Primary Adrenal Insufficiency (Addison Disease)

Decreased production of adrenocortical hormones (glucocorticoids, mineralocorticoids, and adrenal androgens)

Aetiology

  • Involves destruction of the entire adrenal cortex
  • Autoimmune adrenalitis is the most common cause, accounting for ~80-90% of all cases of primary adrenal insufficiency
    • May be part of wider autoimmune syndromes e.g. autoimmune polyglandular syndrome (APS)
    • Associated with other autoimmune diseases - T1DM, autoimmune thyroid disease, pernicious anaemia
  • Infectious adrenalitis - TB, CMV disease, HIV
  • Metastatic malignancy - lung, breast
  • Adrenal haemorrhage
    • Septicaemic infection - Waterhouse-Friderichsen syndrome
    • Disseminated intravascular coagulation (DIC)
    • Anticoagulation treatment

Pathophysiology

  • Decreased mineralocorticoids
    • K+ retention, Na+ loss
    • Hyperkalaemia, hyponatraemia, volume depletion and hypertension
  • Decreased glucocorticoids → hypoglycaemia
  • Excess pigmentation reflects excess ACTH from pituitary
    • ACTH molecule contains sequence for MSH within it
    • ACTH is degraded by proteases eventually exposing MSH

Clinical presentation

  • Signs and symptoms occur once >90% of the gland has been destroyed
  • Vague symptoms - weakness, fatigue, anorexia, N+V, weight loss, diarrhoea, dizziness and low BP, abdominal pain
  • Skin pigmentation (raised POMC) - not seen in hypopituitarism
    • Look 'tanned', as well as black spots in buccal mucosa, dark palmar creases and dark finger spaces

Investigations

  • Adrenal autoantibodies positive in 70%
  • Biochemistry - ↓ Na+, ↑ K+, may be hypoglycaemia (especially in paediatrics)
  • Short synacthen test/Cosyntropin test
    • Measure plasma control before and 30 mins after IV/IM ACTH injection
    • Normal: baseline >250 nmol/L, post ACTH >550 nmol/L
  • ACTH levels very high (results in skin pigmentation)
  • Renin/aldosterone levels - ↑↑ renin, ↓ decreased aldosterone
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Management

Pharmacological management

  • Hydrocortisone as cortisol replacement
    • If unwell IV first
    • Usually 15-30mg PO daily in divided doses
    • Try and mimic diurnal rhyrhm (higher dose in morning)
  • Fludrocortisone as aldosterone replacement
    • Careful monitoring of BP and K+

Education

  • 'Sick day rules' - increase steroid replacement when unwell or undergoing other stress e.g. preoperative
  • Cannot stop suddenly or risk adrenal crisis
  • Need to carry identification - emergency steroid card, alert to long term steroid treatment bracelet
  • There are rules for medical professionals regarding steriod management for interventions/surgery (usually require increased dose)