This article is more than 5 years old. Information may no longer be current.
Adrenal vein sampling, CT ‘imperfect’ tests to identify adrenalectomy candidates
Click Here to Manage Email Alerts
In patients with primary aldosteronism, both adrenal CT scans and more-invasive adrenal vein sampling identified the presence of aldosterone-producing adenomas at similar rates and resulted in similar clinical benefits after 1 year of follow-up, but patients in both groups experienced unexpected surgical failures.
In a diagnostic, randomized controlled trial conducted at 13 Dutch and Polish medical centers, Tanja Dekkers, MD, of the division of vascular medicine at Radboud University Medical Center in Nijmegen, the Netherlands, and colleagues analyzed data from 184 adults with confirmed primary aldosteronism prescribed at least three antihypertensive drugs or with hypertension accompanied by spontaneous or diuretic-induced hypokalemia. Patients were recruited between July 2010 and May 2013. Researchers randomly assigned patients to undergo adrenal CT (n = 92) or adrenal vein sampling (AVS; n = 92). Patients assigned to CT underwent adrenalectomy in cases of a unilaterally enlarged adrenal with a normal contralateral gland; patients with bilaterally enlarged or normal adrenal glands were prescribed mineralocorticoid receptor antagonist therapy. Antihypertensive therapy was initiated and adjusted by treating physicians during follow-up to achieve target blood pressure. Primary outcome was the intensity of antihypertensive medication needed; secondary endpoints included serum potassium level and aldosterone after salt-loading test following adrenalectomy.
Of the 92 patients assigned to undergo CT, 46 underwent adrenalectomy and 46 were prescribed mineralocorticoid receptor antagonist therapy. Of the 92 assigned to AVS, 46 underwent adrenalectomy and 46 were prescribed mineralocorticoid receptor antagonist therapy. Researchers did not observe differences in the intensity of antihypertensive medication required to control BP between patients with CT-based treatment vs. AVS-based treatment, with median daily defined doses of three for both groups. In the CT group, 39 patients (42%) reached target BP vs. 41 patients (45%) in the AVS group. Researchers found no between-group differences in health-related quality of life.
Biochemically, 37 patients (80%) with CT-based adrenalectomy and 41 (89%) of those with AVS-based adrenalectomy had resolved hyperaldosteronism (P = .25).
Researchers observed a nonsignificant mean difference of 0.05 (95% CI, –0.04 to 0.13) in quality-adjusted life-years for the AVS group, associated with an increase in mean health care costs of 2,285 euros per patient (95% CI 1,323–3,248).
“At a willingness-to-pay value of 30,000 (euros) per [quality-adjusted life-year], the probability that AVS as compared with CT constitutes an efficient use of health care resources in the diagnostic workup of patients with primary aldosteronism was less than 0.2,” the researchers wrote.
Adverse events were similar between groups (nine serious events in the CT group vs. 12 serious events in the AVS group).
“Our findings suggest that both CT and AVS are imperfect tests to identify patients who might benefit from adrenalectomy, but each is imperfect for largely unknown reasons,” the researchers wrote. “In the AVS group, we observed a nearly 50% discordance between the diagnostic conclusions derived from the CT and AVS, similar to the results of our systematic review. This finding in the context of identical rates of adrenalectomy and similar outcomes in the CT and the AVS group suggests that both methods identify different patients amenable to adrenalectomy.”
In commentary accompanying the study, Martin Reincke, MD, of Klinikum der Universität in Munich, said the study findings were unexpected and challenged current guidelines.
“In both groups, there were unexpected surgical failures with persistence of primary aldosteronism, leading the investigators to conclude that neither AVS nor CT scans should be considered as gold standard tests for identifying aldosterone-producing adenomas,” Reincke wrote. “Moreover, both approaches apparently identified different subgroups of patients who were suitable candidates for adrenalectomy.” – by Regina Schaffer
Disclosure: The researchers and Reincke report no relevant financial disclosures.
Perspective
Back to Top
John W. Funder
Primary aldosteronism is currently acknowledged to affect 5% to 15% of the hypertensive population. The 2008 Endocrine Society guidelines for primary aldosteronism recommend AVS post-CT for all patients with primary aldosteronism able and willing to undergo surgery if appropriate. The recently published (2016) revised guidelines temper this blanket recommendation, suggesting that young patients with suppressed renin, very high plasma aldosterone concentrations and a unilateral adenoma on imaging might go straight to surgery.
The thrust of the paper by Dekkers and colleagues is that, in terms of outcome, there is no difference between lateralization on the basis of CT and AVS, and thus that the additional costs of AVS are unwarranted. There currently are a number of studies, recently published and submitted for publication, exploring ways to distinguish at least the bulk of patients with a unilateral aldosterone-producing adenoma from those with bilateral adrenal hyperplasia, thus restricting the necessity for AVS to the minority of patients in a gray zone.If the results reported by Dekkers and colleagues were to be generalized, AVS would disappear as a diagnostic modality in publicly funded health care systems, and more than likely as a reimbursable item for private health insurance. This may or may not happen, but the study under discussion has a number of limitations, not all of which are acknowledged by the authors. These include:
• Among the 184 patients with primary aldosteronism under study, only 50 are women, consistent with a major referral bias.
• Entry criteria were spontaneous or diuretic-induced hypokalemia and/or hypertension resistant to three or more agents.
• These patients are at the florid end of the primary aldosteronism spectrum, consistent with the equal numbers of aldosterone-producing adenoma and bilateral adrenal hyperplasia, and despite the relatively modestly elevated starting blood pressure levels.
• Although the primary endpoint was intensity of drug treatment for obtaining target BP after 1 year of follow-up, only 40% to 46% of patients in the various treatment groups achieved target ambulatory BP.
• The antihypertensive regimen chosen — spironolactone up to 200 mg/day (eplerenone up to 400 mg/day) and then additional agents if and as required is uncommon — would not be widely adopted and presumably explains the extraordinary number of adverse events recorded.
• The CT findings sit oddly with the much more plausible findings of AVS.
• Confidence in CT is not bolstered by the report of discordant conclusions between local and central reading of imaging in 14 patients.
• Maintaining the four failed AVS patients in the AVS group, with the treatment decision made on the basis of CT, is not clearly justified.
Clinical trials are challenging, often more so when across many centers. As the authors acknowledge, trends favoring AVS may become significant differences with higher patient numbers. The peculiarities of the trial under review make it not appropriate as a basis for generalization. What it does, however, is to underline the necessity for confident lateralization of aldosterone hypersecretion — for most if not all patients with primary aldosteronism — by procedures other than AVS.
Disclosure: Funder reports financial or business/organizational interests with the Department of Veterans Affairs, Garnett Passe and the Rodney Williams Memorial Foundation and serving as a consultant for Pfizer/Japan.
Click Here to Manage Email Alerts