Evidence that patients with Addison's disease are undertreated with fludrocortisone

Ten patients with Addison's disease, nine with undetectable plasma aldosterone, were found to be sodium and water depleted with high levels of plasma-renin activity despite receiving 0.05-0.1 mg/day of fludrocortisone and optimum doses of glucocorticoid replacement therapy. Fludrocortisone was withdrawn while patients were in hospital on a fixed sodium intake. There was an immediate natriuresis with a further increase in plasma-renin activity. When a daily dose of 0.3 mg of fludrocortisone was given all patients retained sodium and water and gained weight. There was a fall in plasma-renin activity in all patients and an associated fall in blood urea and plasma potassium, and an increase in plasma volume; oedema developed in some patients. At outpatient follow-up, the dose of fludrocortisone was adjusted according to plasma-renin activity. Most patients required 0.2 mg of fludrocortisone to maintain adequate sodium and water balance. These results suggest that patients with Addison's disease on 0.05-0.1 mg of fludrocortisone with undetectable plasma aldosterone levels are currently being undertreated with fludrocortisone. The best way of assessing sodium balance in these patients and their response to fludrocortisone is by measurement of plasma-renin activity in conjunction with 24 h urinary sodium excretion.