Overnight Dexamethasone in Primary Aldosteronism Screening in Patients on Interfering Therapy (ODEPRASC): A Diagnostic Interpretability Study Protocol

Screening for primary aldosteronism (PA) remains exceedingly low, despite the fact that the disorder contributes to or underlies hypertension (HT) in as many as 20% of unselected patients. Conventionally, withdrawal of medications interfering with the renin‒angiotensin‒aldosterone system (RAAS) has been recommended before PA work-up. Previous research showed that combining objective thresholds and 2-day cosyntropin suppression was highly accurate in diagnosing PA among HT patients off interfering drugs. Here, we present the protocol of a study designed to generate and temporally validate aldosterone-to-renin ratio (ARR) thresholds following overnight cosyntropin suppression in PA screening on interfering medications. We hypothesize that overnight cosyntropin suppression with 1 mg dexamethasone will result in 25% higher diagnostic interpretability compared to conventional ARR testing. This single-center study consists of a development and confirmation cohort (both n = 80). Patients with an adrenal incidentaloma are enrolled in a 1-day clinic. Aldosterone-to-renin ratios (ARRs) are determined before and after overnight intake of 1 mg dexamethasone (DXM) on, partially off, and off medications interfering with the RAAS. Emphasis on screening and limitation of PA confirmatory (suppression) tests have been included in the current Endocrine Society guideline on PA due to low evidence of benefits of the latter in diagnosing the disorder. In light of poor PA screening rates, the ODEPRASC study may provide a rationale for an optimized diagnostic approach. Trial Registration: ClinicalTrials.gov identifier: NCT06740838.