Effectiveness of the combined recombinant human growth hormone and gonadotropin-releasing hormone analog therapy in pubertal patients with short stature due to SHOX deficiency.
BACKGROUND
Isolated heterozygous SHOX defects are the most frequent monogenic cause of short stature, and combined therapy with recombinant human GH (rhGH) and GnRH analog (GnRHa) in pubertal patients has been suggested, but there are no data on final height.


OBJECTIVE
The aim of the study was to analyze adult height after rhGH and GnRHa therapy in patients with SHOX haploinsufficiency.


METHODS
Ten peripubertal patients with isolated SHOX defects participated in the study.


METHODS
Five patients were followed without treatment, and five were treated with rhGH (50 mug/kg/d) and depot leuprolide acetate (3.75 mg/month).


METHODS
Adult height sd score (SDS) was measured.


RESULTS
All patients followed without treatment had marked downward growth shift during puberty (height SDS, -1.2 +/- 0.7 at 11.4 +/- 1.4 yr; adult height SDS, -2.5 +/- 0.5). Conversely, four of five patients treated with rhGH for 2 to 4.9 yr associated to GnRHa for 1.4 to 5.8 yr improved their height SDS from -2.3 +/- 1.3 at 11.8 +/- 2.1 yr to a final height SDS of -1.7 +/- 1.6. The difference between the mean height SDS at the first evaluation and final height SDS was statistically significant in nontreated vs. treated patients (mean height SDS change, -1.2 +/- 0.4 vs. 0.6 +/- 0.4, respectively; P <0.001).


CONCLUSIONS
A gain in adult height of patients with isolated SHOX defects treated with combined rhGH and GnRHa therapy was demonstrated for the first time, supporting this treatment for children with SHOX defects who have just started puberty to avoid the loss of growth potential observed in these patients during puberty.
Scalco
Renata C
RC
Unidade de Endocrinologia do Desenvolvimento, Laboratorio de Hormonios e Genetica Molecular LIM/42, Disciplina de Endocrinologia, Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo, 05403-000 Sao Paulo, Brazil.
Melo
Suzana S J
SS
Pugliese-Pires
Patricia N
PN
Funari
Mariana F A
MF
Nishi
Mirian Y
MY
Arnhold
Ivo J P
IJ
Mendonca
Berenice B
BB
Jorge
Alexander A L
AA
D000293:Adolescent; D001827:Body Height / Q000187:drug effects / Q000235:genetics; D002648:Child; D018389:Codon, Nonsense; D004334:Drug Administration Schedule; D004338:Drug Combinations; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006130:Growth Disorders / Q000188:drug therapy* / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics*; D019382:Human Growth Hormone / Q000008:administration & dosage*; D006801:Humans; D016729:Leuprolide / Q000008:administration & dosage*; D008297:Male; D011627:Puberty / Q000187:drug effects*; D011994:Recombinant Proteins / Q000008:administration & dosage; D000074122:Short Stature Homeobox Protein; D016896:Treatment Outcome
D018389:Codon, Nonsense; D004338:Drug Combinations; D018398:Homeodomain Proteins; D011994:Recombinant Proteins; C106071:SHOX protein, human; D000074122:Short Stature Homeobox Protein; D019382:Human Growth Hormone; D007987:Gonadotropin-Releasing Hormone; D016729:Leuprolide