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Tue 1 May 2007 12:00 AM

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Too much of a good thing?

An excess of water- and sodium-regulating aldosterone is often an overlooked cause of high blood pressure.

Although we often talk about high blood pressure as if it were a disease, it really isn't. It is a symptom of trouble somewhere in the body. High blood pressure usually accompanies excess weight, declining kidney function, and arteriosclerosis, the narrowing and stiffening of blood vessels. One often overlooked cause of high blood pressure is a malfunction of the adrenal glands.

The adrenals (once called the suprarenals) are triangular glands that perch atop each kidney. They churn out hormones that affect the stress response and the immune system. They also make aldosterone. This hormone helps manage the body's balance of water, sodium, and potassium. Too much aldosterone makes the kidneys hang on to sodium and water and flush potassium into the urine.

The extra fluid ends up in the bloodstream. This forces the heart to push harder to propel blood on its journey through thousands of miles of blood vessels, which raises blood pressure. Overproduction of aldosterone is known as aldosteronism.

Overactive adrenal glands were once thought to be a relatively rare cause of high blood pressure. That view is changing. A number of studies, including a large Italian study published in the fall of 2006 in the Journal of the American College of Cardiology, suggest that overproduction of aldosterone accounts for up to 5 in 100 cases of newly diagnosed high blood pressure. In people with resistant hypertension, aldosteronism contributes to 20 cases in 100. And there is growing evidence that excess aldosterone adds to heart disease in other ways as well.

Beyond blood pressure

Too much aldosterone may do more than boost blood pressure. Experiments in animals show that excess aldosterone triggers inflammation in blood vessels; turns down production of nitric oxide, a molecule needed to relax blood vessel walls; and dulls the activity of blood pressure "thermostats" known as baroreceptors. These receptors keep blood pressure steady by instantly changing the heart's output or the tension on blood vessels.

Studies in humans have shown that using the drug spironolactone (generic, Aldactone) to block aldosterone's activity improves survival in people with advanced heart failure.

Eplerenone (Inspra) does the same thing for heart attack survivors with damage to the left ventricle, the heart's main pumping chamber. Work under way is exploring whether aldosterone-blocking medications should play a larger role in controlling heart disease.

Looking for clues

The most common cause of excess aldosterone is a benign (noncancerous) growth in one adrenal gland. This is also known as Conn's syndrome. Some people have what's called idiopathic adrenal hyperplasia, an overactivity in both glands for which no particular cause can be found. In rare cases, a cancerous growth in the gland's outer layer causes overproduction of aldosterone.

Aldosteronism is usually silent. There's no pain or other outward manifestation. For most people, the first inkling of it arises when they are diagnosed with high blood pressure and low potassium during a routine checkup. Some people experience signs of low potassium such as headaches and muscle cramps; others notice unusual fatigue, excessive thirst, frequent urination, or numbness or tingling in an arm or leg.

Diagnosing aldosteronism is a several-step process. It usually starts with blood tests for aldosterone and for renin, a protein made by the kidneys. Above-normal aldosterone and below-normal renin raise a red flag.


Confirming the diagnosis is done by temporarily increasing the amount of sodium in the body, either with a high-sodium diet or an infusion of sodium-rich salt water. When the adrenal glands are working correctly, this should turn down aldosterone production. When they aren't, aldosterone levels remain high.

Once it's been established that your body is making too much aldosterone, it is important to find out if it is coming from one or both adrenal glands. An MRI or CT scan of the abdomen can spot an abnormal growth called an adenoma on an adrenal gland. Most adrenal adenomas are not cancerous.

The absence of a suspicious growth suggests bilateral adrenal hyperplasia. If necessary, this can be checked by something called adrenal vein sampling, a slightly tricky procedure in which blood samples are taken directly from the veins draining the right and left adrenal glands.

There's a point to all this testing: Knowing why the body is making too much aldosterone points to the best way to correct the problem.

When a scan turns up an adrenal adenoma, removing the affected adrenal gland can sometimes completely correct both high blood pressure and low potassium. The operation, called adrenalectomy, is almost always done with keyhole (laparoscopic) surgery to minimize recovery time. A person can live a perfectly healthy life with a single adrenal gland, just as one can live with a single kidney.

Overactivity in both glands is usually treated with medication. The drug of choice is typically spironolactone or eplerenone. Both of these medications block aldosterone's action in the kidneys and elsewhere.

All medications for high blood pressure - and these are no exception - work better when combined with a healthy lifestyle. A low-sodium diet is especially important.

Who needs testing?

Aldosteronism isn't the first thing doctors think about when evaluating a patient with hypertension. But it shouldn't be the last thing, either. If a patient has high blood pressure and their potassium level is low for no apparent reason, it's reasonable to have their adrenal activity checked. The same is true if they have trouble keeping blood pressure under control despite medication, a healthy diet and enough exercise. If a patient's aldosterone level is high, lowering it or blocking the effects of this hormone can lower blood pressure and may help protect their heart.

At a glance: Resistant hypertension

Primary aldosteronism contributes to resistant hypertension - high blood pressure that drugs and lifestyle changes haven't managed to control. Resistant hypertension is quite common; up to 40% of people with hypertension are unable to get their blood pressure below 140/90 mm Hg (or 130/80 mm Hg for those with diabetes or kidney disease).Sometimes what looks like resistant hypertension is really a person's failure to take his or her medications, follow a low-salt diet, or otherwise stick with a treatment plan. There are plenty of other causes as well. These include kidney disease, narrowing of the renal artery, aldosteronism, an overactive or underactive thyroid gland, chronic pain, and sleep apnea.Drugs and supplements can sometimes spur resistant hypertension. Possible offenders include nonsteroidal anti-inflammatory agents such as ibuprofen, naproxen, and Celebrex; pseudoephedrine and other drugs in many over-the-counter cough and cold medicines; appetite suppressants; and even herbal supplements such as ginseng and yohimbine.If a person is pretty good about taking their medications and controlling their blood pressure, and it is still out of whack, some detective work is in order. A check for aldosterone or other contributors to hypertension might pay off.

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