GH was isolated in animals in 1945 and in humans in 1956. The first GH treatment took place in 1957, when Maurice Raben of Tufts University Medical School used GH to make a short boy grow six times as fast as before the treatment.
During the initial decades, natural GH was extracted from donated cadavers' tissues. There was a major scarcity of the product, and the treatment was extremely expensive. In 1971 GH was finally synthesized in laboratory. This discovery could have represented a major boom in the treatment, but the Food and Drug Administration (FDA) required more than a decade of studies and tests before authorizing the sale of synthetic GH.
In October 1985, synthetic GH was finally approved by the FDA. Since then, several brands of synthetic GH were introduced in the market. Thanks to increased competition, GH prices diminished drastically during the last decade. Now the treatment can be afforded by average income families. And if the patient has proven GH deficiency, health insurance might sponsor the treatment.
Complications and Risks
After over 40 years of treatment of children with GH deficiency, no significant metabolic, visceral or immunological side-effects have been found. But some rare side effects should be mentioned. A few patients develop hypothyroidism or insulin resistance. There is also a slight increase in slipped growth plates.
The sole serious doubt concerns 18 cases of leukemia reported in GH-deficient (non-Down syndrome) patients 10 to 23 year of age who were treated with GH. This number is calculated to be 1.5 times the rate for healthy individuals, but the comparison is misleading. In order to attribute GH for the increased incidence of leukemia one would need to compare it with the incidence observed in GH-deficient untreated individuals. Unfortunately there is no such data. It is not know whether the increased incidence of leukemia is related to GH-deficiency itself, GH treatment, or neither. Regardless, it is important to notice that the incidence of leukemia is not high: it affects one patient in every 24.000 patient-years1.
The Controversy over Growth Hormone Deficiency Tests
Unfortunately, growth hormone deficiency is far from being an easy diagnosis. The human body continually manufactures GH throughout the day, and the pituitary does it in surges. So there are dramatic ups and downs in our blood concentration of GH. The largest surge of GH occurs at night, one or two hours after sleep. During the day, our blood concentration of GH changes every three hours.
Testing for growth hormone deficiency is indicated only when all other possibilities for slow growth have been ruled out. The available tests require several blood samples and are not very trustworthy. The patient takes an injection of a substance known to stimulate GH (such as clonidine, L.dopa, ornithine, glucagon, etc.) and blood samples are taken several times to measure the rise in GH concentration. The patient will be considered GH-deficient if s/he does not secrete GH at an appropriate level. Most laboratories will perform this test in 3 hours.
In the U.S., most health care professionals would not recommend GH therapy unless the individual is growth hormone deficient. But several practicing doctors don't think too much of the GH deficiency tests. They consider them complicated, uncomfortable and unreliable. A patient might test positive with substance A and negative with substance B.
According to Schulman and Sweitzer, "in the uncertainty over testing, some experts in Europe, especially, but also a minority in the U.S. finally said in so many words: So much for GH tests. Let's try short kids on GH and if they grow they must need it"2.
Growth Hormone Treatment in Down Syndrome (DS)
It is known that children with Down syndrome have a reduced growth pattern. According to Dr. Siegfried Pueschel, the expected height of the adult male with Down syndrome varies from 4 feet, 8 inches (1.42 meter) to 5 feet, 5 inches (1.65 meter). The height of the adult female is approximately between 4 feet, 5 inches (1.34 meter) and 5 feet, 3 inches (1.60 meter)3.
All children with DS would be potential patients for GH therapy if it was not for the fact that several of them test negative in some GH deficiency tests. This is strange because most people with DS have normal growth as a response to GH therapy. Experts like Dr. Castells believe that when children with DS have a good response to GH therapy it might indicate that they need it:
"...What does it matter what the testing shows? If growth velocity accelerates with recombinant GH treatment, they must have insufficient GH production. It has been suggested that a trial test of GH for a period of six months or one year may be important to determine if a deficiency of GH is present. Our data on recombinant GH treatment showed very clearly that GH is effective in treating short stature in Down's syndrome."4The first GH treatments for people with Down syndrome started in the late eighties. The results of these studies are very promising. Most of the treated children have the benefit of normalized head circumference and increased height.
I am the father of Bibiana, a girl with DS. My daughter was 2 year and 10 months old when she was started on GH. At the beginning of the treatment she was 82 cm tall. Her height was normal for children with DS, but extremely short compared to normal children. In fact, she was 13 cm (5.1 inches) below the 50th percentile curve for normal girls.
Bibiana grew up 32 cm during 3 year and 8 months of GH therapy. Now she is a girl of near-average height. She is only 4 cm (1.6 inch) below the 50th percentile curve for normal girls.
I also noticed positive results in head growth, greater muscle strength and decreased fat percentage. There were also some subjective benefits which are difficult to report.
I am not a doctor and this article should not be considered medical advice.
Understanding Growth Hormone by Schulman and Sweitzer's is an excellent introduction for parents. This book is about GH treatment in general. It does not have information about DS.
Doctors and health care professionals might be interested in reading Growth hormone treatment in Down syndrome, published by John Wiley & Sons, New York, 1993, edited by S. Castells and K. E. Wisniewski. This book reports the results of the International Conference on Growth Hormone Treatment in Down's Syndrome. This conference took place in New York on October 1992, and was attended by 125 people. The book includes several papers presented during the conference, a summary of the discussions and two parents testimonials.
|Revised: July 3, 2001.|