Hyperinsulinism is a clinical syndrome characterized by an increase in insulin levels and a decrease in blood sugar. Hypoglycemia leads to weakness, dizziness, increased appetite, tremor, psychomotor agitation. In the absence of timely treatment, hypoglycemic coma develops. Diagnosis of the causes of the condition is based on the features of the clinical picture, functional test data, dynamic glucose examination, ultrasound or tomographic scanning of the pancreas. Treatment of pancreatic neoplasms is surgical. With an extra-pancreatic variant of the syndrome, therapy of the underlying disease is carried out, a special diet is prescribed.
Meaning
Hyperinsulinism (hypoglycemic disease) is a congenital or acquired pathological condition in which absolute or relative endogenous hyperinsulinemia develops. The signs of the disease were first described in the early twentieth century by the American doctor Harris. Congenital hyperinsulinism is quite rare – 1 case per 50 thousand newborns. The acquired form of the disease develops at the age of 35-50 years and more often affects women. Hypoglycemic disease occurs with periods of absence of pronounced symptoms (remission) and with periods of a detailed clinical picture (attacks of hypoglycemia).
Causes
Congenital pathology occurs due to intrauterine developmental abnormalities, fetal growth retardation, mutations in the genome. The causes of acquired hypoglycemic disease are divided into pancreatic, leading to the development of absolute hyperinsulinemia, and non-pancreatic, causing a relative increase in insulin levels. The pancreatic form of the disease occurs with malignant or benign neoplasms, as well as hyperplasia of beta cells of the pancreas. The non – pancreatic form develops in the following conditions:
- Eating disorders. Prolonged fasting, increased loss of fluid and glucose (diarrhea, vomiting, lactation), intense physical activity without the consumption of carbohydrate foods cause a sharp decrease in blood sugar levels. Excessive consumption of refined carbohydrates increases blood sugar levels, which stimulates the active production of insulin.
- Liver damage of various etiologies (cancer, fatty hepatosis, cirrhosis) leads to a decrease in glycogen levels, impaired metabolic processes and the occurrence of hypoglycemia.
- Uncontrolled intake of hypoglycemic drugs in diabetes mellitus (insulin derivatives, sulfonylureas) causes drug hypoglycemia.
- Endocrine diseases that lead to a decrease in the level of counterinsulin hormones (ACTH, cortisol): pituitary nanism, myxedema, Addison’s disease.
The lack of enzymes involved in glucose metabolism (hepatic phosphorylase, renal insulinase, glucose-6-phosphatase) causes relative hyperinsulinism.
Pathogenesis
Glucose is the main nutrient substrate of the central nervous system and is necessary for the normal functioning of the brain. Increased insulin levels, accumulation of glycogen in the liver and inhibition of glycogenolysis leads to a decrease in blood glucose levels. Hypoglycemia causes inhibition of metabolic and energy processes in brain cells. The sympathoadrenal system is stimulated, the production of catecholamines increases, an attack of hyperinsulinism develops (tachycardia, irritability, a feeling of fear). Violation of redox processes in the body leads to a decrease in oxygen consumption by cells of the cerebral cortex and the development of hypoxia (drowsiness, lethargy, apathy). Further glucose deficiency causes disruption of all metabolic processes in the body, an increase in blood flow to brain structures and spasm of peripheral vessels, which can lead to a heart attack. When ancient brain structures (the medulla oblongata and the medulla oblongata, the Varolian bridge) are involved in the pathological process, convulsive states, diplopia, as well as respiratory and cardiac disorders develop.
Classification
In clinical endocrinology, the classification of hyperinsulinemia is most often used depending on the causes of the disease:
- Primary hyperinsulinism (pancreatic, organic, absolute) is a consequence of a tumor process or hyperplasia of beta cells of the islet apparatus of the pancreas. Benign neoplasms (insulinoma) contribute to an increase in insulin levels by 90%, less often – malignant (carcinoma). Organic hyperinsulinemia occurs in severe form with a pronounced clinical picture and frequent attacks of hypoglycemia. A sharp decrease in blood sugar occurs in the morning, due to skipping meals. This form of the disease is characterized by the Whipple triad: symptoms of hypoglycemia, a sharp decrease in blood sugar and relief of seizures by glucose administration.
- Secondary hyperinsulinism (functional, relative, extra-pancreatic) is associated with a deficiency of contrinsular hormones, damage to the nervous system and liver. An attack of hypoglycemia occurs for external reasons: starvation, overdose of hypoglycemic drugs, intense physical exertion, psychoemotional shock. Exacerbations of the disease occur irregularly, practically unrelated to food intake. Daily fasting does not cause detailed symptoms.
Symptoms
The clinical picture of hypoglycemic disease is caused by a decrease in blood glucose levels. The development of an attack begins with an increase in appetite, sweating, weakness, tachycardia and a feeling of hunger. Later, panic states are added: a feeling of fear, anxiety, irritability, trembling in the extremities. With the further development of the attack, there is disorientation in space, diplopia, paresthesia (numbness, tingling) in the extremities, up to the onset of seizures. In the absence of treatment, loss of consciousness and hypoglycemic coma occur. The inter-approach period is manifested by a decrease in memory, emotional lability, apathy, impaired sensitivity and numbness in the extremities. Frequent intake of food rich in easily digestible carbohydrates provokes an increase in body weight and the development of obesity.
In modern practice, there are 3 degrees of hyperinsulinism, depending on the severity of the disease: mild, moderate and severe. A mild degree is manifested by the absence of symptoms of the intercalary period and organic damage to the cerebral cortex. Exacerbations of the disease occur less than 1 time per month and are quickly stopped by medications or sweet food. With moderate severity, seizures occur more often than once a month, loss of consciousness and the development of a comatose state are possible. The inter-criminal period is characterized by mild behavioral disorders (forgetfulness, decreased thinking). Severe degree develops with irreversible changes in the cerebral cortex. At the same time, seizures occur frequently and end in loss of consciousness. In the inter-approach period, the patient is disoriented, memory is sharply reduced, tremor of the extremities is noted, a sharp change of mood and increased irritability are characteristic.
Complications
Complications can be divided into early and late. Early complications that occur in the coming hours after an attack include stroke, myocardial infarction due to a sharp decrease in the metabolism of the heart muscle and brain. In severe situations, hypoglycemic coma develops. Late complications appear several months or years after the onset of the disease and are characterized by impaired memory and speech, parkinsonism, encephalopathy. The lack of timely diagnosis and treatment of the disease leads to depletion of the endocrine function of the pancreas and the development of diabetes mellitus, metabolic syndrome, obesity. Congenital hyperinsulinism in 30% of cases leads to chronic hypoxia of the brain and a decrease in the full mental development of the child.also Jira SQL Software Agile Soap UI
Diagnostics
Diagnosis is based on the clinical picture (loss of consciousness, tremor, psychomotor agitation), the history of the disease (the time of onset of the attack, its connection with food intake). The endocrinologist clarifies the presence of concomitant and hereditary diseases (fatty hepatosis, diabetes mellitus, Cushing syndrome), after which he prescribes laboratory and instrumental studies. The patient is given a daily measurement of blood glucose (glycemic profile). When deviations are detected, functional tests are performed. The fasting test is used for the differential diagnosis of primary and secondary hyperinsulinism. During the test, C-peptide, immunoreactive insulin (IRI) and blood glucose are measured. An increase in these indicators indicates the organic nature of the disease.
To confirm the pancreatic etiology of the disease, tests for sensitivity to tolbutamide and leucine are carried out. With positive results of functional tests, ultrasound, scintigraphy and MRI of the pancreas are indicated. In secondary hyperinsulinism, ultrasound of the abdominal cavity and MRI of the brain are performed to exclude neoplasms of other organs. Differential diagnosis of hypoglycemic disease is carried out with Zollinger-Ellison syndrome, the onset of type 2 diabetes mellitus, neurological (epilepsy, brain neoplasms) and mental (neurosis-like conditions, psychosis) diseases.
Treatment
Treatment tactics depend on the cause of hyperinsulinemia. With organic genesis, surgical treatment is indicated: partial resection of the pancreas or total pancreatectomy, enucleation of the neoplasm. The volume of surgery is determined by the location and size of the tumor. After surgery, transient hyperglycemia is usually noted, requiring medication correction and a low-carbohydrate diet. Normalization of indicators occurs a month after the intervention. In inoperable tumors, palliative therapy is carried out aimed at preventing hypoglycemia. In case of malignant neoplasms, chemotherapy is additionally indicated.
Functional hyperinsulinism primarily requires treatment of the underlying disease that caused increased insulin production. All patients are prescribed a balanced diet with a moderate reduction in carbohydrate intake (100-150 grams per day). Preference is given to complex carbohydrates (rye bread, pasta from durum wheat, whole grains, nuts). Meals should be fractional, 5-6 times a day. Due to the fact that periodic seizures cause patients to develop panic states, a psychologist’s consultation is recommended. With the development of a hypoglycemic attack, the use of easily digestible carbohydrates (sweet tea, candy, white bread) is indicated. In the absence of consciousness, intravenous administration of 40% glucose solution is necessary. With convulsions and severe psychomotor agitation, injections of tranquilizers and sedatives are indicated. Treatment of severe attacks of hyperinsulinism with the development of coma is carried out in the intensive care unit with detoxification infusion therapy, administration of glucocorticoids and adrenaline.
Prognosis and prevention
Prevention of hypoglycemic disease includes a balanced diet with an interval of 2-3 hours, drinking enough drinking water, giving up bad habits, as well as glucose control. To maintain and improve metabolic processes in the body, moderate physical activity is recommended in compliance with the diet. The prognosis for hyperinsulinism depends on the stage of the disease and the causes that caused insulinemia. Removal of benign neoplasms in 90% of cases provides recovery. Inoperable and malignant tumors cause irreversible neurological changes and require constant monitoring of the patient’s condition. Treatment of the underlying disease with the functional nature of hyperinsulinemia leads to regression of symptoms and subsequent recovery.