Curriculum · Metabolic and Endocrine and Diabetes Mellitus
Addison disease (primary adrenal insufficiency)
What it is
Addison disease is primary adrenal insufficiency, a disease of the adrenal gland itself, with low cortisol, high ACTH, and low aldosterone with high renin. In secondary adrenal insufficiency the interference is with corticotropin secretion by the pituitary gland, so cortisol and ACTH are both low while aldosterone and renin are normal; the ACTH deficiency may be isolated or occur in conjunction with other pituitary hormone deficiencies. In tertiary adrenal insufficiency the interference is with corticotropin releasing hormone, CRH, secretion by the hypothalamus.
Causes and risk
Autoimmune destruction of the adrenal glands is the commonest cause of hypoadrenalism, accounting for 80% of cases. The other primary causes are tuberculosis, metastases such as from bronchial carcinoma, meningococcal septicaemia, that is Waterhouse Friderichsen syndrome, HIV and antiphospholipid syndrome. The secondary causes are pituitary disorders such as tumours, irradiation and infiltration.
How it presents
The patient is tired all the time, with lethargy, weakness, anorexia, nausea and vomiting, weight loss and salt-craving. The signs are hyperpigmentation, especially of the palmar creases, vitiligo, loss of pubic hair in women, and hypotension. Hyperpigmentation appears in primary disease only, due to the high ACTH levels: it is caused by the melanocyte-stimulating hormone, MSH, like effect of the elevated plasma levels of ACTH, since ACTH shares some amino acids with MSH and also produces an increase in MSH in the blood. The biochemistry is hypoglycemia, hyponatremia, hyperkalemia and a normal anion gap metabolic acidosis, and eosinophils may be elevated in primary adrenal insufficiency. Hyperpigmentation and the combination of hyperkalemia, hyponatremia and hypotension are more often seen in primary adrenal insufficiency, and hypotension in any case is Addison until proven otherwise.