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 (GH⁶⁷) given as one (GH^67×1; n = 35) or two daily injections (GH^33×2; n = 36), or to remain on a single 33 µg/kg/day dose (GH^33×1; n = 40). Growth was assessed as height_SDSgain for prepubertal, pubertal and total periods, as well as AH_SDS versus the population and the midparental height. <b><i>Results:</i></b> Pubertal height_SDSgain was greater for patients receiving a high dose (GH⁶⁷, 0.73) than a low dose (GH^33×1, 0.41, p &lt; 0.05). AH_SDS was greater on GH⁶⁷ (GH^67×1, -0.84; GH^33×2, -0.83) than GH³³ (-1.25, p &lt; 0.05), and height_SDSgain was greater on GH⁶⁷ than GH³³ (2.04 and 1.56, respectively; p &lt; 0.01). All groups reached their target height_SDS. <b><i>Conclusion: </i></b>Pubertal height_SDSgain and AH_SDS were dose dependent, with greater growth being observed for the GH⁶⁷ than the GH³³ randomization group; however, there were no differences between the once- and twice-daily GH⁶⁷ regimens.