Context: Primary aldosteronism (PA) accounts for 510% of all hypertension and 2025% of refractory cases. Diagnosis is important as PA is associated with increased morbidity and mortality compared with essential hypertension, and up to 50% of patients may benefit from unilateral adrenalectomy. Screening requires measurement of plasma renin activity (PRA) or concentration (PRC), and plasma aldosterone concentration (PAC), to yield an aldosterone:renin ratio (ARR). The finding of low plasma renin and raised ARR triggers further investigation.
Case: A 70-year-old man, with hypertension, hypokalaemia, suppressed PRA and markedly raised ARR, was referred to our centre for further investigation. However PRC, in the absence of confounding medications, was not consistent with PA. Suspecting an erroneous PRC result, we measured PAC (526 pmol/l), PRC and PRA on an independently drawn sample, which confirmed markedly divergent findings (PRA <0.2 nmol/l per hr (reference range (RR) 0.53.1); PRC 57 mU/l (RR5.460)), yielding strongly positive and strongly negative ARR screening respectively: PRA-derived ARR >2630 (RR<750); PRC-derived ARR 9.2 (RR<84). Further analysis revealed non-linear dilution of PRC, and polyethylene glycol precipitation was consistent with antibody interference, confirming PRC estimation to be unreliable in our assay. Moreover, repeat testing using an alternative PRC immunoassay platform demonstrated a PRC consistent with both the PRA result and a diagnosis of PA (PRC 5.5 mU/l (RR 11-32), ARR 95.6 (RR<84)). The patient proceeded to 11C-metomidate PET-CT, with the demonstration of bilateral nodular adrenal disease, which has responded well to mineralocorticoid receptor antagonist therapy.
Conclusion: This is the first reported case of PRC assay interference. As measurement of renin concentration (mass) is increasingly used to screen for PA, clinicians should be alert to this possibility, especially when a clearly measurable renin result, seemingly ruling against PA, is discordant with the clinical context.