Addison’s disease (primary hypoadrenalism)

Pathophysiology:

• In this uncommon condition
• Destruction of the entire adrenal cortex
• Glucocorticoid, mineralocorticoid and sex steroid synthesis are, therefore, all reduced
• This differs from hypothalamic-pituitary disease, in which mineralocorticoid secretion remains largely intact (being predominantly stimulated by angiotensin II)
• In Addison’s disease, reduced cortisol levels lead (through a feedback loop) to increased CRF (corticotrophin releasing factor) and ACTH (adrenocorticotrophic hormone) production
• The increased ACTH production leads, directly, to hyperpigmentation
• Women > men

Causes of primary hypoadrenalism:

• Autoimmune disease (>90% in UK)
• TB (<10% in UK)
• Infiltration (rare)

Symptoms of Addison’s disease:

• Weight loss
• Syncope (from postural hypotension)
• Anorexia
• Malaise
• Weakness
• Fever
• Depression
• Impotence
• Diarrhoea
• Nausea/vomiting
• Confusion

Signs of Addison’s disease:

• Postural hypotension
• Pigmentation (especially of new scars)
• Loss of weight
• Dehydration
• Loss of body hair

Investigations:

Once Addison’s is suspected, investigation is urgent. If the patient is severely ill or very hypotensive, hydrocortisone 100mg should be given IM together with IV saline.

Single cortisol measurements:

• Are of little value
• A random cortisol of <100nmol/L during the day is highly suggestive
• A random cortisol of >550nmol/L makes the diagnosis unlikely (but not impossible)

The short ACTH stimulation test:

• An absent or impaired cortical response is seen, confirmed if necessary by a long ACTH stimulation test to exclude adrenal suppression by steroids

A 0900hr plasma ACTH level:

• A high level (>80ng/L) with a low to normal cortisol confirms primary hypoadrenalism

Electrolytes and urea:

• Hyponatraemia
• Hyperkalaemia

Blood glucose:

• May be low (with symptomatic hypoglycaemia)

Adrenal antibodies:

• Present in many cases of autoimmune adrenalitis

CXR/AXR:

• May show evidence of TB and/or calcified adrenals

Serum aldosterone:

• Is reduced with high plasma renin activity

ACTH (Synacthen) tests:

Short (to exclude primary adrenal failure):

1. Tetracosatrin 250μg IV/IM at time 0
2. Measure plasma cortisol at times 0, +30mins
3. Normal test result will show cortisol at time +30mins >600nmol/L

Long (to demonstrate or exclude adrenal suppression):

1. Depot tetracosatrin 1mg IM at time 0
2. Measure plasma cortisol at times 0, +1, +2, +3, +4, +5, +8 and +24hrs
3. Normal test result will show a maximum of >1000nmol/L

Treatment:

• Long-term treatment is with replacement glucocorticoids and mineralocorticoids.
• TB must be treated if present or suspected

Adequacy of glucocorticoid dose is judged by:

• Clinical well-being
• Normal cortisol levels during the day whilst on replacement hydrocortisone

Fludrocortisone replacement is assessed by:

• Restoration of serum electrolytes to normal
• BP response to posture (it should not fall >10mmHg systolic after 2 minutes standing)
• Suppression of plasma renin activity to normal

Patient advice:

All patients requiring replacement steroids should:

• Carry a steroid card
• Wear a medic-alert bracelet (which gives details of their condition)
• Keep an up-to-date ampoule of hydrocortisone at home in case oral therapy is impossible

Acute hypoadrenalism:

The major deficiencies are of salt, steroid and glucose. Assuming normal CVS function, the following procedures are required:

• 100mg of IV hydrocortisone
• 1L normal saline given over 30-60mins
• Subsequent saline requirements may be for several litres within 24 hours (assess with CVP line if necessary)
• Hydrocortisone 100mg IM 6-hourly, until the patient is clinically stable
• Dextrose should be infused if there is hypoglycaemia
• Oral replacement medication is then started, initially hydrocortisone 20,g 8-hourly, reducing to 20-30mg in divided doses over a few days
• Fludrocortisone is unnecessary acutely as the high cortisol doses provide sufficient mineralocorticoid activity – it should be introduced later