Surgery for the treatment of arterial hypertension in patients with unilateral adrenal incidentalomas and mild autonomous cortisol secretion (CHIRACIC): a multicentre, open-label, superiority randomised controlled trial

Abstract

Background: Adrenal incidentalomas are found in 3-10% of adults undergoing abdominal imaging. Of these, 30-50% are responsible for mild autonomous cortisol secretion (MACS), which is frequently associated with hypertension. The impact of adrenalectomy on hypertension in patients with unilateral incidentalomas and MACS remains uncertain. The aim of the CHIRACIC study was to prospectively assess the impact of surgical excision of the incidentaloma on blood pressure with a randomised trial combining accurate blood pressure measurement and standardisation of antihypertensive treatment.

Methods: CHIRACIC was a multicentre, superiority, open-label, parallel, randomised controlled trial performed at 17 university hospitals in France, Italy, and Germany. Adults with hypertension with MACS entered a run-in phase to confirm hypertension with multiple home blood pressure measurements (HBPM) before blood pressure was normalised with standardised stepped-care antihypertensive treatment. Eligible participants were then randomly assigned (1:1) to adrenalectomy or conservative management. Randomisation was blocked (random block size of 4 and 6) and stratified by intensity of antihypertensive treatment. Participants were followed up for 13 months and systematic attempts were made to gradually reduce antihypertensive treatment. The primary endpoint was the proportion of normotensive participants using HBPM who reduced their antihypertensive treatment in the intention-to-treat population at study completion. Key secondary endpoints included 24 h ambulatory blood pressure measurement (ABPM), mean change in antihypertensive treatment, and the proportion of participants with antihypertensive treatment at study completion. This study was registered with ClinicalTrials.gov, NCT02364089, and is completed.

Findings: Between April 9, 2015 and Nov 23, 2022, 78 patients were enrolled, and 52 eligible participants were randomly assigned to adrenalectomy (n=26, 23 underwent adrenalectomy and completed the study) or conservative management (n=26, 25 completed the study). The median age of participants was 63·3 years (IQR 57·4-68·2) and 36 (69%) were female. At study completion, a reduction in antihypertensive treatment with normal HBPM was observed in 12 (46%) of 26 participants treated with adrenalectomy and in four (15%) of 26 treated conservatively (adjusted risk difference [RD] 0·34 [95% CI 0·11 to 0·58]; p=0·0038). Similar results of smaller magnitude were observed for systolic blood pressure during 24 h ABPM. There were ten (43%) of 23 participants still needing antihypertensive treatment in the adrenalectomy group and 24 (96%) of 25 in the conservative management group (adjusted RD -0·58 [95% CI -0·78 to -0·38]; p<0·0001). Mean antihypertensive treatment step was 0·8 (SD 1·1) in the adrenalectomy group and 3·0 (1·4) in the conservative management groups (adjusted difference -2·05 [95% CI -2·61 to -1·50]; p<0·0001]. The number of patients with normal systolic HBPM and no hypertensive treatment was 12 (52%) of 23 in the adrenalectomy group and none in the conservative management group. Serious adverse events occurred in eight (35%) of 23 participants in the adrenalectomy group and eight (31%) of 26 participants in the conservative management group. Three serious adverse events for three (13%) participants were related to the surgery (post-surgical wall pain and hypotension).

Interpretation: MACS associated with unilateral adrenal incidentalomas is responsible for secondary hypertension that can be safely improved by minimally-invasive adrenalectomy.

Funding: French Ministry of Health and the German Research Foundation.