Despite being the size of an almond, the hypothalamus is one of the most complex and vital structures of the human brain. It regulates essential functions that we take for granted in our daily lives. It works together with another vital structure called the pituitary gland. They are both deeply located in the most hidden part of the brain making them difficult to study.
Markers of hypothalamic dysfunction in children with hypothalamo-pituitary tumours or pituitary maldevelopment
Dr Manuela Cerbone
University College London
4 June 2018
The term hypothalamic syndrome refers to patients with hypothalamo-pituitary damage, unresponsive to conventional therapies. The wide spectrum of symptoms can include eating disorders, abnormal behaviour, thermoregulation, thirst and issues with sleep, memory and reproduction.
At present, clear diagnostic criteria for hypothalamic dysfunction are lacking. In the last decades, the role of hypothalamic hormones in appetite and weight regulation has received growing attention, yet correlation with neuroimaging markers has been difficult because the conventional brain images taken with Magnetic Resonance Imaging (MRI) techniques cannot precisely define the hypothalamic boundaries or its nuclei. Surgeons must rely on imprecise grading of damage to avoid further hypothalamic harm in children with tumours of this region.
Advanced MRI techniques have been successfully used to characterize paediatric brain tumours while previous studies have linked distinct hypothalamic abnormalities to specific hormonal patterns. Novel MRI techniques and biomarkers of appetite, thirst and behavioural dysregulation should be useful tools for studying, understanding and diagnosing hypothalamic dysfunction.
This project focuses on the quality of life of children surviving brain cancer. This study is especially relevant to children with tumours involving the hypothalamo-pituitary region for whom current therapies are inadequate to better the long-term, life-limiting, conditions resulting from midbrain damage.
These co-occurring conditions include severe obesity, diabetes, hormone deficits, neuro-behavioural and sleep disorders, chronic fatigue, poor reproductive and vocational outcomes, and visual impairment.
The team hope that this study will give voice to survivors of so-called “benign” brain tumours (that are rather “malignant” by location!) and for whom high survival rates are compromised by high morbidity and impaired long-term quality of life from the burden of hypothalamic damage. This is caused by disease location and regrowth and by the recurrent long-term chemotherapies, surgeries and radiation, necessary to effect “cure”.
This project arose from the need of developing precise diagnostic tools for hypothalamic dysfunction. The results of this research will hopefully improve diagnostic accuracy and guide the development of a clinical questionnaire to recognise hypothalamic dysfunction and reduce time to diagnosis.
Better understanding of this condition will lay the groundwork for future research into novel targeted medical treatments and neurosurgical strategies to improve survival and reduce long-term complications.
This project will contribute to raising awareness of this debilitating condition and promote interdisciplinary clinical and research collaborations to improve care for these children with life-threatening and multisystem problems.
This project involves a collaboration between the Paediatric Endocrine Team at Great Ormond Street Hospital (GOSH) and the Developmental Imaging and Biophysics Section (DIBS) at the UCL GOS Institute of Child Health (ICH).
The Neuroendocrine Division at GOSH cares for the largest single-centre cohort of children with Hypothalamo-Pituitary disorders in the UK. The Chemical Pathology Laboratory at GOSH is fully equipped to perform Enzyme-Linked Immunosorbent Assay (ELISA) and has already hosted a clinical PhD student for the development of biochemical assays for the measurement of hypothalamic peptides. The DIBS at ICH has access to advanced MRI facilities and expertise. The GOSH Neuroradiology Team has experience of interpreting brain images of complex and rare paediatric diseases.
The key members of this project are Dr Manuela Cerbone, Prof Mehul Dattani, Dr Helen Spoudeas and Prof Christopher Clark.
Dr Cerbone will have a pivotal role in the development/planning of the protocol, patient recruitment and data collection/analysis.
She will be collaborating with various professionals in the DIBS ICH and GOSH Neuroradiology Departments for image analysis, and with clinical laboratory scientists and a previous PhD Student at GOSH for the hypothalamic peptides measurement. They will be linking with external laboratories (Newcastle, Manchester and Cambridge) for some of these hormone analyses.
Prof Mehul Dattani and Dr Helen Spoudeas are the GOSH lead clinicians for congenital neuroendocrine disorders and for the late endocrine effects of childhood brain tumours, respectively. They have active research programmes in these fields.
Prof Christopher Clark has a longstanding research interest on the application of novel neuroimaging methods for the understanding of neurological disability.