Date of Award

2011

Document type

Thesis

Degree Name

MD (Medical Doctor)

First Supervisor

Professor Christopher J. Thompson

Keywords

Craniopharyngioma, Mortality, Hypothalamic Diseases, Ireland.

Abstract

Craniopharyngioma (CP) patients suffer from high rates of morbidity and mortality. The aim of this study was to describe hypothalamic morbidityand establish the standardised mortality ratio for CP patients attendingthe national neurosurgical unit in Ireland; to investigate abnormalities ofthirst, sleep disorders and somnolence, glucose tolerance and abnormalhormonal responses to food intake, in CP patients.

The standardised mortality ratio for craniopharyngioma patients in this study was 8.75, with a predominance of deaths due to cardiovascular andrespiratory disease. Over 80% of CP patients had panhypopituitarism, including diabetes insipidus. Four patients with diabetes insipidus had adipsia, which is associated in the published literature with increased morbidity and mortality. Tumour recurrence ocurred in 46%, and hydrocephalus was diagnosed in 40% of CPs. Sixty-six percent of CPs were obese and 26% were overweight.

Seventy-one percent of CP patients suffered from somnolence and 46%were diagnosed with sleep apnoea; thus not all somnolence in CP wasexplained by sleep apnoea. Somnolence responded to treatment with continuous positive airway pressure therapy or modafinil.

Abnormal glucose tolerance was identified in 40% of CP patients, who were insulin resistant and obese or overweight. The CP patients with abnormal glucose tolerance were older when diagnosed with CP than those with normal glucose tolerance.

CP patients had similar ghrelin levels to normal weight controls, which suggested that excess ghrelin was not the explanation for obesity in CP. However serum ghrelin levels in CP patients suppressed after food ingestion and were lower in patients with apnoea than in those without apnoea, which suggested that the hypothalamus remained sensitive to ghrelin signalling.

This study confirms the previous reports of high rates of morbidity and mortality in CP patients and identifies new targets for treatment of morbidity, such as dysnatraemia, somnolence and abnormal glucose tolerance.

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Comments

A thesis submitted to the Royal College of Surgeons in Ireland for the degree of Doctor of Medicine from the National University of Ireland in 2011.