Itsenko-Cushing syndrome (Cushing's syndrome)

Most often, the disease develops as a result of long-term administration of large doses of glucocorticoids to the patient for the purpose of treating a number of autoimmune pathologies.

The syndrome includes:

• Cushing's disease is an excessive synthesis of adrenocorticotropic hormone (ACTH) by the pituitary gland, which triggers a number of hormonal changes. Accounts for 80% of all pathological conditions included in the syndrome.
• Corticoliberin-ectopic syndrome - develops in most cases with bronchial carcinoma (up to 46%), lung cancer (up to 20%), pheochromocytoma (up to 23%), malignant tumor of the thyroid gland (up to 7%). Rarely, ectopic ACTH production is affected by neoplasms at other sites. This condition accounts for up to 18%.
• Iatrogenic cancer of the adrenal cortex is a malignant formation that appears as a result of the influence of various medical treatment and diagnostic procedures on the body (drug and radiation therapy, surgical trauma). Iatrogenic tumors include adenomas, adenomatosis, and adenocarcinomas. Iatrogenic cancer accounts for 1–2%.

In all conditions included in the syndrome, hypercortisolism is observed - increased production of cortisol (adrenal hormone), which causes similar symptoms of Itsenko-Cushing syndrome. Depending on the etiological factors, treatment of the disease can be either conservative or surgical.

Causes of Itsenko-Cushing syndrome

The main causes of Itsenko-Cushing syndrome

- increased production of hormones by the adrenal cortex. Most often, the cause of this anomaly is a tumor that produces excessive amounts of ACTH. The tumor can form in various organs, most often in the bronchopulmonary system, less often in the genitourinary system. Increased synthesis of ACTH affects the functions of the adrenal glands, which begin to secrete glucocorticoids in increased quantities. In addition, a tumor can form in the adrenal cortex, and in this case, increased synthesis of glucocorticoids will also be observed. Obesity, pregnancy, alcohol abuse for a long time, and a number of mental illnesses can lead to an increase in the level of glucocorticoid hormones in the body. The condition that occurs as a result of exposure to these factors is called pseudo-Cushing's syndrome.

Another reason for the development is long-term therapy of autoimmune diseases with the use of large dosages of drugs containing glucocorticoid hormones. In endocrinology, there is not only a syndrome, but also Itsenko-Cushing's disease

. Despite the obvious similarity of symptoms, the causes of these pathologies are different. The cause of the disease is a disturbance in the hypothalamic-pituitary system, most often a small benign tumor of the pituitary gland (microadenoma) affecting the glandular tissue. This pathology is characterized by severe neuroendocrine disorders.

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Signs and symptoms of Cushing's syndrome

Symptoms of Itsenko-Cushing syndrome are as follows:

• Obesity - deposition of adipose tissue occurs in the upper part of the body, while the limbs remain thin.
• The appearance of purplish-pink stripes on the skin due to the breakdown of collagen and overstretching with fat.
• Cycle disruption in women, development of infertility.
• Formation of pigment spots on the elbows and in skin folds, acne, and the appearance of excess body hair.
• Decreased libido and erectile dysfunction in men.
• Progressive osteoporosis and, as a consequence, bone fractures.
• A decrease in the body’s immune defense, which causes the development of infectious diseases of the skin and a number of other organs.
• Cardiac arrhythmia, arterial hypertension.
• Impaired carbohydrate metabolism and the development of steroid diabetes.
• Muscle weakness (including myocardium), resulting from the breakdown of proteins.

Complications of Itsenko-Cushing syndrome are extremely dangerous for the health and life of the patient. Increased secretion of cortisol leads to the destruction of protein structures in the body. Protein breaks down in muscle and bone tissue, in internal organs, which subsequently leads to dystrophic changes and atrophy of these tissues and organs.

When the disease occurs, glucogenesis is impaired. Excessive amounts of glucose are absorbed by the intestines, which leads to the development of steroid diabetes. Lipid metabolism disorders manifest themselves in the form of fat deposits in some areas of the body and atrophy in other areas due to differences in the sensitivity of organs and tissues to glucocorticoids. Electrolyte imbalance is manifested by hypokalemia (low potassium in the blood) and hypernatremia (increased sodium concentration in the blood). In this case, hypertension, intestinal obstruction, urolithiasis, respiratory disorders, and weakness may develop.

Signs of the disease

The most serious complication of Itsenko-Cushing syndrome is disruption of the myocardium. With dysfunction of the heart muscle, arrhythmia, decompensated heart failure, and cardiomyopathy develop. Hypercortisolism also suppresses the immune system, so patients with Itsenko-Cushing syndrome are prone to infectious diseases, furunculosis, and fungal skin lesions.

In severe cases, it develops:

• Stroke.
• Paralysis and paresis.
• Pyelonephritis.
• Decompensated renal failure.
• Sepsis.
• Osteoporosis, characterized by multiple fractures.
• Sympathoadrenal crisis (vomiting, hypotension, confusion, abdominal pain, acidosis).

Hypercortisolism in pregnant women usually leads to miscarriage or childbirth with complications. Patients diagnosed with Itsenko-Cushing syndrome die precisely from complications of the pathology.

Publications in the media

Regarding the treatment of this disease, you can contact the Surgical Department No. 2 of the Clinic of Faculty Surgery named after. N.N. Burdenko

Itsenko-Cushing syndrome (Cushing's syndrome) is hypercortisolism caused by an increase in the content of endogenous or exogenous GCs in the blood. Endogenous GCs appear due to their overproduction by the adrenal cortex in the presence of: • glucosteroma; • hyperproduction of ACTH by the anterior lobe of the pituitary gland (presence of adenoma; in this case they speak of Itsenko-Cushing’s disease); • ACTH-secreting tumors of various organs (primarily the lungs; in this case they speak of the syndrome of ectopic ACTH production). Exogenous GCs cause drug-induced Itsenko–Cushing syndrome, which occurs much more often than spontaneous; usually develops in patients receiving GCs for a long time for various diseases (for example, autoimmune diseases).

Statistical data. Most often, Itsenko–Cushing syndrome is iatrogenic in nature. In the United States, the incidence of Itsenko–Cushing syndrome, caused by endogenous hyperproduction of GCs, is 13 cases per 1 million population. Of these, 70% are caused by Itsenko-Cushing's disease with the presence of an ACTH-producing adenoma, 15% by ectopic ACTH production, and 15% by a primary adrenal tumor (glucosteroma). The predominant gender is female (5:1). Predominant age: for Cushing's syndrome caused by pituitary or adrenal adenoma - 25-40 years, for ectopic ACTH production due to lung cancer - elderly age.

Etiology

• Treatment of GC: usually Itsenko-Cushing syndrome occurs with systemic use of GC, but it can develop with intra-articular administration of GC and even inhalation use. The range of diseases for which GCs are prescribed is very wide and includes a variety of rheumatological, nephrological, pulmonary and neurological pathologies; In addition, the use of GC is possible in the presence of transplanted tissues and organs.

• Endogenous hyperproduction of GC due to: •• the presence of ACTH-producing pituitary adenoma (as part of Itsenko-Cushing's disease), which, when large, compresses the pituitary tissue and suppresses the production of most pituitary hormones, as well as leading to ophthalmological disorders; •• lesions of the adrenal glands: glucosteroma (adenoma or carcinoma), macro- or micronodular hyperplasia (a simultaneous increase in hyperproduction of both GC and androgens by cells of the reticular or zona fasciculata of the adrenal cortex is possible) •• ectopic production of ACTH by cancer cells in oat cell or small cell carcinoma lung.

Pathogenesis

• Increased ACTH synthesis leads to adrenal and extra-adrenal effects •• Adrenal - increased content of GC and androgens in the reticular layer of the adrenal cortex. To a lesser extent, ACTH affects the increase in the concentration of mineralocorticoids •• Extra-adrenal - hyperpigmentation of the skin and mucous membranes (in 10% of cases) and mental disorders

• Increased HA production is a key point in the pathogenesis of Itsenko-Cushing syndrome/disease. Effects: •• Catabolic effect on protein and carbohydrate metabolism leads to atrophy of muscle (including cardiac) tissue and skin, as well as hyperglycemia with the development of steroid diabetes (in 20% of cases). In the pathogenesis of steroid diabetes, relative insulin deficiency (with increased gluconeogenesis in the liver) and insulin resistance also play a role •• Anabolic effect on fat metabolism leads to obesity (more than 90% of cases) •• Mineralocorticoid activity promotes activation of the renin-angiotensin-aldosterone system with the development of arterial hypertension and hypokalemia. The GC potentiation of the effect of catecholamines and biogenic amines (in particular, serotonin) has a certain significance in the pathogenesis of arterial hypertension. •• The catabolic effect on bone tissue leads to a decrease in the ability of bone tissue to fix calcium and the development of osteoporosis (more than 80% of cases). A certain role in the pathogenesis of osteoporosis is played by a decrease in GC reabsorption of calcium in the gastrointestinal tract, which is associated with inhibition of the processes of hydroxylation of calciferol •• Suppression of specific immunity leads to the development of secondary immunodeficiency •• Increased secretion of androgens (testosterone) by the adrenal glands leads to a decrease in the gonadotropic function of the pituitary gland and the development of sexual disorders • • Changes in the secretion of other tropic hormones - decreased levels of growth hormone and TSH, increased levels of prolactin.

Clinical manifestations

• Symptoms of a fat metabolism disorder define a Cushingoid appearance: •• Moon face (deposition of fat on the face) •• Deposition of adipose tissue on the neck (“buffalo hump”) and upper torso (especially noticeable above the collarbones), but not on the extremities (“colossus hump”) with feet of clay").

• Symptoms of carbohydrate metabolism disorders - steroid diabetes or decreased glucose tolerance with rapidly increasing hyperglycemia and/or glycosuria.

• Symptoms of protein metabolism disorders: •• Muscle weakness - steroid myopathy: patients have difficulty climbing stairs, rising from a low chair, raising their arms •• Red-violet stretch marks on the skin of the abdomen, chest and thighs •• Predisposition to ecchymosis (due to increased capillary fragility) •• Slow wound healing •• Predisposition to infections due to immunodeficiency.

• Symptoms of impaired water-electrolyte metabolism: an increase in BCC due to water and sodium retention.

• The presence of an ACTH-producing pituitary adenoma (as part of Cushing's disease) leads to the appearance of ophthalmological disorders, headaches, galactorrhea and other disorders (see Pituitary adenoma).

• Other disorders: •• Arterial hypertension (newly detected or progressive) •• Lipid metabolism disorders (increased synthesis of both HDL and LDL, triglycerides) contribute to the rapid progression of atherosclerosis of the coronary arteries and the development of coronary artery disease •• Petic ulcers, sometimes asymptomatic, especially in patients receiving high doses of GC •• Osteopenia and osteoporosis (up to osteoporetic fractures); avascular necrosis of the femur is also possible •• Disorders of hormonal regulation of the reproductive system (dysmenorrhea, amenorrhea, infertility) •• Acne, hirsutism •• Formation of trophic ulcers and pustular skin lesions (due to the development of secondary immunodeficiency) •• Hyperpigmentation of the skin and mucous membranes (ACTH effect ), usually in areas of skin friction - an important differential diagnostic sign for identifying excess ACTH production •• Emotional lability, depression, cognitive disorders •• In children - growth retardation.

Adrenal crisis. Emergency condition; may occur in patients with Itsenko-Cushing syndrome due to abrupt cessation of GC intake, as well as if the dose of GC is not increased when the patient develops any acute disease. In addition, it occurs in the postoperative period after removal of an ACTH- or GC-producing tumor.

Clinically manifested by arterial hypotension, abdominal pain, vomiting and disturbances of consciousness. Laboratory changes include hypoglycemia, hyponatremia, hyperkalemia, and metabolic acidosis.

Laboratory data. The main goal is to determine the hyperproduction of HA in the patient’s body with the simultaneous determination of ACTH content (the condition for reliable results is that the patient does not have an acute illness). The first step is to assess the dependence/independence of manifestations on ACTH • To identify overproduction of GC, it is necessary to detect increased levels of cortisol itself or its metabolites in the blood or in the urine (increased daily urinary excretion of free cortisol or 17-hydroxycorticosteroids [17-OX]) • • An increase in the concentration of cortisol in the blood at night (preferably closer to midnight) of more than 7.5 mcg% is a reliable sign of Itsenko-Cushing syndrome. Even more reliable is the detection of elevated levels of cortisol in the blood for several days in a row. Currently, methods for determining the content of cortisol in saliva (saliva collection at home) have been developed, but their use is limited due to high cost • An increase in the level of ACTH in plasma to 20 pg/ml (the most significant increase at night) is an important differential diagnostic sign •• With glucosterome due to excessive production of cortisol, the secretion of ACTH by the pituitary gland is suppressed, which leads to a decrease in its level in plasma (less than 5 pg/ml) •• In the syndrome of ectopic ACTH production or ACTH-serating pituitary adenoma, its concentration is 10–20 pg/ml and higher.

However, to identify Itsenko-Cushing syndrome, two screening tests are usually used (more convenient).

• Daily cortisol excretion test. This is the most reliable test for detecting daily hyperproduction of HA. An increase of more than 3–4 times (relative to the upper limit of normal) indicates an undoubted diagnosis of Itsenko–Cushing syndrome/disease, while with an increase of 2–3 times it is necessary to carry out differential diagnosis with Itsenko–Cushing pseudosyndrome. When performing the test, you should make sure that the patient correctly collected daily urine - to do this, you need to determine the amount of creatinine in the same daily urine.

• Overnight dexamethasone suppression test is a primary diagnostic test for suspected Cushing's disease or syndrome (administration of exogenous GC normally leads to a decrease in the production of ACTH and, therefore, cotrizol). The patient takes 1 mg of dexamethasone orally at 11 o'clock in the evening, and the next morning at 8 o'clock the serum cortisol level is determined •• Serum cortisol concentration less than 1.8 mcg% indicates normal suppression of ACTH and cortisol by dexamethasone and allows excluding the diagnosis of Itsenko-Cushing syndrome . In this case, the test is considered sensitive, there is no need to further clarify the diagnosis •• In patients with Cushing's disease or syndrome, the cortisol concentration during this test exceeds 1.8 μg% (usually 5–10 μg%). When such results are obtained, the test is not considered sufficiently specific, since false positive results are possible (obesity, alcoholism, stress, chronic renal failure, anorexia, bulimia; taking phenobarbital, contained, for example, in drugs such as Corvalol, Valocordin, tamoxifen, rifampicin).

If further examination is necessary, the following tests are used.

• The standard dexamethasone suppression test is a reliable test for the diagnosis of Cushing's syndrome/disease, although the sensitivity and specificity of this test is approximately 70%. Suppression of the hypothalamic-pituitary-adrenal axis is studied by administering low-dose dexamethasone (0.5 mg dexamethasone divided into 8 doses, every 6 hours orally for 2 days) with measurement of serum cortisol concentrations and urinary 17-OX levels on the second day. day (expected to decrease). Currently, a combination of the standard dexamethasone suppression test with additional administration of corticoliberin (1 mcg/kg IV 2 hours after taking the eighth dose of dexamethasone) is considered promising. The test can also detect a reduction in 17-OX excretion by more than 50%.

• The overnight high-dose dexamethasone suppression test is more convenient to perform than the standard test. It is used when ACTH levels are intermediate between 5 and 10 pg/ml. Serum cortisol concentrations are determined at 8 a.m. for two consecutive days, and 8 mg of dexamethasone is taken at 11 p.m. on the first day. A drop in serum cortisol levels of more than 50% on the second day indicates a pituitary origin of excess ACTH rather than ectopic ACTH production or primary adrenal pathology.

• Corticoliberin stimulation test. Corticoliberin is administered parenterally and after 15 minutes the levels of ACTH and cortisol are measured. In Itsenko-Cushing's disease, the levels are usually elevated (for cortisol - more than 1.4 μg%), the absence of a response indicates an ectopic or adrenal genesis of hypercortisolism.

Other criteria • Neutrophilic leukocytosis (sometimes more than 11´109/l) • Hyperglycemia and glycosuria • Hyperlipidemia • Hypokalemia • Lymphopenia • Eosinopenia.

Instrumental data. The use of special research methods must be preceded by a thorough laboratory examination.

• X-ray of the skull reveals macroadenomas of the pituitary gland (10% of cases), X-ray of the lumbar spine reveals osteoporosis. However, for diagnosing Itsenko–Cushing syndrome and disease, this method is currently considered to be of little information.

• If Itsenko-Cushing's disease (pituitary origin of excess ACTH production) is suspected, it is necessary to conduct imaging studies of the head •• CT scan of the head with the introduction of contrast can detect about 50% of pituitary adenomas •• MRI with gadolin contrast - the method of choice - allows us to detect about 75% of such tumors •• Often, even with MRI, no changes are detected due to very small microadenomas or diffuse hyperplasia of the corresponding pituitary cells. In this case, it is useful to separately determine the ACTH content in the blood from the inferior petrosal sinus and peripheral veins. Blood samples are taken from peripheral veins and (by catheterization) from the inferior petrosal sinus of the dura mater. A ratio of the level of ACTH in the sinus blood to the level of ACTH in the peripheral veins of more than 2.0 is observed in Cushing's disease, while a ratio of less than 1.5 is characteristic of the syndrome of ectopic ACTH production.

• If pathology of the adrenal glands is suspected, the following diagnostic procedures are performed •• CT scan of the abdominal cavity, which makes it possible to detect enlargement of the adrenal glands (if their size is more than 4-6 cm, carcinoma should first be excluded, for which it is possible to conduct a targeted aspiration biopsy under CT control). Uniform enlargement of both adrenal glands suggests Cushing's disease or ectopic ACTH production syndrome. Enlargement of one adrenal gland in the presence of the corresponding clinic suggests glucosteroma • Radioisotope study using 19-iodocholesterol labeled with radioactive iodine reveals bilateral hyperplasia in the case of Cushing's disease or ectopic ACTH production syndrome, in glucosteroma - asymmetric absorption of the drug.

• If ectopic ACTH production syndrome is suspected: •• CT scan of the chest and abdominal cavities •• Scintigraphy labeled with octreotide (cells of neuroendocrine tumors have receptors for somatostatin).

Diagnostic tactics. Suspected on the basis of anamnestic and clinical data, Itsenko-Cushing syndrome, after exogenous intake of GC (even inhalation or intra-articular) has been excluded, requires verification through a thorough laboratory examination aimed at identifying the source of GC hyperproduction and the dependence of the condition on ACTH. Special instrumental research methods (of the head, adrenal glands or chest cavity) are prescribed for final verification of the diagnosis after a hypothesis about the cause of Itsenko-Cushing syndrome has been formulated, based on laboratory findings.

Differential diagnosis • Functional hypercortisolism in alcoholism (currently referred to as “alcohol-induced pseudo-Cushing syndrome”) and pregnancy • Depressive disorders - they are often manifested by changes in the functions of the hypothalamic-pituitary-adrenal system with hyperproduction of GC and secondary development of moderate Itsenko-Cushing syndrome. On the other hand, Itsenko-Cushing syndrome can manifest itself as emotional lability and depression, so the combination of both conditions requires a careful search for the root cause • Obesity, occurring with arterial hypertension and carbohydrate metabolism disorders • Adrenogenital syndrome.

TREATMENT

General tactics. Treatment for Cushing's syndrome/disease depends on the cause. Iatrogenic syndrome (treatment is mandatory in this case as well) involves the gradual withdrawal of GCs (with their replacement, if necessary, with other immunosuppressants).

For Itsenko–Cushing syndrome with overproduction of HA, the method of choice is surgical removal of the causative tumor (pituitary gland, adrenal glands, lungs). If surgical treatment is ineffective or impossible (which is more often the case with ectopic ACTH secretion syndrome or metastatic carcinoma), drug treatment is attempted. Unfortunately, the latter often turns out to be ineffective, and then they resort to bilateral adrenalectomy. For ACTH-producing pituitary adenoma, they often resort to, among other things. to radiation therapy.

Drug therapy. To provide “medicinal adrenalectomy,” drugs such as mitotane, ketoconazole, and aminoglutethimide are used. However, at doses that cause a decrease in cortisol synthesis, these drugs are often toxic. Therefore, when prescribing them, it is necessary to carefully monitor the patient, assessing the effectiveness of the therapy by the level of daily cortisol excretion • The drug of choice for long-term use is ketoconazole. It inhibits both the synthesis of cortisol and, most likely, ACTH • Currently, studies are being conducted on the effectiveness of drugs that reduce the secretion of ACTH and corticoliberin - bromocriptine, octreotide, valproic acid, cyproheptadine.

Radiation therapy. It is used when treatment - surgical or medicinal - is ineffective, usually in combination with them. Radiation therapy increases the effect of drug treatment.

Surgery

• The method of choice for Cushing's disease is transsphenoidal resection of the pituitary adenoma with the maximum possible preservation of its functions. Endoscopic techniques are now becoming available. The operation is successful in 60–80% of cases and is accompanied by the subsequent establishment of normal function of the pituitary gland and adrenal glands and the cure of Itsenko-Cushing syndrome. If conventional surgical treatment is ineffective, it is necessary to keep in mind the possibility of performing surgery on the pituitary gland using MRI guidance.

• In case of ectopic ACTH production, surgical treatment of the identified tumor is performed; if this is not possible, drug treatment or bilateral adrenalectomy is indicated.

• For adrenal tumors, unilateral adrenalectomy is usually performed.

• Bilateral adrenalectomy is indicated in two cases: •• ineffectiveness of previous therapy (surgical, radiation, drug); •• the need to quickly normalize the concentration of cortisol in the blood. The procedure cures Cushing's disease, but the patient develops Addison's disease and needs lifelong replacement of steroids (GC and mineralocorticoids). In addition, in some cases, after adrenalectomy, Nelson's syndrome develops, in which the pituitary adenoma begins to grow rapidly, because it is no longer inhibited by elevated cortisol levels.

Complications • Osteoporosis • Predisposition to purulent-inflammatory diseases • Hirstutism • Diabetes • Arterial hypertension • Adrenal crisis • Panhypopituitarism • Diabetes insipidus • It should be borne in mind that with an increased content of HA in the blood, the clinical picture of acute pathology of the abdominal cavity can be extremely poor.

Forecast. Depends on the cause of the condition, as well as the possibility and effectiveness of surgical treatment.

Reduction. 17-OX - 17-hydroxycorticosteroids.

ICD-10 • E24 Itsenko-Cushing syndrome

Diagnosis of Itsenko-Cushing syndrome

Diagnosing the disease is difficult; numerous tests, hardware and laboratory examinations will be needed.

Diagnosis of Itsenko-Cushing syndrome includes:

• Urinalysis to determine the daily excretion of free cortisol.
• Dexamethasone tests: small and large. A small test consists of a step-by-step determination of the cortisol level in the blood before taking a glucocorticosteroid and after taking it. The drug used is dexamethasone, a hormonal agent with an antihistamine and anti-inflammatory effect. After taking dexamethasone, cortisol concentrations normally decrease by half or more. During illness, cortisol levels increase or remain unchanged. A large dexamethasone test is carried out in a similar way, the only difference is in the dose of medication. The goal is differential diagnosis of Itsenko-Cushing syndrome and determination of its specific type.
• MRI of the brain to exclude pituitary adenoma.
• Computer or magnetic resonance examination of the adrenal glands.
• X-ray diagnostic methods make it possible to identify complications of the disease, compression fractures of the spinal column.
• General blood test and blood biochemistry to detect diabetes mellitus of steroid genesis and electrolyte disturbances.

Based on the results of diagnostic procedures, treatment tactics are selected, the dosage of medications is individually selected, and a treatment protocol is drawn up.

Tests and diagnostics

If a person notices some of the signs described above, he needs to immediately contact an endocrinologist.

To establish a diagnosis, the doctor initially conducts an examination, after which he prescribes the patient the necessary set of studies:

• Laboratory testing of blood and urine for hormone . It is imperative to determine the level of corticosteroids and ACTH.
• Hormonal tests are also carried out. To do this, the patient initially donates blood to determine the level of hormones, after which he takes a drug ( Sinacthen , Dexamethasone , etc.) and after a certain time donates blood again.
• Biochemical blood test - allows you to determine the presence of disorders in the body, as well as identify diabetes mellitus .
• An x-ray of the skull and sella turcica area is taken to determine the size of the patient's pituitary gland.
• Computed tomography and magnetic resonance imaging are carried out to study in detail the features of the pituitary gland and brain structures.
• X-ray of skeletal bones - carried out to determine the presence of osteoporosis and pathological fractures.

Treatment of Itsenko-Cushing syndrome

Choosing a treatment regimen for Itsenko-Cushing syndrome

depends on the reasons that caused the development of this pathology. Therapy is carried out in the endocrinology department of the hospital.

In case of drug syndrome, individual therapeutic regimens and minimum doses of drugs are selected in order to reduce the negative effect of glucocorticoids on the body. Drug treatment of Itsenko-Cushing syndrome involves the use of dopaminergic pharmaceuticals that inhibit the secretion of adrenocorticotropin, antiserotonin drugs, and steroid synthesis blockers. There are two types of inhibitors used: those that only block steroid production, and those that block synthesis while simultaneously causing destruction of cortical cells. As soon as the diagnosis of Itsenko-Cushing syndrome is established, corticosteroid hormone blockers are immediately prescribed. They are used before surgery, as well as after irradiation.

For tumors of the pituitary gland, lungs, and adrenal glands, surgical removal of the tumor focus is indicated. Modern visual diagnostic techniques make it possible to make an accurate diagnosis of Itsenko-Cushing syndrome and establish the location and volume of the cancer focus. This is important in order to choose the optimal surgical tactics and not harm healthy tissues during the operation.

Adenomectomy is effective in 80% of cases. After intervention and a short course of replacement therapy, hypothalamic-pituitary connections are restored in a relatively short time. The percentage of relapse ranges from 12 to 20. With unilateral adrenalectomy, proton therapy is effective in the pituitary area in the absence of a pituitary tumor. Bilateral adrenalectomy is performed in extreme cases. After surgery, patients undergo replacement therapy for life, are regularly monitored by a specialist, and do not engage in heavy labor.

Patients for whom surgery is contraindicated (in extremely severe forms of the disease) may undergo radiation therapy. The course of treatment in this case is six weeks. Radiation is also indicated for malignant neoplasms with metastases. If it is impossible to remove the tumor, drug treatment is carried out with the drugs Ketoconazole and Mitotane. Before the operation, the patient must undergo medication preparation.

For this purpose the following is prescribed:

• To reduce glucose - insulin.
• Antihypertensive drugs.
• Calcium preparations to strengthen bone tissue.
• Potassium preparations.
• Antidepressants.
• Anabolic steroid.

For adrenal hyperplasia, destruction methods are now often used. Under visual diagnostic control (ultrasound or CT), a sclerosing substance is injected, which destroys the hyperplastic tissue of the adrenal glands. The sclerosing agent consists of 96% ethyl alcohol and a radiopaque component (76% urografin) 3:1. Typically, destruction is used in combination with radiation and/or surgery.

In a comprehensive treatment program, symptomatic medications are prescribed:

• Antihypertensive drugs.
• Medicines that lower glucose levels.
• Potassium preparations.
• Therapy for osteoporosis: calcitonins, vitamin D, bisphosphonates, anabolic steroids.
• Antidepressants and sedatives.
• Vitamins and immunostimulants.

All patients with the syndrome, especially postoperative ones, are observed for a long time by an endocrinologist, neurologist, gynecologist-endocrinologist, and cardiologist.

Classification

During the diagnostic process, endogenous and exogenous hypercortisolism is determined.

• Endogenous Cushing's syndrome is a consequence of too active production of glucocorticoids by the adrenal glands.
• Exogenous Cushing's syndrome is a consequence of taking glucocorticosteroid drugs in too large doses for the purpose of replacement therapy. This form of the disease can develop regardless of the form of medication: it can be either tablets or injection solutions, or local remedies.

In turn, the following forms of endogenous hypercortisolism are distinguished:

• ACTH-independent , that is, primary. It is also classified into several different types.
• ACTH-dependent , that is, secondary. In this case, an excessive amount of ACTH is synthesized by the pituitary gland or, in more rare cases, by a tumor located outside the pituitary gland. Less often we talk about ectopic secretion of CRH.

ACTH-independent hypercortisolism is associated with the following phenomena:

• Autonomous tumors of the adrenal glands are adenomas, usually single, less often multiple. Those tumors that originate from the zona fasciculata produce only the hormone cortisol. Other types of tumors - mixed or tumors from the reticular zone - in addition to cortisol, also synthesize androgens . When there is an excess of cortisol in the body due to inhibition of the secretion of CRH and ACTH, the tissues of the adrenal cortex atrophy - both the affected and healthy glands. Sometimes multiple adrenal cortex nodules also appear.
• Macronodular adrenal hyperplasia - this form is associated with ectopic receptors in the adrenal cortex that respond to stimulation by atypical stimuli. Most often it is a gastric inhibitory peptide that is released after eating in the digestive tract. But stimulating factors can be other - vasopressin, catecholamines, TSH, LH, hCG , FSH, high concentrations of estrogen, prolactin .
• Micronodular adrenal hyperplasia is a familial form and a sporadic form, when adrenal hyperplasia is provoked by immunoglobulins . As with other forms of independent hypercortisolism, atrophy of the adrenal tissue between the nodules may occur.

Prevention of Itsenko-Cushing syndrome

Prevention of Itsenko-Cushing syndrome comes down to the use of timely therapeutic measures and avoidance of complications, since irreversible consequences kill up to 50% of patients. With malignant corticosteroma, up to 25% of patients overcome the five-year mark. The prognosis is relatively favorable if the cause is Cushing's syndrome

- corticosteroma is benign, with 80% of patients having a functioning adrenal gland. Survival and quality of future life are affected by timely diagnosis, the presence of complications, the effectiveness of drug therapy and surgical intervention.

In order to prevent Itsenko-Cushing syndrome in order to prevent irreversible consequences, it is necessary to regularly undergo screening tests and be observed by specialists, not to work in hazardous work, especially on night shifts, and to avoid physical activity.

Itsenko-Cushing syndrome is a disease that includes several pathological conditions, the development of which is caused by increased synthesis of glucocorticoids in the body, which has a negative effect on the functioning of a large number of organs. This includes impaired reproductive function. To restore it in Itsenko-Cushing syndrome, if you want to have children, contact the AltraVita clinic. We will help you solve the problem.

Treatment with folk remedies

In the process of treating the disease, traditional methods can help normalize the increased appetite due to hormonal imbalance. It is also appropriate to use herbal remedies that normalize blood pressure . But with such a complex diagnosis, the patient must first discuss the use of any traditional method of treatment with the attending physician. Such methods are only auxiliary in the process of main therapy.

The following traditional methods of treatment can be used:

• Take equal parts of dried raw herbs: nettle, knotweed, horsetail, Icelandic cetraria, pikulnik. Mix everything thoroughly and add 0.5 liters of water. Bring to a boil and keep for 15 minutes over very low heat. Strain and drink 100 g of decoction twice a day after meals.
• Take equal parts of the leaves of the following plants: lungwort, black currant, viburnum, string. Pour 0.5 liters of boiling water and leave for 1 hour. Drink 20 g of infusion 3 times a day. Since lungwort is one of the most effective medicinal plants for the treatment of Cushing's disease, you can prepare a decoction of this herb (30 g of dry raw material per 1 liter of water) and drink a glass of the decoction three times a day.
• Take equal parts of dried raw herbs: licorice and parsley root, juniper fruits, lovage and dandelion herbs. Pour 1 liter of boiling water over everything and leave for 12 hours. Drink 100 g of infusion 3 times a day.
• Take 50 g of mulberries, black and white, pour 0.5 liters of boiling water over them and keep for half an hour over very low heat. Drink this remedy instead of tea.
• Pour 20 g of dry calamus root into 300 ml of boiling water and keep on low heat for 10 minutes, without bringing to a boil. Drink 10 ml 3 times a day.
• Verbena officinalis herb (15 g) pour 200 ml of boiling water, wait half an hour. Drink half a glass 2 times a day.
• Take equal parts of motherwort, chamomile, mint, rosehip and skullcap, mix and measure 3 tbsp. l. raw materials. Pour 1 liter of water and leave for one hour. Drink half a glass 3 times a day.
• Take equal parts of hawthorn, fennel, chokeberry, valerian root, horsetail and cornflower. Grind everything and 3 tbsp. l. raw materials pour 0.5 liters of boiling water. After 30 min. strain and drink 70 g 4 times a day.

Consequences and complications

It is very important to start treatment for Cushing's syndrome promptly. If this is not done, the disease can lead to dangerous consequences. People with severe disease may develop the following complications:

• pyelonephritis;
• osteoporosis;
• stroke;
• sepsis;
• chronic renal failure
• urolithiasis disease;
• fungal and purulent skin lesions;
• threat of miscarriage;
• death.

List of sources

• Belchenko L.V. Clinical, biochemical and computed tomographic criteria for the diagnosis and treatment of Itsenko-Cushing’s disease. Author's abstract. dis. Ph.D. honey. Sci. Moscow 1991, 25 p.
• Clinical endocrinology. Guide / Ed. N. T. Starkova. — 3rd ed., revised. and additional - St. Petersburg: Peter, 2002. - pp. 62-81. — 576 p.
• Komissarenko I.V., Efimov A.S. Treatment of Itsenko-Cushing's disease. //Problem Endocrinology.// 1973, T.19, No. 1, P108-112
• Marova E.I. Algorithm for diagnosis and treatment of Itsenko-Cushing's disease // Probl. endocrinol. -1992. No. 1. - P. 39
• Tishenina R.S. Hormonal and metabolic aspects of Itsenko-Cushing's disease and various forms of obesity. Author's abstract. diss doc med. Sci. Moscow 1990, 49 p.

Forecast

In many ways, the prognosis will depend on how quickly therapy for the disease was started and whether it was carried out correctly. According to statistics, after transsphenoidal adenomectomy it is possible to quickly achieve stable remission in 84–95% of cases. Serious complications after surgery occur in 2–3% of cases.

Proton irradiation as an independent method is 96% effective, provided that it is carried out on young people in case of a mild form of the disease. When proton irradiation is used with adrenalectomy , the treatment is effective in 82% of cases. However, it is important that such patients are regularly monitored by an endocrinologist.

If treatment is completely ignored, then irreversible changes leading to death develop in 40-50% of cases.