The hypothalamus is a small but vital structure of the brain regulating multiple essential functions of the body such as thirst, hunger-satiety, sleep-wake cycle, blood pressure, heart rate, behaviour and thermoregulation. The hypothalamus is also tightly connected with another vital structure of the brain, the pituitary gland, which represents the master regulatory gland of the endocrine system. The hypothalamo-pituitary system regulates growth, puberty, reproduction, salt and water balance and stress response. Hypothalamic dysfunction (HD) is a rare, complex, highly variable and poorly understood life-limiting disorder significantly compromising quality of life, increasing disability and causing premature mortality from its secondary life-threatening complications. Current diagnostic tools are do not allow clear differentiation between hypothalamic and more manageable pituitary disorders and conventional qualitative neuroimaging techniques are unable to accurately anatomically define the hypothalamus. As a result, the endocrine phenotypes of these children are highly unpredictable and targeted interventions are lacking. The proposed project aims to identify, with the help of advanced quantitative MRI, structural and functional hypothalamic abnormalities and to correlate anatomical findings with specific hormonal patterns and clinical symptoms. The ultimate aim is to develop prediction models directly translatable into clinical practice. We will be studying hypothalamic dysfunction in children with congenital midline brain lesions as well as in children surviving brain tumours. The proposed study is directly relevant to any children with acquired or congenital lesions of the hypothalamo-pituitary axis, for whom current therapies are inadequate to ameliorate life-limiting obesity, risk of secondary type 2 diabetes mellitus and neuro-behavioural disorders, or improve health-related quality of life.