Correspondence

Is Luteinizing Hormone–Releasing Hormone Agonist Justified in Short Adolescents?

N Engl J Med 2003; 349:192-193July 10, 2003

Article

To the Editor:

In their article on the effects of luteinizing hormone–releasing hormone agonist in the treatment of adolescents with short stature, Yanovski et al. (March 6 issue)1 predict that the deficit in bone mineral density will not be recovered, as has been shown in other interruptions of puberty and in constitutional delay.2 Constitutional delay, however, is generally regarded as a developmental variation. Data on bone density after constitutional delay are sparse and contradictory; data from the cited series2 conflict with data from two others,3,4 although all three were appropriately designed. Stating that a deficit in bone mineral density follows constitutional delay is premature.

In her editorial, Lee5 proposes indications for the diagnostic referral of short children to pediatric endocrinologists: a height below the 3rd percentile, stature that is not commensurate with the parents' heights, or a growth rate below the 25th percentile. The first has significant resource implications, requiring 120,000 consultations annually in the United States. More than 95 percent of short children will be found not to have disease; rather, they will be found to have stature that is appropriate for their genetic potential, constitutional delay, or both.6 As Lee states, to detect a pathologic process, primary physicians must monitor growth rates and consider the parents' heights for all children. In most cases, investigations and referral are not necessary.7

Shayne P. Taback, M.D.
Elizabeth A.C. Sellers, M.D.
Heather J. Dean, M.D.
Winnipeg Children's Hospital, Winnipeg, MB R3E 0Z2, Canada
tabacksp@cc.umanitoba.ca

7 References

1. 1

   Yanovski JA, Rose SR, Municchi G, et al. Treatment with a luteinizing hormone-releasing hormone agonist in adolescents with short stature. N Engl J Med 2003;348:908-917
   Full Text | Web of Science | Medline

2. 2

   Finkelstein JS, Neer RM, Biller BM, Crawford JD, Klibanski A. Osteopenia in men with a history of delayed puberty. N Engl J Med 1992;326:600-604
   Full Text | Web of Science | Medline

3. 3

   Moore B, Briody J, Cowell CT, Mobbs E. Does maturational delay affect bone mineral density (BMD)? Horm Res 1997;48:Suppl 2:91-91 abstract.
   

4. 4

   Bertelloni S, Baroncelli GI, Ferdeghini M, Perri G, Saggese G. Normal volumetric bone mineral density and bone turnover in young men with histories of constitutional delay of puberty. J Clin Endocrinol Metab 1998;83:4280-4283
   CrossRef | Web of Science | Medline

5. 5

   Lee MM. Is treatment with a luteinizing hormone-releasing hormone agonist justified in short adolescents? N Engl J Med 2003;348:942-945
   Full Text | Web of Science | Medline

6. 6

   Voss LD, Mulligan J, Betts PR, Wilkin TJ. Poor growth in school entrants as an index of organic disease. BMJ 1992;305:1400-1402
   CrossRef | Web of Science | Medline

7. 7

   Taback SP, Dean HJ. Short stature. In: Moyer VA, ed. Evidence-based pediatrics and child health. London: BMJ Books, 2000:334-40.
   

Author/Editor Response

Height that falls below the 3rd percentile is a well-established definition of short stature and has been a standard criterion in pediatrics for determining the need for further evaluation.1,2 Although the majority of children with a height below the 3rd percentile (more than 2 SD below the mean) have no organic disease, community screening studies have identified a pathologic process in 12 to 18 percent of these children.3,4 Revision of the criteria for referral of children with short stature — such as the change from the 3rd to the 0.4th percentile, proposed by some clinicians in the United Kingdom — would have resulted in an inability to identify two of the eight cases of silent disease detected in the Wessex Growth Study5 and would miss a percentage of children with growth hormone deficiency and other organic causes of short stature whose heights fall between these two percentiles. Thus, the use of more stringent criteria will decrease the number of unnecessary referrals but may result in the exclusion of children with disease from needed evaluation and therapy.

Mary M. Lee, M.D.
Duke University Medical Center, Durham, NC 27710
lee00140@mc.duke.edu

5 References

1. 1

   Plotnick L. Growth, growth hormone, and pituitary disorders. In: McMillan J, DeAngelis C, Feigin R, Warshaw J, eds. Oski's pediatrics: principles and practice. 3rd ed. Philadelphia: Lippincott–Raven, 1999:1776-87.
   

2. 2

   Schaff-Blass E, Burstein S, Rosenfield RL. Advances in diagnosis and treatment of short stature, with special reference to the role of growth hormone. J Pediatr 1984;104:801-813
   CrossRef | Web of Science | Medline

3. 3

   Lindsay R, Feldkamp M, Harris D, Robertson J, Rallison M. Utah Growth Study: growth standards and the prevalence of growth hormone deficiency. J Pediatr 1994;125:29-35
   CrossRef | Web of Science | Medline

4. 4

   Shu SG, Chen YD, Chi CS. Clinical evaluation of short children referred by school screening: an analysis of 655 children. Acta Paediatr Taiwan 2002;43:340-344
   Medline

5. 5

   Voss LD. Changing practice in growth monitoring. BMJ 1999;318:344-345
   CrossRef | Web of Science | Medline