the decrease in intelligence and encephalopathy usually persist, which leads to the loss of professional skills and the former social status. In men, with frequent bouts of hypoglycemia, impotence may develop.
Neurological examination of patients with insulinoma reveals asymmetry of periosteal and tendon reflexes, uneven or decreased abdominal reflexes, pathological reflexes of Rossolimo, Babinsky, Marinescu-Radovich, nystagmus, paresis of the upward gaze, etc. Due to the polymorphism and non-specificity of clinical manifestations, patients with insulinoma may be misdiagnosed with epilepsy, brain tumors, vegetative-vascular dystonia, stroke, diencephalic syndrome, acute psychosis, neurasthenia, residual neuroinfection phenomena, etc.
Diagnostics
To determine the causes of hypoglycemia and differentiate insulinoma from other clinical syndromes allows a complex of laboratory tests, functional tests, visualizing instrumental studies. The fasting test is aimed at provoking hypoglycemia and causes the Whipple triad pathognomonic for insulinoma: a decrease in blood glucose to 2.78 mmol /l or lower, the development of neuropsychiatric manifestations against the background of fasting, the possibility of stopping the attack by oral administration or intravenous glucose infusion.
In order to induce a hypoglycemic state, an insulin-suppressive test with the introduction of exogenous insulin can be used. At the same time, there are inadequately high concentrations of C-peptide in the blood against the background of extremely low glucose levels. Carrying out an insulin provocation test (intravenous glucose or glucagon) promotes the release of endogenous insulin, the level of which in patients with insulinoma becomes significantly higher than in healthy individuals; at the same time, the ratio of insulin and glucose exceeds 0.4 (normally less than 0.4).
With positive results of provocative tests, topical diagnostics of insulinoma is performed: ultrasound of the pancreas and abdominal cavity, scintigraphy, MRI of the pancreas, selective angiography with blood sampling from portal veins, diagnostic laparoscopy, intraoperative ultrasonography of the pancreas. Insulin has to be differentiated from drug and alcohol hypoglycemia, pituitary and adrenal insufficiency, adrenal cancer, dumping syndrome, galactosemia, etc. states.
Treatment
In endocrinology, surgical tactics are preferred in relation to insulinoma. The volume of the operation is determined by the localization and size of the formation. With insulinoma, both tumor enucleation (insulinomectomy) and various types of pancreatic resections (distal, head resection, pancreatoduodenal resection, total pancreatectomy) can be performed. The effectiveness of the intervention is assessed by dynamic determination of blood glucose levels during the operation. Postoperative complications may include pancreatitis, pancreatic necrosis, pancreatic fistulas, abdominal abscess or peritonitis.
With inoperable insulinomas, conservative therapy is carried out, aimed at relieving and preventing hypoglycemia, with the help of hyperglycemic agents (adrenaline, noradrenaline, glucagon, glucocorticoids, etc.). With malignant insulinomas, chemotherapy is performed (streptozotocin, 5-fluorouracil, doxorubicin, etc.).
Forecast
Clinical recovery occurs in 65-80% of patients after surgical removal of insulinoma. Early diagnosis and timely surgical treatment of insulinoma lead to regression of changes from the central nervous system according to EEG data.
Postoperative mortality is 5-10%. Relapse of insulinoma develops in 3% of cases. The prognosis for malignant insulinomas is unfavorable – the survival rate for 2 years does not exceed 60%. Patients with a history of insulinoma are registered at the dispensary by an endocrinologist and a neurologist.