Primary Aldosteronism: The Role of Adrenal Venous Sampling

The challenge

The triad of hypertension, hypokalemia, and an aldosterone-producing adenoma (APA) of the adrenal gland was first reported by Jerome W. Conn, M.D., in 1955.

Unilateral adrenalectomy in patients with an adrenal adenoma normalizes hypokalemia in all patients, normalizes blood pressure in at least a third of patients, and improves hypertension in nearly all patients.

In patients with idiopathic hyperaldosteronism (IHA), however, a unilateral or bilateral adrenalectomy seldom corrects hypertension. Patients with IHA should be treated not surgically but medically with a mineralocorticoid receptor antagonist. Therefore, determining the subtype of primary aldosteronism (PA), APA vs IHA, is critical in directing treatment.

Distinguishing between APA and IHA

Selective adrenal venous sampling (AVS) for aldosterone was first proposed in 1967 as a test to distinguish between APA and IHA. However, it is an invasive and difficult technique, and both adrenal veins must be sampled for meaningful comparison.

Adrenal CT scan of woman with poorly controlled hypertension

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Diagram of algorithmic approach to subtype evaluation

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Computed tomography (CT) was initially thought to be a good test to distinguish among the subtypes of PA. Because of the prevalence of nonfunctioning cortical adenomas, however, hormonal hyperfunction cannot be inferred simply from the presence of an adrenal nodule. Additionally, APAs that are 3 or 4 mm in diameter may escape detection on CT, and patients with a unilateral APA may have bilateral adrenal nodules on CT—one that is nonfunctional and one that is hypersecreting aldosterone.

An algorithmic approach to subtype evaluation of a patient with primary aldosteronism helps determine when AVS is needed in patients with PA. Because adrenal incidentalomas are uncommon in young patients, when a solitary unilateral macronodule (>1 cm) and a normal contralateral adrenal are found on CT in a patient with PA, unilateral adrenalectomy is reasonable to consider. In addition, many patients prefer pharmacologic therapy and, therefore, do not require AVS. Using this approach, AVS is done in approximately 20% of patients with PA at Mayo Clinic.

Patients with an APA have more severe hypertension, more frequent hypokalemia, higher plasma (>25 ng/dL) and urinary (>30 μg/24 h) levels of aldosterone, and are younger than those with IHA. Patients with these findings are considered to have a high probability of APA. These findings, however, are not absolute predictors of unilateral (vs bilateral) adrenal disease. Therefore, AVS is an essential diagnostic step in most patients with PA, to distinguish between unilateral and bilateral adrenal aldosterone hypersecretion.

Adrenal venous sampling in right and left adrenal veins

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During the procedure, the adrenal veins are sequentially catheterized through the percutaneous femoral vein approach under fluoroscopic guidance, and correct catheter tip location is confirmed with injection of a small amount of contrast medium. Blood is obtained by gentle aspiration from both adrenal veins.

Successful catheterization may require an array of catheter configurations, either available from manufacturers or custom-made with steam shaping during the procedure to facilitate access to the adrenal veins. The placement of side holes very close to the catheter tip may enhance the progress of the blood draw.

At centers with experience with AVS, the complication rate is 2.5% or less. Complications may include:

• Symptomatic groin hematoma
• Adrenal hemorrhage
• Dissection of an adrenal vein

Results of bilateral adrenal venous sampling (AVS) in the patient with primary aldosteronism who had a CT scan and AVS radiographs

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Aldosterone and cortisol concentrations are measured in the blood from all 3 sites (right adrenal vein, left adrenal vein, and inferior vena cava). All blood samples should be assayed at 1:1, 1:10, and 1:50 dilutions—absolute values are mandatory. Accurate laboratory assays for cortisol and aldosterone are keys to successful interpretation of the AVS data.

Mayo Clinic has now performed AVS in more than 400 patients. For patients with PA who want to pursue the surgical treatment option, AVS is an essential diagnostic step.

Points to remember

• Primary aldosteronism (PA) affects between 5% and 10% of all patients with hypertension.
• PA has more than one cause, and most patients with PA have bilateral idiopathic hyperaldosteronism (IHA).
• Because patients with IHA should be treated medically not surgically, distinguishing between aldosterone-producing adenoma (APA) and IHA is critical in directing treatment.
• For patients with PA who want to pursue the surgical treatment option, adrenal venous sampling (AVS) is an essential diagnostic step.