Indiana University Research & Creative Activity

A Child's Life

Volume 25 Number 2
Spring 2003

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woman in laboratory
Ora Hirsch Pescovitz
Photo by Office of Visual Media, IU School of Medicine
growth chart

Not Just an Apple a Day

by Julie Sturgeon

When it comes to 21st-century pediatric problems, there are few researchers moreinvolved or thoughtful than Ora Hirsch Pescovitz, executive associate dean for research affairs at the Indiana University School of Medicine. Also director of pediatric endocrinology and diabetology and the Edwin Letzter Professor of Pediatrics, Pescovitz is both clinical and basic investigator—she has published in 150 scientific publications and has served as president of the Society for Pediatric Research, the world's largest pediatric research organization.

Pausing between dean's office meetings, hospital visits, and time on the lab bench, Pescovitz offered her expert take on the causes and consequences of some of thorniest issues affecting childhood health: widespread diabetes, puberty as early as 6 or 7, and growth hormone use.

Growth Hormone.

Since Pescovitz began concentrating on this area 20 years ago, researchers have learned a tremendous amount about growth hormone and achieved major advances in understanding the genetic causes of growth disorders. Prior to 1985, the only way doctors could get their hands on growth hormone involved harvesting human cadavers.

"That obviously restricted the availability," Pescovitz says. "And in fact there were some significant complications associated with its use, which is why it was withdrawn." Some children whose families resorted to this treatment died of a serious neurological disorder closely related to Mad Cow disease. Growth hormone extracted from cadavers was later replaced by genetically engineered versions.

Of course, children with growth disorders don't always respond to growth hormone treatments. "There are still a number of situations where we don't understand why children do not grow," says Pescovitz.

Pescovitz's research in the growth hormone area led her to discover a new polypeptide, present in the hypothalamus and testes, that is related to a factor called growth hormone-releasing hormone. She holds an intellectual property status patent for the find. At present, she and other researchers know this polypeptide plays a role in regulating normal spermatogenesis (sperm formation) and normal hematopoiesis (blood cell formation). She also knows the polypeptide is made by the hypothalamus and has actions in the pituitary gland. The polypeptide's full physiological functions in human adults and children remain to be seen, however: "We're still in the stage of evaluating its role in rodents," Pescovitz says.

The puzzles of growth hormone research are complicated by difficult bioethical questions that parents and pediatricians alike must consider, as the development of growth hormone products continues: What is normal stature, what is genetic short stature, and should we treat children to make them taller just because we can?

"What if you said you could treat every child under the fifth percentile (for height)?" Pescovitz muses. "Then what would you do with everyone in the new fifth percentile after the shift?"

Precocious Puberty.

In recent years, controversy over children's sexual development has hit the newsstand headlines. Is puberty in the 21st century becoming "precocious," and is such early development O.K? While some pediatric endocrinologists have argued that puberty as early as age 7 is normal, Pescovitz remains firm that puberty in a girl younger than age 8 or a boy younger than 9 is clearly precocious.

But she questions whether there is really a "trend" toward early puberty at all.

"Personally, I'm not 100 percent convinced there are significant trends toward earlier onset of puberty, with the exception of children with increased obesity," Pescovitz says. "If you look at the age of onset from the early 1900s to the early 2000s, there is no question the age has decreased," she concedes. "But the latter half of the 20th century isn't exactly clear."

Pescovitz's research in this area has shown that once nutritional gains made in the first half of the 20th century that affected the entire American population are accounted for, no additional triggers appeared to lower the age of puberty.

Such thinking saved one 7-year-old girl whose family practitioner labeled her early development normal; Pescovitz's evaluation revealed a brain tumor causing the early puberty signs.

One consequence of true precocious puberty—if left untreated—is what the medical community calls premature epiphyseal fusion. Although a child may be tall at age 6, the growth plates fuse prematurely, leading to a shorter-than-normal adult who finished achieving height at the same time her peers shot up. "It's a major handicap in adult life to (be a male) under 5'2 or (a female) under 4'8," Pescovitz sympathizes.

Not to mention the psychosocial experiences that precocious children have to endure in gym lockers, public swimming pools, pajama parties, and other common gatherings. In light of these consequences, Pescovitz says treatments like Lupron injections, which reduce the progression of secondary sexual characteristics such as breasts, pubic hair, and menstrual cycles in children, are "miraculous." But she still seeks answers to the basic question: Why do some children enter puberty on the ends of the bell curve? At present, she notes, environmental disrupters have been implicated in affecting human reproductive system functions and the onset of puberty, but far more investigation is needed to determine the impact of chemicals, toxins, diet, and other environmental factors.


Although Pescovitz says she consider each of the disorders she treats serious, diabetes among America's youth alarms her, since it carries the most significant risk for morbidity and, despite major advances toward diagnosis and control, still lacks a cure. In her trademark upbeat fashion, Pescovitz translates this into an opportunity.

"As scientists who are interested in the well-being of children," she says, "we have to look at the disorders that have the greatest affliction, cause the most harm, the most pain, the most suffering, the most short- and long-term morbidity.

"Diabetes is all-encompassing for families," she continues. "I don't really know if I could do what we ask most parents of children with diabetes to do in their lives." Pescovitz ticks off the hurdles: a regimented lifestyle that requires set sleeping hours and diets, the constant risk of blood sugars plummeting too low or skyrocketing, the glucose checks as often as 10 times per day.

Then there's the financial impact that the lobbyist in Pescovitz can't ignore. As president-elect of the Society for Pediatric Research in 2001, Pescovitz testified before the House of Representatives Committee on Appropriations' Subcommittee on Labor, Health and Human Services, and Education. At the time, the combined costs of cardiovascular, endocrine, nutritional, and metabolic diseases were estimated to be $232.1 billion annually, more than 12 times the size of the NIH budget. "Imagine the economic and societal savings that are possible if we invest in preventing these diseases during childhood and adolescence," she pleaded with representatives on Capitol Hill.

That's partially why her team follows more than 1,000 children with diabetes based at the Riley Hospital for Children. Thanks to researchers such as Linda DiMeglio, assistant professor of pediatrics at the IU School of Medicine, Riley stands in the forefront of using insulin pumps in children and toddlers, an advance that introduces more flexibility into the sleeping hours of a diabetic child.

And Pescovitz's husband, Mark, IU professor of surgery, immunology, and microbiology, has spearheaded development of a novel approach to preventing progression of Type 1 diabetes. He is on an IU team that has received a $2 million National Institutes of Health grant to participate in a seven-year Type 1 diabetes trial. If they can halt autoimmunity from destroying the pancreas, the hope is they can stop the disease's progression in children.

"We have advances, but not cures. There is no magic bullet," Pescovitz reiterates. That's why she is delving once again into questions whose answers could prevent more children from streaming into her office to receive a diabetes diagnosis.

"When I started in pediatric endocrinology, we never saw Type II diabetes in children. It was unheard of, and today it's not uncommon," Pescovitz reports. "We know our genes haven't changed in that 20 years, so it means there is something environmental influencing this."

Pescovitz observes that public schools have decreased physical education classes in the budget-cutting crises sweeping their districts, that schools now boast vending machines stocked with potato chips and pop, that meal portions in America have super-sized in the past two decades.

"Just look at the portions people eat today compared to what they eat in other countries or what you put on your plate as a child," she says. "It's a matter of finding which environmental aspects are the bigger triggers. I don't think it's a toxin in the air or water▀it's something we are doing to ourselves and to our children."

Yet Pescovitz shuns the image of herself as Chicken Little, alarming parents over every study, every finding. Instead, she urges education interpreted according to a family's own genetic propensities. For example, families whose members never struggle with obesity or diabetes shouldn't sweat an occasional trip through McDonald's drive-thru. If diabetes is present in your family tree, vigilance is crucial.

"Individualize the risks," Pescovitz says. "The public shouldn't conclude there's too much confusing information, so (they will) ignore it. Just the opposite."

Julie Sturgeon is a freelance journalist in Indianapolis.