Addison's disease symptoms in men. Addison's disease and its symptoms

The adrenal cortex produces vital hormones - glucocorticoids and mineralocorticoids. In addition, a small amount of sex hormones is also produced in this endocrine organ.

If the cortex is affected by any pathological process, then the patient develops serious illness Primary adrenal insufficiency (Addison's disease). This chronic pathology has many consequences for the whole organism and even threatens life.

The prevalence of the disease is small. There are 40-60 cases of pathology per 100 thousand of the population. Women suffer from Addison's disease much more often. Especially this difference in the structure of morbidity by sex of patients has become noticeable recently.

Why does the disease occur

The cause of Addison's disease in most cases is autoimmune inflammation. Antibodies to the body's own cells produce defense systems. The immune system mistakes the adrenal cortex for foreign tissue and begins to destroy it. When most of the endocrine cells have already died, the first symptoms of bronze disease appear.

What can provoke an autoimmune aggression? Physicians cannot unambiguously answer this question. Probably, the pathology of the body's defenses is associated with heredity, genetic mutations, excessive insolation (sunlight, solarium), and adverse environmental conditions.

The autoimmune process is responsible for 80–90% of cases of the disease. The destruction of the adrenal cortex can occur for other reasons. So, in adverse social conditions, the disease provokes tuberculosis. To date, this infection is the cause of about 10% of all cases of chronic adrenal insufficiency.

Less commonly, the cause of the disease is trauma, surgical destruction, thrombosis, benign or malignant tumor.

Whatever caused primary adrenal insufficiency, its clinical picture and principles of treatment differ slightly.

Signs of illness

Symptoms of the disease are associated with insufficiency of glucocorticoids and mineralocorticoids. Some of the symptoms appear due to the excessive stimulating effect of the pituitary gland. Endocrine cells in the brain try to increase the work of the adrenal cortex by releasing large amounts of tropic hormones (primarily adrenocorticotropin). Melanostimulating hormone is also synthesized in the pituitary gland. With Addison's disease, too much of it is released and because of this, hyperpigmentation of the skin and mucous membranes appears. The dark coloration can be so pronounced that it has become the source of another name for the disease - "bronze" disease (see photo). The first signs of hyperpigmentation appear in places where the skin rubs against clothes, in natural folds and in place. surgical sutures or scars.

Characteristic bronze skin color

A patient with Addison's disease is troubled by severe general weakness. Fatigue can be so severe that it is difficult for the patient to get out of bed, take a few steps, or just sit.

The disease is always accompanied by hypotension. Blood pressure during the day is almost always below 90/60 mm Hg. Art. If the patient gets up abruptly, then hypotension increases. When changing the position of the body, there may be episodes of dizziness, darkening in the eyes, loss of consciousness.

Primary insufficiency of the adrenal cortex leads to disruption of the digestive tract. The patient loses his appetite. Body weight begins to decrease rapidly. There are changes in food habits. There may be cravings for salt.

Work disruptions digestive system manifested by nausea and vomiting, diarrhea. These phenomena contribute to the rapid depletion of the body.

The emotional state of patients is usually depressed. Specialists often diagnose depression and other disorders. In severe cases, psychosis (delusions, hallucinations, aggressive behavior) may develop.

Addisonian crisis

Addisonian crisis - this condition develops due to an acute insufficiency of cortical hormones. Without treatment, the crisis leads to the death of the patient.

signs sharp deterioration states:

• severe muscle pain;
• vomit;
• a sharp drop in blood pressure;
• psychosis;
• loss of consciousness;
• convulsions.

Blood tests reveal a sharp drop in glucose and sodium, an increase in the concentration of calcium, potassium and phosphorus.

How is the diagnosis established?

Examination for suspected primary adrenal insufficiency is carried out by an endocrinologist. Diagnosis of Addison's disease includes a standard or short test with adrenocorticotropin. Additionally, the patient is prescribed a blood test for cortisol, renin, blood sugar, electrolytes, adrenocorticotropin and a complete blood count.

The disease is characterized by:

• there is not a sufficient increase in cortisol levels during trials;
• blood cortisol is reduced;
• renin and ACTH are elevated;
• hyponatremia;
• hyperkalemia;
• an increase in neutrophils and eosinophils in the general blood test;
• hyperglycemia (increased blood sugar).

Medical tactics

Treatment of chronic adrenal insufficiency requires hormone replacement therapy. This tactic involves the appointment of glucocorticoids and mineralocorticoids on an ongoing basis.

Usually the patient receives medicines in the form of tablets. 60-70% of the daily dose is prescribed before breakfast, the rest - before lunch.

If there is a risk of deterioration of health (crisis), then the dose of drugs is increased by 50-100%. Such measures are needed for acute diseases, operations, injuries, etc.

If the patient develops a sharp drop in blood pressure, then hormones begin to be injected (hydrocortisone).

Addisonian crisis is treated with simultaneous administration of hydrocortisone, sodium chloride and glucose.

We explore the causes and symptoms that manifest Addison's disease. We will also study how the diagnosis is carried out and what medications are used for treatment, which can increase the duration of a normal life.

What is Addison's disease

Addison's Disease is metabolic pathology, with which adrenal glands produce hormones in insufficient quantities .

In this condition, the secretion of the adrenal glands is unable to meet the physiological needs of the body, resulting in acute symptoms, which, if left untreated, can threaten the life of the patient.

The disease can affect anyone at any age, but usually occurs around 40 years of age. It is assumed that the incidence on a global scale is 1 case for every 100,000 people.

What hormones are secreted by the adrenal glands The adrenal glands, which are endocrine glands, are located to the right and left of the spine at the level of the last thoracic vertebra, on top of both kidneys. Each of the 2 adrenal glands is made up of two different parts. The outer part, which is the true gland that secretes hormones, and is called the adrenal cortex, and the internal nervous tissue, called the medullary region. The area of ​​the adrenal cortex, in turn, is divided into three separate layers that produce hormones: Mineralocorticoids: a set of hormones belonging to corticosteroids (derived from the degradation of cholesterol), the function of which is to regulate the balance of mineral salts (sodium and potassium, and therefore water balance). They are produced by the adrenal cortex, which is known as the glomerulus. The main of these hormones is aldosterone, whose secretion increases in proportion to the increase in the blood concentration of potassium, which is a regulator of blood pressure. Glucocorticoids: More specifically, cortisol and cortisone, which speed up metabolic reactions and break down fats and proteins into glucose inside the cell. Stimulation of the production of these hormones is carried out through adrenocorticotropic hormone (produced by the pituitary gland of the brain). Androgens and estrogens. Androgens are secreted in large quantities, and estrogens only in small doses. All this happens to both women and men. In the medullary region, two neurotransmitter, which have very similar chemical properties: epinephrine and norepinephrine.

From what has been said, it is clear that:

• decreased production of aldosterone causes an imbalance of water, sodium and potassium in the body, which is determined by the expulsion of sodium and the retention of potassium. This condition can lead to hypotension (low blood volume) and dehydration;
• cortisol deficiency causes metabolic disorders and hypoglycemia problems, which makes the body weak.
• decrease in androgens can lead to decreased desire, hair loss and loss of sense of well-being due to mental problems.

Symptoms of low adrenal hormone levels

Symptoms of the disease depend on the level of concentration of hormones of the adrenal cortex in the blood. The decrease in concentration, in most cases, is associated with the destruction of adrenal cells. Destruction, as a rule, develops slowly.

Thus, the clinical picture of Addison's disease in initial stage characterized by very mild and non-specific symptoms, which slowly progresses as destructive lesions of the gland spread.

When the damage covers 90% of the secreting cells, chronic adrenal insufficiency develops.

Summarizing the main symptoms of Addison's disease, the following should be noted:

• Asthenia. Decreased muscle strength to the point where it is difficult to perform daily activities. Fatigue is present even at rest or after an absolutely insignificant effort.
• hypotension. Accompanied by dizziness, and in severe cases even fainting and falls. Decreased blood pressure, which decreases further when standing upright, is a direct result of low aldosterone levels. This hormone blocks the excretion of sodium in the urine. Low levels of aldosterone lead to loss of sodium and fluid, resulting in a decrease in blood volume and blood pressure.
• hypoglycemia. Decreased blood sugar levels as a result of low cortisol levels. A decrease in the concentration of the latter, in fact, reduces gluconeogenesis, namely the production of glucose from proteins and lipids, causing hypoglycemia. This is exacerbated by hypotension and asthenia.
• Dehydration. It is caused by excessive diuresis caused by the loss of sodium salts in the urine. Accompanied by an irresistible craving for salty foods.
• Weight loss and anorexia. This is a consequence of hypoglycemia and impressive fluid loss in the urine.
• Skin hyperpigmentation. Pigmentation can be observed both on the skin exposed to the sun, and on hidden areas of the body that are usually not accessible to the sun. sun rays: oral mucosa, gums, skin folds, scars, etc. All this comes from the fact that the pituitary gland stimulates the adrenal glands to produce more corticotropin, which, in turn, stimulates the production of melanin, which is responsible for skin pigmentation.
• Gastrointestinal. That is, nausea, vomiting, diarrhea, abdominal cramps.
• pain in joints and muscles.
• Migraine.
• Mood related problems: irritability, excessive anxiety, bad mood and melancholy, and in severe cases depression. All these problems are associated with reduced secretion of androgens, which act on the psyche, providing a sense of general well-being.
• Loss of body hair. The symptom is also associated with low androgen levels.

In a small number of cases, the symptoms of the disease, instead of chronic form, develop quickly and suddenly, this state is called acute adrenal insufficiency or Addison crisis. This situation requires immediate medical attention and proper patient care.

symptomatology, which characterizes the Addison crisis, consists of the following:

• Sharp and excruciating pains that cover the abdomen, back, lower part or legs.
• Fever and confusion, trouble making meaningful conversations.
• Vomiting and diarrhea with danger of dehydration.
• Very low blood pressure.
• Loss of consciousness and inability to stand.
• Very low blood glucose.
• Very low sodium levels in the blood.
• High levels of potassium in the blood.
• High levels of calcium in the blood.
• Involuntary muscle contractions.

Causes of Addison's disease - primary and secondary

The hormonal deficiency that is characteristic of Addison's disease can be caused by problems originating either from the adrenal glands (primary adrenal insufficiency) or from other sources (secondary adrenal insufficiency).

When primary adrenal insufficiency a decrease in hormone levels is a consequence of the destruction of glandular tissue cells, which, in turn, can be caused by:

• immune system error. Which, for unknown reasons, recognizes the cells of the adrenal cortex as foreign and destroys them, leading to the development of pathology.
• Granulomas from tuberculosis. In this case, granulomas are the result of an inflammatory process caused by a viral infection.
• Fungal infections or cytomegalovirus infections. They occur in patients suffering from immunosuppressive disorders.
• Primary or metastatic adrenal tumors(most often lymphoma or lung cancer).
• Bleeding from the adrenal glands. An example of such a disease is the Waterhouse-Frideriksen syndrome. This is severe bleeding resulting from a severe bacterial infection, usually caused by Neisseria meningitidis meningococci.
• adrenal infarction. Necrosis of the connective tissue of the gland due to insufficient blood supply.
• genetic mutations that affect the functioning of the adrenal glands. They are quite rare.

When secondary adrenal insufficiency the adrenal glands remain functional and efficient, and low hormone levels are the result of:

• Problems with the pituitary gland. It is responsible for the secretion of adrenocorticotropic hormone, which has the task of stimulating the adrenal cortex.
• Stopping corticosteroid therapy. Such therapy is often carried out in the case of patients suffering from asthma and rheumatoid arthritis. A high level of corticosteroids reduces the level of adrenocorticotropic hormone in the blood. A decrease in the latter leads to a sharp decrease in the stimulation of adrenal cells, which ultimately causes a kind of atrophy. Restoring their normal operation may take a considerable time (about 6 months). During this period, the patient may have an Addison's crisis.
• Violation of steroid biosynthesis. To produce cortisol, the adrenal glands must receive cholesterol, which is converted through appropriate biochemical processes. Therefore, in any situation where the flow of cholesterol to the adrenal glands stops, a state of cortisol deficiency develops. Such situations, although very rare, occur with Smith-Lemli-Opitz syndrome, abetalipoproteinemia syndrome, and certain medications (eg, ketoconazole).

Diagnosis of adrenal insufficiency

The doctor makes the first assumption of the diagnosis based on the patient's history and a detailed analysis of symptoms and signs. This hypothesis is then tested by a series of surveys and tests.

Blood analysis, which should include:

• Low levels of cortisol.
• High levels of ACTH.
• Low cortisol response to ACTH stimulation.
• The presence of specific antibodies to the adrenal system.
• The sodium level is below 130.
• Potassium level over 5.

Measuring Glucose After Insulin Injection. Insulin is administered to the patient and blood sugar and cortisol levels are measured at regular intervals. If the patient is healthy, blood sugar levels decrease and cortisol levels increase.

Stimulation of the adrenal glands by ACTH. The patient is injected with synthetic adrenocorticotropic hormone, and then the cortisol concentration is measured. Low levels indicate adrenal insufficiency.

CT scan abdominal cavity. Determines the size and any anomalies of the glands.

Magnetic resonance imaging of the Turkish saddle(the region of the skull where the pituitary gland is located). Identifies possible malfunctions in the pituitary gland.

Therapy for Addison's disease - restore hormone levels

Regardless of the cause, Addison's disease can be deadly, so the hormones that the adrenal glands produce in insufficient quantities must be supplied to the body.

Treatment of the disease involves the introduction of:

• Corticosteroids. In particular, fludrocortisone, to compensate for the deficiency of aldosterone and cortisone.
• Androgens. The introduction in sufficient quantity improves the feeling of well-being, and therefore improves the quality of life.
• Sodium supplements. Serve to reduce fluid loss in the urine and increase blood pressure.

When Addison crisis immediate treatment is needed because it is very life-threatening for the patient.

Treatment includes:

• Hydrocortisone.
• Saline infusions to increase blood volume.
• The introduction of glucose. To increase blood sugar levels.

Due to the danger of a sudden Addison's crisis, patients suffering from the disease should wear emergency medical bracelet. In this way, the medical staff will be immediately notified of the alarm.

Life expectancy in Addison's disease

Correctly treated Addison's disease life expectancy is normal. The only possible danger may come from the Addisonian crisis. Therefore, patients are advised to wear an information bracelet, as well as a cortisol injection syringe in case of emergency.

The British physician Thomas Addison in 1855 first described clinical manifestations disease caused by damage to the adrenal cortex. It is called Addison's disease. According to modern data, this is an endocrine pathology caused by the loss of the ability of the adrenal glands to synthesize the required amount of hormones. The main role is played by the lack of cortisol.

The prevalence of reported cases is about 1 per 100,000 population. But doctors do not consider these numbers reliable, as patients with mild symptoms may not seek medical attention. medical care, and the level of detection in different countries world is too different in its capabilities.

So, in Denmark, the USA revealed 4-6 cases per 100,000 population, in the UK - 3.9. Some scientists argue that Addison's disease most often develops in women aged 30-50 years. Others insist that there is no connection with age, gender and race. General opinion: women are much more severely ill than men.

The pathology should not be confused with the well-known Addison-Birmer anemia. Thomas Addison described it 6 years earlier and considered it one of the manifestations of chronic adrenal insufficiency. By its nature, hematopoietic disease can be part of the signs of hypocorticism or develop as an independent disease.

Classification

The functioning of the peripheral endocrine glands is necessarily associated with the organ where they are located, and the "orders" of the hypothalamic-pituitary system. According to this principle, the disruption of the adrenal cortex is divided into:

• on the primary - the adrenal cortex is affected;
• secondary - all initial changes occur in the pituitary gland (anterior lobe) or hypothalamus (brain stem region), and then disrupt the regulation of adrenal hormone production.

How does the adrenal cortex work in normal and pathological conditions?

In the cortical layer of the adrenal glands, the following types of hormones are formed:

• glucocorticoids (cortisol, cortisone, deoxycortisol, corticosterone and dehydrocorticosterone);
• mineralcorticoids (aldosterone);
• dehydroepiandrosterone (precursor of androgens).

Each type of hormones of the adrenal cortex is responsible for its function.

The role of glucocorticoids

Of all the glucocorticoids, cortisol is the most active. The effect on the body is very multifaceted. Anti-stress effect in case of injuries, state of shock, massive blood loss provided through:

• adaptation of blood pressure, vascular wall, myocardium to stress factors;
• regulation of erythrocyte production by the bone marrow.

Effect on metabolism

Cortisol is involved:

• in the biochemical process of synthesis in the liver of glucose from amino acids, creates a protein "depot" in the muscles to maintain energy balance;
• blocks the breakdown of sugars;
• replenishes glycogen stores (for energy extraction) in the muscles and liver;
• accumulates fats;
• supports aldosterone in sodium and water retention.

Anti-inflammatory protection

Provided through:

• blocking enzymes and autoantibodies involved in the inflammatory response;
• decrease in capillary permeability;
• reduction of oxidative processes;
• scar growth disorders;
• inhibition of cells that create conditions for allergies;
• reducing the susceptibility of tissues to histamine and serotonin, with an increase in adrenaline sensitivity.

The effect on immunity depends on the concentration in the blood: at low concentrations - stimulate, at high - suppress.

In addition, glucocorticoids:

• increase the secretion of acid and pepsin by the glands of the gastric mucosa;
• affect the work of the brain (information processing, evaluation of taste, smell).

The most significant in case of insufficiency of the adrenal cortex is the loss by the body of the ability to "extract" and replenish the energy balance. Patients appear great weakness. The symptom often leads to a late diagnosis because people associate it with age and don't consider it important.

With a lack of glucocorticoids in the body develops:

• a change in the sensitivity of cells to insulin, followed by a violation of all types of metabolism;
• hypoglycemia and a drop in the energy reserves of glycogen in the liver;
• reduced immunity to infectious pathogens;
• any kind of stress reactions proceed violently;
• drops due to myocardial weakness cardiac output possible development of heart failure;
• an increase in the synthesis of ACTH increases the level of β-lipotropin in the blood, this substance has a melanocyte-stimulating effect, the property is manifested by the formation of such a sign as skin pigmentation (hence another name for the pathology - bronze disease).

Photo of pigmentation on the cheekbones of a woman with bronze disease

Mineralocorticoids, role in the mechanism of development

Aldosterone is an activator of the synthesis of a protein carrier of sodium molecules. Under the influence of the hormone, it undergoes reabsorption in the tubules of the kidneys and is retained in the blood. Sodium is always followed by water. At the same time, potassium is excreted into the urine. This mechanism maintains and raises blood pressure in the event of shock, is extremely important in bleeding, loss of fluid through sweat, profuse vomiting and diarrhea.

The synthesis of aldosterone is stimulated by:

• renin-angiotensin system of the kidneys;
• pituitary adrenocorticotropic hormone;
• sodium and potassium ions, with accumulation in the epithelium of the tubules.

Induced hypotension is important in the pathogenesis of cortical insufficiency in Addison's disease. Mineralocorticoid deficiency contributes to increased sodium and water excretion, potassium retention. A pronounced imbalance of electrolytes leads the body to a state of dehydration (dehydration). The volume of circulating blood decreases, blood pressure drops.

In secondary adrenal insufficiency associated with impaired ACTH synthesis, a normal electrolyte balance in the blood test is often observed.

Androgen deficiency leads to impaired synthesis of sex hormones. This is especially important in the development of the disease in adolescence. In adult men and women, productive function is impaired.

Possible causes and mechanism for the development of disorders

For primary insufficiency, the causes may be:

• autoimmune effects (idiopathic atrophy of the adrenal cortex), US researchers believe that this includes up to 70% of cases, there have been reports of the significance of AIDS;
• tuberculous inflammation, syphilis;
• amyloidosis;
• underdevelopment of the glandular apparatus (hypoplasia);
• tumor of the adrenal gland or metastases in it;
• destruction of glandular tissue by toxic substances;
• genetic disorders in the process of synthesis of hormonally active substances;
• decrease in the sensitivity of the adrenal tissue to "orders" from higher centers transmitted by pituitary adrenocorticotropic hormone (ACTH).

The tumor of the left adrenal gland compresses the glandular cells, causing their destruction

At secondary insufficiency adrenal glands (it is called the hypothalamic-pituitary), the main factor in pathogenesis is the defeat of the anterior pituitary gland with a lack of adrenocorticotropic hormone. Its concentration in the blood is not enough to stimulate the glandular cells of the adrenal glands.

The reasons are due to:

• a local tumor in the brain stem or pituitary gland;
• consequences of ischemic attack, stroke;
• prolonged stressful situations;
• head injury;
• radiation therapy of the brain in certain diseases;
• birth trauma in children during the first days of life;
• hormonal changes in women during pregnancy, during menopause.

Addison's disease in such cases is often combined with a decrease in thyroid function, diabetes mellitus, polyglandular insufficiency syndrome (of all endocrine glands).

What determines the development of the iatrogenic form?

Doctors are forced to isolate the iatrogenic form of the disease, depending on the treatment used. Modern therapy many systemic diseases can not do without corticosteroids. They are prescribed, for example, to patients with psoriasis, lupus erythematosus, asthma, nonspecific ulcerative colitis, autoimmune thyroiditis and other pathologies of internal organs.

Patients have to take drugs for long courses according to vital indications. In this case, the own glandular cells of the adrenal glands atrophy, the connection with the hypothalamic-pituitary system of regulation is broken. If you stop taking the drugs, a "withdrawal syndrome" develops with severe insufficiency. Dosage reduction should be done in stages.

Symptoms

Symptoms of Addison's disease develop gradually, go unnoticed for a long time until a person has a sharp need for increased production of hormones to fight stress, a severe infection. Here it becomes clear that the body is not able to organize the fight against damaging factors and compensate for losses.

Areas of pigmentation may be combined with white spots (vitiligo)

The following signs of disturbed hormonal balance appear:

• increasing fatigue, gradually worsening over time;
• muscle weakness;
• trembling in the hands, tremor of the head;
• possible cramps in the limbs (often associated with eating dairy products);
• lack of appetite, impaired swallowing, weight loss;
• constant desire for salt and thirst;
• frequent nausea, diarrhea, vomiting, sometimes abdominal pain;
• hypotension is orthostatic in nature (pressure drops when standing), sometimes accompanied by fainting;
• areas of hyperpigmentation of the skin appear in open places, on the face, hands, neck, lips, nipples become bluish-black;
• the patient notices deviations in the psyche: irritability, anxiety, irascibility, followed by depression;
• women and girls note the irregularity or cessation of menstruation;
• for men, the occurrence of impotence is typical;
• excess potassium in the blood contributes to such manifestations as paresthesia and paralysis.

Patients are characterized by an exacerbation of symptoms in the spring-summer season.

How does an Addisonian crisis occur?

Against the background of the gradual course of the disease, the patient may develop a clinic of acute adrenal insufficiency. The pathology is called the Addisonian crisis. The reason is:

• prolonged lack of treatment;
• insufficient dosage of drugs;
• meeting a patient with a severe stressful situation;
• the need for surgical intervention;
• injury;
• infection.

A similar condition develops with the "withdrawal syndrome" of glucocorticoid drugs in patients with healthy adrenal glands due to functional disorders in the secreting cells.

The patient's condition is regarded as serious:

• sudden severe pain in the abdomen, lower back or legs;
• continuous vomiting, diarrhea;
• shock develops;
• arterial pressure is sharply reduced;
• consciousness is confused;
• possible acute psychosis;
• the expressed tachycardia, arrhythmias is registered;
• a significant amount of urine is excreted;
• there are signs of dehydration (dry skin, mucous membranes);
• possible fever.

The crisis lasts from several hours to three days. Treatment of Addison's disease during a crisis course requires immediate professional assistance: fluid administration, normalization of the electrolyte composition, compensatory dosage of hormones.

A brown coating is visible on the patient's tongue and teeth due to the addition of erythrocyte hemolysis, iron deficiency

Diagnostics

Diagnosis of Addison's disease is based on a combination of clinical and laboratory findings. Initial manifestations in the form of increased fatigue, weakness are often mistaken for neurasthenia. But further changes suggest increasing adrenal insufficiency.

• asthenia;
• neuropsychic changes;
• gastroenterological disorders;
• predisposition to oncology;
• cardiovascular signs;
• melasma manifestations;
• anemia.

The presence of a combination of these syndromes indicates Addison's disease. If they are allocated each separately, then the diagnosis is considered unreliable or erroneous.

The classic laboratory findings are electrolyte shifts:

• hyponatremia;
• hyperkalemia;
• hypercalcemia;
• hyperphosphatemia.

Especially if they are detected against the background of reduced hematocrit, glucose and high levels of urea in the blood. Perhaps an increase in the number of eosinophils, normo- and hyperchromic anemia. Special studies on hormones are to determine the level of cortisol and ACTH in plasma, their ratio:

• if the level of cortisol is low, and ACTH is elevated, one can assume the primary nature of adrenal insufficiency;
• with a simultaneously low level of ACTH and cortisol, the condition is regarded as a secondary insufficiency.

In the event of an urgent need for surgical treatment the dosage of the administered Hydrocortisone is determined theoretically. In the context of the planned preparation of the patient for surgery, if Addison's disease is suspected, but hormone levels are normal, a provocative test is performed. Its meaning: to introduce ACTH to the patient and check the cortisol content. If there is no reaction, primary adrenal insufficiency is diagnosed.

To diagnose secondary insufficiency, tests are carried out simultaneously:

• on the effect of ACTH stimulation - after intramuscular injection prolonged drug with ACTH during the day with interruptions, blood is examined for cortisol, its level rises after the first hour;
• insulin resistance;
• the effect of glucagon.

When making a diagnosis, the manifestations of Addison's disease are compared with Conn's disease, Itsenko-Cushing's disease (hyperaldosteronism, excessive production of ACTH in the anterior pituitary gland with hypercortisolism).

Aldosteronism refers to changes caused by an increase in the production of aldosterone. The disease is primary and secondary.

Conn's syndrome ( primary aldosteronism) is associated with overproduction of adrenal tumors. Its symptoms are characterized by:

• muscle weakness;
• hypertension;
• seizures;
• polyuria;
• no edema;
• in the blood test - hypokalemia;
• in urine - increased excretion of aldosterone.

Itsenko-Cushing's syndrome is pathogenetically associated with increased production of glucocorticoids. Occurs under the influence of a tumor that synthesizes ACTH (pituitary, lungs, adrenal glands) or in people who have been treated with hormones for a long time for autoimmune diseases.

Treatment

Treatment of Addison's disease requires the use of replacement therapy hormones.
For primary deficiency:

• to compensate for the loss of cortisol, hydrocortisone is prescribed;
• with a decrease in aldosterone - Fludrocortisone (Kortineff, Florinef), you may have to switch to a salt-free diet or reduce intake.

Cortineff has a 100 times stronger mineralocorticoid, 10 times the anti-inflammatory effect of Hydrocortisone (not all pharmaceutical companies retain the second letter "F")

Patients with secondary adrenal insufficiency do not require replacement of mineral corticosteroids. These substances continue to be synthesized normally. All dosages of drugs are selected individually.

Adequate therapy is indicated by sufficient fluid intake and the cessation of orthostatic hypotension. Some patients have to use drugs to lower blood pressure, because fludrocortisone causes hypertension in them.

Difficulties are caused by simultaneous concomitant diseases. If activation of the infection is observed, the dosage of Hydrocortisone is doubled. It is important for concomitant diabetes to revise the dosage of insulin if necessary. In the presence of severe nausea, vomiting, prescribing drugs in tablets does not make sense. Only injections are used.

Patients with chronic adrenal insufficiency are taught self-management for unexpected manifestations. They are advised to always carry a special bracelet or card with them so that strangers know which drug to administer in case of unconsciousness.

In the picture of the Addisonian crisis, the patient's life is threatened by a drop in blood pressure, arrhythmias caused by an increase in potassium in the blood, and hypoglycemia. Therefore, on an emergency basis, intravenously administered:

• Hydrocortisone;
• saline (0.9% sodium chloride);
• Dextrose (instead of sugar).

Hydrocortisone is infused continuously drip for 24 hours

Usually there is an improvement. Then they switch to tablet forms of Hydrocortisone preparations, if necessary, Fludrocortisone. The recovery of the patient also depends on the treatment of the cause that provoked the crisis. If the culprit was stress, then the liquids are poured much less.

1. At high temperatures against the background of dehydration, drugs of the Aspirin group are used very carefully.
2. Antipsychotics will be required to affect the nervous system. Drugs with a short-term effect are preferred.
3. Symptomatic agents should be coordinated with the level of electrolytes in the plasma, the response of blood pressure.
4. Vitamins C and B 1 are shown. You can use folk remedies to strengthen the immune system, since most often the adrenal glands suffer from autoimmune reactions.

Patients are advised to protect themselves from any infections, more often to be checked for infection with tuberculosis. Addison's disease with compensated support medicines does not reduce active life. The presence of any symptoms requires a full diagnosis.

Addison's disease or bronze disease is a pathological lesion of the adrenal cortex. As a result, the secretion of adrenal hormones decreases. Addison's disease can affect both men and women. The main risk group is people in the age group of 20–40 years. Addison's disease is characterized as a progressive disease with a severe clinical picture.

The causes of Addison's disease are pathological, including autoimmune (Autoallergy), processes that destroy the adrenal cortex (tuberculosis, syphilis, adrenal hemorrhages, bilateral primary or metastatic tumors of the adrenal glands, amyloidosis, lymphogranulomatosis, and so on). Sometimes chronic adrenal insufficiency is secondary and develops as a result of dysfunctions of the hypothalamic-pituitary system (hypothalamic-pituitary insufficiency).

What it is?

Addison's disease is a rare endocrine disorder that causes the adrenal glands to lose their ability to produce enough hormones, primarily cortisol. This pathological condition was first described by the British physician Thomas Addison in his 1855 publication entitled Constitutional and Local Consequences of Diseases of the Adrenal Cortex.

Characteristic

This disease is characterized by the following clinical symptom complex: 1) asthenia and adynamia, 2) pigmentation of the skin and mucous membranes, 3) disorders of the gastrointestinal tract and 4) Decrease in arterial blood pressure.

Symptoms of bronze disease

Asthenia and adynamia (physical and mental fatigue and impotence) are the earliest, permanent and important symptoms of bronze disease. Most often, the onset of the disease cannot be accurately determined. Without any forerunners, phenomena of rapid fatigue gradually develop from work that was usually performed before without much fatigue; there is a feeling of general weakness that develops with a normal lifestyle. Feelings of fatigue and general weakness, depending on the case, progress more or less quickly, intensify and lead the patient to a state of irresistible general weakness and even complete physical impotence.

Muscular asthenia is expressed in varying degrees of feeling of rapid fatigue and exhaustion of forces that occur after any more or less strong physical exertion: walking, physical work, in some patients in advanced stages of the disease, even after eating or changing body position in bed. Sometimes muscle strength can be preserved, but, characteristically, muscles tire extremely quickly and cannot, in contrast to healthy ones, do work for a long time.

To identify this characteristic muscle fatigue (muscle asthenia), the patient is asked to sequentially squeeze the dynamometer several times by hand, and with each subsequent time the dynamometer will show smaller and smaller numbers, corresponding to the decreasing muscle strength each time.

In addition to muscular asthenia, mental asthenia and intellectual apathy usually develop simultaneously. Due to adynamia and asthenia, the patient is forced to first reduce his work, rest more often, and then quit it completely and go to bed. General weakness can be so pronounced that the patient can hardly turn in bed, hardly answers questions, since even the slightest conversation tires him, avoids eating. The patient is usually fully conscious. Only in the final stage of a severe form of the disease can there be mental disorders, depression, delirium, convulsions, and finally, coma ending in death.

Skin pigmentation (melasma) is the most important, conspicuous, usually attention-grabbing symptom that characterizes the name of the disease. Due to the abundant deposition of iron-free pigment (melanin) in the cells of the malpighian layer of the skin, the skin acquires a peculiar dirty gray, brown, bronze or smoky color, sometimes resembling the skin color of a mulatto or black man. This melasma, barely noticeable at first, may appear already during the period of asthenia, less often melasma is the first and early symptom.

Starting on the face, pigmentation can capture the entire surface of the skin or be localized in certain favorite places: on open parts of the body exposed to light (on the forehead, neck, back surface of the hands, interphalangeal joints, on the palmar folds), on places where and Normally, there is a large deposition of pigment (on the pectoral nipples, scrotum, external genital organs, around the navel and anus), and finally, the skin areas that are irritated and rubbed with folds of clothing, belts, garters, bandages, as well as places of former boils, burns, mustard plasters. Sometimes much darker spots appear on the face against a general dark background, ranging in size from a pinhead to a lentil. Along with strong pigmentation, there are areas of skin that are poorly pigmented or even completely devoid of normal pigment, which stand out sharply against the background of the surrounding dark skin - the so-called vitiligo, or leucoderma.

Often there is the appearance of brown, slate-gray or black spots of various sizes and shapes on the mucous lips, gums, cheeks, on the soft and hard palate, on the mucous membrane of the foreskin, glans penis and small lips. Pigmentation of the mucous membranes is a very important, almost pathognomonic sign of Addison's disease. However, it should be noted that in rare cases dark spots on mucous membranes can occur without symptoms of Addison's disease. In some cases of rapidly developing Addison's disease, pigmentation of the skin and mucous membranes may be absent, just like in erased, non-symptomatic forms and in the early stages of the disease.

Gastrointestinal disorders are very common. Bad appetite bad taste in the mouth, salivation, a number of dyspeptic phenomena in the form of belching, sensations of pressure and heaviness in the epigastric region, and finally, abdominal pain disturbs patients, appearing without any apparent reason. A frequent symptom is nausea and vomiting of clear, viscous, colorless mucus, sometimes with an admixture of bile, appearing in the morning on an empty stomach, immediately after getting out of bed, reminiscent of morning vomiting in alcoholics. In more severe, progressive cases, vomiting occurs more often and not only on an empty stomach, but also after eating and drinking. From the side of the intestine, mainly constipation is observed, less often diarrhea, replacing periods of constipation. Sometimes diarrhea has a profuse cholera-like character. The secretion of gastric juice is different in different cases and stages of the disease; a definite pattern is not observed, but in advanced cases, hypo- and achlorhydria is more often observed. Diarrhea can be either gastrogenous in the presence of achylia, or it can appear due to increased excitability of the vagus nerve with reduced tone of the sympathetic nerve, or due to loss of influence of the adrenal glands on the sympathetic nerve.

Simultaneously with gastrointestinal disorders, and sometimes independently of them, pains appear in the lower back, in the hypochondrium, sides, chest or limbs. These pains are sometimes sharp, sometimes appearing, sometimes constant, aching, dull, not aggravated by pressure, not radiating anywhere. Pain in the pit of the stomach can sometimes appear in the form of seizures, accompanied by nausea and vomiting, and resemble gastric crises with tabes. The appearance of acute attacks of pain throughout the abdomen may give rise to merging with acute peritonitis.

The disorders of the gastrointestinal tract described above can sometimes dominate the overall picture of the disease. However, forms are not uncommon when they are expressed to a more or less weak degree, or even may be almost completely absent throughout the disease. In any case, the presence of these disorders contributes to weight loss and weakening of patients, and before that already in a state of adynamia and asthenia.

A decrease in arterial blood pressure (arterial hypotension) is an important and common symptom. The maximum blood pressure is below 100-90, even falling to 60 mm, the minimum decreases accordingly, although to a lesser extent, and the pulse pressure decreases. In rare cases, there is no hypotension or blood pressure is only slightly lowered. Arterial hypotension depends on a decrease in the tone of the nervous sympathetic system, which occurs either as a result of anatomical changes in the adrenal glands, or from a decrease in their function or from anatomical changes in the abdominal plexuses and nodes of the sympathetic nerve.

In addition to these main main symptoms, a number of changes in some organs and systems should be pointed out. So in the blood, in most cases, a number of deviations from the norm are noted. Moderate anemia of the hypochromic type is usually observed. With a normal number of leukocytes, most often there is lymphocytosis with neutropenia; rarely eosinophilia and monocytosis. Speaking of lymphocytosis, it should be noted that the so-called status thymico-lymphaticus is often observed. The number of platelets, the duration of bleeding time, blood coagulation do not give any special deviations from the norm. There is no parallelism between the severity of the disease and the morphological picture of the blood.

In most cases, low fasting blood sugar levels are found. Accordingly, the hypoglycemia curve of sugar at the end of the load with glucose or after an intramuscular injection of 1-2 mg of adrenaline does not give such a big rise as in healthy people, the fall of the curve does not occur after 2 hours, but much later, and there is no fall below the initial figure. In relation to carbohydrates, increased endurance is noted; sugar is not detected in the urine either after a heavy load of carbohydrates, or after intramuscular injection of even 2 mg of adrenaline.

On the part of the cardiovascular system, in addition to the already mentioned arterial hypotension, there is a small, weak filling and tension, a rhythmic, usually frequent pulse. The heart and aorta are often hypoplastic. Inorganic systolic murmurs are heard due to anemia and altered nutrition of the heart muscle. Patients complain of a number of abnormal unpleasant sensations, in the form of palpitations, shortness of breath during movements and the slightest physical exertion.

Tuberculous process is often observed in the lungs different degrees development and compensation. The usual examination of urine does not give deviations from the norm, but a decrease in the concentration ability of the kidneys and a decrease in the release of water during water load are often noted. The function of the gonads in clearly expressed cases is almost always reduced: in men - a decrease in libido and a weakening of potency; in women - often amenorrhea; conception is rare and pregnancy is often terminated prematurely

On the part of the neuropsychic sphere, in addition to adynamia and asthenia, increased excitability, irritability, and mood variability may initially be observed, but soon, with the progression of the disease, this is replaced by increased fatigue, loss of strength, indicated above as the main symptoms of adynamia and asthenia, lack of energy, indecision, apathy , indifference and depression to a complete stupor. Dizziness up to fainting is a common occurrence. In rare cases, delirium, convulsions and coma occur in the final stage.

Patients complain of chilliness. The temperature is normal or even low if there is no active process in the lungs or associated infections.

What does Addison's disease look like: detailed photos

The photo shows what part of the arm looks like with Addison's disease (bronze disease):

Skin pigmentation in Addison's disease

Forms of Addison's disease

If the main cardinal symptoms are present, then this is a clearly expressed typical form of the disease. However, there are often incomplete, erased forms of the disease (formes frustes), where there is one or two main symptoms, and then the disease presents great difficulties for recognition.

There are: 1) asthenic, 2) gastrointestinal, 3) melasma, 4) pain forms. The latter should include the so-called false peritonitis form, in which sudden severe abdominal pain, persistent constipation, vomiting, an inverted or swollen abdomen, general depression and increasing cardiac weakness leading to death come to the fore.

To obscure, erased forms, one should also include those states of adynamia, asthenia and hypotension that occur without melasma, more or less chronically, which are sometimes based on no anatomical changes in the adrenal glands and which are considered as states of hypofunction of the adrenal glands and the sympathetic system.

In children, Addison's disease is characterized by severe pigmentation, diarrhea, pronounced neuropsychic phenomena and a rapid course, ending in death. In old age, severe asthenia, adynamia, apathy, drowsiness come to the fore; death occurs with symptoms of cachexia. Pigmentation, on the contrary, is mild.

Diagnosis

When recognizing the disease in the presence of melasma, one must keep in mind all other physiological and pathological conditions in which the appearance of a similar pigment is also observed.

So, we must remember about increased pigmentation during pregnancy, chronic diseases of the uterus and ovaries; about a tan that spreads to all places exposed to radiant energy (the sun, ultraviolet rays of a quartz lamp, x-rays); about pigmentation on the skin of vagrants and people who rarely wash themselves, do not change linen, and suffer from lice; about bronze cirrhosis of the liver with or without diabetes mellitus, in which there is an increase in the liver, spleen and often glycosuria; about the so-called biliary melasma in some hepatic patients, especially those suffering from chronic obstructive jaundice in cancer of the head of the pancreatic gland or the papilla of Vater; about pigmentation in Gaucher's disease (splenomegaly, heredity and familial nature of the disease), about pellagra, about Graves' disease, about various kinds of cachexia (with tuberculosis, cancer, pernicious anemia) usually without pigmentation of the mucous membranes; finally, about arsenic melasma.

The diagnosis of the disease in the early stages in the absence of pigmentation is always difficult, since asthenia and gastrointestinal disorders can also be observed in diseases that have nothing to do with the Addisonian symptom complex. A careful study of other diseases, observation of patients, progression of the disease, the appearance of other main symptoms and especially pigmentation of the skin and mucous membranes confirm the diagnosis.

When recognizing single-symptomatic incomplete forms of the disease in the absence of melasma, the following should be used: 1) a test for provocative pigmentation (more or less strong pigmentation develops at the site of the set fly or mustard plaster); 2) dynamometric determination of muscle fatigue; 3) definitely the dynamics of the sugar curve in the blood before and after the end of the glucose load or intramuscular injection of 1-2 mg of adrenaline; 4) test pas increased endurance to carbohydrates; 5) lymphocytosis, monocytosis and frequent hypereosinophilia in the blood; 6) signs of status thymico-lymphaticus; 7) increased endurance of addisons to extracts of the thyroid gland and the posterior pituitary gland.

Etiology

As the etiological moments of the disease, adrenal tuberculosis should be put in the first place; this is followed by congenital absence or hypoplasia of the adrenal glands, infections: syphilis, diphtheria, typhus, influenza, various neoplasms and destructive processes and the form of hemorrhages, sclerosis and degeneration of the adrenal glands.

Injuries, wounds, air contusions, intestinal infections and even mental shocks are noted as etiological moments in the development of both clear and erased forms of bronze disease and the so-called symptoms of benign functional adrenal insufficiency or addisonism phenomena.

pathological anatomy

Microscopic examination of pigmented areas of the skin and mucous membranes reveals excessive deposition of grains of brown-black melanin pigment (not containing iron) in the cells of the malpighian layer and the connective tissue of the skin.

In 70% of cases, they find affected by tuberculosis in different stages, almost completely destroyed adrenal glands. Often, tuberculous granuloma affects the adjacent parts of the nervous sympathetic system and the solar plexus. Thus, the process that destroys the adrenal glands very often produces changes in important areas of the abdominal part of the sympathetic nerve. Only rarely is tuberculosis of the adrenal gland the only active focus. More often there is a tuberculous lesion in other organs, especially in the lungs.

In the absence of tuberculous lesions, the following were found: congenital absence, aplasia or hypoplasia of the adrenal glands, hypoplasia and atrophy of the adrenal medulla and the entire chromaffin tissue, hypoplasia or cirrhotic degeneration of the adrenal glands due to diffuse syphilitic processes, gums and after acute infections, amyloidosis, damage by malignant neoplasms, cystic degeneration, cavernous angioma, hemorrhages and hematomas, vein thrombosis, embolism of adrenal vessels, necrosis, suppuration and even echinococcus.

In the vast majority of cases, along with these or other lesions of the adrenal glands, changes are observed on the part of the abdominal sympathetic nodes and nerves (regeneration and pigmentation nerve cells, semilunar nodes, sclerosis and degeneration of nervous tissue, hypoplasia, destruction and disappearance of chromaffin tissue scattered along the tract of the sympathetic nerve).

In very rare cases, no changes were found in either the adrenal glands or the sympathetic nervous system. Sometimes found thymus persistens, hyperplasia of the lymphatic glands, tonsils and lymphatic tissue at the root of the tongue.

Course and forecast

The course and prognosis of bronze disease are very diverse depending on the etiological factors, on the nature of the underlying disease, on the tendency to progress or subside and recover, and on the associated diseases.

Therefore, both acute cases are observed, ending in death in a few days, and subacute, in which death occurs after 6-12 months. Finally, cases of chronic benign course are far from rare, lasting for many years with spontaneous stops of the process and relapses. Cases of recovery are also described, especially with syphilitic etiology and reversible processes in the adrenal glands or the sympathetic nervous system, which underlie the appearance of the Addisonian symptom complex in the so-called benign functional adrenal insufficiency.

It must be remembered that addisons are not resistant to many harmful influences, such as: physical fatigue, mental shock, trauma, acute infections and various intercurrent diseases - all this can worsen the course of the disease, unbalance the patient and hasten the fatal end.

Addison's disease is a fairly rare endocrine pathology. Its development is based on destruction ( destruction) tissues of the outer ( cortical) adrenal layer. Such destruction can be provoked by various factors. They can be harmful bacteria e.g. mycobacteria), fungi ( candida, cryptococcus), viruses ( cytomegalovirus, herpes, etc.), genetic, immune, microcirculatory ( violation of the blood supply to the adrenal cortex) violations ( ).

Damage to the cortical layer of the adrenal glands leads to a violation of the secretion of steroid hormones, primarily aldosterone and cortisol, which regulate water-salt, protein, carbohydrate, lipid metabolism in the body. They are also involved in the implementation of stress reactions, affect blood pressure, the total volume of circulating blood.

Various symptoms can occur in Addison's disease, such as increased fatigue, general weakness, dizziness, decreased ability to work, headache, thirst, cravings for salty foods, muscle weakness, myalgia ( muscle pain), muscle cramps, abdominal pain, nausea, vomiting, menstrual irregularities, low blood pressure, hyperpigmentation ( skin darkening), vitiligo, tachycardia ( cardiopalmus), pain in the heart, etc.

The structure and functions of the adrenal glands

The adrenal glands are paired endocrine glands. Each adrenal gland right or left) is placed on the superomedial ( top inner side) surface of the upper end ( poles) of the corresponding kidney ( right or left). Both adrenal glands have approximately the same mass ( about 7 - 20 g each). In children, the adrenal glands weigh slightly less ( 6 g). These glands are located in the retroperitoneal fatty tissue at the level of the XI-XII thoracic vertebrae. Retroperitoneal tissue is located in the retroperitoneal space - an area located behind the posterior leaf of the parietal ( parietal) peritoneum lining the posterior wall of the abdominal cavity. The retroperitoneal space extends from the diaphragm ( respiratory muscle that separates the thoracic and abdominal cavities) to the small pelvis ( anatomical region just below the abdominal cavity). In addition to the adrenal glands, it contains the kidneys, pancreas, aorta, inferior vena cava and other organs.

The left adrenal gland has a semilunar shape, the right one is triangular. In each of them, the anterior, posterior and renal surfaces are distinguished. With their back surface, both adrenal glands are adjacent to the diaphragm. Renal ( lower) their surface is in contact with the upper pole of the corresponding kidney. The right adrenal gland in the retroperitoneal space is located slightly higher than the left. With its front surface, it adjoins the inferior vena cava, liver and peritoneum. The left adrenal gland contacts the pancreas, the cardia of the stomach, and the spleen anteriorly. On the anteromedial ( front inner side) the surface of each of the adrenal glands is the so-called gate ( hilum), through which of them ( from the adrenal glands) exit the central veins ( hereinafter referred to as the adrenal veins).

Each adrenal gland has one central vein. The left adrenal vein then drains into the left renal vein. Venous blood from the right adrenal gland is transported through the right adrenal vein immediately into the inferior vena cava. In the gates of the adrenal glands, lymphatic vessels can also be found, through which the lymphatic fluid enters the lumbar lymph nodes ( nodi lymphatici lumbales) located around the abdominal aorta and inferior vena cava.

Arterial blood enters the adrenal glands through branches of the superior, middle, and inferior adrenal arteries ( a. suprarenalis superior, a. suprarenalis media, a. suprarenalis inferior). The superior adrenal artery is a continuation of the inferior phrenic artery. The middle adrenal artery arises from the abdominal aorta. The inferior adrenal artery serves as a branch of the renal artery. All three adrenal arteries under the connective tissue capsule that covers each of the adrenal glands form a dense arterial network. Small vessels depart from this network ( about 20 - 30), penetrating into the thickness of the adrenal glands through their anterior and posterior surfaces. Thus, arterial blood enters the adrenal glands through numerous vessels, while deoxygenated blood is removed from these endocrine glands only through one vessel - the central ( adrenal) vein.

The innervation of the adrenal glands is carried out due to the branches extending from the solar, renal and adrenal nerve plexuses, as well as the branches of the phrenic and vagus nerves.

Inward from the connective tissue capsule is the cortical substance ( outer layer) adrenal gland, which accounts for about 90% of the entire parenchyma ( fabrics) of this body. The remaining 10% in the adrenal gland is occupied by its medulla ( inner layer of the adrenal gland), which is located under the cortical substance, directly, in the very depths of the gland. The cortex and medulla have a different structure, functions and embryonic origin. cortex ( adrenal cortex) is represented by loose connective and glandular tissue. This layer on anatomical sections has a yellowish-brown color.

The outer layer of each of the adrenal glands is usually divided into three zones - glomerular, fascicular and reticular. The zona glomeruli is the outermost layer cortex and is localized, directly, under the capsule of the adrenal gland. The reticular zone borders on the adrenal medulla. The bundle zone occupies a middle position between the glomerular and reticular. The zona glomeruli produce mineralocorticoids ( ), in the bundle - glucocorticosteroids ( cortisol and cortisone), and in the reticular - androgens. The adrenal medulla has a brownish-red color and is not divided into any zones. In this area, catecholamines are synthesized in the adrenal glands ( epinephrine and norepinephrine).

The adrenal glands are vital organs and perform a variety of functions through the production of a number of hormones with specific properties. As mentioned above, mineralocorticoids are produced in these endocrine glands ( aldosterone, deoxycorticosterone, corticosterone), glucocorticosteroids ( cortisol and cortisone), androgens and catecholamines ( epinephrine and norepinephrine). The secretion of aldosterone and cortisol by the adrenal glands is vital for a person. Aldosterone is the only mineralocorticoid that the adrenal glands secrete into the blood. This steroid hormone contributes to the retention of sodium, chlorides and water in the body and the excretion of potassium along with urine. It contributes to an increase in systemic arterial pressure, the total volume of circulating blood, affects its acid-base state and osmolarity. Aldosterone regulates the proper functioning of the sweat and gastrointestinal glands.

Cortisol, like aldosterone, is also a steroid hormone. It has a wide range of effects on metabolism metabolism) in organs and tissues of the body. Cortisol stimulates the formation of large amounts of glucose and glycogen in the liver and inhibits ( blocks) their utilization in peripheral tissues. This contributes to the development of hyperglycemia ( an increase in blood glucose levels). In adipose, lymphoid, bone and muscle tissue, this hormone stimulates the breakdown of proteins. In the liver, on the contrary, it activates the synthesis of new proteins. Cortisol also regulates fat metabolism. In particular, it promotes the breakdown of fats in some tissues ( for example, fatty) and lipogenesis ( formation of new fats) in others ( torso, face). This glucocorticoid is the main stress hormone that helps the body adapt to the action of various stress factors ( infections, physical overexertion, mental or mechanical injuries, surgical interventions and etc.).

Androgens are produced by the cells of the reticular cortex of the adrenal glands. Their main representatives are dehydroepiandrosterone, etiocholanolone, androstenediol and androstenedione.

Testosterone and estrogens are practically not produced by the adrenal glands. Androgens, which are produced in large quantities in the adrenal glands, have a much smaller effect on body tissues than do the main sex hormones. So, for example, testosterone in its activity exceeds the action of androstenedione by 10 times. Androgens are responsible for the development of secondary sexual characteristics, such as a change in voice, body hair, the development of genital organs, etc., regulate metabolism, increase libido, that is, sexual desire.

Catecholamines ( epinephrine and norepinephrine), which are formed in the adrenal medulla, are responsible for the adaptation of the body to acute environmental stressors. These hormones increase heart rate and regulate blood pressure. They are also involved in tissue metabolism ( metabolism), through inhibition of insulin release ( a hormone that regulates blood glucose levels) from the pancreas, activation of lipolysis ( fat breakdown) in adipose tissue and breakdown of glycogen in the liver.

Causes of Addison's Disease

Addison's disease is an endocrine disease that occurs as a result of the destruction of the tissues of the adrenal cortex under the influence of certain harmful factors. In another way, this disease is also called primary hypocorticism ( or primary adrenal insufficiency). This pathology is enough rare disease and is statistically found in only 50 to 100 new cases per 1 million adults per year. Primary hypocorticism occurs much more often than secondary.

Secondary adrenal insufficiency is a separate endocrine disease and does not belong to Addison's disease, as it appears as a result of a violation of the secretion of adrenocorticotropic hormone by the pituitary gland ( ACTH), which serves as a natural stimulant for the functioning of the adrenal cortex. This hormone controls the production and secretion of hormones ( mainly glucocorticosteroids and androgens) adrenal cortex. In conditions of ACTH deficiency, bundle ( average) and mesh ( internal) zones of the adrenal cortex undergo gradual atrophy, which leads to adrenal insufficiency, but already secondary ( since the root cause of the disease is not in the adrenal glands themselves).

In Addison's disease, all three areas of the cortex are affected at once ( cortex) adrenal glands - glomerular, fascicular and reticular, therefore, it is believed that primary hypocorticism is clinically more severe than secondary. It should also be noted that all the symptoms that occur in a patient with Addison's disease are associated only with the destruction of the adrenal cortex, and not their medulla, the possible destruction of which ( depending on the cause of primary hypocorticism) does not play any role in the mechanism of development of this pathology. As mentioned a little above, Addison's disease occurs as a result of the action of certain damaging factors on the adrenal cortex. They can be various microorganisms ( bacteria, fungi, viruses), autoimmune processes, neoplasms ( tumor or metastatic lesion of the adrenal glands), genetic disorders ( e.g. adrenoleukodystrophy), impaired blood supply to the adrenal cortex ( DIC, antiphospholipid syndrome).

The most common causes of Addison's disease are:

• autoimmune damage to the tissues of the adrenal cortex;
• adrenalectomy;
• metastatic lesion of the adrenal cortex;
• fungal infections;
• adrenoleukodystrophy;
• antiphospholipid syndrome;
• DIC;
• Waterhouse-Frideriksen syndrome.

Autoimmune damage to the tissues of the adrenal cortex

In the vast majority of all new cases ( in 80 - 90%) Addison's disease occurs as a result of autoimmune destruction of the adrenal cortex. Such destruction appears due to a violation of the normal development of the immune system. cells of the immune system lymphocytes) in such patients upon contact with adrenal tissue ( through the blood) begin to perceive it as alien. Because of this, they are activated and initiate the destruction of the adrenal cortex. An important role in the process of autoimmune destruction is played by autoantibodies secreted into the blood by lymphocytes.

Autoantibodies are antibodies ( protein, protective molecules) directed against their own tissues ( in this case against the tissues of the adrenal cortex), which specifically bind to various structures on the cells of the adrenal cortex and, thereby, cause their death. The main types of autoantibodies observed in the blood of patients with autoimmune Addison's disease are antibodies to adrenal steroidogenesis enzymes ( )-21-hydroxylase ( P450c21), 17a-hydroxylase ( P450c17P450scc).

Tuberculosis

Tuberculosis is an infectious disease caused by mycobacteria ( usually Mycobacterium tuberculosis). Tuberculosis of the adrenal glands is the second most common cause of primary hypocorticism. In the vast majority of cases, this form of tuberculosis is secondary, that is, infection of the tissues of the adrenal cortex occurs already in the presence of a tuberculosis focus in the patient's body, which is located in some other organ ( e.g. lungs, bones, liver, kidneys, etc.). Infection transfer ( harmful mycobacteria) to the adrenal glands from the primary affected organs most often occurs hematogenously ( by blood). Getting inside the adrenal glands, mycobacteria begin to multiply and destroy their normal tissue, while destruction is often noted not only of the cortex, but also of the medulla of these endocrine glands. The first symptoms of Addison's disease, provoked by tuberculosis, begin to occur in a patient only after mycobacteria destroy a significant proportion of the tissues of the adrenal cortex ( about 80 - 90%). That is why it is quite difficult to diagnose this form of the disease in the early stages.

Adrenalectomy

Addison's disease can also occur as a result of bilateral adrenalectomy. An adrenalectomy is surgical removal one or both adrenal glands for medical reasons. Most often, bilateral adrenalectomy is performed in patients with a tumor lesion of both adrenal glands. Removal of two adrenal glands is often carried out in persons suffering from Itsenko-Cushing's disease. In this endocrine disease, pituitary tissues produce adrenocorticotropic hormone in excess ( ACTH), which makes the adrenal cortex work more intensively, which is accompanied by the development of hypercortisolism ( increased secretion of hormones by the adrenal cortex).

Metastatic lesion of the adrenal cortex

In some cases, the adrenal cortex can be affected by tumor metastases. Metastasis is a situation in which tumor cells from a primary cancer site located in one organ are brought into the blood stream ( or, for example, through the lymph) to other organs ( not necessarily adjacent). Having penetrated into secondary organs, malignant cells begin to multiply intensively, which is accompanied by the formation of new ones ( but already secondary - child) tumors, which are called metastases. Metastasis is one of the complications of most malignant neoplasms and is absolutely not typical for benign tumors. Metastases in the adrenal cortex are observed in 57% of cases of breast cancer, in 32% of cases of melanoma ( malignant tumor of pigment cells - melanocytes), in 38% of cases of bronchogenic lung cancer. Also pretty common cause Addison's disease associated with metastatic lesions of the adrenal cortex is non-Hodgkin's large cell lymphoma ( malignant disease of the blood).

Fungal infections

A fungal infection is rarely the cause of Addison's disease. Primary hypocorticism is most often observed with paracoccidioidomycosis, coccidioidomycosis, systemic ( widespread) histoplasmosis, candidiasis, blastomycosis, cryptococcosis. The most common cause of Addison's disease of all the above types of mycoses is paracoccidioidomycosis, caused by fungi of the genus Paracoccidioides Brasiliensis. This type of mycosis is mainly found in the population of Latin America. With paracoccidioidomycosis, the lungs, mucous membrane of the upper respiratory tract, lymph nodes, and in some cases the skin and adrenal glands are affected. In tissues damaged by harmful fungi, granulomas are formed ( inflammatory nodules), microabscesses ( small cavities filled with pus) and areas of focal necrosis ( dead tissue areas).

HIV infection

The patient has HIV infection ( disease resulting from infection with the human immunodeficiency virus) may be the cause of Addison's disease. The fact is that with HIV infection, patients develop a serious immunodeficiency state, in which their body fights hard enough against any infections, as a result of which they often suffer from a variety of infectious diseases. The presence of impaired immunity and frequent systemic infections ( e.g. fungal infections, cytomegalovirus infection and etc.) under certain circumstances can cause primary hypocorticism ( since the presence in the body of any infection, sooner or later, will lead to damage to the tissues of the adrenal cortex). It is believed that in patients with HIV infection latently ( is hidden) ongoing Addison's disease is noted in 8 - 11% of all cases.

Adrenoleukodystrophy

Adrenoleukodystrophy ( ALD) is an inherited disease resulting from a deletion ( removal) a specific region on the long arm of the X chromosome. The ALD gene is localized in this region, which encodes the structure of the enzyme lignoceroyl-CoA synthetase, which is involved in the oxidation of long-chain fatty acids ( JK) in the cells of the central nervous system, adrenal glands and other tissues. With adrenoleukodystrophy, this enzyme is not produced, as a result of which a large amount of fat accumulates in the nervous tissue and in the adrenal cortex ( JFA along with cholesterol esters), which gradually leads to their degeneration and death. This pathology is most often registered in men ( adrenoleukodystrophy is an X-linked recessive disease).

There are various clinical variants of the course of adrenoleukodystrophy, and not always with this disease, the tissues of the adrenal cortex can be seriously affected. For example, in some of these patients, neurological symptoms predominate ( juvenile form of adrenoleukodystrophy), while signs of Addison's disease may be absent for a long time ( especially at the beginning of the disease).

In addition to the adrenal glands and the central nervous system, adrenoleukodystrophy often develops primary male hypogonadism ( testicular failure), which can affect the reproductive capacity of men. Adrenoleukodystrophy is the third leading cause of Addison's disease ( after autoimmune destruction of the adrenal cortex and adrenal tuberculosis). The associated neurological symptoms associated with ALD make the prognosis of Addison's disease less favorable than other causes of primary hypocorticism.

Antiphospholipid Syndrome

antiphospholipid syndrome ( APS) is a pathological condition characterized by a violation of blood clotting and the appearance of blood clots in various vessels. APS is caused by antibodies ( protein, protective molecules) to phospholipids of cell membranes of platelets, endotheliocytes ( cells that line the inner surface of blood vessels). It is believed that the occurrence of such antibodies in the blood of patients is associated with a malfunction of the immune system.

Antiphospholipid antibodies have a direct damaging effect on the endothelium ( inner wall) vessels, inhibit the production of special proteins by endotheliocytes ( prostacyclin, thrombomodulin, antithrombin III) possessing anticoagulant ( anticoagulants) properties, as a result of which they ( antibodies) contribute to the development of thrombosis. In the antiphospholipid syndrome, in very rare cases, bilateral adrenal vein thrombosis can occur, which can cause damage to the tissues of the adrenal cortex ( due to impaired venous outflow from the tissues of the adrenal glands) and the development of Addison's disease.

DIC

The tissues of the adrenal cortex are quite often affected in the syndrome of disseminated intravascular coagulation ( DIC), which is one of the pathologies of the hemostasis system ( system that controls the liquid state of the blood and stops bleeding). At the first stages of DIC, numerous small blood clots form in various tissues and organs ( blood hypercoagulability), which subsequently ( in the later stages of this syndrome) is complicated by consumption coagulopathy ( i.e. exhaustion of the coagulation system), accompanied by a severe violation of blood coagulation and the development of hemorrhagic syndrome ( in various bodies and tissues spontaneous, difficult to stop bleeding occurs).

The causes of DIC can be a variety of conditions, such as severe mechanical trauma, hemolytic anemia ( decrease in the number of red blood cells in the background of their excessive destruction), leukemias, tumors, systemic bacterial, viral, fungal infections, autoimmune diseases, intrauterine fetal death, placental abruption, transfusion incompatible blood etc. In DIC, numerous small thrombi can be found in the vessels of the tissues of the adrenal cortex, which are the direct cause of microcirculation disorders, circulatory disorders, cell death of the glomerular, fascicular and reticular zones and the development of primary adrenal insufficiency ( Addison's disease).

Waterhouse-Frideriksen Syndrome

Waterhouse-Friderichsen syndrome is a pathology resulting from acute hemorrhagic infarction of both adrenal glands ( that is, a massive hemorrhage into the tissues of the adrenal glands) and commonly seen in sepsis ( severe, systemic, inflammatory condition caused by the spread of infection throughout the body from the primary focus). With sepsis, DIC often develops, which, in fact, serves as the direct cause of hemorrhage into the adrenal glands. With such internal bleeding, the tissues of the adrenal glands quickly overflow with blood. The blood flow in them slows down sharply, venous blood from the adrenal glands is not removed, and new arterial blood does not enter in sufficient quantities. Because of this, the cells of the adrenal cortex quickly die. Adrenal insufficiency develops. The rapid overflow of the adrenal glands with blood in the Waterhouse-Friderichsen syndrome is provoked not only by a violation of blood clotting ( caused by DIC), but also by the peculiarities of the blood supply of the adrenal glands themselves.
Most often, Waterhouse-Frideriksen syndrome occurs with sepsis that develops against a background of meningococcal infection.

The pathogenesis of Addison's disease

pathogenesis ( development mechanism) Addison's disease is caused by a deficiency in the body of aldosterone, cortisol and excess secretion of melanocyte-stimulating hormone. Aldosterone is an important hormone that regulates the body's sodium and water levels, the amount of potassium and hemodynamic status. It acts on the kidneys and causes them to retain sodium and water in the body ( in exchange for potassium), thus preventing their rapid removal from the body. With aldosterone deficiency, the kidneys begin to quickly excrete sodium and water in the urine, which leads to rapid dehydration of the body, disruption of the water and electrolyte balance in the body, thickening of the blood, slowing down of blood circulation and blood supply to peripheral tissues. Against the background of these changes, the cardiovascular system is most seriously affected ( increased heart rate, heart pain, decreased blood pressure, etc.), gastrointestinal tract ( abdominal pain, nausea, constipation, vomiting, etc.), central nervous system ( fainting, convulsions, mental disorders occur, headache and etc.). Violation of the excretion of potassium from the body during primary hypocorticism contributes to its accumulation in the blood and the development of the so-called hyperkalemia, which has harmful effect on the work of the heart and skeletal muscles.

The absence of cortisol in the body makes it very sensitive to stress factors for it ( for example, infections, physical overexertion, mechanical injuries, etc.), under the action of which, in fact, the decompensation of Addison's disease occurs.

Cortisol is one of the hormones that regulate carbohydrate metabolism in the body. It stimulates the formation of glucose from other chemicals ( gluconeogenesis), glycolysis ( glycogen breakdown). In addition, cortisol has a similar effect on the kidneys as aldosterone ( that is, it contributes to the retention of water and sodium in the body and the removal of potassium). This hormone also affects protein and fat metabolism, increasing the breakdown of proteins and the accumulation of fats in peripheral tissues. Cortisol interacts well with thyroid hormones and catecholamines, that is, the hormones of the adrenal medulla. Cortisol deficiency in Addison's disease leads to a violation of carbohydrate, protein, fat metabolism and a decrease in overall resistance, that is, the body's resistance to stress.

Patients with Addison's disease often have hyperpigmentation of the skin ( increased deposition of melanin pigment in the skin). It is caused by an excess of melanocyte-stimulating hormone in the blood, which stimulates melanocytes ( pigment cells) skin to the production of melanin. Such an excess occurs due to the fact that during primary hypocorticism in the pituitary gland, the concentration of the precursor common for melanocyte-stimulating and adrenocorticotropic hormones, proopiomelanocortin, increases. Proopiomelanocortin has no hormonal properties. According to its chemical structure, it is a large protein molecule, which, when split ( certain enzymes) is divided into several hormone peptides ( adrenocorticotropic, melanocyte-stimulating, beta-lipotropic hormones, etc.). Increased levels of melanocyte-stimulating hormone in the blood gradually cause darkening of the skin, which is why Addison's disease is also called bronze disease.

Symptoms and signs of Addison's disease

Patients with Addison's disease, when contacting a doctor, most often complain of their general weakness, increased fatigue, chronic fatigue, recurrent headache, dizziness, and fainting. They often experience anxiety, anxiety, increased internal stress. In some patients, neurological and psychiatric disorders can be detected ( memory impairment, decreased motivation, negativism, loss of interest in ongoing events, increased irritability, depression, depression, impoverishment of thinking, etc.). All these symptoms are due to disorders in all types of metabolism ( carbohydrate, protein, lipid, water-electrolyte) in the brain.

In primary hypocorticism, patients experience progressive weight loss. This is due to the constant loss of fluid by the body, the presence of anorexia in them ( lack of appetite) and a true decrease in the amount muscle mass. They often have muscle weakness, myalgia ( muscle pain), muscle cramps, tremors ( ), loss of sensation in the extremities. Muscular symptoms can be explained by disturbances in water and electrolyte balance ( in particular, increased levels of potassium and calcium in the blood) that are commonly seen in these patients.

Quite common in Addison's disease is a variety of gastrointestinal ( gastrointestinal) symptoms in the form of nausea, vomiting, constipation ( sometimes diarrhea), diffuse ( common) abdominal pain. Patients are constantly craving salty foods. In addition, they are constantly worried about the feeling of thirst, so they often drink water. Often such patients for a long time are observed by a gastroenterologist due to the fact that they have various diseases of the gastrointestinal system ( e.g. stomach ulcer, duodenal ulcer, spastic colitis, gastritis), and adrenal insufficiency remains undetected for a long time. Gastrointestinal symptoms in Addison's disease tend to correlate with the degree of anorexia ( lack of appetite) and weight loss.

One of the main symptoms of Addison's disease is hypotension ( low blood pressure). In most patients, systolic blood pressure ranges from 110 to 90 mmHg, and diastolic blood pressure may fall below 70 mmHg. In the initial stages of the disease, hypotension can only be orthostatic in nature ( that is, blood pressure will fall when changing body position from horizontal to vertical). In the future, arterial hypotension begins to occur when the body is exposed to almost any stress factor for a person. In addition to low blood pressure, tachycardia may also occur ( cardiopalmus), pain in the heart, shortness of breath. Sometimes blood pressure may remain within normal limits, in rare cases it may be elevated ( especially in patients with hypertension). In women suffering from Addison's disease, the menstrual cycle is sometimes disturbed. Periods either disappear completely ( i.e. amenorrhea) or become irregular. This often seriously affects their reproductive function and results in various problems associated with pregnancy. In men with this disease, impotence appears ( erectile dysfunction of the penis).

Hyperpigmentation in Addison's disease

Hyperpigmentation ( skin darkening) in Addison's disease is one of the most important symptoms characteristic of this pathology. There is usually a clear correlation ( addiction) between the duration of the presence of adrenal insufficiency in the patient, its severity and the intensity of the color of the skin and mucous membranes, since this symptom occurs in patients one of the first. In most cases, exposed areas of the body that are constantly in contact with sunlight begin to darken first. Most often they are the skin of the hands, face and neck. In addition, there is an increase in pigmentation ( melanin deposits) in the area of ​​those parts of the body that normally have a fairly intense dark color. We are talking about the skin of the scrotum, nipples, perianal zone ( skin around the anus). Then the skin of the folds on the palms begins to darken ( palmar lines), as well as those areas on which folds of clothing constantly rub ( this is observed in the area of ​​the collar, belt, elbow bends, etc.).

In some cases, in some patients, the mucous membrane of the gums, lips, cheeks, soft and hard palate may darken. In later stages, diffuse hyperpigmentation of the skin is noted, which can have a different severity. The skin can acquire a smoky, bronze, brown tint. If Addison's disease is caused by autoimmune destruction of the adrenal cortex, then often against the background of pigmentation on the skin, patients may develop vitiligo ( pigmentless, white patches). Vitiligo can occur almost anywhere on the body and come in a variety of sizes and shapes. It is easy enough to detect, since the skin of such patients is much darker than the spots themselves, which creates a clear contrast between them. Very rarely, skin hyperpigmentation may be absent or minimal in Addison's disease ( inconspicuous), this condition is called "white addisonism". Therefore, the absence of darkening of the skin is not yet proof that this patient does not have adrenal insufficiency.

Diagnosis of Addison's disease

Diagnosis of Addison's disease is currently not a difficult task. The diagnosis of this pathology is made on the basis of clinical ( history taking, physical examination), laboratory and beam methods research. At the first stage of diagnosis, it is important for the doctor to understand whether the symptoms are in fact ( for example, hyperpigmentation of the skin, low blood pressure, general weakness, abdominal pain, nausea, vomiting, impaired menstrual cycle and etc.), detected ( through clinical examinations) in the patient who applied to him, signs of primary adrenal insufficiency. To confirm this, he assigns him the passage of some laboratory tests ( complete blood count and biochemical blood test, urinalysis). These studies should reveal the presence in the patient in the urine and in the blood plasma of a reduced level of adrenal hormones ( aldosterone, cortisol), increased concentration of adrenocorticotropic hormone ( ACTH), renin, as well as a disturbed state of the water-electrolyte state of the blood, carbohydrate metabolism and certain disorders in the cellular composition of the blood.

In addition, in addition to laboratory tests, short-term and long-term diagnostic tests. These tests are stimulation. The patient is injected intramuscularly or intravenously with artificially synthesized adrenocorticotropic hormone ( ACTH), which is produced under the commercial name of synacthen, synacthen-depot or zinc-corticotropin. Normally, when ingested, these drugs should stimulate the adrenal cortex, as a result of which its tissues will begin to intensively secrete hormones ( cortisol), the concentration of which is determined in the blood 30 and 60 minutes after the administration of the drugs. If the patient is ill with Addison's disease, then the adrenal glands will not be able to adequately respond to stimulation with synacthen ( or synacthenom depot, or zinc corticotropin), as a result of which the level of adrenal hormones in the blood plasma will remain unchanged.

After confirming the presence of Addison's disease in a patient, it is important for the doctor to establish its etiology. Because in the vast majority of cases ( in 80 - 90%) the cause of this endocrine disease is an autoimmune lesion of the tissues of the adrenal cortex, then the patient needs to donate blood for an immunological study. With it, it will be possible to detect antibodies to the enzymes of adrenal steroidogenesis ( the formation of steroid hormones)-21-hydroxylase ( P450c21), 17a-hydroxylase ( P450c17), side chain cleavage enzyme ( P450scc), which are markers ( indicators) primary autoimmune hypocorticism. If such antibodies were not detected, then the next diagnostic test to be prescribed is a biochemical blood test for the content of long-chain fatty acids in it ( JK).

Identification of JAD is an important diagnostic sign of adrenoleukodystrophy, which is the third most common cause of Addison's disease. In the case of a negative result for the presence of JFA in the blood, the patient is usually prescribed the passage of radiation studies ( computed tomography, magnetic resonance imaging) needed to visualize the structure of the tissues of the adrenal cortex. These studies, as a rule, confirm the presence of cancer metastases or a tuberculous focus in the adrenal glands.

Diagnostic measures for DIC, Waterhouse-Frideriksen syndrome, antiphospholipid syndrome, fungal infections, HIV infection are quite difficult to consider, since there are many factors that influence the choice of one or another diagnostic method. It all depends on the specific situation. In addition, all these pathologies are quite rare causes of Addison's disease, and it is not always so easy to suspect the presence of adrenal insufficiency in them.

Diagnostic methods used to detect Addison's disease

Method name	Why carry out this study?
Anamnesis	When collecting an anamnesis, the doctor asks the patient about the complaints that bother him and about the conditions that contributed to their appearance. The main symptoms of Addison's disease are fatigue, general weakness, dizziness, headache, fainting, restlessness, anxiety, thirst, craving for salty foods, muscle weakness, myalgia ( muscle pain), muscle cramps, abdominal pain, nausea, vomiting, menstrual irregularities, etc.
Visual inspection	An external examination of patients suffering from Addison's disease can reveal increased skin pigmentation, vitiligo, weight loss, arterial hypotension ( low blood pressure), various mental disorders ( memory impairment, decreased motivation, loss of interest in ongoing events, increased irritability, depression, depression, etc.), tremor ( involuntary trembling of fingers), loss of sensation in the extremities.
Radiography and computed tomography	CT scan ( CT) and magnetic resonance imaging ( MRI) are used to detect metastases, tuberculous foci in the adrenal glands. Radiography is usually prescribed to detect tuberculosis in the lungs. CT and MRI of the brain and spinal cord are prescribed to confirm the diagnosis of adrenoleukodystrophy.
Magnetic resonance imaging
General analysis blood	In Addison's disease, anemia can be detected in the general blood test ( decrease in the number of red blood cells and hemoglobin), lymphocytosis ( an increase in the number of lymphocytes), neutropenia ( decrease in the number of neutrophils), eosinophilia ( an increase in the number of eosinophils), elevated ESR ( sedimentation rate of erythrocytes) .
Blood chemistry	A biochemical blood test can detect hypoglycemia ( low glucose), hyponatremia ( lower sodium levels), hypochloremia ( chlorine reduction), hypercalcemia ( high calcium content), hyperkalemia ( high potassium content), reduced levels of cortisol, aldosterone, increased concentration of adrenocorticotropic hormone ( ACTH), renin. If a doctor suspects adrenoleukodystrophy in a patient as the cause of the development of Addison's disease, then he may also prescribe an analysis for the content of long-chain fatty acids in the blood ( JK).
Immunological blood test	An immunological blood test is ordered to confirm autoimmune genesis ( origin) adrenal insufficiency. In such cases, the patient should be tested for blood levels of antibodies to adrenal steroidogenesis enzymes ( the formation of steroid hormones)-21-hydroxylase ( P450c21), 17a-hydroxylase ( P450c17), side chain cleavage enzyme ( P450scc). Such a study can also detect antibodies to the human immunodeficiency virus ( HIV) and systemic fungal infections, which may be one of the causes of Addison's disease. In addition, immunological analysis is often prescribed for suspected antiphospholipid syndrome, in which anticardiolipin antibodies, antibodies to B-2-glycoprotein 1, and lupus anticoagulant can be detected in blood plasma ( VA).
General and biochemical analysis urine	Urinalysis can reveal an increase in its daily volume, hypostenuria ( decrease in the relative density of urine), elevated sodium, reduced aldosterone, 17-hydroxycorticosteroids ( general content various types glucocorticoids produced in the adrenal cortex), as well as 17-ketosteroids ( androgens produced by the adrenal cortex).
Diagnostic tests	Short-term ( with synacthen) and long ( with synacthen depot or zinc corticotropin) diagnostic tests for Addison's disease reveal a significant decrease in the secretion of hormones by the adrenal cortex during their stimulation.
Biopsy of adrenal tissue	Biopsy ( microsurgical operation aimed at taking a piece of tissue for cytological examination) adrenal tissue is extremely rare. In most cases, it is done to clarify the nature of the damage to the tissues of the adrenal cortex.
General sputum analysis	A general sputum analysis is prescribed in cases where the doctor suspects a tuberculous lesion of the patient's adrenal cortex.

Treatment of Addison's disease

For the treatment of Addison's disease, lifelong drug therapy is prescribed, which allows you to constantly replenish the deficiency of adrenal hormones ( corticosteroids). For this purpose, patients are prescribed hormone replacement drugs, which are of two types. The first type of hormonal preparations includes medicines that correct the balance of mineralocorticoids in the body. The second type of hormone prescribed for Addison's disease includes drugs that increase the level of glucocorticoids in the blood. Both types of hormones must always be combined and used in parallel.
Cortineff is usually prescribed as a replacement mineralocorticoid ( or fludrocortisone). Should be drunk in the morning once a day). Daily dose, as a rule, is selected individually and always ranges from 0.05 to 0.2 mg. The adequacy of the appointment of Cortineff should be constantly under clinical and laboratory control.

Patients receiving medical treatment with this hormonal drug should have normal blood pressure, potassium, sodium, and renin concentrations ( a specific enzyme produced by the kidneys) in blood plasma. In addition, they should not show signs of puffiness ( e.g. swelling in the legs, arms, face), as it will indicate fluid retention in the body, which will serve as an indirect sign of an overdose of Cortineff. The selection of the dosage of this drug during pregnancy is carried out taking into account the level of potassium in the blood and blood pressure. In this case, the dosage often has to be increased, due to the fact that certain hormonal changes occur in the pregnant woman's body.

Replacement mineralocorticoids in Addison's disease should definitely be prescribed in combination with synthetic glucocorticoids. Depending on the duration of their action, the latter are divided into three groups ( short, medium and long acting). Short acting glucocorticoids hydrocortisone, cortisone) can be assigned either two ( morning and afternoon), or three ( morning, afternoon and evening) times a day. Intermediate-acting drugs ( prednisolone) usually need to be consumed twice a day ( morning and afternoon). A third type of glucocorticoid ( dexamethasone), which have a long duration of action and are not excreted from the body for a long time, it is recommended to drink once a day ( morning or late evening). All types of hormonal medications should be used after meals.

Therapeutic regimens for prescribing glucocorticoids for the treatment of Addison's disease

Group of glucocorticoids	Name of the drug	Time of receipt	Dosage
(three-time scheme)	Hydrocortisone	In the morning	15 - 20 mg
		After lunch	5 - 10 mg
		In the evening	5 mg
	Cortisone	In the morning	25 mg
		After lunch	12.5 mg
		In the evening	6.25 mg
Short acting glucocorticoids (two-time scheme)	Hydrocortisone	In the morning	20 mg
		After lunch	10 mg
	Cortisone	In the morning	25 mg
		After lunch	12.5 mg
Intermediate acting glucocorticoids	Prednisolone	In the morning	5 mg
		After lunch	2.5 mg
Long acting glucocorticoids	Dexamethasone	Morning or late evening	0.5 mg

As in the case of mineralocorticoids, for effectiveness drug therapy synthetic glucocorticoids ( hydrocortisone, prednisolone, dexamethasone, cortisone) should also be closely monitored. With proper treatment, the patient should disappear the main signs of Addison's disease - general weakness, fatigue, chronic fatigue, recurrent headaches, dizziness, hunger, arterial hypotension ( reduced blood pressure), hyperpigmentation on the skin, neurological and mental disorders ( memory impairment, decreased motivation, loss of interest in ongoing events, increased irritability, depression, depression, etc.) and etc.

After the start of treatment, body weight usually begins to return immediately, and excessive weight gain should not occur ( this would be a sign of a glucocorticoid overdose). Gastrointestinal ( gastrointestinal) symptoms on the background of hormone replacement therapy with mineralocorticoids and glucocorticoids should also disappear fairly quickly. It should be remembered that hormonal drugs that are prescribed for adrenal insufficiency have a sufficient number of side effects and contraindications, so you must strictly adhere to that course of treatment ( and those dosages of drugs) as prescribed by the doctor.

If it has been determined that Addison's disease was caused by a tuberculosis infection, then the patient should be given additional treatment, which should include antibiotics ( rifampicin, streptomycin, isoniazid, ethambutol, etc.). Antibacterial agents for tuberculosis are prescribed according to special therapeutic regimens and are selected individually. With fungal infection of the adrenal cortex, systemic antifungal drugs are prescribed ( e.g. ketoconazole, fluconazole, etc.). In antiphospholipid syndrome, in addition to hormonal therapy, anticoagulants of indirect action are prescribed ( warfarin, acenocoumarol, etc.) and antiplatelet agents ( aspirin). The choice of treatment tactics for DIC and Waterhouse-Friderichsen syndrome always depends on their etiology, severity and presence of complications. With a metastatic lesion of the adrenal cortex, surgery, as a rule, will not give anything useful to the patient, so he is treated only with hormone replacement therapy.

Mineralocorticoids and glucocorticoids should not be taken in tablet form if the patient has a gastrointestinal disorder. In such cases, it is better to administer the drug as an injection ( parenterally). The fact is that disturbances in the gastrointestinal system can seriously affect the absorption of hormonal drugs into the blood, as a result of which the normal daily dosing regimen will be spoiled. If a patient with Addison's disease needs elective surgery for any reason ( for example, removal of the appendix, gallbladder, hernia, etc.), then on the days before surgery, he should be given a course of hydrocortisone injections of 50 mg every 8 hours. Immediately before the operation, he needs to inject 75 - 100 mg of hydrocortisone intramuscularly. During the operation, he should inject 75 - 100 mg of this drug diluted in a glucose solution.

After surgery, the first four days the patient needs to inject hydrocortisone 50 mg every 6 to 8 hours. On the 5th - 6th day, the dose of hydrocortisone is reduced. At this time, you should enter 50 mg 2 times a day and use prednisone in tablet form, 5-10 mg 2-3 times a day. From 7 to 8 days, the patient is transferred to the usual regimen of therapeutic treatment with glucocorticoids, which should already be taken in full in the form of tablets. The dosage of mineralocorticoids is selected individually. Such a drug therapeutic regimen in the preoperative, operational and postoperative periods is necessary in order to prepare the patient's body for severe stress, which is surgery.

Diet for Addison's disease

The diet for Addison's disease should be aimed at replenishing the deficiency of sodium and fluid in the patient's body, as well as restoring his carbohydrate, protein and fat metabolism. In a day, such patients are shown the use of an increased amount of table salt ( 20 - 25 g) and water. Due to the fact that a significant amount of potassium is retained in their body, they are also recommended to consume less products ( e.g. coffee, tea, cocoa, raisins, spinach, nuts, mushrooms, etc.) rich in this chemical element. In order to restore metabolism ( metabolism) such people need to consume more food rich in vitamins of groups A, B, C, D.
Their diet should have a high energy value, which will soon ( with properly assigned drug treatment ) will help them quickly gain normal weight.

Patients with Addison's disease should consume an increased amount of protein per day ( 1.5 g/kg body weight), carbohydrates ( 450 - 500 g/day) and fats ( 120 - 130 g/day). The diet should be fractional. It is worth eating 4-5 times a day in small portions. The diet must include foods that stimulate appetite and gastrointestinal secretion ( e.g. meat broths, sauces, pickled vegetables, eggs, etc.), which are quite often violated in such patients.

Foods that are indicated and contraindicated in Addison's disease

Examples of Foods to Eat for Addison's Disease

Examples of foods that are not desirable to consume with Addison's disease

broths ( meat and fish); pickled or pickled vegetables; stew or fish; sauces ( meat, fish, vegetable); salted or smoked meat or fish products; eggs ( fried or boiled); canned food ( meat, fish and vegetable); dairy ( milk, butter, cottage cheese, sour cream, feta cheese, cheese, etc.); jam; fruits and berries ( apples, oranges, grapes, pears, strawberries, grapefruit); fruit and vegetable juices; cereals ( semolina, wheat, rice, barley).

beverages ( coffee, tea, cocoa, alcohol, carbonated drinks); raisin; nuts; vegetables ( spinach, Brussels sprouts, kohlrabi, beets); mushrooms; cereals ( buckwheat, oatmeal); peaches; chocolate; dried apricots; legumes ( peas, soybeans, lentils).

What is an Addisonian crisis?

Addisonian crisis ( acute adrenal insufficiency) is a life-threatening condition that can occur with Addison's disease. Addisonian crisis can occur in a patient in various stressful situations ( for example, during surgery, in case of severe mechanical injury, infectious disease, physical overstrain, etc.). Such a crisis is not uncommon in patients who receive inadequate hormone replacement therapy. In addition, acute adrenal insufficiency can occur when Addison's disease has not yet been diagnosed in a patient. Addisonian crisis is characterized by various symptoms. Its main symptoms are indomitable vomiting, nausea, aversion to food, diarrhea, a sharp decline blood pressure, a significant slowdown in the pulse, increased pigmentation on the skin, severe pain in the abdomen, legs, back pain, loss of consciousness, mental and neurological disorders ( lethargy, delirium, convulsions, stupor, hallucinations, etc.) and etc.

If a patient develops an Addisonian crisis, they should be hospitalized immediately. Treatment in such situations is reduced to a massive rehydration ( that is, an intravenous infusion of liquid to the patient), hormonal and etiotropic therapy. Glucose solution is usually used as rehydration solutions. Hormone therapy includes intravenous administration patient with high doses of hydrocortisone ( 100 mg) several times a day. Further, the dose of this drug is gradually reduced. With such high dosages hydrocortisone, the patient does not need to prescribe mineralocorticoids ( cortineff). The latter most often begin to prescribe to the patient at the moment when the daily dosage of glucocorticoids drops below 100 mg / day. When the patient's condition stabilizes, he is smoothly transferred to drugs in tablet form. Etiotropic therapy prescribed for the Addisonian crisis is required to eliminate the very cause that could cause it. In most cases, antibiotics are used as such therapy ( in the event that the Addisonian crisis was caused by an infectious disease).

How does Addison's disease manifest itself in women?

Addison's disease in women manifests itself in the same way as in men. All patients with this pathology have cardiovascular ( decreased blood pressure, palpitations, pain in the heart, shortness of breath), gastrointestinal ( nausea, vomiting, diarrhea, lack of appetite, abdominal pain, craving for salty foods, intense thirst ), dermatological ( vitiligo, hyperpigmentation of the skin) symptoms and signs. In women with Addison's disease, body weight decreases, they periodically feel increased internal tension, fear, anxiety, and anxiety.
They constantly have general weakness, increased fatigue, reduced performance. They often find it difficult to get out of bed in the morning.

In most patients, one can observe a depressed state, lack of initiative, increased irritability, memory impairment, and indifference to what is happening around. They often complain about the presence of muscle weakness, myalgia ( soreness in the muscles), tremor ( involuntary trembling of fingers), violations of the sensitivity of the skin of certain areas on the lower and upper extremities. In women suffering from this disease, some irregularities in the dynamics of the menstrual cycle can sometimes be detected. Menstruation, in some cases, may simply not occur ( i.e. amenorrhea) or be irregular and untimely, which sometimes affects reproductive function and results in problems associated with conceiving a child.

How are Itsenko-Cushing's and Addison's diseases related?

Itsenko-Cushing's disease is an endocrine disease in which the adrenal glands produce excessive amounts of glucocorticosteroids. This condition is also called hypercortisolism. The mechanism of development of this disease is associated with a violation of adequate secretion of adrenocorticotropic hormone by the pituitary gland of the brain ( ACTH), which normally should control the blood levels of glucocorticosteroids secreted by the adrenal cortex. In Itsenko-Cushing's disease, patients have a constant, uncontrolled production of large amounts of ACTH and their release into the blood.

Under conditions of high concentration of adrenocorticotropic hormone in the bloodstream, the adrenal glands begin to function more intensively, which is accompanied by a periodic release of new portions of glucocorticosteroids into the blood ( cortisol). One of the methods for the treatment of Itsenko-Cushing's disease is bilateral adrenalectomy ( removal of both adrenal glands), after which adrenal insufficiency always develops ( Addison's disease).

Is there secondary Addison's disease?

secondary disease Addison is not. In medicine, there is a so-called secondary hypocorticism ( or secondary adrenal insufficiency). Addison's disease primary hypocorticism or primary adrenal insufficiency) occurs when the adrenal cortex is damaged by some harmful factor, as a result of which its cells die and stop synthesizing and secreting hormones into the blood ( mineralocorticoids, glucocorticosteroids and androgens). With secondary hypocorticism, the tissues of the adrenal cortex are not damaged, they remain healthy. With this pathology, the production of adrenocorticotropic hormone (ADH) is disrupted ( ACTH) in the pituitary gland, which is located in the brain. Through this hormone, the pituitary gland regulates the secretion of glucocorticosteroids and androgens into the blood by the adrenal cortex.
Adrenocorticotropic hormone has a direct stimulating effect on fascicular cells ( Where are glucocorticosteroids formed?) and mesh ( where are androgens formed) zones of the adrenal cortex. ACTH has little to no effect on the production of mineralocorticoids by the adrenal glands ( aldosterone).

In secondary hypocorticism, the pituitary gland produces little adrenocorticotropic hormone (ADH). or stop making it altogether.), as a result of which the tissues of the adrenal glands, dependent on this hormone, cease to function normally. This is how secondary adrenal insufficiency develops. Such deficiency differs from Addison's disease not only in pathogenesis ( origin of the disease), but also by clinical symptoms, as well as by some laboratory parameters. These differences are used by doctors in the differential diagnosis of these two pathologies.

Differential diagnosis of primary and secondary hypocorticism

sign	Primary hypocorticism ( Addison's disease)	Secondary hypocorticism
Aldosterone level in the blood	Short	Fine
The level of cortisol in the blood	Short	Short
Adrenocorticotropic hormone level(ACTH)in blood	High	Short
Hyperpigmentation of the skin and mucous membranes	Present	Missing
Arterial hypotension	strongly expressed	Moderate or mild
General weakness	strongly expressed	Moderate or mild
Functional test with synacthen	Negative ( adrenal glands do not respond to stimulus)	Positive ( adrenal glands respond to stimulus)
Gastrointestinal symptoms	strongly expressed	Moderate or mild
Thirst	strongly expressed	None or mild
cravings for salty foods	strongly pronounced	None or mild
Weight loss	strongly pronounced	strongly pronounced