Addison's disease (adrenal insufficiency)

Question 1

Define Addison’s disease

Answer 1

• Primary adrenocortical insufficiency.
• Destruction of the adrenal cortex leads to glucocorticoid (cortisol) and mineralocorticoid (aldosterone) deficiency

Question 2

What are the causes of Addison’s disease?

Answer 2

• 80% autoimmune in UK
• TB (commonest cause worldwide)
• Adrenal metastases (eg from lung, breast, renal cancer)

Question 3

What are the symptoms of Addison’s disease?

Answer 3

• Lean, tanned, tired, tearful
• +- weakness, anorexia, dizzy, faints, flu-like myalgias/arthralgias
• Mood: depression, psychosis, low-self esteem
• GI: nausea/ vomiting, abdo pain, diarrhoea/ constipation
• Pigmentated palmar creases & buccal mucosa (↑ACTH cross-reacts with melanin receptors)
• Postural hypotension
• Vitiligo (depigmentation of parts of skin)

Question 4

Outline the investigations and findings in Addison’s disease

Answer 4

• ↓Mineralocorticoids (aldosterone)
  
  • ↓Na⁺ & ↑K⁺
  • Metabolic acidosis
• ↓Glucocorticoids (cortisol)
  
  • Hypoglycaemia
• ↑Ca2⁺
• Oesinophilia

1. Short ACTH Stimulation Test
   
   • ↑ACTH → ↑Cortisol
   • 250ug Tetracosactise IM
     
     • eg Synacthen, a synthetic analogue of ACTH
   • Measure plasma cortisol at 0 & ½ hrs
   • Cortisol >550nmol/L – Addisons excluded
     
     • Steroid drugs affect assays
     • Pregnancy & contraceptive pill↑cortisol due to ↑cortisol-binding globulin
2. Inappropriately high 9am ACTH levels (>300ng/L) – not always the case in 2^ndary causes;
3. 21-Hydroxylase adrenal autoantibodies
   
   • 21-Hydroxylase
   • Cytochrome p450 enzyme
   • Involved in biosynthesis of aldosterone & cortisol
   • +ve autoimmune disease in >80% (UK)
4. Plasma renin & aldosterone (assess mineralocorticoid status)

Imaging

• AXR/ CXR for past TB? Upper zone fibrosis or adrenal calcification
• Adrenal CT for TB? Histoplasma? Metastatic disease?

Question 5

Outline the treatment for Addison’s disease

Answer 5

• Replace steroids: ~15-25mg hydrocortisone daily in 2-3 doses
• Mineralocorticoids to correct postural hypotension, ↓Na+ & ↑K+ (fludrocortisone)
• Poor responce = suspect autoimmune

Question 6

Define secondary adrenal insufficiency

Answer 6

Not addison’s!

• Iatrogenic (long term steroid therapy suppressing HPA axis)
• Others are rare