Addison's disease (E&M)

Question 1

What is Addison’s disease?

Answer 1

Primary adrenal insufficiency - destruction of adrenal cortex –> decreased production of adrenocortical hormones - glucocorticoids (cortisol) and mineralocorticoids (aldosterone)

Question 2

What are the main steroids that are deficient in Addison’s disease? (3)

Answer 2

• cortisol
• aldosterone
• dehydroepiandrosterone (DHEA) + sulfated conjugate (DHEA-S)

Question 3

What is Addison’s disease the commonest cause of?

Answer 3

Adrenocortical failure in the UK

Question 4

What are the main causes of Addison’s disease? (3+3)

Answer 4

• autoimmune (more developed countries)
• tuberculosis (more common worldwide)
• metastases
• (meningococcal septicaemia –> Waterhouse-Friderichsen syndrome)
• (HIV)
• (antiphospholipid syndrome)

Question 5

What are some risk factors for Addison’s disease? (8)

Answer 5

• female sex
• adrenocortical antibodies
• adrenal haemorrhage
• autoimmune diseases
• coeliac disease
• TB/non-TB infection
• sarcoidosis
• anticoagulant use

Question 6

What is an Addisonian crisis?

Answer 6

A sudden worsening of symptoms and drop in cortisol levels, caused by:

• sudden withdrawal of steroids if patient on long-term steroids
• sepsis
• surgery

Question 7

What are the clinical features of Addison’s disease? (7)

Answer 7

• fatigue
• anorexia
• weight loss
• hyperpigmentation (low cortisol = increased ACTH –> increased POMC –> increased a-MSH)
• nausea, vomiting, abdominal pain
• postural hypotension
• hypoglycaemia –> dizziness

Question 8

What might you see on examination in Addison’s disease? (2)

Answer 8

• hyperpigmentation - exaggerated over pressure points on elbows, area of buccal hyperpigmentation where teeth pinch mucous membrane while chewing
• hypotension (can be postural)

Question 9

Why does hyperpigmentation occur in Addison’s disease?

Answer 9

Low cortisol –> negative feedback increases ACTH –> increased POMC –> increased alpha-MSH

Question 10

What are the features of an Addisonian crisis? (2)

Answer 10

Severe hypovolaemia and hyponatraemia

Question 11

What are the first-line investigations for Addison’s disease?

Answer 11

• ACTH stimulation test (short synACTHen test)
• morning serum cortisol
• plasma ACTH
• serum electrolytes
• U&Es

Question 12

What is the definite investigation done in Addison’s disease?

Answer 12

ACTH stimulation test (short synACTHen test):

• plasma cortisol measured before and 30min after giving Synacthen 250mg IM
• Synacthen should stimulate cortisol secretion but does not happen in Addison’s disease
• serum cortisol <550nmol/L indicates adrenal failure

Question 13

When do we do morning serum cortisol for Addison’s disease?

Answer 13

• done if short Synacthen test is unavailable e.g. in primary care
• 9am blood test (cortisol peaks in morning) - if low, suspect Addison’s disease
• > 500nmol/L = very unlikely
• 100-500nmol/L = prompt ACTH stimulation test
• <100nmol/L = definitely abnormal

Question 14

What electrolyte abnormalities might be seen in Addison’s disease (1/3 undiagnosed patients)? (3)

Answer 14

• hyperkalaemia
• hyponatraemia
• hypoglycaemia

Question 15

What might we see on ABG in Addison’s disease?

Answer 15

Metabolic acidosis with normal anion gap

Anion gap = (Na + K) - (HCO3 + Cl)
Normal = 8-14mmol/L

Question 16

What do we look for in FBC in Addison’s disease?

Answer 16

Anaemia and eosinophilia in some

Question 17

What are some differential diagnoses for Addison’s disease? (7)

Answer 17

• adrenal suppression due to corticosteroid therapy (low ACTH due to suppression)
• secondary/tertiary adrenal insufficiency (pituitary/brain lesion, low ACTH and other pituitary hormones)
• haemochromatosis
• hyperthyroidism
• occult malignancy
• anorexia nervosa
• SIADH

Question 18

How do we manage stable patients with Addison’s disease?

Answer 18

Lifelong glucocorticoid + mineralocorticoid replacement:
Hydrocortisone given in 2/3 divided doses (glucocorticoid) + fludrocortisone (mineralocorticoid)

Question 19

When are hydrocortisone doses given (Addison’s disease)?

Answer 19

Majority given at start of first half of day and rest given in second half (2/3 doses per day –> 20-30mg)

Question 20

What do we have to ensure if patient with Addison’s disease also has hypothyroidism?

Answer 20

Give hydrocortisone BEFORE thyroxine (to prevent precipitating an Addisonian crisis)

Question 21

How does Addison’s disease treatment change during intercurrent illness?

Answer 21

Hydrocortisone dose doubled, fludrocortisone dose stays the same

(If severe intercurrent stress - IV hydrocortisone - stress dose)

Question 22

How do we manage an Addisonian crisis? (3)

Answer 22

• IV hydrocortisone (100mg bolus)
  
  • followed by 50mg every 6h until stable
  • fludrocortisone not needed as high cortisol exerts weak mineralocorticoid action
  • oral replacement after 24h and tapered to maintenance doses over 3-4d
• rapid IV fluid resuscitation
• glucose (50mL of 50% dextrose) - hypoglycaemia

Question 23

What are some complications of Addison’s disease? (4)

Answer 23

• secondary Cushing’s syndrome (over-replacement)
• osteopenia/osteoporosis (over-replacement, decrease glucocorticoid if no other cause)
• treatment-related hypertension (over-replacement –> mineralocorticoid hypertension and hypokalaemia)
• Nelson’s syndrome (rapid enlargement of a pre-existing corticotroph adenoma after bilateral adrenalectomy due to severe Cushing’s)