ESPE Abstracts (2016) 86 RFC6.3

Effect of Very Early Growth Hormone (GH) Treatment on Long-term Growth in Girls with Turner Syndrome (TS): A Multicenter, Open-Label, Extension Study

Marsha Davenporta, Patricia Fechnerb, Judith Rossc, Erica Eugsterd, Nan Jiae, Hiren Patele, Anthony Zagare & Charmian Quigleyd

aUniversity of North Carolina, Chapel Hill, North Carolina, USA; bSeattle Children’s Hospital, Washington, USA; cThomas Jefferson University, Philadelphia, Pennsylvania, USA; dRiley Hospital for Children, Indiana University School of Medicine, Indianapolis, Indiana, USA; eLilly USA, LLC, Indianapolis, Indiana, USA

Background: Late initiation of GH results in suboptimal adult height for many women with TS. In a landmark, randomized, controlled, clinical trial (“Toddler Turner” study) we showed that 2 y of early GH (ET group) started at 1.98±1.01 y, resulted in height SDS difference of 1.6±0.6 SDS vs. early untreated group (EUT).

Objective and hypotheses: It was unclear if early height gains would result in taller adult heights, so patients were followed to near adult height (NAH) in a long-term extension.

Method: Auxology, bone age x-ray, laboratory and safety assessments were obtained annually. Tympanometry and audiology assessments were performed at baseline, 10 y, 16 y or study endpoint. GH treatment was at the discretion of the investigator and subject’s local physician. The primary efficacy measure was last height available when height velocity was ≤2.0 cm/y or bone age was ≥14.5 y (near-adult height (NAH)).

Results: Of 88 eligible subjects, 69 entered the extension (ET=36; EUT=33); 68 received GH (average 41±14 μg/kg per d) and NAH was available for 51 after 12.98±2.62 y (ET=25) and 11.08±2.63 y (EUT=26) GH treatment. At entry to extension (ET vs EUT), chronological age was 8.46±1.19 y vs 8.54±1.28 y, bone age 9.12±1.45 y vs 8.51±1.56 y, and height SDS −0.68±1.21 vs −1.29±1.24. NAH SDS was: ET, −1.37±1.09 (153±7 cm) at age 14.64±0.25 y; EUT, −1.60±1.21 (152±8 cm) at age 15.26±0.23 y (P=0.590). Height SDS at ages 10, 13, and 16 y were −0.66±1.16 vs −1.28±1.17 (n=62); −1.29±1.24 vs −1.87±1.16 (n=58); and −1.66±1.11 vs −1.69±1.30 (n=36). ET subjects attained thelarche slightly earlier than EUT (11.60±0.33 vs 11.96±0.34 y (P=0.038)) and had earlier start of estrogen replacement (12.11±0.96 vs 12.66±1.34 y (P=0.143)). Of 69 subjects, 1 died of leukemia, ≥1 serious adverse events (AE) were reported for 11 and non-serious AE for 66. Three cases of de novo neoplasia (colon adenoma, ganglioneuroma and medulloblastoma) were reported. There was no difference between groups for abnormal tympanometry/audiometry results.

Conclusion: Girls with TS who received 2 y of GH starting at age 2 were somewhat taller (non-significant) at ages 10 y, 13 y and NAH than controls. Both groups attained NAH ~10 cm greater than if untreated, based on historical data. To our knowledge, this study represents the longest longitudinal follow-up of a TS cohort.