Lateralizing Asymmetry of Adrenal Imaging and Adrenal Vein Sampling in Patients With Primary Aldosteronism

Norio Wada; Yui Shibayama; Takashi Yoneda; Takuyuki Katabami; Isao Kurihara; Mika Tsuiki; Takamasa Ichijo; Yoshihiro Ogawa; Junji Kawashima; Masakatsu Sone; Takanobu Yoshimoto; Yuichi Matsuda; Megumi Fujita; Hiroki Kobayashi; Kouichi Tamura; Kohei Kamemura; Michio Otsuki; Shintaro Okamura; Mitsuhide Naruse; JPAS/JRAS Study Group

Disclosures

J Endo Soc. 2019;3(7):1393-1402. 

In This Article

Patients and Methods

Patients

Twenty-seven centers participated in the JPAS. Patients with confirmed PA who underwent AVS from January 2006 to October 2016 were enrolled in the study. Baseline clinical findings, the results of AVS, and the post-treatment outcomes were recorded electronically using the internet registry system (the EPS Corporation, Tokyo, Japan). Data security and maintenance of registered data were outsourced to the EPS Corporation. The study protocol was approved by the ethics committees of each center.

The diagnostic procedure for PA was based on the guidelines of both the Japan Endocrine Society[12] and the Japan Society of Hypertension.[13] The screening for PA was based on a ratio of plasma aldosterone concentration (PAC; in picograms per milliliter) to the plasma renin activity (PRA; measured as ng/mL/h) of >200, after the patients had changed medications from potentially interfering antihypertensive drugs to calcium channel blockers and/or α-blockers, where applicable. The diagnosis of PA was established by at least one positive result in confirmatory testing, including the captopril challenge test, the upright furosemide-loading test, and the saline-loading test.

Imaging

The CT images were interpreted by radiologists at each participating center. In this study, nodular lesions were defined as those ≥10 mm in diameter. Nodular lesions <10 mm and equivocal lesions were registered as "suspected nodular lesions," and "enlarged lesions" were classified as normal.

AVS

Blood samples obtained via AVS were generally collected 30 minutes after administration of ACTH from both adrenal veins and the inferior vena cava (IVC) at a point distal to the renal vein. The sampling point of both adrenal veins was located at the central vein. The protocol for ACTH administration varied among centers. Eighteen centers used a bolus injection of 250 μg of cosyntropin and eight used a bolus injection of 200 μg (or 250 μg) followed by continuous infusion of 50 μg (or 100 μg, or 250 μg) of cosyntropin. One center used a continuous infusion of cosyntropin. Two centers sampled simultaneously from the left and right adrenal veins. In the remaining centers, sampling was carried out sequentially. Catheterization was considered successful if the selectivity index) was >5, calculated as the ratio of cortisol concentration between the adrenal vein and the IVC after administration of ACTH.

Unilateral disease was defined by a lateralization index >4, calculated as the ratio of aldosterone to cortisol between the dominant and nondominant side. Apparent bilateral aldosterone suppression was defined by an aldosterone-to-cortisol ratio in both adrenal veins bilaterally lower than that measured in the IVC. Patients with apparent bilateral aldosterone suppression according to AVS results were excluded from the study.[14]

Analysis

The data from the JPAS were studied retrospectively. The patient characteristics and biochemical examinations at diagnosis were investigated. Hypokalemia was defined as either a serum potassium level <3.5 mmol/L or receiving potassium supplementation. The estimated glomerular filtration rate was calculated according to the formula for Japanese people.[15] Left-right differences in lateralization diagnoses were evaluated from the results of CT scans and AVS. In patients who underwent adrenalectomy, we estimated postoperative clinical and biochemical outcomes over either a 6- or 12- month follow-up, referring to the Primary Aldosteronism Surgery Outcome study.[16]

Assay Methods

PAC and PRA were measured using commercially available kits. PAC was determined by RIA (SPAC-S Aldosterone kits;[17] Fuji Rebio, Tokyo, Japan) at all centers. The reference range of PAC in the supine position was 30 to 159 pg/mL. PRA was measured by RIA or enzyme immunoassay. The reference range of PRA in the supine position was 0.3 to 2.9 ng/mL/h (PRA-FR RIA kits;[18] Fuji Rebio) in 15 centers; 0.2 to 2.3 ng/mL/h (PRA enzyme immunoassay kits,[19] Yamasa, Choshi, Japan) in seven centers; and 0.2 to 2.7 ng/mL/h [PRA RIA kits, Yamasa; or Renin RIA beads kits,[20] Fuji Rebio; (N.B., these products are identical, because the vender has been replaced)] in four centers. Plasma active renin concentration (ARC) was measured by immunoradiometric assay (Renin IRMA-FR;[21] Fuji Rebio) in one center. The reference range of ARC in the supine position was 2.5 to 21.4 pg/mL. For statistical analysis, the ARC value was converted to PRA by dividing by 5, according to the Japan Endocrine Society guideline.[12]

Statistics

The data were analyzed and compared using BellCurve for Excel (Social Survey Research Information, Tokyo, Japan). Continuous variables were expressed as either mean ± SD or median and interquartile range. Continuous variables were analyzed using either the one-way ANOVA or the Kruskal-Wallis test, as appropriate. Comparison of frequencies between two groups was estimated by either the χ 2 test or the Fisher exact test, as appropriate. Statistical significance was achieved when the Pvalue was <0.05.

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