Endocrinopathies in paediatric-onset Aquaporin 4 (AQP4) antibody neuromyelitis optica spectrum disorder

Abstract

Objective: Neuromyelitis optica spectrum disorder (NMOSD) is well-characterised syndrome. The discovery of Aquaporin 4 antibodies (AQP4-Ab), which are now an integral part of the diagnostic criteria, has directly influenced the diagnosis and management of these patients. This has resulted in expansion of the clinical phenotypes to include patients with brain disease even in the absence of optic neuritis and transverse myelitis. The association with endocrinopathies was first described in patients with recurrent optic neuromyelitis prior to the discovery of AQP4-Ab. Here we wanted to assess the prevalence of endocrinopathies in a paediatric onset cohort of AQP4-Ab NMOSD. Methods: Clinical, demographic and treatment data were prospectively collected from 25 consecutive paediatric onset AQP4-Ab positive patients seen in the nationally commissioned Oxford NMO service. Parental consent was obtained for publication of relevant clinical information. Results: All patients fulfilled the current diagnostic criteria for NMOSD5. A total of 15 patients (60%) had symptoms of endocrinopathies. These included: morbid obesity (BMI>40, n=8), hyperinsulinaemia (n=5), hyperandrogenism (n=5), amenorrhoea (n=5), hyponatraemia (n=4), short stature (n=3) and central hypothyroidism (n=2). When comparing patients with endocrinopathies to those without, there was no difference in the patients’ demographics, clinical presentations at onset and relapse, or cumulative dose of steroids received. Patients with endocrinopathies were more likely to have abnormal brain MRI 12/15 vs 3/10 (p=0.034). Morbid obesity was seen in 7/8 (87.5%) of children of Caribbean origin and only in one child of non-Caribbean origin (p=0.002). Conclusion: Endocrinopathies are prevalent (60%) in children with AQP4-Ab NMOSD, with morbid obesity in 86% of afflict children of Caribbean origin. This is likely to be multifactorial but the cohort presented here is too small to disentangle any of those factors. Importantly, the endocrinopathies resulted in significant disabilities. Endocrine surveillance and early aggressive weight management is required for patients with AQP4-Ab NMOSD.