ADDRESSING THE CONCERNS ABOUT RECENT DEATHS AND THE RELATIONSHIP TO GROWTH HORMONE

ADDRESSING THE CONCERNS ABOUT DEATHS AND THE RELATIONSHIP TO GROWTH HORMONE

Janalee Heinemann, Executive Director

I have been getting emails and calls of concern about a report of seven deaths worldwide of children who were on growth hormone. In the interest of our membership, I want to keep all parents and care providers updated with the latest on this issue. As always, I am committed to sharing with you honest and straightforward information. Having been very involved with this issue, I want to assure you that while there may be reason for concern, I believe there is no reason to panic.

We have been sending information on deaths known to us at PWSA (USA) to our medical boards and Dr. Martin Ritzen from Sweden. (For our newer members, Dr. Ritzen is considered one of the most renowned researchers in the world on growth hormone and PWS.) At PWSA (USA) we have followed 58 deaths from 2001 to March 2003. Of those, there is conjecture that one MAY be related to growth hormone treatment which is included in the two deaths reported from the USA. The other five deaths we have heard about were not from the USA. To keep this in perspective, we also know hundreds of children with PWS who have been placed on growth hormone (GH) without reported adverse effects and are doing well.

The following is a short summary of the issues, as I know them. Please keep in mind, I am not a medical physician, and PWSA (USA) is not making a formal statement. I have however asked four key physicians to review what I have written, and all agree that I have included all of the information available at this time. Dr Martin Ritzen responded, “It is well written and brings up the important note to all parents that respiratory problems may be a serious concern, with or without GH treatment.”

While it is unclear what relationship growth hormone had, if any, with the seven deaths worldwide, keep in mind that almost all of the other deaths reported to us were of children and adults with PWS who were not on GH. These events have heightened our awareness that our children are at risk in general due to respiratory issues.

Respiratory issues combined with obesity appear to be a major risk factor for our children with PWS (See our article on this topic that was in the March-April 2003 edition of The Gathered View.) and the main risk factor identified in starting growth hormone (GH). It has recently come to light that there may be a slight risk in starting a child that is very obese and already having apnea problems on growth hormone (the deaths were early in the start of the treatment) with the possibility of slightly increasing the tonsils to the point of obstruction and apnea.

The safest course would be to perform a sleep study test prior to receiving growth hormone if there is ANY respiratory concerns – and then repeating the study after a few months of being on growth hormone. (This advisory/ indication will come out officially in the near future.) Of course, many of our children should have a sleep study test with or without GH since we are finding that many have some form of obstructive respiratory problem. If obstructive apnea problems are added to the lack of central hypoventilation/apnea response, then many of our children and adults are at risk with or without GH treatment. (Central hypoventilation is a disorder of decreased breathing rate or depth particularly during sleep.) In the case of a child who is obese with apnea, they should not only have a sleep study test, but also see an ENT to consider having tonsils and adenoids removed.

A child with PWS should begin a weight loss program prior to starting GH since obesity is a risk factor. The dilemma lays in the fact that weight loss is easier while on GH treatment, so waiting to start GH delays the success of a weight loss program. If is important for parents to understand that GH is only an adjunct to diet and other external controls.

Based on the above, Pfizer Inc. (formally Pharmacia) changed the labeling to include the following contraindication and warning,

"CONTRAINDICATIONS: Growth hormone is contraindicated in patients with Prader-Willi syndrome who are severely obese or have severe respiratory impairment.
WARNINGS: There have been reports of fatalities with the use of growth hormone in pediatric patients with Prader-Willi syndrome who had one or more of the following risk factors: severe obesity, history of respiratory impairment or sleep apnea, or unidentified respiratory infection. Male patients with one or more of these risk factors may be at increased risk. Patients with Prader-Willi syndrome should be evaluated for upper airway obstruction before initiation of treatment with growth hormone. If during treatment with growth hormone patients show signs of upper airway obstruction (including onset of or increased snoring), treatment should be interrupted. All patients with Prader-Willi syndrome should be evaluated for sleep apnea and monitored if sleep apnea is suspected. All patients with Prader-Willi syndrome should have effective weight control and be monitored for signs of respiratory infections, which should be diagnosed as early as possible and treated aggressively.”

Recent data indicates that GH actually improves respiratory function in PWS. One study results states: “Peak flow rate, percentage vital capacity, and forced expiratory flow rate improved and number of hypopnea and apnea events and duration of apnea events trended toward improvement after GH intervention." Effects of Growth Hormone on Pulmonary Function, Sleep Quality, Behavior, Cognition, Growth Velocity, Body Composition, and Resting Energy Expenditure in Prader-Willi Syndrome (2003) Haqq AM, Stadler DD, Jackson RH, Rosenfeld RG, Purnell JQ, Lafranchi SH - Portland, Oregon. The Journal of Clinical Endocrinology & Metabolism 88(5):2206-2212.

In addition Dr. Martin Ritzen recently wrote to me, “I might add that we did a similar study in Sweden before and after GH, and found improved respiratory response (with GH) Lindgren AC, Hellström LG, Ritzén EM, Milerad J 1999 Growth hormone treatment increases CO(2)-response, ventilation and central respiratory drive in children with Prader-Willi syndrome. Eur J Pediatr 158:936-940.

PWSA (USA) would like to perform a more comprehensive study of the deaths of those with PWS who are reported to us. Our goal would be to apply for funding and hire a medical student or fellow to help us to analyze data including the study of autopsies, and get more detailed information on the medical history of the child or adult with PWS who died. As the only national membership organization for Prader-Willi syndrome, and with a bereavement program in place, we have the data on deaths -- but do not have the time to perform an adequate review.

My greatest concern is that we may regress to the days when endocrinologists were reluctant to put a child with PWS on GH. So much positive about GH has occurred beyond height -- such as improved body composition, increased muscle function, and increased energy. The fact that we have recently put our thirty -year-old son, Matt, on the PWS adult growth hormone study is the best example of my continuing confidence in the important role that growth hormone has in providing quality of life and improved health in our children and adults with PWS. (Matt was on GH from fourteen years of age to nineteen and then off ten years prior to the current adult study.) As I write, Matt has lost approximately thirty pounds in three months! Is this all due to initiating small doses of GH? We think it is due to a combination of GH and a new exercise routine of walking a school track 4-6 laps daily. But, we know from experience, that prior to the growth hormone, he could walk the track all day and not have that kind of success!

At this time, there is no recommendation to discontinue GH therapy in PWS. The multiple beneficial effects of GH therapy in children with PWS are well documented. The company which has approved labeling for GH therapy in children with PWS, Pfizer (Pharmacia), and the Lawson-Wilkins Pediatric Endocrine Society, the major pediatric endocrine group in the U.S., have both reviewed the available information and are expected to issue summary statements. PWSA USA will keep its membership informed of this progress.

We will keep our members updated with as much objective information as we can for the health and well being of all of our children with Prader-Willi syndrome. Meanwhile, those who have specific questions regarding GH therapy in PWS are advised to discuss them with their physician. If your physician has additional questions, they can contact Pfizer Medical Information at 800-323-4204.

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