An Endocrine Prologue

     The interest in ‘endocrine’ glands began in antiquity when the most obvious organs accessible to the knife, the testes, were sometimes removed either to make the harem safe, or to extend the duration of the male soprano voice into adulthood. On a culinary note, testicular removal made a rooster into a capon which was much more palatable. The other common presentation of endocrine disease was thirst, copious production of urine and weight loss. Descriptions of this condition can be seen in medical literature from Egyptian papyri, and from Indian, Chinese, Greek and Arab sources. In the second Century AD, Aretaeous of Cappadocia^[1] coined the name ‘diabetes’ though it was not till the 17th Century that the English anatomist and physician, Thomas Willis added ‘mellitus’ to diabetes in view of the sweet nature of the urine produced.

It was, however, the emergence of anatomy and physiology as scientific disciplines that concentrated minds upon those tissues of the body which looked like glands or organs and had a rich blood supply yet had no ducts (blood-glands). ^[2]   

A Thyroid Narrative

     The other gland relatively accessible to the knife, particularly if enlarged, was the thyroid. The Chinese used burnt sponge and seaweed to treat goitre over many millennia. In 150 AD, Hippocrates and Plato recognised this treatment and thought that the thyroid gland lubricated the larynx. Thomas Wharton, anatomist in 1656, wrote

A Greek Shield

about the anatomy of the gland that he thought it was there to heat the larynx. He named it ‘thyroid’ after the ancient Greek shield with a similar pronunciation. In German, the thyroid is ‘die Schilddrüse’, the shield gland. Two other anatomists, from Holland Frederik Ruysch in the 17^th, from Switzerland Albrecht Von Haller in the 18^th Century and Thomas Wilkinson King who was

Swiss gargoyle with nodular goitre^[3]

a physiologist in the early 19^th Century Britain, each wondered whether the thyroid elaborated a secretion which was carried away by the veins.

Painting of a goitrous cretin from the Swiss Alps^[3]

Thyroid history in the 19th Century, however, was a tale of three streams which converged as knowledge of its function emerged. These streams were Iodine, Goitre and Cretinism/hypothyroidism.

In 1811, the French chemist Bernard Courtois was extracting soda from burnt seaweed because of a shortage of the usual woodash. He tried to clear the deposit on the bottom of his copper extraction vessels with sulphuric acid and immediately noticed an intense violet vapour which condensed in the form of crystals. By circuitous routes, the crystals eventually reached both the French chemist Joseph Louis Gay-Lussac and, with the permission of Napoleon, Sir Humphrey Davy. 

Sir Humphrey Davy by Thomas Phillips

Each chemist separately identified a new chemical element which they agreed to call  “iode”, or iodine, from the Greek word for violet.

It is not clear why iodine then became the focus for the treatment of thyroid enlargement. Initially suggested by Dr William Prout in London, 1816^[4], it was John Elliotson from St Thomas’ Hospital who used it for goitre in 1819. In 1820, the Swiss physician Jean Francois Coindet used a tincture of iodine more widely with initial success. His treatment was questioned and fell into disrepute when some individuals developed hyperthyroidism (Jod-Basedow syndrome). In 1825, David Scott used iodine to treat goitre in Assam, India and in 1831, the French chemist Jean-Baptiste Boussingault used iodised salt in present day Columbia for the same condition. In 1835, Caleb H Parry followed by Robert James Graves from Ireland described hyperthyroidism with

Robert Graves

goitre and noted an ophthalmopathy. The German physician Karl Adolph von Basedow independently reported similar cases in 1840 and firmly linked hyperthyroidism with the associated ophthalmopathy. In 1851, the French physician Caspar-Adolphe Chatin discovered that certain goitrous areas of Europe were associated with a low environmental iodine. While the national scientific community in France remained sceptical about Chatin’s evidence, iodine prophylaxis for goitre began in earnest.

The History of Diabetes

    In 1815, the French chemist Michel Eugene Chevreul in Paris showed that the sweet tasting substance in the urine of patients with diabetes was glucose. In 1848, Hermann Von Fehling, a German chemist, developed a qualitative test for glucose in urine but it was not until 1889 that the pancreas became implicated in diabetes. Oscar Minskowski and Joseph von Mering, both German and working at the University of Strasbourgh, showed that dogs in whom the pancreas was removed developed diabetes mellitus. In 1893, The Frenchman Edouard Hedon showed that grafting pancreatic tissue back into the animal prevented diabetes from occurring. Something being secreted by pancreatic tissue was important for the prevention of diabetes. In the same year, the French scientist Gustave-Edouard Laguesse wondered whether the islands of tissue left after pancreatic duct ligation that had been described in 1869 by the German pathologist Paul Langerhans, might just be the source of the substance that controlled glucose levels. The concept of internal secretion by that time was close.

Contributions from Physiology and Anatomy

     In 1849, the German Physiologist Arnold Adolph Berthold performed a classic ‘endocrine’ experiment while studying maleness in chickens.

Arnold Berthold

He took 6 male chickens,castrated 4 and left 2 to develop rooster characteristics such as combs and wattles. Two castrati became chicken eunuchs or capons with soft flesh. In the final two, he transplanted the testes back into the abdominal cavity and found they developed normally as roosters. He concluded erroneously that the testes conditioned the blood to result in normal development. It was not until 1935 that pure testosterone was isolated.

In 1850, Thomas Blizzard Curling correlated the absence of thyroid tissue at autopsy in two children with cretinism. Come 1855, when physiological conundrums attracted the brightest of minds, the French physiologist Claude Bernard hypothesised that the liver might somehow secrete  glucose into the blood while in the same year, Thomas Addison, an Edinburgh graduate working in Guy’s Hospital,  proved, by autopsy, that suprarenal

Thomas Addison

gland destruction was present in 11 cases with weakness, vomiting and skin pigmentation which he understood to indicate chronic adrenal insufficiency but he was not believed at the time. In 1871, Charles Hilton Fagge presented a paper describing four children with sporadic cretinism and wondered whether the thyroid had ‘wasted’. Two years later in 1873, William Gull of Guys Hospital described hypothyroidism in adult life as creating a cretinoid appearance with a thick tongue. In 1877, William Ord described ‘mucous oedema’ and proposed the term ‘myxoedema’ for the adult condition. He also described the ‘practical annihilation’ of the thyroid gland at autopsy in these patients.

A Surgical Contribution

Emil Kocher

     In 1882, Jaques-Louis Reverdin from Geneva and in 1883, Emil Theodor Kocher from Berne, both Swiss surgeons, noted that after total thyroidectomy, myxoedema was common. Because of this, they each experimented  by conserving part of the gland during thyroidectomy, and no further cases of myxoedema occurred. ^[5] Although they did not understand what was happening, these surgeons had provided the medical community with the key to understanding the importance of the thyroid gland. Kocher went on to be awarded the NOBEL prize for medicine in 1909 for work relating to the surgical and medical treatment of thyroid disease.

In 1883,  Felix Semon, a trainee laryngologist, later Sir Felix, suggested, to much ridicule from medical colleagues, that myxoedema and cretinism were one and the same condition, namely the effects of hypothyroidism. What he managed to do was to encourage his surgical colleagues to  survey the experience of thyroid surgeons Europewide. Reporting in 1888 and using experimental work on thyroidectomised

Sir Victor Horsely^[7]

monkeys by Sir Victor Horsley ^[6], the renowned scientist/surgeon who followed on in neurosurgery from Sir William Macewan, the report vindicated Semon and concluded that myxoedema was almost certainly due to loss of thyroid function and could lead to cretinoid features. Horsley went on to advocate surgical grafting of sheep thyroid into patients with myxoedema and in 1890, Bettencourt and Serrano of Lisbon had success with resolution of some clinical features in a case grafted under the breast. They then tried hypodermic injections of thyroid juice in 1891 and reported these beneficial too. The function of thyroid was now clear though the mechanism remained a mystery.

In 1891, Horsely and Professor George Redmayne Murray also continued along these therapeutic lines and

George Redmayne Murray^[8]

and used hypodermic injections of sheep thyroid extract into a patient with myxoedema and described a dramatic improvement. Murray provided details of his method of preparation and administration of the extract. Later that year, after publications from H W MacKenzie and E L Fox who had separately treated hypothyroid patients with thyroid extract by mouth, he changed to oral administration of pooled sheep thyroid extract with similar effect and so oral replacement therapy for glandular hypofunction was born.

 

 Parathyroids, Pituitary and Adrenal 

     Ivar Sandstrőm, Uppsala medical student in 1887, confirmed the existence of the parathyroid glands in 50 autopsies and in 1901, the French physiologist Eugene Gley linked the absence of parathyroids after thyroid surgery to tetany which was often a sequel. ^[9]

Although the pituitary gland had been recognised in previous years at autopsy, for instance in studies of the two Irish Giants, its clinical role was more difficult to define because of its position in the centre of the skull. Clinical interest in the pituitary gland mainly arose from the studies and description of Acromegaly by Drs Pierre Marie, French neurologist, and José Dantas de Souza-Leites from Brazil in 1886 ^[10].

In 1893, George Oliver was interested in extract of adrenal gland to treat low blood pressure. He listed the help of Edward Shafer, Professor of Physiology at University College, London and found that his extract greatly raised the blood pressure in dogs. They both went on to discover that the effect was due to extract of medulla and not cortex.

Clearly, the important parts of the ‘endocrine’ or blood-gland jigsaw were gradually being assembled and one-by-one, the glandular origins of clinical deficiency syndromes were becoming clearer. The work on insulin, in particular, clearly pointed to a pancreatic source for a secretion of some sort preventing diabetes.

The Fog Clears

     In 1905, the British physiologists Ernest Starling and his brother-in-law William Bayliss discovered something in the blood that caused the pancreas to secrete digestive juices.

Professor Ernest Starling^[10]

Their experiment was in two parts. Firstly, they had used a completely denervated loop of duodenum, activated it by food, and found it stimulated pancreatic juice flow. Thinking that it must be something in duodenum, they liquified duodenal mucosa, injected it into the denervated animal model and found again that pancreatic juice flowed. Starling and Bayliss realised that a substance, which they called ‘secretin’, passed from the stimulated duodenum to the pancreas to stimulate it by virtue of the circulation of blood and not by the nervous system. They confirmed this hypothesis on the second experiment. Starling proposed after consultation with a classics trained colleague that such substances were called ‘hormones’ after the Greek ‘ormao’ – to excite, and at this precise point in history, a new speciality called  ‘endocrinology‘ emerged. It studied substances produced by one tissue and then transported by the circulation of blood to another tissue, called the target.

First use of the word ‘hormone’ in 1905^[2]

The final part of the jigsaw, the concept of circulating hormones, had fallen into place in the early 20th century. The work by Frederick Grant Banting, Charles Best, John J R MacLeod and James Collip in extracting an insulin soup from atrophied pancreatic glands, purifying it, and by 1921,  using the purified material in clinical practice was a monumental moment in the history of endocrinology. They had learned the lessons of the past and even had a name for the substance because in 1909, the Belgian physician Jean de Mayer had named the putative substance produced by the Islets of Langerhans, “insulin”.

When supplies of the purified animal sourced insulin reached the UK in May 1923, they saved the life of Dr Robert (Robin) Daniel Lawrence, a Scot from Aberdeen, among many others. Lawrence became one of the first UK physicians in diabetes at King’s College Hospital, London. He later co-founded the Diabetic Association with author and historian Herbert George (H G) Wells which later became the British Diabetic Association.

Although physiologists and the new ‘endocrinologists’ were unable to directly quantitate the actual hormones at this time, indirect ways were devised by them and physiologists to measure the ‘exciting’ effects of hormones on other tissues. It would be another 40 years before clinical measurement of insulin in blood would be possible but at least in 1921, there was a rational treatment for diabetes and myxoedema.

 References

[1].    Milestones in the history of diabetes mellitus: The main contributors. World Journal of Diabetes, 2016, Jan 10; 7 (1): 1-7.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4707300/

[2]      Starling Review: Ernest Starling and ‘Hormones’: An historical commentary, by John Henderson. Journal of Endocrinology, Volume 184, Issue 1, 2005, pages 5-10. 

http://ressources.unisciel.fr/biocell/chap11/res/03_hormone_starling_henderson.pdf

[3]     By courtesy of the European Thyroid Association and from the 4th Annual Meeting in Berne, 1971, President Prof H. Studer.

[4]       A History of Iodine Deficiency Disorder Eradication Efforts, by J Woody Sistrunk and Frits van der Haar, in ‘Iodine Deficiency Disorders and Their Elimination’, Editor Elizabeth N Pearce, Associate Professor of Medicine, Boston University School of Medicine, Boston, MA,  Springer 2017. Accessed on 12 February, 2018.

http://books.google.co.uk/books?id=Fo4JDgAAQBAJ&pg=PA5&lpg=PA5&dq=Chatin+endemic+goitre&source=bl&ots=KoK32iNVAi&sig=kK57jlxisqy2PsafOxFeVZFypcc&hl=en&sa=X&ved=0ahUKEwiVtITzpZ7ZAhUsC8AKHRK8BoEQ6AEIRzAG#v=onepage&q=Chatin%20endemic%20goitre&f=false

[5]       Hypothyroidism and Thyroid Substitution: Historical Aspects by J Lindholm and P Laurberg, 2011. Journal of Thyroid Research, Volume 2011, Article ID809341. Accessed 12th February, 2018.

http://hindawi.com/journals/jtr/2011/809341/

[6]     The Discovery of Thyroid Replacement Therapy.  JLL Bulletin: Commentaries on the   History of Treatment Evaluation. Stephan D Slater, 2010. Accessed 20 November 2017.

jameslindlibrary.org/articles/the-discovery-of-thyroid-replacement-therapy/

[7].   In. ‘Sir Victor Horsely, an inspiration’. BMJ. 2006; 333, 1317.

[8].    By courtesy of The James Lind Library.

[9]      The History of Parathyroids. Accessed 20th November, 2017.

http://endocrinesurgeon.co.uk/index.php/the-history-of-the-parathyroids

[10]     In the land of Giants: the legacy of Jose Dantas de Souza Leite. Accessed 20 November, 2017.

http://scielo.br/pdf/anp/v73n7/0004-282X-anp-73-7-0630

H W Gray

J A Thomson

 

 

 

 

An Endocrine Unit Is Born

     Glasgow Royal Infirmary (GRI) entered the 20th Century with real pressures on the Board of Management to improve the surgical block to permit surgical specialisation and anaesthetic advances. Wisely, they chose to rebuild though this required agreement with GRI donors for the legal transference of running expense to the capital account. There was pressure too on the St Mungo’s College Governors who ran the medical school from 1888 without the University of Glasgow medical students who had followed their teachers to the Western Infirmary. While a University education was preferable, most individuals of modest means had chosen St Mungo’s and GRI because of cost. However, in 1901, Carnegie Trust grants to pay class fees became available for less well-off medical students and so a University degree became possible for this group. At the same time, the supply of medical students from England, Ireland and Wales began to dry up with the opening of new Medical Schools in the provincial cities of England. It was an existential problem for St Mungo’s College, a staffing issue for GRI which required young doctors for locum and house-officer posts and a waste of superb teaching facilities.

The University Returns to Glasgow Royal Infirmary

     The solution to the lack of medical students came in 1907 thanks to the Trust of the late Dr Thomas Muirhead and the insight of Sir Donald MacAlister, University Principal of the time which led to a rapprochement between University and GRI. The Muirhead Trust not only agreed to endow St Mungo’s College with a University Chair in Medicine and one in Obstetrics, but as a serendipidous caveat, insisted that the College and the University work together again for training medical students. The College agreed to endow two new University chairs themselves and also to continue their policy that medical teaching was open to women on equal terms with men, another key stipulation of the Trust. In 1911, after tying up loose ends, the Muirhead Chairs of Medicine and Obstetrics and Gynaecology were filled at GRI as were the St Mungo Chair of Surgery and the St Mungo-Notman Chair of Pathology. The clinicians at GRI were now training both the College students and those on the MB course in clinical medicine and surgery although evidence suggests that the University Professors only taught the MB course. After 37 years on its own, GRI had returned to its role as a major teaching hospital in Glasgow.

The first Muirhead Professor of Medicine at GRI was Walter King Hunter in 1911. He graduated with a BSc in 1888 and MB 2 years later. After postgraduate study in neurology in London and Paris, his MD in 1897 entitled ‘The Aetiology of Beri-beri’ received commendation.

Walter King Hunter

He went on to receive a DSc from the University in 1901. While passionate about neurology, Hunter also published on haematology while he was on the junior visiting staff of the Royal Hospital for Sick Children. He quickly became assistant physician at GRI and used his knowledge of the histopathology of the nervous system to study the effects, on the CNS, of venoms of 5 different Indian snakes in collaboration with Captain George Lamb of the Indian Medical Service. This work was published in the Lancet in 6 instalments between 1904 and 1906. By 1906, he had become physician to GRI and Lecturer in Practice of Medicine to Queen Margaret College of the University. At this time, he was also consultant physician to the Glasgow Royal Mental Hospital and visiting physician to Bellefield Sanatarium in Lanark. Experience here permitted him to contribute a chapter on ‘Treatment’ in Maylard’s Abdominal Tuberculosis in 1908.

After his appointment to the Muirhead Chair, he was recognised as an inspirational bedside teacher of clinical medicine in the mould of Sir William T Gairdner and was known by the nickname ‘Uncle Walter’ by his housemen and and generations of students.

He died in 1947^[1] as one of the most distinguished physicians of his generation in Scotland.

The second Muirhead Professor of Medicine was Archibald Wilson Harrington, a

Archibald Wilson Harrington

graduate of Glasgow in 1900 and MD in 1903. Elected to the junior staff at GRI in 1906, he  gained the Fellowship of the Royal Faculty of Physicians and Surgeons of Glasgow (FRFPS ) in 1912, becoming assistant physician at GRI in 1913. Harrington served in the RAMC in the Balkan theatre with health consequences which continued throughout his professional life. Returning to consultant practice at GRI at the end of the war, Harrington was appointed lecturer in clinical medicine in the University in 1925. In 1927, he contributed an excellent teaching chapter ‘Examining the Heart’ to Finlayson’s Clinical Medicine, 1927 edition and with a keen perception of character, appointed Joseph Houston Wright^[2] to be his personal assistant.

Joe Wright

 

Joe Wright went on to be an outstanding clinician and cardiologist at GRI, President at RFCPS, Glasgow and member of the University  Court.

Harrington was a shy man who was, nevertheless, worth getting to know in light of his wide knowledge and experience. He always taught by example and his junior staff and students learned quickly. Harrington had an inquisitive mind but, in keeping with the post-war era, did not publish as much as his predecessor.

Professor Harrington left office in 1945 and died 1953^[3].

Clinical Practice and Biochemistry in the Early 20th Century

      At GRI in the early 20^th century, most senior staff were part-time generalists called visiting physicians and surgeons and made half of their living in private practice in consulting rooms down town. Many were Professors in the St Mungo’s Medical School with associated teaching and lecturing responsibilities. From 1911 to 1945, the University Muirhead Professors were also part-time with private practice. From 1884, the junior Dispensary Physicians were re-named Assistant Physicians and 4 years later, the just qualified residents were re-named house physicians.

Dry thyroid tabs

All the physicians would use the new preparation of dry thyroid or thyroid extract, from porcine or bovine sources, as replacement therapy for their patients with myxoedema and for those following thyroidectomy if required.

From 1923, they would also have used parenteral insulin for ketoacidotic crises of type 1 diabetes assisted by the new Department of Biochemistry established in 1926 under the then Dr David Paton Cuthbertson^[4], Lecturer in Pathological Biochemistry but based at GRI. However, blood sugar measurement would only be performed during working hours in the laboratory. In the evening and during the night, the-out-of hours assay of of blood sugar had still to be done by the house officers themselves using the Folin-Wu method and this situation continued until 1966 when a rudimentary out-of-hours service was introduced.

David Cuthbertson in the first Biochemistry laboratory at GRI^[5]

Cuthbertson gained a BSc from Glasgow in 1921 then MB in 1926. He was at GRI for 8 years during which time he actively published his research into the effects of injury, infection, bed rest or impaired mobility on metabolism.

Sir David Cuthbertson

This was a tour de force at this time and provided a much needed insight into the body reaction to stress from wherever it came.

During this early period of his career, Cuthbertson provided the foundation for modern nutritional therapy for seriously ill or injured patients. What he showed was trauma stimulated catabolism and that the source of the loss of nitrogen in urine was skeletal muscle. he became Director of the Rowatt Research Institute, Aberdeen between 1945 and 1965. He was later knighted, and received a CBE and DSc from Glasgow University. Cuthbertson remained a senior research fellow at GRI until his death in 1989.

Endocrinology Emerges 

     Eric Gordon Oastler, a Glasgow graduate and clinician, sowed the seeds of Endocrinology as a distinct speciality at GRI from his experiences in the physiology laboratories of Oxford where he distinguished himself with a First Class Honours BA in 1928 and an MA in 1934.

Eric Oastler

His first appointment to GRI was as an extra physician to the out patient department in 1931. Successive promotions quickly found him as assistant physician in 1934. Endocrinology in Glasgow germinated with his appointment as Professor of Physiology at St Mungo’s College Medical School, GRI in 1932 where he lectured to the medical students.

He was awarded a Rockefeller travelling medical fellowship and spent the academic year of 1934/35 working with Professor James Howard Means of Massachusetts General Hospital, Boston as resident fellow in medicine at Harvard Medical School. Professor Means had developed the Basal Metabolic Rate as an important indirect test for thyroid dysfunction and had explored treatment for thyrotoxicosis with external X-ray therapy. This research was a forerunner of radioactive iodine therapy. Oastler worked with Dr Saul Hertz in the laboratories at Harvard, and using an experimental hypophysectomised rat model, were the first to demonstrate thyroid stimulating hormone (TSH) in the urine and blood of hypothyroid patients but not in normal or thyrotoxic patients. These findings were important because they suggested strongly, for the first time using rats, that thyrotoxicosis was a primary thyroid disorder and not related to increased secretion of TSH. This work was reported in the Journal called ‘Endocrinology’ which was also known at the time as ‘The Bulletin of the Association for the Study of Internal Secretions’.

Oastler returned to the Royal Infirmary as the St Mungo Professor of Physiology in 1935 and pursued his increasing interest in clinical endocrinology but particularly in female disorders and adrenal disease.

Following active service in the war, he spent several years as senior physician at the Southern General Hospital, Glasgow, preparing that Institution to take medical students in 1950. In 1953, and during this time as a general endocrinologist at the Southern General, Oastler wrote an incisive review of Endocrine Exophthalmos for the Ophthalmological Society which was published in their Transactions Volume 73. He returned to the GRI in 1956 as physician in charge of second floor medicine becoming an honorary lecturer in clinical medicine and endocrinology at the University of Glasgow as well as consulting physician and head of endocrinology at the GRI and Royal Samaritan Hospital for Women. In accordance with the prevailing academic influence in the Infirmary which was low key in the late 1940s and early 1950s, he published rarely but mainly in gynaecological endocrinology. Despite his experience in thyroid disease and thyroid ophthalmopathy, Oastler agreed that in view of the UDM laboratory involvement, isotope support services and major clinical research interests, Edward McGirr and the University Department of Medicine on first floor would look after the clinical thyroid work at GRI.

Other activities included membership of the board of management for Glasgow Northern Hospitals and membership of the Western Regional Hospital Board, 1955-61, and vice-chairman, 1959-60.

Oastler will be remembered for his work on adrenal pathology and the later fruitful cooperation with Dr James (Jim) K Grant, Senior Lecturer in Steroid Biochemistry, who developed the highly respected regional Steroid Laboratory at GRI.^[6] 

Oastler, noted for his booming English accent, retired in 1967 and has been described by an individual who worked with him as the consummate Clinical Endocrinologist in the classical era prior to immunoassays and sophisticated imaging techniques. He is also remembered affectionately as an astute and knowledgeable clinician, a respected teacher, an able administrator, and for his sartorial elegance.

Dr Oastler died in 1990. ^[7]

Early Trainees in Medicine and Endocrinology

     William Gifford (Giff) Whyte, a Glasgow graduate, was a senior registrar with Dr Oastler for many

Giff Whyte

years on second floor. He was a highly regarded clinician and general endocrinologist who published mainly as supporting author in work concerning measurement of adrenocortical and gonadal function, obesity, hypertension and Addison’s disease. Working with Professor Robert B Goudie, he demonstrated autoantibodies to adrenocortical antigen in idiopathic Addison’s Disease. Whyte moved to South Lanarkshire in 1968 as a consultant with Robert Walker^[8] where he was part of the team who first recognised and published on Phenformin induced lactic acidosis in 1972.

Dr Whyte retired in 1986 and died in 2007.

     Stuart G McAlpine, a Glasgow graduate, was registrar in the University Medical Unit with Professor Davis on first floor medicine and was tasked with explaining the number of cases with hepatosplenomegaly at the medical clinics.

Stuart McAlpine

While initially interested in liver disease, for which he was awarded an MD with commendation, McAlpine also published studies on hypothyroidism, dysthyroid eye disease and nerve palsy in diabetes. He moved to Dumfries and Galloway Royal Infirmary in 1957 and 2 years later, to cardiology on 3^rd floor under Dr Joseph (Joe) Wright. McAlpine became consultant physician with an interest in Cardiology with Dr Hugh Conway at the Royal Alexandra Infirmary, Paisley in 1963 and retired in 1988.

 

 

     Ivor MD Jackson, a Glasgow graduate, was registrar with Eric Oastler on second floor medicine from 1963 and published widely in general endocrinology, thyroid disease, obesity and diabetes. He worked with the registrar in diabetes, Dr Keith Buchanan^[9], on an assay of insulin and with Dr Margaret McKiddie, senior house officer in the diabetic unit, on carbohydrate metabolism in Turner’s and Klinefelter’s Syndromes.

Ivor M D Jackson

Jackson left GRI in 1969 to work with Professor Reginald Hall of the University of Newcastle-upon-Tyne. He was awarded a US post-doctoral Research Fellowship with Professor Seymour Reichlin initially at the University of Connecticut and later at Tufts University in Boston, Massachusetts where Reichlin succeeded Edwin Astwood as Head of the Endocrinology Unit. Twelve years later, he moved to Brown University Hospital, Providence, Rhode Island becoming Professor of Endocrinology, Diabetes and Metabolism and Head of

Professor Ivor Jackson

Department. Jackson published broadly across endocrinology but had specific interests in experimental and clinical neuroendocrinology, neuropeptide regulation and studied the role of Gamma Knife Radiosurgery in pituitary tumours. This dedicated stereotactic machine is a recognised alternative to microsurgery. With others, he contributed to the identification and characterisation of the gene for the TRH precursor.

Professor Jackson retired in 2012.

     Tarek H A Hassan, a Cairo graduate, was senior house officer with Eric Oastler on second floor medicine from 1963 and published with Jackson on pituitary function testing and with the thyroid team on simple goitre and toxic diffuse goitre. Hassan has many academic and cultural distinctions, awards and decorations.

      Matthew G Dunnigan, a Glasgow graduate, was not an endocrinologist in training but in 1961, while working at GRI, surveyed the Asian population in Glasgow and discovered late rickets and osteomalacia.

Matthew Dunnigan

He successfully treated this issue of public health with 25-OH Vit D supplementation of the flour that families used to make chapattis. Metabolic bone disease such as rickets was soon to migrate from nutritionists to be ensconced in endocrinology in the late 1960s with the discovery that the kidney, as an endocrine organ, metabolises the 25-OH VitD to 1,25-OH VitD, which is the active hormone. In his further research at Stobhill General Hospital in 1974, he noted members of a family with partial lipodystrophy featuring, in addition, insulin resistance, diabetes mellitus, dyslipidaemia and liver steatosis. Dunnigan linked his cases with a German family reported with a similar inheritance in 1975 by J Köbberling of the University of Göttingen. The condition became known as the Köbberling-Dunnigan syndrome ^[10].

 References

[1].      Obituary. Walter King Hunter. The Lancet Nov 22, 1947. Accessed 11th May 2018.

https://ac.els-cdn.com/S0140673647908003/1-s2.0-S0140673647908003-main.pdf?_tid=8dff450d-7153-4f32-b42b-14c7c6986aa4&acdnat=1526029794_21699e005de5c0e9b7a36105fecba73f

[2].    Obituary for Dr Joseph Houston Wright.

http://munksroll.rcplondon.ac.uk/Biography/Details/4905

[3].      Obituary. Archibald Wilson Harrington. British Medical Journal, July 18, 1953. Accessed 11th May, 2018.

https://www.bmj.com/content/2/4828/152.5

[4]       “Sir David Cuthbertson,” History of Pathological Biochemistry at Glasgow Royal, accessed Nov 20, 2017,

http://www.elliottsimpson.com/history/glasgow4royalmid60stopresent.html

[5].   Image courtesy of Craig Richardson and the Glasgow Royal Infirmary archive.

[6]       “James K Grant,” History of Steroid Biochemistry at Glasgow Royal, accessed Nov 20, 2017,

http://www.elliottsimpson.com/history/glasgowendocrine.html

 [7]       “Eric Gordon Oastler,” Lives of the Fellows of the Royal College of Physicians, accessed November 20, 2017,

http://munksroll.rcplondon.ac.uk/Biography/Details/3354

[8].    Obituary for Professor Keith Buchanan.

http://munksroll.rcplondon.ac.uk/Biography/Details/5679

[9].        “Robert Sibbald Walker: Obituary,” accessed 11th December, 2017 

http://www.heraldscotland.com/news/12435748.Robert_Sibbald_Walker/

[10]       “Dunnigan-Koberling syndrome: an autosomal dominant form of partial lipodystrophy,” QJM: An International Journal of Medicine, Vol 90, Issue 1 (01 January 1997): 27-36, accessed November 20, 2017,

https://academic.oup.com/qjmed/article/90/1/27/1549447

H W Gray

J A Thomson

 

 

 

 

Development of Specialist Academic Medicine

A Laboratory Focus Appears in Royal Infirmary Medicine

     Leslie John Davis initially trained as a research medical scientist at the Wellcome

Leslie J Davis

Bureau of Scientific Research. Thereafter he was appointed to the staff of the Wellcome Tropical Research Laboratories in Khartoum and practiced laboratory and clinical medicine there from 1927 to 1930.  Davis then became Professor of Pathology at Hong Kong University from 1931 to 1939 but left before the outbreak of hostilities. After a short spell as director of medical laboratories in Bulawayo in Southern Rhodesia, he returned to Edinburgh during the Second World War as an assistant and then lecturer in the Department of Medicine to work in medicine and haematology with Stanley Davidson (later Sir Stanley).

University of Glasgow Tower

In 1945, Davis was appointed the third Muirhead Professor of Medicine in the newly formed University of Glasgow, Department of Medicine (UDM) at the Royal Infirmary (GRI). It is likely that the Principal Sir Hector Hetherington and the Medical Dean George Wishart saw in Davis, an opportunity to modernise East Glasgow hospital medicine and bring into the hospital, a research programme based on sound scientific and academic principles introducing laboratory methods into clinical medicine as well as maintaining the reputation of the UDM at Glasgow Royal Infirmary for first class clinical practice and teaching.  The closure of the Saint Mungo’s College building provided Davis with all the accommodation required to set up a laboratory based Department of Medicine adjacent to the Infirmary. The St Mungo College building had been the base for the St Mungo’s Medical School  which had opened in 1888 and only closed in 1945 along with Anderson College on Dumbarton Road following a report from the Goodenough Committee which recommended closure of all extra mural medical Colleges. Davis was therefore able to attract young medical graduates to his Unit who had the desire to apply science to clinical practice. Around nuclei of clinical research programs, young researchers were attracted by the buzz and the energy of the Unit and their involvement in clinical teaching. Funding for these young researchers at GRI was usually found from Hall Fellowship, McIntyre or Ure Research Scholarships and were keenly contested.

As the first full-time University of Glasgow Professor of Medicine at GRI, Davis began transforming his new department into a teaching and clinical research facility by appointing his senior lecturers strategically.

Willie Watson

His senior appointments were Alex Brown his deputy, Edward McGirr, Stuart Douglas, Jim Ferguson and Alex McFadzean. Tom McEwan provided the NHS focus. His juniors included Arthur Kennedy, Stuart McAlpine, Albert Baikie, Robert Pirie, Robert Hume, Jock Adams, William (Willie) C Watson and George P McNicol.

Professor Leslie J Davis

Despite a lack of broad clinical experience, Davis forged a  centre of excellence in academic medicine at the Royal Infirmary. His strong background in Pathology meant that his own specialty interests lay mainly in Haematology which was the predominant activity of the UDM during his tenure of the Chair of Medicine. He published work and co-authored a book on megaloblastic anaemias with Alex Brown and worked on nitrogen mustard therapy for lymphoma. Davis regularly published on haemopoietic drugs and treatments and surveyed both the ESR in clinical practice but also the educational value of the classical medical history. He quickly became recognised as a first class clinical haematologist and by his careful choice of appointments, established a reputation of his University clinical unit for excellence in clinical practice and teaching. Davis’  laboratory-based department of medicine in the Saint Mungo College allowed him to use his experience to mentor his staff on the application of scientific skills to clinical practice and research. He gradually transformed a mainly clinical hospital into one favourable to laboratory-based research, clinical innovation and sub-specialisation.

LJ, as he was known by, retired in 1961 aged 60, moved to Yarmouth and, being keen on sailing, signed on with the Royal National Lifeboat Institution to help crew the local lifeboat.

Professor Davis died in 1980.^[1][2]

Development of Specialist Academic Medicine

     Edward McCombie McGirr. CBE, D.Sc., a Glasgow graduate with B.Sc in 1937 and MB (Hons) 1940, joined the Royal Army Medical Corps and served in India with rank of major until demobilisation in 1947.

Edward M McGirr

He obtained his MRCP in India while on active service on the advice of Max (later Sir Max, then Lord) Rosenheim and also spent time in Thailand. Professor Davis appointed him on the recommendation of Professor  John (later Sir John) McNee (Department of Medicine, Glasgow Western Infirmary) initially as a Clinical Assistant in Medicine within the fledgling UDM in 1947 and a few months later, as registrar at the same time as Dr Alex McFadzean (Brunton prize winner of his year) who later became Professor of Medicine in Hong Kong in 1950.

McGirr shared the lecturing and teaching of medical students, took responsibility for the dental student lectures, and shared the general medical responsibilities on wards 2 and 3 on first floor medicine at GRI and in ward A3 at Eastern District Hospital, Duke Street. The Eastern District Hospital had been built in 1904 as an acute hospital and was the first in Scotland to have a psychiatric assessment unit attached. At this time, the hospital medical wards were really pre-discharge wards though the psychiatric unit had enlarged and represented the mental health beds for GRI.

McGirr almost certainly would have been aware of the groundbreaking work reported in 1938 by Saul Hertz,  Arthur Roberts and R D Evans^[3] where the first ever biokinetic study of radioactive iodine-128 was performed in rabbits and the Hertz and Roberts reports on the first use of cyclotron produced radioactive iodine (90% Iodine-130 and 10% Iodine 131) in the treatment and investigation of patients with thyrotoxicosis in 1946. The confirmatory study by E M Chapman and R D Evans in similar cases and the work of S M Seidlin,  L D Marinelli and E Oshry when the first therapy doses of radioactive iodine were given to patients with thyroid carcinoma confirmed that thyroid investigation and therapy had changed irrevocably. Observing these medical publications from the United States supporting the use of new cyclotron and later on, reactor- acquired radioisotopes of iodine when their production was de-classified in 1947, McGirr quickly realised that Medicine, and especially thyroid disease, could be transformed by the application of these exciting, scientific, technological and pharmacological advances to the study, investigation and treatment of disease.

Funded by the GRI, he immediately started training in the biology of radioactivity at one of the early courses at the Royal Postgraduate Medical School in Hammersmith, London and with this, began a lifelong passion for the use of radioisotopes to facilitate medical diagnosis, treatment and research.

Following a year’s sabbatical with Prof J B Stanbury at Harvard University, Boston in 1950, he returned to Glasgow and was able eventually to perform innovative and classic laboratory work on the aetiology of familial goitrous cretinism in a family of tinker patients of Dr JH Hutchison, later Professor of Child Health and with Dr Elspeth Clement, biochemist in the UDM who was responsible for much of the technical work. The pedigree of the tinker (gypsy) family extended over 160 years and revealed ten goitrous cretins. McGirr showed conclusively, in work that is still quoted and which took 6 years to complete, that enzymatic defects that caused dyshormonogenetic goitre were present in West of Scotland families. When a piece of thyroid tissue from one of them became available surgically, the biochemical defect was defined as deficiency of the enzyme iodotyrosine dehalogenase and revealed that it was transmitted as an incompletely recessive characteristic carried by an autosomal gene. This led to the award of MD with honours and The University of Glasgow Bellahouston Medal. It is interesting to note that Oastler and McGirr had both spent their sabbaticals at Harvard and each would have been been influenced by Saul Hertz, Oastler writing the important paper on the aetiology of hyperthyroidism with him in 1936 and McGirr being inspired by the many uses of radioactive iodine in thyroid disease in the early 1950s.

On return, McGirr was grateful for the sound guidance and support of his friend Sam Curran, nuclear physicist, later Sir Sam Curran, who had been a member of the Manhattan Project during the war and who had joined the Department of Natural Philosophy at Glasgow University in 1946. He later became Principal and Vice-Chancellor of the University of Strathclyde.

Sir Sam Curran

Curran provided McGirr with a supply of radioactive sodium-24 which has β- decay with a half-life of 14.9 hours. He also provided him with his first Geiger-Müller counter to detect the beta particles externally. One of McGirr’s first publications in 1952 was on the clearance of this Na²⁴ from ischaemic skeletal muscle and another on the effects of intermittent venous occlusion on this clearance. Although the technique appeared to have few clinical applications, it confirmed to McGirr that radioactivity was a safe tool which was going to change the face of medicine. He also attempted to investigate the vascularisation of skin grafts for Tom Gibson but again radioactive Sodium was unable to provide meaningful data.

I¹³¹ in use from 1954

Reactor acquired radioactive iodine -131 (¹³¹I) had remained classified after the war and it only became commercially available in the UK around the 1953-4. By that time, McGirr had acquired scintillation counters which enabled him to accurately measure the amount of the isotope in tissue and blood samples. The scintillation counter had been invented by Sam Curran in 1944 while he had been at the Radiation laboratory, Berkeley, California.

Concurrently, McGirr was developing a screening and diagnostic service for thyroid disease and polycythaemia and was helped  initially by the GRI physicist, Walter Jackson. Later, the Regional Physics Department directed by Dr

Early Radio-Isotope Unit Report form

JMA Lenihan, provided advice and assistance, supplied the radioisotopes and monitored staff exposure to radiation.

Using test doses of ¹³¹I, a 24-hour uptake of thyroidal ¹³¹I and a 48-hour protein-bound iodine (PB¹³¹I) were routinely performed on all patients. He also developed a procedure for labelling red cells with radiochromium to estimate blood volumes in polycythaemia and administered intravenous radiochromium for its treatment.

Early scan of neck with G-M counter after 131-I showing a lingual thyroid only

It was from this Department that McGirr published on the first ever patient where there was accumulation of radio iodine in the ectopic thyroid tissue in the tongue with an absence of uptake in the usual site (see Fig). In the early 1950s, McGirr also developed the GRI as a treatment centre for hyperthyroidism using the thionamide drugs developed by Professor Edwin B Astwood in Boston. He organised a thyroid outpatient clinic within the University Medical Unit (UMU) in the lecture room of ward 3, supported by the Radioisotope Department, to investigate the clinical value and effectiveness of these drugs. In addition, from 1954, he supervised and trained others in the early use of ¹³¹I for treatment of hyperthyroidism. This was to be the forerunner of the nascent speciality of Nuclear Medicine. With Drs Provan Murray and John A Thomson’s support, McGirr published one of the first series of 900 cases of hyperthyroidism treated with ¹³¹I in the UK in 1964.

On Prof Davis retiral in 1961, McGirr was appointed the fourth Muirhead Professor of Medicine. His department became one of the pioneers for establishing new specialities in Glasgow and for attempting new techniques. He himself was one of the few clinicians in the UK in the early 60s to see the potential for the rapidly developing field in which radionuclides were used to diagnose and treat human disease. He chaired a groundbreaking report on Isotope Services for the Scottish Home and Health Department in 1968 and chaired the First and Second Reports of the Intercollegiate Committee on Nuclear Medicine in 1971 and 1975. He became an influential supporter of Nuclear Medicine, as it was soon known, and was the British Nuclear Medicine Society’s Second President in 1969/70.

From 1961, when appointed to the Muirhead Chair, Edward McGirr gathered round him

George McDonald

individuals who were keen to expand the academic credentials of his Unit. As technologies improved, he fostered leaders and potential leaders in the medical specialities of Endocrinology  (Drs Provan Murray and John A Thomson), Respiratory Disease (Dr F Moran), Nuclear Medicine (Dr W R Greig), Medical Computing (Tommy Taylor), Rheumatology (Dr W W Buchanan), and Clinical Haematology (Dr George MacDonald).

 

Those in Haemostasis and Coagulation (Dr Stuart Douglas), Gastroenterology (Dr W C Watson) and Renal Disease (Dr Arthur Kennedy) had already been appointed by L J Davis.

Arthur Kennedy

He managed to coordinate the efforts of these leaders of academic medicine yet held the reins loosely to avoid stifling what he recognised was the inevitable specialisation of hospital medicine. If LJ Davis were to be described as the father of academic medicine at the Royal Infirmary, then Edward McGirr could well be described as the father of specialist academic medicine since it prospered and developed quickly under his guidance.

Over subsequent years, McGirr gathered around him many young men and women with a similar passion for endocrinology and thyroid disease who each went on to contribute in areas of Endocrinology, Nuclear Medicine or both, either in the UK or abroad. He fostered them in practical ways and encouraged them to spend time in the USA to train further or learn new research techniques.

The Grays at the UDM Ball

McGirr was a firm believer in the proverb ‘all work and no play makes Jack a dull boy’. He was aware that a happy Unit worked better than an unhappy one and was keen to reduce the load on juniors by trying new ways of working. Encouraged by his wife Diane who had trained as a physiotherapist, he would organise a Unit Ball once a year where medical staff and their wives, nursing sisters, ward nurses and technical staff could put on their glad rags and celebrate the passing of another year with one another in a relaxed social environment. This event was not to be missed and was usually a glamorous affair.

McGirr was admired by his junior staff, mentoring his young lecturers and Fellows formally when advice was sought and informally at coffee time in the staff room after the ward round. He was known to help individuals  access the materials they required for their research. While McGirr could be a tough opponent to those who had their sights on the real estate of the UDM, he had a warm personality and when illness struck members of staff, he would enquire regularly on their health and for their recovery. If problems arose for his staff over which he had the power to influence, he usually made the attempt. One former member of staff recalls the UMU with McGirr at the helm as an ‘academic Camelot’.

McGirr was not afraid to venture into the arena of national politics and would contribute to ‘Standpoint’, an open forum for discussion of the local paper, The Glasgow Herald of the day. The issue of underfunding of the National Health Service and the effects of this upon medical staffing and the quality of the hospital environment for staff and patients appeared close to his heart. His most notable quotation was that ‘Life saving must take precedence over face saving’, a reference to the use of ‘Health’ as a political football. His most simple suggestion to the politicians – ‘a moratorium on change’.

He was an able ‘safe-pair-of-hands’ and this was quickly recognised within and beyond the University precincts.

Professor Edward McGirr graduates DSc, 1994

McGirr was elected President of the Royal College of Physicians and Surgeons of Glasgow 1970-1972, and during this time, steered the College into the mainstream of national postgraduate teaching and examining by membership of the Joint Committee of Higher Medical Training 1970, Faculty of Community Medicine 1972 and the Common Final Part 2 of the MRCP UK in 1972. He became Dean of the Faculty of Medicine of the University of Glasgow in 1974 , Administrative Dean in 1978 and chaired many national bodies influencing health care and standards. He was latterly awarded both a CBE in 1978 for services to Medicine and an honorary DSc (Glasgow) 1994.

After retirement, McGirr kept contributing and published regularly in the Scottish Medical Journal  becoming a philosopher, observer, historian and commentator on the politics of the Health Service and the history of Medicine.

Edward McGirr is remembered fondly as an accomplished and kindly physician, an intellectual and academic with a national and international influence, and a man with a friendly twinkle in his eye.

Professor McGirr died in 2003^[3][4]

 

References

 [1]     ” Leslie J Davis: Obituary,” British Medical Journal, Volume 281, 29      November, 1980. Accessed November 20, 2017

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1714820/pdf/brmedj00049-0064.pdf

 [2]     “Leslie John Davis”: Lives of the Fellows of the Royal College of Physicians, accessed February 23, 2018.

http://munksroll.rcplondon.ac.uk/Biography/Details/1189

[3].      Saul Hertz, and the birth of radionuclide therapy

https://dash.harvard.edu/handle/1/33029717

 [4].     “Professor Edward McCombie McGirr: Obituary,” accessed November 20, 2017.

http://www.heraldscotland.com/news/11991531.Professor_Edward_McCombie_McGirr_His_energy_and_intelligence_developed_academic_medicine/

[5].     “Professor Edward McCombie McGirr”: Lives of the Fellows of the Royal College of Physicians, accessed February 23, 2018.

http://munksroll.rcplondon.ac.uk/Biography/Details/5343

H W Gray

J A Thomson

 

 

 

General Endocrinology and Thyroid Combine

     Two strands of general endocrinology gradually developed at Glasgow Royal Infirmary (GRI) in 1968 under Edward McGirr’s direction with J A Thomson leading general endocrinology and thyroid disease on Oastler’s retiral and IT Boyle leading the second comprising calcium metabolism and metabolic bone disease in all its forms. Diabetes care continued to be run by Dr Alex Imrie, Chief of 4th floor Medicine.

 Development of Academic Endocrinology

     Dr John A Thomson, a Glasgow graduate, obtained a McIntyre Research Fellowship in thyroid disease under Edward McGirr in the University Medical Unit (UMU) of GRI in 1960 after his National Service. The first part of his training was a 2-week course on radioisotopes run by Dr John M A Lenihan, physicist to the Western Regional Hospital Board and Dr Bill Mulligan of Glasgow University Veterinary School. In the Radioisotope Department, Thomson was taught the techniques of thyroid investigation including the 24-hour thyroid uptake of ¹³¹I, the 48-hour PB¹³¹I and early thyroid scanning with a Geiger-Müller counter. Thomson’s other duties included labelling of red cells with radiochromium to estimate blood volumes in polycythaemic cases. He also learned to assess the dose of ¹³¹I therapy for hyperthyroidism and the dose of intravenous radiochromium for polycythaemia.

John A Thomson

In the early 1960s, Murray and he worked and published on an experimental 9-tube Anger type gamma camera with a 5 inch crystal produced by EKCO Electronics Limited and also set up renography in the renal unit. McGirr decided that Thomson should spend a year with Oastler in wards 4 and 5 that allowed him to explore other aspects of general endocrinology. To complete his academic training and credentials in endocrinology, Thomson and family then spent a year’s sabbatical at Harvard University in Boston on a US Public Health Service Fellowship with Professor Irving Goldberg studying the biochemistry of thyroglobulin. Thomson returned to Glasgow in 1967 just before Oastler retired.

In 1968, he was appointed Senior Lecturer in the UMU with special responsibility for endocrinology at GRI and the Royal Samaritan Hospital for Women, Glasgow and in 1981 became Reader.

Throughout this time of great change in endocrine diagnosis and technology, he retained a special interest in, and published widely on, topics related to clinical and laboratory thyroid diagnosis, pituitary disease with particular reference to prolactin secreting microadenomata and neuroendocrine treatment by either drugs or the increasingly sophisticated neurosurgical techniques of transsphenoidal microsurgery with Graham Teasdale, later Sir Graham. Thomson’s team followed up the infertile women who had selective removal of microadenomas and showed that fertility could be restored. He also published on both adrenal and gonadal disorders. Surprisingly for a clinician ‘par excellance’, he liked the challenges of the laboratory and worked closely with successive biochemists in the UDM. Elma M McDonald was experienced in plasma iodide measurements, de-iodination defects and protein bound iodine-127 while Joyce M Bissett complemented Thomson in the area of thyroglobulin biochemistry. Sheila G Baird also specialised on thyroglobulin biochemistry and compared techniques for free thyroxine measurement.

The New and Old GRI Campus^[1]

Dr John A Fyffe worked on the accuracy of measurements of free thyroxine and tri-iodotyrosine and Dr Rhoda Wilson specialised on the immunological parameters of thyroid disease, antioxidant systems and their role in disease processes and the immune effects or side effects of various antithyroid drugs. This latter work was in co-operation with Professor Ewan Smith of the Department of Pure and Applied Chemistry at The University of Strathclyde.

During his period running endocrinology training, Thomson was a challenging mentor and teacher for the junior staff not only in endocrinology but also internal medicine where he was a knowledgeable and insightful clinician. He encouraged general physician trainees to remember ‘hormones’, to question the status quo from the beginning of any clinical problem, and to remember Occam’s Razor.

Thomson retired in 1998 having overseen monumental advances in the diagnosis and treatment for endocrinology patients over his professional lifetime. The large number of junior staff who passed through the UMU during their medical or endocrinology training will remember him as a highly regarded physician, for his excellent teaching in medicine and endocrinology and his mentoring of those who wanted to start original work.

     J Anthony (Tony) Boyle, a Glasgow graduate, was persuaded by Professor McGirr to join the UDM in 1962 to work with Murray and Thomson in thyroid disease.

Tony Boyle

He first published with them on the assessment of a gamma camera for thyroid imaging in 1964 then continued on endocrine themes in 1965 and 66. He worked on many projects with W R Greig including work on the diagnosis and treatment of goitre including genetic factors gleaned from a study of twins, work on iodine deficiency factors from a study of a goitrous area of Scotland and Sudan, and he was part of the group who looked at the effect of X-ray irradiation on thyroid as part of the Iodine -125 hypothesis espoused by Greig.

From 1967, as senior lecturer in Medicine, his endocrine publications diminished in number as he embarked on rheumatological studies but also cooperating with others in the creation of the Centre for Rheumatic Diseases, Baird Street which opened in 1965 with head of Rheumatology, Dr W W Buchanan. He also became Editor of the Scot Med J around this time.

In 1970, he began a new career working in the drug industry and eventually moved to the United States of America.

Boyle died of post surgical complications in 2008. ^[2]

Trainees in Medicine and Endocrinology

      Dr John F B Smith – a graduate of St Andrews/Dundee, joined the UMU in 1966 as registrar in medicine and

John Smith

worked with Greig on the radiobiological consequences of radioactive iodine-131, iodine-125 and X – irradiation on thyroid cells in the laboratory and in thyroid clinical practice . He moved to the Western Infirmary as Senior Registrar in Medicine with Dr Olaf Kerr  in 1970 and to Falkirk Royal Infirmary as consultant physician in 1973. Smith became consultant physician at Stirling Royal Infirmary in 1976 and developed a successful private practice. He retired in 2014.

 

 

     Alan A Glynne – a graduate of Edinburgh, joined the UMU as registrar in 1968 and

Alan Glynne

worked on immunoglobulin levels in thyroid disease and the treatment of acromegaly by cryosurgery. After further training in Manchester, he became a consultant physician for the Cromwell, Wellington and Parkside Hospitals, London with an office in Harley Street.

 

 

     Mary A Wright, a graduate of Glasgow, joined the UMU as Junior then Senior House

Mary Watson

Officer followed by her appointment as Hall Fellow.

She helped compare the adrenocorticotrophic effects of two synthetic polypeptides and also published on an appraisal of student performance with Ann Ferguson and George P McNicol.

As Mary A Watson, she returned to the UMU with Charles D Forbes^[3] and developed an interest in computer assisted learning.

Charles Forbes

Subsequently, Watson worked at the Western Infirmary, Glasgow with J Douglas Briggs in the renal transplant unit and studied cell-mediated immunity before and after renal allografts, drug effects on immunity and hepatitis vaccination studies. She retired in 2004.

 

     W F Bremner – a Glasgow graduate with MA in 1964, BSc in 1968 and MB 1971, worked

Fraser Bremner

in the UMU in medicine/endocrinology for a short time in the mid 1970s and worked up anterior pituitary function during cardiopulmonary bypass for open heart surgery. He also studied the treatment of thyrotoxicosis with radioiodine-125 with WR Greig and colleagues. Training in cardiology thereafter, he emigrated to Loyola University Medical Center, Chicago, USA in 1978 and embarked upon cardiological practice.

Bremner died in 2002. ^[4]

 

 

      Susan Fraser – a Glasgow graduate, followed training in endocrinology as a registrar at

Susan Fraser

the Western Infirmary Glasgow by her appointment as registrar in medicine/endocrinology to the UMU in 1972 and senior registrar in 1973. Following maternity leave, she became consultant in Care of the Elderly at GRI in 1976 and the Southern General Hospital in 1979. Fraser retired in 2003.

 

 

 

 

There were also many young doctors from abroad keen to spend time with Thomson to learn general endocrinology.

     Edgar (P L) So – a graduate of Hong Kong, came to the University Department of Medicine in 1968 from

Edgar So

Professor A J S McFadzean’s^[5] Department in Queen Mary Hospital, Hong Kong on a Hong Kong Government Scholarship for postgraduate training in clinical endocrinology. Working with John A Thomson, So gained experience in general endocrinology and, in particular, thyroid disease which included the Nuclear Medicine aspects of thyroid imaging and therapy. He returned to Hong Kong in 1970 and worked for two years in the University Department of Medicine with Professor Sir David Todd^[6]  on cortisol metabolism in glucose-6-phosphate dehydrogenase deficiency. So became consultant in Medicine to the Queen Elizabeth and Princess Margaret Hospitals and Saint Paul’s Hospital. In 1978, he took up private specialist practice in internal medicine and endocrinology in the Causeway Bay Region.

     Irene Gavras, a Greek graduate, trained in endocrinology in the UMU in the early 1970s. She published on thyrotoxicosis complicating autoimmune thyroiditis.

     Abdul M Nurein – a Sudanese doctor worked with Thomson and Boyle before leaving for Saudi Arabia.

     Abdul Fattah Lakhdar –

Abdul F Lakhdar

a Benghazi graduate, came in 1977 to the UMU for general training and in endocrinology. After further training at the Royal Alexandra Infirmary, Paisley and Stobhill General Hospital, he returned to Libya as associate Professor in Medicine. Since 2004, he has been consultant endocrinologist at Whipps Cross University Hospital, London.

 

 

 

     Prof Jemal Abdulkadir –a graduate of McGill University, came to the UMU and to Dr Thomson in 1979 to complete his endocrinology training.

Jemal AbdulKadir

In 1980, he returned to Ethiopia as the first endocrinologist and played a key pioneering roll in the organisation of diabetes management in that country and in the African continent. Prof Abdulkadir was one of the first few Ethiopian physicians to introduce modern Western medicine to Ethiopia. He not only established one of the first dedicated diabetes clinics in the country but also played a key role in establishing the Ethiopian Diabetes Association. Abdulkadir died in 2013. ^[7]

 

 

     Athena Kolyannis from Greece and Kirtida Acharya from Kenya both trained in endocrinology with Thomson in the UMU in the early 1990s. Acharya gained experience in diabetes and nuclear medicine at GRI, returned to Kenya in 2000 becoming lecturer in medicine and Honorary physician/endocrinologist to the Kenyatta National Hospital in Nairobi. As part of her research profile, she has worked with the Kenya Camel Association on the role of camel milk in glycemic control.

     Mohammed Lamki, graduate of Egypt, and originally from Oman, joined Thomson and Boyle in the early 1990s to train in medicine and endocrinology. He returned to Oman in the mid 1990s as consultant endocrinologist in Muscat.

     Malik Mumtaz, graduate of Universities Sains Malaysia (USM), joined the UMU in the early 1990s training in

Malik Mumtaz in national dress

medicine, endocrinology, mineral metabolism  and nuclear medicine under the auspices of the Royal College of Physicians overseas training programme. He returned to Kota Bharu and joined the USM medical school there in the mid 1990s first as lecturer then as senior lecturer and Associate Professor. He left to take up the post of visiting consultant physician in full time private practice at Island Hospital in Penang in 2008 where he practises medicine, endocrinology and administers radioactive iodine. Research areas include diabetes, osteoporosis and endocrinology. He is a member of the Malaysian Clinical Practice Guidelines Committee for osteoporosis and diabetes.

     MSc Candidates. From 1980, the following individuals obtained an MSc thesis in endocrinology working with Thomson in the UMU at GRI. Omar Hijleh, Khalid Al Sammar, M Zamah Shaikh and Fatheya Fardullah Alawadi.

Temporary Transfer of Endocrinology to Diabetes

     Kenneth (Ken) R Paterson and Miles Fisher, both Glasgow graduates and established

physicians in Medicine, Diabetes and Endocrinology, took over the management of referrals for pituitary and adrenal diseases from 1998 until 2004 when Colin Perry was appointed physician in Medicine, Endocrinology and Diabetes at GRI.

Paterson became consultant Physician in Medicine and Diabetes in 1986 becoming heavily involved in the local diabetic services advisory group and in SIGN.

Ken Paterson

He was also involved in Diabetes UK. His interests included diabetic epidemiology and population screening as they related to improvement in diabetes care. Paterson’s  parallel interest was in clinical pharmacology and therapeutics which led to his chairmanship of the New Drugs Committee of the Scottish Medicines Consortium (SMC) which was a lifeline for patients with rare conditions and expensive therapies.  This was followed by chairmanship of the SMC itself.

Paterson retired fully in 2017.

 

 

Miles Fisher became consultant in Medicine and Diabetes in 1990 and became interested

Miles Fisher

in the premature atherosclerotic disease associated with Diabetes. In particular, he concentrated upon the possibility of preventing or delaying the onset of the Diabetes itself. Fisher looked first at cardiovascular drugs such as those acting upon the renin-angiotensin system and beta-blockers and explored their anti-diabetic properties. He also looked at the thiazolidinediones and was particularly focussed upon the reduction of inflammatory mediators associated with atherosclerosis or cerebrovascular (CV) disease which might provide a benefit for populations with type 2 diabetes. Finally, his team explored the use of glucagon-like peptide 1 receptor agonists as a class of injectable therapies for their benefit in preventing CV events.

Fisher retired partially in 2018.

References

[1].     Image courtesy of Craig Richardson and the Glasgow Royal Infirmary archive

[2]      “Tony Boyle: Obituary,” Legacyia, accessed 20 November 2017.

legacy-ia.com/obituary/boyle-tony/569863?s_source=nqgl_her

[3]       “Charles D Forbes: Obituary,” from the British Medical Journal, Volume 358, Page 280, ref J3595, 19-26 August, 2017.

http://www.bmj.com/bmj/section-pdf/949835?path=/bmj/358/8118/Comment.full.pdf

 [4]      “W Fraser Bremner: Obituary,” from the Chicago Tribune on September 18, 2002 and accessed November 20, 2017.

http://articles.chicagotribune.com/2002-09-18/news/0209180180_1_cardiology-clinic-preventive-cardiology-group

[5].      Alexander James S McFadzean obituary, accessed 2nd July, 2018

http://www.europepmc.org/backend/ptpmcrender.fcgi?accid=PMC1612825&blobtype

[6].     Sir David Todd obituary, accessed 3rd July, 2018

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(17)32600-4/fulltext

[7]       “Jemal Abdulkadir: Obituary,” accessed November 20, 2017.

http://www.ethiosports.com/2013/11/27/in-memoriam-professor-jemal-abdulkadir/

 

H W Gray

J A Thomson

 

 

 

 

 

 

Nuclear Medicine Emerges from Endocrinology

     Edward McGirr saw the advantages and crucial importance of using ¹³¹I in the investigation and treatment of his thyroid patients. His enthusiasm was clearly infectious for a succession of young aspiring endocrinologists who saw the potential in developments in radiopharmaceuticals and in new imaging technologies. He encouraged his protégées to explore the scope of the new clinical speciality, advised the Scottish Home and Health Department and chaired the first two Intercollegiate Committees on Training in Nuclear Medicine.

 Link with Radio Iodine

     Dr I Provan Murray, a Glasgow graduate in 1952, was a Hall Tutorial Fellow at the Western Infirmary. Training under Prof Sir Edward Wayne, he developed a clinical and research interest in thyroid disease and its diagnosis.

I Provan Murray

Murray joined Edward McGirr in the University Department of Medicine (UDM) at Glasgow Royal Infirmary (GRI) in 1958 to learn isotopic methods of diagnosis and to complete his training as an endocrinologist with a special interest in thyroid diseases. Awarded a Rockefeller Foundation Fellowship, he worked for 2 years with Professor JB Stanbury at Harvard University at the Massachusetts General Hospital, Boston from 1959 to 1961.

When he returned from the USA, he took over the management of Radioisotopes and continued to publish on thyroid diagnosis and imaging until 1963 when he accepted a position at the Prince of Wales Hospital, Sydney as Associate Professor of Medicine at the University of New South Wales where he founded the first Australian Department of Nuclear Medicine. He had a major role in the development of Nuclear Medicine in Australia.

Professor Murray died in 2000. ^[1]

Nuclear Medicine Gathers Strength

     William (Bill) R Greig, an Aberdeen graduate and fine amateur football player, joined the UMU in 1964 from the Christie Hospital and Holt Radium Institute, Manchester having trained in endocrinology at Aberdeen Royal Infirmary Department of Medicine. He came as registrar, but was promoted quickly to a Wellcome Clinical Research Fellowship in 1966 and Senior Wellcome Research Fellowship in 1969.

Bill Greig ^[2]

Having a background in endocrinology and research in radiotherapy, his major interest at that time was the treatment of hyperthyroidism with radioactive iodine. Based upon laboratory research that he had undertaken in Manchester, Greig proposed novel and imaginative ideas for the thyroid radiobiology of radioactive iodine therapy. His hypothesis related to the particulate nature of the emissions of ¹²⁵I and stated that it should irradiate the inner parts of the thyroid follicular cells that synthesize hormone to a greater extent than follicular cell nuclei thus producing a lower rate of post-treatment hypothyroidism than with ¹³¹I. A large trial of iodine-125 therapy was conducted in Glasgow which showed, surprisingly, that iodine-125 had no advantage over iodine-131.

With Boyle, he studied pharmacological tests for adrenal reserve, with particular reference to rheumatology and clinical use of steroids in therapy. Together, they conducted a large study of twins that provided the inheritance pattern of simple goitre, thyroid dysgenesis, toxic diffuse goitre, abnormalities of serum lipids, and autoantibody expression. With others, Greig embarked upon a study of simple goitre both locally and abroad and showed a goitrous area in Nithsdale, Scotland, and iodine deficiency in the Darfur region of Western Sudan.

In 1968, he was given special responsibility for the Radioisotope Department by Edward McGirr. The Department had just changed from black and white scanning to the new coloured scintiscanning to produce the image of radioactivity distribution in the organ.

Maureen Gray tests the new scintiscanner in 1968

Up till that time, imaging of thyroid, brain and liver was performed with isotopes of iodine, mercury and gold but rapidly, pertechnetate imaging became the norm since its low energy gamma energy provided clearer images and the collimators became lighter making the engineering of their movement more simple. Lung perfusion scanning then became possible as a routine for the Department.  Greig was

Scintiscanning of thyroid before and after TSH

ably supported in all matters technical by physicist Dr Leslie Hooper initially from 1966 and later by Dr RG Bessent from 1972. Staff levels in Nuclear Medicine increased incrementally with the rise in workload. Ina Cuthbert became senior technologist with Billy Neilson and Maureen Gray her deputies. Greig also appointed Joan Simpson as nursing sister in Nuclear Medicine.

Bill Greig and the Nuclear Enterprises Camera, side room ward 3

Greig became senior lecturer in the UDM in 1970 and developed the department further by expanding the repertoire of the imaging and functional tests into pancreas and bone. He also re-equipped the now re-named Department of Nuclear Medicine with a Nuclear Enterprises (NE) small field-of-view gamma camera which was housed in the lecture room of ward 3 . It was in that side room 25 years previously, that Edward McGirr had held the first thyroid clinic specialising in the use of the new antithyroid drugs from the USA. There were technical issues with this trial of  the Department’s first gamma camera and the purchase of an Ohio-Nuclear small field-of-view camera which followed shortly thereafter was a relief. Although this camera was more advanced and had better spatial resolution, the small field still required more images to cover each organ and so studies took longer to perform. It was the acquisition, in the mid-1970s, of a large field-of-view General Electric Maxi camera that was the game-changer for the effectiveness of the imaging.

Billy Neilson inspects his new large view camera

This camera expanded the repertoire of the Department to permit imaging of structures that  required a single view of large segments of the body. More effective bone imaging with the new technetium-99m phosphonates was now possible as was hippuran renography covering kidneys, ureters and bladder simmultaneously and liver and spleen imaging combined. The electronic kit that came with the camera also provided our physicist colleagues with their first pure digital interface for image quantitation.

Large view Gamma Camera

Concurrently, Greig was the secretary for the Intercollegiate Committees on Nuclear Medicine in 1971 and 1975. He helped Edward McGirr to clarify the different technical and clinical responsibilities of medical physicist, physician in Nuclear Medicine and radiologist with a special interest in the speciality and therefore played a significant role in the clarification and definition of the responsibilities and scope for the new ‘physician in Nuclear Medicine’. At this point, while continuing his own basic research into the radioprotection of the thyroid and working clinically in the wards of the University Department of Medicine, he enthused young endocrinologists and other physicians to consider the potential for investigation and treatment with radionuclides.

Tc-99 in rat thyroid

Gray studied iodine and technetium dynamics in human and animal thyroid, McDougall took a hard look at the treatment of hyperthyroidism with radioactive iodine-131 and -125, Fogelman and Citrin produced ground-breaking studies on the ^99mTc bone scanning agents while McKillop made advances in quantitating ²⁰¹Tl images in coronary artery disease.

Bill Greig tests the whole body monitor

Greig and Bessent looked at the concept of whole body uptake of pertechnetate labelled phosphates and developed a monitor for the whole body in order to measure 24 hour retention of bone agents. Basically this ingenious device moved a recumbent subject past a large and sensitive detector which measured the pertechnetate retention 24 hours after intravenous injection of the dose of bone scanning agent. For the first time, this provided the medical community with a simple clinical measurement of osteoblastic function.

Greig still found time to be Editor of the Scottish Medical Journal between 1974 and 1978. However, just as this gifted man was contemplating the move of Nuclear Medicine to a purpose built department in the Queen Elizabeth building, he had to retire on health grounds in 1979.

Greig died 30th December 1982 at the age of 47. ^[3]

 Apprentices in Nuclear Medicine

     I Ross McDougall, a Glasgow graduate, joined the University Medical Unit (UMU) in 1969 as lecturer and worked closely with Greig on a trial of ¹²⁵I treatment for hyperthyroidism.

Ross McDougal

He also worked upon hyperthyroidism diagnosis/treatment and on aspects of student performance. Following a Harkness Fellowship with Professor Joseph Kriss at Stanford University in 1972-74, he took up his lecturer post again at the UMU after his fellowship but returned to Stanford in 1976 as Associate Professor of Medicine and Radiology in the Nuclear Medicine Department.

Prof Ross McDougal

McDougall continued to work in Nuclear Medicine and, ultimately, PET at Stanford, while being absorbed by the clinical management of thyroid cancer and hyperthyroidism. His interests included  the management of differentiated thyroid cancer, the use of recombinant human thyrotrophin in thyroid cancer, the role of radioiodine-131 in the management of whole body scan negative/Thyroglobulin positive cases and the place of F-18 Fluorodeoxyglucose Positron Emission Tomography in the management of thyroid cancer.

He has authored a useful textbook on Thyroid Disease and co-authored two excellent books specifically on Thyroid Cancer.

Professor McDougall retired from practice in 2016^[4].

      Henry (Harry) W Gray, a Glasgow graduate, joined the UMU in 1966 as Ure Research Scholar, became Hall Fellow then Lecturer in Medicine in the UDM and worked

Harry Gray

with Greig on thyroid disease and radioactive iodine therapy for thyrotoxicosis. He worked on the physiology and autoradiography of technetium pertechnetate-99 and -99m in human and animal thyroid, and on the development of dynamic radionuclide tests for thyroid diagnosis including the i.v perchlorate discharge test. He also experienced work on endemic goitre both in Sudan and Dumfriesshire with Greig. Greig organised that Gray spend 18 months working as a Fellow in Nuclear Medicine with Professor Henry Wagner Jnr at The Johns Hopkins Hospital, Baltimore, USA from 1974-76. After returning to GRI and completing specialist training in endocrinology and diabetes, Gray was appointed consultant physician to the UMU in Medicine, Thyroid and Nuclear Medicine in 1977 and was given special responsibility for the

Harry Gray

medical care of Care of the Elderly and Plastic Surgery at Canniesburn Hospital.

While publishing on V/Q imaging for Pulmonary Embolism, infection imaging and sentinel node imaging for head and neck cancer, he continued his clinical interest in thyroid diseases including thyroid cancer working with Thomson. On Thomson’s retiral, he worked on and led thyroid disease clinically with Drs Denis StJ O’Reilly, consultant biochemist and J Brian Neilly, consultant physician in medicine, respiratory medicine and nuclear medicine.

Gray retired in 2007

 

James (Jim) H McKillop, a Glasgow graduate with BSc, 1970 and MB, 1972 joined the UDM in 1973 and became Lecturer in 1975. Working with Greig, Bessent and A Ross Lorimer, he demonstrated the value of ²⁰¹Tl imaging in coronary artery disease (CAD) and made the first attempts at quantitative analysis.

Prof Jim McKillop

In the late 1970s, he was awarded a 2 year Harkness Fellowship in Nuclear Medicine at Stanford where he worked with McDougall, Professor Joe Kriss, and Dr Michael Goris in aspects of nuclear cardiology, bone imaging and imaging of infection.

Ross Lorimer

On returning to Glasgow, he became Senior Lecturer in 1982 and continued his fruitful collaboration in nuclear cardiology with Lorimer, Ian Hutton, Ann Tweddell and William Martin of The Department of Clinical Physics and Bioengineering. Important work was completed and published on myocardial perfusion imaging in Coronary Artery Disease, the monitoring required and response to therapy.

Anne Tweddell

McKillop became the 5th Muirhead Professor of Medicine in 1989 on the retiral of Professor Arthur Kennedy. His continued interest in tumour imaging led to an investigation of the efficacy of ²⁰¹Tl in a wide range of cancers. With Colin S McArdle and Timothy G Cooke ^[5], he evaluated imaging of colorectal metastases in liver and their palliation using radiolabelled microspheres. Given his long-standing interest in thyroid disease, he joined the team of Wilson, Thomson and Prof Ewan Smith of the Department of Pure and Applied Chemistry at the University of Strathclyde to investigate the link between immune disorders and thyroid function, free radicals and the antioxidant effects of antithyroid drugs.

McKillop moved to The University and became Head of the Glasgow University Undergraduate Medical School from 1999 till 2006. Along with GMC Council membership (2009-2016), he chaired the GMC Undergraduate Board and Audit and Risk Committee and in 2012, The Review of Good Medical Practice.

Professor McKillop retired in 2011.

     Dennis L Citrin, a Glasgow graduate, joined the UMU in 1971 and worked with Greig and

Dennis Citrin

Bessent on a comparison of the new ^99mTc labelled bone scanning agents and compared their sensitivity to radiographs. In malignant disease, he explored their indications and prognostic value and looked at quantitation in bone imaging to assess metastatic response to treatment. He was an energetic and no-nonsense guy and was caught up in his ability to assess prognosis for the cancer patients who passed through the Department. It was no surprise when he applied for and awarded a Fellowship in Oncology at Madison, Wisconsin in 1978. He thereafter became an oncologist specialising in breast cancer at various institutions in the US.

John G Turner, a graduate from Christchurch, New Zealand, joined the Nuclear

John Turner

Medicine Department in 1977 as an experienced endocrinologist and worked with Greig, Bessent and others. Initially as a West of Scotland Post Graduate Committee Scholar, he was also supported by Christchurch Hospital. Turner contributed to the Departmental research into cardiac imaging and bone scanning with McKillop and Fogelman. He was also heavily committed to the development of thyroid investigation with a new gamma camera system and the preparation of thyrotoxic patients for radio iodine therapy.

Turner returned to Christchurch, New Zealand in 1979 and became a consultant physician in medicine, endocrinology and nuclear medicine in Christchurch Hospital. He retired in 2010.

     John Davidson, a graduate of the University of Glasgow, joined the Department of Nuclear Medicine as Senior Registrar in 1988 and while training, continued to work in diabetes with Ken Paterson exploring insulin adverse reactions and the subsequent clinical problems in diabetes management. He also worked in thyroid disease with John A Thomson and Harry Gray.  His main interest in Nuclear Medicine related to the technical aspects of imaging for bowel infection. Davidson was appointed as consultant physician in Medicine, Nuclear Medicine and Diabetes to Ninewells Hospital, Dundee in 1993.

Brian Neilly

     Brian Neilly, a graduate of Dundee University, joined the Department of Nuclear Medicine as Senior Registrar in 1993 having explored pruritus in diabetes mellitus and the interrelationships between neuroendocrine activity and Cor Pulmonale.  After his appointment to a consultant post in Medicine and Nuclear Medicine in 1995, he developed multiple roles both in medical education and research ethics and established himself in Disorders of Sleep. In addition to his professional lifetime involvement in thyroid diseases and their management and special interest in parathyroid imaging, he was President of the British Nuclear Medicine Society (BNMS) in 2012.  Neilly represented the UK on the European Study of the diagnosis of pulmonary embolism and advised BNMS on the Medical Radionuclide supply for the UK. His interest in neuroendocrine tumours was rekindled when he worked on the availability of the Lu-Dotatates for treatment of metastatic neuroendocrine disease.

     Malik Mumtaz, who has been mentioned before was a graduate from the University of Kuala Lumpur and joined the Department of Nuclear Medicine in 1992 as an endocrinologist in training and participated in the research of the Department. He returned to Malaysia in 1994 to become a consultant endocrinologist.

Scientists in Nuclear Medicine

     Dr Leslie Hooper joined the Radio-Isotope Department in 1966 and supervised the in-vitro studies with radioisotopes. She also installed  the Department’s first black and white rectilinear scanner which provided a spatial feel to the distribution of radioactivity, especially in the thyroid gland. This was crucial for diagnosis and for the first time, permitted the function of thyroid nodules to be assessed.

     Rodney G Bessent, an Oxford D.Phil., joined the Nuclear Medicine Department at GRI in 1972 and remained there till his retiral in 2003.

Rodney Bessent

Bessent provided the physics support for most of the routine and research studies carried out by the department during that period. His expertise, scientific rigour and constructive criticism were a crucial component of these studies. He was a member of the University Department of Clinical Physics and Bio-Engineering (DCPB). Bessent’s main interest was in developing computing in the Nuclear Medicine Department. He wrote most of the software for the Department’s first gamma camera image processing computer and guided the development through several generations of hardware and software, with the essential input of a succession of assistant medical physicists, to a fully networked departmental image acquisition and reporting system. His particular interest was in image enhancement and in extracting quantitative information from nuclear medicine images, especially dynamic sequences.

His presence and experience gave the scientific impetus for the development of the department from early scanning to complex gamma camera technology. The Department became an excellent training ground for both physicists and technologists in Nuclear Medicine under his watch and he navigated the seas surrounding the different professional bodies in Nuclear Medicine with ease.

Bessent retired in 2002

     Dr Alison A Bolster, a graduate and PhD from the University of Glasgow took over from Bessent in early 2004. A member of the University department of Clinical Physics, she continued Bessent’s interest in both quantification of nuclear medicine images and

Alison Bolster

in teaching and training.

She held a number of roles associated with clinical scientist training within the Institute of Physics and Engineering in Medicine (IPEM) and was responsible for the nuclear medicine component of clinical scientist training for Glasgow.

With the introduction of SPECT-CT imaging to the department in 2007 she assisted with the introduction of multi-modality imaging and began to develop its use in a number of areas including quantification.

References

 [1]      “I Provan C Murray: Obituary,” accessed from The Royal Australian College of Physicians Roll on 20 November 2017.

https://members.racp.edu.au/page/library/college-roll/college-roll-detail&id=104

[2].      Image courtesy of The University of Aberdeen

[3]     “William (Bill) R Greig: Obituary,” accessed from British Medical Journal Volume 286, Page 565, 2 February, 1983.

http://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC1546553&blobtype=pdf

[4]      “I Ross McDougall retires”. ‘Thank You Dr. McDougall for 40 Years of Continuous Service’ accessed from Stanford Medicine, Radiology Division on 20 November, 2017

http://med.stanford.edu/radiology/news/2016/mcdougall-retires.html

[5]      “Timothy (Tim) G Cooke: Obituary,” accessed from the Herald, 23 August, 2008 on 20 November 2017.

http://www.heraldscotland.com/news/12370455.Professor_Timothy_Cooke/

H W Gray

J A Thomson

 

 

 

 

A Quantum Leap in Diagnosis and Therapy

     This chapter is dedicated to developments in the laboratory measurement of circulating hormones and the increasing roles for non-clinical scientists in all aspects of endocrine diagnosis in the mid to late 20th Century. It also recognises the major contributions of surgical , radiological and oncology colleagues in the diagnosis and treatment of endocrine disease.

Growth of Biochemistry

In 1954, the Royal Infirmary was fortunate with the appointment of Thomas Symington (later Sir Tom) to the St Mungo-Notman Chair of Pathology. Earlier he had worked upon the adrenal medulla, its hormones and their functional properties. Following his appointment, he embarked upon intensive research into the adrenal cortex particularly relating it to acute events. This work led him to propose a functional zonation of the adrenal cortex and highlighted for him and others, the need to measure the adrenal hormones for clinical use.

Dr James Caithness Eaton graduated firstly with a B.Sc (Glasgow) in applied chemistry in 1927 and then after a period of time in industry, with an MB (Glasgow) in 1935. He was immediately appointed a full-time biochemist at the Victoria Infirmary, Glasgow where he developed a leading and comprehensive biochemistry service.

James C Eaton^[1]

In 1947, he was appointed to a lectureship in clinical biochemistry and became consultant biochemist to GRI. He used his experience and organisational flair to develop a first class department which was initially situated on Castle Street. He also had clinical responsibility for the metabolic ward where he collaborated with clinical colleagues to study sulphaemoglobinaemia, renal failure, calcium metabolism and the effect of surgical trauma on nitrogen metabolism. Eaton was the doyen of clinical biochemists in Glasgow of his time and inspired his colleagues in their increasing roles in clinical management. His initial role in endocrinology included bioassays for 17-oxogenic and 17-oxosteroids.

Dr Eaton died in 1966^[2].

In 1960, Symington approached Dr James (Jim) K Grant who had become one of the major figures in steroid biochemistry of his time.

Tom Symington and Jim Grant^[3]

He was working with Professor Frederic G Marrian in the Chemistry Department of the University of Edinburgh. Grant accepted Symington’s invitation to come to GRI as Senior Lecturer in steroid biochemistry within Professor J Norman Davidson‘s Department at the University and was provided with laboratories in the Department of Pathology at GRI where an adrenal unit was forged.

Symington became Director of the Institute of Cancer Research in London in 1970 and retired 1977. He received a knighthood in 1978 and died in 2007.^[4]

On the advice of Symington, McGirr and Oastler, the West of Scotland Regional Steroid Laboratory Service was established in 1962 under Grant’s direction to provide a clinical service for the measurement of steroids in blood, urine and tissue. The new laboratory used chromatographic and fluorometric techniques then added immunoassay in the 1970s. The Department flourished under Grant’s direction and developed impressive research credentials. He became Reader in 1968, was Editor of the Journal of Steroid Biochemistry, and retired in 1981 after a distinguished career characterised by a boundless energy and enthusiasm.

The father of clinical biochemistry at Glasgow Royal Infirmary (GRI) was undoubtedly Prof Henry Gemmel Morgan who was appointed to the Chair of Pathological Biochemistry at GRI as the single consultant chemical pathologist in 1965.

Prof H Gemmel Morgan^[5]

This was a shrewd appointment and presaged a burgeoning of the role of clinical and scientific biochemists in clinical endocrinology and the management of patients.

Temporary Lab for Clinical Biochemistry, McLeod Street, 1964-1977^[6]

Gemmel had established his endocrine credentials by obtaining a Fulbright Research Fellowship with Prof John Eager Howard at the John’s Hopkins Hospital for the year 1956/57 to study calcium metabolism and bone disease. He had an impeccable research approach and methods and managed to halt central Government from fortifying food with excessive doses of Vitamin D by picking up the first signs of hypercalcaemia in children. He wrote an undergraduate textbook for clinical biochemistry which was used worldwide and at his time at GRI, led a first-class clinical biochemistry service  recruiting medical staff who contributed widely in the speciality. He opened ‘The Institute of Clinical Biochemistry’ at GRI in 1977 in the new Hospital development.

The Institute of Clinical Biochemistry, GRI, opened 1977^[6]

Morgan retired in 1988 and died in 2006.

     During the period from 1968 to 1998, enormous progress was made in the biochemical diagnosis and clinical treatment of endocrine patients. In the mid 1960s, however, the only in vitro test of thyroid function was the Protein Bound Iodine-127 in blood. This was a difficult and dangerous chemical analysis that Dr Elma McDonald performed in a special laboratory in the St Mungo’s building at GRI. A technique did appear briefly to measure serum thyroxine (T4) by competitive protein binding which used the high affinity of thyroxine binding globulin for T4 as part of a displacement assay but this was overtaken by subsequent events.

From Chemistry to Immunoassay

     The development of highly specific sheep and rabbit antibodies for T4 and other hormones in the late 1960s changed the management of thyroid disease at a stroke as the antigen-antibody binding assay principle greatly improved the sensitivity and specificity and the capacity to measure accurately, low concentrations of hormones in plasma or serum. Berson and Yalow developed this technique to measure insulin and published in 1960. Concurrently, Roger Ekins was developing a similar assay for T4 measurement by radioimmunoassay in London but never received credit since he published later.

In the mid 1960s, Edward McGirr was a member of the Subcommittee in Radioimmunoassay of the Committee on Laboratory Services of the Scottish Office. Naturally, he strongly supported the development of a first class radioimmunoassay facility at GRI as a national initiative funded by the Scottish Home and Health Department. In 1972, Dr John G Ratcliffe and his wife Dr Wendy Ratcliffe were persuaded by Professor Gemmel Morgan to establish a new radioimmunoassay unit (RIAU) within the Department of Clinical Biochemistry, GRI, but with the financial support from the Scottish Home and Health Department. Other appointments within GRI biochemistry at that time included Dr Graham H Beastall who was appointed lecturer in Steroid Biochemistry and Drs Brian Cook and Mike Wallace into Dr Grant’s department . These critical appointments heralded a great leap forward in diagnosis and management of endocrine disorders at GRI. ^[7]

     John G Ratcliffe, a graduate of Oxford, and formerly Lecturer in Chemical Pathology at St Bartholomew’s, trained with Professor John Landon, an acknowledged leading expert on hormone measurement at the time. John Ratcliffe’s DM (Oxford) in 1972 was entitled ‘Development and application of corticotrophin RIAs’. His main areas of interest during his years in Glasgow included methods of hormone analysis; hypothalamic-pituitary pathophysiology; clinical biochemistry of the thyroid; quality assessment of hormone assays; hormone-related peptides in malignancy; tumour markers; and predictive value, strategy and effectiveness of biochemical tests.

John and Wendy Ratcliffe

Within weeks of arriving, John had taken control not only of the equipment purchase but the decor of the  temporary laboratories in portacabins. The internal walls of the cabins were re-painted from grey to bright orange, to cheer up the occupants. These laboratories provided temporary accommodation for the RIAU which was later transferred to Stobhill Hospital for some years then came back to be within the new Biochemistry building in Phase 1.

Drs Wendy Ratcliffe,  Christina E Gray and Carole Spencer, joined the newly formed RIAU in 1973 and carried out the initial assay development for thyroid hormones, Growth Hormone and TSH. Dr Gordon Challand joined later followed by Dr Graham Beastall in 1976 and Dr Mike Wallace in 1978. During the 1970s numerous other technical, scientific and medical staff worked in the laboratories and made significant contributions to the development of assays for clinical use. The scientists and PhD students included Fraser Logue, Richard Chapman, Ranald Sutherland, Jim Podmore, Layth Ayoub and Russel Burt, while Drs John Vince and Elizabeth A Cowden completed MDs. This time was an exciting and highly rewarding period of their lives as they saw rapid progress in the introduction of new techniques for quantitation of hormones including thyroid hormones, pituitary peptides, gonadal and adrenal steroids as well as drugs and tumour markers. At that time, many assays were ‘firsts’ within the UK and beyond, and they resulted in significant advances in clinical diagnosis and research^[8].

Christina Gray

Dr Mike Wallace died suddenly in 2011 ^[9].

Christina Gray had come from the Royal Hospital for Sick Children where she had been working with Dr William Hamilton on steroid metabolism in children with cystic fibrosis.

Under Ratcliffe’s leadership, the measurement of thyroid, other peptide/protein hormones and key tumour marker assays advanced rapidly. Working closely with Angus Munro of the Scottish Antibody

Mike Wallace

Production Unit initially based at Law Hospital, antibodies from rabbits and sheep were prepared in-house for the steroid and peptide/protein hormone tests while radio iodine labelled hormones were produced within the RIAU or were purchased from commercial sources. The pure hormones that were used to produce the antibodies were often sourced from industry, but also could be produced in-house. Within a few short years, the RIAU became the specialist endocrine laboratories for Scotland and one of a handful of expert laboratories in the UK. GRI endocrinology had more than 30 hormones assays at its disposal at this stage and the biochemist became an integral and essential member of the endocrine team at the regular multidisciplinary team conferences for difficult cases.

The Ratcliffes left Glasgow in 1981 when John was appointed Professor of Chemical Pathology at Manchester and later moved to the prestigious Chair of Clinical Biochemistry in Birmingham. Over this period, John carried out Undergraduate and Postgraduate teaching, Hospital and University Administration, and held many advisory and consultant posts at Regional, National and International level. He also served on numerous Editorial Boards and Professional Committees and was the Director of the Wolfson Research Laboratories Birmingham (funded by the Department of Health) from 1986-1995. His personal research interests from his time at GRI remained and he continued to publish widely.

John Ratcliffe retired in 1995 and died in 2017.^[10]

     Graham H Beastall. CBE. , graduate of Liverpool (BSc. and PhD in steroid biochemistry), joined the Department of Steroid Biochemistry as Lecturer under James (Jim) K Grant in 1972.

Graham Beastall 1976

In 1976, he transferred to the RIAU as Senior then Principal Biochemist. When Grant retired in 1981 and Ratcliffe moved to Manchester, the steroid laboratory became part of Professor Morgan’s Department. The RIAU joined with the steroid laboratory to become the Combined Endocrine laboratory service and was directed by Beastall who became a top-grade biochemist.

The repertoire of the combined endocrine unit had by then expanded to more than 50 different assays, making it the largest unit of its type in the UK. Among Beastall’s research interests included all biochemical aspects of neuroendocrinology, hypogonadism and measurement of parathormone.

President Graham Beastall

He became recognised by his colleagues in medicine and medical science over the next 20 years as one of the most distinguished scientists in the field. Professional roles included Chair, President and Past President of the Association for Clinical Biochemistry (ACB), Vice President of the Royal College of Pathologists, Secretary of the European Communities Confederation of Clinical Chemistry and Laboratory Medicine (EC4) and Chair of the IFCC Congress and Conference Division. He has been awarded the ACB Foundation Award and the EC4 Distinguished Officer Award. In 2007, Beastall became CBE for ‘Services to Clinical Science’.

Beastall took early retirement in 2009 to become President of the International Federation of Clinical Chemists.

     The availability of hormone measurements by radioimmunoassay completely turned around the work of the endocrinologist. Clinical diagnosis was greatly improved and extended and that led to improvements in the management of a wide range of disorders including thyroid, pituitary, infertility and GI tract which were unthinkable in the 1960s. Key tumour marker assays were also developed and neonatal screening programmes for hypothyroidism and neural tubes begun.

Technical advances 

Labels used for testing were initially radioactive, hence ‘radioimmunoassay’. In the late 1960s, the bioassay for TSH requiring a biological response would give a normal of around 5 U/L. A decade on and radioimmunoassay would be able to detect one tenth to one hundredth of this concentration of TSH in serum. By 2000, immunoassay would be able to detect one hundredth to one thousandth of this concentration of TSH. The appearance of commercial platforms (immunoassay testing) and high quality assays using non-isotopic labels made these high quality tests available to all clinical laboratories.

Fraser Logue

     Fraser Logue succeeded Wendy Ratcliffe in 1981 and went on to develop a monoclonal IRMA ‘sandwich’ assay for PTH which was an enormous achievement and was one of the first available in the world at that time.

 

 

Endocrine Pathology

     Dr Anne Marie McNicol , a Glasgow graduate, was Reader in the University Department of Pathology at GRI. She, Dr Alan Foulis and colleagues in the Department of Pathology provided essential guidance for the endocrine multidisciplinary team.

Anne Marie McNicol

She had a particular interest in diseases of the adrenal cortex and was a regular contributor at consensus conferences and reviews and was the European Editor of ‘Human Pathology’. She was a lucid and sought-after contributor in textbooks such as Muir’s Textbook of Pathology and wrote extensively on the surgical pathology of endocrine and neuroendocrine tumours, in particular, the advances in molecular pathology which assisted in firming up prognosis. She was a valued member of the endocrine team and represented the College of Pathologists on the group which produced guidelines for the management of thyroid cancer in 2002 and 2007.  She was also Past President of the International Endocrine Pathology Society and the UK Endocrine Pathology Society. McNicol also had a particular interest in the molecular pathology of pituitary tumours. She had a working link with the University of Queensland, Brisbane, Australia and contributed to the research output of their Department of Molecular and Cellular Pathology. McNicol developed an international reputation for the rigour and clarity of her work.

She retired in 2015.

Endocrine Neurosurgery

     Graham Teasdale, a Durham graduate, at the Neurological Institute at the Southern General Hospital, Glasgow, was the first in Scotland to specialise in pituitary microsurgery using techniques espoused by Jules Hardy in Canada, Charles Wilson in San Francisco and Rudo Fahlbusch in Munich.

Sir Graham Teasdale

Teasdale’s individual focus and research related to the removal of a one-millimetre strip around the pituitary adenoma that was untouched by many neurosurgeons. He believed that in the majority of cases, this ‘pseudocapsule’ of compressed normal tissue contained hypersecreting tumour cells. Teasdale found that this tweak was the key to removing hypersecretion of prolactin yet retaining normal pituitary function. The results of the Glasgow endocrinologists in treatment of pituitary tumours were thereby equal to the best in the world.

Teasdale was knighted for services to Neurosurgery and Victims of Head Injuries.

 

Endocrine Surgery

Thyroid surgery has always been numerically, the most important endocrine operative

Ian MacLenan

procedure carried out at Glasgow Royal Infirmary. In the 30s and 40s, Alfred Mackenzie Clark was the specialist surgeon. In the late 50’s to the mid 70s, Mr Ian MacLennan and Mr John SF Hutchison on second floor surgery performed the majority of operations,

Harry Burns

while Harry Burns in the university surgical unit, later Sir Harry, took over in the 1980s with John Baxter.

John Baxter

In the 1990s, when Harry Burns departed to specialise in Public Health, thyroid surgery was taken over by Ear, Nose and Throat (ENT) surgeons, namely Kenneth (Ken) MacKenzie, Gerald (Gerry) McGarry and latterly, Omar Hilmi. Improvements in parathyroid recognition and blood supply preservation in ENT surgery meant that hypoparathyroidism became a rare event postoperatively.

 

 

Endocrine Oncology

     Nicholas (Nick) Reed, a graduate of the Royal Free Hospital School of Medicine, joined the Glasgow Institute of Radiotherapeutics and Oncology, now known as the Beatson Oncology Centre, in 1984.

Nick Reed

On the retiral of Thurston Brewin in 1987. he took over the thyroid cancer practice and organised a multidisciplinary thyroid cancer clinic (MDT) at GRI with thyroid physicians and surgeons and spearheaded a multidisciplinary regional network meeting of physicians, pathologists and thyroid cancer surgeons. Alongside Reed’s interest and experience in the treatment of gynaecological cancer, came his special interest in all aspects of non-surgical treatment of thyroid and neuroendocrine cancer which involved radionuclide therapy with radioiodine, MIBG, Lutetium peptide receptor radionuclide therapy as well as chemotherapy. As a founder member and chair of the UK and Ireland Neuroendocrine Tumour Society (UKINET) and member of the European Neuroendocrine Tumour Society (ENETS), he has contributed widely in research and was made Professor of Oncology in 2012.

Endocrine Imaging

Advances in imaging for endocrinology were rapid after the 1960s. Professor Ian Donald and colleagues first introduced ultrasound into clinical obstetric practice. Ultrasound was later brought into the routine imaging capability of a Radiology Department and became particularly helpful in defining thyroid nodular disease and the risk of thyroid cancer.

Ian Donald demonstrates obstetric ultrasound

Post contrast CT of macroadenoma

Crucial advance in structural imaging came in 1974 with the EMI Computed Tomographic scanner (CT). Modern whole body systems are now faster, more comfortable and more highly resolving than could ever have been imagined on their introduction.

MRI Pituitary

Magnetic Resonance Imaging (MRI) was adopted in the late 1970s using strong magnetic fields, radio waves and electric field gradients to produce exquisite anatomical images without ionising radiation.

PET-CT reveals treatment response

Nuclear Medicine techniques using a gamma camera to image organ or glandular function at a cellular level or Positron Emission Tomography (PET) cameras to measure  function at a molecular level have helped to select the best therapy, monitor the response to treatment and identify individuals at risk of disease.

     Dr Fat-Wui Poon, a graduate of Aberdeen, joined the team at Nuclear Medicine in 1990 as a consultant and provided guidance for the endocrine team on ‘imaging’.

Fat-Wui Poon

In addition to his colorectal experience, Poon worked on dual-isotope subtraction SPECT-CT imaging in parathyroid adenoma localisation and the use of MRI in nuclear medicine positive/CT negative vertebral scans in suspected metastases. As Clinical Lead of the West of Scotland PET Centre at the Beatson Oncology Centre from 2007, he led the clinical applications of PET-CT in the modern multimodality imaging environment.

Poon retired in 2014.

 

References

[1].    Photograph provided to Dr Elliot Simpson by Dr R Helen Eaton, top-grade biochemist, who retired from the Victoria Infirmary in 2002.

[2].    Dr James C Eaton. Obituary. British Medical Journal. 178:16 July, 1966.

[3].   Image courtesy of Alistair Tough, Archive Department, Mitchell Library, Glasgow, 2018.

[4].       Sir Thomas Symington obituary.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1976537/

[5].   Image courtesy of Craig Richardson and the Glasgow Royal Infirmary archive.

[6].    Courtesy of Dr Elliot Simpson and taken from the Professor Gemmel Morgan Symposium, 1988.

[7]        From ‘Clinical Biochemistry in Scotland’ by Elliott Simpson, November 2016. Under Glasgow, section Glasgow Royal Infirmary Endocrine Unit.

http://www.elliottsimpson.com/history/glasgowendocrine.html

[8].    Wendy Ratcliffe, personal communication.

[9].       “A Mike Wallace: Obituary,” from The Association of Clinical Biochemists News. Issue 573, page 29, January 2011.

http://www.acb.org.uk/docs/default-source/publications/acb-news/2011/January.pdf

[10].   “Professor John Ratcliffe: Obituary,” from ACB News. Issue 656, 35-36, December, 2018. Last accessed December, 2018.

http://www.acb.org.uk/docs/default-source/publications/acb-news/2018/December.pdf

H W Gray

John A Thomson

 

 

 

 

 

Endocrinologists of the Future

     Many individuals trained with John A Thomson in general endocrinology in the University Medical Unit (UMU) and they each went on to contribute in different areas of the speciality.

The Diaspora

      Ian D Hay, BSc (Hons) and MB, 1972, was Hall Fellow in the UMU between 1974-78 working for a PhD and published mainly in neuroendocrinology and neurosurgery for pituitary tumours.

Ian Hay

He spent time at The Mayo Clinic as Senior Clinical Research Fellow from 1978-81 and returned to Edinburgh in 1981 to be the Sir Stanley Davidson Lecturer in Medicine with Professor Sir Christopher RM Edwards at the Western General Hospital. Hay was one of the prime movers in the formation of the Caledonian Society for Endocrinology in 1981 being the first secretary/treasurer. Since his permanent return to the Mayo Clinic in 1984, Hay’s main research focus has been in the management of patients with thyroid cancer and in particular, papillary thyroid cancer (PTC). He worked closely with William M McConahey as he was developing the AGES prognostic scoring system for PTC. In 1993, he published on the advanced MACIS prognostic scoring system and in 1996 was awarded the Paul Starr Award from the American Thyroid Association for his work.He has maintained a database of more than 4,400 PTC cases and has contributed enormously to outcome prediction in PTC and its optimal management. He has also developed Ultrasound guided percutaneous ethanol ablation for papillary microcarcinoma and nodal metastases. In 2005 he was appointed the Richard F Emslander Professor in Endocrinology and Nutritional Research.

Professor Hay has been honoured by the Mayo Clinic, not only for his knowledge of thyroid cancer but also his compassionate care for problems both simple and complex. He is known for his graceful and engaging approach to his patients and his gregarious nature which lightens his consulting room.

Ian and Eileen Hay

The Mayo Clinic has also honoured Professor Hay and his wife Professor Eileen Hay with the first Kalkhoven endowed Chair in clinical medicine named after a distinguished clinician couple. Eileen’s direction was toward gastroenterology. She became a nationally prominent transplant hepatologist and dedicated physician educator. In 2018, the Penske Foundation endowed a Professorship in Clinical Medicine in honour of Ian D Hay and J Eileen Hay, the first recipient being Carole A Warnes, leader in adult congenital heart disease.

 Elizabeth Anne Cowden, a Glasgow graduate, joined the UMU in 1975 and published on the neuroendocrinology of prolactin and its receptors in kidney.

Elizabeth Anne Cowden

She became interested in the pituitary as a sideline to the role of prolactin in the adaptation of the salmon kidney to change from sea to fresh water and was part of the team, including John Thomson and Sir Graham Teasdale, that established that it was possible to retain normal pituitary function while selectively removing the prolactin secreting microadenoma responsible for infertility. They also showed that fertility could be restored after surgery.

In 1983, she obtained a position with Dr H Frieson at the University of Manitoba, Winnipeg and continued her neuroendocrine studies. She later became Head of Medicine at Dalhousie University, Halifax, Nova Scotia but moved back to Winnipeg in 2006.

     Douglas Ingham, a Glasgow graduate, joined the UMU in 1993 as registrar in medicine

Douglas Ingham

and endocrinology. Training in endocrinology and mineral metabolism provided an incredibly diverse range of experience. Ingham reviewed decades of clinical outcomes following transsphenoidal hypophysectomy with Thomson and Teasdale and worked with IT Boyle and others on osteomalacia masking hyperparathyroidism. Following a move to the endocrine unit at The Western Infirmary working with John Connell and Anna Dominizcak and a period of training in Edinburgh, Ingham became consultant physician in acute medicine, endocrinology and diabetes at Hairmyres Hospital, South Lanarkshire in 2004. In 2014, he moved to Frankfurt as an Internist in medicine and endocrinology.

Islets of Endocrinology and Diabetes

     James (Jimmy) E Thomson, a Glasgow graduate, joined the University Medical Unit (UMU) as registrar between 1974-77 and trained in

Jimmy Thomson

medicine and endocrinology. He worked with John A Thomson on the sensitivity and specificity of thyroid function tests and noted discrepancies in T4 measurements in pregnancy between radioimmunoassay and competitive protein binding.  He developed an assay for free T3 in the lab using competitive protein binding and this appeared to be clinically useful. Thomson also studied the effect of iv heparin on the hypothalamo-pituitary-thyroid axis. With John A Thomson, he explored the problems in diagnosis of Cushing’s syndrome.

Thomson was appointed consultant physician in endocrinology/diabetes at Inverclyde Royal Hospital in 1978 and retired in 2007.

     Howard Cohen, a Liverpool graduate, joined the UMU in 1977 and published on

Howard Cohen

neuroendocrinology, the investigation and treatment of short stature and issues around growth and puberty in boys. During a one year sabbatical in adolescent endocrinology in 1982-83 with Prof Melvin M Grumbach at the University of California, San Francisco, he researched on the gonadotrophin response to gonadotrophin releasing hormone in boys with growth hormone deficiency and developed a bioassay for testosterone in the laboratory. He became consultant in Medicine, Endocrinology and Diabetes in South Lanarkshire in 1984.

Cohen retired in 2008.

     Donald W M Pearson, a Glasgow graduate, joined the UMU in 1979 and spent two years

Donald Pearson

working with Thomson, Gray and McKillop in endocrinology and nuclear medicine. He spent time with Ratcliffe in the laboratory on an assay for plasma thyroglogulin and published on thyroid function testing and the predictability of Graves’ disease remission. He moved to Aberdeen as Lecturer in Medicine in1981 and was appointed consultant physician in medicine/diabetes in 1984.

 

 

 

     Michael Small, a Glasgow graduate, joined the UMU in 1979 in endocrinology and

Mike Small

medicine progressing to Senior Registrar in 1984. He published widely on the interrelationships of thyroid disease, diabetes and haemostasis. Small was appointed in Administrative Charge of the Diabetes Services for West Glasgow (Western Infirmary/ Gartnavel Hospital) in 1987. Thereafter, he became lead clinician in Scotland for the Clinical Standards Board reviews of Diabetes Care and also the Chair and Trustee of Diabetes UK (Scotland) for over 10 years.

Small retired in 2015.

 

     Colin Semple, a graduate of Oxford (Physiological Sciences) and Glasgow (MB),

Colin Semple

joined the UMU as registrar in 1981 and published widely in endocrinology including neuroendocrinology and the effect of illness on the secretion of androgens in the male. He had a particular interest in Cushing’s syndrome and its treatment with both microsurgery and drugs. After completing his training, he was appointed consultant physician in Medicine and Diabetes/Endocrinology at the Southern General Hospital in 1988. At this time, he became involved and published on the accreditation process for European internists. This led to the formation of standards of practice and training in the European scene.

Semple retired in 2013.

      Derek Gordon, a Glasgow graduate with BSc (Hons) 1974 and MB 1979, joined the UMU

Derek Gordon

as registrar in 1983. He developed a research interest in neuroendocrinology, more specifically pubertal development in males, the hypogonadal male and the use of pulsatile LHRH and HCG therapy in inducing puberty. He also investigated the endocrine effects of the treatment of pituitary tumours. Gordon was appointed consultant physician in general medicine, diabetes and endocrinology at Law Hospital in 1992 and for Stobhill and GRI Hospitals in 1996.

Gordon retired in 2015.

 

 

     Douglas McCruden – a Glasgow graduate with BSc (Hons) Physiology 1970 and MB

Douglas McCruden

1972, worked in the UMU as a senior registrar in endocrinology 1985/86. During this period, he majored on assessing the treatment of prolactinomas and of acromegaly by cryosurgery or microsurgery. McCruden became a consultant physician at the Vale of Leven Hospital in 1986 and retired in 2009.

 

 

 

 

     Linda Buchanan, a Glasgow graduate, joined the UMU for 2 years in 1988 and worked

Linda Buchanan

with Thomson, Wilson, McKillop and Smith on immune disturbance and free radicals in thyroid disease, particularly hyperthyroidism, and antioxidant effects of carbimazole therapy. She also had an interest in the abnormal steroid metabolism of hirsute women. Buchanan is currently a physician with an interest in endocrinology/diabetes at Forth Valley Royal Hospital.

 

 

 

     James J (Jimmy) Walker, a Glasgow graduate, joined the UMU in 1978 as an obstetrician attracted for one year of his MRCOG studies by the gynaecological endocrinology at the Samaritan Hospital.

Jimmy Walker

He worked with Thomson in reproductive health, particularly infertility and early pregnancy as well as hirsutism and the menopause. He also worked with Wilson on the immunological changes of normal pregnancy, recurrent miscarriage and pre-eclampsia and the role of thyroid function that continues today. Walker became Professor of Obstetrics in Leeds in 1994.

Other obstetricians who spent time in gynaecological endocrinology with Thomson include Laura Cassidy who became a consultant in Greenock then Paisley when they merged. She contributed to work on problematic diabetic pregnancies and was an important supporter of women in training.

Rottenrow Maternity Hospital

Marjory A MacLean worked with Rhoda Wilson on the immunologic parameters of normal pregnancy and recurrent miscarriage. She became a consultant in Ayrshire. Douglas Mack published on hyperemesis gravidarum and thyrotoxicosis with Thomson, became a consultant in Glasgow, and is now retired.

The Royal Maternity and Woman’s Hospital, Rottenrow closed in 2001 and moved to the GRI site as the Princess Royal Maternity Hospital.

     John Quin, a Glasgow graduate, trained as an Senior house officer at the Southern General Hospital under Dr John Ireland.

John Quin

He became medical registrar at GRI on second floor in medicine and diabetes with Dr Angus McCuish and Dr Ken Patterson but also spent a year in general endocrinology and thyroid disease with Dr John A Thomson and metabolic bone disease with Professor Iain T Boyle. During this time, he published case reports on thyroid abscess, hypothyroid tamponade and adverse effects of drugs on thyroid. He worked mainly in diabetes and with others looked into the bone density and turnover in premenopausal women with Type I Diabetes. He also published with others on the use of IGF-1, GF binding proteins, glomerular charge and diabetic effects on haemostasis, fibrinolysis and blood rheology. Quin became Senior registrar in endocrinology/diabetes at King’s College Hospital and continued his interest in insulin resistance and IGF-1 ultimately becoming Consultant Physician for the Royal Sussex County Hospital.

Quin was Regional Adviser for the RCP, London, became Associate Dean for the Kent, Surrey and Sussex Deanery and was an elected councillor for the London College. He retired June 2016 to write professionally.

 

     Colin Perry, a Glasgow graduate, became Lecturer in the University Department of

Colin Perry

Medicine in 2000. He has published on adrenal endocrinology and in particular, phaeochromocytoma diagnosis by comparing the accuracy of urinary free metanephrines, vanillyl mandelic acid and catecholamines and plasma catecholamines. Perry has also studied associated genetic syndromes and endocrine oncology and has interests in endocrine conditions and diabetes in transition from the paediatric to the adult clinic.  Experimentally, he has attempted to dissociate insulin’s metabolic and vascular actions and in particular, studied the role of adipocytokines in regulation of vascular endothelial function.

Perry became consultant physician and endocrinologist to GRI in 2004.

H W Gray

J A Thomson

 

 

 

Bone Targeted

     Metabolic bone diseases in all their forms drove the second strand of endocrinology at Glasgow Royal Infirmary (GRI). Such conditions reduce bone strength with resulting fragility fractures, bone deformities and serious disability. Historically, rickets had always been endemic in Glasgow largely because of poor diet and reduced UV-light exposure. The frequency of rickets had reduced in the early part of the 20^th century when knowledge of its causation and need for Vitamin D (25-D) supplementation were acted upon by Public Health. A blip occurred in the late 1950’s when it reappeared among the Asian immigrant children. Dr Matthew G Dunnigan, GRI, discovered this and solved the problem by fortifying the chapatti flour with 25-Vitamin D. The complex interactions between parathyroid glands, calcium metabolism and Vitamin D intake remained a bit of a mystery, however, until the discovery of the hormone calcitonin precipitated an unprecedented focus on bone metabolism.

 Mineral Metabolism Develops

     Iain T Boyle, D.Sc (Strath), a Glasgow graduate with First class Hons B.Sc in Biochemistry, 1958 and MB, 1962, joined Professor Edward McGirr on a research grant in 1963 to study thyroid disease and endocrinology.

Iain T Boyle

His eyes turned from thyroxine to calcium metabolism when he was released to take up an associate research post at the Royal Post Graduate Medical School with Prof Ian MacIntyre working on the newly discovered hormone, calcitonin. He soon realised that most excitement in the field was into the understanding of Vit D metabolism and most of the effective work on Vitamin D at that time was being done in the laboratory of Prof Hector DeLuca in Madison, Wisconsin.

Stuart Douglas

Professor A Stuart Douglas^[1]of the University Medical Unit (UMU), GRI, arranged through his friend Prof Bob Schilling (of Schilling test fame) at the Department of Medicine, Madison, that Boyle be provided a grant to work with DeLuca in biochemistry and a Welcome Research travel grant was also obtained. In October 1970, Boyle and family headed to Madison for his study of the effect of renal failure upon Vitamin D metabolism. After Boyle had perfected the surgical procedures required to set up his rat model, Fraser and Kodicek from Cambridge co-incidentally published work strongly suggesting that the active metabolite of Vitamin D was 1.25-dihydroxyvitamin D (1.25D) and that it appeared to be synthesised in the kidney. All of a sudden, Boyle was centre stage and roped into many collaborative studies with gifted young biochemists.

During his two years at Madison, Boyle was an essential member of the team that made spectacular breakthroughs in understanding of Vitamin D metabolism. He published over 9 highly regarded papers with DeLuca and contributed to the appreciation that 1.25D is a much more fundamental molecule than just being a key player in calcium metabolism.

Boyle returned to GRI in 1972 and established a clinic for metabolic bone diseases. In 1973, he gave the Alexander Fletcher Memorial Lecture of the RCPS of Glasgow entitled ‘the Kidney – an endocrine organ controlling calcium metabolism’. He was provided with a ward at Belvedere Hospital for his patients until 1982 when he took over management of a metabolic ward in the new Queen Elizabeth building of the Royal Infirmary. This enabled him, and his team which included Dr Frances Dryburgh from Biochemistry, who had studied under Dr Chris Nordin of the Western Infirmary, to establish the benefits of the new bone-active drugs. These included the calcitonins in Paget’s Disease, Sudek’s Atrophy and osteoporosis; 1.25D in renal osteodystrophy, hypoparathyroidism, and Vitamin D resistant osteomalacia; the bisphosphonates in osteoporosis, Paget’s Disease and malignancy-associated hypercalcaemia.

Brendan Boyce

Working with Dr Brendan Boyce of the University Department of Pathology, came the discovery that aluminium and bisphosphonates could cause focal rather than diffuse osteomalacia in dialysis patients and those with Paget’s disease. A further new discovery with Boyce was the mechanism of aluminium inhibition of mineralisation in dialysis patients leading to hypercalcaemia that could be mistaken for tertiary hyperparathyroidism. Boyle worked for many years with Rosemary Dargie at the Mineral Metabolism Clinic.

Rosemary Dargie

She helped Boyle with the clinical load while working herself on the sensitivity to vitamin D in hypoparathyroid women who change their oestrogen status.

Boyle became involved in developments in radionuclide bone imaging and its quantitation in Nuclear Medicine and in the screening potential of dual energy X-ray bone densitometry. He worked initially with Bill Greig on the 24 hour retention of phosphonate bone scanning agents using the whole body monitor and later with Ignac Fogelman and Dennis Citrin in assessing the qualities of bone scanning agents for assessing the normal function of osteoblasts. An uncollimated gamma camera was found to be a more simple and accurate measure of measuring whole body retention of technetium labelled bone scanning agents.

Prof Iain T Boyle

He became Reader in 1985, visiting Professor in the Department of Pharmacy and Physiology at the University of Strathclyde in 1994 and DSc (Strathclyde) in 2000.

Iain was a charming polymath whose wide interests in philately, cartography, books and art endeared him to his patients and those who worked closely with him.

Professor Boyle died in 2001^[2].

Mineral Metabolism for the 21st Century

Alastair McLellan, a Glasgow graduate, and an established consultant endocrinologist at

Alastair McLellan

the Western Infirmary, took over the management of the Bone Unit in 1999 after Boyle’s retiral on ill health grounds. His main interest was in metabolic bone disease and he specialised on the regulation of bone density, the fragility fracture cycle, secondary prevention of fracture, the fracture liaison service and DEXA scanning.

McLellan retired partially from clinical practice in 2012 to become Post Graduate Dean in Medicine and completely in 2015 while continuing the Deanship.

References

[1]       “A Stuart Douglas: Obituary,” Lives of the Fellows of the Royal College of Physicians, accessed 20 November 2017.

http://munksroll.rcplondon.ac.uk/Biography/Details/1312

[2]      “Iain T Boyle: Obituary,” Lives of the Fellows of the Royal College of Physicians, accessed 20 November 2007

http://munksroll.rcplondon.ac.uk/Biography/Details/5248

 

H W Gray

J A Thomson

 

 

 

Bone Apprentices

     Professor Iain T Boyle enthused many able young researchers in medicine, endocrinology or the medical specialities to work with him in mineral metabolism in the University Medical Unit (UMU).

The Nuclear Medicine Connection

     Ignac Fogelman, a Glasgow graduate, joined the UMU in 1975 and effortlessly combined

Ignac Fogelman

his interest in radionuclide bone imaging with that of metabolic bone disease with Boyle on a number of fronts. He studied the whole-body retention of Technetium labelled phosphonates (bone scanning agents) using either a whole body monitor or a non-collimated gamma camera as a quantitative measure of skeletal metabolism and demonstrated the value of this technique in monitoring the progression of metabolic bone diseases and their response to therapies This provided the team with an easily measurable, non-invasive, quantitative index of skeletal metabolism.

Prof Ignac Fogelman

Fogelman proceeded to demonstrate its clinical value in the clinical assessment of metabolic bone disease and its response to therapy. He also assessed the effect of bisphosphonates on bone turnover and studied osteoporosis.

In 1983, Fogelman was appointed consultant in Nuclear Medicine at Guy’s Hospital where he continued work in metabolic bone disease, osteoporosis and Nuclear Medicine.

He retired in 2015 and died in 2016^[1]

     M Linda Smith, a Glasgow graduate with BSc (Hons) in Anatomy 1975 and MB 1978, was appointed as a research registrar in Nuclear Medicine, to the thyroid clinic and metabolic bone disease in 1980.

Linda Smith

She became heavily involved in the assessment of various bisphosphonates as diagnostic or therapeutic agents and in osteoporosis prevention with Boyle. She effectively managed two longitudinal studies on the prevention of osteoporosis in women, both of which utilised Nuclear Medicine techniques in the assessment of bone turnover.

As the clinical importance of bone disorders became apparent, and the OP clinic grew exponentially, Smith recognised increasingly, the value of ‘combined care’ in cases of hyperparathyroidism who often required surgical intervention.

After training in Nuclear Medicine at Cambridge from 1984, Smith became consultant in Nuclear Medicine at the Royal Liverpool and Broadgreen University Hospital Trust in 1989.

She retired in 2014.

The Rheumatology Connection

     Stuart Ralston, a Glasgow graduate, joined the UMU in 1981 within a general medical rotation, becoming Senior Registrar in 1984-86 and gaining special experience and insights managing metabolic bone disease while working with Boyle.

Prof Stuart Ralston

From 1986/87, he worked with Dr D A Pitkeathly and Dr John Hunter, Rheumatologists at the Southern General Hospital and from 1987 to 1989, with Dr Hilary Capell and Professor Roger Sturrock, at the Centre for Rheumatic Diseases at Glasgow Royal Infirmary (GRI).

Working with Boyle in ward 64, he developed a major research interest in the aetiology and treatment of cancer-related hypercalcaemia and also the mineralisation defect in bisphosphonate treated Paget’s disease. He also studied osteoporosis and metabolic bone disease in rheumatologic conditions, and calcium homeostasis.

Ralston became Wellcome Senior Research Fellow in Clinical Science under Prof George Nuki in Edinburgh in 1989 and spent time in the laboratory, gaining experience in modern molecular biology. In 1991, he received a personal chair from The University of Aberdeen as Director of the Institute of Medical Sciences. He returned to Edinburgh in 2005 as Professor of Rheumatology and Director of the Edinburgh Clinical Trials Unit based in the Rheumatic Diseases Unit, Western General Hospital, Edinburgh.

He is the lead clinician for Osteoporosis in NHS Lothian and the Clinical Director for Rheumatology and Gastroenterology and acts as an advisor to the Scottish Medicines Consortium and the European Medicines Agency. Professor Ralston was a member of the Commission for Human Medicines between 2010 and 2012 and was appointed chair of the Commission for Human Medicines in 2013.

The Endocrinology and Diabetes Connection

     Stephen J Gallacher, a Glasgow graduate, was registrar then Lecturer in Medicine in the

Stephen Gallacher

UMU from 1987 to 1995. While training fully in endocrinology and diabetes during this time, most research was with Boyle and related to the management of hypercalcaemia of whatever cause, the clinical use of bisphosphonates, the treatment of Paget’s disease, osteoporosis, bone turnover and the in vitro and in vivo diagnosis of hyperparathyroidism. Gallacher moved to the Southern General Hospital in 1995 as Consultant in Medicine, Endocrinology and Diabetes and has been instrumental in the development of Fracture Liaison Services locally for patients with osteoporosis, post fracture, to determine future fracture risk. This is now accepted as the standard of care worldwide.

     Andrew (Andy) P Gallagher, a Glasgow graduate with B.Sc (Hons) in 1985 and MB in

Andy Gallagher

1988, came to the UMU in 1994 to complete his endocrinology training with both Thomson and Boyle. His interests included the use of Insulin-like Growth Factor-1 treatment in severe insulin resistance and in Mineral Metabolism, the management of osteoporosis and fracture and particularly, its relationship with Vit D deficiency. Gallagher became consultant endocrinologist at Law Hospital, Carluke in 1996 then moved to the Victoria Infirmary/Southern General Hospital in 2001.

 

     John Hinnie, a St Andrews graduate with B.Sc (1975) and Ph.D (1978) in Biochemistry and MB Glasgow (1987), was appointed Lecturer in Medicine in the UMU in 1996 and

John Hinnie

while training in Endocrinology and Diabetes, continued to publish on lipoprotein subfraction distribution, the prevalence of familial hypocalciuric hypercalcaemia and calcium homeostasis. Hinnie also studied exercise to exhaustion in McArdle’s Disease with and without creatine supplementation. He developed a particular interest in the genetics of the calcium sensing receptor and has been cited twice in the Human Genome Mutation Database for novel mutations of this particular receptor.

In 2000, Hinnie became consultant in Medicine, Endocrinology and Diabetes at the Victoria Infirmary and now the Queen Elizabeth University Hospital.

A Caledonian Society for Endocrinology is Born

Over the decades, a succession of able individuals joined the UMU to work with Thomson and Boyle in endocrinology, each contributing in different areas of the speciality.

The Anchor, Cambridge 1981

Some took their expertise and research know-how to other continents. Many of them, Consultants and junior staff, met at ‘The Anchor’ on the river Cam in Cambridge in 1981 during a conference on Endocrinology to plan for a new forum for discussion and promotion of the exciting developments in clinical endocrinology in Scotland. It was open to any person working in the field which included diabetes.

Logo of Caledonian Society for Endocrinology

And so , The Caledonian Society for Endocrinology was born. The inaugural membership from GRI included Drs Graham Beastall, Iain T Boyle, Howard N Cohen, Ignac Fogelman, Christina E Gray, Ian D Hay, Jim H McKillop, Colin G Semple, John A Thomson and A Mike Wallace. The inaugural meeting took place on the 11 November 1981 when Professors Graham Teasdale and Christopher Evans debated the optimum management for prolactinoma.

 

 

References

[1].         “Ignac Fogelman: Obituary,” from Gopinath Gnanasegaran et al, European Journal of Nuclear Medicine and Molecular Imaging Volume 43, pages 2273-2274, 2016.

https://link.springer.com/content/pdf/10.1007%2Fs00259-016-3501-7.pdf

 

H W Gray

J A Thomson

 

Endocrinology pushes the Boundaries of Science

     Advances in Endocrinology around the Millennium continued to be seen in the measurement of hormone levels by biochemistry, the drugs and peptide/protein hormones available for treatment and the genetic tools required to research inherited maladies and to guide the treatment of families thus afflicted.

Technical Advances in Biochemistry

     From the 1980s onwards, Graham Beastall CBE established the Combined Endocrine Unit in Biochemistry at Glasgow Royal Infirmary (GRI) with a national and international reputation for development of hormone assays for clinical work and research. This required biochemical and immunological innovation, leadership through tough choices, and hard work by the whole Department. At one point in the 90s, there were more than 50 different hormone assays available for measurement at the laboratory, many of them highly specialised and for research use only. There were problems emerging relating to immunoassay methods and the lack of specificity of the technique with interference from endogenous antibodies and matrix effects. Add to that the increasing cost of high volume commercial hormone immunoassays and the challenge to laboratory budgets was inescapable.

Measurement by mass-spectrometry – normal ranges

Thankfully, technological advances impacted favourably upon the workload of the Endocrine Biochemistry Unit. The development of simple bench-top mass spectrometers linked to gas or liquid chromatographic separation led to hormone and peptide/protein assays that were sensitive, highly specific and inexpensive to perform in all biochemistry departments in Scotland. Such mass-spectrometric assays are now the standard method for small molecules such as steroids.

Clinical Biochemists in Endocrinology

Frances Dryborough

     In the 70s and 80s, medical biochemists began to play a role in the clinical management of out patients. By then, Frances Dryburgh, a Glasgow graduate, had been participating in the Mineral Metabolism clinic for many years with Boyle and had worked on multiple aspects of calcium metabolism including ionized calcium, urinary Sodium and Phosphate excretion, hypercalcaemia, renal failure and hyperkalaemia, among others. She retired in 1999.

 

 

 

      Denis StJ O’Reilly, a graduate of Cork (MB) and Birmingham (MSc), was appointed consultant biochemist at GRI in 1984 and shortly thereafter, began his clinical

Denis O’Reilly

involvement with Thomson and Gray in thyroid disease and with Gray and Neilly after 1997 when Thomson retired. Among his many research interests, he worked upon exercise tolerance in McArdle’s Disease, problems of enteral feeding and parenteral nutrition. His main research interest was in the problems of the application of biochemical measurements in the diagnosis and monitoring of the treatment diseases, especially due to the nonspecific systemic effects of inflammation. He also studied thyroid hormone replacement, contributed to the debate concerning the detection of over and under replacement from in vitro tests and explored outcomes of pregnancy complicated by thyroid disease.

O’Reilly retired in 2012.

     William (Bill) Fraser, a Glasgow graduate with BSc (Hons) and MB, trained at GRI and spent time at the thyroid clinic with Thomson. He worked on the monitoring of thyroid

Bill Fraser

patients receiving thyroxine replacement and antithyroid drug treatment effects. Later, he spent time at the mineral metabolism clinic with Boyle and worked on parathyroid hormone measurement, cancer associated hypercalcaemia and parathyroid scanning. He became Professor in Clinical Biochemistry at the Royal Liverpool Hospital in 2001 and Head of Clinical Chemistry in 2008. He was appointed Professor of Medicine at Norfolk Medical School, the University of East Anglia in 2011.

 

 

     Janet Horner, a Glasgow graduate with BSc (Hons) Physiology and MB, worked both

Janet Horner

with Boyle researching the use of markers of bone turnover in osteoporosis and with Thomson and colleagues in thyroid disease. One of the more important findings was that the vitamin D requirements in women with hypoparathyroidism can change if their oestrogen status alters. An awareness of this can avoid hypercalcaemia.

Horner left to take up a locum consultant post at the Stoke Mandeville and John Radcliffe Hospitals in 2000 and a substantive consultant post with Leeds Teaching Hospital NHS Trust a year later. She returned to Hairmyres and Monklands from Leeds as Consultant Clinical Biochemist in 2007 and then to GRI as Consultant in Clinical Biochemistry in 2012 to work in the Macewan building continuing her work in endocrinology and bone disease, particularly osteoporosis.

Clinical Genetics and Molecular Analysis

     From the late 1960s and early 1970s, and in one professional lifetime, endocrinology had morphed from a purely clinical specialty reliant upon family history, symptoms and clinical signs for diagnosis to one predicated upon precise measurement of multiple hormone levels, with specific drug treatments and highly specialised neurosurgical techniques available when required. With time, however, these measurements and clinical experience began to open up the occasional inconsistency between the hormone level and end organ effect. At this juncture, the science of clinical genetics began to increase its role in endocrine investigation. Step by step in the 1980s and 1990s, it became possible to investigate whether families had Mendelian disease and later, whether they had the genetic variants (disease subtypes) of endocrine disease. Advances in clinical genetics has made possible a range of molecular tests to elucidate the cause of the malady and in some cases, to permit targeted treatment.

Genetics laboratory

These genetic tests were initially the provenance of a limited number of specialist academic laboratories. These laboratories were regularly used in, for example, families with Multiple Endocrine Neoplasia syndromes, MEN 2 in particular. Cascade genetic testing was used to pick up those asymptomatic and biochemically normal family members who required invasive treatment such as thyroidectomy to eliminate the risk of medullary thyroid cancer. Genetic testing would also be important for the management of a patient with a single phaeochromocytoma since, depending upon the genetic mutation, the contralateral gland might also require removal to eliminate risk of tumour in that organ. As their importance increased, these laboratories were consolidated into a national NHS network for genetic testing of which there are 4 in Scotland. The rapid advances in molecular genetics since the millennium and the new understanding of endocrine pathophysiology which they bring, has only been realised because of the rapid and affordable sequencing of the genetic code in individuals which is now possible. One can now confirm a clinical diagnosis through hormone measurement and then determine the specific cause through molecular testing.

Recombinant Hormone Production

In the late 1970s, a novel molecular technique using the human gene coding for insulin was used to produce human insulin and in 1982, it became available commercially to patients under the name, Humulin. This eliminated the annoying allergic effects of pig and bovine insulin in insulin-requiring diabetics. After such success with insulin, the search was on to find the genes coding for other hormones that could be of value in endocrine therapy. Recombinant parathyroid hormone (PTH) has been produced in a similar fashion to human insulin and immediately became a candidate for therapy in osteoporosis ^[1].

PTH molecule

PTH stimulates bone formation while bisphosphonates reduce bone resorption so, despite the need for parenteral administration, it is likely that PTH will have an important role in patients resistant to conventional therapy. Recombinant Growth Hormone (GH) replacement for those with anterior pituitary failure is now also possible using the gene coding for GH and eliminates the risk of prion or viral infection. Whether this drug, which requires parenteral administration, will be used only in children with pituitary failure to prevent dwarfism or also in normally developed adults with acquired anterior pituitary failure remains to be seen.

Recombinant thyrotrophin (TSH) has also been produced and is used in the management of patients who have been treated for thyroid cancer. To assess for possible metastatic disease, thyroxine replacement therapy should be stopped prior to ¹³¹I imaging and thyroglobulin (Tg) measurement but this results in a period of hypothyroidism. Recombinant thyrotrophin, however, can be used without stopping thyroxine in those patients who had negative imaging studies in the past and who only require a post-TSH stimulated Tg measurement.

Summary

     Over the last two centuries, GRI has seen a number of distinguished and gifted individuals on it’s staff who have transformed clinical practice worldwide.

GRI Bi-Centennial pin

GRI has also seen the contributions of enumerable, devoted, yet unsung individuals in the daily round of treatment and teaching. Their gifts to the Royal have included their inspiration, skills and dedication which have been provided for their generation of patients and junior staff. It has been said that a gift must be passed on to others or it ceases to be a gift. The same can be said about an institution like GRI. A teaching hospital first and foremost, it’s doctors, nurses and scientists have each received their own gifting in part from the previous generation.

Sunrise from GRI^[2]

They, in their turn, will continue this cycle of caring and teaching into the future and follow in the footsteps of generations of past staff.

As the sun rises upon yet another day of caring and teaching at Glasgow Royal, one can confidently predict that its enormous contribution over the years to the health and welfare of the citizens of Glasgow and of the wider world will continue as a beacon for generations to come.

Endocrinology at Glasgow Royal had its roots in physiology from its birth in 1932 as a clinical specialty in the Saint Mungo’s College. It expanded slowly in the 1950s and 60s with the help of chemistry and radioiodine then matured rapidly in the 1970s with a partnership between clinical medicine, biochemistry, pathology, radiology and neurosurgery. The speciality finally came of age in the 80s and 90s with the addition of molecular analysis and recombinant techniques to point to, and further research, the best options for diagnosis, prevention and treatment of endocrine problems.

I think you will agree that, for GRI and endocrinology, it’s been quite a journey so far!!!

H W Gray

J A Thomson

References

[1]       Perry C G, Connell J M. Key Developments in Endocrinology. Practitioner. 2003 Jul; 247 (1648) :555, 558, 562 passim. Review. PubMed PMID: 12879561.

[2].     Sunrise from Glasgow Royal Infirmary.  With permission of Andrew McLaren, MSci. Photographer.

Acknowledgements

     This project has taken considerable time and effort but has also been a learning experience. I have come to appreciate, not only the technical intricacies of blogging, but also my privilege in working with this group of creative individuals over so many years. Contributing together as a team as well as striving individually in their own specialised areas, these doctors, nurses and scientists have contributed immensely to the reputation of the Royal Infirmary, Glasgow as a centre of excellence for medicine, surgery, nursing and, in particular, endocrinology.

I would like to thank all who have contributed to this Blog and for their encouragement as it was built up. John A Thomson has edited with precision and I am grateful for his memory of events and people. I am especially grateful to Graham Beastall who has not only guided me through the fascinating history of endocrine biochemistry, but has also supported me in the completion of Blogs starting ‘A Quantum Leap…..’ and ‘Endocrinology pushes …..’.

Andrew McAinsh, Librarian at the Royal College of Physicians and Surgeons of Glasgow has been most helpful in the retrieval of data. Craig Richardson of the Medical Illustration Department of GRI has found many of the old images of the hospital and has been most helpful and industrious. Alistair Tough, head of the Archives Section at the Mitchell Library has been most helpful  with advice and direction about the archives of GRI.

A final thanks to my wife for her patience and encouragement.

H W Gray