Cushing syndrome is a pathological symptom complex that occurs due to hypercorticism, i.e. increased secretion of the hormone cortisol by the adrenal cortex or prolonged treatment with glucocorticoids. It is necessary to distinguish Cushing syndrome from Cushing disease, which is understood as secondary hypercorticism that develops with pathology of the hypothalamic-pituitary system. Diagnosis includes examination of cortisol and pituitary hormones, dexamethasone test, MRI, CT and adrenal scintigraphy. Treatment depends on its cause and may consist in the cancellation of glucocorticoid therapy, the appointment of steroidogenesis inhibitors, surgical removal of an adrenal tumor.
Meaning
Glucocorticoid hormones are involved in the regulation of all types of metabolism and many physiological functions. The work of the adrenal glands is regulated by the pituitary gland by secretion of ACTH, an adrenocorticotropic hormone that activates the synthesis of cortisol and corticosterone. The activity of the pituitary gland is controlled by hypothalamic hormones – statins and liberins.
Such multi-stage regulation is necessary to ensure the coherence of the body’s functions and metabolic processes. Violation of one of the links in this chain can cause hypersecretion of glucocorticoid hormones by the adrenal cortex and lead to the development of the disease. In women, Cushing syndrome occurs 10 times more often than in men, developing mainly at the age of 25-40 years.
There is a distinction between Cushing syndrome and Cushing disease: the latter is clinically manifested by the same symptoms, but it is based on a primary lesion of the hypothalamic-pituitary system, and hyperfunction of the adrenal cortex develops a second time. Patients suffering from alcoholism or severe depressive disorders sometimes develop pseudo-Cushing syndrome.
Causes
Cushing syndrome is a broad concept that includes a complex of various conditions characterized by hypercorticism. According to modern research in the field of endocrinology, more than 80% of cases of Cushing syndrome are associated with increased secretion of ACTH by pituitary microadenoma (Cushing disease). Pituitary microadenoma is a small (no more than 2 cm), more often benign, glandular tumor producing adrenocorticotropic hormone.
In 14-18% of patients, the cause of ushing syndrome is primary damage to the adrenal cortex as a result of hyperplastic tumor formations of the adrenal cortex – adenoma, adenomatosis, adenocarcinoma.
1-2% of the disease is caused by ACTH-ectopic or corticoliberin-ectopic syndrome – a tumor secreting corticotropic hormone (corticotropinoma). ACTH-ectopic syndrome can be caused by tumors of various organs: lungs, testicles, ovaries, thymus, parathyroid, thyroid, pancreas, prostate. The frequency of the development of drug Cushing syndrome depends on the correctness of the use of glucocorticoids in the treatment of patients with systemic diseases.
Hypersecretion of cortisol in Cushing syndrome causes a catabolic effect – the breakdown of protein structures of bones, muscles (including the heart), skin, internal organs, etc., eventually leading to dystrophy and tissue atrophy. Increased glucogenesis and absorption of glucose in the intestine causes the development of a steroid form of diabetes. Disorders of fat metabolism in Cushing syndrome are characterized by excessive fat deposition in some areas of the body and atrophy in others due to their different sensitivity to glucocorticoids. The effect of excessive cortisol levels on the kidneys is manifested by electrolyte disorders – hypokalemia and hypernatremia and, as a consequence, increased blood pressure and aggravation of dystrophic processes in muscle tissue.
The heart muscle suffers the most from hypercorticism, which manifests itself in the development of cardiomyopathy, heart failure and arrhythmias. Cortisol has a depressing effect on the immune system, causing patients with Cushing syndrome to be prone to infections. The course of the disease can be mild, moderate and severe; progressive (with the development of the entire symptom complex in 6-12 months) or gradual (with an increase over 2-10 years).
Cushing syndrome symptoms
The most characteristic feature of Cushing syndrome is obesity, detected in patients in more than 90% of cases. The redistribution of fat is uneven, according to the kushingoid type. Fat deposits are observed on the face, neck, chest, abdomen, back with relatively thin limbs (“colossus on clay feet”). The face becomes moon-shaped, red-purple in color with a cyanotic tinge (“matronism”). The deposition of fat in the area of the VII cervical vertebra creates a so-called “climacteric” or “bison” hump. In this pathology, obesity is distinguished by thinned, almost transparent skin on the backs of the palms.
On the part of the muscular system, there is muscle atrophy, a decrease in muscle tone and strength, which is manifested by muscle weakness (myopathy). Typical signs accompanying Cushing syndrome are “sloping buttocks” (a decrease in the volume of the femoral and gluteal muscles), “frog belly” (hypotrophy of the abdominal muscles), hernias of the white line of the abdomen.
The skin of patients with Cushing syndrome has a characteristic “marble” shade with a well-marked vascular pattern, is prone to peeling, dryness, interspersed with areas of sweating. On the skin of the shoulder girdle, mammary glands, abdomen, buttocks and thighs, bands of stretching of the skin are formed – striae of purple or cyanotic color, from a few millimeters to 8 cm long and up to 2 cm wide. There are skin rashes (acne), subcutaneous hemorrhages, vascular asterisks, hyperpigmentation of individual skin areas.
With hypercorticism, thinning and damage to bone tissue often develops – osteoporosis, leading to severe painful sensations, deformities and fractures of bones, kyphoscoliosis and scoliosis, more pronounced in the lumbar and thoracic spine. Due to compression of the vertebrae, patients become stooped and smaller in stature. In children with Cushing syndrome, there is a lag in growth caused by a slowdown in the development of epiphyseal cartilage.
Cardiac muscle disorders are manifested in the development of cardiomyopathy, accompanied by arrhythmias (atrial fibrillation, extrasystole), arterial hypertension and symptoms of heart failure. These formidable complications can lead to the death of patients. With Cushing syndrome, the nervous system suffers, which is expressed in its unstable work: inhibition, depression, euphoria, steroid psychoses, suicidal attempts.
In 10-20% of cases, steroid diabetes mellitus develops during the course of the disease, which is not associated with pancreatic lesions. Such diabetes occurs quite easily, with a long-term normal level of insulin in the blood, quickly compensated by an individual diet and hypoglycemic drugs. Sometimes poly- and nocturia, peripheral edema develop.
Hyperandrogenism in women accompanying Cushing syndrome causes the development of virilization, hirsutism, hypertrichosis, menstrual cycle disorders, amenorrhea, infertility. Male patients show signs of feminization, testicular atrophy, decreased potency and libido, gynecomastia.
Complications
The chronic, progressive course of Cushing syndrome with increasing symptoms can lead to the death of patients as a result of complications incompatible with life: decompensation of cardiac activity, stroke, sepsis, severe pyelonephritis, chronic renal failure, osteoporosis with multiple fractures of the spine and ribs.
An urgent condition in Cushing syndrome is an adrenal (adrenal) crisis, manifested by impaired consciousness, arterial hypotension, vomiting, abdominal pain, hypoglycemia, hyponatremia, hyperkalemia and metabolic acidosis.
As a result of reduced resistance to infections, patients with Cushing syndrome often develop furunculosis, phlegmon, suppurative and fungal skin diseases. The development of urolithiasis is associated with osteoporosis of bones and the excretion of excess calcium and phosphates in the urine, leading to the formation of oxalate and phosphate stones in the kidneys. Pregnancy in women with hypercorticism often ends in miscarriage or complicated childbirth.
Diagnostics
If a patient is suspected of having Cushing syndrome on the basis of amnesic and physical data and the exclusion of an exogenous source of glucocorticoid intake (including inhalation and intra-articular), the cause of hypercorticism is first found out. Screening tests are used for this:
- determination of cortisol excretion in daily urine: an increase in cortisol by 3-4 times or more indicates the reliability of the diagnosis of Cushing syndrome or disease.
- a small dexamethasone test: normally, taking dexamethasone reduces cortisol levels by more than half, and there is no decrease in Cushing syndrome.
A large dexamethasone test allows differential diagnosis between the disease and Cushing syndrome. Taking dexamethasone leads to a decrease in cortisol concentration by more than 2 times from the initial one; there is no decrease in cortisol in the syndrome.
In the urine, the content of 11-OXY (11-oxy-ketosteroids) is increased and 17-CS is reduced. There is hypokalemia in the blood, an increase in the amount of hemoglobin, red blood cells and cholesterol. To determine the source of hypercorticism (bilateral adrenal hyperplasia, pituitary adenoma, corticosteroma), MRI or CT of the adrenal glands and pituitary gland, adrenal scintigraphy is performed. In order to diagnose complications of Cushing syndrome (osteoporosis, compression fractures of the vertebrae, rib fractures, etc.), radiography and CT of the spine, chest are performed. Biochemical examination of blood parameters diagnoses electrolyte disorders, steroid diabetes mellitus, etc.
Cushing syndrome treatment
With the iatrogenic (medicinal) nature of Cushing syndrome, it is necessary to gradually cancel glucocorticoids and replace them with other immunosuppressants. With the endogenous nature of hypercorticism, drugs that suppress steroidogenesis (aminoglutetimide, mitotan) are prescribed.
In the presence of a tumor lesion of the adrenal glands, pituitary gland, lungs, surgical removal of neoplasms is performed, and if it is impossible, one– or bilateral adrenalectomy (removal of the adrenal gland) or radiation therapy of the hypothalamic-pituitary region. Radiation therapy is often performed in combination with surgical or medical treatment to enhance and consolidate the effect.
Symptomatic treatment includes the use of hypotensive, diuretic, hypoglycemic drugs, cardiac glycosides, biostimulants and immunomodulators, antidepressants or sedatives, vitamin therapy, drug therapy of osteoporosis. Compensation of protein, mineral and carbohydrate metabolism is carried out. Postoperative treatment of patients with chronic adrenal insufficiency who have undergone adrenalectomy consists of constant hormone replacement therapy.
Forecast
If treatment is ignored, irreversible changes develop, leading to death in 40-50% of patients. If the cause of the syndrome was a benign corticosteroma, the prognosis is satisfactory, although the functions of a healthy adrenal gland are restored only in 80% of patients. In the diagnosis of malignant corticosteroids, the prognosis of five–year survival is 20-25% (on average 14 months). In chronic adrenal insufficiency, lifelong replacement therapy with mineral and glucocorticoids is indicated.
In general, the prognosis of Cushing syndrome is determined by the timeliness of diagnosis and treatment, the causes, the presence and severity of complications, the possibility and effectiveness of surgical intervention. Patients are under dynamic observation by an endocrinologist, heavy physical exertion, night shifts at work are not recommended for them.