Background: Adrenal insufficiency (AI) results from deficient production/action of glucocorticoids (GCs), with or without deficiency of mineralocorticoids (MC) and adrenal androgens. GC treatment is essential but some patient needs MC therapy to allow sodium(Na+) retention, potassium(K+) excretion and to maintain normal plasma volume and blood pressure. Much attention has focused on optimization of GC replacement but no consensus exists for optimization of MC therapy in primary AI. Our aim was to explore the relationship between MC dose, Plasma renin concentration (PRC) and clinically important variables to determine the most helpful in guiding MC dose titration.
Design: We performed an observational, retrospective analysis on 1107 assessments from 281 patients (242 with salt-wasting CAH(SW-CAH) and 39 with Addisons disease(AD)) recruited from local databases and the international congenital adrenal hyperplasia registry (www.i-cah.org). Subgroup analysis was made in adult patients (age>=18years) and a longitudinal analysis performed in 92 patients with SW-CAH(median time between assessments 560 days,range 332082). PRC, electrolytes, BP and anthropometric parameters were assessed for their utility in optimizing MC replacement dose.
Results: PRC (normal range 11-32 μUI/mL) was low, normal or high in 30%,15% and 55% of patients respectively with wide variability in MC dose (37.7%, 16.6%, 15.4% and 11.7% of patients were on fludrocortisone 100.50.150 and 200 μg/day respectively) and PRC (median 47 μUI/mL, range 0.13166). Patients with high PRC had lower Na+ levels (with no change in K+), higher mean arterial pressure (MAP), BMI, age and were on the highest total daily MC dose. Univariate analysis demonstrated a direct relationship between MC dose and PRC (P<0.001), and an inverse correlation with potassium (P<0.001). Using multiple regression modelling, only Na+ was able to predicted PRC. MC dose predicted K+, but not MAP or PRC. In the longitudinal analysis, Na+ concentration at final follow-up visit was associated with the change (Δ) in PRC (B=139.538, P<0.001). There was no relationship between ΔPRC and final MAP, K+ or MC dose. No correlation was found between ΔMC dose and ΔPRC,K+, Na+ or MAP. Observations were similar in patients with SW-CAH and AD.
Conclusions: The lack of relationship between MC dose and PRC calls into question its utility as an aid to optimise and titrate MC replacement dose. This may reflect variability in sampling with respect to posture, timing and concomitant medications, but suggests that in clinical practice, emphasis should be placed on ensuring normalization of serum electrolytes in the optimization of MC replacement.
18 - 21 May 2019
European Society of Endocrinology