Classification of adrenal insufficiency
The disease is classified according to several criteria to precisely determine the level and extent of damage to the neuroendocrine system.
By the level of the primary defect:
- Primary glandular: direct damage to the adrenal tissue itself.
- Centrogenic: the problem lies in the hypothalamo-pituitary system (lack of corticoliberin or ACTH).
- Iatrogenic: a mixed variant, most commonly arising from medical intervention (prolonged steroid therapy).
By origin: congenital and acquired forms are distinguished.
By scale of involvement:
- Total (loss of all organ functions).
- Partial (impairment of only certain hormone production).
Based on this, three main types of Addison's disease are conventionally distinguished: primary (glandular), secondary (centrogenic), and iatrogenic.
Etiology of various forms
Each form has its own specific causes of development.
Primary form is associated with destruction or anomalies of the adrenal cortex:
- Destructive processes: autoimmune aggression (including in combination with lesions of other glands, such as parathyroid glands), tuberculosis, amyloidosis, intoxications, tumors, and metastases.
- Genetic and congenital defects: familial adrenal hypoplasia, adrenoleukodystrophy, cholesterol metabolism enzyme deficiencies, congenital ACTH unresponsiveness.
Secondary form is caused by centrogenic disorders. The pathology is localized in the hypothalamus or pituitary gland. These can include tumors, ischemia, hemorrhages, the effects of radiation therapy to this area, as well as congenital anomalies. The pathogenesis comes down to a deficiency of ACTH and/or CRH.
Iatrogenic form develops as withdrawal syndrome. If a patient has been treated with glucocorticoids for a long time, their own hypothalamo-pituitary-adrenal system becomes suppressed. The adrenal cortex atrophies and loses its function. Abrupt cessation of medication leads to acute insufficiency.
Pathogenesis of main clinical manifestations
The symptoms of Addison's disease are very diverse and affect many body systems.
- Muscle weakness and fatigue (myopathy). Caused by electrolyte imbalance (accumulation of $K^+$ ions and impaired $Ca^{2+}$ transport in muscles), energy starvation of myocytes due hypoglycemia, as well as atrophy and dystrophy of muscle tissue.
- Arterial hypotension. Develops due to a combination of four factors: decreased tone of arteriolar smooth muscle cells (SMCs), a drop in their sensitivity to pressor hormones (catecholamines), decreased myocardial contractility, and reduced circulating blood volume (hypovolemia).
- Hyperpigmentation of the skin and mucous membranes. Characteristic exclusively of the primary form. Due to cortisol deficiency via negative feedback, the adenohypophysis begins to excessively secrete ACTH and melanocyte-stimulating hormone, leading to darkening of the integument.
- Polyuria, hypohydration, and hemoconcentration. Aldosterone deficiency (hypoaldosteronism) disrupts sodium and water reabsorption in the kidneys. This causes increased urination (polyuria), fluid loss by the body (hypohydration), and, consequently, blood thickening (hemoconcentration).
Briefly: answers to topical questions
How does aldosterone deficiency disrupt the water-electrolyte balance?
Aldosterone deficiency leads to the development of hypo-osmolar hypohydration, in which salt loss predominates over water loss. Due to hypoaldosteronism, reabsorption processes in the renal tubules are disrupted, causing the following shifts:
- Polyuria — decreased sodium and fluid reabsorption entails increased diuresis, hypovolemia, and hemoconcentration.
- Hyponatremia — loss of sodium ions in the urine.
- Hyperkalemia — retention of potassium ions in the body due to impaired excretion.
What laboratory markers are used to confirm the diagnosis of Addison's disease?
Laboratory changes in Addison's disease reflect adrenal cortex hormone deficiency and associated metabolic shifts. According to sources:
- Cortisol / corticosteroids — cortisol deficiency or decreased corticosteroid synthesis.
- ACTH — in primary insufficiency, corticotropin secretion increases via negative feedback.
- Glucose — hypoglycemia in cortisol deficiency.
- Electrolytes — hyponatremia; hyperkalemia is indicated in hypoaldosteronism, while one source indicates hypokalemia for aldosterone deficiency.
What clinical manifestations are characteristic of acute adrenal insufficiency (addisonian crisis)?
Acute adrenal insufficiency (adrenal crisis) is characterized by the following main clinical manifestations:
- Acute hypotension — a sharp drop in blood pressure.
- Body hypohydration — dehydration.
- Systemic circulatory failure, leading to collapse and fainting.
To memorize the causes of the secondary form (pituitary pathology), use the rule "I-H-T" (Ischemia, Hemorrhage, Tumors).
Class and exam questions
Why does the skin darken in Addison's disease?
Hyperpigmentation occurs only in the primary form. When the adrenals are damaged, cortisol levels drop, and the pituitary gland (trying to stimulate the adrenals) increases the production of ACTH and melanocyte-stimulating hormone, which causes the darkening.
What is iatrogenic adrenal insufficiency?
This is a form of Addison's disease that occurs upon abrupt withdrawal of glucocorticoids after prolonged treatment. Due to therapy, the adrenal glands atrophy and cannot quickly restore hormone production.
What are the mechanisms of arterial hypotension development in this disease?
Arteriolar tone and their sensitivity to catecholamines decrease, myocardial contractile function drops, and circulating blood volume decreases due to fluid loss (polyuria).
What causes muscle weakness in Addison's disease?
It is caused by electrolyte disturbances (excess potassium, calcium problems), energy deficit (hypoglycemia), and structural changes — atrophy of muscle fibers.
What else to study on this topic
- Disorders of cavitary and membrane digestion in corticosteroid deficiency
- Mechanisms of hypoglycemia development
- Changes in body hair growth in hypocortisolemia
- Differential diagnosis of primary and secondary adrenal insufficiency
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