Syndrome and Icenko-Cushing's disease( hypercorticism) - Causes, symptoms and treatment. MF.

Isenko-Cushing's syndrome or hypercorticism is a condition caused by prolonged exposure to the body of high levels of glucocorticoid hormones, the most important of which is cortisol.

Cortisol is produced in the cortical layer of the adrenal glands. The main stimulator of cortisol production is adrenocorticotropic hormone( ACTH).ACTH is produced in the pituitary gland - the endocrine gland located at the base of the brain. The development of ACTH is stimulated by corticotropin-releasing hormone, which is produced in the hypothalamus - the brain department that controls the endocrine system of the body.

Cortisol performs vital tasks in the body. It helps maintain blood pressure in the cardiovascular system, reduces the inflammatory response of the immune system, balances the effect of insulin, increasing blood glucose levels, regulates the exchange of proteins, carbohydrates and fats. One of the most important tasks of cortisol is to help the body respond to stress. For this reason, women in the last 3 months of pregnancy and professional athletes tend to have high levels of cortisol. People who suffer from depression, alcoholism, malnutrition and panic disorders also increase cortisol levels.

Normally, when the amount of cortisol in the blood is adequate, the pituitary gland produces less ACTH.And with a decrease in cortisol in the blood, the content of ACTH increases, to stimulate the production of glucocorticoids by the adrenals. This ensures that the amount of cortisol produced in the adrenal glands is sufficient to meet the daily needs of the body.

Causes of hypercortisone

Excessive cortisol is possible in the following cases:

1. Prolonged intake of glucocorticoid hormones such as prednisolone, dexamethasone, for the treatment of bronchial asthma, rheumatoid arthritis, systemic lupus erythematosus and other inflammatory diseases, or to suppress immunity after organ transplantation - exogenous( caused by external influence) hypercortisone .
2. Adenoma( benign tumor) of the pituitary gland is the main cause of Cushing's syndrome. Hypercorticism caused by the adenoma of the pituitary gland, the domestic doctors call a disease of Itenko-Cushing , all other cases of hypercorticism - in fact, the Itenko-Cushing syndrome. The adenoma of the pituitary gland secrete an increased amount of ACTH, while ACTH, in turn, stimulates the excess production of cortisol. This form of the syndrome affects women five times more often than men.
3. Ectopic production syndrome ACTH is a condition in which benign or malignant( cancerous) tumors outside the pituitary gland produce ACTH.Tumors of the lungs cause more than 50% of these cases. The most common forms of ACTH-producing lung tumors are ovate or small cell carcinoma tumors. Men suffer 3 times more often than women. Other less common types of tumors that can produce ACTH are thymomas( thymus tumors), pancreatic tumors, and thyroid cancer.
4. Adrenal Tumors .Sometimes Cushing's syndrome is caused by pathology, most often by a tumor, by the adrenal glands, which release an excessive amount of cortisol. In most cases, adrenal tumors are benign( adenomas).Adrenocortical carcinoma, or adrenal cancer, is the least common cause of Cushing's syndrome. Carcinomas of the adrenal cortex usually cause a very high increase in the level of hormones and the rapid development of symptoms. A very rare cause of adrenal Cushing's syndrome is hyperplasia of the adrenal cortex, i.e.a pathological increase in the number of cortical cells. With all adrenal forms of the Itenko-Cushing syndrome, the level of ACTH in the blood is lowered.
5. Family form of Cushing's syndrome .Most cases of Cushing's syndrome are not inherited. However, very rarely the cause of this syndrome is a hereditary disease - a syndrome of multiple endocrine neoplasia, i.e.the propensity to develop tumors from one or more endocrine glands. In this disease, along with a tumor of the adrenal glands, tumors of the parathyroid glands, pancreas and pituitary gland that produce the corresponding hormones can be present.

Symptoms of the Itenko-Cushing syndrome

Most patients with hypercortisia are obese. Weight gain is one of the earliest signs of illness. The deposition of fat tissue occurs mainly in the trunk, face, neck. And limbs, on the contrary, are thinned.

Syndrome Itenko-Cushing

In childhood and adolescence, as a rule, along with obesity, the growth rate slows down.
Skin changes are very characteristic for hypercorticism. The skin becomes thin, bruises, bruises, which pass very long, are noted. There may appear wide purple-pink, purple stretches on the abdomen, thighs, buttocks, arms and chest.

Strias with Isenko-Cushing's syndrome

Sometimes patients complain of back pain, ribs, hands and feet when walking. This is because Cushing's syndrome often leads to osteoporosis. Osteoporosis means a decrease in bone density, a violation of their structure, increased brittleness and reduced strength, which can lead to fractures, even with the slightest trauma.

The Itenko-Cushing syndrome is accompanied by fatigue, muscle weakness, irritability, anxiety, and rarely changes in the psyche.

One of the earliest symptoms of the syndrome is increased blood pressure. Since glucocorticoids inhibit the effect of insulin, often with hypercorticosis, the blood sugar level rises, and symptoms of diabetes mellitus appear( thirst, frequent, profuse urination, etc.).

Women usually have excessive hair growth on the face, neck, chest, belly skin and thighs. Menstruation can become irregular or stop. Men report a decrease in libido.

In case of any of their symptoms of hypercortisy, and especially their combinations, it is necessary to seek medical help as soon as possible.

Diagnosis of Itenko-Cushing's syndrome

The task of the first stage of diagnosis is to establish whether there is an increase in the level of cortisol. To do this, use a special test - the determination of cortisol in daily urine.

In the urine of a patient collected over a 24-hour period, the level of cortisol is determined. Levels higher than 50-100 mcg per day for adults confirm Cushing's syndrome. The upper limit of normal values ​​varies in different laboratories, depending on the measurement methodology used.

Once an increase in cortisol levels is detected, it is necessary to detect the exact location of the process that leads to excess production of cortisol.

A sample with dexamethasone helps distinguish patients with excess ACTH production due to pituitary adenoma from patients with an ectopic ACTH-producing tumor. The patient takes dexamethasone( synthetic glucocorticoid) inside every 6 hours for 4 days. In the first 2 days, lower doses of dexamethasone are given, in the last 2 days, higher doses are given. Urine collection is performed daily before dexamethasone is administered and then every day of the test. With pituitary adenoma, the level of cortisol in the urine decreases, and with an ectopic tumor outside the pituitary, the level of cortisol does not change. For the test, it is necessary to stop taking such drugs as phenytoin and phenobarbital for one week.

Depression, alcohol abuse, high levels of estrogen, acute disease and stress can lead to the wrong result. Therefore, preparation for the test should be thorough.

Stimulation test with corticotropin-releasing hormone .This test helps to distinguish patients with pituitary adenoma from patients with the syndrome of ectopic production of ACTH and the cortisol-secreting tumor of the adrenal glands. The patient is injected with corticotropin-releasing hormone, which causes the pituitary to produce ACTH.When the pituitary adenoma level of ACTH and cortisol in the blood increases. Such a response is very rarely observed in patients with the syndrome of ectopic ACTH production and almost never in patients with cortisol-secreting adrenal tumor.

The next stage of diagnostics is direct visualization of endocrine glands .The most commonly used are ultrasound studies of the adrenal glands, computed tomography or magnetic resonance imaging of the pituitary gland, adrenal glands. To establish the ectopic foci of ACTH production, ultrasound, computer or magnetic resonance imaging of the corresponding organ( usually the thorax, thyroid, pancreas) is used.

Treatment of Isenko-Cushing syndrome

Treatment depends on the specific cause of excess cortisol and may include surgical, radiation or medication.

If the cause of the syndrome is the long-term use of glucocorticoid hormones for the treatment of another disease, it is necessary to gradually reduce the dose to the minimum dose sufficient to control this disease.

For the treatment of pituitary adenoma, the most widely used surgical removal of the tumor, known as transsphenoidal adenomectomy .Using a special microscope and very thin endoscopic instruments, the surgeon approaches the pituitary through the nostril or hole made under the upper lip, and removes the adenoma. The success of the operation depends on the skill of the surgeon, is more than 80 percent when performed by a surgeon with extensive experience. After the operation, the production of ACTH by the pituitary gland decreases sharply, and patients receive replacement therapy with glucocorticoids( for example, hydrocortisone or prednisolone), this is usually required during the year, then the production of ACTH and glucocorticoids is restored.

For patients who have contraindications to surgery, it is possible to perform radiation therapy .This method takes 6 weeks, the effectiveness is 40-50%.The disadvantage of this method is the delay in improvement, the effect may come in a few months or even years after the irradiation. However, the combination of radiotherapy and drug therapy mitotan( Lizodren) can help accelerate recovery. Mitotan suppresses the production of cortisol. Treatment with mitotane alone can be successful in 30-40% of cases.

There are other drugs used in hypercortisy alone or in combination: aminoglutethimide, metirapone and ketoconazole. Each of them has its own side effects, which doctors take into account when prescribing therapy for each patient individually.

In the syndrome of ectopic AKTG production, surgical removal of the ACTH-secreting tumor is most preferable. In cases where the tumor is detected at an inoperable stage, adrenalectomy is used - adrenal removal. This operation somewhat alleviates the symptoms in this category of patients. Sometimes it is used and medicamental treatment( Metirapone, Aminoglutethimide, Mitotan, Ketoconazole).

With adrenal tumors, the surgical method is the basis for treating both benign and malignant adrenal tumors.

Doctor endocrinologist Fayzulina N.M.