Pituitary Stalk Interruption Syndrome: Phenotype, Predictors, and Pathophysiology of Perinatal events.

Purpose: There is limited data regarding Pituitary Stalk Interruption Syndrome (PSIS) from India. Moreover, the pathophysiological link between perinatal events and PSIS is unclear. We aim to elucidate the predictors of PSIS among patients with growth hormone deficiency (GHD) and perinatal events in PSIS by comparing cohorts of PSIS and genetically proven GHD without PSIS. Methods: : Among 179 GHD patients, 56 PSIS and 70 genetically positive GHD (52- GHRHR , 15- POU1F1, and 3- PROP1 ) patients were included . Perinatal events, clinical anomalies, pituitary hormone deficiency, and imaging findings were recorded. We compared subgroup of PSIS-isolated GHD (PSIS-IGHD) with GHRHR -IGHD and subgroup of PSIS-combined pituitary hormone deficiency (PSIS-CPHD) with POU1F1/PROP1 -CPHD. Results: : PSIS patients (45 males, median age: 12.5 years) most commonly presented with short stature. At last follow up (median age: 17.35 years), gonadal (during pubertal-age), thyroid and cortisol axes were affected in 81.6%, 62.5%, and 62.5%. 10/13 (77%) of PSIS children with initial IGHD diagnosis manifested hypogonadism during pubertal age. Male predominance, sporadic presentation, clinical anomalies were significantly higher in both PSIS subgroups than the respective genetic subgroups. Breech presentation was higher in PSIS-CPHD than POU1F1/PROP1- CPHD (44.4% vs 5.5%, p=0.004). Neonatal hypoglycemia (22% vs. 0%, p=0.05) and jaundice (42 vs. 5%, p=0.004) were higher in PSIS-CPHD than PSIS-IGHD. Conclusion: Later age at presentation and frequent hypogonadism were observed in our PSIS cohort. Male sex, sporadic presentation, clinical anomalies, and breech presentation predicted PSIS at presentation. Breech presentation in PSIS is likely due to stalk interruption rather than hormonal deficiency.