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

Abstract

Background/Aims: 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. Methods: 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. Results: Pubertal height_SDSgain was greater for patients receiving a high dose (GH⁶⁷, 0.73) than a low dose (GH^33×1, 0.41, p < 0.05). AH_SDS was greater on GH⁶⁷ (GH^67×1, -0.84; GH^33×2, -0.83) than GH³³ (-1.25, p < 0.05), and height_SDSgain was greater on GH⁶⁷ than GH³³ (2.04 and 1.56, respectively; p < 0.01). All groups reached their target height_SDS. Conclusion: 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.

Growth hormone prescribing and initial BMI SDS: Increased biochemical adverse effects and costs in obese children without additional gain in height

“…In our unselected cohort of patients, there are numerous diagnoses included, and these may affect the response to treatment with rhGH. Formal dose response studies have clearly described a relationship between gain in height and growth hormone dose [27, 28], and high and low dose IGF-I generation tests also relate GH dose to increment in IGF-I [29]. Greater weight and higher growth hormone dose have been identified as predictors of first year growth response in previous cohorts of patients [26].…”

Insight into human pubertal growth by applying the QEPS growth model

“…The end of pubertal growth has typically not been specifically identified, and measurements have instead been based on when adult height was attained. Therefore, the total pubertal height gain has been defined as the amount of growth observed from the onset of pubertal growth until adult height, with the duration of pubertal growth defined as the time period from the onset of puberty to the attainment of adult height [2, 12, 14]. …”

Growth hormone (GH) dose-dependent IGF-I response relates to pubertal height gain

“…In children with low GH secretion diagnosed with idiopathic isolated GHD (IIGHD), we have also reported that GH dosing, mimicking the physiological pubertal increase in GH secretion, has a dose-dependent effect on the gain in height SDS until AH. In this randomized GH-treatment trial, pubertal height gain SDS and AH SDS were greater in children randomized to a high GH dose (67 μg/kg/d) than a standard dose (33 μg/kg/d) [ 18 , 19 ]. The hypothesis of the present analysis of prospectively collected data in the aforementioned clinical trial was that the IGFs would follow the normal pubertal change in GH-deficient children receiving a higher, more physiological, GH dose during puberty.…”