Tuesday, June 28, 2011

Primary Aldosteronism: An Approach

Someone asked in the chatbox for me to elaborate on why the CT scan isn't definitive in the diagnostic evaluation of primary aldosteronism. This is probably too long of an explanation to fit in there, so I thought I'd write a post about it.

Primary aldosteronism implies that the adrenal(s) is autonomously making inappropriate amounts of aldosterone, independent of the usual kidney-mediated renin-angiotensin system. The evaluation is undertaken usually in one of two situations- the discovery of an adrenal incidentaloma, or in the investigation of resistant hypertension.

In these cases, the first step is to document autonomous aldosterone secretion; we do this by means of a morning serum aldosterone and renin activity assuming that interfering drugs are not in the picture. A positive screening test includes an elevated aldosterone level, typically greater than 15 ng/dL, and an elevated aldosterone to renin ratio. Many of us use 15 or even 20:1. If this is positive, we move on to the confirmatory biochemical test of showing nonsuppressed aldosterone levels despite a good amount of salt in the system. This can be done by oral salt loading and measurement of 24-hour urine Sodium (should be greater than 200) with concomitant high urinary aldosterone (more than 12).

Alternatively, one can do the IV Saline suppression test showing a high (greater than 10) serum aldosterone despite 2 liters of Normal Saline.

(diagram pilfered fromNature Clinical Practice Endocrinology & Metabolism 2005)

At this point, you've documented that the patient is making inappropriate amounts of aldosterone and that the problem lies within the adrenal (ie not a case of renal artery stenosis leading to secondary hyperaldosteronism). However, as it turns out there are several subtypes of primary aldosteronism:

The exam-favorite Conn's syndrome or aldosterone-producing adenoma is often quoted.

However there can often also be adrenal hyperplasia which can bilateral.

(will not really mention the rare glucocorticoid remediable aldosteronism).

And so the problem is although you know the patient has the biochemical pathology, you don't know which adrenal is causing it. And without going into too much detail, as it turns out nonfunctioning adrenal adenomas are not uncommon, while adrenal hyperplasia may often not be visible on CT or MRI. And so, even if you see a juicy 2 cm right adrenal adenoma, you won't know if this is the source of the high aldosterone, or if this was just an innocent bystander while it's really microscopic pathology in the LEFT gland that's churning out the hormone and causing the blood pressure problems. And the last thing you want to do is to have your surgeon colleague remove the wrong gland, only to find out post-op that your patient remains hypertensive and hypokalemic.

And so, if you look at many of the guidelines out there, IF a patient is deemed to be a good surgical candidate, then often adrenal vein sampling for aldosterone (often normalized to cortisol, to correct for the dilutional effect of the converging veins) is required to lateralize the lesion. And AVS is a technically challenging procedure that only the most experienced of interventional radiologists can do skillfully.

The good news is, medical treatment with Spironolactone is usually very successful. So for most of my patients I try to direct them in this route, rather than the surgical. Because the truth is, if it's hypertension that they're hoping to cure, with many patients (first degree relative with hypertension, or prolonged history of hypertension etc) even if the surgeon took out the correct adrenal, they will STILL be hypertensive (though improved). There, a longish explanation for a fascinating clinical problem. I'd direct you to the Endocrine Society Clinical Practice Guideline if you wanted more bedtime reading.