Although traditionally considered rare, primary hyperaldosteronism is increasingly recognized as one of the most common forms of secondary hypertension. During the 46th Congress of the Cardiology Society of the State of São Paulo (SOCESP 2026), held June 4-6, experts warned that the condition may be present in up to one fifth of patients with resistant hypertension, yet it remains underdiagnosed.

According to Weverton Ferreira Leite, who holds a PhD in cardiology from the Heart Institute at the University of São Paulo Medical School, primary hyperaldosteronism behaves like an “iceberg,” with classic cases marked by hypokalemia or obvious adrenal abnormalities representing only the visible tip of the disease. Although its estimated prevalence ranges from 5% to 14% in primary care settings — and can rise to 30% in referral centers — only a small fraction of cases is actually detected. “We treat millions of patients blindly, as if they had primary hypertension,” he said.

According to Leite, many patients end up being diagnosed with essential hypertension without the underlying cause being investigated. “This entire patient population in which we have not identified primary hyperaldosteronism receives a diagnosis of primary hypertension and is treated without effectively seeking a cause,” he said. As a result, the opportunity to offer targeted treatments, including the use of mineralocorticoid receptor antagonists and, in selected cases, surgical treatment, is lost.

In addition to masking a potentially treatable cause of hypertension, primary hyperaldosteronism exposes patients to a cardiovascular risk that often remains hidden. “Excess aldosterone causes cardiovascular and renal damage regardless of blood pressure levels. Target organ damage is amplified,” he emphasized.

Data presented by Leite during the session showed that patients with the condition have an approximately 1.5-fold higher risk for atrial fibrillation (AF), a twofold higher risk for kidney disease, and a 2.6-fold higher risk for heart failure. The risk for stroke is also about 2.5 times higher.

What Leads to Underdiagnosis

For decades, primary hyperaldosteronism was associated with what was considered a classic profile: difficult-to-control hypertension accompanied by hypokalemia and, often, an adrenal adenoma easily identifiable on imaging studies. In practice, however, the reality is different. Data from the Endocrine Society 2025 meeting presented by Leite show that only 9%-37% of patients with confirmed primary hyperaldosteronism have hypokalemia.

“Many physicians still follow the old dogma and only suspect hyperaldosteronism if the patient has low potassium. But this indicator should not discourage screening for primary hyperaldosteronism,” he emphasized. This is because hypokalemia can interfere with aldosterone production and artificially lower the aldosterone to renin ratio (ARR). “It’s the classic false negative. But not only that: Hypokalemia is a late or inconsistent sign,” he warned.

According to Leite, another common misconception that contributes to underdiagnosis is expecting to find an adrenal nodule before considering the diagnostic hypothesis. In about two thirds of cases, excess aldosterone stems from bilateral adrenal hyperplasia, without the presence of the classic adenoma that many doctors still associate with the disease.

The focus should always be on the biochemical dissociation between renin and aldosterone, he stated. In general, primary hyperaldosteronism is characterized by inappropriately elevated aldosterone levels accompanied by renin suppression, a pattern that can be identified even in the absence of hypokalemia or obvious abnormalities on imaging studies.

The Challenges of Universal Screening

The proposal to expand screening gained momentum following the publication of the Endocrine Society’s 2025 guidelines, which suggest investigating primary hyperaldosteronism in all individuals with hypertension through measurement of aldosterone, renin, and the ARR. However, the document itself classifies this recommendation as conditional, emphasizing that its implementation must take into account factors such as resource availability, local expertise, and the capacity of the healthcare system.

The challenges of integrating this strategy into routine practice were also discussed during the conference. Rui Manuel dos Santos Póvoa, who holds a master’s degree and a PhD in cardiology from the Federal University of São Paulo (UNIFESP), presented the results of a screening study he conducted at the hypertension clinic of the São Paulo State Public Servants Hospital between June 2023 and March 2026.

A total of 623 patients with resistant hypertension were evaluated through aldosterone and renin measurement. At the end of the investigation, 28 had a confirmed diagnosis, corresponding to 4.5% of the sample. Regarding the financial investment, the screening cost approximately Brazilian reais (R) 38,000 (roughly $7330), with an estimated cost of R 58 (approximately $11) per test performed.

According to Póvoa, the rate of positive results was lower than expected when compared to figures reported in the literature. “4.5% is a very low figure compared to data from the literature, which reports average values of 9% in the general population with hypertension and nearly 30% in those with resistant hypertension,” he noted.

Part of this discrepancy can be explained by characteristics of the diagnostic process itself. “We have several methods for measuring aldosterone, and in all of these methods, inter-assay agreement is very poor. There is no adequate international reference standard,” he stated.

Póvoa also highlighted the lack of consensus on cutoff values for the ARR, as well as the variability of results across different laboratories. “The reproducibility of the test within the same institution is suboptimal. The same patient may test positive at one institution and negative at another,” he warned.

Who Should Be Screened

Despite the limitations of the tests, current major guidelines and consensus statements recommend prioritizing screening in higher-risk groups.

During the session, Póvoa highlighted among these patients those with resistant or refractory hypertension, spontaneous or diuretic-induced hypokalemia, severe hypertension, obstructive sleep apnea, a family history of early-onset hypertension or stroke at a young age, as well as those with an adrenal incidentaloma identified on imaging studies.

The goal of screening is to identify patients who may benefit from targeted treatment. This is because, once the diagnosis is confirmed, the therapeutic strategy depends on the disease subtype.

What Changes Once the Diagnosis is Confirmed?

Once the diagnosis is established, identifying the disease subtype becomes critical for guiding treatment. According to Celso Amodeo, PhD, a nephrologist and cardiologist at the Federal University of São Paulo, primary hyperaldosteronism should be seen not simply as a form of secondary hypertension but as an aldosterone-mediated cardiovascular and renal disease.

“In reality, today the primary goal is not only to lower blood pressure but also — and especially for those treating patients with hyperaldosteronism over the long term — to reduce these patients’ excess cardiovascular risk,” he stated.

According to Amodeo, the treatment strategy depends on the disease subtype. In cases of unilateral aldosterone production, usually caused by a hormone-producing adenoma, laparoscopic adrenalectomy is considered the treatment of choice. In patients with bilateral adrenal hyperplasia, however, the approach is typically pharmacologic, based primarily on the use of mineralocorticoid receptor antagonists, such as spironolactone.

In medically managed cases, current treatment goals go beyond blood pressure control. According to the specialist, treatment should aim to normalize potassium levels, raise previously suppressed renin levels, and reduce the cardiovascular and renal impact associated with excess aldosterone. Persistently very low levels of renin during the follow-up may indicate insufficient control of the disease.

The distinction between the two scenarios is made through evaluation of the adrenal glands, usually with thin-slice CT scanning and, in selected cases, by adrenal vein catheterization, considered the gold standard for determining the lateralization of hormone production prior to surgery.

Early Diagnosis Changes the Prognosis

When initiated early, treatment can alter the natural history of the disease. According to Amodeo, both surgery and appropriately managed medical treatment can promote regression of left ventricular hypertrophy, reduce the risk for AF, and contribute to the stabilization of renal function.

Based on long-term follow-up studies, the specialist demonstrated that unilateral adrenalectomy is associated with lower cardiovascular mortality, a lower incidence of AF, reduced need for antihypertensive medications, and a higher likelihood of hypertension remission.

For Amodeo, these results reinforce the importance of early diagnosis. “We shouldn’t wait years of follow-up before treating patients,” he stated. According to him, patients identified in the early stages of the disease tend to have less established vascular damage and a greater likelihood of achieving lasting benefits from the intervention.

According to the specialist, after surgery, approximately 30%-60% of patients can achieve normal blood pressure without the need for medication. Even among those who continue to use antihypertensive medications, it is common to observe a reduction in the number of drugs and the doses required for blood pressure control.

HiperAldo Brasil

As part of efforts to reduce underdiagnosis of the disease, João Vicente da Silveira, MD, cardiologist, Heart Institute, Hospital das Clínicas, Faculty of Medicine, University of São Paulo, presented the HiperAldo Brasil project at the conference — a collaborative network focused on training professionals, standardizing clinical practices, and establishing a national registry for the disease. According to the specialist, the initiative aims to integrate referral centers and expand the collection of Brazilian data on primary hyperaldosteronism.

This story was translated from Medscape’s Portuguese edition.