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
1st line management of ADs
Corticosteroid replacement:
-
Hydrocortisone
Fludrocortisone is recommended once daily for mineralocorticoid replacement (50-300 micrograms)
Other management of ADs
- Androgen replacement - mainly in women
-
Patient education:
- Patients should be advised regarding medication compliance and not missing doses
- Advise patients to wear a MedicAlert bracelet or carry steroid cards in case of an Addisonian crisis
- Advise patients todoubletheir glucocorticoid dose (hydrocortisone) if they develop an intercurrent illness
Complications of Addison’s
- Secondary Cushings due to excess hormone replacement
- Secondary Hypertension
- Osteoporosis + Osteopenia
- Addisonian crisis - drop in glucocorticoid levels usually due to non-compliance with medication
What is an Addisonian crisis?
state of acute insufficiency of adrenocortical hormones.
It most often occurs on a background of established Addison’s disease due to precipitating factors such as poor medication compliance, infection, trauma, surgery, and myocardial infarction.
Who will have an Addisonian crisis
In those with Addison’s disease, 40% of patients will experience one crisis
Aetiology of Addisonian crisis
- Steroid withdrawal: any patient on long term steroids should not abruptly withdraw their medication
- Severe dehydration
- Sepsis or surgery: resulting in acute exacerbation of pre-existing adrenal insufficiency (e.g. Addison’s disease)
- Meningococcal infection:meningococcal sepsis can lead to adrenal haemorrhage (Waterhouse-Friderichsen syndrome)
Pathophysiology of Addisonian crisis
Drop in level of corticosteroids 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.
In a crisis, there is also accompanying haemodynamic instability due to sodium and, therefore, fluid loss.
Signs of Addisonian shock
- Hypotension
- Hypovolemic shock
- Reduced GCS - consciousness
- Confusion
- Pyrexia - increased temperature
Symptoms of Addisonian shock
- Nausea and vomiting
- Abdo pain
- Trigger e.g. infection or MI
Investigations for ADs
- 12-lead ECG:hyperkalaemic changes include flat P waves, short QT interval, broad QRS, ST depression, and tented T waves
- VBG:can be conducted quickly and will reveal metabolic acidosis with hyponatraemia and hyperkalaemia. Patients may also be hypoglycaemic
- U&E’s: hyponatraemiaandhyperkalaemia; acute kidney injury may be present due to hypovolaemia causing pre-renal injury
- FBC and CRP:leukocytosis and raised inflammatory markers may suggest an underlying infection as the precipitant
- TFTs:hypothyroid states may mimic an Addisonian picture
Definition of secondary adrenal insufficiency
Secondary adrenal insufficiency is adrenal hypofunction due to a lack of adrenocorticotropic hormone (ACTH).
What is adrenal suppression?
decreased cortisol production as a result of negative feedback on the hypothalamic-pituitary-adrenal axis, caused by excess glucocorticoids.
Consequence of adrenal insufficiency
decreased production of both corticotropin-releasing hormone from the hypothalamus and adrenocorticotropic hormone from the pituitary gland, leading to a decrease in serum cortisol levels.
Aetiology of secondary AI
Iatrogenic - commonest cause. Due to long term steroid use leading to suppression of the HPA axis
- Hypothalamic pituitary disease - resulting in reduced ACTH production
- Removal of pituitary tumour - the remaining ACTH-secreting cells in the pituitary gland may be sluggish in their recovery, resulting in a period of adrenal suppression
Pathophysiology of AI
- Decreased levels of ACTH resulting in decreased glucocorticoid (CORTISOL)
- Mineralocorticoid production remains intact
Presentation of Secondary AI
Similar presentation to Addison’s disease.
However, no hyperpigmentation as there is no excess ACTH
Investigations for Secondary AI
Same as with Addison’s disease
- ACTH levels are low and mineralocorticoid production is intact in secondary hypoadrenalism - can be used to differentiate from Addison’s
Management of secondary AI
- Adrenals will recover if long-term steroids are slowly weaned off - but this is
a long and difficult process - ORAL HYDROCORTISONE - replacement of glucocorticoids
