IT TAKES ONE TO KNOW ONE
Richard Noto, M.D., insists the concern over using human growth hormone to treat children who are small is absurd. His research is helping to explain why.
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ABOVE: Richard Noto loves New York, if his education and training are any indication. He received a B.S. from York College of the City University of New York; an M.D. degree from Mount Sinai School of Medicine; a pediatric residency at Beth Israel Medical Center; and two pediatric endocrinology fellowships from New York Hospital-Cornell Medical Center and North Shore University Hospital. |
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"Johnny is off the chart." When a pediatrician tells this to parents of short children, it means their child is not even within height range of other children the same age. Testing for an HGH deficiency comes next. These color-coordinated charts, which reflect the differences in gender, are filled out by hand, a vestige of an earlier age when there was no remedy for short stature. |
Tall Wins
"What happens to short children emotionally can be serious. Our society places great emphasis on height. Children who are short for their age have problems because playmates tease them unmercifully and teachers treat them as though they were younger rather than just smaller. Parents tend to do this, too. The children don't act their age because it's not expected of them…it is very important to provide emotional support for a child with growth hormone deficiency and to emphasize the child's many good qualities, so that his height does not limit his perspective."
A child's growth hormone deficiency can occur by itself or in combination with one or more other hormone deficiencies. These factors may cause a total shutdown or just a partial one, which would allow production of a small amount of growth hormone, but not enough to support normal development. Any child who is the same height as children two or more years behind him in age, or who deviates from a previously normal growth pattern, should be evaluated by a doctor. Testing and evaluating the child will take several months before treatment begins. "In the end," says Dr. Noto, "about 10 percent of the children who are brought to see me for a diagnosis never start treatment because their parents change their minds when they learn about possible side effects, the shot-a-day schedule and a commitment for years."
hGH Discovery
Richard Noto was 8 years old in 1958, the year endocrinologist Maurice Raben, M.D., of New England Medical Center in Boston injected HGH into a dwarf child. The child began to grow normally, and for the next 30 years, thousands of children were injected with hGH derived from the pituitary glands of cadavers. The federal National Hormone and Pituitary (NHP) Program was the only source of supply and there was never enough to satisfy the demand. Moreover, when a child reached a height of 5 feet, the treatment protocol required that HGH be withdrawn and given to another child who had not previously received any. In 1985, this reasoning became moot when science triumphed over supply and demand. Actually, no one knew it at the time, but the natural hormone was killing people from contamination.
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Savion Hill, 4, of Stamford, Conn., was 15-1/4" at birth while his twin brother, Satchel was 1/4" longer. By their first birthday, there was a 5-inch and 10-pound difference between them. After a few visits to endocrinologists at Yale, where mother Melanie Hill says there "was no plan of action," she was steered by her pediatrician to Richard Noto, M.D. Consultation with Lawrence Shapiro, M.D., a specialist in rare genetic diseases at the College, led to a genetic cause for his short stature: a transposition of chromosomes 1 and 8, with a loss of matter on one of the chromosomes. Savion's mom started giving him shots the summer of his third birthday and the dosage has been increased twice. "He's been good about getting the shots right from the beginning," she smiles. |
Between 1963 and 1985, some 7,700 people received human growth hormone made from cadavers by the federal program. Twenty-six of them eventually came down with Creutzfeldt- Jakob Disease (CJD), a fatal neurologic infection comparable to "Mad Cow" disease in cattle. People in other countries who received HGH also got CJD; in France, 89 out of 1,700 people treated with hGH got it, and in England, 38 people out of 1,848. Many became ill decades after treatment. The longest incubation on record is approaching 40 years.
In 1985, Genentech, the first biotechnology company in the U.S. to produce a genetically engineered drug, received FDA approval to market Protropin, a synthetic and therefore safer version of human growth hormone that differed from the natural product by just one amino acid. Within a year, Eli Lilly achieved the perfect match—a 191-amino acid hGH that was physically, chemically and biologically identical to the hormone produced by a human pituitary gland. (There are currently five pharmaceutical companies manufacturing hGH in the U.S.) It seemed that a cure for growth hormone deficiency was as close as the corner drugstore. But now that the supply would be plentiful, critics stalled its possible widespread use with a new issue. Should children who were short, but did not test positive for an hGH deficiency, also be treated? While the question continues to spark debate—something akin to the argument about whether children born deaf should receive cochlear implants—the parents of short children and pediatric endocrinologists continue to decide about treatment on an individual basis. Furthermore, the tools of molecular biology and gene research began turning up evidence that testing negative for HGH deficiency did not make a short child "normal." Scientists have found many other causes of short stature that can benefit from treatment with hGH; they expect to uncover more.
Really Short
"There is something different about these kids who are off the growth chart, growing less than two inches a year, that growth hormone repletes what might be missing. We're talking about the shortest 1.2 percent of children. Without the growth hormone, these boys would end up at 5 feet 2 inches, and girls would measure less than 5 feet," Dr. Noto says. "An HGH deficiency is only one reason why a child is short," he continues. "Now we know that patients who are short have had problems all along in producing HGH, or have defects in their growth hormonal action. Even children of short parents should be evaluated for other conditions. The FDA has approved growth hormone treatment for renal failure, Turner's syndrome, idiopathic short stature and, uh huh, children small for their gestational age who have not caught up by the age of two. As for the kids with kidney failure, hGH happens to also have a medicinal effect that makes them feel much better….
Hidden Effects
"Those who criticize using growth hormone for non-growth hormone deficient children don't understand the problems these children have. As they are growing so slowly, we keep finding more and more things that may be wrong with them. We are not treating children who are normal in terms of their height and growth rate. We are treating children who are short and not growing well. That is why we are performing our latest study—to determine a hormonal basis for why children are born small for their gestational age and do not catch up."
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There are infrequent side effects that seem to affect the children who are more severely deficient than most. "There can be fluid retention, with puffy hands and feet, headaches and sometimes hives from an allergic reaction," says Dr. Noto. "The sudden growth spurt also can promote joint pains, carpal tunnel syndrome and rarely, problems with the hips. Adults who got hGH as children have a slightly greater risk for colon cancer, and a link also has been seen with adults and carpal tunnel syndrome." The FDA approved the use of hGH for adult patients in 1996.
As a pediatrician, of course, Dr. Noto sees only children, but there are adults who've been coming since childhood. His growth hormone patients constitute only 30 percent of his practice, but like his offices, they are everywhere. He sees patients at Munger Pavilion at the College and at Westchester Medical Center, where he is director of the Congenital Hypothyroidism Diagnostic and Treatment Center; Saint Vincent's on Staten Island, Phelps in Sleepy Hollow, Good Samaritan in Suffern, Sound Shore in New Rochelle, Our Lady of Mercy in the Bronx and an office in Middletown, Orange County, N.Y.
"My secretary writes everything down for me so I know where I'm going," Dr. Noto admits. The parents of short children will find him, wherever he is.