Insulinoma - Diagnosis

Insulinoma diagnostics is based on the patient's examination and anamnesis. From the anamnesis it is possible to determine the time of the attack, its connection with food intake. The development of hypoglycemia in the morning hours, as well as when skipping a meal, with physical and mental stress, in women on the eve of menstruation speaks in favor of insulinoma. One of the constant symptoms characteristic of it is considered to be a feeling of hunger, although the latter is far from an obligatory sign of the disease. Also, the widespread idea of increased appetite in these patients is not true. It is created due to the fact that patients themselves usually discover a quick and pronounced effect from eating food, which prevents or stops an attack that has just begun. This makes them carry flour and sweets with them as a "medicine", although they do not feel a special need for food as such. Physical examination methods do not play a special role in the diagnosis of insulinoma due to the small size of the neoplasms.

An important place among the functional diagnostic methods for this type of tumors rightfully belongs to various tests. The classic Wipple triad has not lost its importance, which can be determined in clinical conditions by conducting a fasting test. In 1938, Wipple postulated that if a patient experiences hypoglycemia attacks on an empty stomach and the blood sugar level falls below 50 mg% (2.7 mmol/l), and the attack itself is stopped by intravenous administration of glucose, then such a patient should be expected to have an insulin-secreting tumor. Indeed, in a healthy person, night and longer fasting moderately reduces the level of glycemia and, what is especially characteristic, significantly reduces the insulin content in the blood. The latter may practically not be detected. When there is a tumor constantly producing an excessive amount of insulin, the secretion of which is not subject to physiological regulation mechanisms, then under fasting conditions, prerequisites for the development of hypoglycemia are created, since there is no glucose intake from the intestine, and liver glycogenolysis is blocked by tumor insulin. A hypoglycemic attack with a drop in glucose levels below 2.7 mmol / l in most patients occurs 12-16 hours after the start of fasting. Along with this, in some patients, its period before the onset of hypoglycemic manifestations lasts from several hours to several days. In very rare cases, a fasting test does not confirm the presence of the Wipple triad, despite a morphologically verified pancreatic tumor. A fasting test can be performed using a biostator. Thus, to maintain the glycemia level at least up to 4.4 mmol/l, glucose consumption in normal people will be no more than 0.59 mg/(kg-min), while in patients with insulinoma it will be no less than 1.58 mg/(kg-min). However, it is impossible to evaluate such a test clinically.

Due to the direct effect of hypoglycemia on the central nervous system, EEG is of considerable interest. It has no diagnostic value in the interictal period. This method is of particular importance during acute hypoglycemia. In its initial stages, the EEG alpha rhythm becomes more frequent and increases in amplitude, and as the attack develops, during the period of stunning, the alpha rhythm waves become slower and suppressed, and slow A-waves appear, indicating a decrease in the level of consciousness. After the patient is injected with a glucose solution into the vein, rapid restoration of the alpha rhythm can be observed. It is advisable to use an electroencephalogram when performing a fasting test, since A-waves can be recorded even in the absence of obvious clinical manifestations of hypoglycemia, which helps to avoid its severe manifestations. Since 1961, a test with tolbutamide (rastinone) has been introduced into clinical practice for the differential diagnosis of insulinoma. The latter, when administered intravenously to patients with functioning beta-cell neoplasms, reduces the glycemia level by more than 50% after 20-30 minutes, while in patients with hypoglycemia of other genesis - by less than 50%. During the entire test (1.5 hours), the glucose level should be recorded every 15 minutes. The test is conveniently carried out under EEG control for early detection of hypoglycemic manifestations in the central nervous system. If the latter are present, the test is stopped by intravenous infusion of glucose solution. Another stimulating test in the diagnosis of insulinoma is a test with L-leucine, which is given orally at a rate of 0.2 g per 1 kg of the patient's body weight. The maximum effect occurs after 30-45 minutes. The test is assessed and technically carried out similarly to the rastinon load. Both tests are contraindicated in patients with an initial glycemia level of less than 2.3 mmol / l.

Diagnosis of insulinoma is based on the use of some other tests, for example, with glucose, glucagon, arginine, cortisol, adrenaline, calcium gluconate, but they are less specific.

Among the laboratory parameters in case of suspected insulinoma, a special place is occupied by the study of immunoreactive insulin (PRI). As practice has shown, not all cases with proven insulinoma have elevated values. Moreover, in addition to its normal levels, there are also reduced ones. Further study of this issue demonstrated that the secretion of proinsulin and C-peptide are more valuable, and the values of immunoreactive insulin (IRI) are usually assessed simultaneously with the glycemia level. An attempt was made to combine these two parameters using the insulin-to-glucose ratio. In healthy people, it is always below 0.4, while in most patients with insulinoma it is higher and often reaches 1. Currently, great importance is attached to the C-peptide suppression test. Within an hour, the patient is given insulin intravenously at a rate of 0.1 U/kg. If the C-peptide level decreases by less than 50%, one can assume the presence of an insulin-secreting tumor. Not so long ago, its existence could be proven only during surgery by careful examination and palpation of the pancreas. However, the vast majority of these neoplasms do not exceed 0.5-2 cm in diameter, so in 20% of patients the tumor cannot be detected during the first, and sometimes second and third surgery - occult forms. Malignant insulinomas make up 10-15%, a third of which metastasize. In 4-14% of patients, insulinomas are multiple, about 2% of neoplasms are located outside the pancreas - dystopia. The impossibility of preliminary judgment on the scope of surgical intervention in each specific case forces the surgeon to be ready to perform everything from a relatively simple enucleation of an easily detected adenoma to total pancreatectomy. For the purpose of topical diagnostics of insulinomas, three main methods are currently used: angiography, portal system catheterization and computed tomography of the pancreas.

Angiographic diagnostics of insulinomas is based on hypervascularization of these neoplasms and their metastases. The arterial phase of the tumor is represented by the presence of a hypertrophied artery feeding the tumor and a fine network of vessels in the area of the lesion. The capillary phase is characterized by a local accumulation of contrast agent (tumor spot symptom) in the area of the neoplasm. The venous phase is manifested by the presence of a vein draining the tumor. Signs of the capillary phase are detected more often than others. The positive result of the angiographic method is 60-90%. The greatest difficulties arise in detecting tumors up to 1 cm in diameter and in localizing neoplasms in the head of the pancreas.

The difficulties of localizing insulinomas using computed tomography are due to their small size. Such tumors, located in the thickness of the pancreas, do not change its configuration, and do not differ from normal tissue of the gland in terms of the absorption coefficient of X-rays, which makes them negative. The reliability of the method is 50-60%. Recently, a method of catheterization of the portal system has been proposed to determine the level of IRI in the veins of various parts of the pancreas. Its maximum value can be used to judge the localization of a functioning neoplasm. Due to technical difficulties, this method is usually used when the results of the study obtained during the two previous ones are negative.

Echography in diagnostics of insulinomas has not received wide application due to excess body weight of patients, since fatty tissue is a significant obstacle for ultrasound wave. Nevertheless, this method can be useful in intraoperative localization of neoplasms.

Ultimately, topical diagnostics using modern research methods in 80-95% of patients with insulinomas allows us to establish the localization, size, prevalence and malignancy (metastases) of the tumor process before surgery.

Differential diagnosis of insulinoma is carried out with non-pancreatic tumors, nesidioblastosis and artificially induced hypoglycemia.

Non-pancreatic tumors with hypoglycemia differ in their size. Most of them have a mass of over 2000 g and a comparatively smaller number - no more than 1000 g. The clinical picture and the nature of glycemia in these cases are almost identical to the clinical picture in patients with insulinoma. Most often, liver tumors develop - Nadler-Wolf-Eliott syndrome, adrenal cortex tumors - Anderson syndrome and various mesenchymomas - Doege-Petter syndrome. Neoplasms of this size are easily detected by physical examination methods or conventional X-rays.

A special place in the differential diagnostics of insulinoma is occupied by hypoglycemia in children caused by the total transformation of the ductal epithelium of the pancreas into b-cells. This phenomenon is called nesidioblastosis. The latter can only be determined morphologically. Clinically, it is manifested by severe hypoglycemia that is difficult to correct, which forces us to take urgent measures to reduce the mass of pancreatic tissue. The generally accepted volume of surgery is 80-95% resection of the gland.

Great difficulties in diagnosing insulinoma may arise when patients secretly use exogenous insulin preparations. This should be kept in mind when examining health workers. The motives for artificially induced hypoglycemia in most cases remain unclear even after consulting a psychiatrist. The main evidence of exogenous insulin use is the presence of insulin antibodies in the patient's blood, as well as a low C-peptide content with a high level of total IRI. Endogenous secretion of insulin and C-peptide is always in equimolar ratios.

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