susan cohen

This just in from MedPage Today. I don't know the details, and it is based on one study, but it echoes the worst fears expressed in "Normal at Any Cost" about the unknown long-term consequences of giving large doses of growth hormone to boost height in healthy kids...

EU REGULATORS QUESTION SAFETY OF HORMONES

By John Gever, Senior Editor, MedPage Today
Published December 10, 2010

The European Medicines Agency (EMA) has announced a safety review of somatotropin products, in light of a new study suggesting a long-term increase in deaths.

"The review will look into all available data on somatropin to reassess the benefit-risk balance of these medicines," the agency said in a statement.

Somatotropin products are recombinant analogues of human growth hormone. The EMA review is focusing on those it has approved as well as others approved by individual European drug authorities.

In the U.S., brand names include Humatrope, Norditropin, Nutropin, Omnitrope, Saizen, Serostim, and Tev-Tropin.

The EMA said French drug regulators had received data from a long-term epidemiological study following patients who had received growth hormone treatments as children. Called SAGhE, the study has collected data on about 7,000 patients who started somatotropin therapy from 1985 to 1996.

"The study results suggest an increased risk of mortality with somatropin therapy compared to the general population. The risk appears to be particularly increased when high doses are used," above those recommended on the products' approved labels, the EMA indicated.

It did not specify the magnitude of the increased risk. The agency said more details would be presented next week at an advisory committee meeting.

Patients in the study had received the drugs for growth hormone deficiency or short stature of unknown cause.

"Based on this observational study alone, the risk cannot be associated with certainty to the growth hormone treatment. The results need to be confirmed and complemented with further analyses," according to the EMA statement.

FDA officials did not respond immediately to a request for comment.

NEED I SAY MORE? EXCELLENT STUDY:

When kids won't grow, doctors keep treating: study
By Genevra Pittman

NEW YORK | Mon Aug 30, 2010 10:24am EDT

NEW YORK (Reuters Health) - When it comes to treating very short kids with growth hormone, some doctors may be just as swayed by their own attitudes about being short as by data, suggests a new study.

The authors found that many doctors would keep treating kids with growth hormone, and often increase their doses, if the kids still didn't grow much after a year on the treatment - especially when the doctors had strong feelings about how being short affects a kid's emotional well-being. The pattern was especially true for very short boys.

"What parents hear as medical advice may be little more than a doctor's own cultural assumptions," Susan Cohen, a journalist and the author of Normal at Any Cost, told Reuters Health. "They seem to think it's such a tragedy to be an extremely short boy."

Most doctors agree that kids who are low on growth hormone - a protein produced by the pituitary gland - should be treated. What's more controversial is what to do with the kids who have normal levels of growth hormone, but are still in the shortest 1.2 percent of kids their age, which qualifies them for treatment under Food and Drug Administration (FDA) guidelines.

Some researchers say these kids should be treated, if only for the chance to avoid the teasing and embarrassment that often comes with being the shortest kid in school; others argue that doctors could be unnecessarily putting kids at risk by treating them - and say that short kids generally turn out okay anyway.

Treatment with growth hormone costs about $22,000 a year, the authors say - which might or might not be covered by insurance. With as many as 500,000 children in the U.S. meeting FDA criteria for the treatment, the drug has a potential market in excess of $10 billion, they add.

Led by Dr. J. B. Silvers of Case Western Reserve University, the study authors surveyed 656 pediatric endocrinologists on how they would treat different hypothetical kids who were very short but didn't have a deficiency in growth hormone or another clear medical condition. For each case, they presented doctors with factors including a kid's gender, current height, projected adult height, and whether or not the family wanted growth hormone treatment. Doctors were asked if they would start that kid on growth hormone.

Then, the researchers gave the doctors more options: one year later, here's how much that kid grew, and here's how the family now feels about growth hormone. Do you stop treatment, continue with the same treatment, or up the dose?

When deciding whether or not to start a child on growth hormone, doctors generally answered in line with current FDA guidelines. But when it came to kids who barely grew after a year on growth hormone, many rejected conventional recommendations, which say treatment should be stopped if a kid grows less than 2 centimeters a year.

When the doctors were presented with a case of a kid who grew 1 cm in a year on growth hormone, 60 percent of them recommended upping the dose, 14 percent thought it should be kept the same, and 26 percent voted for stopping treatment. Doctors were more likely to keep kids on growth hormone when the kids had been shorter to begin with, when families still wanted treatment, and when they themselves believed that being very short takes an emotional toll on kids.

More than 1 in 4 of the doctors also responded that growth hormone has a positive impact on very short kids, even if it ends up having no major effect on their adult heights.

Cohen, who was not involved with the study, called that finding "astounding."

"You have to remember that these are healthy kids," she said. "The long-term risks of giving a child who already has normal levels of growth hormone more are not known. It is an experiment."

Dr. Leona Cuttler, one of the study's authors who is chief of endocrinology and diabetes as well as director of the Center for Child Health & Policy at Rainbow Babies & Children's Hospital in Cleveland, said that collectively, doctors' decisions to continue or to stop medicating kids have a huge impact on growth hormone use overall. "The decisions ... affect so many children at potentially high costs," she told Reuters Health.

Dr. Paul Saenger, a pediatrics professor at the Albert Einstein College of Medicine who was not involved with the study, said that regardless of doctors' own thoughts about being short, in the real world decisions about starting or continuing growth hormone are usually made by the family. In some cases, "the patient just says, 'I don't want it anymore,'" he told Reuters Health. "I think that a lot of it is driven by the interplay of physician and parent and patients, which is very complex."

Both doctors and parents can be influenced by drug companies who push the message that it's a medical problem for a kid to be very short, Cohen said. But, "height is only one thing about us," she cautioned, and research shows that these kids don't grow up with more psychological issues than other kids.

She says the right question to be asking parents of very short kids should be: "how much risk are you willing to take with a healthy child for what may be a few extra inches or may be really nothing at all?"

"Normal at Any Cost" is on Library Journal's list of best books of 2009, in the consumer health section.

The American Library Association's journal Choice has named "Normal at Any Cost" an Academic Outstanding Title in 2009. The honor went to fewer than 700 titles out of some 25,000 published, and is based on the importance of a work as well as the way it's written. Basically, these titles are those recommended as essential for all undergraduate library collections.

We are honored, of course, and hope that it will lead to getting this story into the hands of more undergraduate students -- especially those who will become doctors, but also young people who will be making decisions in the future about their own children.

Today, as well, a successful gene therapy treatment was announced that apparently cured a rare degenerative brain disease in young boys. Nobody can doubt that this is a breakthrough and a triumph. Without spoiling the moment for those families who now have hope for the first time, I can't help thinking about the early celebrations over making dwarfed children grow after decades of medical failure. And I wonder whether it will be years, or decades, before gene therapy is offered for enhancements rather than cures.

It doesn't get any better than the review of "Normal at Any Cost" in Science Times, the New York Times health and science section. Dr. Abigail Zuger in the July 28 edition really got what we were after, which is more than telling the history of height, fascinating as that is. She perceived the story's relevance to the health care debate, and its importance as a cautionary tale for those who intend to become doctors. Here are a few choice quotes:

"...its overtones of both “Gossip Girl” and the Book of Ecclesiastes make it irresistible...""Susan Cohen and Christine Cosgrove, both experienced medical journalists, know how to tell a story, and they could not have picked a better allegorical case study of modern medicine than the story of children’s height...""'Normal at Any Cost' tells its own story with a pace and fluency sadly rare in medical journalism, and like the best in all literature, it illuminates the surrounding landscape as well."

"Normal at Any Cost" has been selected as the July non-fiction book for the Women's Bioethics Project's book club. From their blog:

"Normal at Any Cost would also make a great text for introductory high school or college bioethics courses because it manages to tackle in an accessible and compelling manner a wide range of bioethical issues from the medicalization of social problems, the pharmaceutical industry’s influence on physician education, limits of informed consent, definition of therapeutic v. enhancement interventions, to the appropriate allocation of medical resources (social justice considerations).

Read it this summer."

The New England Journal of Medicine review found Normal at Any Cost "compelling." That was the first sentence. The last was this:

"This book serves as a timely reminder for parents and physicians that caring for children is a sacred trust, and that the short-term and long-term well-being of the children must be considered carefully with every treatment decision for every child, every time."

Hooray! In between,the tone of the review was defensive. My sense was that, since the review was written by two doctors, one wanted to stress the value of the cautionary tale we tell, while the other felt compelled to defend pediatric endocrinologists. We are very happy to see this story move into the hands of physicians and to encourage response and debate of the issues it raises.

My personal quibble with the review is that it makes a book that is based on years of reporting and a lot of thought sound as if it is a screed. Just one example: They say we "suggest" that companies marketed growth hormone off-label. We don't "suggest" it. We report that two manufacturers paid large criminal fines for promoting growth hormone off label -- for use in short,normal kids.

We have sent a brief letter to the editor clarifying that we don't, as the reviewers write, say that those who treat healthy kids for height are "evil." What we do write in the book is that the best and worst motives combined. We acknowledge parents' concerns for their kids, doctors' desires to help, researchers' search for knowledge. But those combined with the fact that there is a whole lot of money to be made. On the other hand, there were few incentives to follow up and investigate the effects of these treatments decades later -- which is why we focus on people who suffered tragic consequences, while acknowledging that others remain glad they were treated.

There are doctors who have been very appreciative of "Normal at Any Cost," including the Danish pediatric endocrinologist who wrote a customer review on Amazon uk saying the book was not only thoughtful but "essential reading" for physicians. And the blogging doc who said it should be on everybody's reading list.

Now, we've been asked to write an essay for The Lancet, which is the major medical journal published in England. Can't wait for the reaction to that.

Been reading about glowing marmosets, drug-producing goats, and speaking mice. Not of the Disney variety, but created in laboratories in the pursuit of science.

There is a whole trangenic world out there -- a research community that takes genes from one organism and inserts them into another. (My favorite link for scientists is the one called: "Have They Made Your Mouse Yet?") Major medical institutions all have trangenic centers churning out chimeras and hybrids in order to study cancer, or Alzheimer's, or the impact of new drugs.

All of this may seem far afield from the story of treating kids for height. I mean, it might be tempting to stick a giraffe gene into an embryo, except that: it wouldn't work, there is no one height gene, and no one wants a kid with a long, long neck, anyway. Also, it would be unethical. Wouldn't it?

The point is that the world of scientific discovery and the ability to manipulate genes is fast-moving. The glowing marmosets, for example, mark the first time that a primate (yeah, like us) has been successfully genetically altered so that it also passed that alteration on to its offspring. (Yeah, some of the babies glow, too.) So, it's worthwhile for us to think about what lines we personally might or might not cross, and not just leave it to the bench scientists and the academic bioethicists.

Among the many stories that "Normal at Any Cost" tells is the way cures for diseases become treatments for disabilities, then for disadvantage, until they are eventually offered to fufill desires for perfection. Especially when there is money to be made. Another story within the story: New medical technologies get used long before anyone knows the long-term consequences.

No, I don't think there will ever be kids born with a giraffe gene or two. Now a kid who glows in the dark... hmmm. You'd never need to buy a nightlight! And, someday she could read "Normal at Any Cost" under the covers without a flashlight.

In her May 30 column for The Times of London’s "Times Online," Anna Moore – who is 5/1" -- wrote about the painful procedure of leg lengthening.

"Twig. Squirt. These were only a couple of my childhood nicknames. I can’t recall feeling hurt by them, though. For some reason the jokes about me being the smallest child of my year usually went over my head — in every sense.

It must have been a very different story for Hajnal Ban, an Australian local politician recently outed as the author of a book entitled God Made me Small, Surgery Made me Tall. Ban had her legs broken and stretched by screws, wires and surgery because she was concerned that her height would hold her back at work. The procedure cost Ban $40,000 in Siberia and ensured that she went from 5ft 1in (155cm — my height) to 5ft 4in."

Moore finds this difficult to comprehend, because her own experience – with friends, boyfriends, and jobs, has been positive. She goes on to talk about the use of human growth hormone. Many anxious parents choose to attempt to boost their children’s heights because of bullying at school. Bullying and teasing are real problems. But Moore quotes David Sandberg, a University of Michigan psychologist who’s spent 20 years working with short children and their parents seeking hGH treatment: “If bullying is the reason behind it, getting hormones is a terrible response. It’s like telling them, ‘Yes, there’s a problem, the bullies have a point. A syringe will fix it’.”

We visited Sandberg when he was working at a growth clinic at the University of Buffalo, a visit we describe in the book. He likes to point out that height is only one aspect of who we are, and that what’s important is the story we tell about ourselves. Sandberg also wrote this comment to The Times article, which was published online:

"I recommend the recently published book Normal at Any Cost: Tall Girls, Short Boys, and the Medical Industry's Quest to Manipulate Height (by Christine Cosgrove, Susan Cohen) which is both well written and based on extensive research. For those interested in the topic, it's a page-turner."

The feedback we've gotten about "Normal at Any Cost" has been fascinating, and often personal.

There was the woman who remembers her parents arguing over whether to stunt her growth. Her father won the argument, by begging her mother to please tell him she wasn't doing this so their daughter would end up cute and cuddly for some football player. Throughout her childhood, this woman remembers her father saying things such as: good things come in small packages, but better things come in taller packages. She is a 6'2" attorney, married, and there was a picture in the Chronicle of her pole dancing -- upside down with her long, long legs fully exposed. She is grateful she wasn't treated.

There was the 90-year-old woman who wrote the paper that she had always liked herself, and she was also over six feet.

There were women who had been treated, and said they were grateful. Though one wrote that she'd had two bouts of breast cancer and would never know whether or not the estrogen pills had been to blame. She still prefered to go through life at 5'11" than taller.

We also got a letter from a man who belongs to a group called the National Association of Short Statured Adults, who said this was a book he'd been waiting to read for quite a while. He wrote: "Part of what we do at NOSSA is try to educate people about issues of heightism and of course one of our platforms is the use of HGH in children. Genentech, Pfizer and Eli Lilly promote the idea that being a short male isn't a very good thing, while we say otherwise. It's not being short that is bad, it is how us short people are treated that is the real atrocity. Maybe these phamaceutical companies can come up with a drug to treat the part of the brain that contributes to the thought that someone is superior to another based on a physical trait.
Now, wouldn't that be a money maker? LOL"