The Changing Face of Hypopituitarism in Modern Endocrinology

Abstract

The impact of advances in medicine, neurosurgery and critical care on clinical practice in modern endocrinology is not entirely clear. This is because reports in current literature include various confounders. Furthermore, it is becoming increasing recognised that hypopituitarism can be caused by pathologies outside the pituitary gland, such as traumatic brain injury and subarachnoid haemorrhage. The objective of this thesis is two-fold. Firstly is to examine the variables associated with pituitary dysfunction in modern clinical endocrinology. To do this, the thesis will investigate a spectrum of pituitary pathologies associated with varying degrees of hypopituitarism. This will compromise patients with pituitary apoplexy, non-functioning pituitary adenoma (NFPA) and subarachnoid haemorrhage (SAH). Secondly, given that growth hormone deficiency (GHD) is increasingly recognised as a consequence of subarachnoid haemorrhage, this thesis will investigate the impact of growth hormone replacement (GHR) on survivors of subarachnoid haemorrhage who have developed growth hormone deficiency. This is novel as there are currently no publications reporting on the use of growth hormone exclusively in this group of patients. Data about patients with pituitary apoplexy and NFPA were collected retrospectively. Patients with SAH were prospectively screened for GHD with dynamic pituitary function testing. Patient with GHD received 36 weeks of GHR and underwent a series of quality of life, cardiorespiratory and metabolic assessment before and after treatment with GHR. In the cohort of patients with pituitary apoplexy, rate of hypopituitarism was high regardless of management pathway (73-91%). Recovery or preservation of visual function was good. Management should be directly by visual symptoms rather than for preservation of endocrine function. In the cohort of patients with NFPA, hypopituitarism was associated with tumour size, gender and age. After pituitary surgery, women were more likely to experience improvement in pituitary function, whereas men were more likely to experience deterioration in endocrine function. Patients with improved pituitary function had higher serum prolactin levels at presentation. It was also demonstrated that the effect of pituitary surgery of different axes is variable, with ACTH axis most likely to change. In the cohort of patients with SAH, it was demonstrated that the rate of hypopituitarism (19%) and specifically GHD (14%) was relatively low when dynamic and confirmatory pituitary testing protocol was employed. GHR is associated with improved weight, BMI, cardiorespiratory fitness, mood and quality in patients who have developed GHD after SAH.

Date of Award	1 Aug 2018
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Philip Kalra (Supervisor) & Tara Kearney (Supervisor)