Background Patients with diminished growth hormone (GH) secretion are candidates for GH therapy (GHT). The GH stimulation test (GHST) is considered the gold standard for the diagnosis of GH deficiency (GHD), yet its efficacy has been questioned. In this study we explore the GHST and PV's ability to define GHD and determine their individual ability to predict GHT outcomes. Subjects and Methods A database at a Pediatric Endocrinology center was queried for patients aged 6-18 yrs who underwent a GHST, MRI, and GHT between 1/2018 - 1/2021. Patients with a first follow up (FU) between 3 and 9 months were included; of these patients, second FUs were included if they occurred between 9 and 15 months. Patients with relevant comorbidities, those with GHST peak ≥ 10.0 ng/mL, and nonadherent patients were excluded. MRIs were acquired on a Philips 1.5 or 3.0 T scanner (2mm slices) and PV was calculated using the ellipsoid formula (LxWxH/2). PV and height were converted to SDS. Response to treatment was defined as change in height SDS over the assessed time interval. A multiple linear regression was utilized to analyze the response to GHT relative to peak GH and PV, with initial height and age at stimulation included as covariates. The relationship between peak GH and PV SDS was analyzed with a Pearson correlation Results The first FU ranged between 3.1 and 8.9 months, and the second FU ranged between 9.0 and 14.9 months. 145 patients had one FU, and 83 patients had two FUs. Peak GH and PV SDS were not correlated (r=0.03). Patients who were relatively shorter for their age and gender at stimulation had higher growth rates in the first interval, but not in the second interval. Both PV and peak GH provided information about response to GHT. PV SDS negatively predicted the relative growth response to treatment in the first interval (slope=-0.03, p=0.048). However, PV only explained 3.7% of variation in growth. PV SDS was not a useful predictor of response in the second interval (slope=-0.01, p=0.693). Peak GH was a predictor of response to GHT in the first interval only after accounting for age at stimulation and initial height (slope=-0.01, p=0.032; r2=0.01). Peak GH was a predictor of response in the second interval (slope=-0.02, p=0.040), explaining 5.1% of the variation in growth. Conclusion Since peak GH and PV were not correlated, they likely reflect different physiological processes. PV and peak GH both provide information about response to GHT, so they should both be utilized to determine eligibility for GHT. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Background MRIs of the brain in patients with short stature have shown a number of abnormalities. Some of these radiological findings can have clinical significance. Here we have looked at MRI results in such a population. Objective To review the value and significance of the prevalence of all abnormal MRI findings of children with short stature who are to undergo growth hormone therapy (GHT). Materials and methods This study involved a retrospective review of MRI findings in all children prescribed GHT within a pediatric health network's database from Jan 2020 to Aug 2021. Post-gadolinium contrast enhanced brain and pituitary MRIs utilizing 2 mm slices were used to calculate pituitary volume. Pituitary volume was calculated using the ellipsoid formula (LxWxH/2). Pediatric patients diagnosed with non-acquired GHD or ISS, with MRIs having been performed between Jan 2020 and Aug 2021 and having been prescribed GHT by Aug 2021 were included in this study. Patients who experienced other endocrine abnormalities such as SGA, Turner Syndrome, and Noonan Syndrome were excluded. Patients with obstruction of sellar and parasellar religion due to movement artifacts or magnetic interference on their MRIs were also excluded. Results Of one hundred and twelve patients found, eighty one met criteria for inclusion in this study. Of the eighty one MRIs reviewed, twenty eight children, 34.6%, had normal pituitary anatomy and fifty three, 65.4%, had a pituitary abnormality. Out of the fifty three with a pituitary abnormality, forty three subjects, 81.1%, were determined to have a small pituitary volume, including significant pituitary hypoplasia. Ten subjects (18.9%) had an enlarged pituitary volume (pituitary hyperplasia). Of these ten patients who had an enlarged pituitary volume, eight were pubertal (80%). Nine children with a pituitary abnormality (16.9%) had additional structural anomalies on their MRIs. One had a small left frontal developmental venous anomaly. Two had Rathke's cleft cysts. Two had pars intermedia cysts. One had a small right parietal developmental venous anomaly. One had a small left parietal developmental venous anomaly. One had a left cerebellar tonsillar ectopia bordering on chiari malformation (.5 mm away on the coronal plane). One had a small lobulation (semi-bulbous projection) of the anterior pituitary gland, superior and anterior to the infundibular stalk. Conclusion Prevalence of brain abnormalities in children with short stature who are to undergo GHT is significant and warrants MRI evaluations in these subjects. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m., Monday, June 13, 2022 12:58 p.m. - 1:03 p.m.

We have shown that short children have significantly reduced pituitary volume (PV)s and have speculated PV as a cause for diminished chronic growth hormone (GH) secretion and poor growth. In this study, we further elucidate the role of PV in the etiology of short stature (SS) in a larger cohort of siblings (SBs).The database of a Peds Endo Center between 2013-21 was queried for siblings with SS who underwent a GH Stimulation test (GHST) and MRI evaluation. Their results were compared with normal controls (NCs) as previously reported. 129 SBs of 60 families were compared to 170 NCs. SBs were divided into 3 groups (GPs). GP1 (n=79) consisted of families with only GHD. GP2 (n=12) contained families with only ISS SBs. GP3 (n=38) comprised families with mixed GHD and ISS. SBs <11 yrs and >11 yrs were considered prepubertal (prePB) and pubertal (PB), RSP. The mean (MN) and median (MD) age for both prePB and PB SBs were significantly different (p 0.05). The 32 PB patients in GP3 had a mean PV of 316.17± 197.53 mm3, which was significantly different from that of the PB NCs of 424.6 ± 138.4 mm3 (p<0.001). Out of 38 children in GP3, 18 passed the GHST and 11 of those children who passed demonstrated a small pituitary gland (61%). 78% of prePB SBs had small PVs, while 88% were GHD. 66% of PB SBs had small PVs, while 70% of PB SBs were GHD. 71% of all SBs had small PVs, while 77% were GHD. When combined, GHST and PV identify the etiology for SS in 92% of subjects. The GHST and PV together identify more patients of SS who should qualify and benefit from GH therapy than the GHST alone. Since ages were significantly different and present as a limitation to this study, future studies should strive for age match control Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Patients with a small posterior cranial fossa may present with cerebellar tonsillar herniation through the foramen magnum, known as Chiari malformation (CM). The relationship between CM, pituitary volume (PV), and growth hormone deficiency (GHD) has not yet been explored and is the subject of this abstract. This study seeks to compare the differences in PV in short patients with CM with a diagnosis of either GHD or idiopathic short stature (ISS), to normal controls (NCs). The database of a Peds Endo Center between 2013-21 was queried for patients with CM and who had undergone MRI evaluation. Patients were separated into 4 groups: CM and GHD, CM and ISS, GHD without CM, and ISS without CM. These groups’ PV results were compared with NCs who we previously reported. The ages of short patients with CM (n=29) were compared to the ages of NCs (n=170); no significant difference was found (p = 0.12). The MN and MD PV for patients with GHD alone were 230.8 ± 89.64 and 217.62mm3, respectively. The MN and MD PV for patients with GHD and CM (n=23) were 246.55 ± 128.0 and 200.5mm3, respectively. The MN and MD PV for CM and ISS (n=6) were 671.54 ± 350.25 and 619.55mm3, respectively. The MN and MD PV for NCs were 364.0 ± 145.2 and 346.0mm3, respectively. The PV of patients with GHD alone were compared to the PV of patients with both GHD and CM; there was no significant difference found (p=1.0). Next, the PV of patients with GHD alone were compared to the PV of patients with both ISS and CM which showed that patients with GHD alone had significantly smaller PV compared to patients with both ISS and CM (p<0.05). Lastly, we compared the PV of patients with both GHD and CM versus patients with both ISS and CM, which showed that patients with both GHD and CM had significantly smaller PVs compared to patients with both ISS and CM (p<0.05). The PV of short patients with CM (n=29) were compared to the PV of NCs (n=170) and there was no significant difference found (p = 0.58). Our study demonstrates that PV is smaller in patients with GHD regardless of whether they have CM or not. We speculate that CM appears to be a radiological finding with no significant impact on PV, whereas GHD appears to have a significant impact on PV. Therefore we speculate the small PV exhibited in patients with CM and GHD appear to be related to GHD. A larger sample size will be needed to further elaborate on this concept. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

Background Pituitary cysts (PCs) may be related to the development of diminished growth hormone secretion because they may limit the proliferation of somatotrophs. This study seeks to investigate the mass effect of PCs on the pituitary function. Methods Patients aged 6-18 with cysts and follow-ups between 2007–21 were compared to normal controls (NCs) aged 6-18 from a neuroradiology center. Pituitary volume (PV) is the volume of the pituitary gland including the cyst, while net pituitary volume (netPV) is the volume of the pituitary gland excluding the cyst. Since NCs did not have PCs, only PV was utilized. PVs and netPVs are reported in mm3. Data were stratified into prepubertal (age < 11 yrs) and pubertal (age > 11 yrs). The Kruskal-Wallis One Way ANOVA on Ranks was utilized to compare multiple means, and the Kruskal-Wallis Multiple-Comparison Z Value test (with Bonferroni adjustment) was utilized for pairwise comparisons. Results The mean and median PVs of prepubertal GHD (n=37), ISS (n=5), and NCs (n=58) were 290.2 ± 109.7 and 305.0, 314.4 ± 100.8 and 299.8, and 246.8 ± 63.7 and 241.6, respectively. The difference between mean PVs of prepubertal GHD, ISS, and NCs was not significant. The mean and median PVs of pubertal GHD (n=58), ISS (n=33), and NCs (n=112) were 391.5 ± 163.5 and 370.2, 409.2 ± 215.8 and 382.9, and 424.2 ± 138.9 and 402.7, respectively. The difference between mean PVs of pubertal GHD, ISS, and NCs was not significant. For netPV, the mean and median values for prepubertal GHD and ISS patients were 252.2 ± 83.3 and 272.2, and 245.2 ± 85.7 and 244.9, respectively. The difference between mean netPVs of prepubertal GHD, ISS, and NCs was not significant. For netPV, the mean and median values for pubertal GHD and ISS patients were 332.7 ± 121.3 and 346.4, and 333.9 ± 146.1 and 330.7, respectively. The mean netPVs of pubertal GHD and ISS patients were both significantly lower than the mean PV of pubertal NCs. The mean and median PVs for cyst patients were 364.8 ± 170.0 and 347.8 which was not significantly different from the NCs. The mean and median netPVs for cyst patients were 307.3 ± 122.9 and 289.0 which was significantly different from the NCs (p<0.001). Conclusion When considering the functional component of the pituitary gland, cyst volume should be subtracted from the overall pituitary gland. Presentation: Sunday, June 12, 2022 12:36 p.m. - 12:41 p.m., Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.