ADRENO-GENITALNYY SYNDROME (Latin adrenalis — epinephral and genitalis — sexual, genital; synonym Cook's syndrome — Apera — Gallet) — the disease caused by hyperfunction of bark of adrenal glands with excessive secretion of androgens. For the first time the syndrome was described by Cook in 1756. Further it was described by various authors, and more often on section found tumors of cortical substance of adrenal glands. In 1886 J. Phillips described this syndrome at the girl with a hyperplasia of cortical substance of adrenal glands at the age of 19 days. The pathogeny and the nature of hormonal disturbances at an inborn hyperplasia of cortical substance of adrenal glands was studied in the fifties 20 century by L. J. Wilkins and A. Bongiovanni. In 1950 L. J. Wilkins offered pathogenetic treatment And. - of the page connected with an inborn hyperplasia of cortical substance of adrenal glands.
Children have a frequency And. - of the page connected with an inborn hyperplasia of cortical substance of adrenal glands according to A. Prader, makes 1: 5000, according to Williams (R. N of Williams) — 1: 50 000.
Etiology can be various. The disease results from a tumor of cortical substance of adrenal glands or its inborn hyperplasia; in the latter case it is hereditary.
Tumors of cortical substance of adrenal glands develop at any age. Its hyperplasia — the hereditary disease, and its symptoms can develop right after the birth or later. The disease often develops at several children in a family. Inheritance is connected with an autosomal recessive gene.
Pathological anatomy is defined by existence of a tumor of cortical substance of an adrenal gland (see. Androsteroma ) or its hyperplasia. In the latter case the weight of adrenal glands can reach 80 — 90 g. The hyperplasia of a mesh zone of cortical substance of adrenal glands, sometimes a hyperplasia of all its three zones is noted. Sometimes in cortical substance of an adrenal gland the adenomas consisting of cells of a mesh zone are found. In ovaries the atrophy with total absence of primary and atretic follicles, cysts with a thickening of a white is observed. In testicles — an atrophy, braking of a spermatogenesis with lack of intersticial cells. The pathogeny of an adrenogenital syndrome at an inborn hyperplasia of cortical substance of adrenal glands is connected with genetic disorders of biosynthesis of steroid hormones as a result of insufficiency of separate enzymes (see the scheme).
Distinguish the following main forms of disturbances.
Blockade delta 5 - pregnenolona (insufficiency 20, 22 desmolases and a gidrok silaz). At this form formation of cortisol at the earliest stages of its biosynthesis is broken. The expressed insufficiency of kortikoid develops that finds clinical implication in heavy, sometimes forts incompatible with life And. - of page.
Absence 3 - beta ol-dehydrogenases and isomerase therefore transformation delta 5 - pregnenolona in progesterone is broken.
Blockade of the S-21-gidroksilirovaniya. This type of defeat is most characteristic for And. - of page, it is connected with insufficiency of 21 hydroxylases necessary for transformation 17 - alpha hydroxyprogesterone in cortisol through 11-dezoksikortizol. Though at this form enough Aldosteronum is formed, at 1/3 patients is defined, except virilescence, a salt depletion syndrome, and formation of cortisol and Aldosteronum very low.
Blockade of the S-11-gidroksilirovaniya — rather rare form of disturbance, is characterized by insufficiency 11 hydroxylases, breaks synthesis of cortisol. Education
11 cortexones at the same time is increased. The last has the expressed mineralokortikoidny activity in this connection clinically this type A. - of page is shown by hypertensia. Virilescence can be expressed slightly less, than at blockade of S-21.
Also forms A are described. - of page, characterized excess products of the etiocholanolone causing the repeating feverish states which are successfully stopped by treatment by the glucocorticoids suppressing supersecretion of etiocholanolone in children.
Insufficiency of formation of cortisol leads to excess allocation of AKTG therefore synthesis of androgens amplifies, noted excess formation of derivatives of progesterone, in particular a pregnantriol, allocation with urine 17 of ketosteroids considerably increases.
The large number of researchers finds it possible to define And. - of page as dysfunction of bark of adrenal glands, at a cut occurs strengthening of formation of one corticosteroid hormones and reduction of education of others. Surplus of androgens can brake sexual development on isosexual (intersexual) type at women. Also antagonistic action of androgens in relation to estrogen at the fabric level is possible.
Clinical picture. Distinguish the following most common forms of a disease.
1. Virilny form — the most frequent, defined by action of androgens, without gross violations glyuko-and mineralokortikoidny function.
2. Solteryayushchy form (salt depletion syndrome) — see below the Adrenogenital syndrome at newborns.
3. Gipertenzionny form, characterized by a persistent hypertension, virilescence.
4. Virilny form with periodic fevers, caused by receipt in blood of significant amounts of etiocholanolone. Headaches, oznoba, abdominal pains, sweats, sometimes prostration, nausea, vomiting, meningeal symptoms are noted. In blood the leukocytosis and significant amounts of etiocholanolone are found.
At all forms A. - of page with virilescence the disease at women is characterized by emergence of men's secondary sexual characteristics: a deep voice, excessive development of muscles of a body, pilosis on a pubis on men's type, a hypertrichosis, emergence of moustaches, beards (see. Hirsutism ). The hypertrophy of a clitoris is noted and periods stop (see. Virilescence ).
If the disease develops in the pre-natal period, then at girls at the birth external genitals can be incorrectly created, and it is difficult to define a sex of the child correctly (see. Pseudohermaphroditism ). Sometimes disturbances of formation of external genitals are expressed so sharply that the hypertrophied clitoris reminds a male penis, the urethra and a vagina open one slotted or round opening at the basis of a clitoris.
At men of disturbance are expressed to a thicket poorly. The gipertenzionny form can be observed. If the disease develops from children's age, there are symptoms of early sexual and physical development on isosexual type (see. Hypergenitalism ).
Patients of low growth, in the childhood are marked out signs of early sexual development owing to what there is an early closing of an epiphysis of bones and a stunt.
The disease is characterized by also accelerated growth of the child, approximately up to 11 — 12 years (anabolic action of androgens) and a bystry stunt in view of early closing of regions of growth.
Diagnosis is established on the basis of clinical inspection of the patient and these laboratory researches. Bystry development of a disease is characteristic at a tumor of bark of adrenal glands. Men have tumors of cortical substance of adrenal glands — androsteromas — are diagnosed generally on datas of laboratory and at X-ray inspection. Clinical data, such as obesity, a hypertrichosis, are flimsy. At women emergence of signs of virilescence is characteristic. Development of symptoms of a disease since the childhood usually happens at an inborn hyperplasia of cortical substance of adrenal glands. At men this disease can be not distinguished long time, especially when a current its favorable and is not present any complications.
Main laboratory diagnostic test And. - of page is increase in content in urine of the general, neutral 17 ketosteroids. At a hyperplasia of cortical substance of adrenal glands the maintenance of a pregnantriol increases in urine.
For differential diagnosis of a tumor of cortical substance of adrenal glands with a hyperplasia by the patient enter dexamethasone (in a dose on 8 mg a day within two days) which in case of a tumor does not cause decrease in maintenance of 17 ketosteroids in urine whereas at patients with a hyperplasia of cortical substance of adrenal glands there occurs falloff of their contents. To children enter dexamethasone in the doses depending on age (see. Dexamethasonal test ). At a suprarenorentgenografiya with administration of oxygen in retroperitoneal cellulose (through a pararectal fat) with the subsequent tomography it is possible to find a tumor of cortical substance of adrenal glands or increase in both adrenal glands that indicates a possible hyperplasia of cortical substance of adrenal glands.
It is necessary to differentiate this disease at women with the virilizing tumors of ovaries, at men — with tumors of testicles and with diseases of c. N of page, proceeding with signs of early puberty (damage of a hypophysis).
Forecast solteryayushchy and gipertenzionny forms A. - of page adverse, virilny — for life favorable.
Treatment at tumors of bark of adrenal glands — operational. At an inborn hyperplasia of cortical substance of adrenal glands — replacement therapy by corticosteroid drugs depending on age of patients and the clinical course of a disease under control of determination of content of 17 ketosteroids in urine.
Treatment of a virilny form A. - of page begins with purpose of a cortisone intramusculary for children up to 2 years in a dose of 25 mg a day, for children of advanced age and adult 50 — 100 mg a day, in 5 — 7 days after reduction of excretion of 17 ketosteroids the dose decreases to supporting, edges is selected individually. At oral administration the dose of a cortisone is usually 2 — 4 times higher, than at intramuscular. A maintenance dose of a cortisone at treatment And. - of page corresponds to a maintenance dose at treatment of adrenal insufficiency. In cases of stressful states it shall be increased. Treatment of a solteryayushchy form — see below the Adrenogenital syndrome at newborns.
Adrenogenital syndrome at newborns. Hereditary defects of biosynthesis of corticosteroids at children of the period of a neonatality can be shown in the form of the heavy clinical syndromes which are quite often a cause of death of the child - — a solteryayushchy form A. - of page (a virilny, gipertenzionny form, and also a virilny form in combination with periodic fevers — see above)
the Clinical picture. Salt depletion syndrome (solteryayushchy form A. - of page according to Wilkins, a syndrome to Debra — Fibigera, interrenalovy intoxication, paradoxical insufficiency of adrenal glands, a diskortitsizm, a pseudo-pylorostenosis) it is shown in the first weeks of life by persistent vomiting, sometimes the fountain. The child loses flesh, dehydration develops, features are pointed, skin gets a gray and earthy shade. Insufficiency of a peripheral krovobrashcheniye — a vascular collapse is expressed, there are frustration of a cordial rhythm, a convulsive syndrome. Quite often at height of crisis there comes the lethal outcome, to-rogo acute vascular insufficiency or a hyperpotassemia is the reason.
The salt depletion syndrome developing at insufficiency in fermental system 18 of oxidases received the name of a hypoaldosteronism (see. Hypoaldosteronism ).
At a solteryayushchy form A. - of page in blood is found a hyperpotassemia, the expressed metabolic acidosis, an azotemia, a hyponatremia. Excretion of sodium and chlorine with urine is considerably increased.
Diagnosis of a solteryayushchy form A. - with at children of the period of a neonatality is based on the following clinical and biochemical signs: 1) emergence of persistent vomiting and symptoms of dehydration on 2 — the 3rd week of life; 2) lack of signs of a hypertrophy of the gatekeeper at a palpation of an abdominal cavity; 3) lack of anomalies from outside went. - kish. a path at X-ray inspection; 4) characteristic biochemical changes in blood (hyperpotassemia, acidosis); under the influence of treatment or intercurrent diseases characteristic for And. - of page the hyperpotassemia can be replaced by a hypopotassemia; 5) considerable excretion of sodium and chlorine with urine; 6) the raised excretion with urine 17 of ketosteroids and a pregnantriola (except some forms); removal of 17 oxycorticosteroids can be normal; 7) characteristic changes of a range of S-21 of corticosteroids of urine — absence or reduced removal of cortisol, cortisone and their tetrahydroderivatives; 8) existence And. - of page at brothers or sisters of the patient.
Methods of antenatal diagnosis are developed And. - of page. For this purpose in the amniotic fluid received by an amniotseptez the maintenance of 17 ketosteroids is defined [Dzheffkout (T. N. And. Jeffcoate) and sotr., 1965] pl of a pregnantriol [J. Nichols, 1969]. The increased content of these connections testifies to a possibility of a disease at a fruit and allows to begin treatment with corticosteroids in the pre-natal period.
At a true pylorostenosis at newborns the hypopotassemia is observed, a gipokhloremichesky alkalosis, removal of sodium and chlorine with urine is sharply reduced, sometimes these electrolytes in urine are not defined at all.
Forecast for life adverse. Performing replacement therapy allows to improve the forecast.
Treatment is directed to substitution of losses of water and electrolytes, to elimination of cardiovascular insufficiency and deficit of the main corticosteroids. For fight against a vascular collapse and dehydration appoint drop intravenous injections of glyukozo-saline solutions from the following calculation: on second day of life the child receives 60 — 90 ml of liquid (depending on weight at the birth); every next day to this quantity add 15 — 20 ml. After the 16th day of life liquid is entered parenterally from calculation to 100 ml on 1 kg of weight a day. Sodium is entered in the quantities necessary for recovery of its datum level in a blood plasma. For calculation of total quantity of the sodium which is required for elimination of deficit the following formula can be used: sodium in milliekvivalenta = 140 — sodium of serum in mekv/l * (the weight of the child in kg * 400)/100, -
where 140 — the average normal content of sodium on liter; the second part of a formula allows to determine approximately the volume of extracellular liquid in liters since it makes about 40% of their weight at newborns. Primerlo 1 mekv sodium contains in 1 ml of 5% of solution of sodium chloride. Therefore the given formula can be transformed: the number of 5% of NaCl solution in ml = 140 — sodium of serum in mekv/l * (the weight of the child in kg / 2,5).
This number of 5% of solution of sodium chloride should be added to a dropper to the calculated volume of 5% of solution of glucose. Reasonablly to add to a dropper also a hydrocortisone at the rate of 5 mg/kg, to intramusculary enter DOCK at the rate of 0,5 — 1 mg/kg. Use ascorbic to - you in high doses (0,5 g a day), the drugs toning vascular system (Cordiaminum, noradrenaline) is shown.
The reason of serious condition of the newborn with And. - of page can serve the expressed hyperpotassemia even in the absence of a vascular collapse and signs of a hyponatremia. In this case drop intravenous injection of isotonic hypertonic salt solution of a pla of glucose (10%) in combination with isotonic solution of sodium chloride is also shown (a ratio 4:1), introduction of 10% of solution of a gluconate of calcium — 1 — 2 ml intravenously (single dose), insulin is reasonable (1 PIECE on each 2 — 4 g of the glucose entered Parenterally). The heavy, unremovable hyperpotassemia can serve as the indication for peritoneal dialysis (see).
The prevention of crises of loss of salt, and also the phenomena of virilescence is reached by prolonged use Prednisolonum (see) according to the standard schemes. According to M. A. Zhukovsky, preventive effect hypodermic replanting of crystals gives DOCK (50 — 125 mg). Treatment of other forms A. - of page at children — see above.
Mental disorders at an adrenogenital syndrome. Cases of the expressed psychoses developing in connection with And. - of page, are rare. However at psychiatric inspection of patients with this disease these or those mental deviations and changes of the personality can be revealed. In general they keep within the psychopathological syndromes characteristic of endocrine diseases — psychopatholike [an endocrine psychosyndrome on Bleylera] and anamnestic and organic. Decrease in mental activity, emotional disturbances and frustration of inclinations are characteristic of the first; for the second — disturbance of intelligence. At And. - of page these syndromes have a number of features. Dominance in their structure of these or those disturbances is defined by the nature of the disease (a hyperplasia, a tumor of an adrenal gland), it tyazhestyo, age and a sex of patients.
At inborn And. - of page in cases of premature sexual development (with the phenomena of a pseudohermaphroditism at girls) is not observed so premature psychosexual maturing. On the contrary, such patients (both girls, and boys) in the behavior and emotional manifestations can be extremely infantile, and their sexual interests are a little differentiated and poorly expressed. The most part of such children is closed, timid, inspired and sensitive. For the emotional sphere of children and teenagers with And. - of page lack of a spontaneity and vivacity of emotions is characteristic. Quite often big physical force of such children and male lines at girls in motility (the corresponding gait, sharpness and impetuosity of movements, tendency to the sports demanding physical force) are combined with dominance in the nature of lines of passivity and shyness.
Intellectual development of children with And. - of page usually normal or slightly lags behind norm; such children can be very purposeful and organized in study and work. At the same time also cases with a sharp delay of intellectual development, the raised inclinations and sexual impulsiveness are observed (sometimes leading to sexual crimes).
At And. - as of page at adult women into the forefront emotional frustration in the form of depressions act (asthenic, asthenohypochondriac, hypochiondrial and senestopathetic); also pseudo-neurotic states (asthenic, hysterical, with navyazchivost), and also actually psychopatholike changes of the personality are frequent (is more often than type of a schizoid psychopathy). Some authors observed psychotic states (depressive and paranoid, paranoid and hypochiondrial, etc.). Frustration of inclinations at women with And. - of page can be shown both by increase, and decrease in sexuality that finds reflection in the content of their experiences (depressive, hypochiondrial, paranoid).
Important feature of mental changes at And. - of page both at adults, and at children (especially teenagers) is a combination of the changes connected with the basic pathological process, with changes of reactive character (reaction to change of appearance). At girls it is expressed by elements of irritability, affective tension, isolation, the lowered background of mood; at adult women situational depressions can be observed.
The scheme of the sequence of the amino-acid remains in molecules of adrenocorticotropic hormone of the person in comparison with a pig, a bull and a sheep.
In the course of diagnosis and clinical assessment of mental disturbances (especially psychoses) at And. - it is important to consider of page that endocrine shifts in the form of a hirsutism or a virilism often occur at true psychoses at women (at schizophrenia, involutional psychoses, etc.). Psychoses in these cases proceed especially adversely and quickly lead to dementia; in a picture of psychosis lines of the raised erotichnost, abundance of the senestopathetic feelings which are often localized preferential in genitals and the crazy ideas of the corresponding content are noted. At boys and men mental disorders are studied insufficiently as such patients well adapt in life and often differ in high intelligence. As a rule, they are carried to strong type of the sexual constitution.
Bibliography: Nikolaev O. V. and E. I Cockroaches. Hormonal and active tumors of bark of an adrenal gland, M., 1963, bibliogr.; Starkova N. T. Viril-ny syndrome, M., 1964, bibliogr.; Wilkins JI. Diagnosis and treatment of endocrine disturbances at children's and youthful age, the lane with English, M., 1963.
And. - page at newborns — Badalyan L. O., Tabolin V. A. and Veltishchev Yu. E. Hereditary diseases at children, M., 1971; Veltishchev Yu. B. Water salt metabolism of the child, M., 1967; Zhukovsky M. A. Children's endocrinology, M., 1971; Bongiovanni A. M of a. Root A. W. The adrenogenital syndrome, New Engl. J. Med., v. 268, p. 1283, 1963, bibliogr.; Nichols J. Antenatal diagnosis of adrenocortical hyperplasia, Lancet, at. 1, p. 1151, 1969; V i 8 s e r H. K. A. Kongenitale Stdrungen der Nebcnnierenrindenfunktion, Triangel (De.), Bd 7, S. 220, 1966, Bibliogr.
Mental disorders at And. - page.— Lebedinskaya K. S. Mental disturbances at children with pathology of rate of puberty, M., 1969; In 1 eu 1 e M. of Endokrinologische Psychiatrie, Stuttgart, 1954, Bibliogr.
H. T. Starkova; Yu. E. Veltishchev (ped.), D. D. Orlovskaya (psikhiat.).