This multicenter prospective study shows that percutaneous CT-guided radiofrequency ablation for aldosterone-producing adenomas using bipolar radiofrequency system achieved normalization of plasma aldosterone concentration or aldosterone-renin ratio of 86.5% (72.0–94.1: 95% confidence interval) on day 84. In this study, diagnostic criteria of unilateral APA was the lateralized ratio ≥ 2.6. This criterion was based on guideline written by Nishikawa et al. in 2009 [17]. More recently, diagnostic criteria of unilateral APA became more strict, and lateralization index has been recommended to be more than 4 [24, 25]. Hence, there is a possibility that non-unilateral lesion was include to our study. We consider normalization rate of aldosterone after the RFA procedure might increase, when this criteria was applied to our data. Based on a previous study, unilateral adrenalectomy for APA resulted in eradication of hypokalemia and resolution or significant improvement in hypertension in 80% patients at long-term follow-up [20]. Therefore, our study indicated that clinical outcome by bipolar RFA could be achieved comparable with surgical adrenalectomy.
A total of 20 out of 35 patients who had been prescribed antihypertensive drugs were allowed to discontinue their use, while the amount of medication was reduced in 8 cases. Furthermore, 28 out of 29 patients who had been prescribed aldosterone antagonists could discontinue their use. Therefore, our results indicate that percutaneous radiofrequency ablation for aldosterone-producing adenomas would reduce the number of antihypertensive drugs and aldosterone antagonists prescribed in patients with primary hyperaldosteronism.
The advantage of the bipolar RFA system over the unipolar system has been reported in the treatment of hepatocellular carcinoma. Chang et al. showed that the bipolar RFA systems required a smaller number of ablation cycles and shorter ablation time than the monopolar RFA systems [26]. However, in this study, RFA sessions were needed more than once per ablation session in 76.3%. A potential reason for requiring multiple sessions of RFA in the adrenal gland tumor was that the adrenal gland has one of the largest blood supply rates per gram of the organ [27]. Furthermore, RFA sessions were added up to 7 until tumor enhancement disappeared on intraprocedural dynamic CT. This strict treatment policy might be one of the reasons why the total ablation time was slightly longer (19.1 minutes) than that in other reports (10–12 minutes) [28–30].
There have been multiple reports of RFA for adrenal adenomas using monopolar RF devices [10–14, 28–30]. They treated APA of the size from 4 to 34 mm. Mortality and major morbidity was not observed in any reports, and minor morbidity ranged 15–24%. Mean ablation time was 10–12.2 minutes. In this study, major morbidity was observed in one intercostal arterial injury case, minor morbidity was 26%. Intercostal arterial injury could happen when inserting the needle through the intercostal area, especially in CT guided procedure, because arteries can not well visualized in non-contrast enhanced CT images. Minor morbidity rate in this study was comparable in previous reports. More recently, Liu et al. reported the use of a monopolar RF system for APA in 36 cases with a mean follow-up duration of 6.2 years in a single facility [28]. The long-term recurrence rate was 0%. Therefore, CT-guided RF ablation was considered as an effective treatment for APA with high sustainable long-term treatment success. However there have been reported only single center study using unipolar devices. This study was unique in terms of its multicenter prospective study design and the use of a bipolar system for RFA of APA.
The normalization of plasma aldosterone concentration or ARR was 86.5% on day 84. One of the causes of clinical failure might have been incomplete ablation of the APA. One of a possible reason is that a residual microadenoma located in the non-ablated area in the treated gland, which could not be detected by conventional AVS. In this study, APA was diagnosed by conventional AVS and dynamic CT, and segmental AVS was not performed in all patients [31]. With segmental AVS, the location of APA in the adrenal gland could be found more precisely. It is more important to detect the accurate location of APA using segmental AVS when performing percutaneous RFA, because non-functional APA and functional microadenoma could coexist on the same side of the adrenal gland.
Regarding complications, intercostal artery injury occurred in one case in this study (2.6%). In a previous study, the rate of major complications caused by RFA, including intercostal artery injury and abscess formation, was reported to range from 0–11.5% [12, 26, 28, 31]. Therefore, this procedure should be performed by a skilled interventional team that has extensive experience with CT-guided procedures in a facility with a CT fluoroscopy and angiography system that helps in case of possible emergent vascular embolization of unexpected bleeding.
From our results, intraprocedural hypertension > 180 mmHg was observed in 43% of cases, whereas a previous study reported that it was observed in only 8–20% of the cases [12, 29]. The reason for this discrepancy is unknown; however, in this study, systolic NIBP was measured continuously from the beginning to the end of the ablation cycle. This might have led to the detection of intraprocedural hypertension occurring for a short time. Another possibility in this study is that many APAs were located close to the adrenal medulla, or a wider range was ablated by the bipolar RFA system, which caused ablation of the adrenal medulla. However, these probabilities were not examined in this study and should be discussed in future.
Our study had limitations. First, the follow-up period was shorter than that in previous studies. Since this study was prospective study and was already censored, the follow-up period can not be extended, but studies on long term outcome are planned. Similar to the study by Liu et al., the effect of RFA on APA is expected to be long-lasting [28]. However, as all patients in our study were on clinical follow-up, long-term results of our cohorts will be presented in future. Second, there has been no comparison between bipolar and monopolar or even surgical approach, this should be considered in the future. Third, histological proof of the adrenal tumor was not obtained in any case. Malignant adrenal tumors were not completely ruled out by histological evaluation.
In conclusion, percutaneous CT-guided radiofrequency ablation for aldosterone-producing adenoma using a bipolar radiofrequency system would be safe and effective. Percutaneous radiofrequency ablation is a less invasive therapeutic option for treating aldosterone-producing adenomas.