Comparison of Sequential versus SimultaneousMethods of Adrenal Venous SamplingCaitlin E. Carr, BA, Constantin Cope, MD, Debbie L. Cohen, MD, Douglas L. Fraker, MD, and

Scott O. Trerotola, MD

PURPOSE: To compare two methods of adrenal venous sampling (AVS) in preoperative localization of adrenal lesionsin primary hyperaldosteronism.

MATERIALS AND METHODS: Twenty-one patients (13 men, eight women) underwent selective adrenal venoussampling between July 2001 and May 2003. One of the 21 patients underwent repeat AVS, for a total of 22 procedures.In half the procedures (n � 11), simultaneous bilateral adrenal venous catheterization and sampling was performedbefore and after intraprocedural adrenocorticotropic hormone (ACTH) administration; in the remaining half (n � 11),sequential catheterization of the left and right adrenal veins was performed during continuous ACTH infusion 1 hourbefore and throughout AVS. Chart review provided procedural data, including sampling intervals and aldosterone/cortisol ratios. Patient records provided clinical data, including blood pressure, serum aldosterone levels, andcomputed tomography and magnetic resonance imaging findings. Surgical pathology reports confirmed unilateraldisease but were not applicable to bilateral disease.

RESULTS: Selective AVS was completed successfully in 21 of 22 procedures (95%); the unsuccessful sampling wasrepeated successfully. Disease lateralized in 13 of 22 cases. Simultaneous bilateral AVS localized unilateral disease inseven of eight cases (88%) and was nondiagnostic in one case (13%), with cases confirmed by surgical pathologyreports. Sequential bilateral AVS localized unilateral disease in four of four cases (100%) confirmed by surgicalpathology reports, with one lost to follow-up. Bilateral disease was diagnosed in six of 22 cases: two of 11 bysimultaneous AVS and four of 11 by sequential AVS. Three of 22 cases demonstrated borderline hormone levels thatfailed to meet the diagnostic threshold for recommended adrenalectomy. Mean elapsed time between acquisition ofright and left samples did not differ between simultaneous and sequential AVS (P � .09). Baseline (prestimulation)sampling did not contribute unique diagnostic information in any case and provided contradictory or confoundinginformation in three of 11 simultaneous AVS procedures (27%).

CONCLUSIONS: Sequential bilateral catheterization does not compromise the reliability of time-sensitive AVS. Bothsimultaneous and sequential AVS are adequate studies; however, obtaining baseline prestimulation samples duringsimultaneous AVS is unnecessary and increases the cost of the procedure.

J Vasc Interv Radiol 2004; 15:1245–1250

Abbreviations: A/C � aldosterone/cortisol (ratio), ACTH � adrenocorticotropic hormone, APA � aldosterone-producing adenoma, AVS � adrenal vein sam-pling, IVC � inferior vena cava

HYPERALDOSTERONISM accountsfor 1%–13% of cases referred for treat-

ment of hypertension (1,2). The adventof adrenal venous catheterization firstimproved the diagnosis of primary hy-peraldosteronism nearly 40 years ago(3). Since then, refinement of the tech-nique has permitted reliable localiza-tion of adrenal gland lesions (1,4–7); ithas been reported that modern adre-nal vein sampling (AVS) distinguishesunilateral aldosteronoma from bilat-eral adrenal hyperplasia with 90%–100% accuracy (4,5,8–11).

Two techniques of AVS, simulta-neous and sequential, are currently inuse. Simultaneous AVS measures al-dosterone and cortisol levels from theright and left adrenal veins and infe-

rior vena cava (IVC) via two accesses(10), and sampling is performed beforeand after adrenocorticotropic hor-mone (ACTH) stimulation. The ratio-nale for dual catheterization and intra-procedural stimulation is based onunpredictable fluctuations in cortico-steroid secretion and potential diag-nostic value of baseline hormone lev-els: the time interval required forsequential AVS may overlap differentstages of adrenal activity, and data be-fore ACTH stimulation may clarifydisease classification (4,10,12). Sequen-tial catheterization uses a single punc-ture site to sample both adrenal veinsand the IVC (13). Continuous ACTH

From the Division of Interventional Radiology, De-partment of Radiology (C.E.C., C.C., S.O.T.); Divi-sion of Nephrology, Department of Medicine(D.L.C.); and Division of Surgical Oncology, Depart-ment of Surgery (D.L.F.), University of PennsylvaniaMedical Center, 1 Silverstein, 3400 Spruce Street,Philadelphia, Pennsylvania 19104. Received March22, 2004; revision requested April 26; revision re-ceived and accepted May 19. From the 2004 SIRAnnual Meeting. Address correspondence to S.O.T.;E-mail: streroto@uphs.upenn.edu

Supported in part by a grant from MedComp, Har-leysvile, PA.

© SIR, 2004

DOI: 10.1097/01.RVI.0000134495.26900.6A

1245

infusion before and throughout AVSreplaces intraprocedural stimulationand consequently forbids baselinesampling. Sequential AVS discountsthe value of data obtained beforeACTH stimulation to achieve reducedtime and cost of the study.

This purposes of this study were tocompare the right/left sampling inter-val with each technique, to evaluatethe diagnostic value of baseline aldo-sterone/cortisol (A/C) ratios, and tocompare the diagnostic yields of si-multaneous versus sequential AVS.

MATERIALS AND METHODS

The institutional review boardgranted exemption for retrospectivestudy of patients referred to the divi-sion of interventional radiology at ourinstitution for adrenal venous sam-pling between July 2001 and May2003. Two interventional radiologists(C.C., S.O.T.), both with more than 10years of experience with AVS, eachperformed 11 AVS procedures, for atotal of 22 procedures. Twenty-one pa-tients, 13 men and eight women with amean age of 50 years (range, 40–68years), were included in the study; onepatient underwent AVS twice becausethe first examination was nondiag-nostic. All patients presented to thereferring physicians with primary hy-peraldosteronism characterized by in-creased peripheral aldosterone levelsand labile hypertension resistant or re-fractory to aggressive treatment withstandard antihypertensive medica-tions. The mean peripheral aldoste-rone level was 44.7 ng/dL (range,16.3–121 ng/dL; reference range,�1.6–16 ng/dL in supine position),mean blood pressure was 164/93 mmHg (range, 140–206 mm Hg systolic,80–120 mm Hg diastolic). Preliminarycomputed tomography (CT) or mag-netic resonance (MR) imaging demon-strated structural abnormalities of theadrenal glands, and subsequent AVSevaluated adrenal function. To com-pare temporal differences between si-multaneous and sequential bilateralAVS, the time interval between ve-nous samples from the right and leftadrenal veins was determined.

Procedures

The choice of technique used wasleft to the discretion of the operator.

Procedures were performed with useof conscious sedation titrated to effect.One operator (S.O.T.) used the sequen-tial technique exclusively, whereas theother (C.C.) used the simultaneoustechnique exclusively. The simulta-neous technique was performed as de-scribed by Doppman and Gill (10).Briefly, the right common femoralvein was accessed twice. Catheterswith an added side hole near the tip(generally 4-F Simmons 1 and 4-F Sim-mons 2 catheters; Cook, Bloomington,IN) were advanced through the rightcommon femoral vein and placed inthe right and left adrenal veins. Retro-grade injection of minimal amounts ofnonionic contrast medium verifiedproper location of the catheters; no at-tempt was made to perform diagnosticadrenal venography. Three thousandunits of heparin were administered in-travenously. Baseline blood sampleswere obtained from the right and leftadrenal veins and sent for aldosteroneand cortisol measurement. An attemptwas made to draw these samples si-multaneously. After baseline sam-pling, ACTH stimulation was per-formed with cosyntropin (Cortrosyn;Amphastar, Rancho Cucamonga, CA)administered as a 0.25-mg bolus, fol-lowed by 0.25 mg in 5 mL normalsaline solution infused over a periodof 10–15 minutes. Blood samples afterACTH stimulation were drawn fromthe right and left adrenal veins andthen the IVC at the completion of thecosyntropin infusion. Again, an at-tempt was made to draw the adrenalsamples simultaneously.

The sequential technique was amodification of the technique ofYoung et al (13) in which patients un-derwent an infusion of ACTH 30 min-utes before and throughout catheter-ization to minimize stress-inducedfluctuations in adrenal activity. Thistechnique foregoes the baseline sam-pling previously described (10); only asingle set of postinfusion samples areobtained from the adrenal veins andIVC after bilateral catheterization witha single catheter. In the sequential pro-cedures, patients received a continu-ous intravenous infusion of cosyn-tropin (0.25 mg/500 mL, 100 mL/h)beginning 1 hour before the sampling(ie, immediately after gaining intrave-nous access) and throughout the sam-pling. Catheterization of the right ad-renal vein was performed via a right

common femoral approach, with useof a 5-F HS2 catheter (Cook) with anadded side hole near the tip, and asample was obtained and sent for al-dosterone and cortisol determination.Retrograde injection of a minimalamount of nonionic contrast mediumverified proper location of the cathe-ter, and again no attempt was made toperform diagnostic adrenal venogra-phy. In the uncommon event that thisshape was unsuccessful, other shapeswere used, always with an added sidehole near the tip. Immediately aftersuccessful sampling, the catheter wasexchanged for a 5-F Simmons 2 cathe-ter (Cordis, Warren, NJ), and catheter-ization of the left adrenal vein wasperformed. Again, retrograde injectionof a minimal amount of nonionic con-trast medium verified proper locationof the catheter. Samples were obtainedfor aldosterone and cortisol determi-nation. The catheter was withdrawninto the IVC and a final set of bloodsamples was drawn and sent for mea-surement of aldosterone and cortisol.

In our clinical laboratory, samplesfrom AVS are identified by the acqui-sition time of the sample, which is re-corded on the procedural flow sheetand the tube of blood by the interven-tional radiology nurse in the room assoon as it is obtained, along with thesite of sampling. We reviewed theflow sheets to determine the timeelapsed between sampling from theright and left adrenal veins during si-multaneous and sequential AVSprocedures.

Sampling Interpretation

Catheter placement in all cases wasconfirmed by laboratory analyses ofblood samples that showed high con-centrations of cortisol in the adrenalvein compared with the IVC; venoussampling was considered selectiveand successful if the plasma cortisollevel in the adrenal vein was an orderof magnitude greater than that in theIVC. To correct for asymmetric dilu-tional effects of peripheral or caval ef-fluent, the ratio of aldosterone to cor-tisol (A/C) in the right and leftadrenal veins was calculated. The dif-ferential between right and left A/Cratios determined lateralization of ad-renal disease: an A/C ratio from a se-lectively sampled adrenal vein thatwas four to five times greater than the

1246 • Sequential versus Simultaneous Methods of Adrenal Venous Sampling November 2004 JVIR

corresponding ratio in the contralat-eral adrenal vein was considered diag-nostic of unilateral disease (12,14). Aspreviously reported by authors de-scribing adrenal vein sampling (12,14),nonlateralization is attributed tobilateral hyperplasia, even though, intheory, bilateral adenomas couldmimic hyperplasia. In practice, thisdistinction does not matter, because ineither event the patient is not a candi-date for adrenalectomy to treathyperaldosteronism.

Treatment

Laparoscopic adrenalectomy wasperformed in patients with AVS-diag-nosed unilateral disease. Surgical pa-thology reports provided morphologicconfirmation of disease, and postoper-ative blood pressure measurements in-dicated clinical response to surgery.Pathology reports classified unilateraldisease as aldosterone-producing ade-noma (APA) or unilateral hyperplasia.The presence of a single dominantnodule led to the diagnosis of APA.The presence of multiple nodules re-sulted in diagnosis of unilateral hyper-plasia if a concomitant postoperativeresponse comparable to that observedin APA was present. Postoperativeblood pressure was recorded as nor-malized, improved, or unchanged.Normalized blood pressure was de-fined as less than 140/90 mm Hg with-out antihypertensive medication, im-proved blood pressure was defined asless than 140/90 mm Hg with medica-tion, and unchanged blood pressurewas defined as greater than 140/90mm Hg with medication. Patients withAVS-diagnosed bilateral disease didnot undergo adrenalectomy. Conse-quently, surgical pathology reportscould not confirm diagnosis of bilat-eral disease.

To evaluate the diagnostic value ofbaseline hormone ratios, data beforeand after ACTH stimulation from si-multaneous AVS procedures werecompared. The data were analyzedwith respect to clinical management ofdisease to determine if baseline sam-pling contributed unique diagnosticinformation.

Statistical Analysis

Statistical analysis was performedwith use of commercially available

software (Excel; Microsoft, Redmond,WA). Room and intersample timeswere compared with use of the Stu-dent t test (two-tailed, unequal vari-ance), with significance determined atP � .05.

RESULTS

Clinical data are shown in Table 1(online only, see www.jvir.org). Pre-procedural adrenal CT/MR imagingrevealed unilateral lesions in 19 of 21patients (90%). AVS results were con-cordant in 12 of 19 cases (63%) anddiscordant in seven of 19 cases (37%)with unilateral findings on CT/MRimaging. AVS demonstrated bilateraldisease in five of seven discordantcases (71%), whereas the remainingtwo (29%) had adrenal disease that lat-eralized to the side opposite that pre-dicted by CT/MR imaging. CT/MRimaging indicated bilateral hyperpla-sia in one of 21 cases (5%). The findingwas corroborated by AVS, which alsodiagnosed an additional five patientswith bilateral hyperplasia despite uni-lateral lesions on CT/MR imaging. Im-aging revealed adrenal glands withinnormal limits in one of 21 patients(5%).

Successful AVS was achieved in 10of 11 simultaneous cases (92%) and 11of 11 sequential cases (100%), for a95% overall success rate. The singlenondiagnostic sampling was a resultof nonselective catheterization of theright adrenal vein and was repeatedwith success; this patient underwentboth simultaneous (patient no. 7, un-successful) and sequential (patient no.15, successful) techniques. There was asingle complication: a vasovagal epi-sode, which responded to atropine.No puncture-site complications oc-curred. Sampling data are shown inTable 2 (online only, see www.jvir.org).

Disease lateralized in 13 of 22 cases(59%): simultaneous bilateral AVS ac-curately localized unilateral disease inseven of eight cases (88%) and wasnondiagnostic in one case (13%; non-selective right adrenal sample), as con-firmed by surgical pathology reports;sequential bilateral AVS accurately lo-calized unilateral disease in four offour cases (100%), as confirmed bysurgical pathology reports. A fifth pa-tient (patient no. 18) diagnosed with aunilateral lesion by sequential AVSwas lost to follow-up. Adrenalectomy

in patients with pathologically con-firmed unilateral disease resulted innormalization of blood pressure ineight of 12 cases (67%) and improvedblood pressure in the remaining fourcases (33%). It can be argued that, inthose patients with a pathologic diag-nosis of unilateral hyperplasia, bilat-eral hyperplasia may have beenpresent. However, one would not ex-pect improvement in blood pressure,and the pathologists in our institutionbelieve this is a distinct entity frombilateral hyperplasia. AVS predictedbilateral hyperplasia in six of 22 cases(27%): two of 11 (18%) by simulta-neous AVS and four of 11 (36%) bysequential AVS. The remaining threecases (14%) demonstrated borderlinehormone levels suggestive of lateral-ized disease that failed to meet thediagnostic threshold for recom-mended adrenalectomy; repeat AVSafter 6 months was advised.

Baseline sampling (before ACTHstimulation) did not contribute uniquediagnostic information in any case andprovided contradictory or confound-ing information in three of 11 simulta-neous AVS procedures (27%). In onepatient (patient no. 6), raw aldosteronelevels and A/C ratios after ACTHstimulation clearly demonstrated lat-eralized disease, but the lack of sup-pression of contralateral adrenal activ-ity at baseline prompted diagnosis ofbilateral disease despite multiplemarkers for a unilateral lesion, includ-ing an attenuated contralateral re-sponse to ACTH and an ipsilateralA/C ratio much higher than the diag-nostic threshold. In the second patient(patient no. 8), data before ACTHstimulation suggested bilateral dis-ease, whereas A/C ratios after ACTHstimulation indicated a unilateral le-sion, which was confirmed by surgeryand subsequent clinical response toadrenalectomy. In the third patient(patient no. 2), data before and afterACTH stimulation demonstrated con-tradictory findings, which precludeddefinitive classification of disease.

The mean time elapsed betweenright and left venous sampling duringsimultaneous bilateral catheterizationwas 3.4 minutes (range, 1–10 minutes)for samples before ACTH stimulationand 2.5 minutes (range, 1–7 minutes)for samples after ACTH stimulation.The mean time elapsed between rightand left venous sampling during se-

Carr et al • 1247Volume 15 Number 11

quential bilateral catheterization was3.7 minutes (range, 2–6 minutes).Mean elapsed time during bilateral ve-nous sampling did not differ betweensimultaneous and sequential AVS (P� .09).

DISCUSSION

Primary hyperaldosteronism, firstdescribed by Conn (15), contributes tohypertension in an estimated 1%–13%of patients in clinical practice (1,2). Al-though hyperaldosteronism afflicts aminority of patients with hyperten-sion, unlike other causes of essential orsecondary hypertension, the conditionis potentially curable by surgical exci-sion of the abnormal adrenal gland. Aspectrum of structural and functionalabnormalities produce hyperaldoste-ronism (4,8,13). The most commonmorphologies are solitary APAs andbilateral adrenal hyperplasia, with re-spective prevalence rates of 55%–65%and 35%–45% (13). Distinction be-tween patterns of disease is essentialfor effective clinical management: ad-renalectomy is curative in 35%–75% ofcases (16) and ameliorative in the re-mainder of unilateral cases, for a cu-mulative 60%–90% normotensivepostoperative outcome (13,16,17); incontrast, surgery is ineffective for bi-lateral disease, and patients requirelifelong medical management forhypertension.

Evaluations of adrenal morphologyand function are imperative for accu-rate diagnosis of primary hyperaldo-steronism. CT and MR imaging maydetect morphologic lesions, but imag-ing is insufficient to diagnose func-tional endocrinopathy: imaging dem-onstrates only the site and size, not thebiologic activity, of an endocrine tu-mor (5,10,11,14,18,19). Moreover, de-spite 91%–92% specificity, the 48%–58% (5,11,12) sensitivity of CT/MRimaging in primary hyperaldosteron-ism suggests that the scans may beequivocal (11,12). These factors, in ad-dition to subjective variability amongradiologists, complicate localization ofadrenal lesions and may preclude ap-propriate management decisions. Nei-ther the absence nor presence of a dis-cernible mass or masses on CT or MRimaging abrogates the need for furtherevaluation by AVS (5,11,13,18,20,21).Bilateral AVS is the most accurate di-agnostic test for primary hyperaldo-

steronism (13,18) and remains the pre-operative gold standard for radiologicclassification of primary hyperaldoste-ronism (1,7,11,19,20).

AVS can be performed by simul-taneous or sequential bilateral cath-eterizations. Doppman and Gill (10)developed a technique used in simul-taneous and sequential AVS to cir-cumvent the primary procedural chal-lenge: sampling right adrenal veineffluent that flows up the back wall ofthe IVC eliminates the need to cathe-terize the right adrenal vein, whichmay complicate sampling in 10%–30%of cases (5,10,17). Doppman was anardent advocate of the simultaneoustechnique, whereas Young et al (13)and the present study describe the se-quential AVS protocol. The two-punc-ture simultaneous technique is basedon theoretical considerations of vari-able hormone secretion rates, and thesingle-puncture sequential techniqueis based on practical considerations ofcost and time. Each approach wasevaluated by analysis of adrenal activ-ity, measurement of time-dependentcatheterization, and assessment ofdata obtained before ACTH infusion.

Proponents of the simultaneoustechnique have argued that sequentialcatheterization might miss a burst ofepisodic aldosterone secretion andthereby yield erroneous results. Nor-mal corticosteroid secretion occurs inan average of eight daily bursts, sepa-rated by intervals of adrenal quies-cence (22,23). Episodic secretion of al-dosterone parallels that of cortisol,which maintains a circadian rhythmpunctuated by peaks and troughs (23).To define a secretory rhythm, the fre-quency of sampling must exceed thefrequency of the rhythm. Researchershave selectively sampled adrenal ve-nous blood at intervals as short as 10minutes with confidence that adrenalactivity is relatively predictable withinthose limits (24). Bilateral adrenal ve-nous samples obtained within the de-fined window therefore should reflectcomparable levels of adrenal activity.Sequential AVS performed with a sin-gle catheter satisfied the time parame-ters, with a mean interval of 3.7 min-utes between right and left adrenalvein sampling. Simultaneous AVS alsosatisfied the time parameters withmean intervals of 3.4 minutes and 2.5minutes for samples taken before andafter ACTH stimulation, respectively.

The consistency of sampling intervaland brief right/left sampling intervalin single-catheter AVS reflect the rela-tive ease with which the left adrenalvein is accessed. This vein is quicklycatheterized after initial samplingfrom the less-accessible right adrenalvein, which may take considerabletime and effort to localize.

A second argument in favor of thesimultaneous technique is the abilityto obtain samples before and afterACTH administration without re-peated catheterization of the adrenalveins. It should be noted that the se-quential technique does not precludeobtaining samples before and afterstimulation, but it would require re-peated catheterization of the adrenalveins.

ACTH stimulation is an undis-puted part of AVS by either technique:altered patterns of steroid secretion oc-cur in unilateral and bilateral hyperal-dosteronism, and ACTH infusion be-fore and/or during AVS minimizesartifact that otherwise could arise fromspontaneous steroid secretion (4,10,22). Stimulation induces cortisol andaldosterone production; invariably in-creased cortisol secretion verifies cath-eter position and variably increasedaldosterone secretion manifests adre-nal lesions (14).

ACTH application helps preventambiguity regarding disease lateral-ization, but support for baseline sam-pling is not universal. Briefly, the ra-tionale for obtaining baseline samplesis as follows: physiologic levels ofACTH stimulate steroid productionby the adrenal cortex; in healthy indi-viduals, ACTH is the primary regula-tor of cortisol secretion and a second-ary mediator of aldosterone release(25). The renin–angiotensin pathwayand serum potassium level are theprincipal regulators of aldosterone.However, under certain conditions, in-cluding primary hyperaldosteronismwith chronic suppression of renin–an-giotensin, ACTH may develop a moreprominent and dominant regulatoryrole for aldosterone production (26–28). Researchers assert that lateraliza-tion of aldosterone secretion is a pre-operative index for successful cure byadrenalectomy (1,4); traditionally, af-ter ACTH stimulation, an A/C ratio ofat least 4:1 or 5:1 between the twoadrenal veins diagnoses unilateral dis-ease (10,11,13). Unilateral disease is

1248 • Sequential versus Simultaneous Methods of Adrenal Venous Sampling November 2004 JVIR

also thought to be more sensitive toACTH than bilateral disease (10,11,26,28); application of exogenous ACTHbefore or during AVS may differenti-ate between APA and bilateral hyper-plasia by accentuating the greater sen-sitivity of aldosteronomas to thestimulus: a brisk unilateral response toACTH with concurrent contralateralattenuation implies APA, whereascomparable bilateral increases in aldo-sterone secretion after an ACTH chal-lenge suggests bilateral hyperplasia(10,18). In theory, A/C values from theadrenal veins and IVC before ACTHadministration provide baseline con-trols against which to measure relativeresponsiveness to ACTH in simulta-neous AVS. However, the standard 4:1or 5:1 threshold for diagnosis of later-alized disease inherently demon-strates differential responsiveness toACTH infusion, and diagnostic accu-racy achieved by sequential AVS inour study suggests that poststimula-tion hormone ratios are adequate in-dexes of unilateral disease. Moreover,it is the samples obtained after ACTHchallenge during simultaneous sam-pling that guide ultimate patient care.For example, data from one patientbefore ACTH challenge did not pre-dict the A/C ratios after ACTH chal-lenge, yet postinfusion results indicatedlateralized disease, which was then di-agnosed and surgically confirmed.

Some argue further that baselinecontralateral adrenal suppression is areliable marker of unilateral disease.According to this theory, aldosteronelevels before ACTH stimulation areuseful localizing parameters and aretherefore valuable determinants ofsurgical efficacy (10). Evaluation ofbaseline suppression often providescorroborating evidence of lateralizeddisease, but reliance on data obtainedbefore ACTH stimulation may con-found interpretation of results afterACTH stimulation, which are inargu-ably invaluable for localization of pri-mary hyperaldosteronism (10). In ourseries, in seven of 10 successful simul-taneous AVS procedures (70%), dataobtained before and after ACTH stim-ulation concurred, and prestimulationdata substantiated the poststimulationdiagnoses. However, in three cases,analysis of preinfusion values con-founded interpretation of poststimula-tion ratios and posed a risk of inappro-priate disease management. Our

results suggest that baseline samplesprovide neither new information nordiagnostic benefit. Because baselinesampling doubles the laboratory costs(ie, twice the number of specimens aresent to the laboratory), it should beabandoned if further studies confirmour findings.

We acknowledge several potentialweaknesses of the study. Lack of sur-gical confirmation of AVS-diagnosedbilateral hyperplasia is a criticism thatcan be applied to AVS performed withany technique. This is a small series,and patients were not randomized tothe techniques described. In one pa-tient (patient no. 2) in whom con-tradictory data were obtained fromsampling before and after ACTH stim-ulation, it is possible that the baselinevalue that indicated lateralization wascorrect; however, all authors appear toagree that poststimulation samples arethe most reliable and therefore it wasthe poststimulation result that guidedtherapy. The only way to be surewould be to subject the patient to apotentially needless adrenalectomy,and to do so would be counter to pre-vailing literature and clinical practice.We did not have 100% follow-up, andsome patients had equivocal results;however, these criticisms applyequally to both techniques. Finally, thetimes applied to the specimens maynot have been exact because the datawere not collected prospectively.

CONCLUSION

This study presents sequential bi-lateral catheterization as an accurateand economical alternative to the two-catheter technique of AVS for pre-operative localization and judiciousclinical management of primary hy-peraldosteronism. Our results do notsupport the use of prestimulation sam-ples because they do not affect man-agement and may in fact confound thediagnosis.

Acknowledgments: The authors thankMedcomp for a grant that supported thisproject, Lori Deslandes for her secretarialsupport, and Myron Weinberger, MD, forhis insight into adrenal venous samplingand hyperaldosteronism.

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1250 • Sequential versus Simultaneous Methods of Adrenal Venous Sampling November 2004 JVIR

Table 1Clinical Data

PatientNo.

BaselineBP

(mm Hg)

SerumAldosterone

(ng/dL) CT/MR Findings AVS Diagnosis PathologyFollow-up

BPFollow-upMedication

Follow-upDuration

(mos)

1 176/100 35.9 3 left nodules Left lateralization UAH Improved Yes 192 140/95 38 NA High titer in left; not

lateralizedNA Unchanged Yes 22

3 154/80 44 Right nodule Right lateralization APA Normalized No 214 160/120 20.5 1 cm right nodule Right lesion; left suppress APA Normalized No 155 152/100 31.1 1.2 cm left nodule Left lesion; right suppress APA Normalized No 86 160/95 57 2 cm left nodule BAH (high right, no left

suppress)NA Unchanged Yes 2

7 161/94 58 1.5 cm rightnodule

Nondiagnostic APA Normalized No 14

8 206/100 71 1.3 cm rightnodule

Right lateralization APA Improved Yes 5

9 167/86 32 1.4 cm left nodule BAH NA Unchanged Yes 2110 159/86 31 1 cm right nodule Right lesion; left suppress UAH Improved Yes 2011 160/86 121 �1 cm left nodule Left lateralization APA Normalized No 2512 158/88 16.3 Normal Moderate left lateralization;

repeat 6 mosNA Unchanged Yes 7

13 164/77 32.5 1 cm left nodule Left lateralization APA Normalized No 414 160/100 39 Right nodule Right lateralization APA Normalized No 1215* 161/94 58 1.5 cm right

noduleRight lateralization APA Normalized No 13

16 150/100 29.3 5 mm left nodule Right high despite leftmass

NA Unchanged Yes 5

17 152/94 34.3 Left nodule BAH NA Unchanged Yes 518 152/80 33 1 cm left nodule Right lateralization – NA NA 1319 156/90 39 Bilateral nodules BAH NA NA NA 920 196/90 51 1.5 cm right

noduleRight lateralization UAH Improved Yes 3

21 184/100 43 Right 1.1 cmnodule

BAH NA Unchanged Yes 4

22 170/82 69 Left adrenal mass BAH NA Unchanged Yes 9

* Same as patient 7. Patients 1–11 underwent simultaneous AVS, patients 12–22 underwent sequential AVS.Note.—BAH � bilateral adrenal hyperplasia; BP � blood pressure; NA � not applicable; UAH � unilateral adrenal hyperplasia.

1

Table 2Sampling Data

PatientNo.

Left Pre-ACTH Right Pre-ACTH IVC Pre-ACTH

Aldosterone(ng/dL)

Pre-ACTHCortisol(�g/dL)

Pre-ACTHAldosterone/Cortisol

RatioAldosterone

(ng/dL)Cortisol(�g/dL)

Aldosterone(ng/dL)

Cortisol(�g/dL) Left Right IVC

1 1,155 14 50 19 18 6 82.5 2.6 3.22 428 24 34 14 24 15 17.8 2.5 1.53 26 33 84 22 39 17 0.8 3.9 2.34 11 20 2,370 33 12 11 0.6 72.7 1.15 473 30 25 28 23 17 15.8 0.9 1.36 1,055 1,009 4,500 509 24 13 1.0 8.8 1.97 212 39 437 20 90 19 5.4 21.6 4.88 42 18 72 19 59 19 2.3 3.9 3.19 73 35 208 26 17 19 2.1 7.9 0.9

10 80 14 4,585 73 45 11 5.7 63.0 4.011 19,760 455 248 36 118 25 43.4 6.8 4.712 – – – – – – – – –13 – – – – – – – – –14 – – – – – – – – –15* – – – – – – – – –16 – – – – – – – – –17 – – – – – – – – –18 – – – – – – – – –19 – – – – – – – – –20 – – – – – – – – –21 – – – – – – – – –22 – – – – – – – – –

PatientNo.

Left Post-ACTH Right Post-ACTH IVC Post-ACTHPost-ACTH

Aldosterone/Cortisol Ratio Sampling Interval (min)

Aldosterone(ng/dL)

Cortisol(�g/dL)

Aldosterone(ng/dL)

Cortisol(�g/dL)

Aldosterone(ng/dL)

Cortisol�g/dL Left Right IVC Pre-ACTH Post-ACTH

1 18,000 797 885 1,570 71 15 22.6 0.6 4.9 4 22 3,100 918 450 399 45 26 3.4 1.1 1.7 3 23 723 990 13,700 836 59 33 0.7 16.4 1.8 2 14 480 1,370 21,950 1,975 36 31 0.4 11.1 1.2 2 25 3,685 880 795 1,850 62 32 4.2 0.4 1.9 2 26 1,485 1,968 14,800 847 88 44 0.8 17.5 2.0 1 27 898 922 102 40 114 34 1.0 2.6 3.3 3 58 438 295 4,050 131 106 28 1.5 30.9 3.8 4 19 2,810 765 5,580 988 38 21 3.7 5.6 1.8 3 2

10 298 36 11,070 1,896 72 30 8.3 5.8 2.4 3 211 20,080 654 386 404 265 27 30.7 1.0 9.9 10 712 5,200 1,460 1,720 1,686 104 38 3.6 1.0 2.7 – 513 3,425 735 965 1,107 79 41 4.7 0.9 1.9 – 214 337 283 5,565 367 86 28 1.2 15.2 3.0 – 315* 843 1,183 13,100 1,675 247 53 0.7 7.8 4.7 – 416 2,830 889 11,040 1,038 96 43 3.2 10.6 2.2 – 517 2,860 1,224 3,800 1,584 87 46 2.3 2.4 1.9 – 418 1,590 1,185 12,500 864 106 48 1.3 14.5 2.2 – 619 1,700 679 3,515 724 98 45 2.5 4.9 2.2 – 320 670 661 4,783 539 88 37 1.0 8.9 2.4 – 321 680 542 1,355 425 106 26 1.3 3.2 4.1 – 222 3,120 1,094 5,185 1,658 68 60 2.9 3.1 1.1 – 4