Addison's disease + adrenal insufficiency Flashcards
Addisons disease definition
Addison’s disease (primary adrenal insufficiency) is caused by destruction or dysfunction of the adrenal cortex.
Results in mineralocorticoid (aldosterone), glucocorticoid (cortisol) and gonadocorticoid (androgens) deficiency
Epidemiology of ADs
- In Europe, the overall prevalence has increased from 40-70 cases per million in the 1960s to more than 140 cases per million in developed countries.
- More common in women
Aetiology of ADs
Autoimmune adrenalitis
Infection - TB (most common worldwide), HIV, Meningococcal infection
Congenital cause - congenital adrenal hyperplasia causes impaired cortisol synthesis
Autoimmune adrenalitis aetiology
most common in western world. Autoantibodies target the adrenal gland and the enzymes involved in steroid synthesis. One of the main targets for autoimmune destruction is the enzyme 21-hydroxylase.
Rare causes of ADs
- Long term steroid use (causes reduced ACTH via negative feedback)
- Etomidate, Mitotane, Aminoglutethimide (reduce cortisol production) - drugs usually used to treat Cushing’s syndrome
RF for ADs
- Female gender
- Autoimmune conditions
- Autoimmune polyendocrinopathy syndrome
- Adrenal haemorrhage
- Warfarin which may predispose to adrenal haemorrhage
- TB
- HIV
Addisons disease pathophysiology
refers to chronic primary adrenal insufficiency(hypoadrenalism) resulting in reduced adrenocortical hormones, including mineralocorticoids (zona glomerulosa), glucocorticoids (zona fasciculata), and androgens (zona reticularis).
Corticosteroid involvement
(glucocorticoids and mineralocorticoids) are involved in renal excretion of potassium and acid as well as sodium reabsorption.
Hence, adrenal insufficiency results in a metabolic acidosis coupled with hyperkalaemia and hyponatraemia.
What are most cases caused by in the UK
Autoimmune destructionof the adrenal glands. These patients are at risk of developing other autoimmune conditions such as vitiligo or thyroid disease, and on occasion, forms part of an autoimmune polyendocrinopathy syndrome (APS).
Signs of ADs
- Hyperpigmentation (caused by increased levels of ACTH) - especially in palmar creases and buccal mucosa
- Vitiligo - due to loss of androgens
- Loss of pubic hair in women
- Hypotension and postural drop
- Associated autoimmune conditions
- Tachycardia
Symptoms of ADs
- Lethargy and generalised weakness
- Loss of libido
- Nausea and vomiting
- Cachexia - weight loss and muscle wasting
- Dehydration
- Salt-cravings
- Collapse and shock (Addisonian crisis)
1st line investigation of ADs
8 - 9 am cortisol: NICE suggests using this first-line in primary care
- <100 nmol/L: highly suggestive of Addison’s; NICE advise admission to hospital
- 100 - 500 nmol/L: refer the patient for an ACTH stimulation test
- > 500 nmol/L: Addison’s is unlikely; this result would be expected in normal people
Gold standard test
ACTH stimulation test (short Synacthen test): Plasma cortisol is measured before and 30 minutes after giving Synacthen 250μg IM (ACTH analogue)
- Failure of an adequate rise in cortisolpost-Synacthen (with peak cortisol levels < 500 nmol/L at 1 hour) suggests Addison’s disease
Other investigations of ADs
- 8 am ACTH:increased due to loss of negative feedback from cortisol
- Adrenal antibodies:anti-21-hydroxylase suggests autoimmune aetiology
- U&Es:mineralocorticoid deficiency causeshyponatraemiaandhyperkalaemia
- Aldosterone/renin ratio:decreased in Addison’s disease due to reduction in mineralocorticoid production
- CT adrenal:
Differential diagnosis of ADs
- Haemochromatosis due to hyperpigmentation
- Hyperthyroidism due to weight loss and tachycardia
- Anorexia nervosa due to weight loss