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.

Background: Patients (PTs) with Chiari malformation (CM) are prone to a wide variety of neurologic symptoms (SX), including headaches (HA), vision abnormalities, and nausea. These SX are attributed to impaired flow of CSF leading to benign intracranial hypertension (BIH). Occasionally, PTs with CM may require growth hormone therapy (GHT). This can potentially increase CSF accumulation and risk of BIH. The literature is limited to a small number of case reports on GHT in PTs with CM. Here, we describe the incidence of neurologic SX in 15 PTs. Methods: Our database was queried for PTs with CM who were treated with GHT from 2010–18 and records were reviewed for adverse events. PTs with neoplastic disease, active inflammation, or acute trauma were excluded. CM was defined as cerebellar tonsils located below the foramen magnum on MRI. Results: Mean and median ages of the 15 PTs (10 male, 5 female) who met inclusion criteria were 15.3 and 11.7 years, respectively. 14 were diagnosed as Type 1 and 1 was diagnosed as Type 2 CM. Tonsillar displacement ranged from 2-21mm, but was not specified in 5 PTs. Indications for GHT included isolated GH deficiency, panhypopituitarism, and chronic renal disease. Duration of GHT ranged from 0.2 to 12.25 years with a mean and median of 3.7 and 1.75 years, respectively. 7% (1 of 15) PTs experienced new-onset SX of BIH that could be attributed to GHT. 8 PTs (53.3%) did not experience any SX consistent with CM before, during, or after GHT. 3 PTs (20%) experienced neurologic SX prior to GHT. 1 PT reported diplopia and abnormal sleep patterns prior to GHT that resolved and did not recur during GHT. 1 PT prior to GHT manifested papilledema, 1 seizure, central sleep apnea, and occipital HA that resolved after posterior fossa decompression. Post-operatively and during GHT, this PT developed and continued to manifest nonpathologic pseudopapilledema. 1 PT continued to have pre-existing seizures and insomnia that did not worsen with GHT. 1 PT (7%) had congenital neurologic abnormalities in addition to CM. This PT had surgery to alleviate BIH caused by congenital hydrocephalus and SX permanently resolved. GHT has been continuous since birth with no new manifestations of CM reported post-operatively. 2 PTs (13%) developed new-onset neurologic SX while on GHT. 1 PT with diabetes experienced HA, 1 report of loss of consciousness, and 1 instance of apnea during periods of hyperglycemia. It was determined that these SX were unrelated to BIH and GHT was not interrupted. 1 PT experienced mild HA and 1 episode of occipital pounding with emesis during GHT. These SX resolved without intervention and GHT was continued without interruption. Despite the complexity of these cases, 0 PTs discontinued GHT. Conclusion: Our study demonstrates that in a majority (93%) of cases, GHT does not cause onset or worsening of SX of BIH in PTs with complicated and uncomplicated CM. GHT should be regarded as a safe treatment in these PTs.

Background: We have previously shown that short children have significantly reduced PVs. In this study, we further define the etiology of SS in a larger cohort of siblings (SBs). Objective: To further investigate the efficacy of PV as an indicator of poor growth. Patients and Methods:Methods: The database of a peds endo center was queried for SBs aged 6–18 yrs who underwent a GHST and subsequent MRI between 2013–19. Their MRI results were compared to randomly selected normal controls (NCs) aged 6–18 yrs seen at a neuroradiology center between 2010–16. Patients with MRI abnormalities were excluded. PVs were calculated using the ellipsoid formula (LxWxH/2). Our previous ROC curve analysis has defined 215.02mm3 and 315.00mm3 as cutoffs for small PVs in prepubertal and pubertal (PB) SBs, respectively (RSP). Growth hormone levels <10 ng/ml or >10 ng/ml diagnosed patients as growth hormone deficient (GHD) or idiopathic short stature (ISS), RSP. Patients: 77 SBs of 37 families were compared to 170 NCs. SBs <11 yrs and >11 yrs were considered pre-PB and PB, RSP. Results: The mean (MN) and median (MD) ages of SBs were 11.6 ± 2.2 and 11.9 yrs, RSP, and the MN and MD ages of the NCs were 12.6 ± 3.4 and 13.2 yrs, RSP. The difference (DIF) in MN age was significant (SG) (p<0.05). The pre-PB SBs and pre-PB NCs had MN and MD ages of 9.3 ± 1.2 and 9.7 yrs, RSP and 8.6 ± 1.4 and 8.6 yrs, RSP. The DIF in MN pre-PB age was SG (p<0.05). The PB SBs and PB NCs had MN and MD ages of 13.0 ± 1.4 and 12.7 yrs, RSP and 14.7 ± 1.9 and 14.6 yrs, RSP. The DIF in MN PB age was not SG (p<0.05). The MN and MD PVs for SBs (n=77) were 220.1 ± 94.0 and 204mm3, RSP. The MN and MD PVs for NCs (n=170) were 364.0 ± 145.2 and 346.0mm3, RSP. The DIF in MN PVs was SG (p <0.001). Stratified by age, the MN and MD PVs for SBs ages 6–11 yrs (n=29) were 166.1 ± 46.8 and 160mm3, RSP, and the MN and MD PVs for NCs ages 6–11 yrs (n=58) were 246.8 ± 63.7 and 241.6mm3, RSP. The DIF in MN PV was SG (p <0.001). The MN and MD PVs for SBs >11 yrs (n=48) were 252.7 ± 100.5 and 227mm3, RSP and the MN and MD PVs for NCs >11 yrs (n=112) were 424.6 ± 138.4 and 403.3mm3, RSP. The DIF in MN PV was SG (p <0.001). 86% of pre-PB SBs had small PVs, while 93% were GHD. 79% of PB SBs had small PVs, while 79% of PB SBs were GHD. 81.8% of all SBs had small PVs, while 84.4% were GHD. When combined, GHST and PV identify the etiology for SS in 96.1% of subjects. Discussion: The GHST recognized the etiology for SS in 84.4% of the SBs, while PV identified 81.8%. Using both criteria together, the etiology for SS was identified in 96.1% of the SBs. 3 of the 4 pre-PB SBs, who did not meet the PV cutoff had PVs within 10% of the cutoff. Conclusion: We have shown that PV is not inferior to the GHST in the diagnosis of SS. Combining the GHST and PV defines the etiology of SS in 96.1% of patients. Jointly, the GHST and PV should be considered the new gold standard for identifying children who qualify for GH therapy. This criteria will significantly diminish the number of patients diagnosed with ISS.

Background: Preliminary studies have demonstrated improvement in metabolic control of patients (PTs) using subcutaneous Continuous Glucose Monitoring systems (CGMs). In this study, we investigated the effect of CGMs on PTs’ glycemic control and compared the change in patient HbA1c levels between sensors. Objective: To determine how CGMs affect metabolic control in PTs and the effect of different sensors on glycemic control. Patients and Methods: 33 PTs with Type 1 diabetes mellitus (DM) who began using a CGM between 2017 and 2019 were selected for inclusion. CGM systems used included DexcomG6™, DexcomG5™, DexcomG4™, Enlite™, Guardian 3™, or Medtronic Sure-T™ sensors. Results: The mean (MN) age of PTs at initial visit was 15.3 ± 5.1 yrs and the MN age at second visit was 15.8 ± 5.1 yrs. The MN time between visits was 5.0 ± 2.4 months (mos). 6 PTs had follow up (F/U) times less than 3 mos, 18 PTs had F/U times between 3 and 6 mos, 6 PTs had F/U times between 6 and 9 mos, and 3 PTs had F/U times greater than 9 mos. The MN and median (MD) HbA1c at the initial visit for all PTs was 8.28% ± 1.48 and 8.10%, respectively. The MN and MD HbA1c at final F/U for all PTs was 7.57% ± 1.11 and 7.50%, respectively. The difference in MN HbA1c was significant (p<0.001). The MN and MD HbA1c at the initial visit for PTs with a F/U time less than 3 mos was 7.55% ± 0.77 and 7.75%, respectively. The MN and MD HbA1c at F/U for these PTs was 7.20% ± 0.79 and 7.20%, respectively. The difference in MN HbA1c was significant (p<0.05). The MN and MD HbA1c at the initial visit for all PTs with a F/U time greater than 3 mos was 8.44% ± 1.53 and 8.10%, respectively. The MN and MD HbA1c at F/U for these PTs was 7.66% ± 1.15 and 7.50%, respectively. The difference in MN HbA1c was significant (p<0.001). The MN change of HbA1c between visits was not significant between PTs who had 3–6 mo, 6–9 mo, and 9+ mo F/U times (p=0.96) 15 PTs had HbA1c levels less than or equal to 8.0%. The MN and MD HbA1c at initial visit for these PTs was 7.20% ± 0.41 and 7.30%, respectively. The MN and MD HbA1c at F/U for these PTs was 6.75% ± 0.47 and 6.80%, respectively. The difference in MN HbA1c was significant (p<0.001). 20 PTs had HbA1c levels greater than 8.0% at initial visit. The MN and MD HbA1c at the initial visit for these PTs was 9.18% ± 1.47 and 8.80%, respectively. The MN and MD HbA1c at F/U for these PTs was 8.26% ± 1.03 and 8.00%, respectively. The difference in MN HbA1c was significant (p<0.001). The MN change in HbA1c between the high HbA1c group (-.92% ± 1.02) and low HbA1c group (-0.45% ± 0.32) was not significant (p>0.05). 25 PTs used a Dexcom™ sensor while 8 PTs used a Medtronic™ sensor. The MN change in HbA1c was not significant between these brands (p>0.05). Conclusion: CGMs improve metabolic control in pediatric PTs with Type 1 DM regardless of initial HbA1c. Further, this improved control is sustained over time. Sensor brands appear to be equally effective at achieving this goal.

Background: The sequential follow-up of simple fluid-filled pituitary cysts (PC) has not been fully elucidated. In this study, we further report our follow up of PCs in a cohort of pediatric patients (PTs). Objective: To further analyze the sequential cyst volume (CV) change in short children. Patients and Methods: A pediatric endocrinology and neuroradiology center was queried for the presence of PCs. PTs who underwent multiple high resolution post-contrast MRIs (1mm slices) were subjects of this study. PTs with additional MRI abnormalities were excluded. Pituitary volumes (PV) and CVs were measured using the ellipsoid formula (LxWxH/2). The percentage of the gland occupied by the cyst (POGO) was measured and calculated. A cyst with a POGO ≤15% was defined as a small pituitary cyst (SPC), and a POGO >15% was defined as a large pituitary cyst (LPC). 34 PTs met inclusion criteria, all of whom were diagnosed with short stature (23 growth hormone deficient (GHD) PTs and 11 idiopathic short stature (ISS) PTs). All PTs were receiving GH during data collection. Results: The mean (MN) and median (MD) ages for these subjects were 10.7 yrs ±3.5 and 11.1 yrs, respectively (RSP). Of the 34 PTs, 24 PTs’ (71%) initial MRI demonstrated a SPC and 10 PTs’ (29%) initial MRI demonstrated a LPC. The MN and MD times between first and second MRIs were 1.23 yrs and 0.83 yrs RSP, with a range (RG) of 0.14 to 4.08 yrs. The MN and MD ΔCV for all PTs was 23.33% ±179.17% and -25.94% RSP, with a RG of -100.00% to 763.94%. The MN and MD ΔPOGO by the cyst for all PTs was 48.59% ±313.26% and -36.84% RSP, with a RG of -100.00% to 1734.79%. The MN and MD ΔCV for PTs with a SPC was 10.68% ±2.65% and 11.09% RSP, with a RG of -100.00% to 763.94%. The MN and MD ΔPOGO by the cyst for PTs with a SPC was 78.33% ±369.96% and -31.34% RSP, with a RG of -100.00% to 1734.79%. The MN and MD ΔCV for PTs with a LPC was -24.60% ±51.89% and -26.57% RSP, with a RG of -88.57% to 91.38%. The MN and MD ΔPOGO by the cyst for PTs with a LPC was -22.79% ±44.90% and -40.46% RSP, with a RG of -80.95% to 47.11%. Statistical analysis showed no significant %ΔCV or %ΔPOGO when comparing male vs. female, SPC vs. LPC, GHD vs. ISS, or pre-pubertal vs. pubertal PTs. Analysis of ΔPOGO of the 24 SPC PTs demonstrated that 4 (17%) of them developed into LPCs. Analysis of the 10 LPC PTs showed that 6 (60%) of them shrunk into SPCs, one of which re-enlarged into a LPC, and another of which fluctuated between LPC and SPC over a period of 7.34 yrs and 9 sequential MRIs. None of the PTs experienced significant sequelae related to their PCs. Conclusion: CV can change greatly over time, however few sequelae should be expected. LPCs tend to demonstrate major changes in size and should be tracked for CV change. A minority of SPCs will develop into LPCs. Prediction of change in CV over time requires more sequential data. Change in CV did not appear to be influenced by GH therapy.