Report on a visit by the Birmingham Local Support Group in February 2002

Professor Paul Stewart and two of his consultant colleagues, Dr Andrew Toogood and Dr Neil Gittoes, kindly conducted members of our Birmingham group upon a guided tour of the recently-completed Clinical Research Facility (CRF) at the Queen Elizabeth Hospital, Birmingham and gave us all some insight into how research into pituitary conditions might impact upon our future care.

Professor Stewart (who is the Co-Director of Birmingham's CRF) started by saying how difficult it had become within the modern NHS framework to carry out patient-orientated clinical research. Without the luxury of being able to admit patients purely for research purposes clinical research has suffered throughout the UK. The Wellcome Trust acknowledged the need to provide such accommodation and three years ago announced funding for five CRFs within the UK, in Cambridge, Edinburgh, Birmingham, Manchester and Southampton. Hopefully, with the success of these CRFs, more units will be formed. CRFs operate through a close partnership between The Wellcome Trust (who provided money to build the CRF) and local NHS Trust and University.

Research projects

The CRF in Birmingham co-ordinates a wide variety of research projects, including a large number of which are endocrine-based. As a result of this, the accommodation must be flexible, coping with patients for a varying lengths of time, from a couple of hours for simple tests, through overnight stays and sometimes, even days in order to carry out intensive studies. This is delivered through a mixture of consulting rooms, out-patient bays comprising both reclining chairs and fully-equipped beds, and a more intensive in-patient area. Very sick patients can be studied in a special environment-controlled room where the ventilation can be totally controlled and the patient can be fed and tended without the need to open the room. Although each area of the CRF is designed primarily for research purposes, an underlying aim of the CRF is to provide full medical care. The CRF also houses a sample processing laboratory, a place to store samples and a core laboratory where human tissues can be analysed under a microscope or even cultured in special flasks. Intensive investigations can be undertaken within the CRF in a purpose built cardiovascular suite and endoscopy room. The CRF also provides an X-ray densitometer machine to accurately measure total body bone, muscle and fat mass. Education into research is an important aspect of CRF activity and, in addition to administrative offices, the facility has seminar rooms, IT equipment and statistical support.

Dr Toogood and Dr Gittoes provided some insight into what pituitary-related research projects were already underway in Birmingham.

Dr Toogood is extending research that he commenced with Professor Steve Shalet in Manchester involving Growth hormone replacement therapy. Studies have shown that the two main areas that are affected by growth hormone deficiency (GHD) are body composition and quality of life. Bone mass also appears to be affected by GHD. Dr Toogood is defining cardiovascular risk factors in 1,000 patients with hypopituitarism from the Birmingham area and seeing whether this is related in anyway to deficient hormones (sex steroids, Cortisol, thyroid hormone, growth hormone). He is planning a large trial of GH replacement therapy in this field.

Another area where GHD is likely to be important is in adults who survived cancer in childhood. These patients are usually GH deficient, not because they had a Pituitary tumour but because the Radiotherapy and/or chemotherapy treatment they received to cure a brain tumour or leukaemia has caused pituitary damage. There are over 3500 such patients in the West Midlands Region, the oldest of whom are now in their mid 30s and have recently been investigated by Dr Toogood. The long-term management of this group will place new demands upon the NHS, and research will be essential to monitor their outcome.

Because obesity is a recognised feature of GHD, in the context of hypopituitarism, the CRF is also looking at whether GH replacement might be used to treat obese patients who have no evidence of pituitary disease.

Possible causes of pituitary tumours

Dr Gittoes explained that he was principally interested in why patients developed pituitary tumours. He performs molecular research on pituitary tumour tissue which has been collected, with consent, from patients undergoing pituitary surgery and has over 180 such samples. This collection provides a very powerful resource for research into the molecular parameters and genes that are expressed in pituitary tumours. Research is being directed at a newly described pituitary tumour-transforming gene (PTTG), originally discovered in rodent pituitary tumours but now also in human pituitary tumours. Another area of research is analysing the secretion of various enzymes in pituitary tumours that might promote either the start or progression of the tumour. One aim of this research is to identify prognostic markers that could be used in any individual case to predict whether a tumour might recur following surgery for example. Gene therapy could also prove to be a useful tool in the future by delivering a beneficial gene to the tumour at the time of surgery, but this research is in its very early stages.

Acromegaly research

The group in Birmingham continues to play a leading role in documenting the long-term effects of acromegaly. This is achieved by "flagging" patients centrally with the Office of National Statistics and, in turn, receiving regular feedback on patient outcome. By performing this on large numbers of patients (across the West Midlands the group have collected over 440 patients), relationships with endocrine parameters such as latest GH and IGF-1 levels can be ascertained. In addition, multi-centre clinical trials are ongoing to evaluate new medical therapies to treat patients with acromegaly including Somatostatin analogues and the growth hormone receptor antagonist, pegvisomant ¹.

The future of research

Finally, the consultants spent time answering many of our questions on varied topics including pituitary radiotherapy, optimal replacement therapy and surgery.

It was truly an exciting day and we extend our thanks to the endocrinologists in Birmingham and the staff of the CRF for hosting us all. In particular, the ability to see first hand state-of-the-art research facilities and hear something about the ongoing research projects within Birmingham was of great reassurance. We all strive for excellence in our clinical management, but must appreciate that ongoing research is essential to make this possible, not only for ourselves, but also for future patients with pituitary disease.

Footnote

¹ Acromegaly treatments are explained in Dr Peter Trainer's article in Issue 24 of Pituitary News.