Prediction of unilateral hyperaldosteronism on adrenal vein sampling using captopril challenge test in patients with primary aldosteronism

Abstract

Captopril challenge test (CCT) is a simple and safe confirmatory test for primary aldosteronism (PA). We investigated the effectiveness of the indices after captopril administration for prediction of unilateral hyperaldosteronism (UHA) on adrenal vein sampling (AVS). We studied 238 patients with PA who had CCT and successful AVS between July 2007 and December 2019 in Sapporo City General Hospital. Receiver operating characteristic (ROC) curve analysis showed that the diagnostic performance for prediction of UHA on AVS in regard to the reduction rate of plasma aldosterone concentration (PAC) after captopril administration was inferior to aldosterone to renin ratio (ARR) and PAC (area under the ROC curve 0.72 vs. 0.84, 0.72 vs. 0.89, respectively, both p < 0.01). Based on the optimal cut-off values in ARR (897 pg/mL/ng/mL/h, sensitivity 64.6%, specificity 93.0%) and PAC (203 pg/mL, sensitivity 73.9%, specificity 93.0%) after captopril administration, the patients were divided into three groups: (1) both positive, (2) one positive, and (3) both negative. The prevalence of UHA on AVS in the three groups were 90.0%, 52.9%, and 7.3%, respectively. In the first group, 31 of 32 patients with unilateral nodular lesion on CT had an ipsilateral unilateral AVS. In conclusion, the combination of postcaptopril ARR and PAC is useful for prediction of laterality diagnosis on AVS. AVS is strongly recommended in patients with both positive or one positive results for the optimal cut-off values of post-captopril ARR and PAC and is weakly recommended in patients with both negative results.

Is adrenal venous sampling always necessary to differentiate between unilateral and bilateral primary aldosteronism? Lesson from the SPAIN-ALDO register

“…We developed a prediction model that included seven clinical variables: dyslipidemia, cerebrovascular disease, SAS, SBP, hypokalemia, PAC at diagnosis, unilateral adrenal nodule >1 cm, and normal contralateral adrenal gland on CT/MRI. This model had an 82% diagnostic accuracy for the differentiation between unilateral and bilateral PA. Our model's global predictive power is comparable to that of several previously published prediction methods [10,16,24]. The present study suggests that patients with a history of hypokalemia, SBP >160 mmHg, PAC > 40 ng/dL, and a unilateral adrenal lesion on CT/MRI are the best predictors of unilateral disease.…”

“…Thus, efforts have been made to identify clinical, biochemical, and imaging predictors of unilateral disease. Low potassium levels were recommended as a predictor of PA subtype by some studies [8, 9,13,14], aldosterone levels at screening and after con rmatory testing by others [9][10][11][12][13][14], and the presence or absence of a nodule at CT scanning or its diameter by others [9]. In the Japan Primary Aldosteronism Study (JPAS), for example, patients with PA who had bilateral or normal CT results and normokalemia had a low probability of UPA in AVS (6.2%), whereas those with a unilateral visible mass on CT and hypokalemia had a high probability of UPA in AVS (70.6%) [15].…”

Do multiple types of confirmatory tests improve performance in predicting subtypes of primary aldosteronism?

“…The PAC at baseline or after loading with SIT or CCT, lowest serum potassium level and adrenal nodule diameter on CT were selected as the predictors. [8][9][10]13,22 There were no missing values for the predictors in the patients studied. Using the holdout method, the analysis was conducted by randomly assigning the eligible patients with PA into two groups: the training (80%) and test (20%) data sets.…”

“…The hyperparameters of the LightGBM were optimized using a grid search; the optimized values included max depth, learning rate, min data in leaf, num leaves and n estimators. The PAC at baseline or after loading with SIT or CCT, lowest serum potassium level and adrenal nodule diameter on CT were selected as the predictors 8–10,13,22 . There were no missing values for the predictors in the patients studied.…”

“…Therefore, it is recommended in the guideline that patients with suspected PA undergo one or more confirmatory tests to definitively confirm or exclude the diagnosis 7 . The saline infusion test (SIT) and captopril challenge test (CCT) are widely used as confirmatory tests, both of which have been useful for predicting subtypes of PA, mirroring the guideline recommendations 8–10 . The guideline of the Japan Endocrine Society recommends undergoing at least two confirmatory tests, 11 and therefore, in Japan, two confirmatory tests are often performed in clinical practice regardless of the result in the initial one.…”