Functional hypercortisolism. Itsenko Cushing's disease (hypercortisolism)

- endocrine disease, characterized by a fairly long-term effect on the human body of an excess amount of cortisol - a hormone synthesized by the adrenal cortex, or abuse of glucocorticoids. Another name for hypercortisolism is Cushing's syndrome.

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

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 of this, 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 Cushing's disease (not to be confused with the syndrome of the same name).
In this case, excess production of ACTH (adrenocorticotropic hormone) occurs, which activates the secretion of cortisol. This characterizes endogenous hypercortisolism.

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

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

Hypercortisolism: symptoms

90% of patients with hypercortisolism have Cushingoid type obesity: 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.

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

In women, hypercortisolism manifests itself:
- hirsutism;
- virilization;
- hypertrichosis;
- disruption 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 failures of the nervous and cardiovascular systems.
"Nervous" symptoms:
- psychosis and stress;
- change from a euphoric state to depression;
- lethargy;
- suicidal attempts.
Cardiovascular symptoms:
- cardiac arrhythmia;
- arterial hypertension;
- heart failure.

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

Hypercortisolism: complications

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

Also, hypercortisolism causes complications in cardiovascular system and in kidney function, which often leads to death:
- decompensation of cardiac activity;
- ischemic stroke;
- renal failure;
- severe pyelonephritis;
- sepsis;
- osteoporosis;
- urolithiasis.

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

Hypercorticism: diagnosis

When diagnosing hypercortisolism, first of all, screening tests are performed - the level of cortisol in the urine is determined during the day. If this level is 3-4 times higher than normal, then this is an indicator of Cushing’s disease or hypercortisolism.
A small dexamethasone test shows that if, when taking dexamethasone, the cortisol level decreases 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 Cushing's disease and hypercortisolism, a large dexamethosis test is performed: with the disease, the level of cortisol decreases by more than 2 times, but with hypercortisolism this does not happen.

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

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

Hypercorticism: treatment

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

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

With the medicinal nature of hypercortisolism, the use of glucocorticoids is gradually replaced with others medicinal preparations immunosuppressive effect.

With endogenous ( inner nature) diseases use drugs that suppress steroidogenesis:
- ketoconazole;
- chloditan;
- mitotane;
- aminoglutethimide.

To treat the symptoms of hypercortisolism, various diuretics, cardiac glycosides, hypoglycemic agents, antidepressants are used...

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

To solve this the most important task, V complex therapy hypercortisolism is used immune drug Transfer factor.
The basis of this drug is made up of immune molecules of the same name, which, when entering the body, perform three functions:
- eliminate failures of the endocrine and immune systems, and contributes 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 various diseases, which (agents) invade the body, and when they invade again, “transmit” this information immune system, which neutralizes these antigens;
- eliminate everything side effects caused by the use of other drugs while simultaneously enhancing them 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.

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

Pathogenesis of hypercortisolism

The basis Itsenko-Cushing's disease constitutes a feedback violation in functional system hypothalamus-pituitary gland - adrenal cortex, characterized constantly high activity pituitary gland and corticotropic hyperplasia 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 increases with the development of symptoms of hypercortisolism. At the core Itsenko-Cushing 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 generalized damage to almost all organs and systems, decreased growth rate, increased body weight, uneven distribution of fat, hirsutism, stretch marks, hyperpigmentation, primary or secondary amenorrhea, osteoporosis, muscle weakness. In terms of symptoms and manifestations, Itsenko-Cushing syndrome is not much different from Itsenko-Cushing disease.

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

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

With Itsenko-Cushing's disease in children, regardless of gender, there is a delay in sexual development with premature appearance sexual hair growth, which can be explained by excess production of the adrenal glands along with glucocorticoids and androgens. Children with Itsenko-Cushing's disease have a tendency to mild 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 with thinning and atrophy of the skin due to a decrease in the content of tissue proteins and increasing capillary permeability.

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

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

At 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 clinical symptoms A distinction is made between a rapidly progressing (over 3-6 months) course and a torpid course of the disease.

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 the blood levels of cortisol and ACTH, as well as increased daily urinary excretion free cortisol and 17-OX.

When the clinical picture is blurred and there is 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 the secretion of ACTH, 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 syndrome ( Large sample 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-OX decreases by more than 50%).

For Itsenko-Cushing's disease the test is positive, but with corticosteroma it is negative. The purpose of topical diagnosis for Itsenko-Cushing's disease is to identify macro- or microadenoma of the pituitary gland and bilateral adrenal hyperplasia.

For Itsenko-Cushing syndrome- a tumor of one adrenal gland is detected with reduced or normal sizes another. To solve this problem use x-ray method research - pathology sella turcica, ultrasound of the adrenal glands, computed tomography, nuclear magnetic resonance imaging, angiography of the adrenal glands.

Differential diagnosis of hypercortisolism

With severe hypercortisolism differential diagnosis carried out between Itsenko-Cushing's disease and corticosteroma, syndrome of ectopic ACTH production. In the erased form - with pubertal juvenile dyspituitarism or hypothalamic pubertal syndrome (PUDS).

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

The outcome of PJP can be spontaneous recovery or, less commonly, transition to hypothalamic syndrome, Itsenko-Cushing's disease.

Treatment of hypercortisolism

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

Hypercortisolism is a disease that develops when the hypothalamic-pituitary system is disrupted and has a multi-symptomatic course.

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

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

How does this disease manifest itself?

The main symptoms most often appear:

1. Obesity;
2. Increased blood pressure;
3. Muscle weakness;
4. Sexual dysfunction;
5. May appear age spots on the skin;
6. Women grow hair on their chest and face.

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

The most dangerous manifestation of hypercortisolism is disruption of the heart and blood vessels, which causes the syndrome arterial hypertension. When pressure increases, headaches and “fly spots” appear before the eyes. Due to metabolic failure, diabetes mellitus and osteoporosis can develop, which is very severe.

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. Symptoms also include a violation nervous system, there may be a sleep disorder, Bad mood, psychoses.

In girls after the start menstrual cycle Amenorrhea (a condition where there are no periods) may occur. Growth and sexual development are delayed, and the voice becomes rough.

What can cause the disease to develop?

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

This disease can develop at any age, but more often it occurs between 20 and 40 years of age.
Reasons may be various injuries head and brain lesions (formations, inflammation), pregnancy, neuroinfection, tumors of the adrenal glands, pancreas, lungs, bronchi. The main cause is considered to be an adenoma of the anterior pituitary gland.

How to identify hypercortisolism?

The doctor must examine the patient, interview him, and then carry out laboratory diagnostics. It is used to determine the daily secretion of cortisol in the bloodstream and the amount of free cortisol in daily urine.

To identify the disease hypercortisolism, you need to carry out small sample with dexamethasone. Thanks to it, a tumor of the pituitary gland can be detected.

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

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

At average and mild degree gravity apply medicines, which will not allow the body to produce excess amounts 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 use surgical treatment. During this procedure, 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 permanent replacement therapy.

Types of hypercortisolism

Functional

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

Secondary

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

The symptoms are very similar to those with ordinary hypercortisolism; metabolism is disrupted, which can cause disturbances in 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 examination (the sella turcica does not increase by much, since corticotropic tumors do not large sizes), an MRI is performed, laboratory examinations hormones, use hormonal tests with dexamethasone or metapyrone.

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

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

When a child is born with low birth weight, low blood pressure and increased urine corticosteroids steroid hormones, then the doctor prescribes glucocorticosteroid drugs, the child must be registered with an endocrinologist and neurologist.

Endogenous

Endogenous hypercorticism 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 in at a young age, increase blood pressure, osteoporosis, muscle atrophy and weakness, trophic changes on the skin, amenorrhea, poor growth in children, the appearance of adrenal tumors.

Subclinical

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

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

Itsenko-Cushing syndrome– disease of the adrenal cortex (AC) 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 neurologist 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 syndrome – CI tumor – corticosteroma, corticoblastoma; Juvenile dysplasia 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 is iatrogenic Cushing's syndrome.

Functional hypercortisolism.

1. Pubertal-adolescent dyspituaitarism (juvenile hypothalamic syndrome).

   Hypothalamic syndrome.

   Pregnancy.

   Obesity.

   Diabetes mellitus.

   Alcoholism.

   Liver diseases.

Etiology

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

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

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

Pathogenesis

For Itsenko-Cushing's disease the mechanisms controlling ACTH secretion are disrupted. 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, and its hyperplasia or adenoma develops. ACTH increases the secretion of corticosteroids - cortisol, corticosterone, aldosterone, androgens by the adrenal cortex. Chronic long-term cortisolemia leads to the development of a symptom complex hypercortisolism– Itsenko-Cushing's disease.

For Itsenko-Cushing syndrome tumors of the adrenal cortex (adenoma, adenocarcinoma) produce an excessive amount of steroid hormones, the “negative feedback” mechanism ceases to function, and a simultaneous increase in the content of corticosteroids and ACTH in the blood occurs.

Clinic

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

Complaints

Patients note a change in their appearance, the development of obesity with red stretch marks on abdominal skin, chest and hips, the appearance of headaches and pain in the bones, general and muscle weakness, sexual dysfunction, changes in hair growth.

Clinical syndromes

Obesity with a peculiar redistribution of fat: its excessive deposition on the face, in the area cervical region spine (“menopausal hump”), chest, abdomen. The face of patients is round (“moon-shaped”), purplish-red, often with a cyanotic tint (“flesh-red”). This face is called the “matron’s face.” Appearance The patients present a great contrast: a red face, a short thick neck, a corpulent 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, inner surface shoulders, hips, and in the area of ​​the mammary glands, wide stripes of stretching appear - strii of a reddish-violet color. Local hyperpigmentation of the skin is often observed, often in places where clothing rubs (neck, elbows, abdomen), petechiae and bruises on the skin of the shoulders, forearms, and shins.

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

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

Virilizing syndrome– caused by an excess of androgens in women: hypertrichosis, i.e. body hair (in the form of abundant fluff on the face and entire body, growth of mustaches and beards, male-type growth on the pubis - diamond-shaped).

Arterial hypertension syndrome. Hypertension is usually moderate, but can be significant, up to 220-225/130-145 mmHg. Hypertension becomes more complicated cardiovascular failure: shortness of breath, tachycardia, swelling in the lower extremities, enlarged liver.

Arterial hypertension is often complicated by damage to the blood 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 developing into glaucoma with visual impairment. Cataracts develop more often than usual.

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

Increased 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.

Osteoporosis syndrome. Manifested by complaints of bone pain various localizations 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 associated with hypercortisolism: protein catabolism in bone tissue leads to bone loss, cortisol increases Ca++ resorption from bone tissue, which causes bone fragility. Cortisol also disrupts the absorption of calcium in the intestines and 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 formation of androgens by the adrenal glands, especially in women.

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

Astheno-vegetative syndrome. Characterized by fatigue and mood disorders from euphoria to depression. Sometimes develop acute psychoses, visual hallucinations, epileptoid seizures, convulsions.

Muscle weakness syndrome. Caused by hypercortisolism and the increased breakdown of protein in muscles caused by it, the development of hypokalemia. Patients complain about severe weakness, which is sometimes so pronounced that patients cannot get out of a chair without assistance. Upon examination, atrophy of the muscles of the limbs and the anterior abdominal wall is revealed.

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

Syndrome of laboratory and instrumental data

V general analysis blood, an increase in the number of red blood cells and hemoglobin level is detected; leukocytosis, lymphopenia, eosinopenia, increased ESR;

hypokalemia, hypernatrium and chloremia, hyperphosphatemia, increased calcium levels, alkaline phosphatase activity, hyperglycemia, glycosuria in some patients.

X-ray, computed tomography and magnetic resonance imaging of the sella turcica and adrenal glands can detect enlargement of the sella turcica, hyperplasia of the tissue of the pituitary gland, adrenal glands, and 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 the disease or Itsenko-Cushing syndrome, functional samples: With Dexamethasone(Liddle test) and Synacthenom-depot (ACTH).

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

Synacthen-depot (ACTH) is administered intramuscularly at a dose of 250 mg at 8 a.m. and after 30 and 60 minutes the content of cortisol and 17-OX in the blood is determined. With Itsenko-Cushing's disease (and normally), the content of the determined indicators increases 2 or more times, with Itsenko-Cushing's syndrome - not. In case of doubt, the so-called “big test”: Synacthen-depot is administered intramuscularly at 8 a.m. at a dose of 1 mg and the content of cortisol and 17-OX in the blood is determined after 1, 4, 6, 8, 24 hours. The result is assessed as in the previous test.

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

Differential diagnosis

Cushing's disease and syndrome

General: the whole clinical picture

Differences:

Table 33

Sign	Itsenko-Cushing's disease	Itsenko-Cushing syndrome
Virilizing syndrome	Weakly expressed in the form of vellus hair	Sharply expressed on the face, body
Obesity syndrome	Significantly expressed	Moderately expressed
P-graphy of the sella turcica (changes)
R-graphy of the adrenal glands (retropneumoperitopeum)	Enlargement of both adrenal glands	Enlargement of one adrenal gland
CT and MRI (computer and magnetic resonance imaging) of the sella turcica	Changes
Radioisotope scan of the adrenal glands	Increased accumulation of isotopes in both adrenal glands	Increased accumulation of isotopes in one adrenal gland
	Increased
	Positive	Negative

Nutritional-constitutional obesity

General: excess body weight, hypertension, mental instability, impaired carbohydrate metabolism, sometimes mild hirsutism.

Differences:

Table 34

Sign	Cushing's disease or syndrome	Obesity
Fat deposition is uniform
Fat deposition on the face and torso
Striae on the skin	Pink, reddish purple	Pale (white)
Muscle atrophy
Circadian rhythm of cortisol secretion		Saved
Test with dexamethasone and ACTH	Reply increased	The answer is normal
X-ray data of the study of the sella turcica, adrenal glands

Hypertension

Differential diagnosis is difficult when increased blood pressure is the only and long-lasting symptom of the disease and Cushing's syndrome.

General: systole-diastolic hypertension.

Differences:

Table 35

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

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

Mild degree– moderately expressed symptoms of the disease, some are absent (osteoporosis, mensis disorders).

Moderate– all symptoms are expressed, but there are no complications.

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

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

Treatment

Diet. Necessary sufficient quantity complete protein and potassium in food, restriction simple carbohydrates(sugars), solid fats.

Mode. Gentle – liberation from heavy physical labor and labor with severe mental overstrain.

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

Gamma therapy (radiation source 60 Co) is used at a dose of 1.5-1.8 Gy 5-6 times a week, total dose 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 side effects are less pronounced.

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

Surgical treatment

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

   Destruction of the adrenal glands in Itsenko-Cushing's disease consists of destroying the hyperplastic adrenal gland by introducing into it contrast agent or ethanol. Used in combination with radiation or drug therapy.

   Transsphenoidal adenomectomy for small pituitary adenomas, transfrontal adenomectomy for large adenomas. In the absence of a tumor, use hemihypophysectomy.

Drug therapy aimed at reducing the function of the pituitary gland and adrenal glands. Drugs used:

A) suppressing ACTH secretion;

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

ACTH secretion blockers are used only as an addition 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) is an antiserotonin drug, prescribed at a dose of 8-24 mg/day for 1-1.5 months.

Blockers of corticosteroid secretion by the adrenal glands. They are also used as an adjunct to other types of treatment.

Chloditan is prescribed at a dose of 2-5 g/day until the function of the adrenal cortex is normalized, then switched 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 for presence of infection, immune stimulants (T-activin, thymalin); antihypertensive drugs, treatment of heart failure; for hyperglycemia - diet, oral hypoglycemic drugs; treatment of osteoporosis: vitamin D 3 (oxidevit), calcium salts, hormones calcitonin or calcitrin (see “Osteoporosis”).

Clinical examination

In a state of remission, patients are examined by an endocrinologist 2-3 times a year, an ophthalmologist, neurologist and gynecologist - 2 times a year, and a psychiatrist - as indicated.

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

5.1. Find the error! The etiological factors of chronic adrenal insufficiency are:

hypertension;

AIDS (acquired immunodeficiency syndrome);

tuberculosis;

autoimmune process in the adrenal cortex.

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

skin hyperpigmentation;

hypotension;

weight gain;

decreased function of the gonads.

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

glucocorticoids;

diet with excess protein;

anti-tuberculosis drug;

limiting table salt.

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

increased blood pressure;

severe loss of appetite;

repeated vomiting;

cerebral disorders: epileptoid seizures.

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

decrease in blood chlorides<130 ммоль/л;

decreased potassium in the blood<2 мэкв/л;

decrease in glucose<3,3ммоль/л;

decreased sodium in the blood<110 мэкв/л.

5.6. Find the error! To provide emergency care for aadisonic crisis, use:

hydrocortisone intravenously;

hydrocortisone intravenous drip;

lasix intravenously;

cardiac glycosides intravenously.

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

determination of ACTH concentration;

adrenal scan;

computed tomography of the sella turcica (pituitary gland);

test with CRH (corticotropin-releasing hormone).

5.8. Find the error! A catecholamine crisis with pheochromoctoma 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 alternation of hyper- and hypotensive episodes.

5.9. Find the error! To relieve a catecholamine crisis in pheochromocytoma, the following is used:

α-blockers – phentolamine intravenously;

vascular agents – caffeine intravenously;

β-blockers – intravenous propracolol;

sodium nitroprusside intravenously.

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

significant hyperglycemia;

symptoms of “acute abdomen”;

severe heart rhythm disturbances;

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 adrenal diseases; identification of risk factors in the anamnesis that contribute to adrenal damage; 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 specific patient with adrenal pathology. Evaluation of the results of general clinical tests (blood test, urine test, ECG) and specific tests confirming damage to the adrenal glands: the content of glucocorticoid hormones, catecholamines in the blood and urine, ultrasound, CT scan of the adrenal glands; provoking tests. Carrying out differential diagnosis with similar diseases. Prescription of treatment for adrenal insufficiency, chromaffin, Itsenko-Cushing syndrome. Providing emergency care for Addisonian crisis and catecholamine crisis.

7. Independent work of students .

In the ward at the patient's bedside he conducts questioning and examination of patients. Identifies complaints, anamnesis, risk factors, symptoms and syndromes that have diagnostic value in diagnosing 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 (hypercortisolism) - a clinical syndrome caused by endogenous hyperproduction or long-term exogenous administration of corticosteroids. The clinical picture of endogenous hypercortisolism was first described in 1912 by Harvey Cushing (1864-1939).

Pituitary ACTH-dependent Cushing's syndrome is referred to as Cushing's disease.

The pathogenesis of the pathological changes that develop in Cushing's syndrome in most organs and systems is primarily based on the overproduction of cortisol. Cortisol in non-physiological concentrations has catabolic effect on protein structures and the matrix of most tissues and structures (bones, muscles, including smooth and myocardium, skin, internal organs, etc.), in which pronounced dystrophic and atrophic changes gradually develop. Violations carbohydrate metabolism consist in persistent stimulation of gluconeogenesis and glycolysis in muscles and liver, which leads to hyperglycemia (steroid diabetes). On fat metabolism excess cortisol has a complex effect: excess deposition occurs in some areas of the body, and atrophy of fatty tissue occurs in others, which is explained by the different sensitivity of individual fat compartments to glucocorticoids. An important component of the pathogenesis of Cushing's syndrome is electrolyte disorders(hypokalemia, hypernatremia), which are caused by the effect of excess cortisol on the kidneys. The direct consequence of these electrolyte changes is arterial hypertension and worsening myopathy, primarily cardiomyopathy, which leads to the development of heart failure and arrhythmias. The immunosuppressive effect of glucocorticoids causes susceptibility to infections.

The most common variant of Cushing's syndrome encountered by doctors in most specialties is exogenous Cushing's syndrome, which develops during glucocorticoid therapy. Mostly people aged 20-40 years are affected.

Symptoms of Cushing's syndrome

Data from a physical examination of the patient (examination) are crucial in the diagnosis of Cushing's syndrome.

Obesity observed in 90% of patients. Fat is deposited dysplastically (Cushingoid type of obesity): on the stomach, chest, neck, face (moon-shaped face of a purplish-red color, sometimes with a cyanotic tint - "matronism") and backs (“menopausal hump”) On the back of the hand, the fatty tissue and skin become noticeably thinner; this is not observed in other forms of obesity. Even in the absence of obesity, extremely severe patients have a redistribution of subcutaneous fat.

Muscle atrophy especially pronounced and noticeable on the shoulder girdle and legs. Atrophy of the gluteal and thigh muscles (“sloping buttocks”) is typical. When the patient tries to sit down and stand up, both of these movements will be significantly difficult, especially standing up. Atrophy of the muscles of the anterior abdominal wall (“frog belly”) leads to the appearance of hernial protrusions along the white line of the abdomen.

Leather thinned, has a marbled appearance with an emphasized vascular pattern, dry, with areas of regional sweating, flaking. The combination of progressive obesity and the breakdown of skin collagen explains the appearance of stretch marks - stretch marks. Striae have a purplish-red or purple color, are located on the skin of the abdomen, inner thighs, mammary glands, shoulders, and their width can reach several centimeters. Acne-type rashes and numerous small subcutaneous hemorrhages are often detected on the skin. Hyperpigmentation in some cases it can be observed with Cushing's disease and ectopic ACTH syndrome. In the latter case, melasma can be especially pronounced, while obesity is very moderate, and in some cases completely absent, as well as the characteristic redistribution of fat.

Osteoporosis is the most severe complication of hypercortisolism, which develops in 90% of patients. The most pronounced changes are in the thoracic and lumbar spine, accompanied by a decrease in the height of the vertebral bodies and compression fractures. On an x-ray, the vertebral body may be completely visible against the background of prominent end plates (“glass vertebrae”). Fractures are very often accompanied by severe pain, sometimes symptoms of compression of the spinal cord roots. Combined with atrophy of the back muscles, such changes often lead to scoliosis and kyphoscoliosis. If the disease begins in childhood, there is a significant delay in the child's growth due to inhibition of the development of epiphyseal cartilage under the influence of excess glucocorticoids.

Cardiomyopathy with Cushing's syndrome it has a mixed genesis. Its development is facilitated by the catabolic effects of steroids on the myocardium, electrolyte changes and arterial hypertension. Clinically, it is manifested by cardiac arrhythmias (atrial fibrillation, extrasystole) and heart failure, which in most cases is the direct cause of death in patients.

Nervous system. Symptoms range from lethargy and depression to euphoria and steroid psychosis. Often there is a discrepancy between scanty complaints and the severity of the condition.

Steroid diabetes mellitus occurs in 10-20% of patients; it is characterized by a mild course and compensation against the background of diet therapy and the prescription of tableted hypoglycemic drugs.

Reproductive system. Excess secretion of adrenal androgens causes the development of hirsutism (excessive male pattern hair growth) in women. Disturbance under the influence of excess androgens in the cyclic release of gonadoliberin causes the development of amenorrhea.

Diagnostics

Determination of basal levels of cortisol and ACTH has low diagnostic value in the diagnosis of Cushing's syndrome. As a screening test, determining the daily excretion of free cortisol in urine is more informative, but this study is inferior in sensitivity and specificity to the small dexamethasone test.

If a patient has symptoms or manifestations of Cushing's syndrome, it is first necessary to prove or reject endogenous overproduction of cortisol using small dexamethasone test. In accordance with the most common protocol, on day 1 at 8-9 am, the patient's serum cortisol level is determined. At 24 hours of the same day (at night), the patient takes 1 mg of dexamethasone orally. At 8-9 am the next day, the patient's serum cortisol level is again determined. Under normal conditions and in conditions not accompanied by endogenous hypercortisolism, after the administration of dexamethasone, the cortisol level decreases by more than 2 times. In any variant of Cushing's syndrome, cortisol production is not adequately suppressed.

In the event that a small dexamethasone test does not properly suppress cortisol levels, it is necessary to conduct a differential diagnosis between pathogenetic variants of Cushing's syndrome, as a rule, between Cushing's disease and adrenal corticosteroma. For this purpose, they carry out large dexamethasone test. Its protocol differs from the small dexamethasone test only in the dose of the drug: the patient is prescribed 8 mg of dexamethasone. In Cushing's disease, after taking dexamethasone, cortisol levels decrease by more than 50% of the original level; with corticosteroma and ectopic ACTH syndrome, this decrease in cortisol levels does not occur.

Topical diagnostics for Cushing's disease means conducting MRI to identify pituitary adenoma. In addition, there is CTor MRI of the adrenal glands, in which, in the case of Cushing's disease, bilateral hyperplasia is detected. The same techniques are used to visualize corticosteromas.

Diagnosis of complications of Cushing's syndrome involves performing an X-ray of the spine to identify compression fractures of the spine, a biochemical study to diagnose electrolyte disorders and steroid diabetes mellitus, etc.

Treatment

Steroidogenesis inhibitors (chloditan, aminoglutethimide) after diagnosis are prescribed to most patients with endogenous hypercortisolism.

Removal of pituitary cortitropinoma is the method of choice for Cushing's disease in a situation where MRI can clearly visualize the adenoma. Remission develops in 90% of operated patients.

Proton therapy to the pituitary gland is indicated for patients with Cushing's disease in whom the pituitary adenoma is not visualized.

Adrenalectomy is the main treatment for adrenal corticosteroma. In some cases, with severe Cushing's disease, when the patient is indicated for proton therapy, a unilateral adrenalectomy is performed, which can somewhat reduce the severity of hypercortisolism.

Symptomatic therapy for hypercortisolism includes the prescription of antihypertensive drugs, potassium, hypoglycemic drugs, and drugs for the treatment of osteoporosis.