Not typical for hypercortisolism. Cushing's syndrome (hypercorticism): causes, symptoms, treatment

Cushing's syndrome (hypercorticism) rarely diagnosed in men and children. This disease is more likely to affect women in the age group from 25 to 40 years.

Hormonal imbalance caused by various reasons leads to pathological changes in metabolism, which is reflected in the appearance.

The main cause of Cushing's disease is overproduction of the hormone cortisol - a product of the adrenal cortex. And the violation of the work of this body can contribute to several factors at once, given below.

Exogenous hypercortisolism

Caused by an overdose or long-term use of steroid drugs (prescribed in the treatment of asthma, rheumatoid arthritis and in the postoperative period after organ transplantation).

Endogenous hypercortisolism

Caused by internal discord in the body. Pituitary dysfunction (increased production of adrenocorticotropic hormone) provokes the release of cortisol by the adrenal cortex. The causes of the disease can be hyperplasia of the adrenal cortex and malignant tumors-corticotropinoma. Places of possible localization - bronchi, ovaries, testicles.

Pseudo Cushing's Syndrome

Symptoms similar to hypercorticism can be obesity, chronic alcohol intoxication, pregnancy, stress, depression, and sometimes taking oral contraceptives.

"To reduce the risk of death and achieve the fastest results in the treatment process, it is advisable to seek help in the first 5 years from the onset of the disease. "

Symptoms of Cushing's disease

1. Rapid and characteristic weight gain. Areas of fat accumulations - face (round and ruddy), abdomen, cervicothoracic region. The arms and legs look disproportionately thin.

2. Muscular atrophy of the shoulder girdle and legs, accompanied by increased weakness and fatigue.

3. Deterioration of the skin condition - hyperhidrosis, increased dryness, marble shade, thinned layer of the surface epithelium, loss of elasticity (appearance of stretch marks) and regenerative functions (slowly healing wounds).

4. Decreased libido.

5. Male-type hair in women, failure and absence of menstruation.

6. Development of osteoporosis. In the initial stage, it is distinguished by joint pain. In the future, it can manifest itself as spontaneous fractures of the limbs and ribs.

7. Due to the negative hormonal effects on the myocardium, there are problems with the work of the cardiovascular system. - cardiomyopathy, angina pectoris, hypertension, heart failure.

8. Often, hypercortisolism goes hand in hand with steroid diabetes.

9. The nervous system reacts to hormonal imbalance with lethargy, depression, euphoria, steroid psychosis.

Cushing's syndrome: treatment

The disease is diagnosed by the results of biochemical blood and urine tests. Further, differential diagnostics is carried out to identify the causes - MRI of the pituitary gland, abdominal cavity, layered radiography, biochemical study of hormones.

When establishing the causes that caused Cushing's disease, an appropriate treatment method is selected, aimed at eliminating the cause and restoring hormonal balance.

Medical option - the appointment of drugs that reduce the production of cortisol.

Radiation therapy - used to influence the pituitary adenoma.

Surgery - is performed to excise neoplasms of the pituitary gland and adrenal cortex, in severe cases, the adrenal glands are removed and hormone replacement therapy is prescribed for life. Efficiency - 70-80%, rapid improvement in the patient's condition.

Often, in the treatment of this disease, complex measures are taken that combine all available methods of treatment.

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

Hypercortisolism: what is it?

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

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

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

• ICD 10 code: E24.0

Pathogenesis

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

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

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

Causes

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

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

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

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

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

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

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

Kinds

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

• Central hypercortisolism.
• ACTH-ectopic syndrome.

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

• exogenous;
• endogenous;
• pseudo syndrome.

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

Exogenous

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

Endogenous

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

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

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

Pseudo Syndrome

Untrue hypercorticism occurs for the following reasons:

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

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

Symptoms of hypercortisolism in women and men

The clinical picture of hypercortisolism is characterized by symptoms:

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

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

Symptoms in women

Hypercortisolism in women is manifested by the following symptoms:

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

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

Signs in men

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

"Nervous" symptoms:

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

Cardiovascular symptoms:

• Heart arythmy;
• heart failure.

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

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

Complications

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

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

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

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

Diagnostics

The following methods are used to diagnose this disease:

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

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

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

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

Outpatient research

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

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

Treatment

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

Medications

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

Radiation therapy

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

Surgical intervention

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

What determines the effectiveness of treatment?

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

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

Syndrome prognosis

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

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

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

Pathogenesis of hypercortisolism

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

Symptoms of hypercortisolism

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

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

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

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

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

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

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

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

Diagnosis of hypercortisolism

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

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

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

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

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

Differential diagnosis of hypercortisolism

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

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

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

Treatment of hypercortisolism

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

A prolonged increase in the blood level of adrenal hormones, glucocorticoids, leads to the development of hypercorticism. This syndrome is characterized by a violation of all types of metabolism, failures in the work of various body systems. The causes of hormonal imbalance are volumetric formations of the pituitary gland, adrenal glands and other organs, as well as the use of drugs containing glucocorticoids. To eliminate the manifestations of the disease, medications are prescribed, and the tumor is affected by radiation methods or removed surgically.

Adrenal hormones and their role

The adrenal cortex produces steroid hormones - glucocorticoids, mineralocorticoids and androgens. Their production is controlled by the pituitary adrenocorticotropic hormone (ACTH, or corticotropin). Its secretion is regulated by the releasing hormone corticoliberin and hypothalamic vasopressin. Cholesterol is a common source for the synthesis of steroids.

The most active glucocorticoid is cortisol. An increase in its concentration leads to the suppression of corticotropin production according to the feedback principle. Thus, hormonal balance is maintained. The production of the main representative of the group of mineralocorticoids, aldosterone, depends on ACTH to a lesser extent. The main regulatory mechanism for its production is the renin-angiotensin system, which responds to changes in circulating blood volume. Androgens are produced in greater quantities in the gonads.

Glucocorticoids affect all types of metabolism. They contribute to an increase in blood glucose, protein breakdown and the redistribution of adipose tissue. Hormones have pronounced anti-inflammatory and anti-stress effects, retain sodium in the body and increase blood pressure.

Symptoms of hypercortisolism

Symptoms of hypercortisolism

A pathological increase in the level of glucocorticoids in the blood leads to the occurrence of hypercorticism syndrome. Patients note the appearance of complaints associated with a change in their appearance and disruption of the cardiovascular, reproductive, musculoskeletal and nervous systems. Symptoms of the disease are also caused by high concentrations of aldosterone and adrenal androgens.

In children, as a result of hypercortisolism, collagen synthesis is disrupted and the sensitivity of target organs to the action of somatotropic hormone decreases. All these changes lead to growth retardation. Unlike adults, it is possible to restore the structure of bone tissue after the pathology has been cured.

Manifestations of hypercortisolism are shown in the table.

Diagnosis of pathology

Regulation of the synthesis and secretion of glucocorticoids - direct (+) and reverse (-) connections

It is possible to suspect a syndrome associated with an increase in the level of glucocorticoids by the characteristic appearance of the patient and the complaints that he makes.

Since the main manifestations of hypercortisolism are associated with an excess of cortisol, its level in daily urine or saliva is examined to make a diagnosis. At the same time determine the concentration of corticotropin in the blood. To clarify the form of pathology, functional tests are carried out - small and large dexamethasone tests.

Types of hypercortisolism and their treatment

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

• Central hypercortisolism.
• ACTH-ectopic syndrome.

Types of hypercortisolism independent of corticotropin are:

• Peripheral.
• Exogenous.
• Functional.

The central form is Itsenko-Cushing's disease

The cause of the pathology is a pituitary tumor. Microadenomas are characterized by sizes up to 1 centimeter. With formations of a larger size, they speak of macroadenomas. They produce an excess amount of ACTH, which stimulates the production of glucocorticoids. The feedback between hormones is broken. There is an increase in the level of corticotropin and cortisol, proliferation of adrenal tissue - hyperplasia.

For treatment, irradiation of the pituitary gland with a proton beam is used. Sometimes combined methods are used - telegammatherapy and removal of one adrenal gland. Large tumors are operated on using an intranasal transsphenoidal or open approach. Additionally, unilateral or bilateral removal of the altered adrenal glands is done.

Of the drugs in the period of preparation for surgery, inhibitors of steroidogenesis are prescribed, which block the formation of adrenal hormones. These include ketoconazole (Nizoral), aminoglutethimide (Mamomit, Orimeten). And also use drugs that reduce blood pressure, normalize blood glucose levels.

ACTH-ectopic secretion

In this case, malignant tumors of various organs produce an excessive amount of substances similar in structure to corticotropin or corticoliberin. They interact with ACTH receptors in the adrenal glands and enhance the synthesis and secretion of their hormones.

Hormonally active volumetric formations are more common in the bronchi, thymus, uterus, pancreas, and ovaries. They are characterized by the rapid development of symptoms of hypercortisolism. After establishing the localization of the tumor, it is removed. If there are contraindications to surgery, inhibitors of steroidogenesis and drugs that correct concomitant disorders are used.

Peripheral hypercortisolism

The formation of the adrenal cortex, which produce an excess amount of hormones, leads to the development of pathology. By their nature, they can be malignant or benign. Corticosteromas, adenocarcinomas are more common, tissue hyperplasia is less common. In laboratory tests, an increase in the concentration of cortisol and a decrease in the level of corticotropin are determined. Tumors are removed surgically. Preoperative preparation is similar to that which is carried out with Itsenko-Cushing's disease.

Exogenous form

In this case, hormonal imbalance is a consequence of taking drugs containing glucocorticoids, which are prescribed for various diseases. Their excessive intake leads to the suppression of the synthesis of ACTH and the production of adrenal hormones. People who take these drugs in high doses for a long time develop all the symptoms characteristic of hypercortisolism. Diagnosis can be made by examination and by establishing characteristic changes in metabolism.

To prevent exogenous hypercorticism, they try to prescribe the lowest possible doses of glucocorticoids. With the development of concomitant conditions of the syndrome - diabetes mellitus, arterial hypertension, osteoporosis, infectious diseases, they are treated.

Functional hypercortisolism

This type of pathology occurs in some patients with diabetes mellitus, liver disease, hypothalamic syndrome, and chronic alcoholism. There is a violation of daily fluctuations in the concentration of corticotropin and cortisol. Perhaps the development of typical signs of hypercortisolism without changes in the structure of the adrenal cortex and pituitary gland. Treatment involves the correction of lifestyle, therapy of the underlying disease and metabolic disorders, the rejection of bad habits.

Total hypercortisolism. Etiology and pathogenesis of hypercorticism. Since the adrenal cortex is a hormone-forming complex of mineralocorticoids, glucocorticoids, androgens, and since steroid hormones partially overlap the biological effects of each other, the pathology of hypercorticism is very mosaic. ACTH serves as a functional regulator for all zones (for the beam zone, its role is undivided), and therefore total hypercortisolism syndrome includes unconditional hyperproduction of glucocorticoids, often with more or less pronounced symptoms of hyperaldosteronism and hyperandrogenism.

According to the etiology and pathogenesis of development total hypercortisolism distinguish the following options:

I. Primary adrenal hypercortisolism as a result of primary hyperplasia of the gland (ACTH-independent) - Itsenko-Cushing's syndrome;

II. Secondary hypercortisolism with excessive hypothalamic-pituitary stimulation of the gland (ACTH-dependent) - Itsenko-Cushing's disease;

III. Secondary hypercortisolism with excessive ectopic production of ACTH outside the hypothalamic-pituitary region;

IV. Iatrogenic hypercortisolism with exogenous administration of corticosteroids.

I. In a quarter of cases, hypercortisolism is associated with a primary tumor lesion of the cortical substance of the gland. This pathology is called ACTH-independent Itsenko-Cushing's syndrome. Most often, this tumor grows from the cells of the zona fasciculata - glucosteroma (with an excess of glucocorticoids). A type of glucosteroma is glucoandrosteroma with excess synthesis in addition to androgens. In this case, the picture of Itsenko-Cushing's syndrome is combined with hyperandrogenism: in boys in the form of premature puberty, in women - virilism.

Another cause of ACTH-independent Itsenko-Cushing's syndrome is primary bilateral non-tumor hyperplasia of the adrenal cortex . It occurs in adolescents and young adults. The leading link in the pathogenesis is recognized as an autoimmune stimulating mechanism, similar to Basedow's disease. Experimentally obtained steroidogenic and mitozogenic (growth) immunoglobulins to the cells of the adrenal cortex. In some cases, primary bilateral non-tumor hyperplasia is considered as a hereditary autosomal dominant variant of the syndrome - Carney's symptom complex. A fairly rare cause of primary hypercortisolism is bilateral hyperplasia of the adrenal cortex. The mechanism of this disorder is thought to be an ACTH-like stimulatory action of a gastro-inhibitory peptide synthesized by the gastrointestinal glands.

II. In the vast majority of cases, the cause of hypercortisolism is a tumor of the anterior pituitary gland - basophilic adenoma, or chromophobic tumors that secrete excess ACTH - adrenocorticotropinomas . Such a pathology in Russia is called Itsenko-Cushing's disease. Its pathogenesis is associated with a mutation of the G protein of the pituitary cells, which has an affinity for corticoliberin, as a result of which adrenocorticotrophs acquire excessive activity for this hypothalamic releasing factor.

"Antediluvian" methods of treating Itsenko-Cushing's disease by resection or extirpation of the adrenal gland with unrecognized pituitary adenomas led to the rapid growth of the same adrenocorticotropinomas due to stimulation of tumor cells of the adenohypophysis with hypothalamic corticoliberin against the background of hypocorticism, and Itsenko-Cushing's disease was replaced by Nelson's syndrome [volumetric tumor growth in the skull without signs of hypercortisolism (if the adrenal glands were resected)].

III. A relatively rare cause of secondary hypercortisolism is ectopic tumors from cells of the diffuse endocrine system (apudomas) that secrete ACTH, less often corticoliberins. This pathology occurs with bronchogenic lung cancer, digestive tract carcinomas, medullary thyroid cancer, tumors of the islets of Langerhans, thymomas. This form of hypercortisolism is sometimes combined with hypersecretion by tumor cells and other biologically active substances - vasopressin, oxytocin, gastrin, etc. In fact, the described pathology is the content of the paraneoplastic syndrome of tumor growth. The level of ACTH in ectopic secretion exceeds it in Itsenko-Cushing's disease.

IV. Iatrogenic hypercortisolism occurs with long-term treatment with medium or short-term therapy with ultra-high doses of glucocorticoids.

Pathogenesis manifestations of total hypercorticism is determined by an excess of hormones of the adrenal cortex as a result of hyperplasia of adrenocorticocytes.

Glucocorticoids are hormones of the universal metabolic cycle. ACTH is an absolute stimulator of their secretion, so the picture of hypercorticism is determined by the effects of both corticosteroids and ACTH itself (for example, one of the results of ACTH action may be skin hyperpigmentation), as well as proopiomelanocortin and its derivatives. The combination with the features of hyperaldosteronism is explained both by the stimulation of ACTH and by the mineralocorticoid effect of large doses of glucocorticoids. Recall that mineralocorticoids are the most important regulators of potassium-sodium and water balance, and androgens are regulators of sexual functions, stress and anabolism processes.

Itsenko-Cushing's disease. A decrease in dopamine activity and an increase in the tone of the serotonergic system of the central nervous system increase the production of corticoliberin, ACTH, and then cortisol (secondary cortisolism) due to a violation of the "feedback" mechanisms. Hypercortisolism does not have an inhibitory effect on the central nervous structures. The disease is characterized not only and not so much by an increase in ACTH secretion as by stimulation of the production of adrenal hormones - cortisol, corticosterone, aldosterone, androgens.

Violations of the hypothalamic-pituitary relationships are combined with changes in the secretion of other tropic hormones of the pituitary gland - the production of growth hormone is inhibited, the content of gonadotropins and thyrotropic hormone decreases, but the secretion of prolactin increases.

The clinic of Itsenko-Cushing's disease is determined by a disorder of all types of metabolism regulated by steroid hormones of the adrenal glands.

Violation protein metabolism in general, it proceeds under the sign of protein catabolism mainly in muscles and mesenchymal elements (myocytes, skin cells, connective tissue, bones, lymphoid organs), and anabolic processes even predominate in the liver and central nervous system. For this reason, myasthenia gravis (muscle weakness), muscle wasting develops. Violation of protein synthesis is reflected in the protein composition of the connective tissue, glycosaminoglycans, protein content in blood plasma (especially albumin), immunoglobulins (antibodies). Increased deamination of amino acids leads to hyperazoturia. Collagenogenesis is inhibited, which leads to thinning and stretching of the skin in places where fat accumulates (a symptom of tissue paper), contributing to the formation of characteristic striae (stretch bands) of purple-violet color due to vasopathies, erythrocytosis and hypertension. In young patients, the growth and metabolism of vitamin D are disturbed. Wound healing is inhibited.

Fat metabolism . by the most X A typical manifestation of hypercorticism is obesity of central localization: against the background of hypotrophy of the limbs, fat is deposited in the abdomen, face, neck, and in the interscapular space. The most likely causes of obesity are polyphagia, hyperinsulinism, uneven distribution of insulin and glucocorticoid receptors in various lipocytes, stimulation of leptin production by corticosteroids, direct lipogenetic effects of ACTH and glucocorticoids. An excess of glucocorticoid receptors is observed in central lipocytes, and insulinism enhances lipogenesis in them, increases the intake of glucose and fatty acids.

An excess of glucocorticoids has a lipolytic effect, causing predominantly type II hyperlipoproteinemia (due to low and very low density lipoproteins, cholesterol, triglycerides), which, according to the mechanism of development, can be attributed to production and retention forms. The development of hyperlipoproteinemia is associated with increased synthesis of triglycerides in the liver, lipolysis, and blocking of apo-B receptors in many consumer cells.

carbohydrate metabolism . Glucocorticoids have a contra-insular effect - they inhibit the work of glucose transporters (glutes-4) in insulin-dependent tissues (lipocytes, myocytes, cells of the immune system) in favor of insulin-independent organs - the central nervous system, heart, diaphragm, and others. In the liver, gluconeogenesis, glucogenesis, glycogenesis are enhanced. In some patients with insufficient reserves of pancreas β-cells, secondary non-insulin-dependent diabetes mellitus is formed, which is complicated by ketoacidosis due to the high ketogenicity of glucocorticoids (which, by the way, is characteristic of insulin-dependent diabetes mellitus). In other patients, in the case of hyperfunction of β-cells of the islets of Langerhans, hyperinsulinism develops, which stabilizes the situation, and obvious steroid diabetes does not occur.

Water-salt metabolism and acid-base balance . They are characterized by sodium retention and the loss of hydrogen and potassium ions, due to which the content of K + in the cells of excitable tissues (neurons, cardiomyocytes, myocytes), as well as in blood plasma and erythrocytes, is significantly reduced. Hypokalemic alkalosis develops. Increased volumes of extracellular fluid and blood (hypervolemia, plethora). The absorption of calcium in the intestine is inhibited, and its excretion in the kidneys is enhanced. Nephrocalcinosis and nephrolithiasis develop, secondary pyelonephritis joins. The result can be kidney failure. A decrease in calcium in the body leads to the development of secondary hyperparathyroidism. Parathyroid hormone activates the transition of bone stem cells into osteoclasts and inhibits the transformation of the latter into osteoblasts. Cortisol also inhibits the transition of osteoclasts to osteoblasts. An increase in osteoclasts and an increase in their activity cause bone resorption. The latter loses its ability to fix calcium, resulting in osteoporosis.

The cardiovascular system . Chronic hypercortisolism causes symptomatic hypertension, the development of which is associated with the following mechanisms:

1) an increase in blood volume (hypervolemia, plethora),

2) increased sensitivity of adrenoreceptors of resistive vessels to pressor factors due to an increase in the sodium content and a decrease in potassium in the myocytes of resistive vessels (that is, due to an increase in their vasomotor tone),

3) edema of smooth muscles of arterioles and venules,

4) activation of the renin-angiotensin system due to stimulation of liver synthesis of α 2 -globulin (angiotensinogen) and endothelin I by glucocorticoids,

5) the inhibitory effect of corticosteroids on the release of atrial natriuretic peptide.

IN immune system secondary immunodeficiency, phagocytic insufficiency are formed, manifested by a decrease in resistance to infectious diseases. Skin bacterial and fungal infections develop. For this reason, and due to an excess of androgens, acne (acne vulgaris) and pustular-papular perioral dermatitis appear.

sexual functions. One of the early and permanent manifestations of Itsenko-Cushing's disease is a violation of sexual function, which is caused by a decrease in the gonadotropic function of the pituitary gland and an increase in the secretion of androgens by the adrenal cortex. In men, the production of androgens by the sex glands is inhibited (due to the suppression of the secretion of GnRH and luteinizing hormone by the feedback control mechanism), libido decreases and impotence develops. Excess androgens in the hormonal set of hypercortisolism in women form hirsutism (excessive hair growth), masculinization (acquisition of a male body type), changes in sexual behavior, dysmenorrhea, amenorrhea, spontaneous abortions, premature birth, secondary infertility, virilization.

Nervous system. Acute excess of glucocorticoids induces euphoria, psychosis, hallucinations and mania, and chronic - depression.

Changes in the blood . Glucocorticoids stimulate erythro- and leukopoiesis, trigger apoptosis of lymphocytes and eosinophils, resulting in the development of erythrocytosis, neutrophilia, lymphopenia, eosinopenia, change the state of the blood coagulation and anticoagulation systems (development of thrombohemorrhagic syndromes).

Partial hypercortisolism. It is due to the pronounced the predominance of the secretion of one group of corticosteroids over the others and is represented by the following types:

1) hyperaldosteronism (primary and secondary);

2) adrenogenital syndrome (hyperandrogenism).

At the same time, there are practically no pure partial forms.

Primary hyperaldosteronism(Conn's syndrome).

I. The cause is tumors of the glomerular zone (aldosteroma) or with ectopic localization (ovary, intestine, thyroid gland). An excess of mineralocorticoids does not inhibit the production of ACTH, unlike glucosters, so atrophy of the healthy part of the adrenal glands does not occur.

II. Benign hereditary glucocorticoid-suppressed aldosteroma.

III. Bilateral hyperplasia of the glomerular zone of the adrenal cortex of unknown etiology. As in the case of micronodular cortical hyperplasia, the role of stimulatory antibodies is discussed in etiology.

IV. When eating licorice root (licorice) and using its preparations, the conversion of cortisol into cortisone is disrupted (the presence of hyperrizinic acid in plant materials inhibits the enzyme 11-β-hydroxylase). In this case, the syndrome of pseudohyperaldosteronism is reproduced. A similar enzyme defect is the cause of the hypertensive form of hereditary adrenal hyperplasia.

V. Lidl's syndrome - pseudohyperaldosteronism due to primary receptor hypersensitivity to aldosterone with its normal content in the blood.

VI. Iatrogenic administration of aldosterone.

In all forms of primary hyperaldosteronism, renin production, in contrast to secondary ones, is low. Hypervolemia through the receptor mechanism inhibits the synthesis of renin.

Secondary hyperaldosteronism. It develops due to the activation of the renin-angiotensin-aldosterone system and proceeds with a high level of renin in the blood plasma. The causes of secondary excessive secretion of aldosterone are:

1) Ischemia of the kidneys caused by damage to the renal arteries;

2) Hypovolemia;

3) Hyponatremia and excessive loss of sodium;

4) Primary non-tumor hyperplasia of cells of the juxtaglomerular apparatus of the kidney ( Bartter's syndrome, excess prostaglandins E 2);

5) Reninomas (tumors of cells of the juxtaglomerular apparatus of the kidney);

6) Pregnancy - estrogens stimulate the synthesis of renin and angiotensinogen.

Pathomorphology. In secondary hyperaldosteronism, there is no tumor and nodular hyperplasia, but hypersecretion and diffuse hypertrophy-hyperplasia are observed.

Manifestations of hyperaldosteronism consist of typical symptoms:

1) electrolyte-water disorders- hypernatremia and water retention (hypervolemia), hypokalemia and loss of hydrogen ions.

2) hypertension. It is accompanied by orthostatic fluctuations (due to potassium excretion, baroreceptors lose sensitivity to changes in systolic and diastolic blood pressure).

3) no edema - the production of atrial natriuretic peptides (atriopeptides) is increased compensatory. This mechanism removes some of the sodium and water and inhibits the formation of edema. Losses of potassium are also accompanied by polyuria, mainly at night.

4) severe hypokalemia generates muscle weakness, a violation of the flow of glucose with a current of potassium into the cell (diabetogenic effect), "hypokalemic nephropathy" with polyuria.

5) alkalosis- a shift in the acid-base balance to the alkaline side (in the distal convoluted tubules, Na + reabsorption occurs in exchange for the release of K + and H +) is accompanied by hypocalcemia with possible tetany.

The main link in the pathogenesis secondary hyperaldosteronism is a very high activity of the renin-angiotensin-aldosterone system, which occurs with severe hyperreninemia and hyperangiotensinemia, which are in antagonistic relationships with natriuretic peptides. Therefore, very high hypernatremia and systemic edema are formed.

adrenogenital syndrome. It is considered as a partial excessive secretion in the adrenal glands of sex hormones. (hyperandrogenism ).

Violations of the production of sex hormones of the adrenal glands is the cause of sexual disorders, collectively called - adrenogenital syndrome. These include:

1. Acquired forms associated with various tumors:

Itsenko-Cushing's disease and syndrome , including glucoandrosteroma,

androsteromes ,

corticoestroms (described individual cases in men).

2. Congenital forms. They are part of the structure of adrenogenital syndrome called "congenital adrenogenital syndrome" or (VDKN). The reason is the variety of gene mutations that block different stages of genetically determined steroidogenesis.

Pathogenesis. Typical female symptoms hyperandrogenism : hirsutism, dysmenorrhea, virilism and acne. In children, the tumor leads to early puberty. Children's growth stops. In girls, the congenital syndrome proceeds according to the heterosexual type and forms pseudohermaphroditism, in boys - according to the isosexual type. In 75% of cases, hypocorticism manifests itself and is accompanied by congenital hyperpigmentation of the skin, loss of salt in the urine (polyuria, hyponatremia, muscle hypotension, hyperkalemia, hypochloremia, acidosis, hypotension), vomiting with a fountain, cravings for salty foods. In 25% of cases, hypocorticism is latent.

Virilism is formed in women: hirsutism, masculinization of the physique, redistribution of fat according to the male type, a rough voice, baldness, atrophy of the mammary glands, oligomenorrhea and amenorrhea, clitoral hypertrophy, physical endurance, changes in sexual behavior stereotypes. In men, such tumors remain unrecognized. They have well-recognized corticoesteromas - malignant tumors with mutant estrogen production that cause feminization - gynecomastia, female body type and behavior, testicular hypotrophy. Congenital forms of adrenogenital syndrome with a metabolic block in the synthesis of cortisol in the direction of androgens require the greatest attention. There are many hereditary causes. They require differential diagnostic differences from true and false hermaphroditism of extra-adrenal and non-endocrine causes and determination of chromosomal sex. Adrenal congenital forms of hyperandrogenism (adrenogenital syndrome) can occur as part of the hypocorticism syndrome with symptoms of gluco- and mineralocorticoid deficiency.

The classic forms of hyperandrogenism are known: virilizing plus salt-losing but only virilizing . The non-classical form is characterized by a late onset of the disease.

The leading link in pathogenesis is the enzymatic block of the conversion of 17-hydroxyprogesterone to 11-deoxycortisol, which leads to excessive conversion of metabolites into androstenedione. Hyperandrogenism develops in utero. At the same time, a deficiency in the synthesis of mineral and glucocarticoids is formed. Against this background, the secretion of ACTH increases according to the feedback mechanism and the growth of the adrenal cortex and androsteroidogenesis is stimulated. The adrenal cortex increases due to the glomerular and reticular zones and resembles the cortex of the cerebral hemispheres. Clinically, adrenogenital syndrome consists of two syndromes – hyperandrogenism and hypocorticism , and predominantly in the form of hypoaldosteronism.

Erased and light forms [ "congenital hyperplasia (dysplasia) of the adrenal cortex" ] occur up to 30%. They are the cause of hirsutism and adrenarche. Hirsutism is a compelling reason to look for 21-hydroxylase defect syndrome. A defect in other steroidogenesis enzymes that create an innate picture of adrenogenital syndrome is extremely rare and is given in special guidelines.