Dealing with Secondary High Blood Pressure

In this article number 4 about high blood pressure:

  • Discovering secondary high blood pressure early on
  • Dealing with renal vascular high blood pressure
  • Finding a tumor that induces secondary high blood pressure
  • Coping with causes that you’re born with and more

Secondary high blood pressure means that a specific disease causes the high blood pressure — the high blood pressure is one of several signs and symptoms associated with the disease. If the person is cured of the disease that’s causing the secondary high blood pressure, then the high blood pressure is lowered. Treatment of the disease often eliminates the high blood pressure.

Although secondary high blood pressure makes up only 5 percent of the total number of high-blood-pressure cases, its causes are important. A careful history, physical exam, and lab evaluation (as we discuss in article 2) can help a physician discover the disease that’s causing your blood pressure to rise. This article introduces you to some of the most common causes of secondary high blood pressure, the way the diagnosis is confirmed in each case, and the appropriate treatment.

As you read the disease descriptions, you may imagine that you indeed have one of them. But chances are, you’re more likely to win the lottery or be hit by a bolt of lightning than contract any one of these rare diseases. Of course, if you do get one, you’ll be the only one on your block. (We recommend that you express your uniqueness some other way!)

The upside of secondary high blood pressure is that after you’re treated for the primary disease, you’re like new — most of the time. The high blood pressure and other signs and symptoms of the disease disappear. Your whole life improves — even your piano playing (if you then take lessons).

So before you let your imagination run wild about having one of these diseases, ask your doctor. If your doctor’s opinion doesn’t satisfy you, then get a second opinion from another physician. Treating the disease or disorder that’s causing the secondary high blood pressure can lower your blood pressure, but lifestyle changes can also lower secondary high blood pressure independent of the disease or disorder. This means that weight loss (see article 9), exercise (see article 12), stopping smoking (see article 11), and reducing salt in your diet (see article 10) can all make a big difference.

Finding Secondary High Blood Pressure Early

Several clues that should prompt an investigation for secondary high blood pressure include the following:

  • Damage to the eyes, kidneys, or heart
  • Family history of kidney disease
  • Flushing spells (when your skin turns red and hot)
  • Increased body pigmentation and pigmented stretch marks
  • Intolerance to heat
  • Loud humming sound in the abdomen (called a bruit)
  • Low potassium level in the blood
  • Poor response to usually effective treatment for high blood pressure
  • Rapid pulse
  • The onset of high blood pressure before age 20 or past age 50
  • Unusually high blood pressure (above 180/120 mm Hg)

If you have any condition in the preceding list, point it out to your doctor. By finding and treating secondary high blood pressure early, you’re more certain to return to normal before permanent changes occur. Some changes such as kidney damage can affect your high blood pressure permanently even when the primary disease or disorder is eliminated.

Evaluating the Role of Your Kidneys in Secondary High Blood Pressure

When high blood pressure is present, the kidneys always get involved. If the high blood pressure precedes the kidney damage, the high blood pressure is primary or essential. But when damage to the kidneys occurs first, then the high blood pressure is secondary. Two main conditions of the kidney — damaged kidney tissue and blocked kidney arteries — can lead to high blood pressure.

Certain drugs (particularly phenacetin, acetaminophen (paracetamol), and the nonsteroidal anti-inflammatory agents) can cause impaired kidney function. They’re associated with wasting salt instead of retaining it though, so high blood pressure isn’t usually the problem. And despite the loss of an entire kidney, a person who donates a kidney doesn’t necessarily develop high blood pressure.

Discovering damaged kidney tissue

Damaged kidney tissue is the most common reason for secondary high blood pressure, accounting for about 50 percent of the cases. Renal (kidney) parenchymal (tissue) hypertension (high blood pressure) results from:

  • A kidney-damaging illness such as diabetes
  • Use of certain medications (see above)
  • An inflammation of the kidney
  • An injury to the kidney
  • A hereditary disease that results in cysts (sacs filled with fluid)

The damaged kidneys don’t function normally and can’t eliminate sodium at a normal rate, resulting in salt and water retention that leads to high blood pressure.

Diagnosing chronic and acute kidney tissue damage

Loss of kidney tissue that leads to high blood pressure can be chronic (slow to develop) or acute (sudden). Some of the diseases and conditions that cause chronic kidney damage are:

  • Chronic obstruction of the ureter (the tube that takes urine from the kidney to the bladder)
  • Cysts that displace normal kidney tissue
  • Damage to the glomerulus (the filtering part of the kidney)
  • Diabetes mellitus (diabetic kidney disease; see below: “The details of diabetic kidney disease” for more information)

The resulting secondary high blood pressure must be controlled because it can damage the kidneys further and lead to even higher blood pressure. It’s a vicious cycle.

High blood pressure also accompanies acute kidney diseases (kidney diseases that occur in days, not weeks or months). Acute kidney disease isn’t cute in any way; it’s a sudden development of a lesion in the kidneys, and the person who develops it is usually pretty sick. Fortunately, it may go away just as rapidly as it develops. Two acute medical problems that can damage the kidneys are the following:

  • Acute glomerulonephritis is seen in children and adults who suddenly pass dark urine and have swelling of the face. Its name comes from the inflammation that affects the kidney’s glomeruli, the structures that filter the blood. The disease can occur after a sore throat caused by a bacteria called streptococcus. The blood pressure rises during the time the patient is ill and is treated with salt restriction and drugs if necessary.
  • Ureteral obstruction occurs when a compression from a tumor or other tissue closes the tubes that carry urine to the bladder. For example, a tumor of the prostate gland can cause the compression. The blockage may be on one kidney or both. Relieving the obstruction usually relieves the high blood pressure.

These two sources of acute secondary high blood pressure are quite rare, representing less than 10 percent of cases involving the kidneys.

Other conditions that lead to acute kidney damage include blockage in the arteries to both kidneys, trauma to the kidneys, or certain X-ray or surgical procedures. For example, certain chemicals used to observe the kidneys during an X-ray may suddenly damage the kidneys, especially in people with diabetes. Surgery that accidentally damages the arteries to the kidneys also leads to a sudden rise in blood pressure. Note: Most acute kidney diseases resolve over time if the person receives the necessary medical support during the acute illness.

Testing for and treating damaged kidney tissue

Blood urea nitrogen (BUN) and creatinine are blood tests that can detect damage to the kidney by measuring products that are normally excreted in the urine. (When the kidneys are damaged, these waste products back up in the blood.) Unfortunately, these tests don’t register abnormality until the latter stages of the disease, when more than half the kidney tissue is damaged.

Fortunately, a microalbuminuria test, which checks for albumin (a protein) seeping out of the kidney and into the urine, can signal kidney disease at an early stage — when protection of the kidneys and reversal of the disease are still possible. Checking the amount of protein in the urine can also be a useful test for the worsening of kidney disease because protein levels increase as kidneys lose more tissue.

A kidney ultrasound (sonogram) is also useful for detecting kidney damage. The ultrasound (sonogram) bounces sound off the kidney to evaluate its shape and size and to detect any kidney tissue loss.

If the various studies don’t make the diagnosis, a kidney biopsy — the removal of tissue for diagnostic examination — can often give a definitive diagnosis.

When the disease has damaged the kidneys so severely that they can no longer perform their filtering function, the kidneys are in end-stage renal disease (also known as kidney failure). At this point, two treatment options exist (see article 6 for more information on both options):

  • Dialysis (mechanically cleaning the blood of poisons): During dialysis, high blood pressure is present and must be controlled. Reducing the amount of fluid in the body usually accomplishes this.
  • Kidney transplant: High blood pressure can be a complication. Transplants are less of a problem when the healthy kidney comes from a person who doesn’t have high blood pressure.

The details of diabetic kidney disease 

Diabetes mellitus, a particularly damaging disease that may affect the kidneys, is the most common cause of kidney damage and kidney failure. The disease usually takes 15 or more years of poorly controlled diabetes to affect the kidneys. Most people that have diabetes mellitus also have high blood pressure and diabetic retinopathy, the characteristic eye disease in diabetes. Certain drugs called ACE inhibitors (see article 13) are particularly helpful in slowing the progression of diabetic kidney disease and may even reverse it. In diabetic kidney disease, the most important treatments consist of controlling blood glucose (sugar), blood pressure, and blood cholesterol. Diabetics should restrict their salt intake as well as their protein, which seems to make the kidney disease worse.

Read more: Diabetes and kidney disease

Handling blocked or narrowed kidney arteries (renal artery stenosis)

Diseases that cause renal (kidney) vascular (blood vessel) hypertension (high blood pressure) block one or both kidney arteries. When the obstruction keeps a kidney from receiving enough blood flow, the kidney secretes renin, an enzyme that ultimately brings on high blood pressure. Because the original obstruction keeps the increased blood pressure from delivering more blood to the kidney, the high blood pressure continues.

The renin acts on angiotensin I (a hormone) to produce angiotensin II, a hormone that causes the contraction of blood vessels. Angiotensin II also stimulates the production of aldosterone, a hormone that causes salt and water retention. I discuss aldosterone in more detail later in this chapter.

Diagnosing narrowed or blocked kidney arteries

Many diseases can cause obstruction or narrowing of one or both of the kidney arteries. These diseases occur in about 6 out of 100,000 people and include:

  • Atherosclerosis: In this process, cholesterol is laid down in the arteries, eventually causing the arteries to narrow. This condition usually occurs in men over the age of 45 and it accounts for two-thirds of all blocked kidney arteries cases.
  • Fibromuscular disease: The kidney artery and the body’s arteries in general become thickened and narrowed, especially in young women under the age of 45 and in children who have the disease.
  • Aneurysms: The kidney artery or the heart’s aorta (the artery leading to the kidney’s artery) can have a defect and balloon out, causing blockage. As a result, the normal passage for blood narrows and blood enters the wall of the artery. The great danger of aneurysms is bursting, which may lead to death through loss of blood.
  • Emboli-clots: These blood clots block the artery.

A bruit, a humming sound in the abdomen, can signal these common causes of kidney artery obstruction. However, it can be heard in only 50 percent of the cases where a doctor listens with a stethoscope over the patient’s abdomen.

Because the kidneys produce increased amounts of aldosterone when the kidney arteries are blocked, the potassium level decreases. So another warning sign is a low potassium level in the blood. This diagnosis is most often associated with high blood pressure (higher than 120 diastolic) that doesn’t respond to treatment.

When a doctor suspects an artery-blocking disease, he can order a study of the arteries to the kidneys. As dye is injected into the kidney arteries, an X-ray displays the size of the arterial passage. This study can help with a diagnosis, but opening up the obstructed artery may not cure the high blood pressure if the disease has been going on for some time.

Treating blocked kidney arteries

About 10 years ago, enthusiasm for treating blocked kidney arteries with angioplasty (kidney artery expansion) was very high. During angioplasty, the surgeon inserts a catheter (a slender, hollow tube) into the artery and widens the artery with a balloon. Then he places a device called a stent in the artery to keep it open permanently.

None of the studies that showed such promise for angioplasty and stenting had random controls (to compare the outcome of a patient who received the angioplasty to a patient who received medical treatment). However, such a study - the ASTRAL study - published in 2009 found substantial risks but no evidence of a worthwhile clinical benefit from revascularization in patients with atherosclerotic renovascular disease. Some of the issues that may make angioplasty less certain as the treatment of choice are:

  • Medical therapy with drugs is highly effective for many years in more than half the patients.
  • Angioplasty fails to lower blood pressure in up to 40 percent of patients.
  • Kidney function gets worse in at least 20 percent of patients treated with angioplasty.
  • The disease recurs in up to 20 percent of patients who are initially successful, although the stent seems to increase the rate of success.

As a result of these findings, angioplasty is now delayed in many patients in favor of drugs, at least until kidney function begins to fall.

Because renin causes the increased blood pressure, an angiotensin-converting enzyme (ACE) inhibitor (a drug that blocks its effect; see above: “The details of diabetic kidney disease”) can reverse the high blood pressure, but it may also reduce blood supply to the obstructed kidney. Patients who can’t tolerate an ACE inhibitor because of the side effect of coughing do well with an angiotensin II receptor blocker, which does not produce a cough (see article 13 for more about drug therapy).

Discovering Hormone-Secreting Tumors That Elevate Blood Pressure

Organs that normally make hormones (chemical messengers that trigger reactions) can develop tumors that also produce hormones. But the tumor’s hormones elevate blood pressure to an abnormal extent. These tumors usually originate in an adrenal gland (one adrenal gland sits on top of each of your kidneys;) but can also arise in nerve tissues. The adrenal glands secrete the following hormones:

  • Epinephrine (adrenaline): Maintains blood pressure and blood glucose
  • Aldosterone: Controls salt and water levels in the bloodstream
  • Cortisol: Maintains blood glucose (sugar) and also plays a role in maintaining blood pressure

Your adrenal glands are on top of your kidney.

Finding an epinephrine-producing tumor

Epinephrine (adrenaline) and norepinephrine (noradrenaline), normal products of the adrenal gland, raise blood pressure, heart rate, and blood glucose during stressful times and causes sweating. Sometimes a pheochromocytoma (a tumor that releases large quantities of norepinephrine) can arise in an adrenal gland or along many nerves.

Diagnosing a pheochromocytoma

A pheochromocytoma is rare, arising in only 6 out of 100,000 people who have high blood pressure. However, the sudden release of a large amount of norepinephrine may be fatal.

A proper diagnosis is crucial because a pheochromocytoma can cause death if the patient experiences severe stress or trauma before the disease is discovered.

The most common, key symptoms of a pheochromocytoma are:

  • Headache
  • Palpitations (the feeling that the heart is beating rapidly
  • Excessive sweating

Note: If high blood pressure is present but the patient feels none of these symptoms, the diagnosis of a pheochromocytoma is extremely unlikely. High blood pressure is sustained in over half the patients with this condition, but it may be intermittent.

Exercise, urination, defecation, an enema, smoking, examination of the abdomen, and anesthesia can bring on these attacks of headache, palpitations, and sweating, which can vary from severe to mild. The usual frequency is once a week, and the duration is less than one hour, but timing can be different for each patient.

Certain cheeses (especially aged cheddar and aged Stilton), beer, and wine that contain a chemical called tyramine may bring on a headache, palpitations, and sweating. Drugs like histamine, glucagon, and phenothiazines can also precipitate these symptoms. A pheochromocytoma is suspected much more often than it actually occurs simply because its symptoms are the same as those of a healthy person who is nervous and upset.

The following steps explain how your doctor proceeds when she suspects a norepinephrine-producing tumor:

  1. A blood test for metanephrine (metadrenaline), a breakdown product of epinephrine (adrenaline), screens for a pheochromocytoma. Breakdown products result when epinephrine is converted to an inactive form in the body.
  2. If your metanephrine level is elevated, the doctor asks you to collect urine for 24 hours. This test checks for the presence of metanephrine and catecholamines (other breakdown products of epinephrine).
  3. If elevated levels of metanephrine and catecholamines are found, a tumor can be located with a computed tomography (CT) or magnetic resonance imaging (MRI) scan (highly sensitive X-rays). Most of these tumors are located in the adrenal gland, but 15 percent of them arise in another location such as the nerve tissue, the abdomen, or the chest cavity. (If the tumor is in one of these locations and is large enough, more than 2 centimeters, the scan can see it there as well). Nevertheless, the surgeon may have to find it during surgery, and usually the surgeon looks for more than the one tumor. About 10 percent of these tumors are malignant.
  4. If a CT or MRI scan doesn’t identify a tumor, then you’re injected with a radioactive substance, metaiodobenzylguanidine (MIBG). (Try saying all that in one breath!) Because pheochromocytomas absorb MIBG, a radiation counter passed over the body can detect the excessive radiation in a particular area to locate the tumor.

Forms of pheochromocytoma run in families as solitary pheochromocytoma or along with other tumors. When several different types of tumors are pre- sent, the condition is multiple endocrine neoplasia and involves other glands. The doctor should look for tumors specifically of the thyroid and parathyroid glands whenever a pheochromocytoma is discovered.

Treating a pheochromocytoma

Surgery removes most pheochromocytomas, but first the patient’s blood pressure has to be under control. The doctor may prescribe dibenzyline to block the action of epinephrine (adrenaline) and control the high blood pressure. A week of dibenzyline or doxazosin, a similar drug, is sufficient, but a patient with severely high blood pressure may need injections of phentolamine in the vein every five minutes until the blood pressure is controlled so surgery can proceed.

If the blood pressure isn’t controlled before this surgery, the death rate can be as high as 50 percent. However, the likelihood of the blood pressure not being controlled first is extremely rare.

The surgery is laparoscopic (minimally invasive removal of the tumor through a small incision in the abdomen). A tube is inserted, and the tumor is localized and removed. This surgery can be done on an out- patient basis, and two weeks later the patient can return to normal activity. By comparison, the old technique of conventional surgery required five to seven days in the hospital and a four-week recovery period.

Like with other secondary causes of high blood pressure, the high blood pressure may persist after surgery if permanent changes have occurred. The patient then needs blood pressure pills (see article 13 for more about drug therapy).

Detecting a tumor that produces aldosterone

The adrenal cortex (the outer covering of the adrenal gland;) secretes aldosterone, an important hormone that’s responsible for retaining salt and eliminating potassium from the body. Primary hyperaldosteronism (a malfunction usually due to an aldosterone-producing tumor in one of the adrenal glands) may produce an overabundance of aldosterone — more than the human body can safely handle. The large amount of aldosterone causes significant sodium retention, potassium loss, and high blood pressure.

Similar to the prevalence of pheochromocytoma (see the “Diagnosing a pheochromocytoma” section earlier in this chapter), the incidence of aldosterone-producing tumors is 2 out of 100,000 people who have high blood pressure. However, some high blood pressure specialists believe that the prevalence of primary hyperaldosteronism is much greater than generally accepted and suggest that:

  • As many as one in ten people with high blood pressure have primary hyperaldosteronism (although not necessarily due to a tumor).
  • Primary hyperaldosteronism should be considered in every case of high blood pressure, even when the potassium is normal.
  • Blood tests should determine the ratio of aldosterone and renin levels in the bloodstream.

Whether this high prevalence of primary hyperaldosteronism proves to be a fact isn’t clear at this time.

Diagnosing an aldosterone-producing tumor

Aldosterone-producing tumors are usually found in people between the ages of 30 and 50, and they affect women more often than men. People with an aldosterone-producing tumor have the following symptoms:

  • High blood pressure (may be as high as 200/120 mm Hg)
  • Increased potassium in the urine
  • Increased sodium in the blood
  • Increased urination (especially after lying down)
  • Low potassium in the blood, leading to muscle weakness

Because the blood pressure can be so high, people who suffer from an aldosterone-producing tumor may experience a stroke (brain attack), damage to the kidneys, or an enlarged heart before the disease is treated (see Part II for more about these consequences of high blood pressure). The low potassium level in the bloodstream can lead to muscle weakness, a reduced secretion of insulin, and diabetes.

Another sign of an aldosterone-producing tumor is a low level of renin versus a significant amount of aldosterone in the bloodstream. Most of the time, elevated aldosterone is secondary to increased renin. But with primary hyperaldosteronism, the renin level is low — a sign that an aldosterone-producing tumor (and not renin) is instigating the aldosterone.

A kidney with insufficient blood pressure produces renin. As we noted in the earlier “Handling blocked kidney arteries” section, the renin causes production of angiotensin II (a strong blood-vessel constriction agent that also triggers the release of aldosterone) from angiotensin I. The elevated blood pressure and increased blood volume result in suppression of renin production. Normally, when a person stands up, renin is released to help increase blood pressure, but because of this tumor, renin doesn’t increase with standing.

The following steps explain how a doctor proceeds when he suspects an aldosterone-producing tumor:

  1. High blood pressure is present and a blood test indicates low potassium. Sometimes a doctor prescribes a diuretic (a drug that promotes the formation of urine by the kidney; see article 13) to lower the blood pressure before he considers and tests for an aldosterone-producing tumor. But, because diuretics also push potassium into the urine (reducing the potassium in the bloodstream), they compromise an accurate reading of potassium loss. In this case, the effect of the diuretic must be removed before the blood is tested.
  2. If you have a low blood potassium and an overabundance of potassium in the urine, the doctor orders a blood test for renin. Renin should be especially high if salt and water are withheld.
  3. If the amount of renin in your blood is, in fact, reduced, then your doctor may use that information to screen for an aldosterone-producing tumor by radiologic studies. The aldosterone level should be measured in the early morning because aldosterone tends to fall at night, even from a tumor. If the aldosterone level is high, the diagnosis is either an aldosterone-secreting tumor or bilateral adrenal hyperplasia — increased aldosterone production in both adrenals as a result of having many nodules. This distinction is important because bilateral adrenal hyperplasia tends to be a milder disease than a tumor, and it doesn’t respond well to surgery.
  4. A CT or MRI scan can usually distinguish a solitary adrenal tumor from bilateral hyperplasia. Occasionally, this scan doesn’t make the distinction because aldosterone-producing tumors tend to be small and the incidence of incidentalomas (innocent growths) on the adrenal gland is high.
  5. If the scan can’t distinguish between a tumor and bilateral hyperplasia, the radiologist puts a tube into the adrenal veins on each side of the body and looks for large amounts of aldosterone in the sample. If one side has much aldosterone and the other side doesn’t, the diagnosis is an aldosterone-producing tumor, not bilateral hyperplasia.
Lapping up licorice can lower your renin

Believe it or not — eating lots of licorice can raise your blood pressure and lower the amount of renin in your bloodstream. An abundance of licorice can block the enzyme that normally converts cortisol (which maintains blood glucose and helps maintain blood pressure) to cortisone (an anti-inflammatory hormone) in the kidney. Because cortisol has some activity similar to aldosterone in test results and cortisone doesn’t, the unusually high concentrations of cortisol clinically imitate aldosterone excess. However, a more accurate picture can be drawn from a patient’s history of licorice eating and his low aldosterone test results. Don’t worry though; the excess usually requires four weeks of eating large quantities (50 to 100 grams) of licorice.

Treating an aldosterone-producing tumor

The treatment of a solitary adrenal tumor that makes too much aldosterone is laparoscopic surgery to remove the tumor. Before surgery, the doctor prescribes spironolactone, a drug that reverses the action of aldosterone, for several days to make the patient chemically normal.

After surgery, the aldosterone level falls, the potassium returns to normal, and the blood pressure returns to normal. Sometimes the blood pressure stays up because the patient also has essential high blood pressure (high blood pressure for which the cause can’t be determined) or because permanent damage has taken place in the blood vessels or the kidneys. This problem occurs most often with individuals who’ve had high blood pressure for five years or longer.

Usually, doctors don’t recommend medical treatment (spironolactone) to reverse the action of aldosterone — particularly in men — because the treatment has significant side effects including breast enlargement, reduced interest in sex, and reduced ability to have an erection. Many patients with a single tumor, however, can’t undergo surgery for some reason or refuse surgery. In this situation, medical treatment has been successful for five years or more.

Note: If the diagnosis is bilateral adrenal hyperplasia (see Steps 4 and 5 in the previous list), the doctor treats it medically with spironolactone. (Removal of the adrenal glands doesn’t generally cure the high blood pressure even though the low potassium improves.)

A new drug, eplerenone, is now the drug of choice for bilateral adrenal hyperplasia and adrenal adenomas (a tumor in one adrenal gland) because it reverses the low potassium and the high blood pressure without causing the sexual side effects of spironolactone.

Managing Cushing’s syndrome

As if the previous two tumors weren’t enough trouble from the adrenal gland, the adrenal gland can be the site of still another secondary high blood pressure source, Cushing’s syndrome, where the adrenal glands make too much cortisol (their main hormone). This syndrome can originate in three different ways:

  1. In about 80 percent of the cases, an excessive production of adrenocorti- cotrophin (ACTH, the pituitary hormone that regulates the adrenal gland) caused by a tumor in the pituitary, stimulates both adrenals to make too much cortisol. If a tumor forms in the pituitary gland, it can cause the adrenals to make too much cortisol and other steroids that have plenty of salt-retaining activity. As a result, the blood pressure rises.
  2. In the remaining 20 percent of cases, a tumor grows within one adrenal gland. When the adrenal tumor makes too much cortisol independently of ACTH, the ACTH is suppressed instead of elevated.
  3. Rarely (less than 2 percent), an adrenal-stimulating hormone from some other tumor in the body (particularly a lung cancer) stimulates the adrenals. This condition is ectopic (from an abnormal site) ACTH production. The result is Cushing’s syndrome, but it tends to be more aggressive, producing low potassium levels. The ectopic source often has some identifying symptom such as cough from a lung cancer.
Diagnosing Cushing’s syndrome

Cushing’s syndrome is associated with high blood pressure that’s difficult to treat. The pressure may be up to 200/120 mm Hg. The syndrome occurs three times more often in women than in men and usually in a person’s third or fourth decade. The death rate from untreated Cushing’s syndrome is high, approximately 13 percent.

Too much cortisol in the bloodstream has other properties that may result in:

  • Diabetes mellitus
  • Easy bruising of the body
  • Loss of bone, which causes spontaneous fractures
  • Obesity of the trunk of the body, thin arms and legs
  • Psychological changes ranging from irritability to severe depression
  • Purplish stretch marks, especially on the abdomen

In addition to high blood pressure, the high ACTH and the pituitary tumor that it represents can cause still other signs and symptoms such as:

  • Headache caused by the pituitary tumor
  • Pigmentation of the body, particularly any stretch marks caused by the ACTH
  • Loss of menstrual function in women due to the adrenals producing excessive amounts of hormones that have masculinizing properties
  • Hairiness in women due to the same masculinizing hormones

Given all these signs and symptoms, Cushing’s syndrome is often considered and relatively easy to prove with chemical tests. The following steps explain how your doctor proceeds when he suspects this condition:

The patient takes 1 milligram of dexamethasone (a steroid hormone much like cortisol) at midnight.

The next morning, the patient has a blood test. If Cushing’s syndrome is not present, that 1 milligram is enough to shut down ACTH, thereby lowering the cortisol in the bloodstream when tested the following morning. However, when a pituitary tumor makes ACTH, or an independent tumor of the adrenal gland makes cortisol, the dexamethasone can’t shut down cortisol production; the cortisol is still elevated.

In another confirmatory study, the following steps occur:

A 24-hour urine collection is tested. High cortisol indicates Cushing’s syndrome.

When the screening test is positive, a blood test then measures the amount of ACTH in the bloodstream. If the ACTH is high, then a pituitary tumor is suspected. But if the ACTH is low, then an adrenal tumor is most likely the cause.

Following a positive blood test or a positive urine test, the patient has a CT or MRI test. If ACTH is high, the doctor orders the test on the pituitary; if ACTH is low, the doctor orders the test on the adrenals. The MRI shows a pituitary tumor, but an abdominal CT may show a tumor in an adrenal gland. If an ectopic source of ACTH is suspected, the CT is directed to look for a tumor in the chest and the abdomen.

Treating Cushing’s syndrome

The first step in treating Cushing’s syndrome is to control the blood pressure with drugs. The use of drugs is the same as for essential high blood pressure (see article 13). After the blood pressure is under control, the treatment is directed to the source of the excess hormone.

  • If the pituitary is responsible through an ACTH-producing tumor, the patient undergoes an operation under anesthesia (don’t worry, you won’t feel a thing) that involves passing a tube through the nose into the pituitary gland for the removal of the tumor. If this isn’t successful or feasible, the patient has X-ray therapy to the pituitary.
  • Sometimes the pituitary can’t be treated (for example, if the patient refuses surgery on the brain). Then both adrenal glands are removed by surgery because the hormones from the adrenals are responsible for most of the signs and symptoms. Afterwards, the patient is treated with steroid replacement.

A complication of this treatment is the growing tumor in the pituitary and an abundance of ACTH. Over a period of ten years or so, the patient’s skin shows significant darkening, a condition known as Nelson’s syndrome. Then the pituitary tumor must be removed because it is enlarging, losing other pituitary hormones, and causing local symptoms like compression on the optic nerve (the nerve for vision).

If the adrenal gland has a tumor that makes too much cortisol independent of ACTH control, that tumor is removed in much the same way as an aldosterone-producing tumor. (See the “Treating an aldosterone- producing tumor” section earlier in this article.)

If ACTH has an ectopic source, then the ACTH is often from a cancer, and chemotherapy may be necessary. After a patient’s pituitary tumor is removed, her cortisol may be abnormally low for as long as six months. She may need support from replacement medication to provide the cortisol, which is essential to life. When her own adrenal gland takes over, the medication can be phased out.

Recognizing a Genetic Disease as the Cause for High Blood Pressure

Congenital adrenal hyperplasia, an inherited disease, is the genetic lack of one or more enzymes that eventually change steroids to cortisol in the adrenal glands. This condition leads to an overproduction of other hormones that have properties similar to aldosterone. When the pituitary gland does not detect sufficient cortisol, it sends out more ACTH to stimulate the adrenals, which then enlarge. The two most common forms of congenital adrenal hyperplasia break down into the following categories:

  • The excessive steroids are:
    • Aldosterone-like, producing high blood pressure and low potassium
    • Masculinizing, causing masculine changes in baby girls so that their genital organs are something between male and female
    • In milder forms, responsible for the early onset of puberty in boys. This symptomatic increase of male hormone activity (like increased hair and menstrual irregularity) can also occur in young girls.  
  • The excessive steroids are aldosterone-like, causing high blood pressure and low potassium, but no sex hormones are made. As a result:
    • Menstruation doesn’t take place, so the disease is first detected at puberty in a girl.
    • The lack of male hormones in boys leads to abnormal development of the male sexual organs, so the disease is found earlier than in girls.

Although these conditions are rare, they’re easily treated if diagnosed early. Both types of patients take cortisol, which shuts off the excessive ACTH and the production of the abnormal steroids. In the second form of congenital adrenal hyperplasia, the patient also takes sex hormones to replace the absent hormones. Because these diseases are hereditary, they occur in certain families more often than others. (The more common form is more often in Ashkenazi Jews; the less common form is more often in Sephardic Jews but in other families as well.) This predictability alerts doctors to look for the condition whenever a new birth occurs in one of these families.

Checking Out Other Causes of Secondary High Blood Pressure

Several other treatable diseases are associated with high blood pressure. Most of them are reversible, and the high blood pressure responds to the correction of the disease unless it’s been present for some time.

Coarctation of the aorta

Coarctation of the aorta is a narrowing of the large artery that leaves the heart. Depending on the severity, the narrowing is usually present at birth though not diagnosed until the teenage years. The narrowing is usually close to the beginning of the aorta but below where the artery branches to the arms. The result is high blood pressure in the arms and lower blood pressure in the legs (which the doctor can observe by simply measuring the blood pressure in the arms and the legs).

The narrowing results in the production of a murmur, a humming sound, which can be heard with the doctor’s stethoscope in the area of the heart. In addition, the doctor is unable to detect a pulse in the groin. The kidneys respond to the lower blood pressure by putting out more renin (see the earlier section “Handling blocked kidney arteries”); the increase leads to even higher blood pressure above the narrowing but not below it.

Children with this condition can have nosebleeds, dizziness, pounding headaches, and, when they exercise, leg cramps. During a careful first examination of any baby, the doctor feels for the pulses in the groin and feet and notes whether pulses are present or not. If not, the doctor can order further evaluation with a CT or MRI of the chest.

The treatment consists of surgery to open the narrow area or sometimes balloon angioplasty, the same technique used to open the narrow blood vessels of the heart. (See the “Treating blocked kidney arteries” section, earlier in this article for more on angioplasty.)

If the coarctation isn’t treated, the patient may die before the age of 40 from complications of high blood pressure.

Too much or too little thyroid hormone

Both hyperthyroidism (too much thyroid hormone) and hypothyroidism (too little thyroid hormone) can be associated with high blood pressure. These conditions may be easy to diagnose if the symptoms are significant, but hypothyroidism is often subtle.

If the patient has a rapid pulse, weight loss, and sweating in addition to high blood pressure, then hyperthyroidism must be considered.

If the patient has high cholesterol and high blood pressure, the diagnosis of hypothyroidism should certainly be considered.

Thyroid disease is so common, and testing for it is so simple, that everyone over age 35 should have a screening blood test. Screening consists of a thyroid-stimulating hormone-level blood test.

Ask your doctor to screen you for thyroid disease beginning at age 35 and every five years thereafter.

Hyperthyroidism and hypothyroidism can be treated easily:

  • Hyperthyroidism: Pills to block thyroid hormone production or a dose of radioactive iodine
  • Hypothyroidism: Replacement thyroid hormone by mouth. One pill a day keeps the person entirely normal — at least as far as the thyroid is concerned!

In both conditions, the blood pressure returns to normal after treatment.

Acromegaly

Acromegaly is a disease resulting from a slow-growing tumor of the pituitary gland that makes too much growth hormone. The excess growth hormone causes sodium retention, high blood pressure, and many other signs:

  • The hands and the feet grow thick.
  • The lips, nose, and tongue are thick.
  • The skin is coarse and oily.
  • The body is weak and sweats excessively.
  • If the disease begins before the bones close (a person normally grows until the growing ends of bones are eliminated, referred to as the bones closing), the patient is extremely tall, often unable to get through doors without stooping way down.

Untreated, acromegaly can cause diabetes, high blood pressure, and heart disease, all resulting in early death. The following steps explain how a doctor proceeds when she suspects acromegaly:

  • The patient takes glucose (the type of sugar in the blood), and then has a blood test that checks for growth hormone levels.
  • If the test shows elevated growth hormone, the next step is a CT of the brain to look for a pituitary tumor. Sometimes, the pituitary appears normal and other tumors in the body produce growth hormone. In this case, radiologic studies may find a tumor elsewhere in the body.

Drugs are available to treat acromegaly, but they’re not entirely successful and have side effects. Instead, surgery is usually recommended. A brain surgeon goes in through the nose and removes the tumor. If the surgery is successful, the skin shows improvement in a few days. It’s most successful when the level of growth hormone isn’t very high.

When surgery is ineffective, radiation to the pituitary can cure the disease but may also cause the loss of other pituitary functions (like the production of hormones that control the thyroid gland, the adrenal gland, and the genital organs). The blood pressure falls when the growth hormone level becomes normal.

Sleep apnoea

Sleep apnoea is a condition in which an individual gasps for breath and snores during sleep following several stops in breathing. It’s significant when it happens five or more times in an hour. The results of the restless sleep are extreme fatigue during the day, headaches, and a tendency to fall asleep when he doesn’t want to such as when driving a car and at work.

Because the lack of breathing occurs many times, the person has a reduction in blood oxygen and an increase in carbon dioxide. The decrease in oxygen causes constriction of the blood vessels with resultant high blood pressure. These people also tend to have increased heart disease.

Sleep apnoea is diagnosed in a sleep laboratory where doctors can observe the person sleeping, snoring, and failing to breathe for many periods of time. After the diagnosis, the person wears a mask that provides positive pressure while he sleeps. This pressure keeps the airway open so he doesn’t experience breathing loss, loud snoring, or gasping for air. Sleeping is much more restful, and the person doesn’t fall asleep during the day. The high blood pressure usually subsides as well.

If the condition has gone on for a long time, the high blood pressure may continue, and pills may be required to control it.

Brain tumour

Brain tumours increase pressure within the brain and the blood pressure throughout the body. The blood pressure rise may not be constant and may mimic a pheochromocytoma. (See more on pheochromocytomas in the “Finding an epinephrine-producing tumor” section earlier in this article.) If the brain tumor can be managed successfully, the high blood pressure returns to normal. If not, blood pressure pills are required to control it.

Burns

The high stress associated with severe burns causes high blood pressure in about 25 percent of severe burn cases. A bad burn also triggers the release of hormones that cause blood vessel constriction. If the patient survives the burn, the blood pressure returns to normal after about two weeks.