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Despite a 'bucketload' of drugs, his blood pressure was perilously high - The Washington Post

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Andrew J. Rosen wasn’t surprised when he was diagnosed with high blood pressure at 39. Both his parents had taken medication for years, which had effectively controlled the condition that affects nearly half of all American adults and frequently runs in families.

But Rosen, who lives in Carlsbad, Calif., was not so lucky. Even on the maximum recommended doses of five drugs, his blood pressure remained stubbornly elevated.

Rosen said he repeatedly asked his doctors whether an undiagnosed condition might be to blame. Each time, he received the same response: He had “essential hypertension” — high blood pressure with no underlying cause.

Sometimes, doctors told him, the condition, also known as primary hypertension, can be difficult to control. Poorly controlled high blood pressure increases the risk of heart disease, stroke, irreversible kidney damage and early death.

More than a decade would elapse before Rosen learned that he had been asking the right question but had been given the wrong answer. His persistently high blood pressure did have an underlying, treatable cause.

“He was on a bucketload of medication,” which was the first clue, noted William F. Young Jr., a Mayo Clinic expert Rosen consulted in 2019. Young said Rosen’s case is “extremely typical” of patients whose delayed diagnosis results in preventable harm.

For a variety of reasons, observed Young, a professor of medicine at Mayo, “physicians often seem to not think about what might be causing” resistant hypertension — high blood pressure that is not controlled by three or more drugs. It is an oversight he is attempting to remedy.

“To be honest,” Young added, “this is one of the simplest things to diagnose.”

White-coat hypertension?

Now 60, Rosen, senior vice president of development for a company that builds rehabilitation hospitals, suspects he developed high blood pressure in his late 20s, although there’s no way to know. He hated having his blood pressure measured, so readings were confined to periodic medical visits.

Those measurements routinely exceeded 140/90 mmHg, the cutoff that then signified hypertension. (It has since been lowered to 130/80.) Rosen said he talked his way out of that diagnosis by assuring doctors he had “white-coat syndrome,” also known as “white-coat hypertension” — readings that are high in a medical setting but otherwise normal. Because of his youth, doctors typically agreed.

In fact, Rosen didn’t know if that was true; he assiduously avoided taking his blood pressure at home. “It was anxiety-producing,” he said. “It was always high.” He hated feeling the cuff squeezing his arm and preferred to assume he did not have high blood pressure.

Not all doctors were persuaded. His allergist in Atlanta, where Rosen was then living, expressed skepticism about the white-coat explanation. “He said, ‘I don’t know. You’re too young for high blood pressure,’ ” Rosen recalled.

In 2001, after his internist diagnosed hypertension, Rosen began taking a beta blocker, a medication that blocks adrenaline. When his blood pressure didn’t budge, his internist added two other classes of drugs: a calcium channel blocker and an ACE inhibitor. When that trio proved ineffective, the doctor increased the doses.

In his mid-40s, Rosen was told he had high levels of cholesterol and Type 2 diabetes, a chronic condition in which the processing of sugar is impaired. Cholesterol-lowering and diabetes drugs controlled those problems.

In 2011, after Rosen moved to the San Diego area, his new primary care doctor changed his blood pressure medications. When that resulted in only a minimal reduction, the doctor added two more drugs.

Frieden says the United States has regressed in its control of hypertension over the last five to 10 years. “One of the ironies of health care is we tend to over treat symptomatic conditions, and under-treat asymptomatic conditions, and the paradigm of that is hypertension… What we’ve seen in the U.S. sadly is that we’ve gone backwards. We have a lower level of hypertension control than we did a decade ago, or five years ago.” (Video: Washington Post Live)

Searching for a zebra

But the elevated readings persisted. “It would be 148/90 when the nurse measured it on the machine several times,” Rosen said. At the end of a visit, Rosen’s doctor would do a quick manual reading and announce that it had dropped to 118/69.

Rosen, whose sister is a physician, was relieved. “I assumed he was a really good doctor," he said. "And I liked his answer.”

But over the next several years, he grew increasingly uneasy. Even though he took his medication faithfully, too many readings were too high to make him believe his blood pressure was under control.

In 2017, after both his parents had undergone cardiac bypass surgery for blocked coronary arteries, Rosen consulted a cardiologist.

The heart specialist ordered a stress echocardiogram, a test that measures how well the heart is functioning. It showed that Rosen’s heart appeared to be normal, but the cardiologist was alarmed by his blood pressure, which was sometimes as high as 179/85, and increased the amount of the one drug Rosen wasn’t taking at the maximum dose. He suggested that Rosen’s hypertension might be the result of a kidney problem, but a kidney scan found nothing.

At this point, Rosen told his family physician he wanted to start looking for a “zebra,” the term doctors use for a rare diagnosis. The doctor ordered tests for a pheochromocytoma, a rare, typically benign tumor that originates in one or both adrenal glands, which sit atop the kidneys.

After tests did not reveal a “pheo,” Rosen was referred to an endocrinologist, a physician who specializes in treating hormone-related diseases.

‘You don’t have it’

Rosen saw the first endocrinologist in November 2018. She suspected he might have the disorder most commonly associated with resistant hypertension — primary aldosteronism (PA), also known as Conn or Conn’s syndrome after University of Michigan endocrinologist Jerome W. Conn, who discovered it in 1954.

PA is caused by a surfeit of aldosterone, a hormone produced by the adrenal glands. Excess aldosterone can cause the kidneys to retain sodium and lose potassium, which raises blood pressure.

The disease can be detected by blood tests that measure the levels of aldosterone and renin, an enzyme made in the kidneys that helps control blood pressure, then calculating the ratio between the two. Further testing is required to confirm the diagnosis and to determine whether one or both adrenal glands are affected. In the latter case, PA is treated with medication. But in 30 percent of cases, PA is caused by a benign tumor on one gland. Surgically removing that gland can normalize blood pressure.

While awaiting the results of his blood tests, Rosen pored over the voluminous clinical guidelines for the diagnosis and treatment of PA issued in 2016 by the Endocrine Society, the international medical organization of endocrinologists.

He discovered that sleep apnea and low potassium levels, both of which he had, are associated with the disease. And he was heartened when his blood tests seemed to point to it.

“To me, this seemed like a really good thing, because it’s treatable,” Rosen said.

But the junior doctor who worked with his endocrinologist ruled out the possibility. “You don’t have it. Your aldo[sterone] is too low,” Rosen remembers being told. Rosen said he protested that his understanding of the 50-page Endocrine Society guidelines, along with his calculation of the blood test ratio, suggested otherwise.

The fellow disagreed. Rosen said he ended the call and immediately began searching for a new specialist.

Soon afterward, Rosen saw a second endocrinologist, who agreed that PA seemed likely. She ordered additional testing along with a CT scan, which provided confirmation. The final step was a technically tricky procedure known as adrenal venous sampling, which involves the insertion of a catheter into the adrenal veins to determine whether one or both are affected. That finding would guide treatment.

After consulting Young, the second endocrinologist advised Rosen to undergo the vein sampling procedure at Mayo. In April 2019, Rosen and his sister flew to Minnesota and met with Young, the clinic’s former chair of endocrinology and a past president of the Endocrine Society.

An interventional radiologist who specializes in the vein sampling procedure found that only one adrenal gland was involved, which meant that Rosen was a candidate for surgery. (“You need only half of one adrenal gland to be totally normal,” Young said.)

In June 2019, Rosen underwent laparoscopic surgery at UCLA Medical Center. Over the next year, he lost 35 pounds and his health improved dramatically. He now needs a low dose of only one blood pressure medicine to achieve readings of 124/80.

“I feel much better now than I did before,” he said. “And I’m much more active.”

But the delayed diagnosis exacted an irreversible toll. Years of uncontrolled high blood pressure caused Stage 3b kidney disease, for which Rosen takes medication and regularly sees a kidney specialist. If his disease worsens, Rosen has been told he may need a kidney transplant.

Alerting doctors

Young said he sees patients like Rosen far too often, a primary reason he has become an evangelist for PA screening.

Although doctors have long been taught that the disease is rare, Young said that recent studies show it is not. Researchers estimate that 5 to 10 percent of people with high blood pressure and 20 percent of those with resistant hypertension have PA. Most don’t know it because they have never been tested.

A 2020 Stanford study found that only 2.1 percent of patients with resistant hypertension were screened for PA; at the University of Minnesota, the figure was 4.2 percent. And a 2003 study from Australia found an unexpectedly large number of PA cases among a group of patients with high blood pressure.

“It’s vastly underdiagnosed and not just in the U.S.,” said Young, who advocates screening everyone with hypertension at least once. “From my perspective, it comes down to clinician awareness. Endocrinologists and nephrologists think of this. Primary care doctors, not so much.”

People with PA are more likely to develop heart and kidney disease and have a poor quality of life, Young noted in a 2018 article. Timely treatment can reduce those outcomes.

Rosen said he, too, has sought to educate his doctors. “I have tried to tell every doctor I go to that if you have a patient on three or more [blood pressure] meds and they’re not well-controlled, you need to test them” for PA, he said, echoing Endocrine Society guidelines.

After his surgery, Rosen said he “sent nice letters to all my old doctors saying, ‘You missed this.’ ” The only doctor he heard from was the first endocrinologist, who called to apologize, saying that the fellow had misinterpreted Rosen’s tests.

Rosen said he hopes his experience spares others. “Every day I wish I had done more research,” he said. “If I had done it 20 years ago, I wouldn’t have kidney damage.”

Submit your solved medical mystery to sandra.boodman@washpost.com. No unsolved cases, please. Read previous mysteries at wapo.st/medicalmysteries.

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