Primary aldosteronism is a condition that is frequently underdiagnosed and difficult to manage because of the severity of hypertension associated with the disease. Learn more about how doctors treat this condition and the best ways to screen for and diagnose it.

What is Primary Aldosteronism?

Adrenal Gland

Primary aldosteronism is a hormonal condition caused by an overproduction of aldosterone in the adrenal glands. It is also called Conn’s syndrome or primary hyperaldosteronism.

Aldosterone plays a crucial role in the body’s renin-angiotensin-aldosterone system (RAAS), which helps keep blood pressure at healthy levels. The RAAS activates in response to low blood pressure. The kidneys start the process by producing an enzyme called renin. Renin initiates the production of other hormones (angiotensin I and II) that also play crucial roles in helping increase blood pressure. The final step of the RAAS cascade involves the production of aldosterone. Aldosterone directs the body to hold onto more salt and water, raising blood pressure. Once blood pressure reaches a healthy level, the RAAS sends signals to decrease aldosterone production.

However, people with primary aldosteronism produce more aldosterone than is needed independent of signals from the RAAS. As a result, it’s common for many patients to develop secondary hypertension, or high blood pressure caused by a specific, potentially identifiable medical condition. Other causes of secondary hypertension include obstructive sleep apnea, kidney disease, and thyroid problems. Secondary hypertension differs from essential hypertension in that the precise cause of the latter is unknown, but factors such as a poor diet or obesity may contribute to the high blood pressure of those with essential hypertension.

Secondary hypertension is often more difficult to treat with medication because of the severity of the blood pressure elevation and the reduced responsiveness, or resistance, to standard treatments. Up to 10% of patients experience treatment-resistant hypertension, despite taking three or more medications for hypertension. Treatment-resistant hypertension increases the risk of cardiovascular disease and other cardiovascular complications, such as atrial fibrillation or stroke.


Who is Most Likely to Have Primary Aldosteronism?

While there are many reasons someone might develop primary aldosteronism, the people who are most likely to have this condition include the following:

  • People with a parent or sibling who had primary aldosteronism
  • Hypertensive patients who struggle to control their high blood pressure despite taking three or more hypertension medications
  • People who have hypokalemia (low potassium levels)
  • People younger than 30 years old with hypertension (early-onset hypertension)


What are the Most Common Causes of Primary Aldosteronism?

The most common cause of primary aldosteronism is the presence of aldosterone-producing adenomas (non-cancerous masses) or nodules in the adrenal gland. People with primary aldosteronism have either unilateral disease (one gland affected) or bilateral disease (both glands affected). An adenoma is the most common cause of unilateral disease. Bilateral adrenal hyperplasia is most common in people with bilateral disease. It refers to small nodules that can cause both adrenal glands to become hyperactive and produce too much aldosterone.

Another rare cause of primary aldosteronism is glucocorticoid remediable aldosteronism. This autosomal dominant disorder affects the genes responsible for aldosterone synthesis.


What are the Symptoms of Primary Aldosteronism?

Primary aldosteronism often causes symptoms in people with moderate to severe hypertension and low potassium levels. The combination of chronic hypertension and low potassium can usually lead to the following symptoms:

  • Fatigue
  • Cramps
  • Headaches
  • A frequent need to urinate

Who should be Screened for Primary Aldosteronism?

People who exhibit some of the following risk factors should be screened for primary aldosteronism:

  • Hypertension measured at >150/100 mmHg on three different readings on different days
  • Hypertension measured at >140/190 mmHg that isn’t responding to at least three hypertensive medications (including diuretics)
  • Hypokalemia (low potassium levels) not attributable to a diuretic
  • People who have a parent or sibling with primary aldosteronism

How is Primary Aldosteronism Screened?

While there are a few different screening tools, blood tests are the most common way to screen for primary aldosteronism.

Specifically, the most common screening blood test is an aldosterone to renin ratio (ARR) test. An ARR test measures the amount of aldosterone in the blood and the plasma renin activity (PRA), and creates a ratio of the two numbers. When aldosterone is being produced in an un-regulated way by a benign adenoma in the adrenal, the resulting salt and water retention should result in renin suppression. This situation results in a high aldosterone to renin ratio. If an individual were dehydrated, the aldosterone level could go up driven by renin and the ratio should be lower because the renin level would not be suppressed. A test showing high levels of aldosterone with low or suppressed renin levels could be a sign of primary aldosteronism.

Blood samples can also be tested to see if someone has low blood potassium levels. When aldosterone directs the kidney to hold onto more salt and water, it reciprocally directs the kidney to excrete potassium. Chronic, long-term elevations of aldosterone can lead to long-term reductions in potassium.

Before performing blood tests to try to determine if PA is present, a patient taking any hypertension medication that affects the RAAS , such as a mineralocorticoid receptor antagonist (MRAs) should be switched to taking drugs that have minimal effects on hormones regulated by the RAAS. The mineralocorticoid receptor antagonists (e.g. spironolactone or eplerenone) block aldosterone’s activity at the receptor and this typically results in very elevated aldosterone levels, making it difficult to diagnose PA in the setting of these drugs.

How is Primary Aldosteronism Diagnosed?

Screening tests are a helpful first diagnostic step. However, additional tests can help determine why someone might have high aldosterone levels and confirm a diagnosis of primary aldosteronism.

Confirmatory testing verifies if the adrenal glands are overproducing aldosterone independent of signals from the RAAS. For example, a patient may be given hypertension medication to see how it affects aldosterone production. Captopril, an angiotensin-converting enzyme inhibitor, is the most common hypertension medication used. Other test options include salt tests, where a patient ingests larger than normal amounts of salt and provides regular urine samples. These samples are then measured for aldosterone levels. Because salt loading should lower renin and then aldosterone, these tests are designed to suppress aldosterone levels which typically will not happen when the aldosterone in produced by the benign tumors in the adrenal gland, as they have lost their ability to respond to the usual cues from the RAAS cascade that control aldosterone levels.

CT or MRI scans can often locate a mass or tumor that is causing adrenal aldosterone overproduction. However, the imaging tests are usually only done after hormonal tests have proven there is excess aldosterone present. To be sure the correct adrenal condition is established, adrenal vein sampling (or adrenal venous sampling) can be performed to determine which adrenal gland (if not both) is producing the excess hormone.

How is Primary Aldosteronism Managed?

If the PA is clearly demonstrated to be due to overproduction of aldosterone from one of the two adrenal glands, surgical removal of that gland can result in substantial improvement if not normalization of the blood pressure. However, if bilateral disease is presence, this is typically managed by treatment with blood pressure medications, rather than surgical removal of both adrenals, as that would result in complete adrenal insufficiency. Even those patients who undergone unilateral adrenalectomy will sometimes fail to achieve blood pressure control or will, over time, develop a recurrence of hypertension driven that may be caused by the development of aldosterone producing adenomas in their remaining adrenal gland. Treatment of primary aldosteronism thus often involves finding ways to manage hypertension and reduce the risk of complications through the use of medications.



Medications can help manage hypertension. MRAs, for example, are commonly administered because they help block the effects of aldosterone. Other medications include angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs).

Many of these medications (ACE inhibitors and ARBs, especially) often become less effective over time. For example, in some patients, aldosterone levels return to or exceed baseline levels despite continued medication adherence (an aldosterone breakthrough). In PA patients in particular, the inability to adequately block aldosterone levels can result in more frequent issues of hyperkalemia.

The goal of CinCor’s ongoing efforts to develop baxdrostat is to develop a selective aldosterone synthase inhibitor that specifically limits the production of aldosterone in this dysregulated condition.


Diet and Lifestyle Changes

Patients can manage primary aldosteronism by increasing exercise frequency, limiting alcohol intake and watching salt intake. Doctors often recommend these lifestyle changes to treat chronic hypertension.



A mass can usually be removed through a laparoscopic procedure. Following the procedure, people with primary aldosteronism usually see either a reduction in blood pressure or a decrease in the number of medications they need to take.

However, in people with bilateral adrenal hyperplasia, where small nodules cause adrenal glands to become hyperactive and produce too much aldosterone, surgical treatment is usually not the best option because it can result in complete loss of adrenal function which can be difficult to manage.