MON-488 - Mineralocorticoid Replacement, Renin, and Clinical Outcomes in Primary Adrenal Insufficiency: A Cross-Sectional Multivariable Analysis

Background
Primary adrenal insufficiency (PAI) requires glucocorticoid (GC) and mineralocorticoid (MC) replacement. Blood pressure and electrolytes guide MC dosing but may be insufficient, as symptoms of MC deficiency can persist. Overlap between GC and MC deficiency symptoms may also contribute to GC escalation. Plasma renin activity has been proposed as an adjunctive marker, though clinical utility remains uncertain.
Objective
1. To determine the association between MC dose or potency and plasma renin activity, sodium or potassium concentration.
2. To determine the association between MC dose or potency and number of adrenal crisis (AC) events requiring emergency room presentation, patient-reported symptoms suggestive of MC deficiency and the need for sick-day GC dosing.
Methods
We conducted a cross-sectional study of adults with autoimmune PAI between 2018-2025. Patients were eligible if 1) treated with fludrocortisone and 2) had survey completed within 6 months of renin plasma activity or electrolyte measurement. Inclusion criteria were met in 53 patients. Data collected included AC frequency, sick-day GC dosing, and symptoms. Plasma renin activity and electrolytes were collected from the medical record. GC doses were converted to hydrocortisone (HC) equivalent doses. MC potency was calculated combining fludrocortisone (0.1 mg = 1) and HC equivalent dose (HC Eq), (HC 10 mg = 0.58).
Results
Of 53 participants (37,70% women; median age at survey completion of 52 years, IQR 40-62; median PAI duration 10 years, IQR 5-24) 29 (55%) patients had renin levels available for assessment and all had electrolyte measurements. HC was the most common GC prescribed, and median HC Eq dose was 20 mg (IQR 20–25). Median MC dose was 0.1 mg (IQR 0.05–0.1) and median MC potency was 2.1 (IQR 1.8-2.5). Median renin was 6.5 ng/mL/h (IQR 3.18-12.43), sodium 139 mmol/L (IQR 137-146) and potassium 4.6 mmol/L (IQR 4-4.8). Renin, sodium or potassium did not correlate significantly with MC dose, MC potency or HC Eq dose. Renin concentrations did not differ by GC type (P=0.62). GC dose was increased ≥1 times in the prior year in 45, 85% patients, while AC occurred in 15, 28%. MC dose, MC potency, and HC Eq dose did not differ between those who experienced AC and those who did not (P>0.5 for all), however reported symptoms of MC under-replacement were more common in those requiring any GC escalation (78% vs 36%, P=0.033). After adjusting for MC potency, GC type (HC vs prednisone) was not associated with a difference in reported AC in the last 12 months (β=0.24, P=0.58).
Conclusion
Plasma renin activity appears to have limited adjunctive value in assessing MC replacement in PAI. Neither MC dose, potency nor HC Eq dose were associated with AC, however symptoms of MC deficiency were more frequent among individuals requiring sick-day GC dosing, suggesting that perceived GC requirements may also reflect inadequate MC replacement.

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