Novel aspects of commonly encountered pituitary adenomas in clinical practice

© 2019 Carmela CaputoClinically relevant pituitary adenomas are common in the general population occurring in 1 per 865-1470 people. Prolactinomas and non-functioning pituitary adenomas account for more than 80% of pituitary adenoma types. My thesis is composed of several studies, undertaken at a single centre specialising in the multidisciplinary care of pituitary diseases, investigating clinical issues pertinent to the management of patients with the above adenomas. The findings of these studies contribute to the understanding of outcomes in the local practice, as well as being an Australian contribution to the international experience of managing these adenomas. Firstly, I examine the issue of valvular heart disease in prolactinoma patients treated with cabergoline therapy. By studying a local cohort and by a systematic review I found that the prevalence of cabergoline-associated valvular heart disease (CAV) in prolactinoma patients to be extremely low, with just three confirmed cases amongst 1800 patients described in the literature. I have shown evidence that a simple annual cardiovascular examination is a suitable screening tool for this rare condition and made recommendations on when to consider a diagnostic echocardiogram. Secondly, I examine two clinical issues affecting patients with surgically treated non-functioning pituitary macroadenomas (NFPMAs): the issues of regrowth and recurrence, and of hormonal outcomes. In the largest Australian cohort of cases with NFPMAs to be described, it was found that residual disease is a common finding post-surgery. In cases with residual disease, regrowth occurred in 40% of these cases compared to only 12.5% in cases without residual disease, at a median of 3.6 years of follow-up. Not surprisingly, larger baseline adenoma size was a predictor of regrowth and recurrence. In multivariate analysis, the presence of residual disease and younger age (under 41 years) at presentation were independent risk factors for regrowth and recurrences. Based on this risk factor of younger age, I have recommended that these cases have lifelong radiological follow-up. Results of hormonal outcomes in cases with NFPMAs treated with surgery showed the novel finding of gender differences in hormonal outcomes, with males having a higher prevalence of multiple (more than two) hormone deficiencies (MHD) at presentation than females, and after surgery. In particular, pre-menopausal females had very few hormone deficiencies post-operatively and demonstrated a propensity to recover function. These gender subgroup differences are the first to be noted in the literature and have important clinical implications particularly for pre-menopausal females where fertility preservation is an issue. I also found that pre-menopausal females had smaller adenomas than males suggesting that they may present earlier in the natural history of the disease. In multivariate analysis, larger adenoma size remained a significant factor associated with post-operative MHD. The final part of this thesis is an exploratory study of intrasellar pressure (ISP) and how it relates to adenoma size and hormonal outcomes in cases with NFPMAs undergoing surgery. I did not find that ISP was correlated to adenoma size, but results did suggest that raised ISP may play a role in more frequent hormone deficiencies at presentation. In this study adenoma size was again noted to be showing a trend towards influencing hormonal outcomes. The findings from this study will require a larger cohort in order to better quantify how ISP and adenoma size interact to contribute to the pathophysiology of hormone deficiencies. In these three studies of NFPMAs adenoma size has emerged as an important factor influencing surgical and hormonal outcomes; smaller adenomas are more likely to be fully resected and less likely to result in hormone deficiencies. This thesis lays the foundations for advocating for the consideration of early surgical intervention of NFPMAs (when adenomas are smaller and earlier in the natural history of the disease), in order to optimise surgical and hormone outcomes. The above should now be an important clinical consideration in the multidisciplinary care of these patients