Primary Aldosteronism: Next Steps in Care

Primary Aldosteronism: Next Steps in Care

Maeson: Today we're diving into a condition that is underdiagnosed. Undertreated, and surprisingly common primary aldosterone or pa, often overshadowed by more familiar causes of hypertension. PA affects approximately 30% of patients with hypertension Yet current screening tools fail to accurately capture primary aldosterone, and fewer than 1% of patients are being screened.

But here's the kicker, If left untreated, primary aldosterone carries a significantly higher risk for cardiovascular, metabolic, and even renal dysfunction than essential hypertension alone, even when blood pressure seems controlled.

So once you've made the diagnosis, what comes next?

[00:01:00] Today I'm joined by my fellow clinical educator, Millicent key we're breaking down the critical clinical steps after diagnosis of PA from confirmatory testing to targeted treatment, and how these steps can be a game changer for long-term outcomes and patience. Millie, thank you for joining me today.

Millie Kee: Thank you, Mason. It is a pleasure to be here with you today to discuss such an important topic.

Maeson: Okay, Millie, let's start big picture here. Can you speak to your experience with hypertension and even your experience with primary aldosterone?

Millie Kee: Yes, I was a nurse practitioner in cardiology for about 15 years, and in endocrinology for about two years. So when I was seeing patients, the idea of primary aldosterone was in my mind. I was thinking about it when I was looking over their history and how they were presenting that day.

Unfortunately, though, I was also seeing patients who had been diagnosed or were soon to be diagnosed with abnormal heart [00:02:00] rhythms or congestive heart failure, other heart issues, or were being sent into the endocrinology clinic because of resistant hypertension, because they had already been placed on several anti-hypertensive medications and it was just not controlling their blood pressure.

And in addition to that, oftentimes these patients who had resistant hypertension or were on several medications to try and get some level of control over their blood pressure were also being labeled non-compliant. Because the thinking is, of course, that if you're on several blood pressure medications, that the blood pressure should be controlled. And oftentimes it was not.

So while I always had primary aldosterone in the back of my mind as a diagnosis and, and was looking for it. These patients unfortunately, had already suffered end organ damage and were already further down the road in the course of their health being changed by the presence of primary aldosterone.

Maeson: Thanks, Millie. So while you had primary aldosterone on your mind, [00:03:00] many providers didn't, which is why you saw patients at risk for primary aldosterone in a space of referral. Right? Cardiology and endocrinology.

Now that we know that primary aldosterone is much more common than initially thought it's necessary to talk about screening and methodology in the setting of primary care. Traditionally, what screening method were you using in clinic?

Millie Kee: Well, primary aldosterone is characterized by both high aldosterone and low rein activity. So traditionally the measurement used to diagnose primary aldosterone or to identify it was the aldosterone to rein ratio, also known as the ARR. However, this screening method did suffer from some drawbacks. One is that, the measurements could be somewhat inconsistent.

The workup was a little bit more complicated, and overall, the testing lacked in sensitivity and missed several individuals with PA as a [00:04:00] result.

Maeson: So knowing that the ARR, that aldosterone RUNIN ratio has these drawbacks, what methodology are we utilizing now to better identify patients with primary aldosterone?

Millie Kee: So now we have a newer screening tool, plasma renin activity, also known as the PRA. This offers a greater level of sensitivity to recognize these at-risk patients for primary aldosterone.

Maeson: And how does the screening methodology work?

Well, First, we use the plasma renin activity to screen for low renin level as an alternative first step to the aldosterone to rein ratio. If the patient has a rein level, less than one nanogram per milliliter per hour,

Millie Kee: Which shows that rein is suppressed.

Then the next step is to use the aldosterone level to categorize these patients. Again, we know that primary aldosterone is characterized by high aldosterone levels.

If the patient has an aldosterone level, less than five nanograms per [00:05:00] deciliter, then They more likely have low rein hypertension if their level is between five to 15 nanograms per deciliter. Likely they have primary aldosterone and less proven otherwise.

If their level is greater than 15 nanograms per deciliter. then overt primary aldosterone is present.

Maeson: Right, so just changing the way that we look at these same analytes in the aldosterone renin ratio, but first looking at whether or not rein is suppressed, right, is renin less than one nanogram per milliliter per hour Then as a follow up, you look for aldosterone and you can characterize the severity of primary aldosterone is

based on their aldosterone level, and interestingly, this methodology can identify patients with primary aldosterone that may have been missed using that a RR or the aldosterone rein ratio.

Millie Kee: Exactly, and I think that's something that's really important to note that not only is this [00:06:00] test giving us an opportunity to identify patients that may have previously been missed with using the aldosterone TOIN ratio, but it also allows us to do so.

Using a simple marker that can be ordered in the primary care or the internal medicine clinic, and that will also allow us to start treatment early on for these patients, which will address the problems with pa, specifically the resistant hypertension, if that's present, and also improve their long-term health.

Maeson: yeah, great point. That this can be something that can be utilized in a space of primary care or internal medicine to help patients sooner. So let's go ahead and switch gears once the patient has been diagnosed with primary aldosterone using this new methodology. Let's talk a little bit more about treatment options in considerations.

Millie Kee: So the way to use this test as a start to treatment is to first look at if the rein level is suppressed and the aldosterone level is [00:07:00] greater than five. If so, then literature supports adding an MRA or a mineral corticoid receptor antagonist to their current medications. You can do this for four weeks and then compare your blood pressure readings.

So what you do is you take a blood pressure reading at the start of. The medication and then again at four weeks after being on the medication. If the patient had a fall in blood pressure that was less than 10 millimeters of mercury, this makes PA unlikely. If however, their change in blood pressure readings was greater than 12 millimeters of mercury, and that means a decrease in their blood pressure readings of greater than 12 millimeters of mercury, then PA is much more probable.

It is also really important to note that if the rein is suppressed and the patient has evidence of hypokalemia or a low potassium level on their lab values, then PA can be confirmed based on that. And you can go ahead and start the medication treatment

Maeson: that's really helpful insight into what clinicians can expect [00:08:00] in terms of blood pressure changes. And now building on that, I'd love to dig a little deeper into the treatment side. Can you tell us a little more about mineralocorticoid receptor antagonists or RAs, how they work and where they fit into the management of primary aldosterone?

Millie Kee: MRAs are also commonly known as potassium sparing diuretics, and these medications work not on aldosterone itself. Instead, they inhibit its effects by blocking its receptors, but their most immediate impact is on hypertension. So they will help patients control their blood pressure and eliminate the sodium that they're retaining, that's increasing their blood pressure, but in a way that does not waste their potassium.

Spironolactone is the most typically prescribed MRA and it's a potent anti-hypertensive When it's added to a patient's regimen, most individuals can reduce the number of blood pressure lowering medications that they require, and some can even control their blood pressure on Spironolactone [00:09:00] alone.

Another MRA medication is a plone, and it's not used quite as commonly. Typically, patients are started on spironolactone initially, and if they're unable to tolerate it, then a plone is used as an alternative.

Both Mrs. Spironolactone and a plone are clinically effective medications, but I think it's also really important to note that both are cost-effective medications

And that makes them very accessible to our patients.

Maeson: okay, so once a patient has started on an MRA, they're usually referred to nephrology or endocrinology for further evaluation.

What does that phase typically look like? I.

Millie Kee: Once the patient's referred to nephrology or endocrinology, the next step may be to confirm primary aldosterone, and if that's done, typically it's gonna be done with what's called a saline infusion test, which evaluates the aldosterone levels in a person in response to [00:10:00] increased sodium and fluid intake.

However, it's important to note that the guidelines which were set forth by the Endocrine Society state that in a patient with spontaneous hypokalemia, which is that low potassium level without a cause resistant hypertension, and a positive or overtly positive screening for pa, then confirmatory testing's not typically indicated, and the patient can safely be placed on a medical management regimen.

Maeson: Okay, so just to summarize really quickly, since low potassium is a potential side effect of pa, if a patient has overt positive or positive screening for PA and hypokalemia or low potassium, that patient can then go straight to clinical management and start a medication.

Can you share with us what that medical management looks like?

Millie Kee: Sure. So we do want to try to determine the cause of pa. This is done by imaging the adrenal glands with an adrenal CAT scan.

[00:11:00] This will exclude large masses that may represent a carcinoma. And while this is very rare, it does need to be evaluated for also, it's going to allow us to specifically look at whether the cause is an adrenal adenoma, which is a benign tumor that occurs on one adrenal gland or adrenal hyperplasia, which is overgrowth and overactivity of the cells in both adrenal glands.

This is also the most common cause of pa. Depending on the results of this, we will then determine whether to refer the patient for a surgical evaluation or continue medical management.

Maeson: So how then do you determine whether or not the patient requires surgical evaluation?

Millie Kee: A large mass or evidence of a carcinoma on the adrenal CTA would absolutely require a surgical evaluation. The guidelines also recommend considering an ADRENALECTOMY or a surgical procedure for those patients who have a unilateral or one-sided aldosterone producing [00:12:00] adenoma. However, if a patient is unable or unwilling to undergo surgery evaluation, then we will typically continue with medication.

Maeson: And what about those individuals with primary aldosterone is due to bilateral adrenal disease?

Millie Kee: These patients will typically respond very well to medication alone and will be successfully treated with an MRA.

Maeson: Interesting. So now that we've talked through the referral process and what the specialist workup entails, I wanna circle back to the treatment side, specifically the mineralocorticoid receptor antagonist.

I know that RAs are often Described as having a strong effect profile, which does cause some providers to feel resistant to administration. Can you expand a little bit on this and why some providers may have some concerns regarding administration of RAs?

Millie Kee: Yes. The most common concern with starting either of these medications is hyperkalemia, which is a concerning elevation [00:13:00] of potassium. However, given that PA patients are usually on the lower end of normal in regards to their potassium level or even have overtly low potassium levels, this is not likely to happen.

But you can usually monitor for this. With periodic lab, a basic metabolic panel or a comprehensive metabolic panel. If the patient's already on other blood pressure lowering medications that have high potassium levels as a side effect, you can also alter those doses to constrain the potassium levels to allow for the MRA to start.

Either way. Once you start an MRA, you should check labs in two to three weeks, and that would include a potassium level, a creatinine, and a renin level as we would expect renin levels to increase in appropriate treatment. Another concern that providers often encounter is gynecomastia. This will occur in Spironolactone because it blocks androgen receptors, which can then lead to breast tissue growth.

In men taking this medication, [00:14:00] most studies place it at anywhere from one to 10%. Stopping the medication should resolve this issue, and these men will typically benefit from a switch to a plone. And finally. What is sometimes seen is a change in EGFR or estimated glomerular filtration rate results.

What happens with that is that aldosterone excess will cause renal Hyperfiltration and then treatment with an MRA or an ADRENALECTOMY if surgery was indicated, often results in this unmasking of renal dysfunction.

So it's not uncommon to see an initial decline in EGFR. On the lab results, this usually offers some providers some concern though, because they have a tendency to associate this with the start of a medication, when really what was happening all along is that this patient with PA was starting to experience renal dysfunction.

And it was not [00:15:00] being caught on the lab result because of the excess aldosterone. So once we treat that excess aldosterone appropriately, we're actually just unmasking that renal dysfunction and beginning to see it on the lab value.

Also in those patients who we've been able to identify that underlying renal dysfunction, they will still benefit from an MRA, .

But it's also important to note that they will best benefit if we're keeping a closer eye on their lab values and checking those labs a bit more frequently.

Maeson: Wow, that's really interesting. So essentially having primary aldosterone is can mask chronic kidney disease and elevate an EGFR. So by taking the proper treatment for primary aldosterone, what we see is a decline in EGFR that. Adequately reflects the kidney function.

I think that this is very powerful and goes to show how we talk about patients with primary aldosterone- ism having an increased risk for cardiometabolic conditions.

Millie Kee: exactly I [00:16:00] think that that speaks to what we know to be true about primary aldosterone, which is that untreated it does lead to a disproportionately higher risk of kidney dysfunction.

But we also know it leads to a disproportionately higher risk of cardiovascular disease and issues like heart attack and heart failure and stroke. when we compare patients with PA to patients who are experiencing essential hypertension only.

And often the only symptom is just high blood pressure.

This really indicates and emphasizes the need for appropriate screening for PA and appropriate treatment once it's properly identified.

Maeson: Thank you so much Millie. I think that's perfectly stated . So before we sign off today, do you have any final thoughts that you'd like to share with us?

Millie Kee: Yes, the guidelines have always directed us to screen certain individuals for PA exceptionally elevated blood pressure or high blood pressure, requiring more than three medications to [00:17:00] control or uncontrolled blood pressure on more than three medications. However, as we go forward, we're really beginning to see that primary aldosterone is common and based on the fact that we know that PA leads to these increased risk, early screening and aggressive medical management is warranted. So ultimately, we really should be screening all patients with hypertension at least once for pa.

Doing so and properly identifying PA and these individuals can really make a great impact on their overall health journey.

Maeson: Excellent. Well, thank you so much for joining me today, Millie, and sharing your expertise with us.

Millie Kee: Thank you, Mason. It was a pleasure to speak with you today.

That's a wrap on this episode of Healthier World with Quest Diagnostics.

[00:18:00] Please follow us on your favorite podcast app and be sure to check out Quest Diagnostics Clinical Education Center for more resources, including educational webinars and research publications. Thank you for joining us today as we work to create a healthier world, one life at a time.