Supplementary Material for: Growth Hormone Dose-Dependent Pubertal Growth: A Randomized Trial in Short Children with Low Growth Hormone Secretion

<b><i>Background/Aims:</i></b> Growth hormone (GH) treatment regimens do not account for the pubertal increase in endogenous GH secretion. This study assessed whether increasing the GH dose and/or frequency of administration improves pubertal height gain and adult height (AH) in children with low GH secretion during stimulation tests, i.e. idiopathic isolated GH deficiency. <b><i>Methods:</i></b> A multicenter, randomized, clinical trial (No. 88-177) followed 111 children (96 boys) at study start from onset of puberty to AH who had received GH 33 µg/kg/day for ≥1 year. They were randomized to receive 67 µg/kg/day (GH<sup>67</sup>) given as one (GH<sup>67×1</sup>; n = 35) or two daily injections (GH<sup>33×2</sup>; n = 36), or to remain on a single 33 µg/kg/day dose (GH<sup>33×1</sup>; n = 40). Growth was assessed as height<sub>SDS</sub>gain for prepubertal, pubertal and total periods, as well as AH<sub>SDS</sub> versus the population and the midparental height. <b><i>Results:</i></b> Pubertal height<sub>SDS</sub>gain was greater for patients receiving a high dose (GH<sup>67</sup>, 0.73) than a low dose (GH<sup>33×1</sup>, 0.41, p < 0.05). AH<sub>SDS</sub> was greater on GH<sup>67</sup> (GH<sup>67×1</sup>, -0.84; GH<sup>33×2</sup>, -0.83) than GH<sup>33</sup> (-1.25, p < 0.05), and height<sub>SDS</sub>gain was greater on GH<sup>67</sup> than GH<sup>33</sup> (2.04 and 1.56, respectively; p < 0.01). All groups reached their target height<sub>SDS</sub>. <b><i>Conclusion: </i></b>Pubertal height<sub>SDS</sub>gain and AH<sub>SDS</sub> were dose dependent, with greater growth being observed for the GH<sup>67</sup> than the GH<sup>33</sup> randomization group; however, there were no differences between the once- and twice-daily GH<sup>67</sup> regimens.