Addison's disease

Question 1

Define Addison’s disease.

Answer 1

Primary adrenal insufficiency.

Affects the adrenal glands, causing decreased production of adrenocortical hormones:
· Cortisol.
· Aldosterone.

Question 2

How much of the adrenal cortex needs to be destroyed to produce adrenal insufficiency?

Answer 2

90%

Question 3

What is the epidemiology of Addison’s?

Answer 3

· Most common in women - 90% of cases.
· Higher rates in developed countries.
· Mostly young people <20.

Question 4

What is the pathophysiology of Addison’s?

Answer 4

1. Decreased production of adrenocortical hormones as a result of either:
   · Destruction of the 3 layers of the adrenal cortex - glomerulosa, fasciculata and reticularis.
   · Disruption of hormone synthesis.
2. Infiltrating diseases such as TB or metastases can also cause destruction of the adrenal medulla.

Question 5

Patients should receive replacement therapy for how long?

Answer 5

For life.

Question 6

What is the aetiology of Addison’s?

Answer 6

Most cases are caused by dysfunction of the autoimmune system with antibodies directed against the adrenal cortex.

These antibodies are specific for autoimmune Addison’s disease.

TB is the most prevalent cause in many countries in which it is endemic.

Less common causes include infectious diseases that lead to adrenal gland destruction:
· Meningococcal infection.
· Systemic fungal infection.
· Opportunistic infection secondary to HIV.
· Metastatic malignancies.
· Drugs.

Question 7

What risk factors can cause Addison’s?

Answer 7

· Female. 
· Adrenocortical antibodies. 
· Adrenal haemorrhage - anti-coagulant use and hypercoagulable states such as meningitis. 
· TB. 
· Metastatic malignancy. 
· Coeliac disease.

Question 8

List the signs and symptoms of Addison’s.

Answer 8

· Fatigue. 
· Anorexia. 
· Weight loss. 
· Hyperpigmentation in mucosa and sun-exposed areas. 
· N&V. 
· Hypotension.

Question 9

What investigations would help diagnose Addison’s?

Answer 9

· U&Es.
· Urea.
· FBC.
· Morning serum cortisol - <83 nanomols/L.
· ACTH stimulation test - - serum cortisol <497 nanomols/L.

Question 10

Would a patient’s urea level be elevated or suppressed?

Answer 10

Elevated.

Question 11

Suggest some differentials.

Answer 11

· Adrenal suppression due to corticosteroid therapy.
· Secondary or tertiary adrenal insufficiency - pituitary or hypothalamic lesions.
· Haemochromotosis.
· Hyperthyroidism.
· Occult malignancy.
· Anorexia.

Question 12

What might a FBC test show?

Answer 12

Anaemia and eosinophilia.

Question 13

What might U&Es show?

Answer 13

Hyponatraemia, hyperkalaemia and rarely hypercalcaemia.

Question 14

What is the treatment option for an adrenal crisis?

Answer 14

1st line - Glucocorticoid and supportive therapy:

· Hydrocortisone sodium succinate IV.

Question 15

What is the treatment option a stable and/or after treatment for acute episode?

Answer 15

1st line - Glucocorticoid plus mineralocorticoid.
· Cortisone or hydrocortisone or prednisolone + fludrocortisone (corticosteroids).

Temporary switch to stress dosing of glucocorticoid.

Question 16

What complications can occur?

Answer 16

· Secondary Cushing’s syndrome - caused by over-replacement of glucocorticoids.
· Osteopenia/Osteoporosis - caused by long-term, excessive glucocorticoid replacement.
· Treatment-related HTN - excessive mineralocorticoid replacement manifests with HTN and hypokalaemia.