Noonan Syndrome and Turner Syndrome Patients Respond Similarly to Long-term Growth Hormone Therapy up to 4 Years: Longitudinal Analysis of Growth Hormone-Naïve Patients Enrolled in the NordiNet® IOS and the ANSWER Program®

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SUN 624-646-Growth: Clinical Trials & Observational Studies
Clinical
Sunday, June 16, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SUN-633
Peter A Lee*1, Judith L Ross2, Isabelle M Oliver3, Birgitte Tønnes Pedersen4, John A Germak5 and Henrik T Christesen6
1Penn State Univ Coll of Med, Hershey, PA, 2Thomas Jefferson University, Philadelphia, PA, 3Hopital des Enfants, Toulouse Cedex, France, 4Novo Nordisk A/S, Søborg, Denmark, 5Novo Nordisk Inc, Princeton, NJ, 6Odense Univ Hospital, Odense, Denmark
Background and Objective: Despite the phenotypic similarities between Noonan syndrome (NS) and Turner syndrome (TS), few studies have compared the growth response to growth hormone (GH) treatment in the two syndromes. We aimed to compare changes in height standard deviation score (HSDS) and corrected HSDS (HSDS−target height SDS) from baseline and up to 4 years of treatment with Norditropin® (somatropin, Novo Nordisk A/S) between NS and TS patients enrolled in the observational European-based NordiNet® International Outcome Study (IOS) and the American Norditropin Studies: Web-enabled Research (ANSWER) Program®.

 Method and Results: Of 195 NS and 1070 TS patients, 22 NS patients (18 males, 4 females) and 255 female TS patients with complete 4-year longitudinal data were included in repeated measures regression analysis. At baseline, NS and TS patients did not differ significantly (mean±SD) in age (NS: 8.8±3.5 yrs; TS: 7.9±3.2 yrs), HSDS (NS: -2.72±0.92; TS: -2.67±0.88), bone age (NS: 7.30±3.65 yrs; TS: 6.73±2.94 yrs) or corrected HSDS (NS: -2.29±1.13; TS: -2.46±1.08). IGF-I SDS was lower in NS (-1.36±1.22) than TS patients (‑0.89±1.52), but this was also not significant. At Y1 and Y2, mean changes in HSDS (DHSDS) from baseline in NS and TS patients were similar (Y1, NS: +0.50, TS: +0.52, P=0.86; Y2, NS: +0.87, TS: +0.82, P=0.72), but diverged after Y3 with a trend towards greater ΔHSDS observed in NS patients (Y3, NS: +1.13, TS: +0.96, P=0.24; Y4, NS: +1.28, TS: +1.03, P=0.11). A trend towards greater corrected DHSDS in Y4 from baseline in NS patients was also observed (NS: +1.26, TS: +1.02; P=0.13).

The mean GH dose over 4 years was similar between patients with NS (49 mcg/kg/day) and TS (48 mcg/kg/day), but a slight decrease in GH dose was observed in TS patients compared to baseline (P=0.02). A negative correlation between DHSDS and baseline age was observed over the first 3 years of GH treatment in NS patients; in TS patients, a negative correlation between DHSDS and age was present at all 4 years.

Conclusions: NS and TS patients responded similarly in mean DHSDS and corrected HSDS over 4 years of GH treatment with greater than +1 SDS gain. The trend towards greater increases in HSDS and corrected HSDS in NS patients may be due to the effect of puberty in NS patients and the decrease in GH dose over time in TS patients. The negative correlation between DHSDS and age for both NS and TS patients highlights the importance of early initiation of GH treatment.

Disclosure: PAL: Research Funding, Ipsen, Research Funding, Eli Lilly & Company, Research Funding, Abbott Laboratories, Consultant, Novo Nordisk, Consultant, Ipsen, Consultant, Abbott Laboratories, Research Funding, Novo Nordisk. JLR: Research Funding, Pfizer, Inc., Research Funding, Novo Nordisk, Research Funding, Eli Lilly & Company, Consultant, Novo Nordisk, Consultant, Eli Lilly & Company, Consultant, Abbott Laboratories. IMO: Study Investigator, Novo Nordisk. BT: Employee, Novo Nordisk. JAG: Employee, Novo Nordisk. HTC: Study Investigator, Novo Nordisk.

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: Novo Nordisk