Addison's Disease

Question 1

What causes primary adrenocortical insufficiency?

Answer 1

• Destruction of the adrenal cortex (glucocorticoid and mineralcorticoid deficiency) by:
  1. Autoimmunity (80%)
  2. TB
  3. Adrenal metastases (lung, breast, renal cancer)
  4. Lymphoma
  5. Opportunistic HIV infection
  6. Adrenal haemorrhage

Question 2

What is the cause of secondary adrenal insufficiency?

Answer 2

1. Long term steroid use suppressing the HPAA axis, only becomes apparent when the steroids are withdrawn
   Other rare causes:
2. Pituitary disease causing low ACTH. No pigmentation as low ACTH and mineralcorticoid production is fine

Question 3

What are the symptoms of adrenal insuffiency?

Answer 3

• Lean, tanned, tired, tearful and weak
• Mood: Depressed, psychosis
• GI: Nausea, vomiting, abdominal pain, diarrhoea, constipation
• Postural hypotension
• Hyperpigmentation (on palmar creases and buccal mucosa)
• Vitiligo

Question 4

Why do you get hyperpigmentation in adrenal insufficiency?

Answer 4

• Decreased cortisol so negative feedback on anterior pituitary is reduced
• More POMC required to synthesise ACTH
• Fragments of this in post translational processing produce MSH which stimulate melanocytes
• ACTH also cross reacts with melanin receptors

Question 5

How would you investigate adrenal insufficiency?

Answer 5

1. U+E - Raised K+ and low Na+, uraemia, raised Ca2+
2. Low blood glucose
3. FBC - Anaemia, eosinophilia
4. SynACTHen test - Addison’s excluded if cortisol rises >550nmol/L
5. 21-hydroxylase adrenal autoantibodies - Positive in autoimmune disease
6. CXR - Finds TB

Question 6

How does ACTH results differ in primary and secondary causes of adrenal insufficiency?

Answer 6

Primary - 9AM ACTH is inappropriately high

Secondary - Low

Question 7

How can you assess mineralcorticoid status in patients with Addison’s?

Answer 7

• Plasma renin and aldosterone

Question 8

What is the treatment for adrenal insufficiency?

Answer 8

1. Replacement of steroids
   - Hydrocortisone daily in 2-3 doses
   - Don’t give late as can cause insomnia
2. Mineralcorticoids to correct postural hypotension
3. Fludrocortisone corrects electrolyte abnormalities (low Na+, high K+)

Question 9

What counselling should you give on steroid use?

Answer 9

• Wear a bracelet to declare steroid use
• Add hydrocortisone 5-10mg before strenuous exercise or activity
• Double steroids in febrile illness, injury or stress
• Don’t suddenly stop the steroids