ADDISONOVA DISEASE (morbus Addisoni; synonym: bronzed disease, chronic primary insufficiency of adrenal glands, insufficiency of adrenal glands) — the disease caused by bilateral defeat of bark of adrenal glands and switching off (akortitsizm) or reduction (gipoadrenokortitsizm) of products of adrenal hormones. The English doctor is called by name Addison (see), for the first time described it in 1849. The disease comes to light more often at the age of 20 — 40 years, is equally frequent among men and women. Spread of the Addisonovy disease fluctuates from 0,03 to 0,1 on 10 000 population.
Addisonov a disease results from destructive processes of various origin in bark of adrenal glands. Tuberculosis (50 — 85% of cases) which develops as a result of a hematogenous disseminirovaniye is the most frequent reason of primary defeat of bark of adrenal glands; usually find specific changes in easy and other bodies in patients with the Addisonovy disease. Cases of the isolated damage of adrenal glands are sometimes observed.
Also hemorrhages in adrenal glands, thrombosis of vessels, syphilis, bilateral tumors or metastasises of cancer in adrenal glands, amyloids, a purulent inflammation of adrenal glands, a lymphogranulomatosis, histoplasmosis can be the cause of the Addisonovy disease. Addisonova a disease can develop also as a result of autoimmune damage of adrenal glands that is confirmed by increase in a caption of the circulating autoantibodies to tissue of adrenal glands. In some cases the disease can be caused by the disturbances in gipotalamo-pituitary system leading to reduction of secretion of AKTG or corticotropin-rileasing-factor. Seldom found family forms of the Addisonovy disease connected with an atrophy of bark of adrenal glands have hereditary character and come to light at gomozigot as a result of autosomal recessive mutation.
The pathological anatomy and a pathogeny
Damage of adrenal glands at the Addisonovy disease has character of widespread destructive or atrophic changes.
Destructive changes can be caused by various reasons. Most often they are connected with a bilateral adrenal tuberculosis. In the drawing the increased and condensed adrenal glands, with extensive fields of a tyromatosis which quite often contain deposits of salts of lime are visible. At microscopic examination on the periphery of sites of a tyromatosis specific inflammatory infiltration from light epithelial cells with impurity of lymphoid elements is found. Here it is possible to meet the single tubercular granulomas containing multinucleate epithelial cells of Pirogov — Langkhansa. At special colourings approximately in half of cases in fringe regions of a tyromatosis mycobacteria of tuberculosis come to light. Tubercular process leads to almost checkmate of adrenal glands; cortical and brain fabric remains only in the form of the single small scattered ochazhok. In the remained sites of bark the atrophy of cells is noted. At a histochemical research in these cells decrease in content of cholesterol is found. At the expressed petrification of curdled masses development of cicatricial changes in retroperitoneal cellulose with formation of rough unions of adrenal glands with kidneys and a liver is observed.
Primary tumors of adrenal glands as well as metastasises of cancer in these glands, can be the cause of the Addisonovy disease only in cases of almost final fracture of adrenal fabric blastomatous process that is observed very seldom.
Destructive changes in adrenal glands as the reason of the Addisonovy disease can be caused also by the amyloidosis, histoplasmosis disseminated koktsidiomikozy. At the same time widespread bilateral defeat of preferential bast layer of adrenal glands is noted.
Atrophic changes. At an atrophy of adrenal glands find the expressed weight reduction of glands. Reduction of the sizes of bodies happens mainly at the expense of thickness of bark. Considerable thinning of a bast layer with disturbance of normal very tectonics of puchkovy and mesh zones is microscopically observed. In a puchkovy zone of bark, in addition to reduction of number of cells and their sizes, disorganization of an arrangement of cellular columns, decrease in maintenance of lipids and enzymatic activity in spongiocytes is noted. Decrease of the activity - 3 - beta oldegidrogenazy indicates a steroid insufficient synthesis of steroids. In periblasts of a puchkovy zone pseudo-tubular structures appear. In a mesh zone there are dystrophic changes with plentiful adjournment of lipofuscin in cells. The glomerular zone of bark remains most often intact. Marrow of adrenal glands undergoes minor changes. They consist in reduction of quantity of chromaffin cells and some increase in stromal fibrous structures.
According to modern representations, development of an atrophy of adrenal glands at the Addisonovy disease is the cornerstone of disturbance in immunological systems of an organism. Confirmation of such look is the expressed hyperplasia of goitrous gland which is almost constantly found at the Addisonovy disease with an atrophy of adrenal glands and lymphoid infiltration in fabrics of many parenchymatous bodies.
In some observations the combination of the Addisonovy disease to autoimmune diseases took place. According to other data, the atrophy of adrenal glands develops because of intoxication of an organism, perhaps, a virus origin.
Clinical displays of a disease are a consequence of falloff of hormonal activity of bark of adrenal glands. In an experiment on animals of manifestation, similar to the Addisonovy disease, arise after removal of cortical substance of adrenal glands.
The xanthopathy and mucous membranes at the Addisonovy disease arises owing to the strengthened chromogenesis of melanin that is connected by action of a desmoenzyme of the DOFA-oxidase on derivatives of a brentskatekhin (dioxyphenylalanine). Note close connection of a melanoderma with deficit of ascorbic acid and with melanoformic hormone. At the Addisonovy disease find reduction of number of basphilic elements in a hypophysis degranulation of basophiles, mainly from delta forms. Heart is reduced the sizes. Microscopically the brown acardiotrophia is defined the narrowing of a gleam of an aorta and large main vessels caused by adaptation of a vascular bed to conditions of long hypotonia Attracts attention. In a pancreas the hyperplasia of the insular device is sometimes noted; occasionally insulyarny adenomas meet. In these cases emergence of a hypoglycemia clinically is defined. Quite often find limfoidnokletochny infiltration in a thyroid gland some increase in intersticial fabric. In a stomach the atrophy to a mucous membrane and reduction of number of obkladochny cells is found. Sometimes there are surface erosions and small ulcers. In a liver and kidneys dystrophic changes are observed. Gonads undergo minor changes. In them moderate atrophic processes are found. Changes in a nervous system at the Addisonovy disease concern some sympathetic gangliyev and are expressed in processes of a sclerosis and atrophy. Such changes sometimes are found in the field of a celiac (solar) texture.
Addisonova a disease is caused by switching off or falloff of products glyuko-and mineralokortikoid (cortisol, Aldosteronum and corticosterone).
The clinical picture
the Disease develops slowly. The first signs — unmotivated weakness and bystry physical fatigue, weight loss. 99% of patients gradually have a xanthopathy (colors of suntan, golden-brown, dirty-brown, bronze) having diffusion character.
The xanthopathy amplifies the body parts which are exposed to a solyation or the strengthened friction. Strengthening of pigmentation of palmar lines, a dorsum of brushes and feet, areas of burn and postoperative hems is characteristic. in places of physiological adjournment of a pigment (nipples of mammary glands, generative organs). At 80% of patients pigmentation of a mucous membrane of an oral cavity is observed (tsvetn. fig. 2), vagina and rectum.
One of characteristic symptoms of the Addisonovy disease is hypotonia with decrease in preferential systolic pressure. Reduction of pulse pressure, minute volume of blood is observed. Heart is reduced in sizes, on an ECG decrease in a voltage of teeth, shift of a ST interval down, a negative tooth of T is noted.
At patients gastrointestinal disturbances are quite often observed (a siizheniye of appetite, a topshot, vomiting, a diarrhea, pains in a stomach). Gastric acidity is reduced, external secretion of a pancreas is reduced. Functions of a liver are broken (belkovoobrazovatelny, anti-toxic, glikogenoobrazovatelny). Increase in tolerance to glucose and signs of a relative hyper dysinsulinism as a result of a lack of glucocorticoids is characteristic.
Disturbance of electrolytic exchange is followed by increase in level of potassium and reduction of concentration of sodium and chlorides in blood serum. Release of potassium with urine decreases, and sodium and chlorides increases.
Changes of function of the central nervous system are characterized by a mental exhaustion, headaches, decrease in memory. In some cases acute psychoses can develop. On the electroencephalogram decrease of the activity of a cerebral cortex and emergence delta and teta-waves is observed.
Function of gonads at an easy form of the Addisonovy disease is broken seldom, at a severe form disturbance of a menstrual cycle at women and decrease in a potentiality at men is observed. Allocation with urine 17-keto-and 17 of oxycorticosteroids, and also Aldosteronum is considerably reduced. In blood the eosinophilia and a lymphocytosis come to light.
Carry Addisonova to the atypical (erased) forms of a disease a disease with characteristic clinical symptomatology, but without pigmentation. Pigmentation is so poorly expressed that usually is not fixed at inspection. The diagnosis of this form is possible only on the basis of data of a laboratory research.
Carry to atypical forms of the Addisonovy disease also the disease proceeding as a hypoaldosteronism (falloff of secretion and allocation of Aldosteronum with urine at normal secretion of glucocorticoids). This form of the Addisonovy disease is caused by the isolated defeat of a glomerular zone of bark of an unknown etiology. Clinically at the same time hypotonia and less expressed pigmentation is observed.
The isolated insufficiency of secretion of AKTG or corticotropin-rileasing-factor (diencephalic and pituitary form of the Addisonovy disease) is characterized by less expressed displays of a disease, positive test of Thorn — Labkharta (see. Thorn test ).
At the wrong treatment addisonichesky crisis, especially against the background of an acute infection, intoxication, toxicoinfection, operation, a physical injury can develop. Increase of symptoms of a krizaaddisonovy disease can be gradual (within several days) and bystry (several hours).
At crisis the aggravation of all clinical displays of a disease is observed, there is pernicious vomiting, prostration, symptoms of dehydration accrue, arterial pressure decreases, there is a smell of acetone from a mouth and acetonuria, is frequent — clonic spasms and the meningeal syndrome which is mistakenly diagnosed as tubercular meningitis. Without treatment consciousness disappears, and the patient fells into a coma which can end with a lethal outcome. During crisis decrease in level of sugar in blood to 50 — 30 mg of %, increase in residual nitrogen and urea of blood, a leukocytosis, acceleration of ROE, emergence in urine of hyaline, granular cylinders, protein is observed. Allocation with urine of metabolites of androgens and glucocorticoids decreases.
the Diagnosis is based on a characteristic clinical picture and laboratory tests. The xanthopathy at the Addisonovy disease needs to be differentiated with the solar suntan which is combined with a hypotonic syndrome, with a xanthopathy at a toxic diffusion craw, at hemochromatosis, a pellagra, an acanthosis, a pruritic dermatosis, chronic malaria, a scleroderma, a solteryayushchy form of nephrite. Pigmentation of a mucous membrane of an oral cavity is observed also at chronic poisonings with arsenic, caustic silver, mercury, lead.
Against the background of correctly carried out treatment exceeds longevity of patients 15 — 20 years, working capacity remains; some labor restrictions are necessary for the patients performing hard physical activity.
Treatment is directed to substitution of insufficiency of function of bark of adrenal glands by means of individually selected dosages of glucocorticoid and mineralokortikoidny drugs. Appoint usually Prednisolonum on 5 — 20 mg or a cortisone in tablets on 25 — 50 mg a day, or a hydrocortisone and a cortisone intramusculary on 12,5 — 50 mg a day.
If the above-stated treatment does not contribute to normalization of arterial pressure, add a mineralokortikoida — cortexone in tablets on 5 — 20 mg a day sublingual or in the form of 0,5% of Solutio oleosa intramusculary 2 — 3 times a week, in the form of hypodermic implantations of 100 — 200 mg (sterile tablets) once in 3 — 6 months, and also in the form of 2,5% of solution of trimethyl acetate DOCK on 25 — 50 mg intramusculary once to 2 — 3 weeks. Treatment is carried out under control of overall health, body weight, arterial pressure and allocation 17-keto-and 17 oxycorticosteroids with urine. Addition to food of sodium chloride is recommended (to 10 g a day).
Antitubercular treatment is carried out only in the presence of active tubercular process in adrenal glands or other bodies.
Treatment of a krizaaddisonovy disease consists in intravenous administration in the drop way 2 — 3 l of isotonic solution of sodium chloride from 5% solution of glucose, 100 — 300 mg of a cortisone or a hydrocortisone or 100 — 200 mg of Prednisolonum a day. At falloff of arterial pressure add 1 — 3 ml of 0,2% of solution of noradrenaline to the solution stated above.
Solutio oleosa of cortexone is entered on 20 — 40 mg a day intramusculary bucketed at 6 — 8 o'clock. Performing antibacterial therapy is recommended at the same time. In 2 — 3 days depending on a condition of the patient glucocorticoids are appointed intramusculary in the decreasing doses, and then transferred to maintenance doses mineralo-and glucocorticoids. Complex therapy of the Addisonovy disease includes the sanatorium treatment which is carried out in sanatoria of the general type. In the presence of tuberculosis of the indication to sanatorium treatment are based on the nature of tubercular process.
Prevention of the Addisonovy disease consists mainly in correctly and timely carried out treatment tuberculosis (see) and other diseases which are etiological factors of the Addisonovy disease.
Bibliography: V. G rams. Diseases of endocrine system and metabolism, L., 1955; Zefirova of G. S. Addisonov disease, M., 1963, bibliogr.; Soffer L., Dorfman R. and Gebrilav And. Epinephral glands of the person, the lane with English, page 207, M., 1966; Shereshevsky N. A. Clinical endocrinology, page 185, M., 1946; Addison T. On the constitutional and local effects of disease of the suprarenal capsules, L., 1855; Brenner O. Addison's disease with atrophy of the cortex of the suprarenale, Quart. J. Med., v. 22, p. 121, 1928—1929; Guttman P. H. Addison's disease, Arch. Path., v. 10, p. 742, 895, 1930; Hall R., Anderson J. Smart G. A. Fundamentals of clinical endocrinology, L., 1969; Human adrenal cortex, ed. by A. R. Currie a. o., Baltimore, 1062; To& d a s I. Die latente Addisonische Krankheit, Z. gee. inn. Med., S. 140, 1970; Paschkis K. E. Ra-koff A.E. a. Gantarow A. Clinical endocrinology, N. Y., 1958; Textbook of endocrinology, ed. by R. Z. Williams, Philadelphia — L., 1963.
G. S. Zefirova; V. B. Zayratjyants (stalemate. An.).