ESPE Abstracts

Background: Hypothalamo-posterior-pituitary (HPP) disorders are complex, life-threatening, and often of uncertain pathogenesis. Oxytocin and AVP/copeptin share production and storage sites, but they are difficult to measure in biological fluids. Correlation with HPP neuroimaging abnormalities has not been previously determined.

Aim: To correlate unstimulated plasma copeptin/oxytocin with hypothalamic volumes/PP location in congenital and tumorous disorders, using a novel segmentation approach for hypothalamic volumetry.

Patients and Methods: Of 66 patients (35M/31F) aged 12.4 ± 3.1 years, followed for 8.2 ± 4.0 years, 36 were tumours and 30 congenital. We prospectively acquired high-resolution brain MR images and simultaneous fasting/early morning copeptin, oxytocin, and plasma/urine osmolality, before any DDAVP dose.

Results: Copeptin correlated positively with urine osmolality (P <0.001, CC:0.687) and hypothalamic volumes in tumours (P = 0.007, CC:0.579), not reaching significance in the congenital (P = 0.067, CC:0.397); but 3 patients with ROHHAD(NET) showed reversed decrements in hypothalamic volume with increasing copeptin. Copeptin was lowest i) in AVP-Deficiency vs hypernatraemia/thirst disorders in ROHHAD(NET) (1.4 ± 0.5 vs 2.5 ± 0.8 pmol/L) and highest in preserved PP function (4.7 ± 2.4 pmol/L) (P <0.001), and ii) if PP was absent vs congenitally ectopic or not assessable due to tumour, and highest if normally positioned (1.8 ± 1.2 vs 3.7 ± 2.2 vs 4.2 ± 2.3 vs 4.8 ± 2.6 pmol/L; P <0.001). All 12 (100%) patients with AVP-Deficiency had copeptin ≤2.1 pmol/L paired with urine osmolalities ≤200 mOsm/kg vs 4.1% of those without AVP-Deficiency (P <0.001). Oxytocin followed a similar but insignificant trend with PP location (absent vs ectopic vs not assessable vs normal: 69.1 ± 25.8 vs 76.5 ± 40.4 vs 74.0 ± 33.7 vs 96.5 ± 42.5 pg/ml; P = 0.096), and correlated with copeptin (P = 0.017, CC=0.395) and hypothalamic volumes (P = 0.011, CC=0.550) only in tumours.

Conclusion: We have, for the first time, shown how the HPP hormones copeptin and oxytocin correlate with hypothalamic volumes as assessed by novel methodology, and PP location, and how they can reflect disease severity and aetiology in a range of congenital and acquired hypothalamic disorders. A cut-off unstimulated copeptin of ≤2.1 pmol/L predicted all patients with AVP-Deficiency with few false positives (4%). We have provided novel insights into how ROHHAD(NET) may differ from classical HPP disorders, perhaps by causing AVP dysregulation rather than deficiency. Oxytocin correlated more precisely with copeptin and hypothalamic volumes in tumours suggesting different mechanisms of disease, evolving mass induced HPP signalling disruption in acquired vs more selective AVP losses/dysregulations in congenital disorders.