Ayuk, John (2010)
M.D. thesis, University of Birmingham.
This thesis defines mortality in acromegaly in a modern patient cohort, elucidates underlying explanations for the increased mortality and explores the impact of treatment, focussing on somatostatin analogue therapy. Results confirm there remains a 30% increase in mortality in patients with acromegaly. Mortality was increased in patients with GH >2µg/L, but not in patients with raised IGF-I. This is the first study showing reduced survival in patients with acromegaly following pituitary radiotherapy. Somatostatin analogue therapy was shown to be efficacious and safe. I also explored factors influencing pituitary tumourigenesis by characterising mRNA levels for 11β-HSD isozymes in normal and neoplastic pituitary tissue. Results demonstrated reduced 11β-HSDl expression and 10-fold increased 11β-HSD2 expression in pituitary tumours compared with normal pituitary, resulting in reduced active glucocorticoid concentrations within the pituitary. This may diminish the antiproliferative effects of glucocorticoids, thus contributing to the process of pituitary tumourigenesis. Finally, I explored complications of pituitary adenomas by evaluating outcome in patients presenting acutely with pituitary apoplexy. Patients presenting without visual deficit or showing evidence of early improvement in visual deficit can be managed without acute neurosurgical intervention. Results of this research will undoubtedly improve the management and outcome of patients with acromegaly and pituitary tumours.
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