Hypertension: revisiting the hormonal connection

Should screening for primary aldosteronism become routine in all patients with hypertension? If a recent review published in Nature Reviews Disease Primers and co-authored by Dr. André Lacroix is any indication, the answer is unequivocal.An endocrinologist at the Centre hospitalier de l’Université de Montréal (CHUM) and a specialist in adrenal disorders, Dr. Lacroix is clear in his recommendation: Family physicians should measure aldosterone and renin in all of their patients with hypertension even before starting treatment.“For 15 years, I’ve been telling my colleagues who treat cardiac arrhythmias and atrial fibrillation that they should screen all their patients. And they still don’t.”Dr. Rémi Goupil, a nephrologist at Hôpital du Sacré-Cœur de Montréal and an expert in resistant and endocrine hypertension, shares that view. Dr. Goupil, who co-chaired Hypertension Canada’s 2025 guideline committee and is currently president-elect of the Société québécoise d’hypertension artérielle, is speaking in a personal capacity. “I am completely in favour of systematic screening of all individuals with hypertension,” he said.He notes, however, that Hypertension Canada has not yet taken an official position on the issue, and that one of its committees is currently developing a clinical practice guideline on primary aldosteronism.More common than once believedFor decades, the condition was considered a rare cause of hypertension. “When I was a medical student, we were taught that primary aldosteronism was a rare disease, perhaps 1% of hypertension cases,” recalled Dr. Lacroix, who has been licensed to practise medicine since 1973. Screening was largely reserved for the most suggestive cases, such as severe hypertension, hypokalemia or an adrenal mass.That picture has changed considerably. The review estimates that primary aldosteronism affects about 5% of patients with hypertension seen in primary care, around 10% of those seen in referral centres and more than 20% of those with resistant hypertension. At comparable blood pressure levels, these patients also have more cardiovascular and renal complications than patients with essential hypertension.Yet the condition is still rarely investigated. Even among patients who meet traditional screening criteria, fewer than 5% are tested, according to data summarized in the Nature Reviews Disease Primers article.“Even when there are clear clinical signs, it’s not something physicians think about,” said Dr. Goupil, who cites screening rates of just 1% to 2% in some databases.This underdiagnosis also reflects the fact that the disease does not always present in its classic form. Laboratory thresholds provide useful benchmarks, but they do not capture the full range of clinical presentations.“The reality is that there is always a very, very large grey zone because the thresholds are set somewhat arbitrarily,” said Dr. Goupil.In some patients, aldosterone levels are not markedly elevated, but renin remains suppressed, indicating inappropriate aldosterone secretion. These subtler forms are also associated with increased cardiovascular risk.“We talk about subclinical primary aldosteronism because the classic features, such as severe hypertension or hypokalemia, aren’t present. There are very few clinical manifestations,” Dr. Goupil explained.Viewing the condition as a continuum substantially broadens its spectrum. The review notes that prevalence could reach 30% when milder forms of renin-independent aldosterone secretion are included.Universal screening under debateFor Dr. Lacroix, the case for universal screening in people with hypertension goes beyond blood pressure control. A patient with primary aldosteronism may achieve normal blood pressure with antihypertensive medication, “but we are not blocking the harmful effects of aldosterone on the body,” he stressed.That can mean missing an opportunity to offer targeted treatment to patients who face a higher cardiovascular and renal risk than those with essential hypertension.This is where Dr. Goupil adds a note of caution. He supports much broader screening, but believes the evidence is not yet strong enough to justify testing every patient with hypertension.“There are no data showing that universal screening actually changes patient outcomes.”Expanding screening to everyone would also involve costs and sometimes difficult-to-interpret results, potentially leading to additional investigations that prove unnecessary or cause complications.“We would be moving ahead with something based on a level of evidence that may not be high enough,” he said.That same hesitation appears in U.S. recommendations. A review published September 16 in JAMA notes that the Endocrine Society suggests screening all patients whose blood pressure was at least 140/90 mm Hg when hypertension was diagnosed, even if it is now controlled.The American Heart Association and American College of Cardiology, meanwhile, maintain a strong recommendation for patients at highest risk—including those with resistant hypertension, hypokalemia, an adrenal mass or certain forms of early-onset hypertension—while stating that screening all adults with hypertension may be considered, although with a weaker recommendation.Cost-benefit analyses conducted in Australia have been encouraging, according to Dr. Goupil. But directly proving that widespread screening reduces strokes, cardiovascular events or renal complications would require very large studies. “My sense is that the evidence will come more from modelling than from clinical trials,” he said.Treating the causeOnce primary aldosteronism is identified, the value of diagnosis becomes very tangible. “When we know the molecular cause of hypertension, we are much better able to treat it in a targeted way,” said Dr. Lacroix.Management then depends on the source of the aldosterone excess. When disease is bilateral or surgery is not being considered, treatment typically includes mineralocorticoid receptor antagonists such as spironolactone or eplerenone.For patients with confirmed unilateral disease who are candidates for surgery, adrenalectomy can lead to remission. A meta-analysis cited in the review found that 44% to 60% of patients who underwent surgery achieved normal blood pressure without antihypertensive medication.Dr. Goupil says he has seen patients treated for “10 to 15 years” with antihypertensive drugs and potassium supplements before the cause of their hypertension was finally identified. “When we do a health assessment and find anemia, we don’t say the solution is a transfusion. We have to find the cause. Hypertension is a bit the same.” In some cases, detecting unilateral primary aldosteronism opened the door to surgery, after which blood pressure returned to normal and medication could be stopped.“It can make an enormous difference in a patient’s life,” he said.Treatment options may also expand. Four aldosterone synthase inhibitors are currently being evaluated in phase II or III trials. New functional imaging techniques may eventually improve the detection and localization of unilateral disease.A challenge for primary careThe next challenge is organizing screening in primary care. From a laboratory standpoint, screening is based mainly on measuring aldosterone and renin, along with potassium.Ideally, blood should be drawn in the morning, without sodium restriction in the preceding days, after approximately two hours of being upright and active followed by 15 minutes seated, while also observing the laboratory’s requirements for renin sample storage and transport.Another consideration is that antihypertensive medications no longer need to be routinely stopped before initial screening.“In the past, that was one of the reasons physicians didn’t order the tests—they thought stopping the medications was too complicated. What we recommend now is to do the testing regardless of the medication,” said Dr. Lacroix.If results are borderline or difficult to interpret, certain treatments can then be stopped and the test repeated.In Quebec, access also depends on how the health system is organized. Testing is available in hospitals, but sample-storage requirements can make access more difficult in some CLSCs, Dr. Goupil noted.For him, “the first barrier is an educational one”: physicians will need support in interpreting results and knowing what action to take.Broader screening also cannot result in automatic specialist referral.“Specialists won’t be able to absorb all these patients,” Dr. Goupil warned.In his view, milder cases could likely be managed in primary care, while younger patients, those with more severe disease or those in whom unilateral disease and surgery are being considered would require specialist assessment.This article has been translated from its original French and first appeared on our sister site Profession Santé.

Hypertension: revisiting the hormonal connection

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