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Department of Endocrinology and Diabetes Mellitus St.Vincent’s Healthcare Group 104 Endocrine Laboratory Service In an effo rt to help rationalise endocrine testing through the South Eastern Health Services St V i n c e n t ’s Unive rsity Hospital has u n d e rt a ken hormonal evaluation in relation to fe rtility disorders for St Michael’s Hospital which had previously been outsourced. To cope with increasing demand generated in this way and in other areas e.g.an increase HbA1c workload of 9% during the year, a Tosoh G7 analyser, which has greater speed and precision was introduced into the laboratory. An application to Clinical Pathology Accreditation (UK) was submitted in the latter half of the year by the laboratory. Eithne Cunningham left in 2003 to undertake a PhD in Trinity College;she was replaced by Anne- Marie Glynn. Research: Clinical Macroprolactin:This year saw the publication of the second of our papers on macroprolacinaemia in the journal Clinical Chemistry (US) which attracted an editorial.The paper and editorial highlighted approximately 10% of the prolactin measurements world-wide which may be misleading.The innocent phenomenon of macroprolactinemia may be interpreted as providing a diagnosis for infertility mainly in women.The papers which have appeared in the leading US clinical endocrinology and laboratory journals,highlight the message that frequent misdiagnosis,unnecessary investigation and inappropriate treatment may be prevented when elevated prolactin levels are submitted to additional relatively simple testing to identify the presence of macroprolactin.The department is undertaking both prospective and retrospective studies to gain insight into the mechanisms whereby macroprolactin arises and the precise impact of failure to diagnose the phenomenon. The ongoing clinical review is under the supervision of Dr James Gibney and the laboratory investigation under the supervision of Dr Tom Smith and Lucille Kavanagh,Research Graduate Student. Weight Management in Type 2 Diabetes: Obesity and weight gain are central to the development of diabetes mellitus and pose major impediments to its successful management. Dr Twani Tuthill in her MD project has retrospectively reviewed the profile of weight change in patients attending the Diabetes Service. Reviewing over 1,000 patients for an average of 5 years,Dr Tuthill noted that a mean weight loss of approximately 4kgs was achieved in the first year. Over the succeeding years there was a gradual return towards baseline. The weight loss achieved was superior to that reported internationally. Patients on diet alone were more successful in losing weight.Analysis of the data suggested that deterioration in diabetes control lead to changes in treatment,i.e. the addition of pharmaceutical agents. Weight gain accompanied the introduction of sulphonylureas and insulin but not metformin.Deteriorating glycaemic control was not dependent on weight gain. In a prospective study the impact of an intensified weight reduction programme for diabetic patients unsuccessful in losing weight fo l l owing conve n t i o n a l t r e a t m e n t ,was also studied by Dr Tu t h i l l .In collabora t i o n with a dietician,exercise therapist and psychologist, weight reduction was achieved in the majority of patients.This intensive form of treatment is successful and deserves extended application to a larger cohort of patients for a longer period. Radioactive Iodine Treatment of Thyrotoxicosis: Radioiodine is an established treatment for thyrotoxicosis.The principle disadvantage is the frequent occurrence of under-activity of thyroid gland following treatment.Dr Husafa Adamali and Dr James Gibney have reviewed results from a 10 year period to examine the outcome of treatment in patients with diffuse toxic goitre and patients with toxic nodular goitre. In addition they have examined the possibility that in patients with toxic nodular goitre the frequency of the development of hypothyroidism is directly related to the level of serum thyroid stimulating hormone (TSH).Their investigations to date have disclosed that while under-activity of the thyroid gland occurs in >50% of patients treated with diffuse toxic goitre, the recurrence is
Department of Endocrinology and Diabetes Mellitus St.Vincent’s Healthcare Group 106 Insulin Pump Therapy, St James Hospital, Dublin,October 21- 22nd 2003 Irish Endocrine Society, Armagh 7-8th November 2003 Office for Health Management Course, Tullamore Court Hotel, 10th November 2003 Diabetes Management:An Integrated Approach. Royal College of Obstetrics and Gynaecology, Regent Park,London,1st December 2003. Publications Kelly SN,McKenna TJ and Young LS. Modulation of steroidogenic enzymes by orphan nuclear transcriptional regulation may control diverse production of cortisol and androgens in the human adrenal. J Endocrinol.2004;181(2):355-65. Suliman AM, Smith TP, Gibney J and McKenna TJ. Frequent Misdiagnosis and Mismanagement of Hyperprolactinemic Patients before the Introduction of Macroprolactin Screening:Application of a New Strict Laboratory Definition of Macroprolactinemia. Clin Chem 2003;49(9) 1504-9. Suliman AM, Freaney R,Smith TP, McBrinn Y, Murray B, McKenna, TJ. The Impact of Different Glucocorticoid Replacement schedules on Bone Turnover and Insulin Sensitivity in Patients with Adrenal Insufficiency. Clin Endocrinol (Oxf) 2003 59(3): 380-87. Smith D, Keane P, Donovan J,Malone K, McKenna TJ,Lithium encephalopathy. J R Soc Med 2003;96(12):590-1. Abstracts The 22nd Joint Meeting of the British Endocrine Societies, Glasgow, UK 24-26 March 2003: Tuthill A,Curran S,McKenna M,O'Shea D and McKenna TJ. Glycaemic control,weight change and treatment :Examining the relationship in Type 2 diabetes. Endocrine Abstracts (2003) 5 P203 Smith TP, Gibney J,Kavanagh L,Dickinson A and McKenna TJ. A more rigorous laboratory definition of macroprolactinaemia with clinical significance. Endocrine Abstracts (2003) 5 P203 Tuthill A,Kelly R,Ryan Y and O'Shea D. Orlistat use outside of clinical trials:The Irish experience. Endocrine Abstracts (2003) 5 P84 McGowan G, Skehan S, Collins C and O'Shea D. Comparison of simultaneous ultrasonography and radio-isotope scanning in hyperthyroid patients as compared with radio-isotope scanning alone. Endocrine Abstracts (2003) 5 P272 The 85th Annual Endocrine Society Meeting,Philadelphia,June 19 th -22 nd : Smith TP, Gibney J,Kavanagh L,Dickinson A,McKenna TJ. A more vigorous laboratory definition of marcroprolactinemia with clinical significance. Book of abstracts P1-641 Irish Endocrine Society 28th Annual Meeting,Armagh, 7 th and 8 th November 2003:Kavanagh L,Smith TP, Gibney J and McKenna TJ. Macroprolactinaemic patients exhibit increased levels of peripheral blood CD5-positive B lymphocytes. Ir. J.Med.Sci. 2003;172(Supple 1):15. Smith TP, Gibney J,Kavanagh L, Fahie-Wilson MN and McKenna TJ. Specificity and clinical utility of methods for the detection of macroprolactin. Ir. J. Med.Sci. 2003:172(Supple 1):15-16. Adamali HI,Gibney J and McKenna TJ. Hypothyroidism is less frequent following radioactive iodine treatment for toxic nodular goitre than Graves’disease. Ir. J.Med.Sci.2003; 172(Supple 1):17. Smith D, Murray B, Gibney J and McKenna TJ. Application of new indices of bone activity for evaluation of the response to treatment of hyperthyroidism and Paget’s disease. Ir. J.Med. Sci.2003; 172(Supple 1):17. Collins O, Noone I and O’Shea D. Neurocardiovascular changes in patients before and after treatment of hypothyroidism. Ir. J.Med. Sci.2003;172(Supple 1):18. McGowan G,Skehan S, Collins C, McKenna TJ and O’Shea D. Comparison of simultaneous ultrasonography and radioisotope scanning in hyperthyroid patients as compared with radioisotope scanning alone. Ir. J.Med.Sci.2003; 172(Supple 1):21. Smith D, McKenna M,Saaidin JN,Al-Aradi A and O’Shea D. Glargine - clinical and patient perspective on a new long-acting insulin. Ir. J.Med Sci.2003;172(Supple 1):30. A Tuthill,VTuthill,C Barrett, M McKenna,D O’Shea.TJ McKenna Diastolic blood pressure, waist circumference and cardiovascular disease in patients with obesity and type 2 diabetes. Ir. J. Med.Sci. 2003;172(Supple 1):36. SN Kelly,T J McKenna, LS Young. Secretogogues induce transcription factor, steroidogenic factor–1 and co-activator, steroid receptor co-activator-1 in the human adrenal gland. Ir. J.Med.Sci. 2003;172(Supple 1):42-43. Staff Medical Director Principal Biochemist Senior Biochemist Laboratory Aide Secretary Professor TJ McKenna Barbara Murray Paula O’Shea Mairead Moore Siobhan Kelly Ms Maria Fitzgibbon,who was Principal Biochemist in the Department has joined the Department of NeuroSciences in Trinity College as Associate Director. Barbara Murray was appointed Principal Biochemist in February 03. Paula O’Shea joined Metabolism as Senior Biochemist in June 03 from the Biochemistry Department. Service Developments / Activities Department of M e t a b o l i s m Departmental Review The Metabolism Laboratory provides a comprehensive analytical and consultation service on metabolic problems for medical and surgical patients of St.Vincent’s Healthcare Group, and acts as a referring centre for specialist markers of bone and renal disease nationally. The Metabolism Laboratory is recognised as the provider of specialist tests of Bone Biomarkers,which are acknowledged internationally as a useful adjunct to the measurement of Bone Mineral Density.The request for these parameters has increased with awareness of their usefulness. Bone Biomarke rs are pri m a ri ly used to monitor the efficacy of anti-resorptive therapy.We and o t h e rs have shown that the short term (3 to 6 months) decrease of bone turnover is significantly correlated with the long term (2 years ) increase in Bone Mineral Density of both spine and hip.With the advent of new treatments such as recombinant PTH,which is associated with both cortical and cancellous bone benefits - the monitoring of such treatment by way of measuring Bone Biomarkers should prove to be clinically useful. An increase in the service for the measurement of Vitamin D continues to highlight the prevalence of Hypovitaminosis D in the Irish as well as in several of the ethnic populations now residing in Ireland. The diabetic patients attending the Diabetic Clinics in St Vincent’s University Hospital,St Michael’s Hospital and St Columcille’s Hospital were provided with the Microalbumin excretion ratio monitoring service. Research / Future Plans The effect on bone remodeling by the administration of glucocortoid therapy was studied and published. The examination of both biochemical and cellular markers of osteoblastic and osteoclastic activity in Breast Cancer patients at high risk of developing skeletal metastases continued. The study of the effect of disorders of Thyroid Hormone on Bone Turnover is progressing. The database of Bone Remodelling and Turnover Indices in metabolic bone disease as well as endocrine disorders are being examined with a view to identifying indices which will simplify clinical interpretation. The impact of eating disorders on bone turnover is being studied in collaboration with the Department of Psychiatry and Mental Health. The laboratory is advancing the accreditation programme to ensure 107
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