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Final Height Outcome after Three Years of Growth Hormone and Gonadotropin-Releasing Hormone Agonist Treatment in Short Adolescents with Relatively Early Puberty

Department of Pediatrics (S.A.v.G., J.M.W.), Leiden University Medical Center, 2333 ZA Leiden, The Netherlands; Tergooi Hospital (G.A.K.), 1250 CA Blaricum, The Netherlands; Department of Developmental Psychology (H.V.-v.B.), Utrecht University, 3508 TA Utrecht, The Netherlands; Subdivision Endocrinology (D.M., S.M.P.F.d.M.K.-S.), Erasmus University Medical Center/Sophia Children’s Hospital, 3015 GJ Rotterdam, The Netherlands; Catharina Hospital (J.J.J.W.), 5623 EJ Eindhoven, The Netherlands; University Medical Center Utrecht/Wilhelmina Children’s Hospital (M.J., L.V.-W., H.V.-v.B.), 3508 AB Utrecht, The Netherlands; Departments of Pediatrics (H.A.D.-v.d.W.) and Radiology (J.C.R.), VU University Medical Center, 1007 MB Amsterdam, The Netherlands; and Diagnostic Center Eindhoven (G.L.), 5611 NE Eindhoven, The Netherlands

Address all correspondence and requests for reprints to: Dr. S. A. van Gool, Leiden University Medical Center, Department of Pediatrics, J6-S, Albinusdreef 2, 2333 ZA Leiden, The Netherlands. E-mail: s.van_gool{at}lumc.nl.

Objective: Our objective was to assess final height (FH) and adverse effects of combined GH and GnRH agonist (GnRHa) treatment in short adolescents born small for gestational age or with normal birth size (idiopathic short stature).

Design and Patients: Thirty-two adolescents with Tanner stage 2–3, age and bone age (BA) less than 12 yr for girls or less than 13 yr for boys, height SD score (SDS) less than –2.0 SDS or between –1.0 and –2.0 SDS plus a predicted adult height (PAH₀) less than –2.0 SDS were randomly allocated to receive GH plus GnRHa (n = 17) or no treatment (n = 15) for 3 yr. FH was assessed at the age of 18 yr or older in girls or 19 yr or older in boys.

Results: FH was not different between treatment and control groups. Treated children had a larger height gain (FH – PAH₀) than controls: 4.4 (4.9) and –0.5 (6.4) cm, respectively (P < 0.05). FH was higher than PAH₀ in 76 and 60% of treated and control subjects, respectively. During follow-up, 50% of the predicted height gain at treatment withdrawal was lost, resulting in a mean gain of 4.9 cm (range, –4.0 to 12.3 cm) compared with controls. Treatment did not affect body mass index or hip bone mineral density. Mean lumbar spine bone mineral density and bone mineral apparent density tended to be lower in treated boys, albeit statistically not significant.

Conclusion: Given the expensive and intensive treatment regimen, its modest height gain results, and the possible adverse effect on peak bone mineralization in males, GH plus GnRHa cannot be considered routine treatment for children with idiopathic short stature or persistent short stature after being born small for gestational age.