Plasma Renin Measurements are Unrelated to Mineralocorticoid Replacement Dose in Patients With Primary Adrenal Insufficiency

Abstract

Context No consensus exists for optimization of mineralocorticoid therapy in patients with primary adrenal insufficiency. Objective To explore the relationship between mineralocorticoid (MC) replacement dose, plasma renin concentration (PRC), and clinically important variables to determine which are most helpful in guiding MC dose titration in primary adrenal insufficiency. Design Observational, retrospective, longitudinal analysis. Patients A total of 280 patients (with 984 clinical visits and plasma renin measurements) with primary adrenal insufficiency were recruited from local databases and the international congenital adrenal hyperplasia (CAH) registry (www.i-cah.org). Thirty-seven patients were excluded from the final analysis due to incomplete assessment. Data from 204 patients with salt-wasting CAH (149 adults and 55 children) and 39 adult patients with Addison 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 MC dose and PRC. Univariate analysis demonstrated a direct positive relationship between MC dose and PRC in adults and children. There was no relationship between MC dose and BP in adults, while BP increased with increasing MC dose in children. Using multiple regression modeling, sodium was the only measurement that predicted PRC in adults. Longitudinally, the change in MC dose was able to predict potassium, but not BP or PRC. Conclusions The relationship between MC dose and PRC is complex and this may reflect variability in sampling with respect to posture, timing of last MC dose, adherence, and concomitant medications. Our data suggest that MC titration should not primarily be based only on PRC normalization, but also on clinical parameters such as BP and electrolyte concentration.

Characterization of patients with adrenal insufficiency and frequent adrenal crises

“…Blood pressure also tended to be lower in the frequent AC group, but only reached significance for diastolic blood pressure at last observation. The latter confirms a recent analysis showing that titration of the mineralocorticoid dose affects potassium levels but not blood pressure or fluid replacement ( 36 ). This suggests that patients with PAI with frequent ACs may be more vulnerable in situations that cause hypotension or a decrease in blood pressure, for example, infections with fever and pronounced sweating.…”

“…A key limitation was the restricted number of clinical and biochemical variables that could be evaluated based on EU-AIR data. For patients with PAI, for example, data on renin were not available owing to the lack of standardisation of the assay across the study centres, and the fact that the value of renin measurement remains highly controversial ( 36 ). A further limitation is the fact that we did not have data on medications and doses regarding the treatment of hypogonadism, hypothyroidism or growth hormone deficiency in patients with SAI.…”

Micro- and macrovascular function in patients suffering from primary adrenal insufficiency: a cross-sectional case–control study

“…Interestingly, daily fludrocortisone dose was not different between Renin high and Renin low , highlighting the importance of other factors besides MC replacement dose in the modulation of RAAS activity, including posture, daytime, dietary sodium intake, volume status and plasma potassium levels [ 29 ]. This is in line with a recently published study by Pofi et al, in which modifications in MC dose were not associated with changes in plasma renin concentrations in a large collective of patients with primary AI [ 30 ]. Dose adjustments of MC replacement therapy might therefore rather be based on clinical characteristics, including blood pressure, salt craving and postural hypotension.…”

Low‐dose desoxycorticosterone pivalate treatment of hypoadrenocorticism in dogs: A randomized controlled clinical trial

“…A high‐normal to mildly increased PRA is targeted in humans with primary adrenal insufficiency 31,32 . Also, mineralocorticoid dosage adjustments are not based solely on PRA in humans, but also on assessments of serum electrolyte concentrations and blood pressure 33 . It is unknown if 1.1 mg/kg DOCP dosages were appropriate for the dogs with increased PRA and normal serum electrolyte concentrations in our study, but all dogs were reported to be well >6 months after study completion.…”