Children with extreme short stature (height) and their families often experience significant
psychological stress related to concerns about adult height. In addition, short stature
often results in life-long emotional, social, and physical obstacles to the affected person.
Normal growth occurs in two phases. The first phase, known as childhood growth, occurs
below the age of 10. The second phase of growth, teen-age or adolescent growth, begins
between the ages of 10 and 15. In addition, puberty marks the time when the bone's growth
plates (epiphysis) begin to close, initiating the completion of linear growth (height).
Some children suffer from a condition called precocious puberty, meaning that puberty begins
at a younger age than normal. The development of medications known as synthetic LHRH
analogs have provided a method to delay puberty and treat these patients.
LHRHa (deslorelin) is a hormone created to act like naturally occurring LHRH. It been used
in patient's diagnosed with precocious (early onset) puberty. The drugs were able to
regress patient's clinical signs of puberty, decrease the levels of adult sex hormones
produced, and slow the rate of bone aging.
Children with extreme short stature and their families frequently experience significant
psychological stress related to concerns about adult height. Additionally, extreme short
stature often presents life-long emotional, social, and physical obstacles to the affected
individual. The onset of puberty in such patients presents a critical management problem
because puberty initiates the process of epiphyseal closure that terminates linear growth.
Until recently, there was no way to delay the onset of puberty in such patients. The
development of synthetic LHRH analogs, however, has provided such a method. Administration
of such analogs to children with precocious puberty caused a regression of their clinical
signs of puberty, a decrease in their gonadotropins and sex steroids, and a slowing of the
rate of bone age advancement.
We propose to treat pubertal children with extreme short stature with a long-acting analog
of luteinizing hormone-releasing hormone (D-Trp6-Pro9-NEt-LHRHa). The goal of LHRHa
treatment in these children is to halt the normal progression into puberty and thereby delay
epiphyseal fusion. We postulate that delay of puberty will prolong pre-pubertal growth
prior to the pubertal spurt and subsequent epiphyseal fusion, and thus will enhance ultimate
height. This study will test this hypothesis through a double-blind, randomized comparison
of the effect of LHRHa and placebo on final adult height. Patients will be treated with
LHRHa or placebo for 4 years, and will then be followed until they have completed puberty
and have stopped growing.
Patients with extreme short stature will qualify for inclusion under this protocol if they
meet the following criteria:
Age 9 through 15.99 years at the start of treatment.
Tanner II-V pubertal development.
Height at least 2.25 S.D. below the median for chronologic age at the time of pubertal
onset, or a predicted adult height at least 2.25 S.D. below median adult height.
The height criterion must be met before study entry, but not necessarily on the actual
date the patient starts to take the protocol injections because advancing puberty may
cause an increase in height velocity that temporarily increases height standard deviation
Unfused carpal and phalangeal epiphyses by bone age x-ray.