Etiology and classification
Depending on the level at which the failure occurred and the cause that triggered it, the disease is divided into two broad groups:
- Primary insufficiency. Develops upon direct destruction of adrenal tissue. This outcome can be caused by infections (particularly tuberculosis), storage diseases (hemochromatosis, amyloidosis), cancer metastases, and autoimmune primary cortical atrophy.
- Secondary insufficiency (of central origin). Occurs due to disorders in the hypothalamic-pituitary system, leading to a critical decrease in ACTH production. The key diagnostic distinction of the secondary form is that the patient lacks characteristic skin hyperpigmentation.
Clinical symptomatology
The symptom complex of Addison's disease develops against the background of progressive disruption of electrolyte and carbohydrate metabolism. Patients rapidly lose weight and suffer from a pronounced asthenic syndrome—increasing general and muscular weakness.
Dermatological manifestations: In primary lesions, melanoderma develops. Skin on exposed areas (due to insolation) and in places of constant friction from clothing acquires a dark gray, brownish tint. The pathogenesis of this phenomenon is associated with the excessive secretion of ACTH and melanotropins. Due to the structural similarity of these hormone molecules, a potent stimulation of melanin deposition occurs.
Involvement of internal organs and the psyche:
- Cardiovascular system: persistent arterial hypotension develops. The mechanism lies in a decrease in circulating blood volume (CBV), which entails a drop in cardiac output and stroke volume.
- Gastrointestinal tract: typical manifestations of dyspepsia (loss of appetite, nausea, vomiting bouts). Diarrhea develops due to large bowel dysfunction.
- Psychoneurological sphere: increased excitability of the nervous system is noted, which in severe cases can develop into psychoses.
Laboratory and instrumental diagnostics
Pathophysiological changes in lab tests directly reflect the deficiency of specific hormones:
- Carbohydrate metabolism (cortisol deficiency). Hypoglycemia is recorded in patients. Clinically, the drop in blood sugar is accompanied by sudden bouts of weakness, intense hunger, profuse sweating, and tachycardia.
- Electrolyte metabolism (aldosterone deficiency). Hyponatremia and hypokalemia are detected in the blood.
- ECG pattern. Instrumentally, a decrease in the overall voltage of waves, ST-segment depression, and the appearance of a biphasic T wave are registered.
Laboratory criteria are used for definitive confirmation of the diagnosis. Basal morning plasma corticosteroid levels drop below 170 nmol/L. As a confirmatory test, the ACTH stimulation test is used: if 30–60 minutes after hormone administration the cortisol increase remains significantly below normal, this indicates a diminished cortical reserve.
Principles of treatment and course
The disease has a chronic course, but symptoms can sharply worsen under the influence of stress, trauma, or the addition of acute infections.
Therapeutic tactics are based on two principles:
- Pathogenetic therapy. It is the main one and requires lifelong adherence. It consists of replacement therapy with glucocorticoids and mineralocorticoids.
- Etiotropic therapy. Used in cases where it is possible to target the cause of the disease (e.g., specific treatment of tuberculosis infection or surgical removal of a tumor focus).
Briefly: answers to topical questions
Which hormone classes are deficient in chronic adrenocortical insufficiency?
In chronic adrenocortical insufficiency (Addison's disease), a deficiency of the entire spectrum of corticosteroid hormones develops.
As a result of damage to the gland tissue, the following classes are deficient:
- Glucocorticoids
- Mineralocorticoids
- Sex steroid hormones
When the pathological bilateral process involves not only the cortex but also the medulla (e.g., due to ischemia, trauma, or hemorrhage), a deficiency of catecholamines is additionally observed.
What specific changes in blood electrolyte balance are characteristic of Addison's disease?
For Addison's disease / primary adrenal insufficiency, the following changes in electrolyte balance are indicated in the sources:
- Hyponatremia.
- Hypokalemia — specifically indicated in the guidelines on chronic adrenocortical insufficiency in cases of aldosterone deficiency.
- Hyperkalemia — in the section on potassium disorders, primary adrenal insufficiency, including Addison's disease, is listed among the causes of hyperkalemia.
What specific glucocorticoid and mineralocorticoid drugs are used for lifelong replacement therapy?
The main principle of treating adrenal insufficiency is lifelong replacement therapy with glucocorticoid and mineralocorticoid drugs.
Specific drugs mentioned in the sources include:
- Hydrocortisone: oral hydrocortisone preparations are indicated for permanent replacement therapy; hydrocortisone is also named the drug of choice for replacement therapy of adrenal insufficiency in patients receiving mitotane.
- Desoxycorticosterone acetate.
- Fludrocortisone — trade name Cortineff.
To easily remember the difference between the forms: in primary insufficiency, the pituitary gland is healthy and "screams" from a lack of hormones (high ACTH) — the skin darkens. In secondary insufficiency, the pituitary "is silent" (low ACTH) — the skin remains fair.
Class and exam questions
Why does hyperpigmentation appear in Addison's disease?
This is a consequence of primary gland damage, in which, via a negative feedback mechanism, the secretion of ACTH and melanotropins increases sharply. Due to the similar structure of these molecules, they stimulate excessive melanin deposition in the skin.
How does hemodynamics change in this pathology?
Persistent arterial hypotension is noted. It occurs due to a decrease in circulating blood volume, leading to a reduction in stroke and cardiac output.
What is the essence of the ACTH stimulation test?
Synthetic adrenocorticotropic hormone is administered to the patient. If the adrenal cortex is depleted, the expected physiological surge of cortisol does not occur within 30–60 minutes.
What else to study on this topic
- Pathogenetic mechanisms of hypoglycemic attacks in cortisol deficiency
- The relationship between large bowel dysfunction and electrolyte disturbances in the development of diarrhea
- Differential diagnosis of storage diseases leading to adrenal atrophy
- Peculiarities of adjusting replacement therapy doses during periods of acute infection and stress
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