Adrenocortical insufficiency
- Lesion
When the adrenals stop making cortisol and aldosterone, the body cannot handle stress. Without treatment, an adrenal crisis can kill.
What it is
Adrenal insufficiency can be primary (the cortex itself is destroyed) or secondary (ACTH is lacking). Acute insufficiency follows abrupt steroid withdrawal, crisis in chronic disease, or massive adrenal haemorrhage such as Waterhouse-Friderichsen syndrome in meningococcal sepsis. Chronic primary insufficiency, Addison disease, requires destruction of most of the cortex and is caused mainly by autoimmunity, with tuberculosis, HIV-related infections and metastases as other causes, especially in Latin America.
Structure
- Autoimmune adrenalitis: small, shrunken glands; cortex replaced by lymphocytes and fibrosis; medulla spared.
- Tuberculosis or fungi: caseating or non-caseating granulomas, enlarged then fibrotic glands, sometimes calcified.
- Metastases: enlarged glands replaced by carcinoma.
- Waterhouse-Friderichsen: both glands become haematomas, with haemorrhagic necrosis beginning in the inner cortex.
- Secondary: thin cortex with preserved zona glomerulosa.
Primary vs secondary adrenal insufficiency
| Feature | Primary (Addison) | Secondary |
|---|---|---|
| Site of failure | Adrenal cortex | Pituitary or hypothalamus |
| ACTH | High | Low |
| Aldosterone | Low | Normal (renin-angiotensin driven) |
| Skin | Hyperpigmentation (POMC, MSH) | Pale |
| Potassium | High | Normal |
| Typical cause | Autoimmune, tuberculosis | Steroid withdrawal, pituitary disease |
Clinical notes
- Fatigue, weight loss, anorexia, nausea, salt craving, postural hypotension and hypoglycaemia.
- Hyperpigmentation of skin creases, scars and mucosa from ACTH and MSH derived from POMC.
- Crisis: shock, vomiting, abdominal pain, fever; treated with hydrocortisone and fluids.
Test yourself
Think of the answer, then tap the question to see it.
Why does primary adrenal insufficiency cause hyperpigmentation?
Low cortisol raises ACTH, which is cleaved from POMC along with MSH; both stimulate melanocytes.
What is Waterhouse-Friderichsen syndrome?
Bilateral haemorrhagic necrosis of the adrenals in overwhelming sepsis, classically meningococcal, with DIC and shock.
Why is hyperkalaemia absent in secondary adrenal insufficiency?
Aldosterone is regulated mainly by renin-angiotensin, not ACTH, so it remains normal.
Elsewhere in DurgiPedia
- Autoantibodies: the table to know
- Cushing syndrome and adrenal insufficiency: the signs
- Hemorrhage: petechiae, purpura, ecchymosis, hematoma, and what blood loss does
Connections
Microorganisms2
Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.
Sources: Adrenal Insufficiency (StatPearls (NCBI Bookshelf), 2025); Autoimmune Addison disease (MedlinePlus, US National Library of Medicine, 2025).
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Representative model, for educational purposes only.