Insulinoma: diagnosis

Diagnosis of insulinoma is based on a patient's examination and anamnesis. From an anamnesis it is possible to reveal time of occurrence of an attack, its or his communication or connection with reception of nutrition. The development of hypoglycemia in the morning hours, as well as missed the next meal, with physical and mental stress, in women on the eve of menstruation speaks for insulinoma. One of the constant symptoms characteristic of it is considered to be a feeling of hunger, although the latter is by no means an obligatory sign of the disease. Also, the widespread perception of increased appetite in these patients does not correspond to reality. It is created due to the fact that usually the patients themselves discover a quick and pronounced effect on the intake of food, which prevents or cures the scarcely begun attack. This makes them carry with them flour and sweet as a "medicine", although they do not feel a special need for food as such. The physical methods of investigation in the diagnosis of insulinoma do not play a special role in view of the small size of the tumors.

An important place among the functional diagnostic methods in this form of tumors is due to various tests. The classical triad Wipple has not lost its value, which in clinical conditions can be ascertained when conducting a test with starvation. In 1938, Wipple postulated that if a patient has fasting hypoglycaemic episodes and the blood sugar level falls below 50 mg% (2.7 mmol / l), and the attack is stopped by an intravenous glucose injection, then such a patient should be expected insulin-secreting tumor. Indeed, in a healthy person, night and longer starvation moderately reduces the level of glycemia and, what is especially characteristic, significantly reduces the insulin content in the blood. The latter can practically not be determined. When there is a tumor that constantly produces an excessive amount of insulin, the secretion of which does not obey the physiological mechanisms of regulation, in conditions of starvation, prerequisites for the development of hypoglycemia are created, since there is no glucose from the intestine, and hepatic glycogenolysis is blocked by tumor insulin. Hypoglycemic attack with a drop in glucose levels below 2.7 mmol / L in most patients occurs 12-16 hours after the onset 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, the starvation test does not confirm the presence of the Wipple triad, despite the morphologically verified pancreatic tumor. A test with starvation can be carried out using a biostator. Thus, in order to maintain the level of glycemia to at least 4.4 mmol / L, the glucose consumption in normal people is no more than 0.59 mg / kg-min, whereas in patients with insulinoma, not less than 1.58 mg / kg -min). However, clinically such a test is impossible to assess.

In connection with the direct influence of hypoglycemia on the activity of the central nervous system, the EEG investigation is of considerable interest. In the interictal period, it has no diagnostic value. This method is especially important in the period of acute hypoglycemia. In its initial stages, the alpha-rhythm of the EEG increases and increases in amplitude, and as the attack develops, during the stunning period, the alpha-rhythm waves become smaller and depressed, slow A waves appear, indicating a decrease in the level of consciousness (Figure 49, a) . After a glucose solution is administered to a patient in a vein, rapid restoration of the alpha rhythm can be observed. An electroencephalogram should be used in a fasting test, since A-waves can be recorded even in the absence of obvious clinical manifestations of hypoglycemia, which avoids its severe manifestations. Since 1961, a trial with tolbutamide (rastonone) has been introduced into clinical practice for the differential diagnosis of insulinoma. The latter, when administered intravenously in patients with functioning beta-cell neoplasms, reduces the level of glycaemia after 20-30 min by more than 50%, while in patients with hypoglycemia of another genesis it decreases by less than 50%. During the entire sample (1.5 h) every 15 minutes, you need to record the glucose level. The sample is conveniently carried out under the control of the EEG for early detection of hypoglycemic manifestations in the central nervous system. In the presence of the latter, the sample is stopped by an intravenous infusion of a glucose solution. Another stimulating test in the diagnosis of insulinoma is a sample with L-leucine, which is given orally at the rate of 0.2 g per kg of body weight of the patient. The maximum effect occurs in 30-45 minutes. The sample is evaluated and technically performed similarly to the load of the planton. Both tests are contraindicated in patients with a baseline glycemia level of less than 2.3 mmol / l.

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

Among laboratory indicators for suspected insulin, a special place is occupied by the study of immunoreactive insulin (PRI). As practice has shown, far from all cases with proven insulinoma there are its increased values. Moreover, in addition to its normal levels, there are lowered ones. Further study of this issue demonstrated that the values of proinsulin and C-peptide secretion are more valuable, and the values of immunoreactive insulin (IRI) are commonly estimated simultaneously with the level of glycemia. Using the ratio of insulin to glucose, an attempt was made to combine these two parameters. In healthy people, it is always below 0.4, while in the majority of patients with insulinoma it is higher and often reaches 1. At present, great importance is attached to the test with suppression of the C-peptide. Within an hour, the patient is injected intravenously with insulin at a rate of 0.1 U / kg. When the level of C-peptide is reduced by less than 50%, one can assume the presence of an insulin secretory tumor. Not so long ago, its existence could be proved only by surgery through careful examination and palpation of the pancreas. However, the overwhelming majority of these neoplasms do not exceed 0.5-2 cm in diameter, therefore, in 20% of patients at the first and sometimes second and third operations the tumor can not be detected - occult forms. Malignant insulinomas are 10-15%, a third of which metastasizes. In 4-14% of patients, insulinomas are multiple, about 2% of the neoplasms are located outside the pancreas - dystopia. The impossibility of a preliminary judgment on the amount of surgical intervention in each particular 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 purposes of topical diagnosis of insulin, three methods are currently used: angiographic, catheterization of the portal system, and the method of computed tomography of the pancreas.

Angiographic diagnosis of insulin is based on the hypervascularization of these neoplasms and their metastases. The arterial phase of the tumor is represented by the presence of a hypertrophic, tumor-feeding artery and a thin network of vessels in the region of the lesion. The capillary phase is characterized by a local accumulation of a contrast agent (a symptom of a tumor spot) in the area of neoplasm. The venous phase is manifested by the presence of a vein swelling tumor. More often than not, signs of a capillary phase are found. The positive result of the angiographic method is 60-90%. The greatest difficulties arise when detecting tumors up to 1 cm in diameter and localizing neoplasms in the head of the pancreas.

Difficulties of localization of insulin with the help of computed tomography are due to their small size. Similar tumors, located in the thickness of the pancreas, do not change its configuration, and the coefficient of X-ray absorption does not differ from the normal tissue of the gland, which makes them negative. The reliability of the method is 50-60%. Recently, a method of catheterization of the portal system has been proposed with the purpose of determining the level of IRI in the veins of various parts of the pancreas. By its maximum value, one can judge the localization of a functioning neoplasm. This method because of technical difficulties is usually used for negative results of the research, obtained during the previous two.

Echography in the diagnosis of insulin wide spread has not been received because of the excessive body weight of patients, since fatty tissue is a significant obstacle to the ultrasonic wave. Nevertheless, this method can be useful for intraoperative localization of neoplasms.

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

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

Nonpancreatic tumors with hypoglycemia differ in size. Most of them have a mass of more than 2000 g and a relatively smaller number - not more than 1000 g. The clinical picture and the nature of glycemia in these cases are almost identical to the clinic in patients with insulinoma. Most often develop liver tumors - Nadler-Wolf-Eliott syndrome, adrenal cortex tumors - Anderson syndrome and various mesenchymomas - Doege-Petter syndrome. Similar size neoplasms are easily identified with physical methods of examination or conventional radiographic ones.

A special place in the differential diagnosis of insulinomas is occupied by hypoglycemia in children caused by total transformation of the pancreatic epithelium into 3-cells, which was called nonsidioblastosis, which can only be established morphologically, it manifests itself as severe, difficult to correct hypoglycemia, which forces us to take urgent measures to reduce the weight of the pancreatic tissue.The usual volume of surgery - 80-95% of the resection of the gland.

Great difficulties in the diagnosis of insulinoma can occur with secret exogenous use of insulin drugs. First of all, this should be remembered when examining health workers. The motives for artificially induced hypoglycemia remain unclear in most cases even after a psychiatrist's consultation. The main evidence for exogenous use of insulin is the presence in the patient's blood of antibodies to insulin, as well as low content of C-peptide at a high level of total IRI. Endogenous secretion of insulin and C-peptide is always in equimolar ratios.

[1], [2], [3], [4], [5], [6], [7], [8]