Despite its diagnostic accuracy, an interventional procedure that sheds light on a common adrenal gland disorder is underutilized—primarily due to challenges performing the procedure and interpreting results, according to recent research.
Adrenal vein sampling (AVS)—in which blood samples are taken from veins exiting the adrenal glands—is considered the gold standard for distinguishing aldosterone-producing adenomas from bilateral adrenal hyperplasia in patients with primary aldosteronism (PA). The distinction is crucial because aldosterone-producing adenomas are curable with unilateral adrenalectomy while bilateral hyperplasia is managed medically. However, AVS is technically challenging, experts say.
“The challenge is mainly due to the right adrenal vein,” said Scott O. Trerotola, M.D., the Stanley Baum Professor of Radiology and associate chair and chief of interventional radiology at the Hospital of the University of Pennsylvania, Philadelphia. “It is variable in appearance, it looks like nearby liver veins and it is very short and tough to get purchase in.”
Although the 2008 Endocrine Society Clinical Practice Guidelines recommend AVS for additional diagnostic information in PA patients, recent research suggests that physicians are not adhering to those guidelines. A study of 20 major referral centers published in the May 2012 issue of the Journal of Clinical Endocrinology and Metabolism found that almost one-third of eligible PA patients over a six-year period were not submitted for AVS despite the procedure’s very low complication rate of between 0.51 percent and 0.61 percent.
“AVS is not performed systematically because it is technically difficult to perform, not readily available at most centers and even more challenging to interpret,” said lead author Gian Paolo Rossi, M.D., chair of internal medicine at the University of Padua, Italy. “Doctors are convinced that it is dangerous, although our study demonstrated that it is not.”
AVS was first used in the 1960s but fell out of favor a decade later as physicians turned to abdominal CT to detect nodules on adrenal glands. Abdominal CT failed to live up to its initial promise, however, as many adrenal nodules were deemed either non-functioning or too small to be seen on CT.
“The accuracy of abdominal CT in correctly detecting aldosterone-producing adenomas was only 53 percent,” recalled William F. Young, M.D., chair of endocrinology at the Mayo Clinic in Rochester, Minn. “As a result, almost one-quarter of patients sent to surgery based on the adrenal CT findings were not cured, while another quarter did not undergo surgery when it would have been curative.”
More centers returned to performing AVS as the inaccuracy of CT as a stand-alone approach became apparent. The Mayo Clinic resumed the procedure in 1990 after a 16-year hiatus. The clinic dedicates one radiologist to perform all AVS procedures, a strategy that helped make Mayo one of the leading centers in the country for PA patients.
“Half of the patients who come to us have experienced failed AVS at another facility,” Dr. Young said.
Also driving the resurgence of AVS is a growing awareness that PA is far more common than initially recognized.
In a large prospective study of patients referred to hypertension centers nationwide in Italy, 11.2 percent were found to have PA, according to research by Dr. Rossi and colleagues published in the November 2006 issue of the Journal of the American College of Radiology. Approximately 5 to 10 percent of people with high blood pressure have PA, according to Dr. Young.
The revived interest in AVS has challenged interventional radiologists to improve their proficiency.
Much of the current research in this area is focused on improving identification and sampling of the right adrenal vein, particularly for less experienced operators. Dr. Trerotola, who performs 40 to 50 AVS procedures a year with a more than 95 percent success rate, has suggested that the inferior accessory hepatic vein (IAHV) can be used as a guidepost to increase the success rate of the procedure.
“The inferior accessory hepatic vein is almost always within one centimeter of the adrenal vein,” he said. “I teach my fellows to look for an IAHV, which is easy to find. If there is one—as in about 60 percent of the population—we turn the catheter posteriorly and the adrenal vein is usually right there. Further, correctly identifying the IAHV helps avoid misinterpreting it as an adrenal vein.”
In a study published in the September 2011 issue of the Journal of Vascular and Interventional Radiology, Dr. Trerotola demonstrated that right AVS was successful in 95 percent of patients with a visible IAHV.
Dr. Trerotola’s study also demonstrated the benefits of using a renal double curve catheter to sample the right adrenal vein, successfully localizing the right adrenal vein in 61 of 73 patients (84 percent).
“Even very experienced interventionalists who have used the catheter say it is much better,” Dr. Trerotola said.
A rapid cortisol assay is another promising avenue toward improved AVS efficiency. Cortisol is a steroid hormone produced by the adrenal gland.
“You need to get a cortisol level to prove you’re in the adrenal vein, but you have to send it out to a lab,” Dr. Trerotola said. “You can’t get it done in a point-of-care setting.”
A rapid cortisol assay would allow radiologists to confirm that they are in the adrenal vein during the procedure rather than having to wait for lab results. A study in the May 2011 issue of European Journal of Endocrinology from the University Hospital Innenstadt in Munich, demonstrated rapid cortisol assays improved the success rate of AVS from 55 to 85 percent, primarily due to improved targeting of the right adrenal vein, however turnaround time was still approximately one hour.
Researchers also have been exploring an image-based approach to AVS using C-arm CT, which is available in most modern angiography suites. By rotating the C-arm during an X-ray exposure, the equipment constructs a CT-type dataset for reviewing cross-sectional images.
Although Dr. Trerotola suggested that this approach might have a role for inexperienced clinicians, there are drawbacks.
“Personally I think the imaging approach is overkill and results in a lot of extra CT scans in this Image Wisely age,” Dr. Trerotola said, referring to the multi-society campaign to reduce and optimize radiation dose.
No matter the technical challenges, experts agree that AVS is an essential tool in speeding appropriate treatment to patients with PA.
“There’s been a big resurgence of interest in AVS and our goal is to teach people how to perform it better,” Dr. Trerotola said. “If we can show more than 90 percent accuracy, then the world will beat a path to our doorstep.”
Access an abstract of the study, “The Adrenal Vein Sampling International Study (AVIS) for Identifying the Major Subtypes of Primary Aldosteronism” in the Journal of Clinical Endocrinology and Metabolism at jcem.endojournals.org/content/97/5/1606.abstract.
Access an abstract of the study, “Adrenal Vein Sampling Using Rapid Cortisol Assays in Primary Aldosteronism is Useful in Centers with Low Success Rates,” in the European Journal of Endocrinology at eje-online.org/content/165/2/301.abstract.
Access an abstract of the study, “The Inferior Accessory Hepatic Vein: An Anatomic Landmark in Adrenal Vein Sampling,” in the Journal of Vascular and Interventional Radiology at www.jvir.org/article/s1051-0443(11)00444-1/abstract.
Access the Endocrine Society Clinical Guidelines at endo-society.org/guidelines/index.cfm.
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