Study of Luteinizing Hormone-Releasing Hormone Analog (LHRHa) in Pubertal Patients With Extreme Short Stature
Study of Luteinizing Hormone-Releasing Hormone Analog (LHRHa) in Pubertal Patients With Extreme Short Stature
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 score.

 Unfused carpal and phalangeal epiphyses by bone age x-ray.