Hypercortisolism syndrome (ICD code 10) is a complex of symptoms that manifest themselves under the influence of increased synthesis of the hormone of the adrenal cortex.

Pathology can manifest itself at any age in any gender.

The syndrome differs from the disease in that in the second case, hypercortisolism occurs secondary, and the pathology of the pituitary gland is primary.

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 hypercortisolism syndrome. Juvenile hypercortisolism is also identified as a separate type and is caused by age-related hormonal changes in the body of a teenager.

Exogenous

Under the influence of external causes, such as the use of drugs containing glucocorticoids for treatment, iatrogenic or exogenous hypercortisolism may develop.

Basically, it goes away after stopping the drug that provokes the pathology.

Endogenous

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

• (pituitary microadenoma);
• bronchial tumors;
• testicular tumors;
• ovarian tumors;
• tumor or .

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

Pseudo-Cushing syndrome

False hypercortisolism 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. In this case, any tumors are absent.

Risk factors

Symptomatically, the syndrome manifests itself with the following specific signs:

1. Obesity, with pronounced fat deposition on the face, neck, and abdomen. At the same time, the limbs become thinner. The syndrome is characterized by a moon-shaped face.
2. Unhealthy redness of the cheeks that does not go away.
3. Bluish stretch marks appear on the abdomen.
4. Acne may appear.
5. Osteoporosis occurs.
6. Disorders of the cardiovascular system, hypertension.

Disorders such as depression or prolonged migraines can be both the cause of hypercortisolism and its symptoms. In addition, appetite with such a disruption of the endocrine system often becomes exorbitant.

A patient suffering from Cushing's syndrome is characterized by the presence of pigmentation in places where the skin is often rubbed by clothing.

Youthful

Hypercorticism in children occurs due to hyperplasia of the adrenal cortex. Symptoms of this disease can appear as early as one year.

In the presence of characteristic symptoms similar to the signs of the syndrome in adults, the following manifestations occur in children:

• susceptibility to disease;
• poor development of mental abilities;
• poor physical development;
• heart defect.

If the disease manifests itself before adolescence, precocious puberty may begin. If the disease manifests itself during adolescence, then there will be a delay in sexual development.

If a newborn child shows all the signs of pathology, then it is quite possible that he has. In more than 80% of cases of Itsenko-Cushing syndrome under the age of one year, the cause is a benign tumor of the adrenal cortex.

In women

Women are 10 times more likely than men to develop hypercortisolism syndrome. The main age category of those affected is middle age.
In women it manifests itself with the following symptoms:

1. Increased hair growth on the lips, chest, arms and legs.
2. Amenorrhea and anovulation are observed.
3. Hypercortisolism in pregnant women provokes miscarriage or heart defects in the child.

Women are more likely to develop severe forms of osteoporosis than men. In fact, this manifestation of the disease can lead to serious forms of disability even before the onset of menopause.

Hypercortisolism syndrome leads to decreased libido in both women and men. In the latter, it also manifests itself as impotence.

Types of hypercortisolism

In the typology of Itsenko-Cushing syndrome, two types of pathology are distinguished: primary and secondary.

Primary hypercortisolism is detected when the adrenal glands themselves are disrupted, with the appearance of a functional tumor of the cortex. Such neoplasms can also occur in other organs, for example, the gonads.

Secondary hypercortisolism is associated with changes in the pituitary gland, when neoplasms in the hypothalamic-pituitary system provoke a hormonal surge.

How can the syndrome occur?

The pathology can be hidden, with a slight increase in hormone synthesis, or pronounced.
Doctors distinguish three forms of manifestation of the disease:

1. Subclinical hypercortisolism, occurs at an early stage or with small forms of tumors, manifested by increased blood pressure and dysfunction of the gonads.
2. Iatrogenic occurs due to exposure to a drug for the treatment of rheumatic diseases, blood. During organ transplantation it is detected in 75% of cases.
3. Functional or endogenous hypercortisolism is detected in cases of serious pathologies of the pituitary gland and diabetes mellitus. Patients with juvenile onset require special monitoring.

Up to 65% of cases are due to iatrogenic hypercortisolism.

Degrees

According to the severity of the disease, three degrees are distinguished:

1. Mild with slight obesity, normal state of the cardiovascular system.
2. Moderate with the development of problems with the endocrine glands, weight gain by more than 20% of your own body weight.
3. Severe with the development of severe complications and severe obesity.

Based on the speed of development of the disease and its complications, we can distinguish: a progressive form (the development period of the pathology is six months to a year) and a gradual form (from 1.5 years or more).

Diagnostics

To diagnose this disease, the following methods are used:

• blood test for corticosteroids;
• hormonal urine tests;
• X-ray of the head, skeletal bones;
• MRI or CT scan of the brain.

The diagnosis is made clearly if all studies are available. It should be differentiated from diabetes mellitus and obesity.

Treatment

Different forms of hypercortisolism require different therapy:

1. Iatrogenic hypercortisolism is treated with hormonal withdrawal
2. When adrenal hyperplasia occurs, steroid suppressive medications such as Ketoconazole or Mitotane are used.
3. When a tumor occurs, surgery and chemotherapy are used. In medicine, radiation therapy is used to treat glandular cancer.

Additionally used:

• diuretics;
• glucose-lowering;
• immunomodulators;
• sedatives;
• vitamins, calcium.

If a patient has had his adrenal glands removed, he will have to suffer for the rest of his life.

The modern method of laparoscopy is used in cases of adrenalectomy. It is safe for the patient and has a minimal rehabilitation period.

Complications

In the absence of treatment or the rapid progression of the disease, life-threatening complications may arise for the patient:

• disturbances in the functioning of the heart;
• cerebral hemorrhages;
• blood poisoning;
• severe forms of pyelonephritis with the need for hemodialysis;
• bone injuries, including a hip fracture or spinal fracture.

A condition requiring rapid assistance measures is considered. It leads to severe damage to body systems, as well as coma. In turn, an unconscious state can provoke death.

Treatment prognosis

Survival and recovery depend on.
Most often predicted:

1. The fatality rate will be up to half of all cases of diagnosed but untreated endogenous hypercortisolism.
2. When a malignant tumor is diagnosed, up to 1/4 of all patients who treat it survive. Otherwise, death occurs within a year.
3. With a benign tumor, the possibility of recovery reaches up to 3/4 of all patients.

Patients with positive dynamics of the disease should be monitored by a specialist throughout their lives. With dynamic monitoring and taking the necessary medications, such people lead a normal lifestyle without losing its quality.

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

Etiology and pathogenesis

Depending on the causes of the disease, there are:

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

Hypercortisolism can be caused by various reasons:

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

Regardless of the cause of hypercortisolism, this pathological condition is always caused by increased production of cortisol by the adrenal glands.

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

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

Separately, iatrogenic hypercortisolism is distinguished, caused by the use of glucocorticoids or corticotropic hormone preparations in the treatment of various, including non-endocrine, diseases.

Central hypercortisolism is caused by an increase in the production of corticoliberin and ACTH and a disruption of the hypothalamic response to the inhibitory effect of adrenal glucocorticoids and ACTH. The reasons for the development of central hypercortisolism have not been definitively identified, but it is customary to distinguish exogenous and endogenous factors that can initiate a pathological process in the hypothalamic-pituitary zone.

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

The listed pathological processes initiate disruptions in regulatory relationships in the hypothalamic-pituitary system and are realized by a decrease in dopaminergic and increased serotonergic influences of the hypothalamus, which is accompanied by an increase in stimulation of ACTH secretion by the pituitary gland and, accordingly, stimulation of the adrenal cortex with an increase in the production of glucocorticoids by cells of the zona fasciculata of the adrenal cortex. To a lesser extent, ACTH stimulates the zona glomerulosa of the adrenal cortex with the production of mineralocorticoids and the zona reticularis of the adrenal cortex with the production of sex steroids.

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

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

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

Hypercortisolism caused by adrenal masses most often results from the autonomous production of glucocorticosteroids (cortisol) by cells primarily in the zona fasciculata of the adrenal cortex (in approximately 20-25% of patients with hypercortisolism). These tumors usually develop on only one side, and about half of them are malignant.

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

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

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

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

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

Symptoms

Clinical manifestations of hypercortisolism are caused by excessive effects of glucocorticoids, mineralocorticoids and sex steroids. Central hypercortisolism is most common in clinical practice.

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

There is thinning of the skin and the appearance of stretch marks (stretch bands) of a purplish-cyanotic color on the chest, in the mammary glands, on the abdomen, in the shoulder area, and inner thighs due to disturbances in collagen metabolism and ruptures of its fibers, reaching a width of several centimeters. The patient's face takes on a moon-shaped shape and has a purplish-cyanotic color in the absence of excess red blood cells, and acne (blackheads) may appear.

Due to a violation of protein biosynthesis and the predominance of its catabolism, muscle wasting (atrophy) develops, which is manifested by sloping buttocks, muscle weakness, impaired motor activity, as well as the risk of hernias of various localizations. Poor wound healing is observed due to impaired protein metabolism.

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

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

Clinical signs of gastric or duodenal ulcers occur with the risk of gastric bleeding and/or ulcer perforation. Due to increased glyconeogenesis in the liver and insulin resistance, glucose tolerance is impaired and secondary (steroidal) develops.

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

Children are characterized by impaired (delayed) growth due to impaired collagen synthesis and the development of resistance to somatotropic hormone.

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

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

Symptoms caused by excess ACTH. Typically found in ACTH-ectopic syndrome and include hyperpigmentation of the skin and minimal development of obesity. In the presence of a pituitary macroadenoma, the appearance of “chiasmatic symptoms” is possible - impairment of visual fields and/or visual acuity, sense of smell and disturbances in liquor outflow with the development of persistent headaches, independent of blood pressure levels.

Diagnostics

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

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

At the stage of advanced clinical symptoms, diagnosing hypercortisolism syndrome is not difficult. Evidence of the diagnosis is provided by data from laboratory and instrumental research methods.

Laboratory indicators:

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

Indirect laboratory signs:

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

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

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

Visualization of the sella turcica and adrenal glands. After confirming the diagnosis of hypercortisolism, studies are conducted to clarify its cause. For this purpose, studies aimed at visualizing the sella turcica and adrenal glands are required:

• to assess the condition of the sella turcica, it is recommended to use MRI or CT, which makes it possible to identify or exclude the presence of a pituitary adenoma (a study with a contrast agent is considered optimal);
• To assess the size of the adrenal glands, CT or MRI, selective angiography, or adrenal scintigraphy with 19-[131 I]-iodocholesterol are recommended (ultrasonography does not reliably assess the size of the adrenal glands and is therefore not a recommended method for imaging the adrenal glands). The best radiological method for visualizing the adrenal glands is CT, which has replaced previously used invasive techniques (such as selective arteriography and adrenal venography), since with the help of CT scanning it is possible not only to determine the location of the adrenal tumor, but also to distinguish it from bilateral hyperplasia. The method of choice for imaging adrenal tumors is the use of positron emission tomography (PET-scan) with the glucose analogue 18-fluoro-deoxy-D-glucose (18 FDG), which selectively accumulates in tumor tissue, or an inhibitor of the key enzyme in cortisol synthesis, 11-β-hydroxylase 11C. -metomidate;
• It is possible to perform a biopsy of the adrenal gland, however, despite the low risk of complications and fairly high accuracy, the study is performed no less frequently, due to modern methods of imaging the adrenal glands.

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

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

Additional diagnostic criteria:

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

Identification of the true focus of ACTH production. If iatrogenic hypercortisolism, central ACTH-dependent hypercortisolism, and hypercortisolism caused by a tumor or isolated adrenal hyperplasia are excluded, the cause of hypercortisolism is most likely ACTH-ectopic syndrome. To identify the true focus of ACTH or corticoliberin production, an examination aimed at searching for a tumor and including imaging of the lungs, thyroid gland, pancreas, thymus, and gastrointestinal tract is recommended. If it is necessary to identify an ACTH-ectopic tumor, scintigraphy with octreotide labeled with radioactive indium (Octreoscan) can be used; determination of the level of ACTH in venous blood taken at various levels of the venous system.

Differential diagnosis carried out in 2 stages.

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

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

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

Treatment

Treatment tactics are determined by the form of hypercortisolism.

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

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

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

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

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

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

In case of iatrogenic hypercortisolism, it is necessary to minimize the dose of glucocorticoids or completely discontinue them. The severity of somatic pathology treated with glucocorticoids is of fundamental importance. In parallel, symptomatic therapy can be prescribed aimed at eliminating the identified disorders.

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

Forecast

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

The main risks of a negative forecast:

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

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

What is Cushing's syndrome

Cushing's syndrome is increased production of cortisol by the adrenal glands. The concentration of cortisol is increased in daily urine and saliva, with a more detailed study there is no normal daily cycle.

Causes of Cushing's syndrome in children

• adrenal hypoplasia or tumors (adenomas, carcinomas);
• high doses of steroid hormones of the adrenal cortex (cortisone) in the treatment of severe underlying diseases, for example, rheumatic diseases, malignant diseases, chronic inflammatory diseases of the digestive tract, for example, Crohn's disease, ulcerative colitis.

Symptoms and signs of Cushing's syndrome in children

• abdominal obesity, moon face, bull neck symptom;
• short stature, stunted growth;
• red stripes on the skin (striae), increased hair growth;
• high blood pressure, decreased glucose tolerance;
• pain in the back and limbs;
• depressive disorder.

Unlike Cushing's syndrome, with primary obesity, the child's growth is not impaired or even accelerated due to the absorption of large amounts of nutrients.

Diagnosis of Cushing's syndrome in children

Body length, body weight, physical development curves (percentile tables), blood pressure.

Laboratory diagnostics: determination of cortisol concentration in urine and/or saliva.

Radiation research methods: determination of bone age, ultrasound examination of the abdominal organs, MRI of the skull.

Treatment of Cushing's syndrome in children

Treatment for Cushing's syndrome depends on its cause. Surgeries and radiation, for example, for tumors of the pituitary gland or adrenal cortex.

Medicines (for example, ketoconazole) that block the synthesis of steroids.

Care

Increased skin vulnerability requires careful care. Repeated daily blood pressure measurements. Timely initiation of bedsore prevention. Balanced nutrition (if necessary, a fasting diet) in obese children.

Mental support for children.

When treated with glucocorticoids, the severity of the manifestations of Cushing's syndrome can be reduced:

• the shortest course of treatment;
• taking medications that imitate the normal daily rhythm of hormone release;
• alternation, for example, taking medications every 2nd day.

Hypercortisolism, or Itsenko-Cushing syndrome, is an endocrine pathology associated with prolonged and chronic exposure to excess amounts of cortisol on the body.

Such effects may occur due to existing illnesses or while taking certain medications.

Moreover, women (especially aged 25-40 years) suffer from the syndrome more often than representatives of the stronger sex. To understand how to treat a disease, you need to understand the symptoms of this pathology and the causes of its occurrence.

There are two main forms of hypercortisolism: exogenous and endogenous.

The first appears with long-term use of steroids (glucocorticoids) or an overdose of these drugs. Indications for the use of these medications include diseases such as asthma, rheumatoid arthritis, and organ transplantation.

Another cause of exogenous hypercortisolism is secondary osteoporosis, which occurs with a sedentary lifestyle.

As for endogenous hypercortisolism, the reasons for its development lie, as they say, inside the body. Most often, the syndrome develops against the background of Itsenko-Cushing disease, accompanied by excessive secretion of adrenocorticotropic hormone from the pituitary gland (hereinafter referred to as ACTH). Hyperproduction of this hormone contributes to the release of cortisol and the appearance of hypercortisolism.

Excessive cortisol production can also be caused by:

• pituitary microadenoma;
• the presence of ectopic malignant corticotropinoma in the ovaries, bronchi and other organs;
• primary damage to the adrenal cortex due to hyperplasia, benign or malignant neoplasm.

It is also customary to distinguish a pseudo-form of hypercortisolism, which is characterized by the appearance of symptoms similar to the signs of Itsenko-Cushing syndrome.

Such symptoms can occur due to obesity, stress, pregnancy, use of oral contraceptives, alcohol abuse, etc.

Causes

Cortisol is a hormone that is produced in the adrenal glands and affects the functioning of various body systems.

In particular, cortisol is involved in the regulation of blood pressure and metabolism, ensures normal functioning of the cardiovascular system, and helps cope with stress.

However, an excess of the hormone is just as dangerous as its deficiency: increased production of cortisol is fraught with the development of Itsenko-Cushing syndrome.

Often the syndrome develops due to the fault of hormones that enter the body from the outside. Particularly dangerous in this regard are corticosteroids for oral and injection use (for example, prednisolone, which has an effect similar to cortisol).

The former help avoid organ rejection during transplantation, and can also be recommended for the treatment of asthma, SLE, rheumatoid arthritis and other inflammatory diseases.

The latter are prescribed for back and joint pain, bursitis and other pathologies of the musculoskeletal system.

As for topical creams and inhalers, they are safer than the above drugs (except in cases requiring the use of high dosages).

To prevent the development of hypercortisolism during treatment with corticosteroids, you should avoid prolonged use of these drugs and follow the dosages recommended by your doctor.

In addition to taking medications, the causes of hypercortisolism may lie in the body itself. For example, increased cortisol production may be associated with improper functioning of one or both adrenal glands.

Sometimes the problem is excessive production of ACTH, a hormone that regulates the secretion of cortisol. Such disorders occur against the background of pituitary tumors, primary lesions of the adrenal glands, and ectopic ACTH-secreting neoplasms. In some cases, familial Itsenko-Cushing syndrome occurs.

Insufficiency of hormone production of the anterior pituitary gland is corrected by hormonal therapy.

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Symptoms of hypercortisolism

An important place in the diagnosis of pathology is occupied by information obtained as a result of a medical examination.

In particular, a characteristic symptom of hypercortisolism is excess body weight.

Fat deposits in Itsenko-Cushing syndrome are concentrated in the face, neck, chest and waist, while the limbs remain thin. With hypercortisolism, the face becomes rounded, and a characteristic blush also appears on it.

While the percentage of body fat increases, muscle mass, on the contrary, decreases. The muscles atrophy especially strongly in the lower extremities and shoulder girdle. There are complaints of weakness, fatigue, pain during lifting and squats. Working out and other types of physical activity are difficult.

Affects hypercortisolism and the reproductive system. Representatives of the stronger sex are characterized by a decrease in libido and the development of erectile dysfunction (impotence), and for women - menstrual irregularities and hirsutism. The latter manifests itself in excess male-pattern hair growth. Hirsutism occurs due to hyperproduction of androgens (male hormones) and is characterized by the appearance of hair in the area of ​​the chest, chin, and upper lip.

The most “popular” manifestation of hypercortisolism from the musculoskeletal system is osteoporosis (it is found in 90% of people suffering from Itsenko-Cushing syndrome). This pathology tends to progress: first it makes itself felt by pain in the joints and bones, and then by fractures of the arms, legs and ribs. If a child suffers from osteoporosis, he or she will be behind in growth compared to his peers.

Hypercortisolism can also be detected by examining the condition of the skin.

With excess cortisol production, the skin becomes dry, thinner, and acquires a marbled tint.

Often there are stretch marks (so-called stretch marks) and areas of local sweating. Healing of abrasions and wounds occurs very slowly.

Hypersecretion of cortisol changes the functioning of blood vessels, the heart and the nervous system. The patient complains of depression, sleep problems, lethargy, inexplicable euphoria, and in some cases steroid psychosis is diagnosed. As for the cardiovascular system, a frequent concomitant of hypercortisolism is cardiomyopathy with a mixed course. This pathology can be caused by a persistent increase in blood pressure, the catabolic effects of steroids on the myocardium, as well as electrolyte shifts.

Typical signs of these disorders are: changes in heart rate, increased blood pressure, as well as heart failure, which can lead to death.

Sometimes, against the background of hypercortisolism, steroid diabetes mellitus develops. It is possible to keep this disease under control with the help of drug therapy using glucose-lowering drugs.

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Excess weight is Itsenko Cushing's symptom

Symptoms of Itsenko-Cushing syndrome

Diagnostics

The first thing that is done when hypercortisolism is suspected is screening tests to determine the daily level of cortisol in the urine. The presence of hypercortisolism or Itsenko-Cushing's disease is indicated by three or four times the excess of cortisol.

Next, a small dexamethasone test is carried out, the essence of which is as follows: if, when using dexamethasone, the hormone level decreases by more than two times, there is no need to talk about any deviations; but if there is no decrease in cortisol levels, a diagnosis of hypercortisolism is made.

A large dexamethasone test, which is carried out in a similar way to a small one, allows you to distinguish hypercortisolism from Itsenko-Cushing's disease. With hypercortisolism, the level of cortisol does not decrease, but with illness it decreases by more than half.

After the above measures, it remains to establish the cause of the pathology. Instrumental diagnostics help doctors with this, in particular computer and magnetic resonance imaging of the adrenal glands and pituitary gland.

As for the complications of excess cortisol production, they can be identified using a biochemical blood test and radiography.

Treatment

To get rid of Itsenko-Cushing syndrome, you need to identify the cause of the elevated cortisol level and eliminate it, as well as balance the hormonal levels.

When the first symptoms of the disease appear, you should visit a doctor as soon as possible: it has been established that the lack of therapy in the first five years from the onset of the pathology can cause death.

Based on the data obtained during the diagnosis, the doctor can offer one of three treatment methods:

• Medication. Drugs can be prescribed either independently or as part of complex therapy. The basis of drug treatment for hypercortisolism is drugs whose action is aimed at reducing the production of hormones in the adrenal glands. Such medications include drugs such as Metyrapone, Aminoglutethimide, Mitotane or Trilostane. They are usually prescribed if there are contraindications to other treatment methods and in cases where these methods (for example, surgery) have proven ineffective
• Operational. It involves transsphenoidal revision of the pituitary gland and excision of the adenoma using microsurgical techniques. This technique is highly effective and results in rapid improvements. If there is a neoplasm of the adrenal cortex, the tumor is removed. The least commonly performed intervention is resection of two adrenal glands, which requires lifelong use of glucocorticoids.
• Ray. As a rule, radiation therapy is recommended in the presence of a pituitary adenoma. This method acts directly on the pituitary gland, forcing it to reduce the production of ACTH. It is recommended to carry out radiation therapy in parallel with other methods of treatment: surgical or medicinal. The most effective combination of radiation exposure and the use of medications aimed at reducing hormone production.

Severe neuroendocrine pathology, in which the hypothalamic-pituitary-adrenal system is disrupted, is a disease that cannot be completely cured, but a person’s condition can be stabilized.

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Thus, the prognosis for treating hypercortisolism with timely consultation with a doctor is favorable. In most cases, it is possible to defeat the pathology without resorting to surgical treatment methods, and recovery occurs quite quickly.

Video on the topic

The cause of Cushing's syndrome in children is high levels of cortisol and other glucocorticoids in the blood.

Cushing's syndrome in children can be either iatrogenic or due to increased secretion of endogenous cortisol, whether as a result of tumors of the adrenal glands or other tissues or hypersecretion of ACTH by the pituitary gland.

Etiology

Cushing's syndrome in children in the overwhelming majority of cases develops as a result of long-term administration of exogenous glucocorticoids, especially in large doses used in the treatment of lymphoproliferative diseases. The diagnosis is usually straightforward, but the complications of such treatment—hyperglycemia, hypertension, weight gain, growth retardation, and osteoporosis—are not easy to manage.

Endogenous Cushing's syndrome in children is often caused by a functioning tumor of the adrenal cortex. Such tumors are usually malignant, although benign adenomas also occur. Signs of excessive secretion of cortisol are often accompanied by signs of hypersecretion of other hormones - androgens, estrogens and aldosterone.

Clinical manifestations

Signs of the disease are clearly visible even in infants. At this age, the disease is usually much more severe than in cases where its first symptoms appear later. Noteworthy is the round face with thick and red cheeks (moon face) and general obesity. With a tumor of the adrenal glands, signs of masculinization are often observed: hypertrichosis of the face and trunk, pubic hair growth, acne, decreased timbre of the voice; in girls - enlargement of the clitoris. Increased virilization may be accompanied by accelerated growth, but it is usually slow and does not reach the 3rd percentile for a given age. Arterial hypertension often develops, sometimes leading to heart failure. Patients are predisposed to infections, which can result in fatal sepsis.

At a later age, the first manifestations of the disease are slowly developing obesity and stunting. Fat deposits are especially noticeable on the face, torso, and the limbs remain thin. Purple stretch marks are often visible on the thighs and abdomen. Sexual development begins later than usual; in other cases, girls develop amenorrhea after menarche. Complaints include severe general weakness, strength and emotional instability. As a rule, osteoporosis is observed, which can lead to pathological fractures.

Laboratory research

Normally, cortisol in the blood is maximum at 8 am, and by midnight it decreases by more than 2 times. The circadian rhythm of cortisol is absent only in early childhood. With Cushing's syndrome in children, this rhythm disappears, the level of the hormone at night and in the morning is almost the same. In an outpatient setting, it is difficult to obtain blood samples at different times of the day, but cortisol can be determined in saliva samples that are easily collected at home at the appropriate time. High levels of the hormone in nighttime saliva in obese children indicate the need for further examination.

Urinary cortisol excretion is increased. Determinations are best carried out in 24-hour urine samples, and the results are expressed as the amount of cortisol (in mcg) per 1 g of creatinine. This ratio does not depend on body size and completeness of urine collection.

A short test is carried out with dexamethasone, prescribing 25-30 mcg (maximum 2 g) of this drug at 11 pm. Normally, but not with Cushing's syndrome, plasma cortisol at 8 a.m. the next morning is below 5 mcg%.

Once the diagnosis of Cushing's syndrome in children is made, it is necessary to determine whether it is caused by a pituitary adenoma, ectopic tumor secretion of ACTH, or tumor secretion of cortisol. The concentration of ACTH in the latter case is sharply reduced, with ectopic secretion of ACTH it is very high, and in children with ACTH-secreting pituitary adenoma it is normal. In ACTH-dependent Cushing's syndrome, the response of ACTH and cortisol to immediate intravenous administration of CRH is enhanced, but in adrenal tumors it is absent. A two-stage test is carried out with dexamethasone, prescribing it at a dose of 120 mcg/kg/day (4 doses) for several days. In children with pituitary disease, high (but not low) doses of dexamethasone reduce blood cortisol, and in ACTH-independent forms of the disease, dexamethasone, as a rule, does not suppress the secretion of cortisol by the adrenal glands.

With the help of CT, it is possible to detect almost any tumor of the adrenal gland with a diameter of more than 1.5 cm. Pituitary adenomas are detected using MRI, but often they are too small and are not detected in this way. The use of gadolinium contrast increases the sensitivity of MRI.

Differential diagnosis

Cushing's syndrome should be suspected in obese children, especially if they have stretch marks or arterial hypertension. With simple obesity, children are usually tall, while Cushing's syndrome in children is characterized by either short stature or slow growth rate. Cortisol excretion often increases in simple obesity, but in these cases the level of cortisol in the night portion of saliva is normal, and taking even low doses of dexamethasone reduces the secretion of the hormone.

Elevated levels of cortisol and ACTH in the absence of manifestations of Cushing's syndrome are observed with generalized resistance to glucocorticoids. In such patients, symptoms may be completely absent, but sometimes arterial hypertension, hypokalemia, and premature false puberty are observed. These manifestations are due to increased secretion of mineralocorticoids and adrenal androgens due to increased ACTH levels. Glucocorticoid resistance involves mutations in the gene encoding the glucocorticoid receptor. A case of pituitary adenoma with biochemical signs of Cushing's disease, but without its clinical manifestations, is described. In this patient, the conversion of cortisone to cortisol was impaired; as a result, cortisol disappeared from the blood faster, protecting the patient from excess hormone.

Treatment of Cushing's syndrome in children

For Cushing's disease in children, the method of choice is transsphenoidal microsurgery on the pituitary gland. The effectiveness of such treatment (with a follow-up period of less than 10 years) is 60-80%. In most cases, a decrease in the concentration of cortisol in the blood and urine in the immediate postoperative period allows one to count on long-term remission. In case of relapses, repeated surgery or irradiation of the pituitary gland is performed.

To treat Cushing's disease in adulthood, cyproheptadine is used, a central serotonin antagonist that blocks ACTH secretion; discontinuation of the drug usually leads to relapse of the disease. Cyproheptadine is rarely used in children. Before surgery, steroidogenesis inhibitors (metyrapone, ketoconazole, aminoglutethimide) are administered to normalize cortisol levels in the blood and reduce complications and mortality in the perioperative period.

If treatment fails or ectopic ACTH secretion from tumor metastases may require removal of the adrenal glands, for which a laparoscopic approach is often used. Adrenalectomy can lead to increased secretion of ACTH by the pituitary adenoma, which is manifested by severe hyperpigmentation of the body. This is called Nelson's syndrome.

For benign adenoma of the adrenal cortex, unilateral adrenalectomy is indicated. Bilateral adenomas also occur; in these cases, the method of choice is subtotal adrenalectomy. Patients undergoing adrenalectomy require corticosteroid replacement therapy before and after surgery.

The article was prepared and edited by: surgeon