Plasma renin measurements are unrelated to mineralocorticoid dose in patients with primary adrenal insufficiency

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Context: No consensus exists for optimization of mineralocorticoid therapy in patients with primary adrenal insufficiency.

Objective: To explore the relationship between mineralocorticoid replacement dose, plasma renin concentration (PRC) and clinically important variables to determine which are most helpful in guiding mineralocorticoid dose titration in primary adrenal insufficiency.

Design: Observational, retrospective, longitudinal analysis.
Patients: 280 patients (with 984 clinical visits and plasma renin measurements) with primary adrenal insufficiency recruited from local databases and the international congenital adrenal hyperplasia (CAH) registry ( Thirty-seven patients were excluded from the final analysis due to incomplete assessment. Data from 204 patients with salt-wasting CAH (SW-CAH) (149 adults and 55 children) and 39 adult patients with Addison’s disease (AD) were analysed.

Main outcome measures: PRC, electrolytes, blood pressure (BP) and anthropometric parameters were used to predict their utility in optimizing MC replacement dose.

Results: PRC was low, normal or high in 19%, 36% and 44% of patients, respectively, with wide variability in mineralocorticoid dose and PRC. Univariate analysis demonstrated a direct positive relationship between mineralocorticoid dose and PRC in adults and children. There was no relationship between mineralocorticoid dose and BP in adults, while BP increased with increasing mineralocorticoid dose in children. Using multiple regression modelling, sodium was the only measurement that predicted PRC in adults. Longitudinally, the change in mineralocorticoid dose was able to predict potassium, but not BP or PRC.

Conclusions: The relationship between mineralocorticoid dose and PRC is complex and this may reflect variability in sampling with respect to posture, timing of last mineralocorticoid dose, adherence and concomitant medications. Our data suggests that mineralocorticoid titration should not primarily be based only on PRC normalization, but also on clinical parameters as BP and electrolyte concentration.
Original languageEnglish
Article numberdgz055
JournalJournal of Clinical Endocrinology and Metabolism
Early online date16 Oct 2019
Publication statusE-pub ahead of print - 16 Oct 2019


  • congenital adrenal hyperplasia
  • salt-wasting CAH
  • primary adrenal insufficiency
  • mineralocorticoid replacement
  • plasma renin concentration
  • fludrocortisone


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