Symptoms of generalized lipodystrophy

The leading symptom of generalized lipodystrophy syndrome is the complete or partial disappearance of the subcutaneous fat layer in patients. According to this feature, two clinical forms of generalized lipodystrophy can be distinguished: 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 with a protruding navel. In the partial form, subcutaneous fat disappears mainly from the trunk, limbs, but not from the face, and some patients even have an increase in subcutaneous fat on the face and in the supraclavicular areas. However, both forms of generalized lipodystrophy reveal quite specific, similar metabolic disorders with the same end results in changing carbohydrate and lipid metabolism. The main ones are insulin resistance, hyperinsulinemia, hyperglycemia, hyperlipidemia. In some cases, not only impaired glucose tolerance develops, but also diabetes mellitus. The disease can occur at any age: in children and in the elderly.

Chronic endogenous hyperinsulinemia largely determines the characteristic appearance of patients, since it leads to the predominance of anabolic processes over catabolic ones. This to a certain extent explains the frequent true hypertrophy of skeletal muscles, moderate prognathism, enlargement of the hands and feet, visceromegaly, phlebomegaly, thickening of all layers of the dermis, hypertrichosis in generalized lipodystrophy syndrome. Chronic endogenous hyperinsulinemia makes itself known by periodic attacks of severe weakness, sweating, tremors, a strong feeling of hunger that occur after physical exertion, during long breaks between meals, and sometimes spontaneously. Insulin resistance in the body of patients with generalized lipodystrophy syndrome worsens over the years and leads to the gradual development of moderate carbohydrate intolerance on average 7-12 years after the onset of the disease. Against this background, hypoglycemia attacks do not disappear, which indicates that hyperinsulinemia persists in patients.

Chronic endogenous hyperinsulinemia in generalized lipodystrophy syndrome promotes excessive proliferation of connective tissue in parenchymatous organs, in the mucous membrane of the gastrointestinal tract and in the walls of blood vessels. Therefore, this disease often causes fibrous changes in the liver and pancreas, as well as dystrophic changes in the stomach and intestines with corresponding symptoms. Hypertrophy of connective tissue formations of the vascular wall (especially large ones) leads to narrowing of their lumen in generalized lipodystrophy syndrome. As a result, patients experience early onset of cardiovascular disorders and deterioration of blood supply to internal organs.

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

Hypothalamic regulation disorder in generalized lipodystrophy syndrome leads to an increase in the basal metabolic rate without disruption of the thyroid gland function, the appearance of hyperpigmentation areas in places where clothing rubs, and frequent lactorea. Hypothalamic disorders in this disease, along with the effect of chronic hyperinsulinemia on the connective tissue formations of the ovaries, cause frequent disruption of ovarian function with various manifestations of hypoluteinism, and in 23-25% of cases, the development of hyperandrogenic dysfunction of the ovaries 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 come across any reports in the literature on the results of studies in this direction, although there is an indication of hypermetabolism in patients with generalized lipodystrophy.

During routine examination of patients with generalized lipodystrophy syndrome, the following changes are usually detected. In the clinical blood test - true moderate erythrocytosis and hyperhemoglobinemia. In the urine - often proteinuria. In the biochemical blood test, attention is drawn to a significant increase in the content of triglycerides, non-esterified fatty acids, total cholesterol and its esters, a low content of ketone bodies even with a pronounced violation of carbohydrate metabolism; acceleration of sedimentation tests, decreased activity of alkaline phosphatase, increased activity of transaminases, moderate hyperbilirubinemia, which is characteristic of fatty degeneration of the liver. An increased content of total protein in the blood plasma is almost always noted. In survey craniography, frequent findings are calcification of the dura mater in the frontal and parietal regions, as well as behind the back of the sella turcica, hyperpneumatization of the sinus of the sphenoid bone, in some patients a large sella turcica in the form of a recumbent oval is determined radiographically. In electroencephalography, signs of dysfunction of the mesodiencephalic structures of the brain are found in almost all patients. The ECG, as a rule, reveals hypertrophy of the myocardium of the left ventricle with concomitant metabolic or ischemic changes; signs of conduction disturbance in the left leg of the bundle of His are common. During examination by an ophthalmologist, spastic angioretinopathy is found in most patients who do not suffer from constant hypertension.

Against the background of pronounced basal and stimulated hyperinsulinemia present in the generalized lipodystrophy syndrome, most patients have normal or slightly reduced glucose tolerance. At the same time, impaired correlation relationships between carbohydrate metabolism indices and the functional state of the pancreas, as well as between carbohydrate and lipid metabolism indices, have been revealed. In generalized lipodystrophy syndrome, a slight decrease in IRI binding to specific insulin receptors on monocytes has been noted. The index of sensitivity to exogenous insulin in patients is slightly reduced and does not differ from that in insulin-independent diabetes mellitus. This indicates that the cause of insulin resistance in generalized lipodystrophy syndrome has an extrareceptor origin.

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

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

It has been shown that in patients with generalized lipodystrophy syndrome, the degree of increase in the content of such lipid metabolism indicators in the blood plasma as free cholesterol, free fatty acids, triglycerides and the total fraction of total lipids is directly dependent on the magnitude of hyperinsulinemia.

It has been established that in generalized lipodystrophy syndrome, the severity of cardiovascular disorders is also directly dependent on the magnitude of hyperinsulinemia. As already noted, patients with generalized lipodystrophy syndrome often have ovarian dysfunction, manifested in the most severe cases by polycystic ovary syndrome with pronounced hyperandrogenism. In generalized lipodystrophy syndrome, a direct dependence of the degree of ovarian hyperandrogenism on the magnitude of hyperinsulinemia has been found.

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

Conventionally, it is possible to identify 4 types of the disease course depending on the age of its onset. For all types of the generalized lipodystrophy syndrome course, the most characteristic were generalized lipodystrophy, signs of early fatty liver degeneration, and clinical signs of chronic endogenous hyperinsulinemia (periodic hypoglycemia and the birth of large children weighing over 4 kg in women with generalized lipodystrophy syndrome), which persisted even after the addition of decreased carbohydrate tolerance. Type I includes patients in whom generalized lipodystrophy syndrome manifested itself at the age of 4-7 years. For most patients in this group, manifestation of generalized lipodystrophy was characteristic of total lipoatrophy. At the same time, a long asymptomatic course of the disease was noted, when lipodystrophy was considered only as a cosmetic defect.

In patients with type I course of generalized lipodystrophy syndrome, minor gynecological status disorders were observed: fertility was usually preserved. The occurrence of a moderate decrease in glucose tolerance and changes in the cardiovascular system - hypertension and myocardial hypertrophy with metabolic changes - was noted at a late stage (30-35 years) after the appearance of the first clinical signs of the disease.

Type II of the generalized lipodystrophy syndrome was observed in patients who became ill during puberty. In this group, both types of redistribution of subcutaneous fat (total lipoatrophy and hypermuscular lipodystrophy) were equally common, and were the first signs of the disease. A high frequency of hereditary forms was noted. The onset of the disease was accompanied by the appearance of hyperpigmentation in places where clothing rubs. Most patients with type II of the generalized lipodystrophy syndrome suffered from early pronounced ovarian function disorders, often manifested by ovarian hyperandrogenism syndrome.

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

Clinical type III of the course of generalized lipodystrophy syndrome was observed in women aged 20-35 years, and the immediate cause of the disease was pregnancy or childbirth. In patients of this group, the disease manifested itself as hypertension, reversible diabetes of pregnancy, enlargement of the facial skeleton, hands and feet. Generalized lipodystrophy (mainly of the hypermuscular lipodystrophy type), unlike other clinical variants of generalized lipodystrophy syndrome, was added later (after 2-4 years).

In patients with type III of generalized lipodystrophy syndrome, early changes in the cardiovascular system similar to those in patients of group II were noted. Moderate carbohydrate metabolism disorders were detected in 35% of patients of group III 6-12 years after the onset of the disease. In addition, a high frequency of lactorea and large (at the upper limit of the norm) sizes of the sella turcica were characteristic.

And finally, type IV of the course of generalized lipodystrophy syndrome includes patients with a late (after 35 years) onset of the disease. For patients in this group, the following were characteristic: manifestation of generalized lipodystrophy syndrome in the form of lipodystrophy of both types, various gynecological disorders, but a low frequency of ovarian hyperandrogenism and lactorea; rapid occurrence and progression of carbohydrate metabolism disorders and cardiovascular complications. In this variant of generalized lipodystrophy syndrome, some frequently encountered manifestations of the disease are sometimes absent.

The presented data show that the most favorable prognostic type is type I of the generalized lipodystrophy syndrome, and the least favorable is type II, the frequency of which is 37.7%. It is noted that disorders of the cardiovascular system occur with the same frequency in all described clinical variants of the generalized lipodystrophy syndrome, which allows us to consider them not a complication, but a manifestation of the generalized lipodystrophy syndrome.

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