All with high blood pressure should be screened for primary aldosteronism
The new clinical practice guideline from the Endocrine Society urges all providers to screen anyone with hypertension for primary aldosteronism.
PA means the adrenal gland over-produces the hormone aldosterone independently of renin, a common phenomenon with modern diets. This leads to kidney sodium retention, volume expansion, and elevated blood pressure (and some potassium loss). Excess aldosterone also causes direct damage to the entire cardiorenal system.
The Endocrine Society recently announced a new clinical practice guideline, published in The Journal of Clinical Endocrinology & Metabolism, that goes into detail about how to diagnose and treat this very common disorder.
“Primary aldosteronism (PA), a primary adrenal disorder leading to excessive aldosterone production by one or both adrenal glands, is a common cause of hypertension. It is associated with an increased risk of cardiovascular complications compared with primary hypertension. Despite effective methods for diagnosing and treating PA, it remains markedly underdiagnosed and undertreated.”
The guideline is widely endorsed by the American Association of Clinical Endocrinology, American Heart Association, European Society of Endocrinology, European Society of Hypertension, International Society of Hypertension, the Primary Aldosteronism Foundation, and the European Society of Cardiology
Primary Aldosteronism
“Primary aldosteronism (PA) is an adrenal disorder, either unilateral or bilateral, resulting in excess adrenal production of aldosterone. In PA, aldosterone production is at least partially autonomous of its normal major regulator, the renin–angiotensin system, circulating levels of which are suppressed. The excess aldosterone leads to renal sodium retention, volume expansion, elevated blood pressure (BP), and, in more severe forms, hypokalemia.”
Compared to high blood pressure without PA (primary hypertension), there are significantly higher risks for coronary artery disease, stroke, heart failure, kidney disease; and reduced psychological well-being and quality of life.
As noted in Medscape:
“Meta-analyses have shown that, compared to people with primary hypertension, those with PA have more than twice the risk for stroke and kidney disease, more than triple for atrial fibrillation, and twice the risk for heart failure.”
Quoting the lead author:
“The goal of this new guideline, Adler said, “is to make it easy to diagnose [PA] and to start appropriate aldosterone-targeted therapy to reduce the excess cardiovascular, stroke, and renal morbidity associated with [PA]. It’s so easy to treat. Part of the problem in the past is we made it so hard to diagnose.”
Vastly under-recognized and under-treated
This condition is very common and hardly ever diagnosed.
“Despite its prevalence and the serious health risks it poses, PA remains largely underdiagnosed and undertreated. This under-recognition contributes significantly to the health care costs associated with hypertension, including the management of complications and related productivity losses.”
And:
“Screening for PA is critically low, often delayed until years after hypertension has been diagnosed, typically following the emergence of severe complications. This may in part be due to misconceptions that PA is only present in the setting of hypokalemia, adrenal macro-nodules, frankly elevated aldosterone levels, or severe hypertension. As a result, many individuals continue to be treated for primary hypertension, thus missing out on targeted treatments or potential cures, and enduring suboptimally managed BP and increased risks of cardiovascular and renal disease. The importance of this is emphasized in the latest major clinical guidelines on hypertension: The 2024 European Society of Cardiology (ESC) guidelines for the management of elevated BP and hypertension suggest screening for PA in all adults with diagnosed hypertension (6). The morbidity and mortality associated with PA are largely preventable.”
Also as noted in Medscape:
“Studies conducted over the past couple of decades suggest that PA prevalence is 5.9% among people with hypertension seen in primary care, 16.2% of younger adults aged 18-40 years with hypertension, 28.1% among adults with both hypertension and hypokalemia, 42% of those with hypertension and atrial fibrillation, and between 11.3% and 19.1% of those with hypertension and type 2 diabetes, according to the document.
Yet, in a study of US Veterans published in 2020, PA screening rates were less than 2% even among those with treatment-resistant hypertension. No improvements in screening rates were found in a more recent follow-up study from the same team.”
Screening and treatment guidelines
The Endocrine Society guideline goes into great detail on how to screen and treat primary aldosteronism, amounting to a state-of-the-art reference. It begins simply:
“PA screening includes measurement of serum/plasma aldosterone concentration and plasma renin (concentration or activity) with determination of the aldosterone to renin ratio (ARR). Potassium is also assessed—not for screening itself—but to aid in the accurate interpretation of aldosterone.”
It then can become more complex dependent on the specific case. Treatment guidelines are also detailed according to the case. When indicated, mineralocorticoid antagonists ( MRAs; aldosterone is a mineralocorticoid hormone) can be a much more effective treatment for hypertension than the usual medications when PA is involved.
Other medications to consider and surgery for certain adrenal tumors are also noted in the highly detailed recommendations offered in the new guideline. Most basically:
PA screening is suggested in all individuals with hypertension
In individuals with hypertension and PA, PA-specific therapy is suggested. Medical treatment with MRAs is preferable to nonspecific antihypertensive therapy. For individuals with lateralizing PA who are surgical candidates and desire surgery, unilateral adrenalectomy is preferred.
Screening for PA should include measurements of serum/plasma aldosterone concentration and plasma renin (concentration or activity).
A positive screen is defined as both a low renin level with inappropriately high aldosterone and an elevated aldosterone to renin ratio. Cutoffs for both values differ by assay and are provided in the document.
Potassium should be measured with aldosterone to aid in interpretation since low potassium can lead to falsely low aldosterone readings.
New medication that inhibits aldosterone is very effective
“Among patients with uncontrolled or resistant hypertension, the addition of baxdrostat, an aldosterone synthase inhibitor, to background therapy resulted in a significantly lower seated systolic blood pressure at 12 weeks than placebo.”
A trial just presented at the 2025 annual congress of the European Society of Cardiology, where it prompted spontaneous applause from the audience, was also simultaneously published online in The New England Journal of Medicine.
The authors state:
“Aldosterone dysregulation plays an important pathogenic role in hard-to-control hypertension. In several studies, baxdrostat, an aldosterone synthase inhibitor, reduced the seated systolic blood pressure of patients with uncontrolled or resistant hypertension.”
Quoted in Medscape, the senior researcher on the trial Bryan Williams, MD, chair of medicine at University College London, United Kingdom called the new class of drugs “a potential game changer” for patients:
“They target the core mechanism contributing to resistant/uncontrolled hypertension and should therefore reduce the future risk of heart disease, stroke, kidney disease, and potentially dementia in these patients,” he said.
Williams, the senior researcher on the BaxHTN trial, called the reduction in blood pressure with baxdrostat “very large” and “remarkably consistent across every subgroup.”
The decreases were observed with 24-hour ambulatory monitoring and at night and were maintained for “several weeks after drug withdrawal,” he said. “This is consistent with the hypothesis that aldosterone is playing a fundamental role in the generation of difficult-to-control hypertension in all of the patients, whatever their makeup, in both uncontrolled and resistant hypertension.”
Baxdrostat was generally well tolerated with no unanticipated side effects, Williams said.
Despite the availability of many treatments, high blood pressure is hard to control. “Elevated blood pressure is still the single most important preventable cause of premature death globally, with about 50% of patients who are treated globally not reaching the recommended treatment targets, and this represents hundreds of millions of people,” Williams said.
The development of baxdrostat and related drugs is “a triumph of scientific discovery,” following the finding that disturbed aldosterone production to be a key driver of hard-to-control hypertension, he said.
“Aldosterone is the master regulator of how the body handles salt and water, and when the levels are inappropriately high, as they become as we age, this can make people less able to eliminate salt, and it drives up blood pressure and contributes to the development of heart failure, heart disease, stroke, and kidney disease,” Williams said.”
