[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [General pathology](https://durgical.com/en/general-pathology/) › [Endocrine system](https://durgical.com/en/general-pathology/areas/endocrine/) › Adrenocortical insufficiency

# Adrenocortical insufficiency

- Lesion

When the adrenals stop making cortisol and aldosterone, the body cannot handle stress. Without treatment, an adrenal crisis can kill.

Updated Nov 12, 2026

## Key points

- Addison disease: autoimmune adrenalitis is the commonest cause in high-income settings (21-hydroxylase antibodies; APS-1 and APS-2); tuberculosis remains important in endemic regions.
- Other causes: HIV-related infections (CMV, MAC), fungi (histoplasmosis, paracoccidioidomycosis), metastases (lung, breast), amyloid, adrenoleukodystrophy, CAH.
- Primary insufficiency: low cortisol and aldosterone, high ACTH: hyperpigmentation, hyponatraemia, hyperkalaemia, hypotension.
- Secondary insufficiency: low ACTH, aldosterone preserved: no hyperpigmentation, no hyperkalaemia.
- Waterhouse-Friderichsen: bilateral haemorrhagic adrenal necrosis in overwhelming sepsis, classically Neisseria meningitidis, with DIC.
- Abrupt withdrawal of long-term steroids is the commonest cause of acute insufficiency.

## 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](https://durgical.com/en/conditions/adrenal-insufficiency/) | Adrenal cortex | Pituitary or hypothalamus |
| [ACTH](https://durgical.com/en/conditions/hypopituitarism/) | 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.

## Memory aid

Addison's patient is tanned by his own pituitary shouting ACTH; the secondary patient stays pale because the shouting has stopped.

## 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.

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## Elsewhere in DurgiPedia

- [Autoantibodies: the table to know](https://durgical.com/en/immunology/autoantibodies-the-table-to-know/)
- [Cushing syndrome and adrenal insufficiency: the signs](https://durgical.com/en/clinical-exam/cushing-syndrome-and-adrenal-insufficiency-the-signs/)
- [Hemorrhage: petechiae, purpura, ecchymosis, hematoma, and what blood loss does](https://durgical.com/en/general-pathology/hemorrhage-petechiae-purpura-ecchymosis-hematoma-and-what-blood-loss-does/)

## Connections

## Related 5

- [Congenital adrenal hyperplasia](https://durgical.com/en/general-pathology/congenital-adrenal-hyperplasia/)
- [Hypopituitarism and posterior pituitary disorders](https://durgical.com/en/general-pathology/hypopituitarism-and-posterior-pituitary-disorders/)
- [Cushing syndrome: causes and the adrenals](https://durgical.com/en/general-pathology/cushing-syndrome-causes-and-the-adrenals/)
- [Hemorrhage: petechiae, purpura, ecchymosis, hematoma, and what blood loss does](https://durgical.com/en/general-pathology/hemorrhage-petechiae-purpura-ecchymosis-hematoma-and-what-blood-loss-does/)
- [Disseminated intravascular coagulation: how consumption causes both clots and bleeding](https://durgical.com/en/general-pathology/disseminated-intravascular-coagulation-how-consumption-causes-both-clots-and-ble/)

## Related conditions 8

- [Adrenal insufficiency](https://durgical.com/en/conditions/adrenal-insufficiency/)
- [Adrenal crisis](https://durgical.com/en/conditions/adrenal-crisis/)
- [Meningococcal disease (meningococcemia)](https://durgical.com/en/conditions/meningococcal-disease/)
- [Autoimmune polyendocrine syndromes (APS-1, APS-2) and IPEX](https://durgical.com/en/conditions/autoimmune-polyendocrine-syndromes-and-ipex/)
- [Tuberculosis](https://durgical.com/en/conditions/tuberculosis/)
- [HIV infection and AIDS](https://durgical.com/en/conditions/hiv-infection-and-aids/)
- [Hypopituitarism (incl. Sheehan syndrome and pituitary apoplexy)](https://durgical.com/en/conditions/hypopituitarism/)
- [Sepsis and septic shock](https://durgical.com/en/conditions/sepsis-and-septic-shock/)

## Microorganisms 2

- [Neisseria meningitidis](https://durgical.com/en/microbiology/neisseria-meningitidis/)
- [Mycobacterium tuberculosis](https://durgical.com/en/microbiology/mycobacterium-tuberculosis/)

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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](https://www.ncbi.nlm.nih.gov/books/NBK441832/) (StatPearls (NCBI Bookshelf), 2025); [Autoimmune Addison disease](https://medlineplus.gov/genetics/condition/autoimmune-addison-disease/) (MedlinePlus, US National Library of Medicine, 2025).

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Representative model, for educational purposes only.

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Source: https://durgical.com/en/general-pathology/adrenocortical-insufficiency/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/general-pathology/adrenocortical-insufficiency/