Optimal Plasma Renin for Primary Adrenal Insufficiency on Replacement Therapy

Target Range and Rationale

The American College of Internal Medicine recommends aiming for plasma renin activity in the upper normal range rather than complete suppression to normal or low-normal levels, with a target range of approximately 20-60 mIU/L 1

Mineralocorticoid replacement should be evaluated primarily through clinical assessment, including asking about salt cravings or lightheadedness, measuring blood pressure in supine and standing positions, and checking for peripheral edema, as recommended by the American College of Internal Medicine 2
Normal blood pressure and absence of salt craving indicate adequate replacement, regardless of mild PRA elevation, according to the American College of Internal Medicine 1, 3
Postural hypotension reflects insufficient mineralocorticoid therapy and/or low salt intake, warranting dose adjustment, as suggested by the American College of Internal Medicine 1, 3

Assessment of PRA can be valuable in patients with features of mineralocorticoid deficiency to guide fludrocortisone dose adjustments, as recommended by the American College of Internal Medicine 1, 3

When evaluating mineralocorticoid adequacy, clinical assessment should be done first, including checking for salt craving, measuring supine and standing blood pressure, assessing for edema, and reviewing symptoms of fatigue or weakness, as recommended by the American College of Internal Medicine 2
Serum sodium and potassium should be measured, as hyponatremia and hyperkalemia suggest under-replacement, and hypokalaemia suggests over-replacement, according to the American College of Internal Medicine 1, 3

Under-replacement is more common than over-replacement and may be compensated by excessive glucocorticoid dosing, potentially predisposing to recurrent adrenal crises, as noted by the American College of Internal Medicine 2

Standard fludrocortisone dosing ranges from 50-200 μg daily, with most patients requiring 50-100 μg/day, as recommended by the American College of Internal Medicine 2
Higher doses may be needed in certain populations, such as children, younger adults, or during the last trimester of pregnancy, and patients should be advised to consume salt and salty foods without restriction, as suggested by the American College of Internal Medicine 2