Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.577520
Title: RNA interference as therapy in a model of Cushing's disease
Author: Munir, Alia
Awarding Body: University of Sheffield
Current Institution: University of Sheffield
Date of Award: 2012
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Abstract:
Hypothesis: That siRNAs could be translated into systemic therapy for Cushing's disease in man. Background and importance: Cushing's disease is an uncommon but devastating condition, with a mean age of onset of 36 years, and a five-fold excess mortality when inadequately treated. Major complications include diabetes, hypertension, osteoporosis, life-threatening infection, depression and psychosis. No established ACTH-Iowering medical therapy exists. 95% of cases are caused by a tiny benign corticotrope adenomas of the pituitary gland, often only millimetres in diameter, and in 40% of cases are invisible on MR!. These adenomas express the prohormone 'Pro-opiomelanocortin' (pOMC), which undergoes post-translational processing to adrenocorticotrophin (ACTH), before secretion into the systemic circulation. ACTH drives the adrenal glands to synthesise and secrete excessive amounts of the hormone cortisol, which causes the clinical condition of Cushing's disease. Invasive neurosurgery aimed at removal of the pituitary tumour, causes long-term remission in only 50% of patients with Cushing's disease and results in hypopituitarism in approximately half. Hypopituitarism is associated with a two-fold excess mortality. Bilateral adrenalectomy is effective treatment but is complicated by life-long hypoadrenalism (two-fold excess mortality) and the development of an expanding, and pituitary mass (Nelson's syndrome) in up to 30% of cases. Use of adrenal steroidogenesis inhibitors is not usually effective in long-term management.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.577520  DOI: Not available
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