Cushing's syndrome (hypercorticism): causes, symptoms, treatment. When does the syndrome of hypercortisolism occur, and what are its forms? Functional hypercortisolism

Hypercortisolism is a disease that develops in violation of the hypothalamic-pituitary system and has a multi-symptomatic course.

This disease was discovered and studied by two scientists: neurosurgeon Harvey Cushing in America and neuropathologist Nikolai Itsenko in Odessa. In their honor, hypercortisolism is otherwise called Itsenko-Cushing's disease.

Glucocorticosteroid hormones are necessary for metabolism in the body, but when they increase, various changes can appear in the body.

How does this disease manifest itself?

The main symptoms most often appear are:

1. obese;
2. Increased blood pressure;
3. muscle weakness;
4. Violation of sexual function;
5. Pigment spots may appear on the skin;
6. Women grow hair on their chest and face.

Obesity in such patients has a peculiar appearance, that is, subcutaneous fat in more accumulates in the supraclavicular region, shoulders and cervical vertebrae, and the abdomen also increases. As a result of the redistribution of fatty tissue, the arms and legs become thin, the muscles atrophy. The face acquires a “moon-shaped” shape, the skin becomes dry and flaky, sores appear that are difficult to treat, the cheeks have a purple-red color. Other symptoms include stretch marks on the chest, hips, abdomen, which are red or purple.

The most dangerous manifestation in hypercortisolism is a violation of the heart and blood vessels, because of this, a syndrome of arterial hypertension occurs. With an increase in pressure, headaches appear, flashing "flies" before the eyes. Due to a metabolic failure, diabetes mellitus, osteoporosis, which is very difficult, can develop.

Hypercortisolism leads to a significant decrease in immunity, which serves as a catalyst for the appearance of ulcers, pustules, pyelonephritis, fungal infections of the nails and skin. Also, symptoms include nervous system, there may be sleep disturbance, bad mood, psychosis.

In girls, after the onset of the menstrual cycle, amenorrhea (a condition when there is no menstruation) may occur. There is a delay in growth and sexual development, the voice becomes rough.

As a result of what the disease can develop?

The causes of this disease have not yet been fully identified, but it has been established that in the fair sex, Itsenko-Cushing's disease occurs ten times more often than in males.

Such a disease can develop in any age range, but more often they get sick in 20-40 years.
The causes can be various head injuries and brain lesions (educations, inflammation), pregnancy, neuroinfection, tumors of the adrenal glands, pancreas, lungs, bronchi. The main cause is considered an adenoma of the anterior pituitary gland.

How to identify hypercortisolism?

The doctor must examine the patient, interview, then laboratory diagnostics are already carried out. With its help, the daily secretion of cortisol in the blood stream and the amount of free cortisol in the daily urine are determined.

To identify the disease hypercortisolism, you need to conduct a small test with dexamethasone. Thanks to it, a pituitary tumor can be detected.

Another pituitary adenoma is determined by X-ray examination of the bones of the skull, CT and MRI of the brain. Using such diagnostic studies, it is possible to determine the location of the tumor, its size, growth, and what tissues it comes into contact with, which is necessary to prescribe the correct treatment for it.

In addition, it is necessary to do a study of the adrenal glands using ultrasound, magnetic resonance and computed tomography.

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.

For moderate and mild severity, apply medications, which 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.

Varieties of hypercortisolism

Functional

Functional hypercortisolism occurs as a result of various diseases, which indirectly increase the content of cortisol in the body. Such ailments include: polycystic ovary syndrome, obesity, cirrhosis of the liver, chronic hepatitis, anorexia, disorders of the nervous system, depression, alcoholism, pregnancy and puberty are other causes of functional hypercortisolism.

Secondary

Secondary hypercorticism in pregnant women develops with an increase in adrenocorticotropic hormone, which is responsible for the work of the adrenal glands. First, the hypothalamus is affected, and then the pituitary gland is affected and its tumor develops, an adrenal adenoma appears.

The symptomatology is very similar to that of ordinary hypercortisolism, the metabolism is disturbed, which can cause a violation of the development and growth of the fetus and even lead to its death. The diagnosis is made on the basis of anamnesis, examination, X-ray craniographic examination (the Turkish saddle does not increase much, since corticotropic tumors are not large), MRI is performed, laboratory examinations of hormones, hormone tests with dexamethasone or metapiron are used.

If a woman became pregnant during the period of time when she had an active stage of secondary hypercortisolism, then an abortion should be performed. To endure and give birth to a child, the disease must be in remission, when blood pressure is normal, metabolism is not disturbed, and replacement therapy is carried out. Only 30% of women with this disease can endure and give birth to a child.

During pregnancy, you need to constantly monitor blood pressure, body weight, edema, hormone levels, urination, and determine the amount of sugar in the blood. You need to visit an endocrinologist every three months, follow a diet low in salt and carbohydrates, eat more fruits and vitamins.

At the birth of a child with low weight, with low blood pressure and with an increase in corticosteroid hormones in the urine, the doctor prescribes glucocorticosteroid drugs, the child should be registered with an endocrinologist and a neuropathologist.

Endogenous

Endogenous hypercortisolism in 80-85% of cases develops with a tumor or hyperplasia of the pituitary gland. It happens:

1. ACTH-dependent hypercortisolism;
2. ACTH-ectopic syndrome;
3. ACTH-independent hypercortisolism;
4. Corticosteroma;
5. Macronodular hyperplasia of the adrenal cortex;
6. Micronodular hyperplasia of the adrenal cortex.

Clinical manifestations include obesity at a young age, increased blood pressure, osteoporosis, muscle atrophy and weakness, trophic changes in the skin, amenorrhea, poor growth in children, and the appearance of a tumor of the adrenal glands.

subclinical

Subclinical hypercortisolism develops with a tumor of the adrenal glands and occurs in 5-20% of people. It can be determined with a hardware examination (ultrasound, MRI, CT). This form is detected by chance, since there are no clinical manifestations or they are less pronounced, the level of cortisol in the daily urine is within the normal range. But if the patient is prescribed surgical treatment, then subclinical hypercortisolism must be excluded so that postoperative complications do not occur.

The adrenal gland is a small paired organ that plays an important role in the functioning of the body. Often, Itsenko-Cushing's syndrome is diagnosed, in which the cortex internal organ produces an excess of glucocorticoid hormones, namely cortisol. In medicine, this pathology is called hypercortisolism. It is characterized by severe obesity, arterial hypertension and various metabolic disorders. Most often, the deviation is observed in women under 40 years old, but often hypercortisolism is diagnosed in men.

general information

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. 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.

Hypercortisolism in women is diagnosed ten times more often than in the representatives of the stronger sex. Medicine also knows Itsenko-Cushing's disease, which is associated with primary damage to the hypothalamic-pituitary system, and the syndrome has a secondary degree. Often, doctors diagnose a pseudo-syndrome that occurs against the background of alcohol abuse or severe depression.

Classification

Exogenous

The development of exogenous hypercorticism is affected by prolonged use of synthetic hormones, resulting in an increase in the level of glucocorticoids in the body. This is often observed if a person is very ill and needs to take hormonal preparations. Often exogenous syndrome manifests itself in patients with asthma, arthritis of the rheumatoid type. The problem can occur in people after organ transplants.

Endogenous

The development of the endogenous type of the syndrome is influenced by disorders that occur inside the body. Most often, endogenous hypercorticism manifests itself in Itsenko-Cushing's disease, as a result of which the amount of adrenocorticotropic hormone (ACTH) produced by the pituitary gland increases. The development of endogenous hypercortisolism is affected by malignant tumors (corticotropinomas) that form in the testicles, bronchi or ovaries. In some cases, primary deviations of the organ cortex can provoke pathology.

Functional

Functional hypercortisolism or pseudo-syndrome is a temporary condition. A functional deviation may be associated with intoxication of the body, pregnancy, alcoholism or mental disorders. Juvenile hypothalamic syndrome often leads to functional hypercortisolism.

With a functional disorder, the same symptoms are observed as with the classical course of hypercortisolism.

The main causes of Itsenko-Cushing's syndrome

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 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.

Development mechanism

If at least one of the above factors is noticed in a person, then a pathological process can be started. The hypothalamus begins to produce a large amount of the hormone corticoliberin, which leads to an increase in the amount of ACTH. Thus, hyperfunction of the adrenal cortex occurs, it is forced to produce glucocorticoids 5 times more. This provokes an overabundance of all hormones in the body, as a result, the function of all organs is disrupted.

External manifestations and symptoms

Adrenal Cushing's syndrome is manifested by many symptoms that are difficult to ignore. The main characteristic sign of hypercortisolism is increased weight gain. A person can acquire a 2nd or 3rd degree of obesity in a short period. In addition to this symptom, the patient has the following deviations:

1. The muscles of the legs and upper limbs atrophy. The person complains of fatigue and constant weakness.
2. The condition of the skin is deteriorating: they dry out, acquire a marble shade, and the elasticity of the skin is lost. A person may notice stretch marks, pay attention to the slow healing of wounds.
3. Sexual function also suffers, which is manifested by a decrease in libido.
4. In the female body, hypercortisolism is manifested by male-type hair growth, the menstrual cycle is disturbed. In some cases, periods may disappear altogether.
5. Osteoporosis develops, in which bone density decreases. At the first stages, the patient is worried about pain in the joints, over time, unreasonable fractures of the legs, arms, and ribs occur.
6. The work of the cardiovascular system is disrupted, which is associated with negative hormonal effects. Diagnosed with angina pectoris, hypertension, heart failure.
7. In most cases, hypercortisolism provokes steroid diabetes mellitus.

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

Pathology of the adrenal glands in children

In a child's body, abnormalities in the work of the adrenal glands occur for the same reasons as in adults. In children with hypercortisolism, dysplastic obesity is observed, in which the face becomes "moon-shaped", the fat layer increases on the chest and abdomen, and the limbs remain thin. The disease is characterized by myopathy, hypertension, systemic osteoporosis, encephalopathy. In children, there is a lag in sexual development, as well as a secondary type of immunodeficiency. Hypercortisolism in children causes them to grow more slowly. In a teenage girl, after the onset of the menstrual cycle, amenorrhea is possible, in which menstruation may be absent for several cycles.

When contacting a specialist, the first thing he will pay attention to is the enlarged face of the child, the cheeks will be painted purple. Due to the fact that there is an overabundance of androgens in the body, the teenager develops increased acne, the voice becomes rougher. The child's body becomes weaker and more susceptible to infectious lesions. If you do not pay attention to this fact in a timely manner, then sepsis may develop.

Possible Complications

Cushing's syndrome, which has progressed to chronic form can lead to the death of a person, because 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.

Hypercortisolism gradually leads to an adrenal crisis, in which the patient experiences disturbances in consciousness, arterial hypotension, frequent vomiting, and pain in the abdominal cavity. The protective properties of the immune system are reduced, resulting in furunculosis, suppuration and fungal infection of the skin. If a woman is in a position and she has been diagnosed with Itsenko-Cushing's syndrome, then in most cases a miscarriage occurs or the pregnancy ends in a difficult birth with many complications.

Diagnostics

If at least one of the signs of adrenal disease occurs, you should contact a medical facility and undergo a comprehensive diagnosis to confirm or refute the diagnosis. It is possible to detect hypercortisolism using the following procedures:

1. Submission of urine for analysis of the determination of free cortisol.
2. Ultrasound examination of the adrenal glands and kidneys.
3. Checking the adrenal glands and pituitary gland using computed tomography and magnetic resonance imaging. Thus, the presence of a neoplasm can be detected.
4. Examination of the spine and chest organs using radiography. This diagnostic procedure is aimed at identifying pathological bone fractures.
5. Donating blood for biochemistry to find out what state the electrolyte balance of the serum is in, to determine the amount of potassium and sodium.

Treatment should be prescribed by a specialized specialist after the diagnosis is made, since it is extremely dangerous to self-medicate hypercortisolism.

Treatment Methods

Treatment of hypercortisolism is aimed at eliminating the root cause of the adrenal abnormality and balancing the hormonal background. If you do not pay attention to the symptoms of the disease in a timely manner and do not engage in treatment, then a fatal outcome is possible, which is observed in 40-50% of cases.

It is possible to eliminate pathology in three main ways:

• drug therapy;
• radiation treatment;
• carrying out the operation.

Medical treatment

Drug therapy involves taking drugs that are aimed at reducing the production of hormones by the adrenal cortex. Drug therapy is indicated in combination with radiation or surgical, as well as in cases where other therapeutic methods have not brought the desired effect. Often the doctor prescribes Mitotan, Trilostan, Aminoglutethimide.

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.

Prognosis for hypercortisolism

The prognosis depends on the severity of the syndrome and when therapeutic measures were taken. If the pathology is detected in a timely manner and the correct treatment is prescribed, then the prognosis is quite comforting. Negative outcomes are affected by various complications. So, patients in whom hypercortisolism has led to cardiovascular abnormalities are at risk of death. The prognosis is disappointing if a person has osteoporosis, pathological fractures have appeared and motor activity has been impaired as a result of myopathy. In case of accession to hypercortisolism diabetes with subsequent complications, the outcome is extremely disappointing.

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

Itsenko-Cushing syndrome- disease of the adrenal cortex (KN) or malignant tumors of non-adrenal localization that produce 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 syndrome Itsenko-Cushing.

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 stripes of stretching 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 region of the 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 down on the face and the entire 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. In 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, visual hallucinations, epileptoid seizures, convulsions develop.

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. It ranges from impaired glucose tolerance to the development of diabetes mellitus ("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

V 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 people who abuse alcohol.

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

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 of 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 the 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 .

Cushing's syndrome (hypercorticism) is a long-term and chronic effect on the patient's body of an excessive amount of adrenal cortex hormones, mainly cortisol. The syndrome can be caused both by some internal diseases and by taking certain medications. According to statistics, women are more susceptible to this disease than men (10 times more), and the main risk group is women aged 25 to 40 years. Due to a strong imbalance of hormones, the patient experiences pathological changes in the appearance and biochemical processes of the body.

Cortisol, which is produced in excess in Cushing's syndrome, in this case can be safely called the hormone of death. In large quantities, cortisol reduces the production of glucose, which is so necessary for most cells in our body, therefore, due to a lack of glucose, some cell functions fade or stop working altogether.

Causes of the development of Cushing's syndrome.

There are many reasons that cause excessive production of adrenal hormones. There are three types of hypercortisolism: exogenous, endogenous and pseudo-Cushing's syndrome. We will analyze each of them separately and the reasons that most often cause them.

Exogenous hypercortisolism.

One of the most common causes of Cushing's syndrome is an overdose or long-term treatment with steroids (glucocorticoids) for another disease. Most often, steroids are used to treat asthma, rheumatoid arthritis, or immunosuppression in organ transplants.

Endogenous hypercortisolism.

In this case, the cause of the disease is already internal disturbances in the body. The most common cause, in about 70% of cases, of the development of the syndrome is Itsenko-Cushing's disease (not to be confused with Cushing's syndrome). In Itsenko-Cushing's disease, there is an increased production of pituitary adrenocorticotropic hormone (ACTH), which, in turn, stimulates the release of cortisol from the adrenal glands. This hormone can be produced by a pituitary microadenoma or an ectopic corticotropinoma. An ectopic malignant corticotropinoma can be located in the bronchi, testicles, and ovaries. Even more rarely, Cushing's syndrome occurs with a primary lesion of the adrenal cortex, for example, hyperplasia of the adrenal cortex or malignant, benign tumors of the adrenal cortex.

Pseudo-Cushing's syndrome.

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 those that contain a mixture of estrogen and progesterone. An increase in the level of cortisol in the blood can even occur in infants when alcohol enters their body along with breast milk.

Signs and symptoms of Cushing's syndrome.

And obesity occurs in 90% of patients, with fat deposited on the face (moon-shaped, rounded face with blush on the cheeks), abdomen, chest and neck, and the arms and legs look thin.

Muscle atrophy is very noticeable on the shoulder girdle and legs. A rapid decrease in the patient is accompanied. Together with obesity, this symptom creates great difficulties for patients when performing any physical activity. Sometimes there is pain during squatting and lifting.

Very often, with hypercortisolism, a thinning of the skin can be observed in a patient. The skin becomes marbled, dry and patchy. The patient is often observed on the body, as well as with any violation of the integrity of the skin, wounds and cuts heal slowly.

In women with Cushing's syndrome, it often develops. Hair begins to grow on the upper lip, chin and chest. All this is due to the fact that the adrenal cortex begins to increase the production of male hormones - androgens. In women, in addition to hirsutism, menstrual irregularities occur (), and in men, libido appears and decreases.

Osteoporosis is the most common symptom (90%) that occurs in patients with hypercortisolism. Osteoporosis first manifests itself in the form of pain in the bones and joints, and then spontaneous fractures of the ribs and limbs can occur. If the disease manifests itself in childhood, then the child becomes noticeably behind in growth development.

With Cushing's syndrome, cardiomyopathy with a mixed course often develops. This condition occurs against the background of arterial hypertension, electrolyte shifts or catabolic effects of steroids on the myocardium. These disorders manifest themselves in the form of heart rhythm disturbances, high blood pressure, heart failure, which in most cases leads to the death of the patient.

Often, in approximately 10 - 20% of cases in patients with hypercortisolism, steroid diabetes mellitus occurs, which can be easily controlled with medications (hyperglycemic drugs).

From the side of the nervous system, signs such as lethargy, depression, euphoria, various sleep disorders and steroid psychosis are observed.

Treatment for Cushing's syndrome (hypercorticism).

Treatment of Cushing's syndrome is primarily aimed at eliminating the cause of hypercortisolism and balancing the hormonal background in the body.

There are three methods of treatment: medication, radiation therapy and surgery.

The main thing is to start treatment on time, because according to statistics, if you do not start treatment in the first five years from the onset of the disease, then death occurs in 30-50% of cases.

Medical method of treatment.

With drug therapy, the patient is prescribed drugs that reduce the production of hormones in the adrenal cortex. Often, drugs are prescribed to the patient in complex therapy or if other methods of treatment have not helped. To treat hypercortisolism, your doctor may prescribe mitotane, metyrapone, trilostane, or aminoglutethimide. Basically, these drugs are prescribed if the surgical operation was ineffective, or it is impossible to carry it out.

Radiation therapy.

This method is especially effective if the disease is caused by a pituitary adenoma. Radiation therapy, when exposed to the pituitary gland, causes it to reduce the production of adrenocorticotropic hormone. Usually radiation therapy is carried out together with medical or surgical treatment. Most often, it is in combination with drugs that this method is used, since it enhances the effect of drug treatment of Cushing's syndrome.

Operational intervention.

In pituitary Cushing's syndrome, transsphenoidal revision of the pituitary gland and excision of the adenoma using microsurgical techniques are often used. Improvements come very quickly, and the effectiveness of this method is 70 - 80%. If hypercortisolism is caused by a tumor of the adrenal cortex, then an operation is performed to remove this tumor. In rare cases, especially in seriously ill people, both adrenal glands are removed, which is why the patient is prescribed lifelong use of glucocorticoids as replacement therapy.

Hypercorticism (Cushing's syndrome, Itsenko-Cushing's disease) is a clinical syndrome caused by excessive secretion of adrenal hormones and in most cases characterized by arterial hypertension, fatigue and weakness, hirsutism, purple striae on the abdomen, edema, hyperglycemia, osteoporosis and some other symptoms.

Etiology and pathogenesis

Depending on the causes of the disease, there are:

• total hypercortisolism with involvement in the pathological process of all layers of the adrenal cortex;
• partial hypercortisolism, accompanied by an isolated lesion of individual zones of the adrenal cortex.

Hypercortisolism can be caused by various reasons:

1. Hyperplasia of the adrenal glands:
   • with primary hyperproduction of ACTH (pituitary-hypothalamic dysfunction, ACTH-producing microadenomas or pituitary macroadenomas);
   • with primary ectopic production of ACTH-producing or CRH-producing tumors of non-endocrine tissues.
2. Nodular adrenal hyperplasia.
3. Neoplasms of the adrenal glands (adenoma, carcinoma).
4. Iatrogenic hypercorticism (long-term use of glucocorticoids or ACTH).

Regardless of the cause that causes hypercortisolism, this pathological condition is always due to increased production of cortisol by the adrenal glands.

Most common in clinical practice central hypercortisolism(Cushing's syndrome, Itsenko-Cushing's disease, ACHT-dependent hypercortisolism), which is accompanied by bilateral (rarely unilateral) adrenal hyperplasia.

Less commonly, hypercorticism develops as a result of ACTH-independent autonomous production of steroid hormones by the adrenal cortex with the development of tumors in it (corticosteroma, androsteroma, aldosteroma, corticoestroma, mixed tumors) or with macronodular hyperplasia; ectopic production of ACTH or corticoliberin, followed by stimulation of adrenal function.

Separately, iatrogenic hypercorticism is distinguished, due to the use of glucocorticoids or corticotropic hormone preparations in the treatment of various, including non-endocrine, diseases.

Central hypercorticism is due to an increase in the production of corticoliberin and ACTH and a violation of the reaction of the hypothalamus to the inhibitory effect of adrenal glucocorticoids and ACTH. The reasons for the development of central hypercortisolism have not been finally named, but it is customary to distinguish exogenous and endogenous factors that can initiate a pathological process in the hypothalamic-pituitary zone.

Exogenous factors affecting the state of the hypothalamus include traumatic brain damage, stress, neuroinfections, and endogenous factors - pregnancy, childbirth, lactation, puberty, menopause.

The listed pathological processes initiate violations of regulatory relationships in the hypothalamic-pituitary system and are realized by a decrease in dopaminergic and an increase in serotonergic effects of the hypothalamus, which is accompanied by an increase in stimulation of ACTH secretion by the pituitary gland and, accordingly, stimulation of the adrenal cortex with an increase in the production of glucocorticoids by cells of the fascicular zone of the adrenal cortex. To a lesser extent, ACTH stimulates the glomerular zone of the adrenal cortex with the production of mineralocorticoids and the reticular zone of the adrenal cortex with the production of sex steroids.

Excess production of adrenal hormones, according to the feedback law, should inhibit the production of ACTH by the pituitary gland and corticoliberin by the hypothalamus, but the hypothalamic-pituitary zone becomes insensitive to the influence of peripheral adrenal steroids, therefore, hyperproduction of glucocorticoids, mineralocorticoids and adrenal sex steroids continues.

Prolonged hyperproduction of ACTH by the pituitary gland is associated with the development of ACTH-producing microadenomas (10 mm) of the pituitary gland or diffuse hyperplasia of corticotropic cells (hypothalamic-pituitary dysfunction). The pathological process is accompanied by nodular hyperplasia of the adrenal cortex and the development of symptoms caused by an excess of the listed hormones (glucocorticosteroids, mineralocorticoids and sex steroids) and their systemic effects on the body. Thus, with central hypercortisolism, the hypothalamic-pituitary zone is primarily affected.

The pathogenesis of other forms of hypercorticism (not of central origin, ACTH-independent hypercorticism) is fundamentally different.

Hypercorticism caused by volumetric formations of the adrenal glands, most often the result of autonomous production of glucocorticosteroids (cortisol) by the cells of the predominantly fascicular zone of the adrenal cortex (approximately 20-25% of patients with hypercorticism). These tumors usually develop on only one side, and about half of them are malignant.

Hypercortisolemia causes inhibition of the production of corticoliberin by the hypothalamus and ACTH by the pituitary gland, as a result of which the adrenal glands cease to receive adequate stimulation and the unchanged adrenal gland reduces its function and becomes hypoplastic. Only autonomously functioning tissue remains active, as a result of which a unilateral increase in the adrenal gland is noted, accompanied by its hyperfunction and the development of appropriate clinical symptoms.

The cause of partial hypercortisolism can be androsteroma, aldosteroma, corticoestroma, mixed tumors of the adrenal cortex. To date, the causes of hyperplasia or tumor lesions of the adrenal glands have not been finally clarified.

ACTH-ectopic syndrome is due to the fact that tumors with ectopic secretion of ACTH also express the gene for the synthesis of ACTH or corticoliberin, so a tumor of extrapituitary localization becomes a source of autonomous hyperproduction of peptides similar to ACTH or corticoliberin. The source of ectopic production of ACTH can be tumors of the lungs, gastrointestinal tube, pancreas (bronchogenic cancer, thymus carcinoid, pancreatic cancer, bronchial adenoma, etc.). As a result of the autonomous production of ACTH or corticoliberin, the adrenal glands receive excessive stimulation and begin to produce an excessive amount of hormones, which determines the appearance of symptoms of hypercortisolism with the development of clinical, biochemical and radiological signs that are indistinguishable from those caused by hypersecretion of pituitary ACTH.

Iatrogenic hypercorticism can develop as a result of long-term use of glucocorticoids or ACTH in the treatment of various diseases, and now, due to the frequent use of these drugs in clinical practice, it is the most common cause of hypercorticism.

Depending on the individual characteristics of patients (sensitivity to glucocorticoids, duration, dose and regimen of drug administration, reserves of their own adrenal glands), the use of glucocorticoid preparations leads to suppression of ACTH production by the pituitary gland according to the feedback law and, consequently, a decrease in endogenous production of hormones of the adrenal cortex with their possible hypoplasia and atrophy. Long-term use of exogenous glucocorticoids may be accompanied by symptoms of hypercorticism of varying severity.

Symptoms

Clinical manifestations of hypercorticism are due to excessive influences of glucocorticoids, mineralocorticoids and sex steroids. The most common in clinical practice is central hypercortisolism.

Symptoms due to excess glucocorticoids. Characteristic is the development of atypical (dysplastic) obesity with fat deposition in the face (moon-shaped face), interscapular region, neck, chest, abdomen and the disappearance of subcutaneous fat in the extremities, which is due to differences in the sensitivity of adipose tissue of different parts of the body to glucocorticoids. In severe hypercortisolism, total body weight may not meet the criteria for obesity, but the characteristic redistribution of subcutaneous fat persists.

There is thinning of the skin and the appearance of striae (striations) of a purple-cyanotic color on the chest, in the area of ​​​​the mammary glands, on the abdomen, in the area of ​​​​the shoulders, the inner thighs due to impaired collagen metabolism and ruptures of its fibers and reaching a width of several centimeters. The patient's face acquires a moon-shaped shape and has a purple-cyanotic color in the absence of an excess of red blood cells, acne (blackheads) may appear.

Due to a violation of protein biosynthesis and the predominance of its catabolism, muscular hypotrophy (atrophy) develops, which is manifested by the obliqueness of the buttocks, muscle weakness, impaired motor activity, as well as the risk of hernias of various localization. There is poor wound healing due to impaired protein metabolism.

As a result of violations of the synthesis of collagen and the protein matrix of the bone, bone calcification is disturbed, its mineral density decreases and osteoporosis develops, which can be accompanied by pathological fractures and compression of the vertebral bodies with a decrease in growth (osteoporosis and compression fractures of the spine against the background of muscle atrophy are often the main symptoms that lead the patient to the doctor). Possible aseptic necrosis of the femoral head, less often the head of the humerus or the distal part of the femur.

Nephrolithiasis develops due to calciuria and against the background of a decrease in nonspecific resistance - this can cause a violation of the passage of urine and pyelonephritis.

There are clinical signs of gastric or duodenal ulcer with a risk of gastric bleeding and / or perforation of the ulcer. Due to increased gluconeogenesis in the liver and insulin resistance, glucose tolerance is impaired and secondary (steroid) develops.

The immunosuppressive effect of glucocorticoids is realized by suppression of the activity of the immune system, a decrease in resistance to various infections and the development or exacerbation of various localizations of infections. Arterial hypertension develops with a significant increase, mainly in diastolic blood pressure, due to sodium retention. There are changes in the psyche from irritability or emotional instability to severe depression or even overt psychosis.

Children are characterized by a violation (delay) of growth due to a violation of collagen synthesis and the development of resistance to somatotropic hormone.

Symptoms associated with excessive secretion of mineralocorticoids. Caused by electrolyte disturbances with the development of hypokalemia and hypernatremia, resulting in persistent and resistant to antihypertensive drugs arterial hypertension and hypokalemic alkalosis, causing myopathy and contributing to the development of dyshormonal (electrolyte-steroid) myocardial dystrophy with the development of cardiac arrhythmias and the appearance of progressive signs of heart failure.

Symptoms due to excess sex steroids. In most cases, they are most often detected in women and include the appearance of a sign of androgenization - acne, hirsutism, hypertrichosis, clitoral hypertrophy, menstrual irregularities and fertility disorders. In men, with the development of estrogen-producing tumors, the voice timbre, the intensity of beard and mustache growth change, gynecomastia appears, potency decreases and fertility is impaired.

Symptoms due to excess ACTH. Usually found in ACTH-ectopic syndrome and include hyperpigmentation of the skin and minimal development of obesity. In the presence of a macroadenoma of the pituitary gland, “chiasmatic symptoms” may appear - a violation of the visual fields and / or visual acuity, smell and CSF flow disorders with the development of persistent headaches that do not depend on the level of blood pressure.

Diagnostics

Early signs of the disease are very diverse: skin changes, myopathic syndrome, obesity, symptoms of chronic hyperglycemia (diabetes mellitus), sexual dysfunction, arterial hypertension.

When verifying hypercorticism, studies are consistently carried out aimed at proving the presence of this disease with the exclusion of pathological conditions similar in clinical manifestations and verification of the cause of hypercorticism. The diagnosis of iatrogenic hypercortisolism is confirmed by the history.

At the stage of advanced clinical symptoms, the diagnosis of hypercortisolism syndrome is not difficult. Conclusive confirmation of the diagnosis are the data of laboratory and instrumental research methods.

Laboratory indicators:

• increased daily urinary excretion of free cortisol by more than 100 mcg/day;
• an increase in the level of cortisol in the blood of more than 23 mcg / dl or 650 nmol / l when monitoring, since a single increase in the level of cortisol is also possible with physical exertion, mental stress, estrogen intake, pregnancy, obesity, anorexia nervosa, drug use, alcohol intake;
• an increase in the level of ACTH, aldosterone, sex hormones to confirm the diagnosis of hypercortisolism has no fundamental diagnostic value.

Indirect laboratory signs:

• hyperglycemia or impaired carbohydrate tolerance;
• hypernatremia and hypokalemia;
• neutrophilic leukocytosis and erythrocytosis;
• calciumuria;
• alkaline reaction of urine;
• an increase in the level of urea.

functional tests. In doubtful cases, functional tests are performed for initial screening:

• the daily rhythm of cortisol and ACTH is determined (with hypercorticism, the characteristic rhythm is disturbed by the maximum level of cortisol and ACTH in the morning and monotonous secretion of cortisol and ACTH is noted);
• small dexamethasone test (Lidll suppression test): dexamethasone is given at 4 mg/day for 2 days (0.5 mg every 6 hours for 48 hours) and suppresses normal ACTH and cortisol secretion, so lack of suppression of cortisolemia is a criterion for hypercortisolism. If the urinary cortisol level does not fall below 30 mcg/day and the plasma cortisol level does not decrease, the diagnosis of hypercortisolism is made.

Visualization of the Turkish saddle and adrenal glands. After confirming the diagnosis of hypercortisolism, studies are carried out to clarify its cause. For this purpose, studies aimed at visualizing the Turkish saddle and adrenal glands are mandatory:

• to assess the state of the Turkish saddle, the use of MRI or CT is recommended, which makes it possible to identify or exclude the presence of a pituitary adenoma (it is considered optimal to conduct a study with a contrast agent);
• CT or MRI, selective angiography, or adrenal scintigraphy with 19-[ 131 I]-iodine cholesterol is recommended to assess the size of the adrenal glands (ultrasonography does not reliably estimate the size of the adrenal glands and therefore is not the recommended method for imaging the adrenal glands). The best X-ray method for visualizing the adrenal glands is CT, which has supplanted previously used invasive techniques (such as selective arteriography and adrenal venography), since CT scanning can not only localize the adrenal tumor, but also distinguish it from bilateral hyperplasia. The method of choice for imaging adrenal tumors is the use of positron emission tomography (PET-scan) with a glucose analogue 18-fluoro-deoxy-D-glucose (18 FDG), which selectively accumulates in tumor tissue, or an inhibitor of the key enzyme of cortisol synthesis 11-β-hydroxylase 11C -methomidate;
• it is possible to perform a biopsy of the adrenal gland, however, despite the low risk of complications and fairly high accuracy, the study is carried out at least, due to modern methods of imaging the adrenal glands.

suppressive test. In the absence of pituitary adenoma or unilateral enlargement of the adrenal gland, a suppressive test is performed to clarify the cause of hypercortisolism:

• large (complete) dexamethasone test (large Liddle test) - 8 mg of dexamethasone per day for 2 days is prescribed and the state of adrenal function after dexamethasone is taken into account. The absence of suppression of cortisol production is a criterion for the autonomy of hormone secretion, which makes it possible to exclude central hypercorticism, and suppression of cortisol secretion is regarded as confirmation of central ACTH-dependent hypercorticism;
• less commonly used test with metopyrone (750 mg every 4 hours, 6 doses). According to the results of the test in most patients with central hypercortisolism, the level of cortisol in the urine increases, and the absence of a reaction indicates a neoplasm of the adrenal glands or their hyperplasia due to an ACTH-producing tumor of non-endocrine tissue.

Additional diagnostic criteria:

• narrowing of the visual fields (bitemporal hemianopsia), congestive nipples of the optic nerves;
• ECG with the identification of signs characterizing myocardial dystrophy;
• bone densitometry with the detection of osteoporosis or osteopenia;
• examination by a gynecologist with an assessment of the condition of the uterus and ovaries;
• fibrogastroduodenoscopy to rule out an ectopic ACTH-producing tumor.

Identification of the true focus of ACTH production. If iatrogenic hypercorticism, central ACTH-dependent hypercorticism, and tumor-induced hypercorticism or isolated adrenal hyperplasia are ruled out, the ACTH-ectopic syndrome is likely to be the cause of the hypercorticism. To identify the true focus of ACTH or corticoliberin production, an examination aimed at finding a tumor and including visualization of the lungs, thyroid gland, pancreas, thymus, and gastrointestinal tract is recommended. If it is necessary to detect an ACTH-ectopic tumor, it is possible to use scintigraphy with octreotide labeled with radioactive indium (octreoscan); determination of the level of ACTH in venous blood taken at various levels of the venous system.

Differential Diagnosis carried out in 2 stages.

Stage 1: differentiation of conditions similar to hypercortisolism in terms of clinical manifestations (pubertal dispituitarism, type 2 diabetes mellitus in women with obesity and menopausal syndrome, polycystic ovary syndrome, obesity, etc.). Differentiation should be based on the above criteria for diagnosing hypercortisolism. In addition, it must be remembered that severe obesity in hypercortisolism is rare; moreover, with exogenous obesity, adipose tissue is distributed relatively evenly, and is not localized only on the trunk. When examining the function of the adrenal cortex in patients without hypercortisolism, only minor violations are usually detected: the level of cortisol in the urine and blood remains normal; the daily rhythm of its level in the blood and urine is not disturbed.

Stage 2: differential diagnosis to clarify the cause of hypercortisolism with the implementation of the above studies. It should be taken into account that the severity of iatrogenic hypercortisolism is determined by the total dose of administered steroids, the biological half-life of the steroid drug and the duration of its administration. In individuals receiving steroids in the afternoon or evening, hypercortisolism develops faster and with lower daily doses of exogenous drugs than in patients whose therapy is limited only to morning doses or the use of an alternating technique. Differences in the severity of iatrogenic hypercortisolism are also determined by differences in the activity of enzymes involved in the degradation of administered steroids and their binding.

A separate group for differential diagnosis are persons in whom computed tomography (10-20%) accidentally reveals adrenal neoplasms without signs of hormonal activity (insendentalomas), which are rarely malignant. The diagnosis is based on the exclusion of hormonal activity in terms of the level and circadian rhythm of cortisol and other adrenal steroids. The management of Incendental is determined by the rate of growth and size of the tumor (adrenal carcinoma rarely has a diameter of less than 3 cm, and adrenal adenomas usually do not reach 6 cm).

Treatment

The tactics of treatment is determined by the form of hypercortisolism.

In the case of central ACTH-dependent hypercortisolism and the detection of pituitary adenoma, selective transsphenoidal adenomectomy is the preferred treatment, and in case of macroadenoma, transcranial adenomectomy. Postoperative, despite the need for replacement therapy, is regarded as a favorable effect, since adequate therapy provides compensation and an incomparably higher quality of life compared to hypercortisolism.

In the absence of a pituitary adenoma with central ACTH-dependent hypercortisolism, various options for radiation therapy to the pituitary gland are used. The preferred method of radiation therapy is proton therapy at a dose of 40-60 Gy.

In the absence of a pituitary microadenoma, steroidogenesis inhibitors are prescribed: derivatives of ortho-para-DDT (chloditan, mitotane), aminoglutethemide (orimethen, mamomit, elipten), ketoconazole (nizoral at a dose of 600-800 mg / day to 1200 mg / day under the control of cortisol).

In the absence of a therapeutic effect, it is possible to perform unilateral and even bilateral adrenalectomy (laparoscopic or "open"). In recent years, bilateral adrenalectomy is rarely performed due to the possible development (progressive growth of ACTH-producing pituitary adenoma).

If a volumetric formation of the adrenal gland with hormonal activity, which determines the syndrome of hypercortisolism, is detected, surgical treatment is indicated, taking into account the size of the tumor and its relationship with surrounding organs and tissues. If there is evidence of malignant growth of adrenocortical carcinoma after surgical treatment, chemotherapy with steroidogenesis inhibitors is used.

Treatment of ACTH-ectopic syndrome is carried out depending on the location and stage of the primary tumor, taking into account the severity of hypercortisolism. In the presence of metastases, the removal of the primary tumor is not always justified; the solution of this issue is the prerogative of surgical oncologists. To optimize the patient's condition and eliminate hypercortisolism, it is possible to use therapy with steroidogenesis inhibitors.

With iatrogenic hypercorticism, it is necessary to minimize the dose of glucocorticoids or completely cancel them. Of fundamental importance is the severity of somatic pathology, which was treated with glucocorticoids. In parallel, you can prescribe symptomatic therapy aimed at eliminating the identified violations.

The need for symptomatic therapy (antihypertensive drugs, spironolactone, potassium drugs, hypoglycemic drugs, anti-osteoporotic drugs) determines the severity of the patient's condition with hypercorticism. Steroid osteoporosis is an urgent problem, therefore, in addition to calcium and vitamin D preparations, antiresorptive therapy with bisphosphonates (alendronate, risendronate, ibandronate) or myacalcic is prescribed.

Forecast

The prognosis is determined by the form of hypercortisolism and the adequacy of the treatment. With timely and correct treatment, the prognosis is favorable, but the severity of hypercortisolism determines the degree of negative prognosis.

The main risks of a negative outlook:

• possible development and progression of cardiovascular pathology (heart attack, stroke, circulatory failure);
• osteoporosis with compression of the vertebral bodies, pathological fractures and impaired motor activity due to myopathy;
• diabetes mellitus with its "late" complications;
• immunosuppression and development of infections and/or sepsis.

On the other hand, the prognosis for tumor forms of hypercortisolism depends on the stage of the tumor process.