ENDO 2018: 100th Endocrine Society Annual Meeting :

AVS Good for All Patients with Primary Aldosteronism Debatable

Patients with primary aldosteronism present with a triad of secondary hypertension, hypokalemia, and an aldosterone-producing adenoma of the adrenal gland, affecting up to 20% of those with treatment-resistant disease.

Endorsement of adrenal venous sampling (AVS) as the preferred method for management of primary aldosterone in the 2016 Endocrine Society Clinical Practice Guidelines2 has been challenged given the findings from the Spartacus trial,3  said session moderator, Gary Hammer, MD, PhD, the Millie Schembechler Professor of Adrenal Cancer, and director of the endocrine oncology program in the Comprehensive Cancer Center at University of Michigan in Ann Arbor, in opening the debate—This house believes that adrenal vein sampling has a major role to play in the management of patients with primary aldosteronism, at ENDO 2018, March 18, 2018, in Chicago, Illinois.

Can adrenal venous sampling benefit all patients with Primary Aldosteronism?

The debate, between William F. Young, Jr., MD, MSc, professor of medicine and chair of the division of endocrinology, metabolism and nutrition, at the Mayo Clinic College of Medicine in Rochester, Minnesota, who argued in favor of AVS almost always, leaned on his preeminence in this field as senior author of the guidelines for treatment of primary aldosteronism.2,4 Self-proclaimed underdog, Paul Michael Stewart, MD, FRCP, professor, and dean of the University of Leeds medical school, UK, offered a compelling argument against reliance on AVS in most clinical settings.5

“Selective adrenal venous sampling (AVS) works well at our institution, but at other institutions, it would depend upon their expertise and needs, which may be different. I think there is no wrong answer,” Irina Bancos, MD, who works under Dr. Young at the Mayo Clinic, told EndocrineWeb before the session began. AVS in which blood samples are taken from the hepatic vein after calcium is administered in order to gather targeted provide information on the location of pancreatic endocrine tumors to inform surgical removal.

Here is how the debate unfolded.

AVS Is the Preferred Treatment for Primary Aldosteronism

In patients with confirmed primary aldosteronism (PA) who have multiple nodes on CT imaging, there is no good answer as to which adrenal gland is causing the problem, said Dr. Young, so adrenal venous sampling is essential.5

“Take a patient who presents with adrenal vein cortisol at five times greater than IVC, and aldosterone levels greater than 4 to 1 or more; this is indicative of a smaller nodule unilaterally causing the problem.6 Following surgery, the aldosterone level of this patient was zero, with no anxiety, reduced weight, and good (lower) blood pressure,” said Dr. Young, and more important, this patient’s PA was cured. 5

There are 80 studies documenting the superiority of AVS over CT or MRI in localizing primary aldosteronism, in particular, two recent studies demonstrating the accuracy of AVS in the diagnosis of an aldosterone-producing adenoma.7,8 Following a CT scan, which lacks the sensitivity and specificity to render an accurate diagnosis,  producing a discordance with a consistency of 56%,”9 he said, Given these convincing findings, “I wouldn’t manage patients with a coin flip when AVS will cure patients of this disease.”

In heading off a potential weakness in his argument, Dr. Young showed a taped interview with his colleague, James C. Andrews, MD, professor of radiology at the Mayo Clinic College of Medicine, who acknowledged that the key to making AVS work is to have a dedicated interventional radiologist on the team who has a consistent protocol, clear channel of communication, and commitment.5

“Cross-sectional imaging lacks the necessary specificity, and the [AVS] procedure isn’t hard,” Dr. Andrews said, “although to identify the correct adrenal and get a sample from the vein requires lots of pictures, an initial learning curve to gain experience, and mentoring to improve our technical accuracy.”

“We can agree that you can’t have a different radiologist every time AVS is ordered, but endocrinologists in the community can build that necessary relationship with a local interventional radiologist,” he said.

In summation,5 Dr. Young said, given the availability of a treatment that will cure PA, shouldn’t every patient have the opportunity to be free of disease, and have their full quality of life restored?

“When surgical treatment is feasible and desirable by the patient, the distinction between unilateral disease and bilateral adrenal aldosteronism must be made by an experienced radiologist, making AVS essential to direct therapy in patients with PA,”7 said Dr. Young“ after all, AVS carries high accuracy and cross-sectional imaging does not.”

His argument on the merits of AVS seemed irrefutable5 but he softened his stance in response to a question from EndocrineWeb about the feasibility of finding an experienced interventional radiologist at every hospital, as a rule, “you can have larger community hospitals who perform at least 25 procedures a year make it work with a dedicated interventional radiologist,” said Dr. Young.

AVS is Not A Good Standard for Most Patients with Primary Aldosteronism

Large discrepancies in the interpretation of AVS results, with five times more AVS procedures deemed unsuccessful even in well-regarded institutions, introduces a substantial level of uncertainty into treatment decisions for patients with primary aldosteronism,11 said Dr. Stewart in establishing his position in this debate.5

Dr. Steward focused on the capability of having AVS performed in most community hospitals, questioning the practicality. “How do we justify AVS in these settings given the risk of complications,” he said when even the success of sample collections at centers of excellence in Germany is less than one-third.12

Given the enormity of the limitations faced by patients with PA who may be candidates for AVS, in addition to the costs, Dr. Steward challenged the concept that adrenal venous sampling should hold such “gold standard” status in managing the majority of patients with APA.2

The reproducibility is just not there, nor is there sufficient robustness.5 It’s clear that we just don’t have the experience to meet the needs of most PA patients, he said. ”[AVS] is possible, but only within settings with sufficient volume,” of patients handled by an experienced interventional radiologist, he said, that’s the vast minority of institutions.

Dr. Stewart indicated that the field has seen significant advances in the molecular understanding of the disease, which has simply raised more questions such as causation of hyperplastic changes in the adrenals, mutations of the contralateral gland, multiple adenomas, bilateral disease, and “dominant versus true autonomy” of disease.13,14

In addition, he said, PA treatment is complicated by the pluripotency of adrenal-associated genes, given irregularities in cortisol and aldosterone levels that occur in the presence of mutations, thus complicating the determination of hypertension-type.14  Given the risks of unilateral uncertainty, getting it wrong and putting a patient through an ineffective surgery, when “there are medical treatments that are just as effective, and proving identical outcomes.9

A more reliable treatment for PA is the administration of mineralocorticoid receptor (MR) antagonists,5 said Dr. Stewart. Concerns that this therapy introduces an increased risk for cardiometabolic events, even mortality was refuted in a study by Hundemer et al,15  who reported that an elevated risk for cardiovascular events was limited to a subset of patients whose renin levels remained suppressed.  As such, provided “you give these patients a big enough dose” of MR antagonists, their risk will not be significantly elevated, said Dr. Stewart.

Age is an Important Cut-off

AVS With regard to AVS, younger patients have demonstrated a higher rate for positive clinical outcomes. As a general rule, it is reasonable to consider surgery in patients under age 35, and possibly up to age 49 years for patients with a typical adrenal lesion on fine cut CT scan, and with a normal contralateral gland,5 Dr. Stewart said.

“Yet, for the mass population, AVS is rarely indicated,” he cautioned, especially when “MR blockade is highly effective,” as blood pressure-reducing alternative to spironolactone.  Moving forward, endocrinologists can look forward to innovations in imaging to improve diagnostic capabilities, but we are not there yet, Dr. Stewart said.

Rebuttal and a Final Word on AVS

Not to be deterred, Dr. Young argued that for patients with PA to suffer with anxiety, depression, hypertension, elevated serum potassium, and weight gain as a result of PA, “the benefits of surgery go far beyond extreme hypertension, and hyperkalemia, given that quality of life issues are a key patient outcomes.3

Getting the last word, Dr. Williams said, given that the vast majority of patients are treated in community hospitals, “how could a gold standard have such uncertainty and a lack of evidence basis? This procedure is not practical or cost effective for the majority of our patients.”

The argument against AVS as first-line therapy for most patients proved more convincing; the initial vote was 36% against AVS having a major role to play, rising to 41% of those voting at the session.5

Clearly, AVS is the preferred treatment for younger patients with PA, provided they have access to a highly experienced interventional radiologist.

Dr. Young and Dr. Stewart had no relevant financial conflicts

Next Summary:
Cardiometabolic Outcomes Better Endpoint in Newly Diagnosed Diabetes
Last updated on

close X