Prevention of Growth Failure in Turner Syndrome: Long-Term Results of Early Growth Hormone Treatment in the “Toddler Turner” Cohort

Abstract

<b><i>Introduction:</i></b> In the randomized “Toddler Turner” study, girls who received growth hormone (GH) starting at ages 9 months to 4 years (early-treated [ET] group) had marked catch-up growth and were 1.6 ± 0.6 SD taller than untreated (early-untreated [EUT]) control girls after 2 years. However, whether the early catch-up growth would result in greater near-adult height (NAH) was unknown. Therefore, this extension study examined the long-term effects of toddler-age GH treatment on height, pubertal development, and safety parameters. <b><i>Methods:</i></b> Toddler Turner study participants were invited to enroll in a 10-year observational extension study for annual assessments of growth, pubertal status, and safety during long-term GH treatment to NAH for both ET and EUT groups. <b><i>Results:</i></b> The ET group was taller than the EUT group at all time points from preschool to maturity and was significantly taller at the onset of puberty (<i>p</i> = 0.016), however, the difference was not significant at NAH. For the full cohort (ET + EUT combined, <i>n</i> = 50) mean (± SD) NAH was 151.2 ± 7.1 cm at age 15.0 ± 1.3 years. NAH standard deviation score (SDS) was within the normal range (&#x3e;−2.0) for 76% of ET and 60% of EUT subjects (68% overall) and correlated strongly with height SDS at GH start (<i>r</i> = 0.78; <i>p</i> &#x3c; 0.01), which in turn had a modest inverse correlation with age at GH start (i.e., height SDS declined with increasing age in untreated girls [<i>r</i> = −0.30; <i>p</i> = 0.016]). No new safety concerns arose. <b><i>Conclusion:</i></b> Although the ET group was taller throughout, height SDS at NAH was not significantly different between groups due to catch-down growth of ET girls during lapses in GH treatment after the Toddler study and similar long-term GH exposure overall. Early initiation of GH by age 6 years, followed by uninterrupted treatment during childhood, can prevent ongoing growth failure and enable attainment of height within the normal range during childhood, adolescence, and adulthood.