Adrenogenital syndrome: treatment, forms, tests and diagnosis. Adrenogenital syndrome

Adrenogenital syndrome is characterized by abnormalities in the functioning and structure of the genital organs. Its exact etiology has not been established. But it is generally accepted that the deviation occurs as a result of excessive production of androgens by the adrenal cortex. Pathology can be caused by tumors (adenocarcinoma, adenoma) or congenital hyperplasia of these glands. The hereditary factor is also given considerable importance.

Adrenogenital syndrome: symptoms

The pathology occurs in both boys and girls. Its symptoms depend on the time of onset and the gender of the affected child. It also affects which form of adrenogenital syndrome occurs. And there are three of them: simple (virile), hypertensive and salt-wasting. Each of them manifests itself either in the postnatal or prepubertal period. Adrenogenital syndrome in girls is expressed in the virile form immediately at birth. This manifests itself in false hermaphroditism. The clitoris is too enlarged and the opening of the urethra opens right at its base. The labia majora resemble a split scrotum. The changes are sometimes so pronounced that it is difficult to determine the sex of the child. At the age of three to six years, hair grows intensively on the back, legs and pubis, and physical development increases. The girl becomes similar to the boy in appearance. Soon her sexual development stops completely. The mammary glands are small. Menstruation in girls is either absent or very scanty and irregular. Adrenogenital syndrome in boys develops starting from two to three years of age. Along with increased physical development, the penis enlarges, excessive hair growth is observed, and sometimes erections appear. But the testicles, despite all this, are infantile and do not develop at all in the future. Both girls and boys grow rapidly, but despite this they remain short and stocky, since the growth zones in the pituitary gland close early.

Adrenogenital syndrome: diagnosis

It's not that difficult to install. It is confirmed by hirsutism, abnormal structure of the external genitalia, and age-inappropriate physical development. There is a high level of 17-ketosteroids in the urine. Difficulties arise, as a rule, not in diagnosis, but in determining the cause of this syndrome. Anomalies in sex discrimination and indications of similar deviations in previous generations indicate congenital hyperplasia. If virilization develops after the baby is born, the presence of a tumor can be determined using computed tomography. It is also necessary to carefully differentiate congenital adrenogenital syndrome from premature sexual development, which is of cerebral-pituitary origin. In the latter case, a biopsy of the testicles reveals the presence of seminiferous tubules with active formation (under the influence of hormones) of male germ cells. Precocious development is also possible in girls. It often occurs with granulosa cell tumors of the ovary. With this pathology, premature development occurs according to the female type, and with adrenogenital syndrome - according to the male type. This is the main difference between them.

Adrenogenital syndrome: treatment

If the pathology occurs against the background of congenital adrenal hyperplasia, corticosteroid drugs are prescribed. Their constant minimum dose does not have any negative effect. But at the same time they suppress the functions of the glands well. Treatment begins with large doses, which is maintained from ten days to a month. Longer use may negatively affect the baby's growth processes. After achieving the effect, the dose is reduced to maintenance, focusing on the level of 17-ketosteroids in the urine. Treatment is carried out under strict medical supervision.

Definition of the concepts of hypertrichosis, hirsutism, virilism.

Adrenogenital syndrome (AGS) is a hereditary pathology associated with insufficient production of enzymes by the adrenal cortex, accompanied by an excess of sex hormones and a lack of glucocorticoids.

The reason for the insufficient secretion of normal hormones of the adrenal cortex in patients with adrenogenital syndrome is a congenital deficiency in the activity of key enzymes of cortisol synthesis, 21-hydroxylase or 11-beta-hydroxylase. Adrenogenital syndrome is a monogenic disease inherited in an autosomal recessive manner. With it, the adrenal glands do not have the ability to synthesize normal cortisol adequate to the body’s needs. A decrease in the concentration of the hormone in the extracellular fluid and blood plasma serves as a stimulus for increased secretion of corticotropin by the adenopituitary gland.

Increased secretion of corticotropin causes adrenal hyperplasia. In this case, the adrenal glands intensively form and release abnormal steroids that have the biological activity of androgens. As a result, women with adrenogenital syndrome develop virilism. Virilism (lat. virilis, male) is the presence in women of secondary male sexual characteristics, that is, hirsutism (male type of hair growth), the skeletal structure and voluntary muscles characteristic of men, a massive clitoris, and a low timbre of the voice. An increase in the content of steroids with androgen properties in the circulating blood leads to a decrease in the secretion of gonadotropins by the adenohypophysis. As a result, sick girls do not develop a normal menstrual cycle.

Congenital deficiency of 21-hydroxylase activity as a cause of adrenogenital syndrome can lead to low synthesis of aldosterone by the adrenal cortex. Aldosterone deficiency causes the body to lose sodium. A decrease in sodium content in the body leads to a decrease in the volume of extracellular fluid.

Classification of adrenogenital syndrome

Congenital adrenogenital syndrome

Uncomplicated (simple) virilizing form.

Virilism with hypertensive syndrome

Virilism with hypotensive syndrome

Acquired adrenogenital syndrome)

Symptoms of adrenogenital syndrome:

1. Viril form is the most common form of adrenogenital syndrome. Associated with 21-hydroxylase deficiency. This form can be corrected if detected in a timely manner and on average accounts for 2/3 of all patients with this pathology. 2. Salt-wasting form - has a more severe course, is much less common, children without proper treatment die in the first months of life. The main symptoms include symptoms of dyspepsia, decreased blood pressure, etc.

3. Hypertensive form is a rather rare form that is not always classified as a separate group. With this form, persistent arterial hypertension begins to appear early, not controlled by taking “heart” medications, which, in the absence of proper treatment, can lead to renal failure and cerebral (cerebral) circulation disorders.

Among the main symptoms are the following:

1. Retarded growth and body weight - patients in early childhood are distinguished by relatively tall height and large body weight, but on average, by the age of 12 years of life, growth stops or slows down, and, as a result, in adulthood, patients are characterized by small stature.

2. Persistent arterial hypertension - often manifests itself in early childhood, but the symptom itself cannot be considered pathognomonic.

3. Dyspeptic symptoms are a nonspecific symptom.

The content of the article

Congenital virilizing adrenal hyperplasia is a genetically determined disease, the development of which is based on the inferiority of enzyme systems in the adrenal cortex, insufficient production of cortisol and increased production of 17-ketosteroids, which have androgenic properties. The disease occurs in people of both sexes.

Etiology of adrenogenital syndrome

The main etiological factor is the congenital deficiency of the adrenal enzyme systems.

Pathogenesis of adrenogenital syndrome

Even in the prenatal period, the fetus develops a deficiency of enzymes responsible for the production of cortisol in the adrenal glands. This leads to a deficiency of cortisol in the blood, which affects the weakening of its inhibitory effect on the production of corticotropin. The content of corticotropin in the blood increases, and therefore there is increased stimulation of the adrenal cortex with hyperplasia of the reticular zone and excessive production of androgens.
Androgens cause virilization of the child’s body: boys experience accelerated growth, premature puberty with an enlarged penis and the appearance of sexual desire; in girls - underdevelopment of the mammary glands, vagina, uterus, deepening of the voice, etc. In cases of more significant deficiency of 21-hydroxylase, aldosterone production may decrease and salt-wasting syndrome may develop (increased excretion of sodium and chlorides in the urine, which leads to dehydration and arterial hypotension ).

Pathomorphology of adrenogenital syndrome

With adrenogenital syndrome, adrenal hyperplasia, hypotrophy or atrophy of the ovaries, uterus, testicles, etc. are detected.

Classification of adrenogenital syndrome

According to the time of development, prenatal (intrauterine) congenital virilizing hyperplasia of the adrenal cortex and postnatal forms are distinguished; according to the clinical course - viril, salt-wasting and hypertensive forms.

Clinic of adrenogenital syndrome

Manifestations of the disease are different and depend on the gender of the patient, time of onset and form of the disease.
The viril form is the most common. Its symptoms are due to the virilizing and anabolic effects of excess androgens. It manifests itself in girls from birth with signs of pseudohermaphroditism: hypertrophy of the clitoris, resembling a penis, underdevelopment of the labia minora, vagina and uterus, enlargement of the labia majora, urogenital sinus. Sometimes changes in the external genitalia are so pronounced that it is difficult to determine the sex of the child. At the age of 3 - 6 years, excessive hair growth is observed on the pubis and back, physical development and muscle strength are increased. In appearance, girls resemble boys. Subsequently, sexual development stops, the mammary glands are poorly developed, menstruation is scanty with an irregular cycle without ovulation or completely absent.
In boys, the virile form noticeably manifests itself from 2 to 3 years of age. They develop intensively physically, their penis enlarges, excessive hair growth appears, and erections may occur. The testicles are infantile and subsequently stop developing.
Despite the fact that at first girls and boys grow rapidly, children remain short and stocky (early closure of the epiphyseal growth zones).
The salt-wasting form of the disease is less common; its manifestations can be found in newborns and children in the first year of life, more often in boys. The most characteristic symptoms: regurgitation, vomiting, rapid weight loss, arterial hypotension, irritability. Due to a violation of water-electrolyte balance, there is a rapid loss of sodium (a consequence of reduced glycocorticoid and mineralocorticoid functions of the adrenal cortex), dehydration. Cyanosis, hyperkalemia, convulsions, and collapse often occur. A patient who does not receive treatment may die.
The hypertensive form of the disease is very rare. In addition to signs of virilism, it is characterized by persistent arterial hypertension with early changes in the vessels of the fundus and kidneys.
In all clinical forms of the disease, brown or café-au-lait skin pigmentation is possible. In the blood, the content of corticotropin is increased; in the salt-wasting form, there is a low level of aldosterone, sodium, chlorides, a high level of potassium, and hypoglycemia occurs. Increased excretion of 17-K.C in urine is noted.

Diagnosis of adrenogenital syndrome

The diagnosis is established on the basis of characteristic clinical symptoms and laboratory data. A diagnostic test with dexamethasone or prednisolone is also used. Genetic sex is determined by the results of a sex chromatin study.

Differential diagnosis of adrenogenital syndrome

Differential diagnosis is carried out with a tumor of the adrenal cortex (androsteroma), premature sexual development of hypothalamic-pituitary origin, tumors of the pineal gland, ovaries and testicles.

Prognosis of adrenogenital syndrome

The prognosis is favorable if the disease is diagnosed early and treatment is carried out systematically. Without timely replacement therapy, acute adrenal insufficiency may develop with sudden death.

Treatment of adrenogenital syndrome

The most rational use of corticosteroid drugs (cortisone and its derivatives), since the basis of the disease is a deficiency in the production of cortisol (hydrocortisone) and mineralocorticoids. Cortisone, prednisolone, or prednisone markedly reduces the urinary excretion of 17-ketosgeroids and biologically active androgens. Treatment begins with large doses.
Preferably, intramuscular administration of cortisone acetate. Daily dose: 10 - 25 mg for infants; 25 - 50 mg for children 1 - 8 years old and 50 - 100 mg for adolescents. Cortisone and its derivatives can be prescribed orally in appropriate doses. The duration of treatment with large doses is either 10 to 30 days. With this treatment, it is possible to reduce the excretion of 17-ketosgeroids to 3.8 µmol/day in young children and to 10.4 - 13.9 µmol/day in older children. Subsequently, once the effect is achieved, treatment is continued with maintenance doses of corticosteroids, guided by the level of urinary excretion of 17-KS. Of the cortisone derivatives, prednisolone and prednisone are effective. Their advantage is a more active suppression of the secretion of corticosterone by the pituitary gland, they retain little sodium in the body, and are well tolerated by children. When prescribed in a daily dose of 10 - 20 mg, urinary excretion of 17-KS is suppressed for a long time.
In the salt-wasting form, urgent administration of sodium chloride, cortisone and deoxycorticosterone is indicated. Usually, 5 mg/kg/day of hydrocortisone, 0.5 - 1 mg/kg/day of DOXA, and 1000 ml of 5% glucose solution with the addition of 20% sodium chloride solution (no more than 4 - 8 g/day) are administered intravenously. With the gradual development of the syndrome, it is sufficient to administer 5 mg/kg with the addition of 3 - 5 g/day of sodium chloride; if necessary, add DOXA 2 mg/day with a gradual increase in the dose of the drug.
In hypertensive forms, the administration of DOX and other hormones is not required, since they retain sodium and water. In such cases, you can limit yourself to prescribing prednisolop.
Timely and systematic (before the end of puberty) treatment with glycocorticoids prevents premature sexual development, promotes normal testicular development, eliminates the development of adrenal insufficiency, and normalizes blood pressure. This treatment is carried out under the control of height, body weight, blood pressure, and bone age. Anomalies in the development of the genital organs in girls are eliminated by corrective operations no earlier than after a year of treatment with glycocorticoids.

Congenital dysfunction of the adrenal cortex (synonym: adrenogenital syndrome in children) includes a group of hereditary enzymopathies. Each of the enzymopathies is based on a genetically determined defect in the enzyme involved in steroidogenesis.

Defects in five enzymes involved in the synthesis of gluco- and mineralocorticoids have been described, resulting in the formation of one or another variant of adrenogenital syndrome in children. All forms of congenital dysfunction of the adrenal cortex are inherited in an autosomal recessive manner.

ICD-10 code

E25 Adrenogenital disorders.
E25.0 Congenital adrenogenital disorders associated with enzyme deficiency.
E25.8 Other adrenogenital disorders.
E25.9 Adrenogenital disorder, unspecified.

What causes adrenogenital syndrome in children?

In 90% of cases, a 21-hydroxylase defect is observed, which can be caused by various mutations of the CYP21 gene, which encodes this enzyme. Dozens of CYP21 mutations leading to a P450c21 defect have been described. A point mutation with partial 21-hydroxylase activity also occurs. With partial deficiency of this enzyme, a simple (viril) form of the disease develops. 21-Hydroxylase is involved in the synthesis of cortisol and aldosterone and is not involved in the synthesis of sex steroids. Impaired cortisol synthesis stimulates the production of ACTH, which leads to hyperplasia of the adrenal cortex. At the same time, 17-OH-progesterone, a precursor of cortisol, accumulates. Excess 17-OH-progesterone is converted to androgens. Adrenal androgens lead to virilization of the external genitalia in a female fetus - a girl is born with false female hermaphroditism. In boys, hyperandrogenemia determines the premature appearance of secondary sexual characteristics (precocious puberty syndrome).

With a significant deficiency of 21-hydroxylase, the hyperplastic adrenal cortex does not synthesize cortisol and aldosterone in the required quantities. in this case, against the background of hyperandrogenemia, salt loss syndrome or adrenal insufficiency develops - a salt-wasting form of the disease.

The non-classical form of 21-hydroxylase deficiency manifests itself in pre- and puberty in the form of adrenarche, moderate hirsutism and menstrual irregularities in girls. Moderate or mild virilization is the result of the point mutation V281L and P30L.

Symptoms of adrenogenital syndrome in children

In the classic virile form of adrenogenital syndrome in children, the external genitalia of the girl are formed according to the heterosexual type - the clitoris is hypertrophied, the labia majora resemble the scrotum, the vagina and urethra are represented by the urogenital sinus. It is not possible to detect obvious disorders in newborn boys. From 2-4 years of age, children of both sexes begin to experience other symptoms of adrenogenital syndrome in children, that is, androgenization: axillary and pubic hair is formed, skeletal muscles develop, the voice becomes coarser, the figure becomes masculinized, and juvenile acne appears on the face and torso. In girls, mammary glands do not grow and menstruation does not appear. At the same time, skeletal differentiation accelerates and growth zones close prematurely, which causes short stature.

In the salt-wasting form of 21-hydroxylase deficiency, in addition to the symptoms described above, children show signs of adrenal insufficiency from the first days of life. First, regurgitation appears, then vomiting, loose stools are possible. The child quickly loses body weight, symptoms of dehydration and microcirculation disorders develop, blood pressure decreases, tachycardia begins, and cardiac arrest is possible due to hyperkalemia.

The non-classical form of adrenogenital syndrome in children is characterized by the early appearance of secondary hair growth, accelerated growth and differentiation of the skeleton. In girls of puberty, moderate signs of hirsutism, menstrual irregularities, and the formation of secondary polycystic ovary syndrome are possible.

11-hydroxylase deficiency, in contrast to 21-hydroxylase deficiency, in addition to symptoms of virilization and androgenization, is accompanied by an early and persistent increase in blood pressure. caused by the accumulation in the blood of the precursor of aldosterone - deoxycorticosterone.

Diagnosis of adrenogenital syndrome in children

Laboratory diagnosis of adrenogenital syndrome in children

All children with abnormal structure of the external genitalia, including boys with bilateral abdominal cryptorchidism, are advised to determine sex chromatin and study the karyotype.
From the first days of life, an increased content of 17-OH-progesterone is detected in the patient’s blood serum. It is possible to conduct a screening test in newborns on the 2-5th day of life - 17-OH-progesterone is increased several times.
Salt loss syndrome is characterized by hyperkalemia, hyponatremia, and hypochloremia.
Urinary excretion of 17-ketosteroids (androgen metabolites) increases.

Instrumental diagnosis of adrenogenital syndrome in children

Bone age according to radiographs of the wrist joints is ahead of the passport age.
An ultrasound scan reveals the uterus and ovaries in girls.

Differential diagnosis of adrenogenital syndrome in children

In children of the first year of life, differential diagnosis of adrenogenital syndrome in children is carried out with various forms of false male hermaphroditism and true hermaphroditism. The main point in diagnosis is karyotyping (karyotype 46XX for the bisexual structure of the external genitalia) and determination of 17-OH-progesterone in the blood serum. The salt-wasting form of congenital dysfunction of the adrenal cortex should be differentiated from pyloric stenosis; difficulties arise in the differential diagnosis of adrenogenital syndrome in children and pyloric stenosis in boys - in this case, hyperkalemia and a high level of 17-OH-progesterone are important in congenital dysfunction of the adrenal cortex.

Treatment of adrenogenital syndrome in children

Drug treatment of adrenogenital syndrome in children

The virile form of adrenogenital syndrome in children requires constant replacement therapy with prednisolone. The dose of the drug is selected individually depending on age and degree of virilization and divided into 2-3 doses. Its doses are distributed evenly throughout the day. The average daily dose of prednisolone is 4-10 mg. This amount of the drug suppresses excess androgen production without causing side effects.

Treatment of the salt-wasting form of adrenogenital syndrome in children during a crisis of adrenal insufficiency is carried out in the same way as the treatment of acute adrenal insufficiency - by drip administration of an isotonic solution of sodium chloride and glucose, as well as parenteral administration of hydrocortisone preparations (10-15 mg/kg per day). The daily amount of hydrocortisone is distributed evenly. The drug of choice is water-soluble hydrocortisone (solucortef). When the condition stabilizes, hydrocortisone injections are gradually replaced with hydrocortisone tablets, and if necessary, a mineralocorticoid - fludrocortisone (2.5-10.0 mcg per day) is added.

Surgical treatment of adrenogenital syndrome in children

Girls aged 4-6 years undergo surgical correction of the external genitalia.

Criteria for the effectiveness of treatment of adrenogenital syndrome in children: normalization of the child’s growth rate, normal blood pressure, electrolytes in the blood serum. The optimal dose of glucocorticosteroids is determined by the level of 17-OH-progesterone in the blood serum, mineralocorticoids - by the content of renin in the blood plasma.

Let's try to analyze this concept in more detail. A syndrome is the characteristic symptoms of a disease. “Adreno” is a concept associated with steroid hormones. – means symptoms of genital disease. Now let's look at this syndrome in full.

Adrenogenital syndrome - increased secretion of steroid hormones by the adrenal cortex, most often androgens. It is known that androgens are male hormones. This means that with increased secretion in the opposite sex, signs characteristic of men appear. The cause of this disease is explained in the definition of adrenogenital syndrome, but there are additional reasons. This is usually a tumor of the adrenal gland or a proliferation of cells in its cortex. Diabetes may be a consequence of adrenogenital syndrome,

Diabetes mellitus is a disease associated with insufficiency of insulin, which is produced by the pancreas, which, in turn, is associated with the adrenal glands. Hypertension is high blood pressure. The course of this disease depends on the nature of the pathological process. A fatal outcome is possible in a situation where a tumor appears, which metastasizes to internal organs and bones.

Diagnostics

Diagnosis will consist of laboratory tests: blood and urine tests. This analysis will show the state of the body as a whole, the presence of an inflammatory process.

Computed tomography methods are used, thanks to which it is possible to accurately determine the state of a person’s genital area. Ultrasound is ultrasound diagnostics, which, like computed tomography, will determine gender, as well as the pathology of internal organs. In case of adrenogenital syndrome, a hormonal study is carried out, which will determine the amount of glucocorticoids, namely, whether it corresponds to the norm.

Prevention

Prevention measures will focus on medical consultation. Adrenogenital syndrome can lead to a congenital disorder of genetic material, which means medical genetic counseling should be carried out.

In order to treat and prevent the development of this syndrome after the birth of a child, glucocorticoids continue to be administered. This will eliminate male characteristics in women. Early detection of the disease will allow the necessary preventive measures to be taken.

In adults

Adrenogenital syndrome is common to both women and men, but is more common in women. The fair half of humanity experiences virile syndrome (growth of a mustache and beard, baldness, hair growth on the torso and limbs, atrophy of the mammary glands, menstrual irregularities, obesity, deepening of the voice). These signs are characteristic of men. However, in men, feminization is observed: kidney atrophy, decreased sexual potency, development of the mammary glands, disruption or cessation of mustache and beard growth. The strong half of humanity ceases to develop according to the male type. What is the treatment for this disease in adults?

For tumors - surgical intervention, for adrenal hyperplasia - treatment with prednisolone. And of course, glucocorticoids, which are administered by injection. If external signs are visible on the face, then it is advisable to undergo plastic surgery, but better at an early age.

In children

More often in children, adrenogenital syndrome is a congenital pathology. What is this connected with? Usually with a gene mutation or heredity. For girls, the situation is difficult, since the girl does not develop as a future mother. This applies to the mammary glands and secondary genitalia.

The genital area in girls with this disease resembles male sexual characteristics. Diagnosis in children using blood tests. Treatment consists of administering prednisolone, as well as sodium chloride and glucose. Children at an early age may be prescribed surgery to correct the genital organs.

Forecast

In most cases, the prognosis is favorable, again, this depends on timely diagnosis, proper treatment, early prevention and the ability to maintain your hormonal levels. If correction of the external genitalia is performed, it is necessary to observe the postoperative regimen and personal hygiene.

Observation by specialists is an important reassessment of one’s own health. It is in such cases that the ability to work is preserved. The prognosis will be unfavorable if diagnosis was not carried out in time and the disease is already at the tumor level. At the last stage, metastases appear.

Exodus

The outcome largely depends on complications. If complications are not identified, metastases have not spread to the internal organs, then the outcome of the disease is successful. A lethal outcome is also possible with adrenogenetic syndrome, since the body system as a whole is affected.

With hypotension, that is, low blood pressure, the outcome will also be fatal. It is known that a decrease in blood pressure can lead to collapse.

Lifespan

People who have a hormonal disease can be cured. Life expectancy will depend on the correction of hormones, that is, maintaining a healthy hormonal background. To maintain reproductive functions, a woman must continue to take hormonal medications.

If surgery is performed, then people continue to live a full life, but always with control over their health. With complications, the fact of life expectancy may be disrupted. To prevent your life from ending abruptly, pay attention to your health! Any disease can be cured, the main thing is to follow all the measures necessary for treatment!