Combined treatment with growth hormone and gonadotropin-releasing hormone analogues in children with isolated growth hormone deficiency.

In subjects with an isolated GH deficiency the inhibition of puberty by GnRH-analogue administration may be attempted to delay the onset, or to prolong the duration, of pubertal maturation in order to improve final height. We report our experience on the matter in 10 subjects (6M, 4F) suffering from isolated GH deficiency with a chronological age ranging from 6.5 to 10.6 years at diagnosis. After a period of 1-5.1 years of GH treatment, GnRH-analogues (long-acting D-Trp-6-GnRH) were added to GH for 12 months, when six subjects were still prepubertal and four in early puberty. During combined therapy, a regression in pubertal development was shown in three out of four children in early puberty, while serum testosterone or estradiol decreased. Height velocity decreased (from 5.23 +/- 1.49 (mean +/- SD) to 4.12 +/- 0.67 cm/year; p < 0.02), whereas height SD scores for bone age increased (from -0.75 +/- 0.42 to -0.47 +/- 0.55; p < 0.02). During the year of combined therapy, bone age increased only 0.57 +/- 0.27 years. The values for predicted height (TW2 and Bayley-Pinneau method) after combined treatment were also higher than those after treatment with GH alone (p < 0.02 and p < 0.001, respectively). Our preliminary data showed that the addition of GnRH-analogues to GH in subjects with isolated GH deficiency reduces the effect of GH on height velocity, but determines an improvement in statural prognosis, although a proper answer will not be obtained until final height has been achieved.