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GH and GnRHa Therapy for Short Stature« Back to Volume 23, Issue 3, November 2007 - Table of Contents This study assessed the final height (FH) and adverse effects of combined growth hormone (GH) and gonadotrin-releasing hormone agonist (GnRHa) treatment in short adolescents with relatively early puberty. Van Gool et al studied 32 adolescents born small for gestational age or with normal birth size, in Tanner stage 2-3, with age and bone age of <12 years for girls and <13 years for boys. Subjects had a height SDS of either <−2 SDS or between −1 and −2 SDS and a predicted adult height (PAH) of <−2 SDS. Patients were randomly allocated to receive GH and GnRHa (n=17) or no treatment (n=15) for 3 years; FH was determined at the age of 18 years or older in girls and 19 years or older in boys. The FH was not different between treated and untreated subjects. However, treated patients had a greater height gain (FH minus PAH at the beginning of treatment) than the untreated patients (4.4 ± 4.9 vs. −0.5 ± 6.4 cm, respectively; p<0.05). Of the treated and control subjects, 76 (60%) had a FH that was greater than the PAH. A significant gain in PAH of 9.3 cm after 3 years of combined therapy was noted in the treated group compared with a 1.2 cm gain in the untreated group. However, during the period of time between treatment discontinuation and FH, 50% of the PAH gain during treatment was lost, resulting in a mean height gain of 4.9 cm (range of −4 to 12.3 cm). Although, treatment did not seem to affect BMI or hip bone mineral density (BMD), the mean lumbar spine BMD and the bone mineral apparent density (BMAD) tended to be lower in treated males. The authors concluded that given the expensive and intensive treatment regimen and the modest height gain attained, as well as the possible adverse effect of therapy on bone mineralization in males, GH and GnRHa treatment can not be considered for routine treatment of short stature in children entering into early puberty. However, treatment could be considered in children, particularly females, with extremely low adult height prediction, early pubertal onset, and considerable psychosocial problems. Van Gool SA, Kamp GA, Visser-van Balen H, et al. Final height outcome after three years of growth hormone and gonadotropin-releasing hormone agonist treatment in short adolescents with relatively early puberty. J Clin Endocrinol Metab. 2007;92:1402-8. Editor’s CommentThe final height of short children entering into puberty at an early age may be quite limited due to premature epiphyseal fusion induced by the early secretion of gonadal steroids. Treatment with GnRHa to delay or halt pubertal onset has been attempted in this group of patients, but the growth velocity of some of them has been noted to decrease to levels below the normal pubertal velocity, possibly as a result of accelerated growth plate senescence induced by previous estrogen exposure. GH treatment in short children with idiopathic short stature or born small for gestational age has been shown to increase final height, particularly if begun at an early age. Combined GH and GnRHa therapy in short children entering into puberty at an early age has been attempted in several studies with a height gain of between 1 to 10 cm and the effectiveness of this form of therapy remains controversial. Treatment response has been generally analyzed by comparing treated patients to patients treated only with GH, to an untreated group not randomly assigned, or to no controls at all; most studies included only females. Treatment of short, but otherwise healthy children with medications that require parenteral administration, close supervision, frequent laboratory testing, and are extremely expensive, should only be considered if the height gain obtained is significant and if the medications are proven to be safe. As clearly stated by the authors, the costs of this form of therapy seem to overshadow the modest benefit in height gain obtained; therefore this form of therapy should not be recommended for routine use in short but otherwise healthy patients who enter into puberty at an early age. Roberto Lanes, MD References - (linked to
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Volume 24 Number 1
May 2008
www.GGHjournal.com
ISSN 1932-9032
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