27th May 2025

Aetiology

Anatomic destruction of the adrenal glands can result in acute or chronic PAI:

• Autoimmunity: antibodies formed against 21-hydroxylase.
• Infection: tuberculosis, P. aeruginosa and meningococcal septicaemia, histoplasmosis, HIV, cryptococcosis.
• Surgery: bilateral adrenalectomy e.g. for phaeochromocytoma.
• Haemorrhagic infarction: antiphospholipid syndrome, anticoagulation, Waterhouse-Friderichson syndrome.
• Trauma.
• Infiltrative disease: e.g. amyloidosis, haemochromatosis, sarcoidosis.
• Metastatic: e.g. lung, breast, kidney cancers.

Metabolic failure tends to be more insidious in onset:

• Genetic conditions: e.g. congenital adrenal hyperplasia (described below), adrenoleukodystrophy
• Drug-induced: inhibitors of cortisol production e.g. ketoconazole or etomidate, or inducers of cortisol metabolism e.g. phenytoin, rifampicin.
• ACTH or glucocorticoid resistance.
• Cytotoxic agents.