Cortisol belongs to the group of glucocorticoids and is one of the major hormones, through which the body regulates the adaptation mechanisms. He takes part in the metabolism of proteins, fats, carbohydrates, amino acids, sodium and calcium (in part), in inflammatory and immune reactions, indirectly affects the reproductive function of men.
Materials for analysis can be blood, saliva, in which total cortisol is determined, or urine - free cortisol. Given the daily rhythm of secretion of the hormone, its content is controlled 2 times a day.
Table 1 - Normal Cortisol Content.
|The time of the material intake (hours)||Contents (nmol / l)|
|In the morning (7 - 9)||171 - 536||7 - 26||60 - 413 (free cortisol)|
|In the evening (18 - 22)||64 - 327||0.6 - 3.3|
Data from different laboratories may differ slightly, which is not significant.
The concentration of free cortisol in daily urine is less reliable. But this analysis is used:
- simultaneously with a blood test for suspected pathology of the pituitary or hypothalamic region;
- for certain difficulties in blood or saliva.
Research results are influenced by stress, hormonal, sedative, hypnotic (phenobarbital) and anticonvulsant (phenytoin) drugs, magnesium sulfate, caffeine and lithium drugs, nicotine and alcohol, rifampicin, licorice and licorice drugs, etc.
Preparation of the patient for the material intake consists in:
- eating food with a normal daily salt content (not more than 3 g) for 3 days;
- rejection of food in 10-12 hours;
- limiting physical activity, psychological stress, drinking strong tea or coffee;
- discontinuation of taking the above medications (if this is not possible, the laboratory technician and endocrinologist should be warned);
- excluding smoking and drinking alcohol;
- state of rest for half an hour before taking the material.
In order to obtain the maximum possible reliability of the research results, analyzes are sometimes repeated several times with an interval of 2 days, and when interpreting them, they take into account the presence of concomitant diseases.
Inaccurate test results can be with overweight, acute infectious and autoimmune diseases, thyroid pathology , liver and diabetes mellitus, which is explained by the mechanisms for regulating the synthesis and metabolism of the hormone briefly described below.
Brief mechanisms of formation and function of the hormone
Being the main glucocorticosteroid of the puchkovy zone of the adrenal cortex, cortisol is synthesized through a series of intermediate transformations from cholesterol that comes with food. Its production and secretion into the blood by the adrenal glands depend on daylight, the rhythm of nutrition, physical or psychological stress, pain, fear, anxiety, and many other factors.
Regulation of cortisol in the blood schematically:
| stress, circadian rhythm → hypothalamus (CRG) → pituitary (ACTH)
↑ ↓ ↑ (feedback negative)
adrenal cortex (cortisol) → target tissue receptors
Regulation is carried out by the adrenocorticotropic hormone of the pituitary (ACTH). ACTH secretion occurs (mainly) under the influence of:
- Corticotropin-releasing hormone (CG), or corticoliberin. It is secreted into the bloodstream of the vascular portal system, which connects the hypothalamus with the pituitary gland, in accordance with the circadian (biorhythm) biorhythm. This provides the beginning of an increase in cortisol levels after a person goes to sleep. It reaches its maximum concentration by 7-9 hours, the minimum - by 22 hours, after which it begins to increase again. Such a biorhythm depends on the duration of daylight and the cyclical feeding.
- Cortisol itself on the principle of "negative feedback" with the hypothalamus (long chain) and the pituitary gland (short chain). A decrease in the hormone in the blood or an increase in the body’s need for it leads to the stimulation of these endocrine glands, and vice versa.
Figure 1 - Regulation of the synthesis of cortisol in the blood
About 8% of total cortisol secreted by the adrenal glands are in the free state of plasma and are an active form that has an effect on the intracellular receptors of target cells or tissues. The rest of it (about 80%) is associated with the transport protein transcortin, produced in the liver, and partially with plasma albumin. It is an inactive (deposited) form, which is the stronger, the more it is affected by estrogens. With increasing needs of the body, the hormone transforms into a free form.
In the process of metabolism, a small part of cortisol is transformed into ketosteroids and replenishes in the body of men those derived from androgens. The main part of the hormone is inactivated in the liver by enzymes and, forming a water-soluble compound with glucuronic acid (about 90%) and sulphates (about 10%), is excreted in the urine. Its free form in the urine is only 1-5%.
The functioning of the hepatic enzyme system of hormone inactivation is predetermined genetically and largely depends on both endogenous (dysfunction of the liver, thyroid gland, etc.) and exogenous factors (food composition and diet, nicotine, alcohol, etc.).
The main role of glucocorticoid hormones, in particular cortisol, is to implement the adaptive mechanisms of the body through the connection of the central nervous system with other systems, organs, tissues and cells.
Under the influence of stress factors (hunger, mental, physical and psycho-emotional stress, diseases, etc.), the level of energy consumption changes, and hence the level of metabolism, which is realized by the influence of cortisol on catabolic (decomposition) and anabolic (update) processes resulting in what happens:
- Increased glucose uptake in the blood by releasing it from the muscle tissue and reducing the consumption by the cells of all tissues except the liver. This is due to increased insulin secretion under stress, which in the absence of glucose leads to severe disturbances and even death.
- Increased glycogen stores in the liver.
- “Allowing” other hormones (a permissive effect) to stimulate the main metabolic processes.
- Activation and induction of glucagon and the main enzymes of gluconeogenesis (the formation of glucose from lactic acid, amino acids and glycerol in the liver and the cortical layer of the kidneys).
- Activation of synthesis, especially in the liver, and the decomposition of proteins, especially in the lymphoid and muscle tissues, into amino acids, which are one of the main components of gluconeogenesis.
- An increase in the rate of decomposition of amino acids due to the activation of aminotransferases (enzymes).
- Stimulation of splitting the subcutaneous tissue of the limbs and the formation of fats from carbohydrates and proteins on the face and other parts of the body.
In addition, the effect of cortisol in the body is manifested in:
- suppression of immune response and inflammatory reactions, which is used in the treatment of immune and allergic diseases, articular inflammatory processes; however, it impairs wound healing and increases sensitivity to infectious pathogens, especially staphylococcal infections;
- mediated (via catecholamines) increase in blood pressure and enhance myocardial function, as well as in reducing the permeability of the capillary wall;
- inhibition of division and growth of fibroblasts;
- enhancing the excretion of potassium from the body and suppressing the effect of antidiuretic hormone; therefore, with a lack of cortisol, sodium and water are retained in the tissues;
- indirectly changing the secretion of male sex hormones: an excess of cortisol causes the same pituitary reaction, leading to a decrease in the secretion of this hormone, and androgens and vice versa.
This multi-causative syndrome develops as a result of exposure to cortisol with prolonged excess of its products in the body (endogenous) or introduction from the outside (exogenous) in order to treat diseases, mainly of an immune nature.
|ACTH-dependent (80 - 85%) - associated with excessive secretion of ACTH||central|
|ectopic||tumors located outside the brain and autonomously producing proteins identical to ACTH (12%) or CRH (less than 1%) - tumors of the lungs or bronchi, gastrointestinal tract or pancreas, thyroid or thymus gland and others|
|ACTH-independent, or Itsenko-Cushing syndrome (15–20%)||peripheral|
|iatrogenic||long-term use of glucocorticosteroid hormones|
|Functional (pseudocouching syndrome)|
Principles of treatment
In the presence of hormone-producing tumors, they are surgically removed (pituitary adenoma, adrenal gland tumor). When it is impossible to use it or the patient refuses, various types of radiation therapy are used. As a preparation for these methods and to alleviate the condition in the postoperative period, steroid synthesis blockers are used - orimeten, maomomit, mitotan, nizoral, hypotensive and antidiabetic drugs, osteoporosis, pyelonephritis, etc. are being treated. When iatrogenic disease is tried to minimize the dosages of glucocorticoids or refuse their use (if available).
There are 4 forms of the disease:
- Adrenal , or primary , resulting from a decrease in cortisol synthesis by the adrenal cortex . This may be due to adrenal lesions of the tuberculous or autoimmune process, sarcoidosis, malignant neoplasm or metastasis of a cancerous tumor, acute ischemia or adrenal infarction in septic and other types of shock, thrombohemorrhagic syndrome, burn disease, polyorgan, burn disease, ad hoc inflammation or other types of shock.
- Pituitary , or secondary , in which a decrease in cortisol levels is due to a decrease in the production of ACTH. It occurs in trauma, tumors, acute circulatory disorders and inflammatory processes in the brain, sarcoidosis, and pituitary amyloidosis.
- Hypothalamic , or tertiary , in which a decrease in cortisol secretion is associated with a decrease in the secretion of CRH. Causes of the defeat of the hypothalamus - an inflammatory process or a tumor.
- Iatrogenic , resulting from abrupt withdrawal of glucocorticoid therapy due to decreased secretion of ACTH, radiation therapy, adrenalectomy (surgical removal of the adrenal glands during hypercorticism) or as a result of the use of drugs that suppress cortisol synthesis.
- weight loss;
- decrease in blood pressure, especially with slight physical exertion;
- headaches and dizziness;
- lack of appetite until refusal of food intake;
- constipation, alternating diarrhea, pain in the upper abdomen;
- tendency to hypoglycemic conditions;
- irritability, psychotic and depressive states.
The treatment consists in the constant use of synthetic glucocorticoids in individually selected dosages (prednisone or dexamethasone) and in the conduct of symptomatic therapy.