Background: Diencephalic syndrome (DS) is a rare disorder of severe emaciation classically associated with infantile Hypothalamochiasmatic low-grade gliomas (HCLGGs) and GH excess. However, diagnostic criteria remain undefined and published literature includes non-specific tumour-related cachexia. In a large optic pathway LGG cohort (n=166), we have previously demonstrated that DS independently predicts multiple tumour progressions and severe endocrine morbidity.
Objective and Hypotheses: To improve diagnostic criteria for DS by determining the sensitivity and specificity of clinical and biochemical parameters and to compare long-term endocrinopathy with contemporaneous age- and tumour location-matched patients.
Method: Retrospective subcohort analysis of patients presenting <2 years with HCLGGs to our centre between 1980 and 2010.
Results: 28/166 infants with HCLGG were diagnosed at a median (range) of 0.9 (0.21.9) years and were followed up for 9.0 (2.428.1) years. 14/28 had DS and were more likely to have hypothalamic involvement (P=0.0006) and metastases (P=0.04) than non-DS patients. Weight (P=0.00001), BMI (P=0.0005) and weight-for-length (WFL) (P=0.0001) SDS were significantly lower in DS patients but height SDS were similar (P=0.3). 6/7 patients in whom fasting GH concentrations were measured had concentrations of >20 ng/ml (median, 32.7 ng/ml). GH excess was more sensitive (86%) and specific (100%, AUC=0.93) than BMI SDS<2 (AUC=0.90), hypothalamic involvement (AUC=0.82) or WFL SDS<2 (AUC=0.79) for the diagnosis of DS. DS patients tended to experience more tumour progressions (P=0.01), require multiple surgeries (P=0.02) and have multiple endocrinopathies, particularly ACTH deficiency (P=0.03).
Conclusion: This is the first attempt to auxologically and biochemically differentiate DS in infantile HCLGG from non-specific tumour-related cachexia. We demonstrate that over 30 years of follow-up there are differences between the endocrinopathies and tumour progressions experienced by DS and non-DS patients. The next pan-European SIOP LGG chemotherapeutic trial is in design with a specific focus on DS, providing a unique opportunity to prospectively study the pathophysiology of this extremely rare disorder.
20 - 22 Sep 2014
European Society for Paediatric Endocrinology