Adrenal insufficiency is a disease that occurs due to insufficient hormonal secretion of the adrenal cortex (primary) or the hypothalamic–pituitary system regulating them (secondary adrenal insufficiency). It is manifested by characteristic bronze pigmentation of the skin and mucous membranes, severe weakness, vomiting, diarrhea, a tendency to fainting. It leads to a disorder of water-electrolyte metabolism and a violation of cardiac activity. Treatment include elimination of its causes, replacement therapy with corticosteroids, symptomatic therapy.
Meaning
The cortical substance of the adrenal glands produces glucocorticosteroid (cortisol and corticosterone) and mineralocorticoid (aldosterone) hormones that regulate the main types of metabolism in tissues (protein, carbohydrate, water-salt) and adaptive processes of the body. Secretory regulation of the activity of the adrenal cortex is carried out by the pituitary gland and hypothalamus through the secretion of hormones ACTH and corticoliberin.
Disease combines various etiological and pathogenetic variants of hypocorticism – a condition that develops as a result of hypofunction of the adrenal cortex and deficiency of hormones produced by it.
Causes
Primary adrenal insufficiency develops when 85-90% of the adrenal tissue is affected.
In 98% of cases, the cause of primary hypocorticism is idiopathic (autoimmune) atrophy of the cortical layer of the adrenal glands. At the same time, for unknown reasons, autoimmune antibodies to the enzyme 21-hydroxylase are formed in the body, destroying healthy tissues and adrenal cells. Also, 60% of patients with primary idiopathic form of adrenal insufficiency have autoimmune lesions of other organs, more often – autoimmune thyroiditis. Tuberculosis of the adrenal glands occurs in 1-2% of patients and in most cases is combined with pulmonary tuberculosis.
A rare genetic disease – adrenoleukodystrophy is the cause of primary adrenal insufficiency in 1-2% of cases. As a result of a genetic defect of the X chromosome, there is a lack of an enzyme that breaks down fatty acids. The predominant accumulation of fatty acids in the tissues of the nervous system and the adrenal cortex causes their dystrophic changes.
Extremely rarely, coagulopathy, tumor metastases to the adrenal glands (more often from the lung or breast), bilateral adrenal infarction, HIV-associated infections, bilateral removal of the adrenal gland lead to the development of primary adrenal insufficiency.
Predispose to the development of atrophy of the adrenal cortex severe suppurative diseases, syphilis, fungal lesions and amyloidosis of the adrenal glands, malignant tumors, heart defects, the use of certain medications (anticoagulants, steroidogenesis blockers, ketoconazole, chloditan, spironolactone, barbiturates), etc.
Secondary adrenal insufficiency is caused by destructive or tumor processes of the hypothalamic-pituitary region, leading to k violation of corticotropic function, as a result of:
- tumors of the hypothalamus and pituitary gland: craniopharyngiomas, adenomas, etc.;
- vascular diseases: hemorrhages in the hypothalamus or pituitary gland, carotid artery aneurysm;
- granulomatous processes in the hypothalamus or pituitary gland: syphilis, sarcoidosis, granulomatous or autoimmune pituitary;
- destructive traumatic interventions: radiation therapy of the hypothalamus and pituitary gland, surgery, long-term treatment with glucocorticoids, etc.
Primary hypocorticism is accompanied by a decrease in the secretion of hormones of the adrenal cortex (cortisol and aldoaterone), which leads to a violation of metabolism and the balance of water and salts in the body. With aldosterone deficiency, progressive dehydration develops due to the loss of sodium and potassium retention (hyperkalemia) in the body. Water-electrolyte disorders cause disorders of the digestive and cardiovascular systems.
A decrease in cortisol levels reduces glycogen synthesis, leading to the development of hypoglycemia. In conditions of cortisol deficiency, the pituitary gland begins to produce ACTH and melanocytostimulating hormone, which causes increased pigmentation of the skin and mucous membranes. Various physiological stresses (injuries, infections, decompensation of concomitant diseases) cause the progression of primary adrenal insufficiency.
Secondary hypocorticism is characterized only by a deficiency of cortisol (as a result of a lack of ACTH) and the preservation of aldosterone production. Therefore, secondary adrenal insufficiency, in comparison with primary, proceeds relatively easily.
Classification
Insufficiency of the adrenal cortex can be acute and chronic.
An acute form of adrenal insufficiency is manifested by the development of a severe condition – an addisonian crisis, which usually represents a decompensation of the chronic form of the disease. The course of the chronic form of adrenal insufficiency can be compensated, subcompensated or decompensated.
According to the initial violation of hormonal function, chronic adrenal insufficiency is divided into primary and central (secondary and tertiary).
Primary insufficiency of the adrenal cortex (1-NN, primary hypocorticism, Addison’s or bronze disease) develops as a result of bilateral damage to the adrenal glands themselves, occurs in more than 90% of cases, regardless of gender, more often in adulthood and old age.
Secondary and tertiary adrenal insufficiency are much less common and occur due to a lack of secretion of ACTH by the pituitary gland or corticoliberin by the hypothalamus, leading to atrophy of the adrenal cortex.
Symptoms
The leading criterion of primary chronic adrenal insufficiency is hyperpigmentation of the skin and mucous membranes, the intensity of which depends on the prescription and severity of hypocorticism. Initially, the exposed areas of the body exposed to solar irradiation acquire a darker color – the skin of the face, neck, hands, as well as areas that normally have darker pigmentation – areola nipples, external genitalia, scrotum, perineum, axillary areas. A characteristic feature is hyperpigmentation of the palmar folds, noticeable against a background of lighter skin, darkening of skin areas that are more in contact with clothing. The skin color varies from a light shade of tan, bronze, smoky, dirty skin to diffuse dark. Pigmentation of mucous membranes (inner surface of cheeks, tongue, palate, gums, vagina, rectum) of bluish-black color.
Less common is adrenal insufficiency with little pronounced hyperpigmentation – “white addisonism”. Often, against the background of hyperpigmentation areas, patients are found to have pigmented light spots – vitiligo, ranging in size from small to large, irregularly shaped, standing out on darker skin. Vitiligo occurs exclusively in autoimmune primary chronic hypocorticism.
In patients with chronic adrenal insufficiency, body weight decreases from moderate weight loss (by 3-5 kg) to significant hypotrophy (by 15-25 kg). Asthenia, irritability, depression, weakness, lethargy, up to disability, decreased sexual desire are noted. There is orthostatic (with a sharp change in body position) arterial hypotension, fainting states caused by psychological shocks and stress. If the patient had a history of hypertension before the development of adrenal insufficiency, blood pressure may be within the normal range. Digestive disorders almost always develop – nausea, decreased appetite, vomiting, epigastric pain, loose stools or constipation, anorexia.
At the biochemical level, there is a violation of protein (decrease in protein synthesis), carbohydrate (decrease in fasting glucose and a flat sugar curve after glucose loading), water-salt (hyponatremia, hyperkalemia) metabolism. Patients have a pronounced predilection for the use of salty food, up to the use of pure salt, associated with the increasing loss of sodium salts.
Secondary adrenal insufficiency proceeds without hyperpigmentation and the phenomena of aldosterone deficiency (arterial hypotension, salt addiction, dyspepsia). It is characterized by nonspecific symptoms: the phenomena of general weakness and attacks of hypoglycemia, developing a few hours after eating.
Complications
The most threatening complication of chronic hypocorticism with untreated or improper treatment is an adrenal (addisonic) crisis – a sharp decompensation of chronic adrenal insufficiency with the development of a comatose state. Addison’s crisis is characterized by the sharpest weakness (up to a state of prostration), a drop in blood pressure (up to collapse and loss of consciousness), indomitable vomiting and loose stools with a rapid increase in dehydration, the smell of acetone from the mouth, clonic convulsions, heart failure, even greater pigmentation of the skin.
Acute adrenal insufficiency (addison’s crisis) according to the predominance of symptoms can occur in three clinical forms:
- cardiovascular, in which circulatory disorders dominate: pallor of the skin, acrocyanosis, cold extremities, tachycardia, arterial hypotension, thready pulse, collapse, anuria;
- gastrointestinal, similar in symptoms to signs of food toxicoinfection or acute abdominal clinic. There are spastic abdominal pains, nausea with indomitable vomiting, loose stools with blood, flatulence.
- neuropsychiatric, with a predominance of headache, meningeal symptoms, seizures, focal symptoms, delirium, lethargy, stupor.
- Addison’s crisis is difficult to stop and can cause the death of the patient.
Diagnostics
Diagnosis of adrenal insufficiency begins with an assessment of anamnesis, complaints, physical data, finding out the cause of hypocorticism. Ultrasound of the adrenal glands is performed. Primary adrenal insufficiency of tuberculous genesis is indicated by the presence of calcifications or foci of tuberculosis in the adrenal glands; with the autoimmune nature of hypocorticism, autoantibodies to the adrenal antigen21-hydroxylase are present in the blood. Additionally, an MRI or CT scan of the adrenal glands may be required to identify the causes of primary adrenal insufficiency. In order to establish the causes of secondary insufficiency of the adrenal cortex, CT and MRI of the brain.
With primary and secondary adrenal insufficiency, there is a decrease in cortisol in the blood and a decrease in the daily release of free cortisol and 17-OXO in the urine. Primary hypocorticism is characterized by an increase in the concentration of ACTH, while secondary hypocorticism is characterized by its decrease. In case of questionable data for adrenal insufficiency, a stimulation test with ACTH is performed, determining the cortisol content in the blood half an hour and an hour after the introduction of adrenocorticotropic hormone. An increase in cortisol levels by less than 550 nmol/l (20 mcg/dl) indicates adrenal insufficiency.
To confirm the secondary insufficiency of the adrenal cortex, a test of insulin hypoglycemia is used, which normally causes a significant release of ACTH and a subsequent increase in cortisol secretion. With primary adrenal insufficiency, hyponatremia, hyperkalemia, lymphocytosis, eosinophilia and leukopenia are detected in the blood.
Treatment
Modern endocrinology has effective methods of treating adrenal insufficiency. The choice of treatment method depends primarily on the cause of the disease and pursues two goals: elimination of the cause of adrenal insufficiency and replacement of hormonal deficiency.
Elimination of the cause of adrenal insufficiency includes drug treatment of tuberculosis, fungal diseases, syphilis; antitumor radiation therapy on the hypothalamus and pituitary gland; surgical removal of tumors, aneurysms. However, in the presence of irreversible processes in the adrenal glands, hypocorticism persists and requires lifelong replacement therapy with hormones of the adrenal cortex.
Treatment of primary adrenal insufficiency is carried out with glucocorticoid and mineralocorticoid preparations. With mild manifestations of hypocorticism, cortisone or hydrocortisone are prescribed, with more pronounced – a combination of prednisone, cortisone acetate or hydrocortisone with mineralocorticoids (deoxycorticosterone trimethyl acetate, DOXA – deoxycorticosterone acetate). The effectiveness of therapy is assessed by indicators of blood pressure, gradual regression of hyperpigmentation, weight gain, improvement of well-being, disappearance of dyspepsia, anorexia, muscle weakness, etc.
Hormone therapy in patients with secondary adrenal insufficiency is carried out only with glucocorticoids, because the secretion of aldosterone is preserved. With various stressful factors (injuries, operations, infections, etc.), corticosteroid doses are increased 3-5 times, during pregnancy, a slight increase in the dose of hormones is possible only in the second trimester.
The appointment of anabolic steroids (nandrolone) for chronic adrenal insufficiency is indicated for both men and women in courses up to 3 times a year. Patients with hypocorticism are recommended to follow a diet enriched with protein, carbohydrates, fats, sodium salts, vitamins B and C, but with a restriction of potassium salts. For the relief of addison’s crisis phenomena,:
- rehydration therapy with isotonic NaCl solution in a volume of 1.5-2.5 liters per day in combination with 20% glucose;
- intravenous replacement therapy with hydrocortisone or prednisone with a gradual dose reduction as the phenomena of acute adrenal insufficiency subside;
- symptomatic therapy of diseases that led to decompensation of chronic adrenal insufficiency (more often antibacterial therapy of infections).
Prognosis and prevention
In case of timely appointment of adequate hormone replacement therapy, the course of adrenal insufficiency is relatively favorable. The prognosis in patients with chronic hypocorticism is largely determined by the prevention and treatment of adrenal crises. With concomitant infections, injuries, surgical operations, stress, gastrointestinal disorders, an immediate increase in the dose of the prescribed hormone is necessary.
It is necessary to actively identify and register patients with adrenal insufficiency and at-risk individuals (long-term corticosteroids for various chronic diseases) with an endocrinologist.