Cortisone: the limits of a "miracle" - includes related articles

Nutrition Health Review, Fall, 1991

One of the miracles recounted in the New Testament was that of the long-paralyzed man who was commanded to stand up and walk.

On the morning of September 21, 1948, an almost as miraculous event began to unfold. A 29-year-old woman, hospitalized at the Mayo Clinic for rheumatoid arthritis so severe that the painful joints of her legs had been locked into immobility, was injected with a tiny amount of an experimental new drug. Unlike the Biblical event, nothing happened immediately.

But here, too, faith intervented, faith on the part of a physician, Philip Showalter Hench, who had devoted much of his career to finding a way to cure or alleviate arthritis. So, despite the apparent failure of the injection, Hench persisted, giving a second injection the next day, still without apparent effect.

But when the patient awoke on the third day, she found to her amazement and joy that the pain had disappeared and that she could swing her legs over the side of the bed and actually walk. Within a week she left the hospital to go on a three-hour shopping spree. Thirteen other severely afflicted patients were also given injections of the new drug, then called compound E. The results were uniformly incredible. Crutches and wheelchairs discarded. Frozen joints turned supple. Swelling and pain largely eliminated.

The new drug was the fruit of a long, patient, often discouraging effort by an American physician, Edward Kendall. Produced by the body in a section of the adrenal gland called the cortex, the drug was found to belong to a widely diverse family of chemicals, called steriods, that includes vitamin D, male and female sex hormones, and the heart drug digitalis.

All of the steroid hormones produced by the adrenal gland, now known as the corticosteroids, influence directly or indirectly many of the body's basic chemical processes. Their main function is to help the body maintain the chemical status quo against disruptive forces. Those forces, all forms of stress, include illness, injury, infection, mental strain, severe exertion, and allergic reaction. Without the adrenal cortex and its products, the body would succumb to the impact of such stress.

One of the corticosteroids found by Kendall, which he called compound B, is now known as corticosterone; another, compound F, we know as cortisol or hydrocortisone; and compound E, wich gained instant fame that September day, has become accepted as a general term for the whole class of these powerful drugs -- cortisone.

Hench's success in applying cortisone to arthritis happened at a time when first the sulfa drugs and then penicillin and other early antibiotics were revolutionizing medicine and introducing the terms "wonder drug" and "miracle medicine" to our common vocabulary. Great things were expected of cortisone.

As one physician put it, "Not only were patients previously crippled with arthritis helped to get back on their feet and become active members of society again, but patients with other so called 'collagen diseases' such as disseminated lupus erythematosus and polyarteritis nodosa were dramatically benefitted; patients with allergies such as bronchial asthma, hay fever, and eczema received impressive relief; patients with some types of leukemia and other malignancies went into temporary remissions; and those wiht numerous other disorders experienced unprecendented improvement from those agents." In addition, a once-fatal affliction, Addison's disease, resulting from a defective adrenal cortex, could not be treated successfully.

It is not surprising, then, that cortisone came to be accepted as a miracle medicine or that within two years Hench and Kendall, together with Swiss researcher Tadeus Reichstein, were sharing the Nobel Prize for medicine and physiology.

But before this miracle could come within reach of those who so desperately needed it, the price had to be brought down. Owing to the difficulty of synthesizing cortisone from ox bile, it was over a thousand times more costly than gold. An intense research effort to reduce the cost was immediately undertaken. This required some incredibly complicated chemical footwork, since an oxygen atom had to be dislodged from its normal place on the steroid framework and moved to another point. This was accomplished, and soon the basic cortisone building block was being produced from steroids in soybeans, Mexican yams, cholesterol in wool fat, and yeast. Within a year, the cost had been reduced by 95 percent. Research to synthesize analogues, or chemical variations, of cortisone was also soon under way.

But even while all this intense research was proceeding, and amidst all the acclaim, awards and great expectations, the miracle was already turning sour. Many patients quickly reverted to their previous condition when the cortisone treatment ceased. And -- even worse -- devastating and frightening side effects often accompanied cortisone treatment. In many instances, those treated exhibited all the symptofms of adrenal excess, called Cushing's disease. Side effects included insomnia, psychotic behavior, growth suppression in children, peptic ulcer, delayed wound healing, hyperglycemia (excessive sugar in the blood), carbohydrate intolerance, muscle weakness, susceptibility to infections, and many others. Surgeons reported death under general anesthesia of patients undergoing minor surgery who had been taking cortisone. In addition, cortisone proved to have a habit-forming potential -- stoppping the drug often brought on withdrawal symptoms such as fatigue, weakness, arthralgia (joint pain), fever, dizziness, lethargy, depression, fainting, dyspnea (difficult breathing), anorexia, and even death.