Original article no longer available

Boston Globe

May 26, 1997

Author: Judy Foreman, Globe Staff

Louise Pace was a happy, 42-year-old commercial real estate broker in Florida when her body began going bananas.   Bruises popped up on her legs, so she went to her doctor, who suspected leukemia. It wasn’t, so the doctor suspected abuse.   When her monthly periods stopped and she developed hot flashes, mood swings and insomnia, her gynecologist said it was early menopause, gave her estrogen and told her to calm down.

A dermatologist said the purple marks on her chest were from sunbathing for too many years. Nobody seemed to know why she suddenly gained 40 pounds and became moon-faced. Or why her hair fell out everywhere, except on her face, where it sprouted.

“I cried every day when I looked in the mirror at my fat, ugly, balding self,” she recalls.   Desperate, she went to a psychiatrist who, she recalls, said she was obsessed with her body and gave her Prozac. She wrote suicide notes and called a college roommate to say goodbye.

That call saved her life, says Pace, now 51 and living in Boston. After four years and 15 doctors, it was the roommate, a medical editor, who got the diagnosis right: Cushing’s syndrome.  Spontaneous cases of Cushing’s, usually caused by tumors in the pituitary or adrenal glands, are rare — about 1,500 cases a year in adults and kids.

But thousands of others develop Cushing’s or some of its symptoms, not because of tumors like Pace’s but because they are taking prescribed steroid drugs such as prednisone.  Over the last five years, steroid prescriptions have grown steadily — to more than 30 million in 1996 alone, according to IMS America, a pharmaceutical market research firm.

And that “is a major problem,” says Dr. George Chrousos, chief of pediatric endocrinology at the National Institute of Child Health and Human Development, even though many doctors have learned to use steroid drugs better than in the past.

Steroid drugs — not to be confused with the anabolic steroids that some athletes use illegally — can be “lifesaving and hugely important in controlling many important diseases,” says Dr. Jerry Avorn, an internist at Brigham and Women’s Hospital who studies drugs and their side effects.

Because of their powerful anti-inflammatory action, they can help combat asthma, chronic lung disease, allergies, rheumatoid arthritis and other auto-immune diseases, certain cancers and rejection of transplanted organs.

But the cost of that benefit can be high.

Dr. David Orth, of Vanderbilt University in Nashville, estimates that 250,000 people a year develop Cushing’s from taking high doses of steroids for long periods. In fact, a person can develop Cushing’s symptoms from taking 20 milligrams of steroids a day for as little as three to six weeks, says Orth, one of a number of endocrinologists, or hormone specialists, who worry that steroids are being overprescribed.

Cushing’s syndrome, or hypercortisolism, occurs when the body’s tissues are exposed to too much of the hormone cortisol.

In a healthy person, cortisol is pumped out every day by the adrenal glands, which sit atop the kidneys. The pituitary gland, which lies just beneath the brain, sends the signal that triggers cortisol production, with the peak output occurring around 8 a.m. — as if nature were providing a jolt to get moving.

And at normal levels, 25 micrograms per deciliter of blood in the morning and about 5 micrograms at night, cortisol is essential to life. It helps regulate blood pressure, energy production, the ability to fight infections and respond to stress. It also seems to keep the immune system in check so that it doesn’t make antibodies that might attack the body’s own tissues. And it seems to balance the effects of insulin in breaking down sugar for energy and to regulate the metabolism of proteins, carbohydrates and fats.

In fact, if you have too little cortisol, you can wind up with Addison’s disease, which President John F. Kennedy had, a condition that can be fatal without hormone replacement.

But too much cortisol — whether produced naturally in the body or taken as steroids — is disastrous, too. It can cause sudden weight gain, especially in the trunk, a florid moon-like face, thin skin, mood changes, muscle weakness, purple stretch marks on the torso, high blood pressure, diabetes, a fatty “buffalo” hump on the neck, depression, and severe osteoporosis.

Left untreated, Cushing’s can be fatal.

In spontaneous Cushing’s, the usual culprit is a tumor in the pituitary gland that sends too many signals to the adrenals to make more cortisol. But tumors in the adrenal glands can also cause excess cortisol production, as can more rare tumors that occur in the lungs and elsewhere.

Whether Cushing’s is caused by tumors or steroids, one result is “severe osteoporosis with devastating consequences,” says Dr. Michael Holick, chief of endocrinology, nutrition and diabetes at Boston Medical Center. “Steroids have a direct effect on bones, causing severe bone wasting. The bones get so thin that a heavy cough can cause fracture of the ribcage.”

No one knows that better than Kathy Carbone, now 48 and a business manager in Richmond, Va., who had a pituitary tumor. Like Pace, Carbone was in her early 40s when the perplexing symptoms began. She spent four years and went to 12 physicians before her disease was diagnosed — also by a friend.

Though Carbone was a very fit aerobics instructor at the time, her bones became so weak she would wake up with spontaneous rib fractures. Her muscles, too, became weak: “If I squatted I would fall over.”

For people like Pace and Carbone whose Cushing’s is caused by tumors, the first step is getting a diagnosis, which includes a series of urine samples collected over 24 hours, then surgery to remove the tumor. But many pituitary tumors — which are usually benign — are so small they can be hard to find amid normal tissue.

For that reason, says Dr. Beverly M.K. Biller, an endocrinologist at Massachusetts General Hospital, it is crucial to find a neurosurgeon who has done “hundreds and hundreds” of the surgeries, usually a procedure called a transsphenoidal adenomectomy, in which the tumor is removed through the nose or an opening below the upper lip.

If you’re in a managed care health plan that requires you to go a specific neurosurgeon, she adds, you “are better off going outside the provider circle if that surgeon is not an expert.”

Like pituitary tumors, about half of adrenal tumors are also benign and can be removed surgically. In almost all cases, this cures the Cushing’s. A malignant adrenal tumor can also be removed surgically, but it must be followed by drugs to suppress cortisol produced by any pieces of the tumor that may have spread, and to curb the cancer.

As both Pace and Carbone can attest, removal of even a benign tumor is just the first step in a long recovery. If surgery cuts cortisol production to zero, the patient is left with a temporary form of Addison’s disease, which must be treated, paradoxically, with hormones, usually prednisone or hydrocortisone.

When Cushing’s is caused by steroids, not a tumor, there are also things you can do.

The most important is to talk to your doctor about reducing the dose. But never suddenly stop steroids on your own — you can go into adrenal failure and die. The goal is to taper off the steroids very slowly.

If you have asthma, chronic lung disease, or rheumatoid arthritis, you may need the steroids just to breathe or walk. Even so, Cushing’s specialists say, you may be able to reduce the dose. And some asthma patients can switch from oral steroids to the inhaled form, which is not absorbed as readily throughout the body.

If you have rheumatoid arthritis, you may be able to taper off some steroids by taking other medications, such as colloidal gold, Plaquenil, Feldene and methotrexate.

For osteoporosis, it may help to take 1,500 to 2,000 milligrams a day of calcium, and 400 International Units of vitamin D. You might also consider taking prescription drugs such as estrogen and Fosamax.

Another strategy is to take steroids only every other day, so you don’t suppress all your own cortisol production. And if you take steroids just once a day, take them at 8 a.m., when your body would normally be making cortisol.

Some day, there may be better drugs that damp down the inflammatory response without so many side effects.

Until then, if you have symptoms that stump your regular doctors, consider seeing a hormone specialist, says Michael Conn, president of the Bethesda, Md.-based Endocrine Society.

And if necesssary, figure things out yourself, says Carbone.

“Anyone who is hurting or seeking answers should take it upon themselves to read, to sit down with medical journals and look up your symptoms,” she says. “I would have been diagnosed far earlier if I had been creative enough to read up on my symptoms.”

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