"They got bandy little legs that stand so low

You've got to pick 'em up just to say hello . . ."

-- from "Short People" by Randy Newman

Randy Newman was joking when he wrote this diatriabe against short people, but discrimination against small folks isn't funny.

Short people, says Dr. Gilbert August, pediatrics endocrinologist at Children's Hospital National Medical Center, "are at a substantial disadvantage in a tall world."

For example, "studies done by psychologists have shown that income is related to one's size to a certain extent," he notes, "and certainly every four years, we get the same story about the taller presidential candidate." And that, he says, does not begin to plumb the psychological problems. His own teen-aged daughter, who is just five feet tall, cannot drive a General Motors car.

"The seat is too low for short people," he says, "so we got a Chrysler."

August has been treating youngsters who have growth hormone deficiency, both the classical kind, which specific tests can uncover, and the more subtle kind, in which children seem to have enough growth hormone factor but it is somehow not stimulating growth. These youngsters will reach a maximum height of five feet for boys, with girls leveling off three or four inches shorter. They simply do not exhibit the normal growth spurts shown by their age groups, and the older they get, the more they seem to fall behind.

An estimated 12,000 American children are classically growth hormone deficient -- they lack a factor produced in the pituitary gland that is essential to the growth process. In some cases there seems to be a strong familial link in the deficiency. In other cases, says endocrinologist Dr. Judith Fradkin, head of the endocrine branch of the National Institute of Arthritis, Diabetes and Digestive and Kidney Diseases (NIADDK), "it just crops up." In some children surgery or various other problems near the pituitary cause the problem.

But there may be many cases in which children whose growth is delayed or retarded for unknown reasons can benefit from growth hormone treatment. Denise Orenstein, executive director of the National Human Growth Foundation -- a support and educational organization for parents of short-statured people and the physicians, psychologists and other health care professionals who treat them -- estimates that there are more than 2 million individuals in this country of short stature as the result of some 200 growth disorders.

Studies ongoing since about 1963 at NIADDK have demonstrated the usefulness of injections of the pituitary growth factor extracted from the pituitary glands of some 50,000 cadavers a year. Gradually, researchers and clinicians like August began to see its success in other growth problems. In the last few years, biosynthetic growth factor, produced by recombinant DNA techniques, was being developed. It looked like Randy Newman and his ilk might have a lot fewer short people to pick on.

But today the entire program is on hold. The human growth factor that was being provided to some 3,500 short children every year -- about 2,300 were receiving it virtually free through the NIH program -- may have, in a very few cases, contained the seeds to a rare but deadly brain disease. In normal circumstances, the affliction, Cruetzfeldt-Jakob disease (CJD), might be expected to strike one in 1 million people, and only one in 10 million under the age of 40.

Then this spring, within the space of a few months, specialists found that three young people (in a total population of no more than 15,000 who had been receiving injections of the natural growth hormone since 1963) had died of CJD -- two cases confirmed and one that followed the classical symptoms. This degenerative, fatal and so-far incurable neurological illness is caused by an infectious agent, possibly some type of virus or, as more recent work has suggested, an infectious protein particle called a prion. It can lurk in the brain, incubating for years, but once symptoms appear, degeneration of the central nervous system progresses rapidly and relentlessly, culminating in an Alzheimer's-like dementia and death, usually within six months to a year.

The NIH specialists moved quickly to suspend the federal growth hormone program. But there was a kind of underground feeling among pediatric endocrinologists that because purification processing had vastly improved since the three victims had been on the growth hormone (all having received hormone processed before 1977) there was little chance of infection from more recent lots. Most still feel this is probably true.

However, after a stern warning about the resistant nature of prions from Nobel laureate Dr. Carleton Gadjusek, the NIH specialist on CJD, virtually all public and private treatments with the human growth hormone have ceased at least until the existing lots of the hormone can be tested. (A few patients in whom cessation of the hormone would cause life-threatening hypoglycemia are still receiving it.) The chance of any more recent participants in the program turning up with CJD is considered remote, and all physicians are emphasizing that there is no cause for panic, nor even great alarm.

Nevertheless, cessation of the program is bad news for the growth-delayed or deficient youngsters. It is especially bad for those youngsters nearing puberty and the end of the time when their bones can continue to lengthen normally.

But the expected imminent approval by the Food and Drug Administration of the biosynthetic product, called Protropin and manufactured by Genentech Inc., offers some hope. Its clinical trials have indicated its efficiency in mimicking the work of the natural hormone, which stimulates production of a blood hormone -- somatomedin -- which in turn works directly on the skeleton to increase growth. (August notes that some growth-retarded children who test normal for growth hormone seem to have a deficiency of somatomedin. These youngsters are among those who do well on growth hormone, he says.)

Genentech recently expanded Protropin's "investigational new drug" (IND) status with the FDA to include a so-called "compassionate use" for children with growth hormone deficiency who are nearing puberty. This will enable them to receive the product outside of normal clinical trials, on the specific request of their physicians. Protropin is also available on the compassionate use basis to those who need the hormone to prevent hypoglycemia. Two other companies -- Eli Lilly and Serono -- are beginning clinical trials of their versions of biosynthetic growth hormone.

So younger children can look forward to re- suming growth either on Protropin, once it is approved, or on the human-derived growth hormone, which experts anticipate will be cleared after about a year of studies. Meanwhile NIH has instituted a massive epidemiological survey to try to determine if any other recipients either died from or show any symptoms of Creutzfeldt-Jakob disease.

Outside of the federal program, the growth hormone is expensive -- up to $10,000 a year per patient, and specialists anticipate that Protropin will not be much cheaper. In some areas, including the Washington metropolitan area, says August, Medicaid and insurance companies have helped defray the costs, but this is not universal and he fears that "it would put the kids who cannot afford this at a serious disadvantage.

"This is not," August emphasizes, "just a cosmetic problem as some would say. It is a problem in the way our society is arranged."

At least one pediatric endocrinologist, Dr. Selna Kaplan, chief of the pediatric endocrine unit at the University of California at San Francisco medical center, thinks society could use a little rearranging.

She has treated short-stature children in clinical trials with both Protropin and the human-derived growth hormone, but, she wonders, "if someone has a problem about being short, is it really their short stature or their feeling of inadequacy or poor body image? And would making them tall really resolve all their concerns about themselves?" She thinks not.

"The problem," she says, "is trying early in life to develop in them a feeling of good self-esteem, not that their whole worth hangs on whether they're going to end up being 5-feet-10 against 5-feet-6.

"But maybe I'm prejudiced because I'm just barely five feet, and I haven't felt that it's been a deterrent in anything I've wanted to do." Resources

*Information on "compassionate use" of Protropin: Physicians with pre-pubertal patients with established growth hormone deficiency should write Genentech Inc., 460 Point San Bruno Blvd., South San Francisco, Calif. 94080. Phone: 415-952-1000.

*National Human Growth Foundation, 4607 Davidson Dr., Chevy Chase, Md. 20815. Phone: 656-7540.

*Greater Washington Chapter, Human Growth Foundation. Suzanne Diffley, president. Phone (evenings) 548-9578.