Abstract
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.