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- endocrine disease, characterized by a sufficiently long exposure to the human body in excess of the amount of cortisol - a hormone synthesized by the adrenal cortex, or the abuse of glucocorticoids. Another name for hypercorticism is Itsenko Cushing's syndrome.

Women are 10 times more likely than men to suffer from hypercortisolism, and mostly between the ages of 25 and 40.

Hypercoticism is manifested by the fact that cortisol in large quantities slows down the production of glucose, which is very necessary for our cells. As a result, the functionality of many cells decreases and tissue atrophy is observed.

Hypercortisolism: causes

There are several causes of hypercortisolism, and the most common of them is Itsenko Cushing's disease (not to be confused with the syndrome of the same name).
In this case, there is an excess production of ACTH (adrenocorticotropic hormone), which activates the secretion of cortisol. This characterizes endogenous hypercortisolism.

Exogenous hypercortisolism occurs as a result of long-term use of glucocorticoids for the treatment of some systemic disease, for example, rheumatoid arthritis, or asthma.

Sometimes there is a so-called pseudo-Cushing's syndrome, which shows all the signs of hypercortisolism, but in fact, it is not. The causes of such pathological manifestations can be:
- obesity;
- alcohol intoxication;
- stress and depression;
- pregnancy...

Hypercortisolism: symptoms

In 90% of patients with hypercortisolism, obesity of the cushingoid type is observed: uneven fat deposits on the face (moon-shaped face), shoulders, neck, abdomen against the background of thin limbs - this type of obesity cannot be confused with any other.

Muscle atrophy is noticeable on the shoulder girdle and especially on the legs, and this is accompanied by constant weakness and fatigue. Against the background of obesity, muscle atrophy creates great difficulties for the patient with hypercortisolism in the process of any physical activity.

In women, hypercortisolism manifests itself:
- hirsutism;
- virilization;
- hypertrichosis;
- failure of menstrual cycles;
- aminorrhea and infertility.

Male hypercortisolism is manifested by problems in the reproductive system: decreased potency and libido, testicular atrophy and gynecomastia.

Also, hypercoticism can manifest itself as a malfunction of the nervous and cardiovascular systems.
"Nervous" symptoms:
- psychosis and stress;
- change from euphoric state to depression;
- lethargy;
- suicidal attempts.
Cardiovascular symptoms:
- Heart arythmy ;
- arterial hypertension;
- heart failure .

A clear symptom of hypercortisolism is the "marbling" of the skin, its dryness and the presence of striae, the "pattern" of blood vessels becomes clearly visible through the skin, rashes and hemorrhages often appear.

Hypercortisolism: complications

One of the most dangerous complications hypercortisolism is an adrenaline crisis, which manifests itself:
- disturbance of consciousness;
- vomiting and high blood pressure;
- hyperkalemia;
- hyponatremia;
- hypoglycemia;
- abdominal pain;
- metabolic acidosis.

Same way, hypercortisolism causes complications in cardiovascular system and in the functionality of the kidneys, which often leads to death:
- decompensation of cardiac activity;
- ischemic stroke ;
- renal failure;
- severe pyelonephritis;
- sepsis;
- osteoporosis;
- urolithiasis disease.

Among other things, hypercortisolism causes premature termination of pregnancy (miscarriage), causes skin problems (fungi, suppuration, boils), as well as steroid diabetes mellitus (without damage to the pancreas).

Hypercortisolism: diagnosis

When diagnosing hypercortisolism, first of all, screening tests are carried out - they determine the level of cortisol in the urine during the day. If this level is 3-4 times higher than normal, then this is an indicator of Itsenko Cushing's disease or hypercortisolism.
A small dexamethasone test shows that if, when taking dexamethasone, there is a decrease in cortisol levels by more than half, then this is the norm, and if this decrease is not observed, then this indicates the presence of hypercortisolism.

To differentiate Itsenko Cushing's disease and hypercorticism, a large dexametose test is performed: during the disease, a decrease in cortisol levels by more than 2 times occurs, and this does not occur with hypercorticism.

To find the source of the pathology, they resort to instrumental diagnostics. For this case, the most effective diagnostic methods are magnetic resonance and computed tomography pituitary and adrenal glands.

To identify complications of hypercortisolism, apply:
- radiography;
- biochemical analysis blood.

Hypercortisolism: treatment

The choice of treatment for this pathology depends on many factors: the cause of its occurrence, the immune status of the patient...

When tumors of the adrenal glands, lungs, pituitary gland are found, they usually resort to their removal. surgical method or to radiation therapy.

With the medicinal nature of hypercorticism, the use of glucocorticoids is gradually replaced by others. medical preparations immunosuppressive action.

With endogenous (internal nature) diseases, drugs are used that suppress steroidogenesis:
- ketoconazole;
- chloditan;
- mitotane;
- aminoglutethimide.

Various diuretics, cardiac glycosides, hypoglycemic drugs, antidepressants are used to treat the symptoms of hypercortisolism ...

Attention!
All these methods treatment of hypercortisolism have one very big drawback: they suppress the human immune system, cause quite severe side effects, which also negatively affect human immunity. But the immune system is the only "foundation" on which the body can rely in the fight against various diseases, and it is its failures that underlie any pathology. And therefore, the attending physician always faces a very difficult task: how to cure a person and at the same time “not lose” his immune status, otherwise all the results of therapy will eventually become useless.

To address this critical issue, complex therapy hypercortisolism, the immune drug Transfer factor is used.
The basis of this drug is made up of immune molecules of the same name, which, once in the body, perform three functions:
- eliminate failures of the endocrine and immune systems, and contribute to their further normal development and formation;
- being information particles (of the same nature as DNA), transfer factors "record and store" all information about foreign agents - pathogens of various diseases that (agents) invade the body, and when they invade again, "transmit" this information immune system, which neutralizes these antigens;
- remove everything side effects caused by the use of other medicines reinforcing them at the same time. therapeutic effect.

There is a whole line of this immunomodulator, from which Transfer Factor Advance and Transfer Factor Glucouch are used in the program " Endocrine system for prevention and complex treatment endocrine diseases, incl. and hypercortisolism.

Itsenko-Cushing's disease- disease of the hypothalamic-pituitary system.

Itsenko-Cushing syndrome- Adrenal cortex disease (KN) or malignant tumors non-adrenal localization, producing ACTH or corticoliberin (cancer of the bronchi, thymus, pancreas, liver), leading to hypercortisolism.

Hypercortisolism can also be iatrogenic and functional.

Itsenko-Cushing's disease was first described by the Soviet neuropathologist Itsenko in 1924 and by the American surgeon Cushing in 1932.

Classification of hypercortisolism (Marova N.I. et al., 1992)

Endogenous hypercortisolism.

1. Itsenko-Cushing's disease of hypothalamic-pituitary origin, pituitary tumor.

   Itsenko-Cushing's syndrome - KN tumor - corticosteroma, corticoblastoma; juvenile dysplasia of CI is a disease of primary adrenal origin.

   ACTH-ectopic syndrome - tumors of the bronchi, pancreas, thymus, liver, intestines, ovaries, secreting ACTH or corticotropin-releasing hormone (corticoliberin) or similar substances.

II. Exogenous hypercortisolism.

Long-term administration of synthetic corticosteroids - iatrogenic Itsenko-Cushing's syndrome.

Functional hypercortisolism.

1. Puberty-youthful dispituaitarism (juvenile hypothalamic syndrome).

   hypothalamic syndrome.

   Pregnancy.

   Obesity.

   Diabetes.

   Alcoholism.

   Liver diseases.

Etiology

The basis of the disease and Itsenko-Cushing's syndrome is a tumor process (benign adenomas or malignant) in the hypothalamic-pituitary region or the adrenal cortex. In 70-80% of patients, Itsenko-Cushing's disease is detected, in 20-30% - the syndrome.

In some cases, the disease develops after a brain injury or neuroinfection.

Women are ill more often (3-5 times more often than men), aged 20 to 40 years, but it also occurs in children and in people over 50 years of age.

Pathogenesis

With Itsenko-Cushing's disease the mechanisms of control of ACTH secretion are violated. There is a decrease in dopamine and an increase in serotonergic activity in the central nervous system, as a result of which the synthesis of CRH (corticotropin-releasing hormone, corticoliberin) by the hypothalamus increases. Under the influence of CRH, the secretion of ACTH by the pituitary gland increases, its hyperplasia or adenoma develops. ACTH increases the secretion of corticosteroids - cortisol, corticosterone, aldosterone, androgens by the adrenal cortex. Chronic prolonged cortisolemia leads to the development of a symptom complex hypercortisolism- Itsenko-Cushing's disease.

With Itsenko-Cushing's syndrome tumors of the adrenal cortex (adenoma, adenocarcinoma) produce an excessive amount of steroid hormones, the mechanism of "negative feedback" ceases to operate, there is a simultaneous increase in the content of corticosteroids and ACTH in the blood.

Clinic

The clinical picture of the disease and Itsenko-Cushing's syndrome differs only in the severity of individual syndromes.

Complaints

Patients note a change in their appearance, the development of obesity with red stretching stripes on the skin of the abdomen, chest and thighs, the appearance of headaches and bone pain, general and muscle weakness, sexual dysfunction, changes in the hairline.

Clinical Syndromes

Obesity with a peculiar redistribution of fat: its excessive deposition on the face, in the area cervical spine ("climacteric hump"), chest, abdomen. The face of patients is round ("moon-shaped"), purple-red, often with a cyanotic tint ("meat-red"). Such a face was called the "face of the matron". Appearance patients presents a great contrast: a red face, a short thick neck, a fat torso, with relatively thin limbs and flattened buttocks.

Dermatological Syndrome. The skin is thin, dry, often flaky, with translucent subcutaneous blood vessels, which gives it a marbled appearance (“marbling” of the skin). On the skin of the abdomen, the inner surface of the shoulders, thighs, in the area of ​​​​the mammary glands, wide stripes of stretching appear - strii of a reddish-violet color. Often there is local hyperpigmentation of the skin, often in places of clothing friction (neck, elbows, abdomen), petechiae and bruising on the skin of the shoulders, forearms, and legs.

Acne or pustular rash, erysipelas are often found on the face, back, chest.

Hair on the head often falls out, and in women, baldness resembles the male pattern.

Virilizing syndrome- due to an excess of androgens in women: hypertrichosis, i.e. body hair (in the form of a plentiful fluff on the face and the whole body, the growth of mustaches and beards, on the pubis, male-type growth is diamond-shaped).

Syndrome of arterial hypertension. Hypertension is usually moderate, but may be significant, up to 220-225/130-145 mmHg. Hypertension is complicated by cardiovascular insufficiency: shortness of breath, tachycardia, edema in the lower extremities, liver enlargement.

Arterial hypertension is often complicated by damage to the vessels of the eyes: narrowing of the arteries, hemorrhages, and decreased vision are detected in the fundus. Every 4th patient has an increase in intraocular pressure, in some cases turning into glaucoma with visual impairment. More often than usual, cataracts develop.

The ECG changes as in hypertension - signs of left ventricular hypertrophy: levogram, RV 6 > 25 mm, RV 6 > RV 5 > RV 4, etc., a decrease in the ST segment with a negative T wave in leads I, aVL, V 5 -V 6 (systolic overload of the left ventricle).

An increase in blood pressure is often the only symptom of the disease for a long time, and changes in the cardiovascular system cause disability and most deaths.

Syndrome of osteoporosis. It is manifested by complaints of pain in the bones of various localization and intensity, pathological fractures. Most often, the spine, ribs, sternum, and skull bones are affected. In more severe cases - tubular bones, i.e. limbs. AT childhood the disease is accompanied by growth retardation.

Changes in bone tissue are associated with hypercortisolism: protein catabolism in bone tissue leads to a decrease in bone tissue, cortisol increases Ca ++ resorption from bone tissue, which causes bone fragility. Cortisol also disrupts the absorption of calcium in the intestines, inhibits the conversion of vitamin D to active D 3 in the kidneys.

Sexual dysfunction syndrome. It is caused by a decrease in the gonadotropic function of the pituitary gland and an increase in the production of androgens by the adrenal glands, especially in women.

Women develop menstrual disorders in the form of oligo-amenorrhea, secondary infertility, atrophic changes in the uterine mucosa and ovaries are observed. In men, there is a decrease in potency, sexual desire.

Astheno-vegetative syndrome. Fatigue, mood disturbances from euphoria to depression are characteristic. Sometimes acute psychoses develop, visual hallucinations, epileptoid seizures, convulsions.

Syndrome of muscle weakness. Due to hypercortisolism and the increased breakdown of protein in the muscles caused by it, the development of hypokalemia. Patients complain of a sharp weakness, which is sometimes so pronounced that patients without outside help cannot get up from a chair. On examination, atrophy of the muscles of the limbs, the anterior wall of the abdomen is revealed.

Syndrome of disorders of carbohydrate metabolism. Ranges from impaired glucose tolerance to development diabetes("steroid diabetes"). Glucocorticoids enhance gluconeogenesis in the liver, reduce the utilization of glucose in the periphery (antagonism to the action of insulin), enhance the effect of adrenaline and glucagon on glycogenolysis. Steroid diabetes is characterized by insulin resistance, very rare development of ketoacidosis, and is well controlled by diet and oral glucose-lowering drugs.

Syndrome of laboratory and instrumental data

in general analysis blood revealed an increase in the content of the number of erythrocytes and hemoglobin levels; leukocytosis, lymphopenia, eosinopenia, increased ESR;

hypokalemia, hypernatri- and chloremia, hyperphosphatemia, increased calcium levels, alkaline phosphatase activity, hyperglycemia, glucosuria in some patients.

X-ray, computed and magnetic resonance imaging of the Turkish saddle, adrenal glands can detect an increase in the Turkish saddle, hyperplasia of the pituitary gland tissue, adrenal glands, osteoporosis; Ultrasound of the adrenal glands is not very informative. With Itsenko-Cushing's disease, a narrowing of the visual fields can be detected. Radioimmune scanning reveals a bilateral increase in the absorption of iodine-cholesterol by the adrenal glands.

To clarify the diagnosis of Itsenko-Cushing's disease or syndrome, functional samples: With Dexamethasone(Liddle test) and Sinaktenom-depot (ACTH).

Dexamethasone is taken for 2 days, 2 mg every 6 hours. Then the daily excretion of cortisol or 17-OCS is determined and the results are compared with those before the test. With Itsenko-Cushing's disease, the value of the studied parameters decreases by 50% or more (the "feedback" mechanism is preserved), with Itsenko-Cushing's syndrome it does not change.

Synakten-depot (ACTH) is administered intramuscularly at a dose of 250 mg at 8 am and after 30 and 60 minutes the content of cortisol and 17-OCS in the blood is determined. With Itsenko-Cushing's disease (and in the norm), the content of the determined indicators increases by 2 or more times, with Itsenko-Cushing's syndrome - no. In a doubtful case, the so-called. "big test": Sinakten-depot is administered intramuscularly at 8 am at a dose of 1 mg and the content of cortisol and 17-OCS in the blood is determined after 1, 4, 6, 8, 24 hours. The result is evaluated as in the previous sample.

Sometimes surgical adrenalectomy with histological examination of the material is used.

Differential Diagnosis

Itsenko-Cushing's disease and syndrome

General: the whole clinical picture

Differences:

Table 33

Obesity alimentary-constitutional

General: overweight, hypertension, mental instability, impaired carbohydrate metabolism, sometimes mild hirsutism.

Differences:

Table 34

Hypertonic disease

Differential diagnosis is difficult when an increase in blood pressure is the only and long-term symptom of the disease and Itsenko-Cushing's syndrome.

General: systole-diastolic hypertension.

Differences:

Table 35

Differential diagnosis of the disease and Itsenko-Cushing's syndrome must be carried out with other endocrine diseases: polycystic ovary syndrome (Stein-Leventhal), pubertal-juvenile basophilism (juvenile hypercortisolism); with Cushingism in alcohol abusers.

By severity Itsenko-Cushing's disease can be: mild, moderate and heavy.

Light degree- moderately pronounced symptoms of the disease, some are absent (osteoporosis, mensis disorders).

Intermediate degree- all symptoms are expressed, but there are no complications.

Severe degree- all symptoms are expressed, the presence complications: cardiovascular insufficiency, primary hypertensive wrinkled kidney, pathological fractures, amenorrhea, muscle atrophy, severe mental disorders.

Flow: progressive- rapid development of the entire clinical picture within several months; t orpid- slow, gradual, over several years, the development of the disease.

Treatment

Diet. You need a sufficient amount of high-grade protein and potassium in food, restriction of simple carbohydrates (sugars), solid fats.

Mode. Sparing - liberation from hard physical labor and labor with pronounced mental overstrain.

Radiation therapy. Irradiation of the hypothalamic-pituitary region is used for mild and moderate Itsenko-Cushing's disease.

Apply gamma therapy (radiation source 60 Co) at a dose of 1.5-1.8 Gy 5-6 times a week, the total dose is 40-50 Gy. The effect appears after 3-6 months, remission is possible in 60% of cases.

In recent years, proton irradiation of the pituitary gland has been used. The effectiveness of the method is higher (80-90%), and the side effects are less pronounced.

Radiation therapy can be used in combination with surgical and medical treatments.

Surgery

1. Adrenalectomy unilateral is indicated for the moderate form of Itsenko-Cushing's disease in combination with radiation therapy; bilateral - with a severe degree, while autotransplantation of a portion of the adrenal cortex into the subcutaneous tissue is carried out.

   Adrenal destruction in Itsenko-Cushing's disease, it consists in the destruction of the hyperplastic adrenal gland by introducing a contrast agent or ethanol into it. It is used in combination with radiation or drug therapy.

   Transphenoidal adenomectomy with small pituitary adenomas, transfrontal adenomectomy with large adenomas. In the absence of a tumor, hemihypophysectomy.

Medical therapy aimed at reducing the function of the pituitary and adrenal glands. Use drugs:

A) suppressing the secretion of ACTH;

B) blocking the synthesis of corticosteroids in the adrenal cortex.

ACTH secretion blockers used only as an adjunct to the main methods of treatment.

Parlodel- a dopamine receptor agonist, at a dose of 2.5-7 mg / day, is prescribed after radiation therapy, adrenalectomy and in combination with steroidogenesis blockers. The duration of treatment is 6-24 months.

Cyproheptadine (Peritol) - an antiserotonin drug, prescribed at a dose of 8-24 mg / day for 1-1.5 months.

Adrenal corticosteroid secretion blockers. They are also used as an adjunct to other treatments.

Chloditan is prescribed at a dose of 2-5 g / day until the function of the adrenal cortex normalizes, then they switch to a maintenance dose of 1-2 g / day for 6-12 months. The drug causes degeneration and atrophy of the secretory cells of the adrenal cortex.

Mamomit- a drug that blocks the synthesis of corticosteroids, is prescribed as a means of preoperative preparation for adrenalectomy, before and after radiation therapy in doses of 0.75-1.5 g / day.

Symptomatic therapy. Antibiotics in the presence of infection, immunity stimulants (T-activin, thymalin); antihypertensive drugs, treatment of heart failure; with hyperglycemia - diet, oral hypoglycemic drugs; treatment of osteoporosis: vitamin D 3 (oxidevit), calcium salts, hormones calcitonin or calcitrin (see "Osteoporosis").

Clinical examination

In remission, patients are examined by an endocrinologist 2-3 times a year, by an ophthalmologist, neurologist and gynecologist - 2 times a year, by a psychiatrist - according to indications.

General blood and urine tests, hormone and electrolyte levels are assessed twice a year. Radiation examination of the area of ​​the Turkish saddle and spine is performed once a year.

5.1. Find the bug! Etiological factors of chronic insufficiency of the adrenal cortex are:

hypertonic disease;

AIDS (acquired immunodeficiency syndrome);

tuberculosis;

autoimmune process in the adrenal cortex.

5.2. Find the bug! The most common clinical signs of Addison's disease are:

skin hyperpigmentation;

hypotension;

weight gain;

decreased function of the gonads.

5.3. Find the bug! In the treatment of chronic adrenal insufficiency, depending on the etiology, the following are used:

glucocorticoids;

a diet high in protein

anti-tuberculosis drug;

salt restriction.

5.4. Find the bug! Addisonian crisis is characterized by:

increased blood pressure;

severe loss of appetite;

repeated vomiting;

cerebral disorders: epileptoid convulsions.

5.5. Find the bug! Addisonian crisis is characterized by electrolyte imbalance:

decrease in blood chloride<130 ммоль/л;

decrease in potassium in the blood<2 мэкв/л;

lowering glucose<3,3ммоль/л;

decrease in sodium in the blood<110 мэкв/л.

5.6. Find the bug! To provide emergency care for aadisonian crisis, use:

hydrocortisone intravenously;

hydrocortisone intravenously drip;

lasix intravenous bolus;

cardiac glycosides intravenously.

5.7. Find the bug! In the differential diagnosis of the syndrome and Itsenko-Cushing's disease, studies are of great importance:

determination of ACTH concentration;

adrenal scan;

computed tomography of the Turkish saddle (pituitary gland);

test with CRH (corticotropin-releasing hormone).

5.8. Find the bug! Catecholamine crisis in pheochromocytoma is characterized by:

significant acute hypertension against the background of normal blood pressure;

persistent hypertension without crises;

significant acute hypertension against the background of elevated blood pressure;

frequent random change of hyper- and hypotensive episodes.

5.9. Find the bug! In the relief of a catecholamine crisis in pheochromocytoma, the following are used:

α-blockers - phentolamine intravenously;

vascular agents - caffeine intravenously;

β-blockers - propracolol intravenously;

sodium nitroprusside intravenously.

5.10. Typically, the most life-threatening complication of a catecholamine crisis is:

significant hyperglycemia;

symptoms of "acute abdomen";

severe cardiac arrhythmias;

Sample answers: 1 -1; 2 -3; 3 -4; 4 -1; 5 -2; 6 -3; 7 -1; 8 -2; 9 -2; 10 -4.

6. List of practical skills .

Questioning and examination of patients with diseases of the adrenal glands; identification in history of risk factors that contribute to the defeat of the adrenal glands; identification of the main clinical syndromes in diseases of the adrenal glands. Palpation, percussion of the abdominal organs. Making a preliminary diagnosis, drawing up a plan for examination and treatment of a particular patient with adrenal pathology. Evaluation of the results of the study of general clinical tests (blood, urine, ECG) and specific samples confirming the defeat of the adrenal glands: the content of hormones of glucocorticoids, catecholamines in the blood and urine, ultrasound, CT of the adrenal glands; provocative tests. Conducting differential diagnosis with similar diseases. Appointment of treatment for insufficiency of the adrenal cortex, chromaffinoma, Itsenko-Cushing's syndrome. Providing emergency care for Addisonian crisis, catecholamine crisis.

7. Independent work of students .

In the ward at the bedside of the patient conducts questioning, examination of patients. Identifies complaints, anamnesis, risk factors, symptoms and syndromes that have diagnostic value in the diagnosis of adrenal disease.

In the training room, he works with a clinical history of the disease. Gives a qualified assessment of the results of laboratory and instrumental examination. Works with teaching aids on this topic of the lesson.

8. Literature .

It is known that the hormones produced by the adrenal cortex perform very important functions in the body. With insufficient or excessive secretion of cortical hormones, various diseases develop. Itsenko-Cushing's syndrome is a complex of symptoms resulting from excessive synthesis of cortical hormones in the adrenal glands. There are several types of this disease, and they all have similar symptoms. The reasons for this state of affairs are many. It can be a tumor, a violation of hormonal regulation and other disruptions in the body. Subclinical hypercortisolism can be completely asymptomatic.

Itsenko-Cushing syndrome, or hypercortisolism syndrome, occurs due to the fact that the hypothalamus secretes a lot of corticoliberins - substances that stimulate the pituitary gland to increase the production of adrenocorticotropic hormone (ACTH), and it, in turn, causes excessive synthesis of hormones of the adrenal cortex.

What types of adrenal hyperfunction are there?

There are primary and secondary hypercortisolism:

• The causes of primary hyperfunction are mainly tumors of the adrenal glands - corticosteromas. They are mainly hormonally active, that is, they produce hormones. A lot of glucocorticoids and a certain amount of androgens and mineralocorticoids are released into the blood. Also, the cause of this type of disorder can be tumors located in other organs that synthesize ACTH-like compounds.
• Secondary hypercortisolism occurs due to disturbances in the work of the hypothalamic-pituitary-adrenal system. A brief description of the mechanism of development of this state is given above. Another cause of secondary hypercortisolism may be pituitary adenoma, which stimulates increased production of ACTH, which in turn leads to a large release of cortical hormones into the blood.

According to the forms of the course, the syndrome of hyperfunction of the adrenal glands is divided into 3 types:

• The subclinical form occurs in the presence of so-called inactive tumors of the adrenal gland. In 10 patients out of 100, a corticosteroma is determined, which secretes cortisol in small amounts, which does not cause clinical manifestations. But according to some signs, it can be concluded that there is a syndrome of hypercortisolism. The patient may experience an increase in blood pressure, disorders in the reproductive system, diabetes mellitus.
• Iatrogenic hypercortisolism is also called medicinal or exogenous. It occurs in patients who have been treated with synthetic corticosteroids for a long time. What is it and in what cases is it applied? Long-term corticosteroids are indicated for inflammatory diseases such as rheumatism, various kidney pathologies, blood disorders, and chronic connective tissue diseases. Also, this group of drugs is prescribed to people who have undergone organ transplantation. Exogenous hypercortisolism occurs in 70% of cases.
• Functional hypercortisolism occurs in people with obesity, diabetes, liver disease, hypothalamic syndrome, and depression. Also, this condition is diagnosed with pubertal and youthful dispituitarism, pregnancy and alcoholism.

Clinical manifestations of the disease

The main symptoms of hypercortisolism:

• Constant fatigue
• Sleep disturbance up to insomnia
• progressive weakness
• Decreased appetite
• Painful sensations in the abdomen
• Change in body weight
• Nausea and vomiting
• Constipation followed by diarrhea
• Increasing muscle weakness
• Decreased muscle tone of the skeleton and internal organs
• Hyperpigmentation of the skin and mucous membranes - melanosis.
• depression
• Dry skin and its increased peeling
• Increasing the amount of hair on the face and body
• Rachiocampsis
• Spontaneous bone fractures
• Osteoporotic changes in the bones
• Fluid retention in the body
• Edema
• Cardiovascular disorders
• neurological disorders.

What therapeutic measures are assigned to patients?

An integrated approach is used to treat hypercortisolism. The main goal of treatment is to stop the clinical manifestations of the syndrome and restore the physiological rhythm of hormone synthesis. Prescribe medications that can suppress the excess synthesis of cortisol and corticotropin. In the case of adrenal hyperplasia or pituitary adenoma, surgery or radiation therapy is indicated.

Drug treatment with inhibitors of the production of corticotropin and corticoliberin is prescribed when central hypercorticism is detected. Usually, patients are prescribed Peritol, a serotonin inhibitor, for a course of 4 weeks. It reduces the production of corticoliberin in the hypothalamus. Also dopamine agonists such as Abergin and Bromergon (Parlodel) for 6 to 10 months.

They reduce the release of corticotropin. In addition, inhibitors of the formation of corticosteroids in the cortical substance of the adrenal glands are prescribed. These are drugs Mamomit and Metapiron. Do not think that such a violation as hyperfunction of the adrenal glands is treated quickly. It takes time for all processes to return to normal. Usually treatment is delayed for 6 months or more.

Symptomatic therapy is aimed at correcting the metabolism of carbohydrates, electrolytes and proteins. Prescribe drugs that lower blood pressure and normalize the work of the heart and blood vessels. Osteoporosis is a frequent complication of adrenal hyperfunction, so prevention of bone fractures is important in the treatment of this syndrome. To normalize protein metabolism, doctors prescribe anabolic steroids, for example, Nerobolil and Retabolil. I regulate carbohydrate metabolism by correcting nutrition if there is a violation of carbohydrate tolerance, as well as by prescribing insulin or sulfonylurea derivatives in case of diabetes mellitus.

Since the syndrome of hyperfunction of the adrenal cortex is accompanied by hypoxia, patients should not take biguanides, and correction of electrolyte metabolism is carried out with potassium preparations. With high blood pressure, antihypertensive therapy is prescribed, and in case of violations of the cardiovascular system, cardiac glycosides and diuretics are prescribed. To prevent osteoporosis, it is recommended to take drugs that accelerate the absorption of calcium in the intestines: vitamin D derivatives. To fix calcium in the bones, Calcitonin and Calcitrin are prescribed. To prevent fractures and other unpleasant complications of osteoporosis, therapy should be carried out for at least 1 year.

Hypercortisolism is a disease of the adrenal glands, which results in a significant increase in the level of cortisol in the body. These glucocorticoid hormones are directly involved in the regulation of metabolism and many physiological functions. The adrenal glands are controlled by the pituitary gland through the production of adrenocorticotropic hormone, which activates the synthesis of cortisol and corticosterone. What happens to people with this syndrome, what causes it and how to treat diseases, we will consider later in the article.

Hypercortisolism: what is it?

Hypercortisolism or Itsenko-Cushing's syndrome is an endocrine pathology associated with prolonged and chronic exposure of the body to an excessive amount of cortisol. Such an effect may occur due to existing ailments or against the background of taking certain medications. Women are 10 times more likely than men to suffer from hypercortisolism, and mostly between the ages of 25 and 40.

In order for the pituitary gland to function normally, sufficient production of specific hormones by the hypothalamus is necessary. If this chain is broken, then the whole organism suffers and this affects the state of human health. For the first time the clinical picture of endogenous hypercortisolism was described in 1912 by Harvey Cushing.

Hypercoticism is manifested by the fact that cortisol in large quantities slows down the production of glucose, which is very necessary for our cells. As a result, the functionality of many cells decreases and tissue atrophy is observed.

• ICD 10 code: E24.0

Pathogenesis

The basis of the disease is a violation of feedback in the functional system of the hypothalamus-pituitary gland - the adrenal cortex, characterized by constantly high activity of the pituitary gland and hyperplasia of corticotropes or, much more often, the development of ACTH-producing pituitary adenomas and hyperplasia of the cortex of both adrenal glands.

As a result, the rate of production and the total daily excretion of almost all fractions of corticosteroids increase with the development of symptoms of hypercorticism. The basis of Itsenko-Cushing's syndrome is the formation of an autonomous benign or malignant tumor of the adrenal gland or adrenal dysplasia.

Hypercortisolism Syndrome leads to to a decrease in libido in both women and men. In the latter, it is also manifested by impotence.

The reasons

To date, doctors have not been able to fully study the causes that affect the dysfunction of the adrenal glands. It is only known that with any factor that provokes an increase in the production of hormones by the adrenal glands, a disease develops. The provoking factors of hypercortisolism are:

• adenoma that has arisen in the pituitary gland;
• the formation of tumors in the lungs, pancreas, bronchial tree, which produce ACTH;
• long-term use of glucocorticoid hormones;
• hereditary factor.

In addition to the above factors, the occurrence of the syndrome can be affected by such circumstances:

• injury or concussion;
• traumatic brain injury;
• inflammation of the arachnoid membrane of the spinal cord or brain;
• inflammatory process in the brain;
• meningitis;
• bleeding into the subarachnoid space;
• damage to the central nervous system.

Sometimes the symptoms of the syndrome can be caused by completely different factors, but this is only a temporary phenomenon and does not mean that a person has true hypercortisolism.

Common causes of pseudo-Cushing's syndrome are obesity, chronic alcohol intoxication, pregnancy, stress and depression, and sometimes even taking oral contraceptives that contain a mixture of estrogen and progesterone.

An increase in cortisol levels in the blood can even occur in infants when alcohol enters their body along with breast milk.

Kinds

Excessive synthesis of glucocorticoids occurs under the influence of corticotropin and corticoliberin or independently of them. In this regard, ACTH-dependent and ACTH-independent forms of pathology are distinguished. The first group includes:

• Central hypercortisolism.
• ACTH-ectopic syndrome.

In medicine, there are three types of hypercortisolism, which are based on the difference in the causes of the pathology:

• exogenous;
• endogenous;
• pseudo syndrome.

In medical practice, there are also cases of juvenile syndrome of hypercortisolism. Youth is singled out as a separate species and is due to age-related hormonal changes in the body of a teenager.

Exogenous

Under the influence of external causes, such as the use of drugs containing glucocorticoids for the treatment, iatrogenic or exogenous hypercorticism may develop. Basically, it disappears after the abolition of the pathology-provoking drug.

Endogenous

Factors in the development of endogenous hypercortisolism may be the following reasons:

• pituitary tumors ();
• bronchi;
• tumors of the testicles, ovaries;
• tumor or hyperplasia of the adrenal cortex.

The provoking tumor of the bronchi or gonads is most often ectopic corticotropinoma. It is she who causes increased secretion of corticosteroid hormone.

Pseudo Syndrome

Untrue hypercorticism occurs for the following reasons:

• alcoholism;
• pregnancy;
• taking oral contraceptives;
• obesity;
• stress or prolonged depression.

The most common cause of pseudo-syndrome is severe alcohol poisoning. However, there are no tumors.

Symptoms of hypercortisolism in women and men

The clinical picture of hypercortisolism is characterized by symptoms:

• progressive weakness;
• constant fatigue;
• insomnia;
• fatigue;
• hypotension;
• mental asthenia;
• lack of appetite;
• nausea;
• vomit;
• constipation,
• alternating with diarrhea;
• stomach ache;
• weight loss.

A pathological increase in the rate of glucocorticoids leads to the appearance of hypercorticism syndrome. Patients complain about changes in appearance and malfunction of the cardiovascular system, as well as the musculoskeletal, reproductive, and nervous systems. The clinical manifestations of the disease are also caused by an increased content of aldosterone and androgens produced by the adrenal glands.

Symptoms in women

Hypercortisolism in women is manifested by the following symptoms:

• hirsutism;
• virilization;
• hypertrichosis;
• failure of menstrual cycles;
• amenorrhea and infertility.

The most "popular" manifestation of hypercortisolism on the part of the musculoskeletal system is osteoporosis (it is found in 90% of people suffering from the syndrome). This pathology tends to progress: first, it makes itself felt with pain in the joints and bones, and then with fractures of the arms, legs and ribs. If a child suffers from osteoporosis, he has a lag behind his peers in growth.

Signs in men

Male hypercortisolism is manifested by problems in the reproductive system: a decrease in potency and libido, testicular atrophy and gynecomastia. Also, hypercoticism can manifest itself as a malfunction of the nervous and cardiovascular systems.

"Nervous" symptoms:

• and stress;
• change from euphoric state to depression;
• lethargy;
• suicidal attempts.

Cardiovascular symptoms:

• Heart arythmy;
• heart failure.

The skin of patients has a characteristic "marble" shade with a clearly visible vascular pattern, prone to peeling, dryness, interspersed with areas of sweating. On the skin of the shoulder girdle, mammary glands, abdomen, buttocks and thighs, stripes of skin stretching are formed - striae of purple or cyanotic color, from several millimeters to 8 cm long and up to 2 cm wide. Skin rashes (acne), subcutaneous hemorrhages, spider veins, hyperpigmentation of certain areas of the skin.

The syndrome negatively affects the hormonal background of the patient, an unstable emotional state is observed: depression alternates with euphoria and psychosis.

Complications

One of the most dangerous complications of hypercortisolism is an adrenal crisis, which manifests itself:

• impaired consciousness;
• vomiting and high blood pressure;
• hyperkalemia;
• hyponatremia;
• hypoglycemia;
• pain in the abdomen;
• metabolic acidosis.

Cushing's syndrome, which has become chronic, can lead to the death of a person, since it provokes a number of serious complications, namely:

• heart decompensation;
• stroke;
• sepsis;
• severe pyelonephritis;
• chronic kidney failure;
• osteoporosis, in which numerous fractures of the spine occur.

Diagnostics

The following methods are used to diagnose this disease:

• blood test for adrenocorticotropic hormone and corticosteroids;
• hormonal urine tests;
• x-ray of the head, bones of the skeleton;
• MRI or CT of the brain.

The diagnosis is made clearly in the presence of all studies. It should be differentiated from diabetes and obesity.

None of the laboratory diagnostic tests for hypercortisolism can be considered absolutely reliable, so it is often recommended to repeat and combine them. The diagnosis of hypercortisolism is established on the basis of increased urinary excretion of free cortisol or dysregulation of the hypothalamic-pituitary-adrenal system:

• daily excretion of free cortisol and 17-hydroxycorticosterone is increased;
• there is no daily biorhythm of cortisol secretion;
• the content of cortisol at 23-24 h is increased.

Outpatient research

• Free cortisol in daily urine. The proportion of false negative results in this test reaches 5-10%, so the study is recommended to be carried out 2-3 times. False-positive results also provoke the use of fenofibrate, carbamazepine, and digoxin, and false-negative results are possible with reduced glomerular filtration (<30 мл/мин).
• Overnight dexamethasone test. False-negative results (i.e., no reduction in cortisol) occur in 2% of healthy individuals and increase to 20% in obese patients and among hospitalized patients.

If in both of the above tests hypercortisodism is not confirmed, its presence in the patient is unlikely.

Treatment

Based on the data obtained during the diagnosis, the doctor may suggest one of three methods of treating hypercortisolism:

Medications

Drugs can be prescribed both independently and as part of complex therapy. The basis of drug treatment of hypercortisolism is drugs, the action of which is aimed at reducing the production of hormones in the adrenal glands. Such medicines include drugs such as Metyrapone, Aminoglutethimide, Mitotan or Trilostane. Usually they are prescribed in the presence of contraindications to other methods of treatment and in cases where these methods (for example, surgical) have been ineffective

Radiation therapy

Radiation therapy is prescribed when the syndrome is provoked by a pituitary adenoma. In this case, radiation exposure is applied to the affected area, which provokes a decrease in the production of adrenocorticotropic hormone. Radiation therapy is combined with medical or surgical treatment. Thus, it is possible to achieve the most positive result in the treatment of hypercortisolism.

Surgical intervention

Pituitary Cushing's syndrome in the later stages needs surgical therapy. The patient is prescribed a transsphenoidal revision of the pituitary gland and the adenoma is eliminated using microsurgical techniques. This therapeutic method brings the greatest effect and is marked by a rapid improvement in the condition after the operation. In severe cases, during surgery, patients remove two adrenal glands. These patients are treated with lifelong glucocorticoids.

What determines the effectiveness of treatment?

Hypercortisolism can have a rapid development, that is, all symptoms appear within 6-12 months, and there may be a gradual development of the clinical picture over 3-10 years. Treatment will depend on the correct diagnosis, the severity of the disease, and the speed with which symptoms develop. Treatment should be aimed at eliminating clinical manifestations and normalizing cortisol levels.

With moderate and mild severity, drugs are used that will not allow the body to produce an excess amount of adrenal hormones, or radiation therapy is prescribed, which reduces the activity of the pituitary gland. If all this does not give the desired effect, then surgical treatment is used. During this intervention, the pituitary tumor is removed. Either an adrenalectomy is performed, that is, the removal of one of the adrenal glands, but after such an operation, constant replacement therapy is necessary.

Syndrome prognosis

If the treatment of hypercorticism syndrome is ignored, irreversible changes develop, leading to death in 40-50% of patients. If the cause of the syndrome was a benign corticosteroma, the prognosis is satisfactory, although the functions of a healthy adrenal gland are restored only in 80% of patients. When diagnosing malignant corticosteromas, the five-year survival prognosis is 20-25% (average 14 months). In chronic adrenal insufficiency, lifelong replacement therapy with mineral and glucocorticoids is indicated.

In general, the prognosis is determined by the timeliness of diagnosis and treatment, the causes, the presence and severity of complications, the possibility and effectiveness of surgical intervention. Patients with hypercortisolism syndrome are under dynamic observation by an endocrinologist, they are not recommended for heavy physical exertion, night shifts at work.

Excessive production of glucocorticoids (produced by the adrenal cortex), which may be due either to the pathology of the adrenal glands themselves (tumor, nodular hyperplasia), or hyperproduction of ACTH (pituitary adenoma). In the first case, this condition is usually referred to as Itsenko-Cushing's syndrome, in the second - Itsenko-Cushing's disease.

Pathogenesis of hypercortisolism

basis Itsenko-Cushing's disease constitutes a violation of the feedback in the functional system of the hypothalamus-pituitary gland - the adrenal cortex, characterized by constantly high activity of the pituitary gland and hyperplasia of corticotropes or, much more often, the development of ACTH-producing pituitary adenomas and hyperplasia of the cortex of both adrenal glands. As a result, the rate of production and the total daily excretion of almost all fractions of corticosteroids increase with the development of symptoms of hypercorticism. At the core Itsenko-Cushing's syndrome lies the formation of an autonomous benign or malignant tumor of the adrenal gland or adrenal dysplasia.

Symptoms of hypercortisolism

For typical symptoms of hypercortisolism characterized by a generalized lesion of almost all organs and systems, a decrease in the growth rate, an increase in body weight, an uneven distribution of fat, hirsutism, striae, hyperpigmentation, primary or secondary amenorrhea, osteoporosis, muscle weakness. Itsenko-Cushing's syndrome in terms of symptoms and manifestations is not much different from Itsenko-Cushing's disease.

Features of Itsenko-Cushing's disease in children is a uniform distribution of fat in 70% of patients, and only 30% - its classical distribution. Typical for Itsenko-Cushing's disease in children is growth retardation (nanism). One of the characteristic features of the lesion of the bone skeleton in Itsenko-Cushing's disease in children is a violation of the order and timing of ossification of the bones of the skeleton, and sometimes the appearance of other signs of pathological ossification.

Neurological signs found in children with Itsenko-Cushing's disease have different severity, but are unstable, transient. This is apparently due to the fact that in most cases they are based on functional changes due to cerebral edema, or dynamic shifts in intracranial pressure due to high hypertension.

With Itsenko-Cushing's disease in children, regardless of gender, there is a lag in sexual development with the premature appearance of sexual hair growth, which can be explained by excessive production of the adrenal glands along with glucocorticoids and androgens. Children with Itsenko-Cushing's disease have a tendency to easy bleeding, hemorrhagic rashes are often observed, which is associated with changes in the blood coagulation system (a significant increase in heparin in the blood, a decrease in the prothrombin index), as well as thinning and atrophy of the skin due to a decrease in the content tissue proteins and increased capillary permeability.

Depending on the degree of myopathic syndrome, trophic disorders, osteoporosis, steroid diabetes, hypertension, mental disorders, immunodeficiency and sexual dysfunction, different degrees of severity of the disease are distinguished.

In a mild form, a combination of 3-4 signs characteristic of hypercortisolism is observed - more often dysplastic obesity, trophic skin disorders, moderate hypertension and sexual dysfunction, mild osteoporosis.

With moderate severity, Itsenko-Cushing's disease develops almost all the symptoms of hypercortisolism.

The severe form is characterized by the presence of complications in the form of decompensation of the cardiovascular system, severe osteoporosis with fractures, etc. Depending on the rate of increase in clinical symptoms, a rapidly progressive (within 3-6 months) course and a torpid course of the disease are distinguished.

Diagnosis of hypercortisolism

The main diagnostic criteria are data on increased activity of the pituitary-adrenal system and the results of topical diagnostics. Itsenko-Cushing's disease is characterized by a simultaneous increase in blood levels of cortisol and ACTH, as well as increased daily urinary excretion of free cortisol and 17-OCS.

With an erased clinical picture and a slight increase in the function of the adrenal cortex, the results of a small dexamethasone test based on the ability of dexamethasone to suppress ACTH secretion are used to prove the presence of pathological and exclude functional hypercortisolism.

A large dexamethasone test allows you to differentiate Itsenko-Cushing's disease and Itsenko-Cushing's syndrome (A large test with dexamethasone is carried out for 3 days - 2 mg of dexamethasone is given 4 times a day or 8 mg per day. The test is considered positive. If on the second and third days the release of 17-OCS is reduced by more than 50%).

With Itsenko-Cushing's disease the test is positive, and with a corticosteroma, it is negative. The purpose of topical diagnosis in Itsenko-Cushing's disease is to identify macro- or microadenomas of the pituitary gland and bilateral adrenal hyperplasia.

With Itsenko-Cushing's syndrome- a tumor of one adrenal gland is detected with a reduced or normal size of the other. To solve this problem, the X-ray method of investigation is used - the pathology of the Turkish saddle, ultrasound of the adrenal glands, computed tomography, MRI, angiography of the adrenal glands.

Differential diagnosis of hypercortisolism

With severe hypercortisolism, a differential diagnosis is made between Itsenko-Cushing's disease and corticosteroma, a syndrome of ectopic ACTH production. With an erased form - with pubertal youthful dispituitarism or hypothalamic syndrome of the puberty period (PYUD).

PJD is characterized by dysfunction of the hypothalamic-pituitary system. Clinical manifestations of this condition are uniform obesity, multiple thin striae, transient hypertension, tall stature (in early puberty), accelerated or normal bone differentiation, folliculitis. Striae on the skin from whitish to purplish red are pathognomonic for PJB. The development of secondary sexual characteristics begins on time, but proceeds quickly and ends prematurely.

The outcome of PJB may be a spontaneous recovery or, less commonly, a transition to the hypothalamic syndrome, Itsenko-Cushing's disease.

Treatment of hypercortisolism

In the treatment of these patients, importance is attached to diet therapy, dehydration therapy, nootropics. Treatment of Itsenko-Cushing's disease surgical, radiation and medical. Both their combination and monotherapy are used.