Addison's disease

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Primary hypoadrenalism


Destruction of the adrenal cortex with reduced secretion of glucocorticoid, mineralocorticoid and sex steroids. Differentiated from hypothalamic-pituitary suppression when mineralocorticoid and sex steroid secretion remains largely unchanged. Destruction of the adrenal medulla is interestingly clinically silent.


This is rare with an incidence of 3-4 per million per year. There is a marked female:male preponderance, most cases caused by auto-immune disorder. Associated with other autoimmune conditions such as diabetes mellitus, pernicious anaemia, thyroiditis. Other causes are infection, Tuberculosis was once a common cause.


  • Can present in 1001 ways - have a very low threshold for doing a short synACTHen test
  • Weight loss
  • Anorexia
  • Malaise
  • Weakness
  • Fever
  • Depression
  • Impotence/amenorrhoea
  • Nausea & vomiting
  • Diarrhoea
  • Confusion
  • Abdominal pain
  • Constipation


  • Hypotension
  • Weight loss
  • Wasting
  • Dehydration
  • Loss of body hair

Differential diagnosis


  • U&E : hyponatraemaia, hyperkalaemia, but may be normal
  • Blood sugar: may be low
  • Short synaACTHen (synthetic ACTH) stimulation test: ACTH 250mg im stat, plasma cortisol 30 min later: Normal cortisol >600nmol/l
  • Autoantibodies to 21-hydroxylase


  • Corticosteroids.
    • The precise regime has evolved to mimic diurnal physiological function but oral regimes do not provide normal quality of life. They may need to take into account enzyme induction in situations such as secondary disease from active tuberculosis. Quality of life in adults has been maximised with a regime of 20 mg hydrocortisone at 0700 hrs and 10 mg at 1900 hrs[1][2] and triple dosing regimes have been tried[3]. Recently it has been reported that continuous s.c. hydrocortisone infusion is more physiological[4].
  • Mineralocorticoids
    • Often not necessary.


Described in 18th century by Thomas Addison.[5]