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


J Endo Soc. 2019;3(7):1393-1402. 

In This Article


In this study, we demonstrated that unilateral nodular lesions seen on CT imaging and unilateral disease according to AVS in patients with PA were observed more frequently on the left side than on the right side. We also showed a distinct divergence of lateralizing diagnoses between CT and AVS. When a patient has unilateral nodular lesions on CT imaging and a bilateral result according to AVS, it is thought that there are coexisting idiopathic hyperaldosteronism and nonfunctioning adrenal tumors. In addition, when a patient has unilateral disease according to AVS results and bilaterally normal image on CT imaging, it is thought that micro-APA may exist. Discordant results in laterality diagnoses between CT and AVS could be caused by nonfunctioning adrenal tumors and micro-APAs. When patients with unilateral nodular lesions on CT imaging and unilateral disease according to AVS on the opposite side were combined, 322 patients (21.6% of all patients) had a nonfunctioning adrenal tumor, 157 patients (10.5%) had micro-APA, and 41 patients (2.7%) had both a unilateral nonfunctioning tumor and micro-APA on the opposite side. When patients with a plasma cortisol concentration <1.8 μg/dL after a 1-mg dexamethasone suppression test were studied for the left-right distribution by both CT imaging and AVS, the concordance rate between CT and AVS was not different from the results in the total study cohort (data not shown). Therefore, it appears cosecretion of cortisol from adrenal tumors does not contribute to discordant laterality between CT and AVS.

A few studies have investigated the relationship between imaging and AVS used to diagnose patients with PA. Dekkers et al.[6] examined 90 patients with PA with results from both CT and AVS and showed unilateral nodular lesions on CT scans were significantly more frequent on the left side [42 (46.7%) vs 7 (7.8%); P < 0.01]. In contrast, unilateral results of AVS were slightly more frequent on the left side, although this difference was not statistically significant [26 (28.9%) vs 22 (24.4%); P= 0.50). Sam et al.[7] reported that in 342 patients with PA, unilateral lesions seen on CT or MRI were significantly more frequent on the left side [125 (36.5%) vs 66 (19.3%); P < 0.01), whereas unilateral results according to AVS showed a nonsignificant tendency for lesions to be on the right side more frequently when the lateralization index criterion was >4 [71 (20.8%) vs 87 (25.4%); P = 0.15). These three studies, including the current study, showed CT imaging enabled detection of significantly more lesions on the left side. The three studies, however, showed differences in the laterality of AVS. The current study and the Dekkers et al. study[6] used AVS results obtained after ACTH stimulation, whereas the Sam et al. study[7] measured AVS at baseline without ACTH stimulation. These differences in the AVS protocol may have influenced the distribution of the laterality diagnoses.

The results of the current study indicated that APAs, micro-APAs, and nonfunctioning adrenal tumors are more likely to occur on the left side, although reason for this skewed distribution remains unclear. We speculate that there may be two explanations for these findings. First, APAs and nonfunctioning tumors may occur in proportion to the volume of the left and right adrenal glands. Schneller et al.[22] reported that the volume of the adrenal glands measured using multidetector CT in 105 healthy volunteers was significantly greater on the left side than on the right side (4.84 ± 1.67 mL vs 3.62 ± 1.23 mL; P < 0.001). Carsin-Vu et al.[23] reported similar results in study of 154 healthy volunteers (4.5 ± 1.6 mL vs 3.8 ± 1.3 mL; P < 0.001). In contrast, Nougaret et al.[24] and Wang et al.[25] reported there were no significant differences in the volume of the left and right adrenal glands (3.8 ± 1.2 mL vs 3.4 ± 1.0 mL and 4.23 ± 0.74 mL vs 4.26 ± 0.86 mL, respectively). However, these two studies had relatively small sample sizes (40 and 80 subjects, respectively). Considering the results of the current study, APAs (>10 mm in diameter), micro-APAs, and nonfunctioning tumors were commonly more frequent on the left side because the volume of the left adrenal gland of a normal subject was greater than that of the right-sided gland.

Second, it may be easier to detect small tumors in the left adrenal gland using abdominal cross-sectional imaging, because of anatomical differences between the left and right adrenal glands and the different constitution of the surrounding organs. In addition, it appears that the compression direction is different between the left and right adrenal glands when imaging is performed in the supine position. Hao et al.[11] reported that in 1376 patients with incidentally discovered adrenal adenomas, excluding functioning tumors, 75% of unilateral adrenal adenomas were found on the left side. In addition, they showed that a higher proportion of small adrenal adenomas were found on the left side. The current study showed the same tendency, with left-sided nodular lesions being significantly more frequent in groups with small nodular lesions (<20 mm in diameter). This finding supports the hypothesis regarding anatomical differences between adrenal glands. Combining these two mechanisms, asymmetric left-side to right-side ratios of 1.63: 1 for CT imaging and 1.28:1 for AVS may have been achieved in the current study.

In the daily practice of managing PA, consideration should be given to the fact that APAs and nonfunctional tumors are more likely occur on the left side. In addition, it is important to consider that the concordance rate between CT imaging and AVS is low when unilateral nodular lesions are observed on CT scans. In particular, in patients with small unilateral tumors <20 mm in diameter on CT scans, it is also important to note that the concordance rate is lower on the left side than on the right side.

This study had several strengths. First, it was a multicenter collaborative study with a large sample size. Imaging diagnosis of all patients was obtained using CT imaging. Although AVS had a different detailed protocol, blood collection was performed after ACTH stimulation and a uniformed position used for blood sampling. Because the definition of a nodular lesion on CT imaging was set at ≥10 mm, bias between radiologists was less likely to have occurred.

There were some limitations to the study. First, we did not directly review CT images. Second, the unilateral results were underestimated because a stringent criterion was adopted for nodular lesions observed on CT scans and unilateral results according to AVS. However, because the determinations were made using the same criteria, judgment of the left-right distribution was thought to be appropriate. Third, the indication for surgery was different at each center, and because follow-up after surgery was not completed in all patients, we were unable to verify the validity of the criteria for subtype diagnosis.

In conclusion, our results suggest that APAs and nonfunctioning adrenal tumors develop more frequently on the left side in patients with PA and that misdiagnosis of CT-based lateralization may occur more frequently on the left side. These findings should be considered when subtyping of PA is performed.