Assessment of
mineralocorticoid replacement
therapy in
Addison's disease relies on clinical features and laboratory measurements, including plasma
renin and
potassium. Previous studies have questioned the value of measuring the plasma
renin concentration (PRC), particularly in the setting of
fludrocortisone overreplacement. The aim of this study was to evaluate the usefulness of plasma
atrial natriuretic peptide (
ANP) measurements as a marker of
sodium and volume status in
Addison's disease. Fourteen patients with
Addison's disease receiving their usual
glucocorticoid doses were placed on various doses of
fludrocortisone (FC; 0 mg, 0.05 mg, 0.1 mg and 0.2 mg) in random order for four 2-week periods. At the end of each period, blood pressure and clinical symptoms were assessed, and blood was drawn for measurement of PRC and
ANP levels. PRC was significantly elevated in patients receiving placebo (54.2 +/- 57.9 ng/mL x h) compared with PRC in those receiving baseline FC (24.7 +/- 42.4 ng/mL x h), 0.1 mg FC (15.2 +/- 25.9 ng/mL x h), and 0.2 mg FC (5.5 +/- 5.7 ng/mL x h).
ANP levels were measured by either an extraction method (
ANP(ext)) or directly from plasma (
ANP(dir)).
ANP(dir) was significantly elevated at 0.2 mg FC (87.1 +/- 20.1 pg/mL) compared with baseline (63.3 +/- 8.1 pg/mL), placebo (56.1 +/- 5.5 pg/mL), 0.05 mg FC (60.5 +/- 16.0 pg/mL), and 0.1 mg FC (65.4 +/- 13.7 pg/mL) values.
ANP(ext) was elevated in patients receiving 0.2 mg FC (42.7 +/- 41.8 pg/mL) compared with that in patients receiving placebo (7.9 +/- 5.4 pg/mL), 0.05 mg FC (16.2 +/- 11.2 pg/mL), or 0.1 mg FC (19.7 +/- 11.1 pg/mL). Our data suggest that PRC is of value in determining
mineralocorticoid underreplacement, whereas
ANP is a more sensitive index of FC overreplacement.
ANP levels may, therefore, be complementary to PRC in adjustment of
mineralocorticoid doses in the upper dose range, where clinical symptoms and signs appear to be of little value.