刘 谦

1. Single-center Outcome of Laparoscopic Unilateral Adrenalectomy for Patients With Primary Aldosteronism: Lateralizing Disease Using Results of Adrenal Venous Sampling 刘 谦 Shigeto Ishidoya, Yasuhiro Kaiho, Akihiro Ito, et al. UrologyVolume 78, Issue 1, July 2011, Pages 68-73

2. Introduction Large numbers of patients with essential hypertension are secondary hypertension associated with adrenal disease. Primary aldosteronism (PA) is the most frequent cause. Patients with PA are 5%-10% of all hypertensive subjects. The number of patients with newly diagnosed PA has been markedly increasing.

3. Introduction Subtype classification of PA: Aldosterone-producing adenoma (APA). Bilateral idiopathic hyperplasia (IHA). Primary unilateral adrenal hyperplasia Aldosterone-producing adrenocortical carcinoma. Glucocorticoid-remediable aldosteronism (or familial hyperaldosteronism type 1). Ectopic aldosterone-producing adenoma

4. Introduction A definitive diagnosis and lateralization are required for adequate treatment against this correctable disease. Especially in differentiating unilateral APA from bilateral IHA, because APA is optimally treated surgically and IHA should be treated medically. AVS should be performed to establish or exclude the unilateral form of PA. The goal of treatment has been to normalize the patients' blood pressure and aldosterone level. when unilateral aldosterone excess has been confirmed, it should optimally be treated using laparoscopic adrenalectomy.

5. Introduction However, routine CT and only selective use of AVS have been are performed to confirm PA. CT findings alone can reliably diagnose the correct lateralization in 37%-44% of patients with PA. We hypothesized that we would detect more patients with CT-negative unilateral PA. Therefore, we routinely conducted AVS for all patients with biochemically proven PA and performed total laparoscopic adrenalectomy, regardless of the CT findings, for those with unilateral aldosterone excess

6. Introduction The present study assessed the clinical effect of the routine use of AVS and investigated the characteristics of the patients undergoing unilateral laparoscopic adrenalectomy in a large cohort.

7. Materials and methods The present study was a retrospective cohort study. Patients with APA seen at a single tertiary care referral center. From 2000 to 2009. A total of 174 consecutive patients with PA. Underwent unilateral laparoscopic adrenalectomy.

8. Case Finding Test The initial screening examination by local physicians for paitients with hypertension: The plasma aldosterone concentration (PAC)/plasma renin activity ratio. Serum potassium measurement. When the patients were suspected to have PA, they were referred to the Tohoku University Hospital for a subsequent confirmatory test.

9. Confirmatory Test The staff endocrinologists performed several biochemical examinations: Captopril suppression test. Adrenal multidetector CT (MDCT). All patients with biochemical evidence of PA were recommended to undergo AVS, regardless of the findings from MDCT, unless the patient was contraindicated for surgery.

10. Adrenal Venous Sampling AVS was performed by a staff radiologist. Bilateral adrenal veins were simultaneously catheterized, Adrenal blood sample was obtained. All patients were given an intravenous injection of 0.25 mg adrenocorticotropic hormone (ACTH), and a second set of blood samples was taken. Successful adrenal venous catheterization was confirmed by monitoring the cortisol levels after ACTH stimulation. No complications during AVS during the present study. We compared the A/C ratio on the higher side to that on the lower side ([A/C]adrenal vein/[A/C]contralateral adrenal vein).

11. Adrenal Venous Sampling Several criteria have been reported to determine the lateralization of aldosterone hypersecretion in patients using AVS. We used a cutoff of 2.6:1 and also adopted an absolute aldosterone concentration cutoff of >1340 ng/dL (after 0.25 mg of ACTH stimulation). Using these criteria, the patients with PA were subclassified as having APA and IHA.

12. Adrenal Venous Sampling A patient whose A/C ratio ([A/C]adrenal vein/[A/C]contralateral adrenal vein) was >2.6:1 and whose absolute aldosterone concentration in the ipsilateral adrenal vein was >1340 ng/dL, was diagnosed, not with IHA, but with APA. When biochemically lateralized patients did not show an apparent adenoma on MDCT, we estimated that: Unilateral aldosterone-producing microadenoma (micro-APA) Unilateral adrenal hyperplasia was present.

13. Unilateral Adrenalectomy The Endocrine Society Clinical Practice Guidelines have recommended laparoscopic adrenalectomy for patients with unilateral aldosterone excess and medical treatment with a mineral corticoid antagonist for patients with bilateral disease. Using this guideline, we performed laparoscopic total unilateral adrenalectomy in 174 patients with unilateral PA. Surgery was undertaken using either a transperitoneal or a retroperitoneal approach according to the patient's condition and surgeon preference.

14. Unilateral Adrenalectomy The patients were monitored for blood pressure, PAC, plasma renin activity, serum potassium, and other factors for 1 week after surgery. The number of antihypertensive agents used was also recorded.

15. Unilateral Adrenalectomy A single pathologist (H.S.) examined all the extirpated specimens. When no apparent macroadenoma was detected in the initial evaluation of the hematoxylin-eosin stained slides, a step section was made and histologic examination, including immunostaining with 3β-hydroxysteroid dehydrogenase (3β-HSD羟基类固醇脱氢酶).

16. Results A total of 174 patients 93 men and 81 women (mean age ± SD 52.0 ± 11.4 years). The median PAC and plasma renin activity level was 22.6 ng/dL (range 6.9-82.1) and 0.2 ng/mL/h (range 0.2-11.2), respectively. The median duration of hypertension was 10 years (range 1-42). All patients underwent total laparoscopic removal of the affected adrenal gland without conversion to open surgery or perioperative death. 3 cases were associated with minor complications. One patient required a blood transfusion. 2 developed temporary subileus.

17. Results

18. Results All 174 patients with a biochemical diagnosis of PA underwent AVS and were confirmed to have unilateral disease. We categorized this cohort into 3 groups according to the CT findings. 74.1% were in the first category (type 1A), which included CT-positive macroadenoma. The second category was CT-negative unilateral aldosterone excess (type 2A). Only 3 patients (1.8%) were diagnosed with adrenocortical hyperplasia (third group, type 3).

19. Results Pathologic examination demonstrated that most patients (n = 42; 24.1%) in the second group had microadenoma (type 2A). In aldosterone synthesis, 3β-HSD is considered an indispensable enzyme, and positive 3β-HSD immunoreactivity in the zona glomerulosa should be considered substantial evidence of excessive aldosterone-producing hyperplasia. In addition, positive immunoreactivity of 3β-HSD with the absence of c17 immunoreactivity is considered characteristic of small excessive aldosterone-producing cortical lesions.

20. Results

21. Representative Patient With Type 2A A 38-year-old man had had a 10-year history of hypertension. The screening and confirmatory tests were positive and compatible with the finding of PA. Adrenal MDCT did not detect any nodules. AVS lateralized the aldosterone secretion to the right. After right total adrenalectomy, we detected a small nodule (2 mm) on hematoxylin-eosin staining, with positive findings for 3β-HSD and negative c17 findings in this lesion.

22. Postoperative Findings The median plasma aldosterone levels were significantly reduced 1 week after surgery. The aldosterone level had normalized (3.6-24 ng/dL) in all (98.9%) but 2 patients (P < .01). The median number of preoperative antihypertensive agents was 3 (range 1-11). The number of medications had decreased profoundly 1 month after adrenalectomy. 34 (19.5%) needed no agents and 56 (32.2%) required only 1. 155 (89.1%) had significant resolution or improvement of hypertension (P < .05); However, 19 patients (10.9%) required the same or a greater number of medications even after unilateral total adrenalectomy.

23. Postoperative Findings

24. Comment The primary objective of adrenalectomy for PA: Normalize the aldosterone excess  lower the blood pressure  prevent additional organ damage. The diagnostic procedure and treatment scheme for patients with PA have long been debated. Patients with unilateral disease can undergo laparoscopic adrenalectomy after the aldosterone excess has been functionally lateralized using AVS. This is the first and largest cohort study to perform unilateral laparoscopic total adrenalectomy according to the recommendations from these guidelines.

25. Comment Our study found unique characteristics regarding microadenoma in PA. Young (2007) referred to 6 subtype classifications of PA: Most common subtypes: APA (35%) Bilateral IHA (60%) We demonstrating PA due to microadenoma and the usefulness of AVS for determining the lateralization.

26. Comment 24.1% aldosterone excess demonstrated an aldosterone-producing microadenoma in our cohort more than we had previously expected. We have established the usefulness of examining the immunoreactivity of 3β-HSD for differentiating microadenoma from adrenocortical hyperplasia. Only 1.8% of the cohort had hyperplasia, almost consistent with the findings from the review by Young (2% of PA). The guidelines have recommended that “the presence of a unilateral form of PA should be established/excluded by bilateral and optimally treated by laparoscopic adrenalectomy.”

27. Comment Taken together, we have proposed a simple subtype category for PA using the AVS and CT findings and including a concept of microadenoma. for pretreatment decision making and be beneficial for both general practice and surgery.

28. Comment The role of AVS in the differentiation of unilateral and bilateral disease has long been discussed. 2 major issues regarding AVS have not yet been resolved.

29. Comment Laparoscopic unilateral total adrenalectomy can lead to satisfying short-term outcomes, regardless of whether a patient has unilateral macro-APA, micro-APA, or hyperplasia. All (98.9%) but 2 patients demonstrated normalization of hyperaldosteronemia postoperatively. Furthermore, 89.1% of patients had resolution of hypertension or reductions in the number of hypertensive medications required monthly. Although our study lacked long-term follow-up data, we are confident that a treatment scheme using AVS-induced lateralization could be useful and practicable.

30. Conclusions AVS can induce adequate lateralization of patients with unilateral aldosterone excess, leading to satisfying short-term treatment outcomes. The subtype classification of PA should be reconsidered in the AVS era, because we found that nearly one fourth of surgically resected patients had had CT-negative micro-APA.