Doctors overlook a curable cause of high blood pressure

Patients aren't being screened for a curable hormonal abnormality that causes hypertension

By Mary Chris Jaklevic

Published February 26, 2022 7:29AM (EST)

Doctor taking patient's blood pressure (Getty Images/Siri Stafford)
Doctor taking patient's blood pressure (Getty Images/Siri Stafford)

This article originally appeared on Undark.

In early 2013, after Erin Consuegra gave birth to her second child at age 28, her health nosedived. She developed worrying symptoms, including extreme fatigue, fluttery heart beats, and high blood pressure. She said her doctor prescribed blood pressure medication and chalked it up to stress.

But Consuegra, an elementary school teacher by training, didn't buy it. "It's like, you think staying home all day with two kids is causing these real medical issues?" she said. "It was offensive to just write it all off to stress and anxiety."

Researching her symptoms online and through family members in the medical field, Consuegra learned of a little-known syndrome called primary aldosteronism, in which one or both adrenal glands, small structures that sit atop the kidneys, overproduce a hormone called aldosterone. Aldosterone increases blood pressure by sending sodium and water into the bloodstream, increasing blood volume. It also lowers potassium, a mineral that Consuegra was deficient in.

Her primary care physician agreed to run a blood test to screen for the condition but insisted that the result was normal and balked at Consuegra's request to see a specialist. "She took it as me questioning her," Consuegra said. Getting a referral, she added, "took a lot of fighting, a lot of tears, a lot of advocacy on my part."

Consuegra's story has a relatively happy ending. Doctors at Vanderbilt University Medical Center eventually diagnosed her with primary aldosteronism and found a small noncancerous tumor, or adenoma, in one of her adrenal glands — known to often be a cause of the condition. After doctors removed the gland in July 2014, her symptoms disappeared.

Millions of other patients are not so lucky. More than six decades after primary aldosteronism was first described in the medical literature, less than 1 percent of cases are diagnosed and treated despite evidence that it is a common cause of high blood pressure, or hypertension.

The syndrome shows up in people with mild, moderate, and severe hypertension — and even in those with normal blood pressure — according to a comprehensive 2020 study. "The prevalence of primary aldosteronism is high and largely unrecognized," the study authors wrote in the Annals of Internal Medicine, adding that it may account for high blood pressure that has no identifiable cause and is typically attributed to genetics, poor diet, lack of exercise, and obesity.

Closing the diagnosis and treatment gap poses a series of challenges, experts say. Many physicians haven't gotten the message that primary aldosteronism is common, so they don't look for it. Screening tests can be tricky to interpret and miss a lot of cases. Complicating matters, primary care groups, whose members treat the bulk of hypertension, have so far declined to help develop relevant guidelines. Research on the syndrome lags behind other diseases, and only a few health systems have a cadre of knowledgeable specialists who provide coordinated care.

Clinicians may dismiss telltale symptoms, leaving patients to turn to Google, bounce from doctor to doctor, or go undiagnosed for years. "Unfortunately, I think my story is super-typical," said Consuegra, whose frustrations led her to start a patient Facebook group. "I don't think anyone has had an easy road to diagnosis."

As a result, patients take standard blood pressure medications that do little or no good and miss out on effective treatments that include not only surgery but low-salt diets and targeted drugs. Missed diagnoses pose additional dangers: Excess aldosterone is toxic to the heart, blood vessels, kidneys, and other organs. Compared to patients with garden-variety hypertension, those with primary aldosteronism have greater risk of kidney disease, heart failure, coronary artery disease, and stroke.

With nearly half of U.S. adults, or 116 million people, classified as having high blood pressure, some experts have warned of a public health crisis hidden in plain sight — one that will demand widespread changes in hypertension treatment. They've called on clinicians to increase their vigilance and more readily prescribe drugs that block aldosterone's effects.

"My personal frustration is seeing patients who've clearly had primary aldosteronism for more than a decade and now have irreversible kidney damage," which may require dialysis, said endocrinologist William Young Jr. of the Mayo Clinic. Young treats about 250 primary aldosteronism patients a year but "compared to what's going on out there," he said, "that's miniscule."

The push for greater recognition of primary aldosteronism isn't new. Since 2008, the Endocrine Society, a medical organization dedicated to the advancement of hormone science and public health, has recommended screening patients who have red flags such as low potassium, an adrenal mass that shows up on a scan, or drug-resistant hypertension — defined as blood pressure that is uncontrolled despite the patient taking three different kinds of antihypertensive medications at their maximally tolerated doses. A family history of early-onset hypertension or stroke before age 40 are other signs. In 2017, the American College of Cardiology and the American Heart Association incorporated the directive into a hypertension treatment guideline.

Screening usually entails a roughly $150 blood test called the aldosterone-to-renin ratio, or ARR. Renin is an enzyme produced by the kidneys that triggers a chain reaction that leads to aldosterone production. When renin is low, aldosterone should be low. But in people with primary aldosteronism, aldosterone can be elevated even when renin is low.

A positive ARR can be followed by additional tests to confirm the diagnosis and determine whether surgery is an option. If one gland is secreting excess aldosterone, removing that gland may cure or improve the disease. Usually both glands are affected, in which case surgery isn't recommended and patients take one of two drugs that block aldosterone.

But physicians haven't followed the guidelines. Recent U.S. studies found ARR screening rates for high-risk patients ranging from 1.3 percent in an urban health system to 3.3 percent at an academic medical center. The largest analysis, which was published in 2021 and involved 269,010 patients with drug-resistant hypertension treated in the U.S. Veterans Health Administration, revealed that just 1.6 percent were tested.

The data show primary aldosteronism is "not top of mind for gatekeepers of hypertension," said Vivek Bhalla, a kidney specialist who directs the Stanford Hypertension Center. Bhalla said he was astounded when a 2020 analysis he led revealed that just 2.1 percent of patients with drug-resistant hypertension were screened.

Yet even those tiny percentages may downplay the problem because they don't account for people without recognizable risk factors, who may nonetheless be on a path to developing severe disease. Some experts suggest studying the cost-effectiveness of expanding the population of patients who should be screened, a point underscored by the 2020 Annals study, which estimated that the syndrome affects one in six people with mild hypertension and one in five with moderate hypertension.

More troubling, the study showed that ARR fails to detect a large fraction of cases, yielding a positive result in people who have the condition as little as 22 percent of the time. False positive results, on the other hand, are uncommon. The authors wrote that ARR "can be a simple and useful screening method" but cautioned against overreliance, noting that arbitrarily high cutoff values and aldosterone's tendency to fluctuate likely contribute to underdiagnosis.

Those revelations "really changed the whole landscape," said Sandra Taler, a Mayo Clinic kidney and hypertension specialist who was not involved in the research. She added that she's become "more meticulous" in looking for primary aldosteronism as a result. "The point of this study is there may not be any clues and it could still be present," she said. "And if you don't look for it you won't find it."

Experts have put forth various explanations for the lack of screening, including the complexity of the process and concerns over expensive follow-up procedures. Given the sheer volume of hypertension patients, physicians typically don't focus on finding root causes. "The temptation for a physician seeing a new patient with hypertension is to say — 'Let's just start off with getting your blood pressure down, and then take it from there,'" Australian medical researcher John Funder, who led the Endocrine Society's most recent guideline effort, wrote in a 2020 editorial in Hypertension.

There are also historic misperceptions that primary aldosteronism is rare and characterized by symptoms such as potassium deficiency. University of Michigan physician Jerome Conn is credited with first describing the syndrome in medical literature in 1956 based on a woman with extreme symptoms that included temporary and occasional paralysis from the hips down. Although Conn and others postulated that rogue aldosterone production is a common cause of hypertension, it took until the 1980s for diagnostic advances to confirm their hunch.

In his editorial, Funder cited "residual ignorance" from the days when medical schools taught that primary aldosteronism was a mild and rare form of hypertension affecting less than 1 percent of patients. Others cite ongoing gaps in educating physicians who think it is too complicated or don't know they should be testing people for primary aldosteronism. Specialty societies have not paired screening recommendations with aggressive efforts to educate physicians about the disorder's prevalence, acknowledged Robert Carey, a professor of medicine at the University of Virginia School of Medicine and Endocrine Society past president, who helped develop the guidelines.

At some institutions, that's changing. Varun Sharma, an associate professor of general internal medicine at Georgetown University, said he wasn't taught how or when to diagnose primary aldosteronism during his medical training. A few years ago he began testing some patients with hypertension and was surprised by frequent positive results. "That was what made me push and also made me feel comfortable telling residents that we ought to be screening more," he said.

Similarly, Bradley Changstrom, an assistant professor of medicine at the University of Colorado School of Medicine, doesn't recall learning about primary aldosteronism as a common cause of hypertension when he was a resident. But he said, "Once I started looking for it I started finding it all the time, practically speaking once a month or so."

"I think if physicians realize how common this truly is," he added, "they would start to look for it more often."

To increase detection, experts have suggested removing a requirement that patients take a hiatus from blood pressure medications prior to screening, liberalizing cutoffs for a positive ARR result, and bypassing ARR for urine excretion tests, which are more reliable but cost more. Some have suggested wider prescribing of drugs to treat primary aldosteronism, even as a first-line hypertension therapy.

Carey said it will be critical to involve primary care societies — including the American Academy of Family Physicians and the American College of Physicians — in developing the next guideline, which he said will take at least two years. He said their endorsement would provide "the strongest message regarding the validity of the recommendations" but such collaboration can be challenging because societies "want to keep their guidelines under their control."

Primary care groups declined to participate in a multi-society task force that developed the 2017 ACC/AHA hypertension guideline, which famously expanded the definition of hypertension to include about 30 million more U.S. adults as well as endorsing primary aldosteronism screening.

The ACP and the AAFP declined interview requests from Undark. In an email, the AAFP said it updates its members on research and "would welcome the Endocrine Society to reach out to us directly to discuss guideline opportunities."

Greater focus on excess aldosterone could advance national progress on blood pressure control, which has stalled, according to the 2020 U.S. Surgeon General's Call to Action to Control Hypertension. Although that 48-page document, like much public health messaging, doesn't mention primary aldosteronism or aldosterone, it notes that only about one in four U.S. adults with hypertension has it under control. Hypertension is a leading risk factor for heart disease and contributes to half a million U.S. deaths annually. Primary aldosteronism, Taler said, "opens up a whole area of research in terms of looking for the cause of high blood pressure."

More detection won't be a silver bullet. No health care system is prepared for a glut of newly diagnosed primary aldosteronism patients, says Carey. Only a handful of U.S. medical centers have a cadre of relevant experts — particularly scarce are radiologists adept a procedure to determine whether surgery is feasible. Care is also often uncoordinated. Bhalla said he created Stanford's hypertension center in 2015 because "it was clear that there was no expert that had taken these people under their wing," referring to patients with primary aldosteronism, but his institution isn't unique. "We practice in these silos in medicine," he said. "And that is not healthy for patient care."

Sweeping improvements are needed in diagnosis and treatment, said Marianne Leenaerts, co-founder of the Primary Aldosteronism Foundation, a patient group launched in 2019. The only drug approved by the U.S. Food and Drug Administration to treat primary aldosteronism, spironolactone, was developed in the late 1950s. It usually lowers blood pressure but has nasty side effects that include erectile dysfunction and painful breast growth in men, and irregular menstrual cycles in women. Another drug of the same class, eplerenone, is prescribed off-label. The Endocrine Society's guideline notes that eplerenone has fewer side effects but is less potent than spironolactone and must be taken more often.

Two new classes of drugs are in testing. Clinical trials are underway for new scanning techniques and procedures that could spare the adrenal gland.

Yet for millions of patients, advances are slow in coming.

Leenaerts, who lives in Canada, believes she had primary aldosteronism for 25 years before it was diagnosed in 2017. Both of her adrenal glands produce excess aldosterone, which means she is not a candidate for surgery, and she does not tolerate either available drug. Instead, she tries to manage her disease with a standard blood pressure-lowering drug and a strict low-sodium, high-potassium diet. At age 58, her liver and kidney functions are declining, and she has insomnia, difficulties with memory and focus, and painful inflammation. Primary aldosteronism has cut short her productive years, she said. While new drugs might help, she added, "At the speed at which I'm declining, it may be too late for me."


Mary Chris Jaklevic

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