SAT-447 Diminished Pituitary Volume May be Linked to Short Stature in Patients with Noonan Syndrome

Abstract

Background: We have previously demonstrated that short children with Idiopathic Short Stature (ISS), Growth Hormone Deficiency (GHD), and their short siblings have significantly diminished pituitary volumes (PV) compared to normal children. In comparison, patients with Turner syndrome have not been found to manifest this finding. We speculate that pituitary hypoplasia may also contribute to short stature in Noonan syndrome (NS) patients. Objective: To compare pituitary volumes between normal children and children with Noonan syndrome. Patients and Methods: A retrospective chart review for NS patients from 2010-16 between the ages of 3-11.5 yrs who underwent a high resolution post-contrast MRI (1 mm slices) was undertaken. 8 patients were identified. 4 of the patients had the PTPN11 gene mutation and formed the P1 group. The other 4 NS patients lacked confirmed PTPN11 mutations. High resolution post-contrast MRIs (1 mm slices) from years 1999-06 in children aged 3-11.5 yrs with seizures and headaches without major pathologic findings were reviewed. 31 children met these criteria and formed the control group. PV was evaluated using the ellipsoid formula (LxWxH/2). The wilcoxon rank sum test was used to compare means of non-parametric data between 2 groups, and a Kruskall-Wallis was used to compare means of non-parametric data between multiple groups in NCSS12. Results: The mean and median age for NS children was 7.92±3.22 yrs and 8.86 yrs, respectively. The mean and median age for the P1 group was 7.04±3.09 yrs and 6.27 yrs, and the mean and median age for the other NS group was 8.81±3.53 yrs and 10.21 yrs. The mean and median age for controls was 6.88±2.70 yrs and 7.08 yrs, respectively. The difference in age between all groups was not significant (p=0.23). Mean and median PV for the NS children were 205.74±52.81 mm3 and 178 mm3 respectively. The mean and median PV for the controls were 294.71±93.85 mm3 and 276.27 mm3, respectively. Mean and median PV for the P1 group was 182±19.40 mm3 and 175 mm3, and the mean and median PV for the other NS group was 229.49±68.03 mm3 and 228.48 mm3. Differences in PV between controls, P1, and other NS was significant (p=0.02). The difference in PV of controls versus P1 was significant (p=0.01). The difference in PV of controls versus all NS patients was significant (p=0.01). The difference between the PV of controls and other NS patients was not significant (p=0.28). The difference between the PV of P1 and other NS patients was not significant (p=0.56). Conclusion: These data suggest that NS patients have significantly lower PV compared to controls, particularly those with the PTPN11 mutation. Our previous work has demonstrated an association between diminished PV, GHD, and ISS. We hypothesize that the diminished PV may be in part responsible for short stature in NS as well. WE SEEK COLLABORATION WITH OTHER INVESTIGATORS TO FURTHER EXPLORE THIS HYPOTHESIS.