GROWING PAINS : A Synthetic Hormone Is Cutting Short a Growth Disorder’s Hold Over Children
Three times a week, Marcia Slaten takes several vials of medication out of the refrigerator in the kitchen of her Canoga Park home, mixes them, and injects a large syringe of the liquid deep into the thigh muscle of Scott, her 14-year-old son.
The condition that she is treating, at a cost of about $2,400 a month, is neither life-threatening nor debilitating.
It is shortness.
Scott is one of about 15,000 children in the United States who remain small because they lack growth hormone, one of many chemicals released by glands such as the thyroid and pituitary to control the proper development of the human body.
Scott’s injections contain a synthetic version of human growth hormone. Produced by bacteria whose genetic code has been modified, the synthetic hormone is the newest drug in the blossoming age of biotechnology.
Source Contaminated
Without the new form of the hormone, such growth-promoting treatments would have come to a halt last year, when the only previous source of human growth hormone--glands from human cadavers--was eliminated after the supply was suspected of being contaminated with a rare, deadly virus.
Now, the synthetic hormone is being used only to treat several thousand rare children who, like Scott, are diagnosed as lacking the actual growth hormone.
But synthetic growth hormone is being tested as a treatment for other, more common causes of shortness. The research is supported by Genentech, which developed the new product and has a 7-year monopoly on its sale, and other drug companies that are looking forward to the day when they may compete for sales.
Genentech has also started a major marketing campaign aimed at pediatricians, and through them at parents, promoting the new drug’s potential. On Friday, the company sponsored a seminar for more than 100 pediatricians at Tarzana Regional Medical Center, which last month opened a Growth Disorders Center. Scott Slaten is one of the center’s first patients.
Most growth specialists are enthusiastic about the new product, but many expressed concern that marketing and the unlimited availability of the synthetic hormone may lead to abuses.
Restrictions Advised
Some also said that because the treatments are extremely expensive, they should be restricted to the most severely stunted children. “If every short kid were prescribed growth hormone, we’d all go broke” because of the effect on health-insurance premiums, said Dr. Mitchell Geffner, a growth specialist at UCLA Medical Center.
Earlier this month, Scott visited Dr. Norman Lavin, the pediatric endocrinologist in charge of the new growth center in Tarzana, for his first checkup since the synthetic-hormone injections were started three months ago.
Many large teaching hospitals in Los Angeles also have centers for treating growth disorders, but the Tarzana center is the first at a small private hospital, and the first in the San Fernando Valley.
Lavin has been seeing Scott for six years. He treated the boy previously with the old, natural version of the hormone, but that treatment stopped along with all the others last year because of the suspected contamination.
Scott’s checkup was a success. He had grown three-fourths of an inch in three months, to 4 feet, 8 inches. At that rate, Lavin said, he may grow as much as three inches in the coming year. Usually, though, growth tapers off after an early spurt, he said.
Lavin marked Scott’s latest height measurement on a sheet of graph paper that also contained a series of smooth ascending lines representing the growth from year to year of an average sample of boys. At every age, Scott’s height was lower than the lowest line on the graph, which represented the heights of the shortest 3% of boys.
First Tested at 2
“Scott was always way under the norm,” said Marcia Slaten. He was first tested at UCLA when he was 2 years old, she said.
If the treatment goes well, her son will reach a height of about 5 feet, 4 inches before his bones stop growing and fuse into their final, adult shape, Lavin said.
Lavin and other endocrinologists stressed that only a fraction of 1% of the estimated two million short children in the United States--those that fall in the shortest 3% of children at a given age--are candidates for synthetic growth hormone.
Heredity Factor
The vast majority of short children are what endocrinologists call “short normal,” Lavin said, and “are short because their parents are short,” he explained.
The other common type of normal shortness is constitutional. X-rays and other tests can often determine that a child is short merely because the development of his skeleton is lagging behind his actual age. In such cases, the body usually goes through a spurt of growth after puberty and catches up to expected proportions, Lavin said.
He said only a small percentage of short children--including those deficient in growth hormone--are diagnosed as “short pathological” and require some treatment.
The process of elimination starts with a complete medical history and a physical. A crucial step is to draw a growth curve, such as the one Lavin has been keeping for Scott.
He said parents should always keep a record of a child’s height and weight at yearly intervals. This quickly allows a physician to assess a patient’s growth in relation to his peers and to spot any abnormal changes in the rate of growth, Lavin said.
“It’s the pattern that counts,” he said. “I’m more concerned if a child falls from the 95th percentile of heights for his age to the 25th percentile than if a child grows in the 15th percentile consistently.”
Disease Could Be Cause
Sometimes, abnormal stunting is caused by hidden diseases such as heart disease, kidney or intestinal problems, Lavin said. In fact, shortness is often a valuable signal that something else is wrong. “If I do find short stature and can’t figure out why, then I start to think there may be an underlying chronic illness,” Lavin said. “It helps to flush out other problems.”
Sometimes a mother’s excessive smoking or alcohol consumption during pregnancy can impede fetal development.
Occasionally, emotional deprivation or punishments such as locking a child in a closet can stunt growth. The brain governs the amount of growth hormone released by the pituitary gland, Lavin said. Although the mechanism is not clear, stress or depression can slow the flow of the hormone.
Rarely, the skull of a child is X-rayed to check for brain tumors that might be affecting the hormone flow. In girls, chromosome analysis is also occasionally performed, to check for a genetic cause of female shortness called Turner’s syndrome.
Still more rare is a lack of thyroid hormone. Least common of all is a deficiency in growth hormone, he said, and tests to determine the condition are done only after all other possible problems are ruled out.
Growth-hormone deficiency is diagnosed by provoking the pituitary with drugs to release its hormone and then measuring the level of the hormone in the blood.
Once a child is started on the synthetic growth hormone, his progress is regularly measured.
Close monitoring is important, Lavin said. If doses of hormone are too high, a child’s skeleton can mature to its adult form before it has grown taller. At a certain stage, the actively growing ends of the bones fuse, and no more growth is possible, he said.
X-Rays Compared
Lavin monitored the effect of Scott’s growth-hormone treatment by checking his bone age through X-rays of his left hand. By comparing an X-ray of Scott’s hand with X-rays taken of average hands year by year, he can get a rough idea of how much growth potential remains.
Lavin flipped through a large volume of X-rays. In each successive image, the long bones of the fingers and small pebble-like bones in the wrist grew, pressed together, and at last--at about 18 in males--fused.
He glanced up at the freshly developed X-ray of Scott’s hand, comparing subtle features with those in the book until he matched Scott’s bone development with an image of the hand bones of the average 12 1/2-year-old. The fact that Scott’s bone age is lagging behind his chronological age of 14 is good, Lavin said. It means that there still are some years of potential growth left.
Lavin said many parents have the impression that treatment with growth hormone will accelerate a child’s growth beyond the height that would normally be expected. As a result, Lavin said, he spends almost as much time counseling families about unrealistic expectations as he does treating shortness.
The treatments at best generally bring a child’s height near what can be predicted by looking at his parents’ heights, but not beyond that. “They’re not going to be playing for the Lakers after we give the hormone to them,” Lavin said.
Lavin agreed with other endocrinologists that the abundance of growth hormone made possible by genetic engineering is a mixed blessing.
It will allow any patients who require it to get their share, but it may also tempt parents and some doctors to treat other causes of shortness--with unknown consequences.
No Previous Problem
“This was never a problem when the product was of pituitary origin,” said Dr. Albert Parlow, who for years has directed a laboratory at Harbor-UCLA Medical Center that isolates growth hormone and other hormones from pituitary glands taken from cadavers.
Some athletes used the hormone in body-building efforts, but not enough was available for widespread abuse, Parlow said.
But, he said, with the synthetic hormone commercially available in large quantities, “I fear there will be temptation with the synthetic product to administer it to normal kids for parents who want to grow a new Kareem Abdul-Jabbar.”
“There is a great potential for misuse of the hormone,” said Dr. Jo Anne Brasel, chief of the division of pediatric endocrinology at Harbor-UCLA Medical Center, which is using the synthetic hormone to treat children with growth-hormone deficiency and is running several research projects to study its use in treating shortness caused by other conditions.
But she said that Genentech has helped to lower the chances of the growth hormone being improperly prescribed by distributing the hormone only to pharmacies at medical centers that have pediatric endocrinologists.
Another factor that will tend to restrict ill-advised use of the hormone is the potential for malpractice suits, said Dr. John Gueriguian, the Food and Drug Administration’s supervising medical officer for use of growth hormone.
He said Genentech’s hormone is approved by the FDA only for treating proven growth-hormone deficiency. “A doctor has the right to use any approved drug for any other indication he thinks is right,” Gueriguian said. “But once a doctor tries to do that, he is taking full responsibility for his actions.”
Costly Treatment
Finally, the high cost of the hormone--between $10,000 and $30,000 per year, depending on the child’s weight--should limit its availability, many doctors said. MediCal and private insurers are now paying for the hormone only in proven cases of severe growth-hormone deficiency, doctors said.
At UCLA, which is treating about 60 children with synthetic hormone, insurers are hesitating to reimburse in cases where the need is judged to be borderline, Geffner said. When dealing with growth disorders, the line between a treatment that deals with a medical condition and one that is meant to improve appearance is hard to measure, he said.
That is the situation confronting Scott Slaten’s family. Marcia Slaten said that when she first started her son on the pituitary-derived hormone three years ago, the family’s insurers covered most of the costs. But, she said, “his hormone levels were in what they call the gray area.” She recently had to switch insurance companies when she changed jobs, she said, and she is now fighting the new insurers for reimbursement.
Slaten said she has commitments from family members to defray the cost if insurers refuse to pay.
When asked if all the trouble and potential expense are worth it for several inches of height for her son, Slaten said, “If you’re a good parent, you take the best shot you can for your children. Even if it doesn’t happen, even if he winds up 5 foot 2, at least you know you tried to do something.”
