Symptoms of generalized lipodystrophy

The leading symptom of the syndrome of generalized lipodystrophy is complete or partial disappearance in patients with the subcutaneous fat layer. On this basis, there are 2 clinical forms of generalized lipodystrophy: total and partial.

The total form of generalized lipodystrophy is characterized by the disappearance of subcutaneous fat from the face and all other parts of the body, often there is protrusion of the navel. In the partial form, the subcutaneous adipose tissue disappears mainly from the trunk and limbs, but not from the face, and in some patients there is even an increase in subcutaneous fat on the face and in the supraclavicular areas. However, in both forms of generalized lipodystrophy, very definite, similar metabolic disturbances with the same end results in changing carbohydrate and lipid metabolism are revealed. The main ones are insulin resistance, hyperinsulinemia, hyperglycemia, hyperlipidemia. In some cases, not only a violation of glucose tolerance, but also diabetes mellitus. The disease can occur at any age: in children and in the elderly.

Chronic endogenous hyperinsulinemia causes a largely characteristic appearance of patients, since it leads to the predominance of anabolic processes over catabolic ones. This, to some extent, explains the true hypertrophy of skeletal musculature, moderate prognathism, enlarged brushes and feet, viscromegalia, phlebomegaly, thickening of all layers of the dermis, hypertrichosis, frequent in the syndrome of generalized lipodystrophy . Chronic endogenous hyperinsulinemia makes itself felt by periodic attacks of severe weakness, sweating, trembling, severe hunger, which occur after physical exertion, with large breaks between meals, and sometimes spontaneously. Insulin resistance in patients with generalized lipodystrophy syndrome has been exacerbated over the years and leads to a gradual development of moderate tolerance of carbohydrates on average 7 to 12 years after the onset of the disease. Against this background, attacks of hypoglycemia do not disappear, which indicates the preservation of hyperinsulinemia in patients.

Chronic endogenous hyperinsulinemia in the syndrome of generalized lipodystrophy promotes an overgrowth of connective tissue in the parenchymal organs, in the mucosa of the gastrointestinal tract and in the walls of the vessels. Therefore, with this disease often there are fibrotic changes in the liver and pancreas, as well as dystrophic changes in the stomach and intestines with the corresponding symptomatology. Hypertrophy of connective tissue formations of the vessel wall (especially large ones) leads to the narrowing of their lumen in the syndrome of generalized lipodystrophy. As a result, patients experience an early occurrence of cardiovascular disorders and a worsening of blood supply to internal organs.

Characteristic of the syndrome of generalized lipodystrophy, significant hyperlipidemia, which is the result of the inability of adipocytes to deposit neutral fats, leads to a rapid development of fatty liver. Clinically, this condition is characterized by severe hepatomegaly, a feeling of bitterness and dryness in the mouth in the morning, with heaviness and dull pain in the right upper quadrant. In combination with the changes in major vessels characteristic of the generalized lipodystrophy syndrome, hyperlipidemia in this disease contributes to the appearance of hypertension and ischemic changes in the myocardium at a young age.

The disorder of hypothalamic regulation leads to a generalized lipodystrophy syndrome in the syndrome of increased basal metabolism without disturbing thyroid function, the appearance of areas of hyperpigmentation in places of clothing friction, and the frequent occurrence of lactorrhoea. Hypothalamic disorders in this disease, along with the effects of chronic hyperinsulinemia on connective tissue formation of the ovaries, cause frequent disruption of the ovarian function with various manifestations of hypolyutenism, and in 23-25% of cases - the development of hyperandrogenic ovarian dysfunction with pronounced virilization phenomena.

An important symptom of generalized lipodystrophy can be considered a state of hypermetabolism, a violation of food thermogenesis. We assume that this may be one of the important factors in the pathogenesis of the disease. We have not met in the literature reports on the results of research in this direction, although there is evidence of hypermetabolism in patients with generalized lipodystrophy.

At routine inspection at patients with a syndrome of the generalized lipodystrophy usually following changes are found out. In the clinical analysis of blood - true moderate erythrocytosis and hyperhemoglobinemia. In urine - often proteinuria. In the biochemical study of blood, attention is drawn to a significant increase in the content of triglycerides, unesterified fatty acids, total cholesterol and its esters, a low content of ketone bodies, even with a marked violation of carbohydrate metabolism; acceleration of sediment samples, decreased activity of alkaline phosphatase, increased activity of transaminases, moderate hyperbilirubinemia, which is characteristic of fatty liver. Almost constantly there is an increased content of total protein in the blood plasma. With survey craniography, frequent findings are calcification of the dura mater in the frontal and parietal areas, as well as behind the back of the Turkish saddle, hyperpneumatization of the sinus of the underlying bone, and in a number of patients a large Turkish saddle in the form of a recumbent oval is determined radiographically. With electroencephalography, practically all patients show signs of dysfunction of mesodiencephalic structures of the brain. On the ECG, as a rule, hypertrophy of the left ventricular myocardium with accompanying metabolic or ischemic changes is detected; regular signs of a violation of conductivity in the system of the left leg of the Hiss beam are regular. When examined by an oculist in most patients who do not suffer from constant hypertension, spastic angioretinopathy is found.

Against the background of generalized lipodystrophy in the syndrome of severe basal and stimulated hyperinsulinemia, normal or slightly decreased glucose tolerance was found in most patients. At the same time, disturbed correlation relationships between the indices of carbohydrate metabolism and the functional state of the pancreas, as well as between the parameters of carbohydrate and fat metabolism, were revealed. In the syndrome of generalized lipodystrophy, there was a slight decrease in the binding of IRI to specific insulin receptors on monocytes. The index of sensitivity to exogenous insulin in patients is slightly reduced and does not differ from that for non-insulin-dependent diabetes mellitus. This indicates that the cause of insulin resistance in the syndrome of generalized lipodystrophy has an off-receptor origin.

When determining the reserves of pituitary hormones in patients with generalized lipodystrophy syndrome, an unreliable increase in the basal level of prolactin was detected: the maximum prolactin level in response to stimulation with tyroliberin is significantly higher than in normal.

When determining the pituitary reserves of growth hormone in patients with the syndrome of generalized lipodystrophy, no differences were found in comparison with the norm.

It was shown that in patients with the syndrome of generalized lipodystrophy, the degree of increase in plasma levels of such lipid metabolism indicators as free cholesterol, free fatty acids, triglycerides and total fraction of total lipids is directly related to the magnitude of hyperinsulinemia.

It was found that in the syndrome of generalized lipodystrophy, the severity of cardiovascular disorders is also directly related to the magnitude of hyperinsulinemia. As already noted, in patients with the syndrome of generalized lipodystrophy, there are often violations of ovarian function, manifested in the most severe cases of polycystic ovary syndrome with severe hyperandrogenia. In the syndrome of generalized lipodystrophy, a direct relationship between the degree of ovarian hyperandrogenia and the magnitude of hyperinsulinemia was found.

These data, along with clinical observations, allow us to conclude that hyperinsulinemia is one of the leading factors in the violation of hormone-metabolic relationships and the formation of a clinical picture in the syndrome of generalized lipodystrophy.

Conditionally, it is possible to identify 4 types of course of the disease, depending on the age of its onset. For all types of generalized lipodystrophy syndrome, generalized lipodystrophy, signs of early fatty liver dystrophy, and clinical signs of chronic endogenous hyperinsulinemia (periodic hypoglycemia and birth in patients with generalized lipodystrophy syndrome of women of large children weighing more than 4 kg) were most typical for the generalized lipodystrophy syndrome, which persisted and after the addition of a decrease in tolerance to carbohydrates. Type I refers to patients who developed syndrome of generalized lipodystrophy at the age of 4-7 years. For the majority of patients in this group, the generalized lipodystrophy was characterized by the type of total lipoatrophy. In this case, there was a long asymptomatic course of the disease, when lipodystrophy was considered only as a cosmetic defect.

Patients with type I syndrome of generalized lipodystrophy had a low degree of violations of the gynecological status: fertility, as a rule, is preserved. The emergence of a moderate decrease in glucose tolerance and changes in the cardiovascular system - hypertension and myocardial hypertrophy with metabolic changes - was noted in the long term (after 30-35 years) after the appearance of the first clinical signs of the disease.

II type of course of the syndrome of generalized lipodystrophy was observed in patients who fell ill during puberty. In this group, both types of redistribution of subcutaneous fat (total, lipoatrophy and hypermuscular lipodystrophy) were encountered with equal frequency, which were the first signs of the disease. High frequency of hereditary forms was noted. The onset of the disease was accompanied by the appearance of hyperpigmentation in places of friction clothing. The majority of patients with type II syndrome of generalized lipodystrophy suffered early manifestations of ovarian function disorders, often manifested by ovarian hyperandrogenism syndrome.

The described group of patients is characterized by a rapid development of a violation of tolerance to carbohydrates, as well as pronounced changes in the cardiovascular system in the form of persistent hypertension, clinical and ECG signs of myocardial ischemia.

III clinical type of course syndrome of generalized lipodystrophy occurred in women 20-35 years old, and the immediate cause of the disease were pregnancy or childbirth. In patients of this group, the disease manifested by hypertension, reversible diabetes of pregnant women, enlargement of the facial skeleton, hands and feet. Generalized lipodystrophy (mainly by the type of hypermuscular lipodystrophy), unlike other clinical variants of the syndrome of generalized lipodystrophy, was joined later (2-4 years later).

Patients with type III syndrome of generalized lipodystrophy noted an early appearance of changes in the cardiovascular system, similar to those in group II patients. Moderate disorders of carbohydrate metabolism were detected in 35% of patients in group III 6-12 years after the onset of the disease. In addition, the characteristic frequency was a large lactorrhea and large (at the upper limit of the norm) the size of the Turkish saddle.

And, at last, IV type of course of the syndrome of generalized lipodystrophy includes patients with late (after 35 years) onset of the disease. Patients of this group were characterized by: manifestation of the syndrome of generalized lipodystrophy in the form of lipodystrophy of both types, a variety of gynecological disorders, but a small frequency of ovarian hyperandrogenism and lactorrhea; rapid occurrence and progression of violations of carbohydrate metabolism and cardiovascular complications. With this version of the syndrome of generalized lipodystrophy, sometimes there are some common manifestations of the disease.

These data show that the most favorable prognostic attitude is type I syndrome generalized lipodystrophy, and the least favorable type II, the frequency of which is 37.7%. It was noted that violations from the cardiovascular system occur with the same frequency in all described clinical variants of the syndrome of generalized lipodystrophy, which makes it possible to consider them not a complication, but a manifestation of syndromageralized lipodystrophy.

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