65. Chronic adrenal insufficiency - etiology, pathogenesis, clinical manifestations.

Chronic adrenal insufficiency – etiology, pathogenesis, and clinical manifestations.

Chronic adrenal insufficiency refers to a gradual, progressive loss of adrenal cortex function, leading to deficiency of glucocorticoids (cortisol), mineralocorticoids (aldosterone), and sometimes androgens.

Etiology

1. 1 Primary adrenal insufficiency (Addison's disease)

Autoimmune adrenalitis (most common in developed countries).

• Often part of autoimmune polyendocrine syndrome (APS type 1 or 2).

Infectious destruction:

• Tuberculosis (important worldwide).
• Fungal infections (histoplasmosis).

Metastatic cancer to adrenals (e.g., lung, breast).

Bilateral adrenal hemorrhage (e.g., antiphospholipid syndrome).

Genetic disorders (congenital adrenal hyperplasia, adrenoleukodystrophy).

1. 2 Secondary adrenal insufficiency

Pituitary disease → decreased ACTH production.

Causes: pituitary tumors, Sheehan syndrome, pituitary surgery or radiation.

1. 3 Tertiary adrenal insufficiency

Hypothalamic dysfunction → decreased CRH.

Often from chronic exogenous steroid therapy → suppression of hypothalamic- pituitary- adrenal (HPA) axis.

Pathogenesis

Primary adrenal insufficiency

1. Destruction of adrenal cortex → ↓ cortisol and ↓ aldosterone.
2. ↓ Cortisol → impaired stress response, hypoglycemia, increased ACTH (loss of negative feedback).
3. ↑ ACTH → hyperpigmentation (due to melanocyte-stimulating hormone activity).
4. ↓ Aldosterone → sodium loss, volume depletion → hypotension, hyperkalemia, hyponatremia.

Secondary and tertiary insufficiency

• Only cortisol deficiency (aldosterone production is typically normal because it is controlled mainly by renin-angiotensin system).
• No hyperpigmentation (ACTH not elevated).

Clinical manifestations

General symptoms

• Fatigue, weakness.
• Anorexia, weight loss.

Gastrointestinal

• Nausea, vomiting.
• Abdominal pain.
• Salt craving (due to hyponatremia).

Cardiovascular

• Hypotension (postural/orthostatic hypotension).

Electrolyte disturbances

• Hyponatremia.
• Hyperkalemia (primary only).
• Hypoglycemia.

Skin

• Hyperpigmentation (primary only).
• Most prominent in sun-exposed areas, pressure points (elbows, knees), palmar creases, buccal mucosa.

Reproductive

• In women: loss of axillary and pubic hair (due to androgen deficiency).

Summary Table