Assessing treatment adherence is crucial to determine adequacy of mineralocorticoid therapy

Abstract

Background: There is no consensus strategy for mineralocorticoid (MC) therapy titration in patients with primary adrenal insufficiency (PAI). We aim to measure serum fludrocortisone (sFC) and urine fludrocortisone (uFC) levels and to determine their utility, alongside clinical/biochemical variables and treatment adherence to guide MC replacement dose titration.

Methods: Multi-centre, observational, cross-sectional study on 41 patients with PAI on MC replacement therapy. sFC and uFC levels (measured by liquid chromatography-tandem mass spectrometry), plasma renin concentration (PRC), electrolytes (Na+, K+), mean arterial blood pressure (MAP), total daily glucocorticoid (dGC) and MC (dMC) dose, and assessment of treatment adherence were incorporated into statistical models.

Results: We observed a close relationship between sFC and uFC (r = 0.434, P = 0.005) and between sFC and the time from the last fludrocortisone dose (r = -0.355, P = 0.023). Total dMC dose was related to dGC dose (r = 0.556, P < 0.001), K+ (r = -0.388, P = 0.013) as well as sFC (r = 0.356, P = 0.022) and uFC (r = 0.531, P < 0.001). PRC was related to Na+ (r = 0.517, P < 0.001) and MAP (r = -0.427, P = 0.006), but not to MC dose, sFC or uFC. Regression analyses did not support a role for sFC, uFC or PRC measurements and confirmed K+ (B = -44.593, P = 0.005) as the most important variable to guide dMC titration. Of the patients, 32% were non-adherent with replacement therapy. When adherence was inserted into the regression model, it was the only factor affecting dMC.

Conclusions: sFC and uFC levels are not helpful in guiding dMC titration. Treatment adherence impacts on clinical variables used to assess MC replacement and should be included as part of routine care in patients with PAI.

Keywords: Addison’s disease; congenital adrenal hyperplasia; glucocorticoids; mineralocorticoids; renin.

Figure 1

Univariate analysis for serum and urine FC levels in a cohort of 41 patients with primary adrenal insufficiency. The dashed line in (B) refers to a two-phase exponential decay equation derived from serum FC levels at different timepoints. Grey areas between the dashed lines in (A), (C) and (D) refer to the 95% confidence intervals of the regression lines.

Figure 2

Univariate analysis for clinical and biochemical variables in a cohort of 41 patients with primary adrenal insufficiency. Grey areas between the dashed lines refer to the 95% confidence intervals of the regression lines.