Addinson's disease (brief)

Question 1

How common is it?

Answer 1

Rare

Question 2

What causes it?

Answer 2

Destruction of the entire adrenal cortex. More than 90% occur because of destruction of the entire adrenal cortex by organ-specific autoantibodies.

Associated with other autoimmune conditions, e.g. autoimmune thyroid disease, ovarian failure, pernicious anaemia and type 1 diabetes mellitus. Rarer causes are adrenal gland tuberculosis, surgical removal, haemorrhage, and malignant infiltration.

Primary hypoadrenalism must be differentiated from secondary (to pituitary disease) or tertiary (to hypothalamic disease) adrenocortical failure or after prolonged corticosteroid treatment for non-endocrine conditions.

Question 3

Signs on examination?

Answer 3

There is an insidious presentation with non-specific symptoms of lethargy, depression, anorexia and weight loss.

Postural hypotension caused by salt and water loss is an early sign.

Hyperpigmentation (buccal mucosa, pressure points, skin creases and recent scars) results from stimulation of melanocytes by excess ACTH in primary hypoadrenalism.

There may be vitiligo and loss of body hair in women because of the dependence on adrenal androgens.

May present as a crisis: vomiting, abdominal pain, profound weakness, hypoglycaemia and hypovolaemic shock

Question 4

Investigations

Answer 4

Are threefold: to demonstrate inappropriately low cortisol secretion, to determine if this is independent or dependent on ACTH secretion, e.g. Primary or secondary/tertiary, and to determine the specific cause.

1. Single cortisol measurement: not overly helpful unless extreme
2. Short ACTH (tetracosactide) stimulation test is the key diagnostic investigation and demonstrates failure of exogenous ACTH to ↑ plasma cortisol. However, it does not differentiate primary and secondary.
3. Plasma ACTH level, a high level with a low cortisol level confirms primary hypoadrenalism. Reduced ACTH and cortisol indicate secondary or tertiary.
4. Adrenal antibodies are detected in most cases of autoimmune adrenalitis

Question 5

Treatment

Answer 5

Lifelong steroid replacement

Hydrocortisone. 20mg on waking and 10mg in evening to mimic diurnal rhythm

Fludrocortisone, a synthetic mineralocorticoid, 50-300 micro gram daily. The dose is adequate when serum electrolytes are normal, there is no postural drop in blood pressure and plasma renin levels are suppressed to within the normal range.