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Final Adult Height in Short Healthy Children Treated with Growth Hormone and Gonadotropin-Releasing Hormone Analogs

Unidad de Endocrinologia Pediatrica Hospital de Clinicas Caracas Caracas 1010A, Venezuela

To the editor:

We read with interest the paper by Pasquino et al. (1) entitled "Adult height in short normal girls treated with gonadotropin-releasing hormone analogs and growth hormone."

They treated 12 girls with idiopathic short stature and normal or early puberty with GH and GnRHa and followed them to final height; twelve girls comparable for auxological and laboratory characteristics treated with GH alone served to better evaluate the efficacy of the addition of GnRHa. The mean period of treatment was 4.6 ± 1.7 yr, and patients received GH at a dose of 0.3 mg/kg/week sc 6 days weekly and depot triptorelin at a dose of 100 µg/Kg every 21 days im. The gain in centimeters calculated between pretreatment PAH and adult height was 10 ± 2.9 cm in patients treated with combined therapy and 6.1 ± 4.4 cm in the GH alone group.

These results contrast with those obtained by Balducci et al. (2) and by Lanes and Gunczler (3) in a similar group of patients. In both these studies, combined treatment with GnRHa and GH did not result in an increase in adult stature after 28.1 ± 5.4 and 30.0 ± 5.2 months of treatment, respectively. The number of patients studied and the baseline auxological and laboratory characteristics of children in all three studies were similar, as was the degree of suppression of gonadotropins following the GnRHa; the dose of both GH and GnRHa were adjusted according to weight in all three studies. The GH dose used by Pasquino et al. was, however, larger (0.6 U/Kg/day in the study by Balducci and Lanes vs. almost 1.0 U/Kg/week in the report by Pasquino et al.) and the treatment period was longer, possibly explaining the difference in final height noted in their study.

It would, therefore, seem, based on the results obtained by these three studies, that treating short patients with early or normally timed puberty for significant periods of time, of up to a mean of 2.5 yr, with combined GH and GnRHa therapy does not contribute to increase their final height above their predicted adult height and that treatment for a significantly longer period of time is needed if one is to obtain an improvement of several centimeters in height prognosis.

It is debatable whether subjecting short, but otherwise healthy, children to daily injections of GH and to im administration of an analog every 3–4 weeks, as well as to regular blood tests for many years, is justified to possibly gain several centimeters in final height. The cost of these medications which in most countries has to be covered by their families, the still controversial benefits of GH alone or of GH and GnRHa on the final height of children with idiopathic short stature, as well as the possible side effects of these medications, have to make us consider the cost-benefit of this invasive form of treatment very carefully.

References

1. Pasquino AM, Pucarelli I, Roggini M, Segni M. 2000 Adult height in short girls treated with gonadotropin-releasing hormone analogs and growth hormone. J Clin Endocrinol Metab. 85:619–622.[Abstract/Free Full Text]
2. Balducci R, Toscano V, Mangiantini A, et al. 1995 Adult height in short normal adolescent girls treated with gonadotropin-releasing hormone analog and growth hormone. J Clin Endocrinol Metab. 80:3596–3600.[Abstract]
3. Lanes R, Gunczler P. 1998 Final height after combined growth hormone and gonadotrophin-releasing hormone analogue therapy in short children entering into normally timed puberty. Clin Endocrinol. 49:197–202.[CrossRef][Medline]

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