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 features

• 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

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

Management

Medical management