Classification of Adrenal Insufficiency
The condition is classified by several criteria to precisely determine the level and scope of neuroendocrine system involvement.
By the level of the primary defect:
- Primary glandular: direct damage to the adrenal tissue itself.
- Centrogenic: the problem lies in the hypothalamic-pituitary system (lack of corticotropin-releasing hormone 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 specific hormone synthesis only).
Based on this, Addison's disease is traditionally divided into three main types: primary (glandular), secondary (centrogenic), and iatrogenic.
Etiology of Various Forms
Each form has specific developmental causes.
Primary form is associated with destruction or anomalies of the adrenal cortex:
- Destructive processes: autoimmune aggression (including in combination with involvement of other glands such as the parathyroids), tuberculosis, amyloidosis, intoxications, tumors, and metastases.
- Genetic and congenital defects: familial cortical hypoplasia, adrenoleukodystrophy, cholesterol metabolism enzyme deficiency, congenital ACTH unresponsiveness.
Secondary form is caused by centrogenic disorders. The pathology is localized in the hypothalamus or pituitary gland. Causes include tumors, ischemia, hemorrhages, the consequences 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 hypothalamic-pituitary-adrenal axis becomes suppressed. The adrenal cortex atrophies and loses its function. Abrupt cessation of medications leads to acute insufficiency.
Pathogenesis of Main Clinical Manifestations
The symptoms of Addison's disease are diverse and affect many body systems.
- Muscle weakness and fatigue (myopathy). Caused by electrolyte imbalance ($K^+$ ion accumulation and impaired $Ca^{2+}$ transport in muscles), energy starvation of myocytes due to hypoglycemia, as well as muscle atrophy and dystrophy.
- Arterial hypotension. Develops due to a combination of four factors: decreased tone of arteriolar smooth muscle cells, loss of sensitivity to pressor hormones (catecholamines), decreased myocardial contractility, and reduced circulating blood volume (hypovolemia).
- Skin and mucous membrane hyperpigmentation. Characteristic exclusively of the primary form. Due to cortisol deficiency and negative feedback, the adenohypophysis excessively secretes ACTH and melanocyte-stimulating hormone, leading to skin darkening.
- Polyuria, dehydration, and hemoconcentration. Aldosterone deficiency (hypoaldosteronism) impairs renal sodium and water reabsorption. This causes increased urination (polyuria), fluid loss (dehydration), and subsequent blood thickening (hemoconcentration).