Definition
Hypocorticism refers to adrenal insufficiency, which may be:
- Primary: Direct destruction or dysfunction of the adrenal cortex (→ Addison disease).
- Secondary: Due to hypothalamic-pituitary axis dysfunction leading to decreased ACTH.
Etiology
Primary (Addison disease):
- Autoimmune adrenalitis – Most common cause in developed countries.
- Tuberculosis – Most common in developing countries.
- Other causes:
- Bilateral adrenal hemorrhage (e.g., Waterhouse–Friderichsen syndrome)
- Infiltrative diseases (e.g., amyloidosis, hemochromatosis)
- Metastatic cancer
- Surgical removal of adrenal glands
- Fungal infections (e.g., histoplasmosis)
- Cytomegalovirus (especially in immunosuppressed)
Secondary:
- Sudden withdrawal of long-term glucocorticoid therapy
- Hypopituitarism
- Pituitary gland surgery or radiation
Pathogenesis
- Destruction of adrenal cortex → ↓ cortisol, aldosterone, and adrenal androgens.
- ↓ Cortisol → loss of negative feedback → ↑ ACTH.
- ↑ ACTH has melanocyte-stimulating hormone (MSH) activity → skin hyperpigmentation.
- ↓ Aldosterone → ↓ sodium and water retention, ↑ potassium → hypovolemia and hyperkalemia.
- ↓ Cortisol and aldosterone contribute to poor stress tolerance → risk of adrenal crisis.
Symptoms
Symptoms usually appear after ≥90% adrenal cortex is destroyed.
Glucocorticoid deficiency: cortisol (zona fasciculata)
- Fatigue, weakness
- Hypoglycemia
- Anorexia, nausea, vomiting, weight loss
- Poor stress tolerance
- Fever
Mineralocorticoid deficiency:
- Hyponatremia, hyperkalemia, hypotension
- Dehydration, dizziness, orthostatic hypotension
- Decreased cardiac output, salt craving
Adrenal androgen deficiency (only relevant in females):
- Loss of axillary and pubic hair
- Decreased libido
Hyperpigmentation (specific to primary only):
- "Suntanned" skin, especially at pressure points (elbows, knuckles)
- Darkened oral mucosa and gums