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Vascular and Interventional Radiology |
1 From the Department of Radiology, Faculty of Medicine, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan. From the 2000 RSNA scientific assembly. Received November 7, 2001; revision requested January 21, 2002; final revision received July 26; accepted August 19. Address correspondence to H.H. (e-mail: hirofumi@m3.kufm.kagoshima-u.ac.jp).
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODS RESULTS DISCUSSIONREFERENCES |
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MATERIALS AND METHODS: Thirty-three patients with unilateral aldosteronomas were treated with SAAE. A 0.2–7.0-mL dose of high-concentration ethanol (HCE) was selectively infused into the feeding arterial branches of the aldosteronoma through a microcatheter by using a coaxial technique. Hormone, electrolyte, and blood pressure levels were evaluated after SAAE. The influence of background factors on SAAE success rate and the influence of age on hypertension in the patients in whom SAAE was successful were assessed with the Fisher exact test and a logistic regression model.
RESULTS: SAAE was successful in 27 (82%) of 33 patients. SAAE success rate was not influenced by sex, age, hypertension duration, family history of hypertension, adenoma site, type of ethanol used, or number of embolized arteries. The destructive effects of SAAE continued for the 6–94-month (mean, 45 months) follow-up period in all patients in whom SAAE was successful. In one patient, aldosteronoma recurred 15 months after SAAE and the second SAAE was successful. Blood pressure decreased in all 11 (100%) patients aged 45 years or younger and in eight (50%) of 16 patients older than 45 years (P = .008). Blood pressure decreased within 4 weeks after SAAE in 15 (79%) of these 19 patients. The rate of blood pressure reduction after SAAE decreased with increasing age, and the correlation was significant (P = .022). None of the 33 patients had severe complications.
CONCLUSION: SAAE with HCE is an effective therapy for aldosteronoma.
© RSNA, 2003
Index terms: Adrenal gland, CT, 862.12111, 862.12112, 862.12115 • Adrenal gland, neoplasms, 862.31 • Alcohol ablation, 862.1264
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTS DISCUSSIONREFERENCES |
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MATERIALS AND METHODS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTS DISCUSSIONREFERENCES |
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Fifteen patients had a right-sided adenoma and 18 patients a left-sided adenoma. Tumor size ranged from 8 to 30 mm in diameter (mean, 14.5 mm), as estimated at CT. Thirty-two patients had a history of hypertension of 8 months to 20 years duration. The duration of hypertension in one patient was unknown. All patients had clinical signs of hypokalemia at presentation. Levels of 17-hydroxycorticosteroids and 17-ketosteroids in the urine were within normal limits. Refusal to undergo surgery and high risk with surgery due to complications such as cerebrovascular disease, pulmonary emphysema, and cardiac disease were considered indications for SAAE. Four patients had a history of cerebral hemorrhage. Our institutional review board approved the study. All patients gave informed consent after the treatment choices of open surgery, SAAE, or (more recently) laparoscopic surgery had been discussed with them.
Imaging and Interventional Procedures
Diagnostic angiography and the interventional procedures were performed by three authors of this article (H.H., H.I., Y.B.) and by some of the authors of our previous report (4). The details of the therapeutic procedures have been reported previously (4): We performed selective venous blood sampling and identified the arteries feeding the adenoma during an initial arteriographic examination. Venous sampling was performed before arteriography to prevent the inadvertent release of hormones. Then, selective arteriography of the inferior phrenic, middle adrenal, and renal arteries was performed. In cases in which it was difficult to recognize the whole adenoma stain, the feeding arteries were identified by using helical CT (not CT fluoroscopy) during adrenal arteriography (27 of 47 arteriographic examinations of feeding arteries) before embolization. This was helpful for confirming the identification of the feeding arteries.
SAAE was performed after the unilaterality of the adenomas was confirmed with use of diagnostic examinations, including hormone level testing of venous blood samples. The hormone data arrived 7–10 days after sampling. We used 4–5-F shepherd’s crook– or cobra-type outer catheters (Excellent EN catheter or Disposable torque catheter; Hanacomedical, Saitama, Japan). Once the adenoma was identified, a microcatheter (Tracker18 or Tracker10; Target Therapeutics, San Jose, Calif) was inserted as superselectively as possible through the outer catheter by means of the coaxial method. HCE was slowly injected into the artery or arterial branch that was feeding the adenoma. When selective insertion of the catheter into the feeding artery was difficult—usually, this was when the feeding blood vessel originated in the inferior phrenic or renal capsular arteries—a blood stream modification was carried out by using microcoils (Tornade; Cook, Bloomington, Ind) or gelatin sponge particles (Gelfoam; Pharmacia and Upjohn, Kalamazoo, Mich) to prevent the ethanol from entering the nontargeted organs. There were 12 such cases. The volume of HCE administered was approximately the same as the volume of contrast medium (iohexol, Omnipaque; Nycomed, Princeton, NJ or iopamidol, Iopamiron; Schering, Berlin, Germany) administered to cause tumor opacification and tumor staining. Immediately after the HCE injection, arteriography was performed at the same catheter position to confirm the disappearance of tumor staining (Figure, parts a and b). Residual tumor staining was treated with additional injections of 0.2–0.5 mL of HCE until follow-up arteriographic results were negative.
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SAAE of all of the detected feeder arteries was performed through a single feeding artery in 19 patients (right artery in eight patients, left artery in 11 patients) and through two feeding arteries in 14 patients (right and left arteries in seven patients each). SAAE was performed a mean of 1.4 times: 22 patients underwent therapy once; nine patients, twice; and two patients, one of whom had a recurrent aldosteronoma, three times. The embolization was repeated when the plasma aldosterone levels either did not decrease or increased again within 1 month after the first SAAE. The interval between the first and either second or third SAAE was usually 2–3 weeks. In almost all cases of second or third SAAE, we embolized different feeder arteries, but in some cases, we embolized the same feeder artery that showed recanalization.
The duration of hospital stay was 22–121 days (mean, 48 days ± 21). Of the 27 patients in whom SAAE was successful, the 14 patients who were treated before 1995 required longer hospital stays (mean, 60 days ± 22) than did the 13 patients who were treated after 1995 (mean, 34 days ± 9). The hospital stay included the days of diagnostic testing and being monitored after SAAE.
Evaluations during and after SAAE
The patients’ blood pressure, pulse rate, body temperature, neurologic signs, electrocardiographic findings, and subjective complaints were monitored during and immediately after SAAE. Hormone and electrolyte levels were measured on day 1 or 2 and weeks 1 and 2 after SAAE. The tumor destruction action of SAAE was estimated on the basis of plasma aldosterone levels after the procedure. We performed follow-up CT (Figure, parts c and d) and adrenocortical scintigraphy (6) 1 week after SAAE to evaluate the effectiveness of the treatment. These imaging data were evaluated by consensus among three authors (H.H., M.N., S.T.). After being discharged from the hospital, the patients underwent follow-up testing of blood pressure and electrolyte and hormone levels every 1–6 months.
Successful eradication of tumor was defined as the persistence of plasma aldosterone and renin activity levels within the normal range for a follow-up period of longer than 6 months. Failed eradication of tumor was defined as an increase in plasma aldosterone levels to above the normal range and persisting suppressed renin activity within 1 month after SAAE. Recurrence was defined as the reappearance of plasma aldosterone levels higher than the normal range and suppressed renin activity more than 6 months after SAAE.
The degree of improvement in hypertension was classified into three groups: normalization, decrease in severity, and no change. Normalization was defined as blood pressure lower than 140/90 mm Hg without the use of antihypertensive medication. Decrease in severity was defined as a decrease of at least 20 mm Hg in the systolic or diastolic blood pressure either without the use of antihypertensive medication or with a decrease in antihypertensive medication dosage.
Statistical Analyses
We used the Fisher exact test and a logistic regression model to evaluate the factors that could affect the success of SAAE—specifically, age, sex, duration of hypertension, family history of hypertension, adenoma site, use of absolute ethanol or the iohexol-ethanol solution, and number of embolized arteries. These statistical tests were also used to evaluate the influence of age on blood pressure decrease. P < .05 was considered to indicate a statistically significant difference.
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RESULTS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTS DISCUSSIONREFERENCES |
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Aldosteronoma Function after SAAE
Regardless of the eventual outcome of SAAE, the plasma aldosterone level returned to normal within 24 hours after SAAE in all patients. In those patients in whom the treatment eventually failed, the plasma aldosterone levels gradually increased to pretreatment levels within 1 month after embolization. SAAE was successful in 27 (82%) of 33 patients. The plasma renin activity and serum potassium levels normalized within 1 month after SAAE in all except one of these 27 patients. One patient’s plasma renin activity remained suppressed for more than 1 month. The mean number of treatments required for successful SAAE of the aldosteronoma was 1.4: 18 patients required one treatment for successful SAAE; seven patients, two treatment courses; and two patients, three treatment courses. Among the 27 patients in whom SAAE was successful, the 14 patients who were treated before 1995 required additional courses of treatment (mean, 1.7 courses ± 0.7) more frequently than did the 13 patients who were treated after 1995 (mean, 1.1 courses ± 0.3).
We looked for factors that potentially could affect the SAAE success rate, including age, sex, duration of hypertension, family history of hypertension, site of adenoma, use of absolute ethanol or the iohexol-ethanol solution, and number of embolized arteries. None of these factors had a statistically significant effect according to Fisher exact test results (Table 1). The logistic regression model revealed that no variables were significantly associated with the SAAE success rate. However, the SAAE success rate did decrease with increasing age, although the association was not significant (P = .099).
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Imaging Findings after SAAE
Nonhelical CT (TCT-900S; Toshiba, Tokyo, Japan) was performed in the 14 patients who underwent SAAE before 1995, so the times of enhancement and the contrast medium (iohexol or iopamidol) injection rates were not uniform. After 1995, 13 patients in whom SAAE was successful underwent helical CT (Xvigor; Toshiba) with contrast medium enhancement. In 12 of these 13 patients, the CT attenuation of the adenoma during the arterial dominant phase decreased by more than 20 HU after SAAE compared with the attenuation measured before therapy. The other patient underwent only helical CT without contrast medium after SAAE, and we could not evaluate the viability of the adenoma.
Scintigraphic assessment was performed in all patients. Before SAAE, the aldosteronoma was visualized as a "hot" (ie, demonstrating greater activity than surrounding tissue) or "warm" (ie, demonstrating slightly greater activity than surrounding tissue) nodule in all patients. After SAAE, these hot or warm nodules disappeared in the successful cases.
Blood Pressure Reduction after SAAE
All but one patient had hypertension of 8 months to 20 years duration (mean, 8.6 years) before they underwent SAAE. One patient had hypertension of unknown duration. Of the 27 patients who were successfully treated with SAAE, nine had a normalization of blood pressure after embolization and 10 had a decrease in blood pressure. Age had a statistically significant effect on long-term blood pressure status after SAAE: Lower blood pressure was observed in 11 of 11 patients aged 45 years or younger and in eight of 16 patients older than 45 years (P = .008, Fisher exact test) (Table 3). Blood pressure decreased within 4 weeks after SAAE in 15 (79%) of these 19 patients and within 2 or more months after SAAE in four (21%) patients (Table 4). The post-SAAE reduction in blood pressure was not influenced by either duration of hypertension before embolization or family history of hypertension. The rate of blood pressure reduction after SAAE decreased with increasing age, and the association was significant (P = .022) when we used the logistic regression model for analysis.
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTS DISCUSSIONREFERENCES |
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The number of courses of SAAE required to completely ablate the adenoma was more frequent before 1995 (mean, 1.7 courses ± 0.7 vs 1.1 courses ± 0.3 after 1995). Although we initially assumed that this was due to difficulty visualizing the absolute ethanol, the use of an iohexol-ethanol solution (5) did not have a significant effect on the SAAE success rate (Table 1). We suspected that this was because there were additional feeding arteries in a substantial number (14 [42%] of 33) of patients.
Owing to the recently developed laparoscopic adrenalectomy procedure, patients are now able to walk around at some point postoperatively the day of the surgery, and the duration of hospital stay is reduced (11–13). SAAE, however, has a number of advantages over open and laparoscopic surgeries. SAAE is performed in an average of 30–120 minutes (4), whereas open surgery usually lasts 133 minutes and laparoscopic surgery 201–316 minutes (11). In addition, the volume of hemorrhage with SAAE is small (5–20 mL) compared with that with open or laparoscopic surgery (77–299 mL) (11). Also, SAAE is performed with local anesthesia and one small incision at the femoral artery. SAAE can also be performed more easily in obese patients than can laparoscopic surgery (14). The rate of successful SAAE of aldosteronoma (82%) in the present study is lower than that reported with open or laparoscopic surgery (
90%) (15,16). However, SAAE can be performed in patients who are at high risk due to complications such as cerebrovascular disease, pulmonary emphysema, and cardiac disease or who refuse to undergo surgery.
Two additional minimally invasive treatments have been described: CT-guided percutaneous local injection of ethanol into an aldosteronoma (17) and CT-guided percutaneous injection of acetic acid into aldosteronomas and cortisol-producing tumors (18). However, the study of these techniques in a larger group of patients is required to validate their effectiveness. A number of techniques have also been suggested as aids to percutaneous CT-guided adrenal biopsy (19,20). However, the rate of complications with CT-guided biopsy of the adrenal glands is higher than that with CT-guided biopsy of other organs (21), presumably because of the small size of these tumors (
2 cm) (22).
Although we observed no serious complications in our study, SAAE is associated with a risk of complications, including hypertensive crisis (23). Previous reports have also described serious complications that occurred during adrenal adenoma ablation with retrograde venous ethanol injection (24) and adrenal arterial embolization to treat Cushing syndrome (25). For such applications, SAAE may be safer than percutaneous CT-guided injection because the patient is treated while in the prone rather than supine position (17–20), and, thus, cardiorespiratory responses can be monitored and cardiopulmonary resuscitation can be rapidly initiated.
Although the needle used for CT-guided percutaneous treatment of adrenal tumors is fine (21-gauge), the frequency of complications (2.8%–5.3%) such as hemorrhage is not influenced by needle size (21,26). Although hemorrhage is a major, potentially fatal complication of percutaneous fine-needle abdominal biopsy (27,28), the mortality rate associated with this procedure is low (0.008%–0.031% [28]). SAAE appears to be safer in cases of severe arterial hemorrhage that require transcatheter arterial embolization because it can be performed immediately.
The rate of blood pressure decrease after SAAE (Table 3) in our study was similar to reported surgical results (15,16,29). There are few reports of the intervals between treatment and the blood pressure decrease. Young et al (30) suggested that it takes 3–6 months before one sees a blood pressure decrease, and Ito et al (31) reported that only 60% of the patients whom they examined during the first 3 months after surgery had lower blood pressure. In our study, most patients (79%) had some decrease in blood pressure within a month; however, a few patients had lower blood pressure up to 8 months after SAAE (Table 4). The rate of lower blood pressure at 1 year after operation has been reported to be 70% (30), similar to our results.
To our knowledge, there are only two reports of the effect of age on blood pressure response to treatment of aldosteronomas: Granberg et al (16) reported that normalization of blood pressure did not correlate with age, and Rutherford et al (14) reported that normalization of blood pressure occurred in six of six patients 50 years or younger. In our study, blood pressure response to SAAE was significantly affected by age (age 45 years vs >45 years, P < .05), and the improvement rate decreased with increasing age (P = .022). This may have been because older patients may also have concomitant essential hypertension (32) or hypertension due to irreversible parenchymal changes (33). Thus, elderly patients with primary aldosteronism but normokalemia may not be suitable candidates for surgical intervention; however, such patients are rarely encountered (4,15,29,33,34).
In the present study, complications with SAAE were uncommon, and all of the complications that did occur resolved within 2 weeks after therapy (Table 5). Pleural effusion was observed in only five of 24 patients who were treated with SAAE of the inferior phrenic artery. Thus, the effusion may have been a reaction to transient ischemia of the diaphragm. In our series, there were no complications such as wound infection, incisional hernia, deep venous thrombus, pulmonary embolus, contusion to the adjacent organ, pneumonia, or intra- or postoperative bleeding requiring blood transfusion and surgical treatment, all of which may occur during laparoscopic adrenalectomy (13,14). In addition, there were no deaths or cases that required surgical intervention.
In conclusion, SAAE is almost as effective as open or laparoscopic surgery for the treatment of aldosteronomas. It causes no serious complications and has better cosmetic results than does laparoscopic surgery. Thus, SAAE should be considered as one of the therapeutic strategies for aldosteronomas. On the other hand, there were a number of therapeutic failures that required subsequent surgery in our study. Greater experience with the SAAE technique, the development of more selective catheters and guide wires, and the careful evaluation of the arteries feeding the adenomas should lead to further increases in the effectiveness of this approach to treating aldosteronomas.
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ACKNOWLEDGMENTS |
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FOOTNOTES |
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Author contributions: Guarantor of integrity of entire study, M.N.; study concepts, M.N.; study design, H.H., H.I.; literature research, H.H., Y.B., H.I.; clinical studies, H.H., Y.B., H.I.; data acquisition, H.H., Y.B., S.T.; data analysis/interpretation, H.H.; statistical analysis, H.H.; manuscript preparation, definition of intellectual content, and editing, H.H.; manuscript revision/review, M.N., H.H.; manuscript final version approval, M.N.
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REFERENCES |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTS DISCUSSIONREFERENCES |
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This article has been cited by other articles:
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  S. M. Patel, R. K. Lingam, T. I. Beaconsfield, T. L. Tran, and B. Brown Role of Radiology in the Management of Primary Aldosteronism RadioGraphics, July 1, 2007; 27(4): 1145 - 1157. [Abstract] [Full Text] [PDF]
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 W. W. Mayo-Smith and D. E. Dupuy Adrenal Neoplasms: CT-guided Radiofrequency Ablation--Preliminary Results Radiology, April 1, 2004; 231(1): 225 - 230. [Abstract] [Full Text] [PDF]
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