• Incidence: 1.00 cases per 100,000 person-years
  • Peak incidence: 30-40 years
  • Sex ratio: more common in females 2:1
<1 1-5 6+ 16+ 30+ 40+ 50+ 60+ 70+ 80+


Autoimmune destruction of the adrenal glands is the commonest cause of primary hypoadrenalism in the UK, accounting for 80% of cases. This is termed Addison's disease and results in reduced cortisol and aldosterone being produced.

Other causes of hypoadrenalism

Primary causes
  • tuberculosis
  • metastases (e.g. bronchial carcinoma)
  • meningococcal septicaemia (Waterhouse-Friderichsen syndrome)
  • HIV
  • antiphospholipid syndrome

Secondary causes
  • pituitary disorders (e.g. tumours, irradiation, infiltration)

Exogenous glucocorticoid therapy

Clinical features



In a patient with suspected Addison's disease the definite investigation is an ACTH stimulation test (short Synacthen test). Plasma cortisol is measured before and 30 minutes after giving Synacthen 250ug IM. Adrenal autoantibodies such as anti-21-hydroxylase may also be demonstrated.

If an ACTH stimulation test is not readily available (e.g. in primary care) then sending a 9 am serum cortisol can be useful:
  • > 500 nmol/l makes Addison's very unlikely
  • < 100 nmol/l is definitely abnormal
  • 100-500 nmol/l should prompt a ACTH stimulation test to be performed

Associated electrolyte abnormalities are seen in around one-third of undiagnosed patients:


Patients who have Addison's disease are usually given both glucocorticoid and mineralocorticoid replacement therapy.

This usually means that patients take a combination of:
  • hydrocortisone: usually given in 2 or 3 divided doses. Patients typically require 20-30 mg per day, with the majority given in the morning dose
  • fludrocortisone

Patient education is important:
  • emphasise the importance of not missing glucocorticoid doses
  • consider MedicAlert bracelets and steroid cards
  • discuss how to adjust the glucocorticoid dose during an intercurrent illness (see below)

Management of intercurrent illness
  • in simple terms the glucocorticoid dose should be doubled
  • the Addison's Clinical Advisory Panel have produced guidelines detailing particular scenarios