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Systematic Review: Diagnostic Procedures to Differentiate Unilateral From Bilateral Adrenal Abnormality in Primary Aldosteronism
7 auth. M. Kempers, J. Lenders, Lieke van Outheusden, G. J. van der Wilt, L. S. Schultze Kool, A. Hermus, ...
Context Primary aldosteronism can involve 1 or both adrenal glands. Surgery is indicated only for unilateral disease. Experts prefer adrenal vein sampling (AVS) to localize the source, but many physicians rely on computed tomography (CT) or magnetic…
Context Primary aldosteronism can involve 1 or both adrenal glands. Surgery is indicated only for unilateral disease. Experts prefer adrenal vein sampling (AVS) to localize the source, but many physicians rely on computed tomography (CT) or magnetic resonance imaging (MRI). Content The authors reviewed 38 studies that compared localization by CT/MRI and AVS. In 37.8% of 950 patients, CT/MRI results disagreed with AVS results. Based on CT/MRI alone, the following would have occurred: surgery for bilateral disease in 14.6% of patients, medical treatment for unilateral disease in 19.1%, and removal of the wrong adrenal in 3.9%. Caution Long-term outcomes, the best indicator of success, were often missing. Implication Because CT/MRI is not reliable, AVS is preferred for staging primary aldosteronism. The Editors Although debate on the true prevalence of primary aldosteronism among the hypertensive population continues, primary aldosteronism is considered a frequent and curable form of hypertension. Depending on the population tested and the tools used to confirm the diagnosis, primary aldosteronism is reported to occur in approximately 5% to 13% of hypertensive patients, predominantly those with severe hypertension (18). Because patients with unilateral adrenal hypersecretion of aldosterone may be cured by unilateral adrenalectomy, differentiating unilateral (most often an adenoma) from bilateral (most often bilateral hyperplasia) aldosterone hypersecretion is important. In patients with bilateral hypersecretion, medical treatment, usually mineralocorticoid-receptor antagonists, is the therapy of choice. In the late 1960s, adrenal vein sampling (AVS) was introduced as a test to distinguish unilateral from bilateral primary aldosteronism (9). Later, computed tomography (CT) and magnetic resonance imaging (MRI) were adopted as the primary procedures with which to differentiate unilateral from bilateral adrenal abnormalities. In a considerable proportion of patients, however, CT and MRI results were found to disagree with those of AVS; CT/MRI would show, for example, a unilateral abnormal adrenal gland when aldosterone hypersecretion actually was occurring in the contralateral gland or bilaterally, or would show bilateral normal or abnormal adrenal glands when aldosterone hypersecretion was occurring in only 1 gland (1014). A recent prospective study of 203 patients showed that operative planning based on anatomical imaging alone would have inappropriately excluded 21.7% of patients from adrenalectomy and would have led to unnecessary sugery in 24.7% (15). Thus, in recent years, AVS has regained popularity. Almost all experts agree that the criterion standard diagnostic test for lateralization of aldosterone secretion is measurement of aldosterone levels in the adrenal veins through AVS (11, 12, 1620). However, AVS has not replaced CT/MRI because it is not universally available and CT/MRI helps the surgeon to accurately localize the adrenal gland. In addition, AVS is a complicated technique with a relatively high chance of procedural failure (for example, when an adrenal vein cannot be adequately cannulated) in inexperienced hands and is more invasive than CT/MRI. Many physicians therefore perform CT/MRI as the first and sometimes only investigation to diagnose laterality of aldosterone secretion. Because misinterpretation of the imaging results could lead to inappropriate treatment, it is essential to know, under the assumption that AVS is the criterion standard test, how often inappropriate treatment decisions would have been made on the basis of CT/MRI findings alone. We performed a systematic literature search and analyzed studies of patients who underwent both techniques. Methods Data Sources and Searches We conducted a systematic search of PubMed, MEDLINE, and EMBASE to find English-, French-, German-, or Dutch-language studies on primary aldosteronism by using the following search terms: ((primary hyperaldosteronism) OR (primary aldosteronism) OR (Conn) OR (hyperaldosteronism) OR (aldosterone-producing adenoma) OR (APA) OR (idiopathic hyperaldosteronism) OR (IHA) OR (primary adrenal hyperplasia) OR (PAH) OR (bilateral adrenal hyperplasia) OR (BAH)) AND ((adrenal venous sampling) OR (AVS) OR (venous sampling) OR (vein sampling) OR (adrenal vein) OR (adrenal venous)). We searched the Cochrane Library using the search string primary hyperaldosteronism or hyperaldosteronism and AVS or adrenal venous sampling for clinical trials published in English, French, German, or Dutch. Searches are up to date through April 2009. We sought to include all studies that performed both AVS and CT/MRI. We assumed that articles that reported on AVS results would also report on CT/MRI findings because CT/MRI is the standard imaging study in patients with primary aldosteronism. Study Selection Two reviewers independently and in duplicate assessed the eligibility of all abstracts. We excluded abstracts if they represented reviews or practice guidelines or if they, with certainty, described only studies in animals or children; patients without primary aldosteronism; or only 1 patient. If we could not make a decision about inclusion solely on the basis of the abstracts, we retrieved and reviewed full-text articles. We considered studies eligible for inclusion if they met the following criteria: 1) original reported results, not previously published or used in earlier studies; 2) adult patients (age> 18 years) with a diagnosis of primary aldosteronism; 3) description of more than 1 patient to avoid publication bias (when only 1 patient is described, there is a high a priori chance that the findings in this patient were unusual, which could imply that such studies are more likely to contain results in which CT/MRI did not agree with AVS results); 4) CT/MRI plus bilateral selective AVS performed in all patients, with the results of both investigations reported; and 5) publication from 1977 onward (CT has been available since that year). We excluded articles if 1) data had already been published (only the most recent publication was used), 2) inclusion bias was suspected because patients with concordant results seemed to have been selectively included or because selective examples of concordant and discordant CT/MRI and AVS results were presumed to have been given, and 3) only discordant results were described. To ensure interobserver consistency, differences in interpretation were resolved by consensus of the 2 reviewers, by group conferences with the other authors, or by referencing the original full-text article. Data Extraction and Quality Assessment We made a database of all studies eligible for inclusion. For each eligible study, we recorded aggregated results for the patients for whom the study reported the following: CT/MRI and AVS results; the techniques of CT, MRI, and AVS (such as slice thickness of the CT/MRI images); use of synthetic adrenocorticotropic hormone (ACTH) during AVS; and the AVS criteria used to determine whether aldosterone secretion was lateralized. For the 950 patients whose CT/MRI and AVS results could be retrieved, we recorded such characteristics as age, sex, blood pressure, and serum potassium level and biochemical variables (such as criteria for diagnosis of primary aldosteronism), as well as treatment strategy and patient follow-up if we could link those characteristics with certainty to these patients. Because the diagnostic criteria for primary aldosteronism differ in their stringency, we subdivided the articles by whether the diagnosis of primary aldosteronism was based on a sodium chloride loading test (the most stringent criterion) or on the aldosteronerenin ratio (less stringent criterion) or plasma aldosterone concentration plus plasma renin activity or plasma renin concentration (less stringent criterion). We also evaluated whether the report mentioned the cutoff value of both the selectivity criterion and the lateralization criterion. The selectivity criterion is used to determine whether blood was drawn selectively from the adrenal veins and not from an adjacent vein; this ratio is calculated for both the left and the right side and is expressed as the CAV/CIVC ratio: [cortisol]adrenal vein/[cortisol]inferior vena cava; when this ratio exceeds a certain arbitrary cutoff value, sampling can be considered selective. The lateralization criterion is used to determine whether aldosterone hypersecretion was unilateral or bilateral by comparing aldosterone and cortisol concentrations in the 2 adrenal veins; this ratio, A/Cips/ACcont, is calculated as [aldosterone]/[cortisol]ipsilateral adrenal vein/[aldosterone]/[cortisol]contralateral adrenal vein (the ipsilateral adrenal vein is the one with the highest [aldosterone]/[cortisol] ratio). When this ratio exceeds a certain arbitrary cutoff value, aldosterone secretion is recorded as lateralized. When we were uncertain about how the authors confirmed the diagnosis of primary aldosteronism, we contacted one of the contributing authors to ask for details about the measurement of aldosterone and renin and whether a sodium chloride loading test had been performed. We also contacted the authors when the article did not specify the criteria used during AVS; of the 31 authors contacted, 22 (71%) responded and 13 (59% of the responders) could provide us with additional information. We excluded articles in which we could not confirm that the authors based the diagnosis of primary aldosteronism on a sodium chloride loading test, aldosteronerenin ratio, or plasma aldosterone concentration plus plasma renin activity. Twenty-one articles reported on the success rate of AVS. Of the 976 procedures performed, 183 were unsuccessful (overall success rate, 81.3%). Data Synthesis and Analysis Assuming AVS is the diagnostic reference criterion test, we analyzed how many times the CT/MRI result agreed or disagreed with the AVS result. The CT/MRI result was considered accurate
Published in
Annals of Internal Medicine
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42
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8 | 2009 |
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