Date of Award

2011

Document type

Thesis

Degree Name

MD (Medical Doctor)

First Supervisor

Professor Paul Stewart

Keywords

Acromegaly, Endocrine System Diseases

Abstract

Acromegaly is a rare disabling disease characterised by excess growth hormone (GH) secretion and circulating insulin like growth factor-l (IGF-I) concentrations. In addition to significant morbidity, acromegaly is associated with increased mortality, which has been demonstrated in a number of retrospective studies with standardised mortality ratios (SMR) between 1.3 and 3 (comprising over 5,000 patients and 1,000 deaths).

Optimum management of patients with acromegaly requires appropriate investigation, treatment and defining targets for therapy that are associated with a reduction in overall morbidity and mortality in these patients. Due to the rare nature of this disease studies are often small and studies related to mortality are often multicentre (a limitation due to different growth hormone and IGF-I assays used in each centre).

With this in mind the West Midlands Acromegaly database was established in 1990 as a collaboration between 16 West Midland Endocrine centres and is centrally located at the Queen Elizabeth Hospital in Birmingham. The West Midlands region has an overall population of 5.7 million. To ensure optimum patient ascertainment, all patients with a diagnosis of acromegaly in each of the referral centres were flagged by physicians. Also, all patients with an elevated GH or IGF-I measurement in the Regional Endocrine laboratory at Selly Oak Hospital Birmingham were also flagged and their case notes assessed for a diagnosis of acromegaly. The Regional Endocrine laboratory at Selly Oak Hospital Birmingham is the regional centre for GH and IGF-I assays these assays, therefore all samples in the study were analysed here. Follow up biochemical and clinical data was recorded in the database. With this data the aims of this thesis were as follows:

  1. Does a basel fasting GH predict the nadir GH during an OGTT or mean GH during a GHDC in the assessment of disease activity during follow up in patients with acromegaly?
  2. What is the degree of discordance between disease activity measured by GH and IGF-I values?
  3. Does exposure to radiotherapy have an effect on the above relationship?
  4. To evaluate the role of baseline prolactin concentrations (and tumour immunohistochemical staining), prior surgery or radiotherapy and pituitary hormonal deficiencies in the response of GH and IGF-I to dopamine agonist therapy and somatostatin analogue therapy.
  5. Assess the relative efficacy of dopamine agonist therapy compared to somatostatin analogue therapy in patients with acromegaly, in routine clinical practice.
  6. To determine the efficacy of SSA in clinical practice compared to that observed in clinical trials (and the relative efficacy of subcutaneous versus long acting preparations of SSA).
  7. To assess the role of radiotherapy on mortality in patients with acromegaly
  8. To access the role of hypopituitarism (in particular the effect of individual pituitary axis deficiency) and their replacement on mortality
  9. To assess the targets for GH and IGF-I which normalize mortality and assess newer ways of assessing the role of GH/IGF-I in mortality in acromegaly.

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Comments

A thesis presented for the award of MD to the Royal College of Surgeons in Ireland, 2011.