7-8 June Manila, Philippines

Transcription

1 FINAL PROGRAMME AND ABSTRACT BOOK 2014 Asia-Pacific endocrine conference: optimal management of diabetes and thyroid diseases 7-8 June Manila, Philippines

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3 Dear delegate, A warm welcome to all attending the conference on 2014 Asia-Pacific endocrine conference: optimal management of diabetes and thyroid diseases. I would like to inform you that as of 28 April 2014 the name of our Foundation changed to EXCEMED - Excellence in Medical Education. The name change will not impact your registration status in this or any other Foundation event. This transition marks an exciting point in the evolution of the Foundation. We are proud to have provided world-class education to thousands of healthcare professionals over the past four decades - as a result, the Foundation has become synonymous with delivery excellence and high-impact CME. As we further develop our scientific and geographical presence it is important to us that our name accurately reflects the independent nature of the education we provide; EXCEMED symbolises our enduring mission to support the best possible outcomes for patients through the medical education we offer. We take pride in our complete dedication to the provision of CME - it is our sole focus and our passion. I wish you an inspiring and successful learning experience here in Manila. Yours sincerely, Rachel Clark CEO, EXCEMED 1

4 General information Venue This live educational conference takes place at the: New World hotel A. Arnaiz Avenue, Makati City Manila, Philippines Language The official language of this live educational conference is English. Scientific secretariat EXCEMED - Excellence in Medical Education Salita di San Nicola da Tolentino, 1/b Rome, Italy Senior Programme Manager: Alessia Addessi T: F: info@excemed.org Specialist Medical Advisor: Davide Mineo EXCEMED is a Swiss Foundation with headquarters in 14, rue du Rhône, 1204 Geneva, Switzerland Organising secretariat Connex Asia Consulting 37A Hong Kong Street - Singapore Congress Coordinator: Suzanna Teh T F suzanna.teh@connex-asia.com 2

5 2014 Asia-Pacific endocrine conference: optimal management of diabetes and thyroid diseases EXCEMED live educational conference: 2014 Asia-Pacific endocrine conference: optimal management of diabetes and thyroid diseases 7-8 June Manila, Philippines Aim Type 2 diabetes mellitus is a growing epidemic in the Asia-Pacific countries, mainly due to the acquisition of a western life-style and the increasing occurrence of obesity. The complications and comorbidities associated with such conditions are an increasing burden to the healthcare systems and professionals of the region, also because of the lack of standardised guidelines for their care and management appropriate in this setting. Thyroid disorders are very common in the Asia-Pacific region, the main reason being the endemic iodine deficiency in such population causing goiter and gland dysfunction. Hypothyroidism, thyroid nodules and eventually cancer are common problems for the healthcare professionals of these countries and represent a challenge for the healthcare systems in terms of early diagnosis, standard of treatment and possibly prevention. EXCEMED is continuing its efforts to spread knowledge about the latest achievements in the field of diabetes and thyroid disorders by organising a dedicated annual meeting in the 2014, tailored to endocrinologists, diabetologists and general practitioners involved in managing the care of these important diseases. The aims of this live educational conference are to review the most significant achievements of research in this field, and to share the best practice for the clinical management of such diseases in daily practice. Learning objectives After attending this live educational conference, participants will have up-to-date knowledge about the research and clinical management of diabetes and thyroid disorders, and particularly will be able to: Improve the proper use of oral anti-diabetic agents in different conditions Appraise the insights of complications and comorbidities associated with diabetes for a better management in daily clinical practice Recognise the burden of thyroid disorders from their diagnosis to different therapies Apply international standards for managing conditions such as thyroid disorders in pregnancy and differentiated thyroid cancers Target audience Endocrinologists, diabetologists, general practitioners, and all healthcare professionals from the Asia-Pacific region involved in managing either diabetes or thyroid diseases. 3

6 Accreditation EXCEMED ( is accredited by the European Accreditation Council for Continuing Medical Education (EACCME ) to provide the following CME activity for medical specialists. The EACCME is an institution of the European Union of Medical Specialists (UEMS), The CME 2014 Asia-Pacific endocrine conference: optimal management of diabetes and thyroid diseases held on 7-8 June 2014 in Manila, Philippines, is designated for a maximum of 9 (nine) hours of European CME credits (ECMEC). Each medical specialist should claim only those credits that he/she actually spent in the educational activity. EACCME credits are recognized by the American Medical Association (AMA) towards the Physician's Recognition Award (PRA). To convert EACCME credit to AMA PRA category 1 credit, please contact the AMA. EXCEMED adheres to the principles of the Good CME Practice Group (gcmep) follow us on EXCEMED_Cardio 4

7 Scientific organisers George Kahaly Department of Medicine I Gutenberg University Medical Center Mainz, Germany Roberto Mirasol St. Luke s Medical Center Section of Endocrinology, Diabetes and Metabolism Quezon City, Philippines This live educational conference is endorsed by MEMS (Malaysian Endocrine & Metabolic Society) We value your opinion! We are continually trying to develop and improve our educational initiatives to provide you with cutting-edge learning activities. During this conference you will be asked to answer a real-time survey and after you will be receiving an online survey to better tailor our future educational initiatives. We thank you for participating! 5

8 Faculty members Su-Ynn Chia The Endocrine Clinic Mount Elizabeth Medical Centre Mount Elizabeth, Republic of Singapore Patricia Gatbonton Department of Medicine Our Lady of Lourdes Hospital Manila, Philippines George Kahaly Department of Medicine I Gutenberg University Medical Center Mainz, Germany Mohamed Mafauzy Health Campus Universiti Sains Malaysia Kelantan, Malaysia Nanny N.M. Soetedjo Endocrinology and Metabolism Division Internal Medicine Department Hasan Sadikin General Hospital Faculty of Medicine Padjadjaran University Padjadjaran, Indonesia Iris Thiele Isip Tan University of the Philippines College of Medicine Manila, Philippines Paolo Vitti Department of Endocrinology and Metabolism University of Pisa Pisa, Italy Roberto Mirasol St. Luke s Medical Center Section of Endocrinology, Diabetes and Metabolism Quezon City, Philippines Nemencio A. Nicodemus University of the Philippines College of Medicine Ateneo School of Medicine & Public Health Endocrinology, Diabetes & Metabolism Manila, Philippines Rakesh Sahay Osmania Medical College & Osmania General Hospital Hyderabad & Mediciti Hospital Hyderabad, India Bipin Sethi Department of Endocrinology Care Hospitals Hyderabad, India 6

9 Scientific programme

10 Scientific programme Saturday, 7 June Opening welcome and introduction R. Mirasol (Philippines) - G. Kahaly (Germany) Session I Managing diabetes and related disorders Session II Complications and comorbidities associated with diabetes Chair: R. Mirasol (Philippines) Real-time survey L1: Facing the epidemic of diabesity in the Asia- Pacific region today R. Mirasol (Philippines) L2: Metformin as first line therapy in diabetes: hypoglycaemia and beyond M. Mafauzy (Malaysia) L3: Second line therapies in diabetes: from incretins to insulins N.N.M. Soetedjo (Indonesia) Coffee Break L4: Tools for improving adherence to treatment in diabetes I. Tan (Philippines) RT: Pharmacological management of pre-diabetes: pros and cons Lunch Revisiting real-time survey Chair: R. Mirasol (Philippines) Real-time survey L5: Diabetes and autoimmunity G. Kahaly (Germany) L6: CVD in the setting of diabetes: a growing problem in clinical practice B. Sethi (India) L7: Pathophysiology of diabetic neuropathy and its possible treatments R. Mirasol (Philippines) Revisiting real-time survey Coffee break Session III From iodine deficiency and goiter to thyroid dysfunction Chair: G. Kahaly (Germany) Real-time survey L8: Iodine intake, thyroid function and neurocognitive development: a key relationship N. Nicodemus (Philippines) L9: Diagnosis and management of hypothyroidism in its different causes S.Y. Chia (Republic of Singapore) L10: Graves disease: pathophysiology and management G. Kahaly (Germany) Revisiting real-time survey End of the first day Legend: L : Lecture; RT : Round table; W : Workshop 8

11 Sunday, 8 June 2014 Session IV Thyroid disorders in special conditions and thyroid cancer Chair: P. Vitti (Italy)08.40 Real-time survey L11: Cardiovascular implications of thyroid dysfunctions G. Kahaly (Germany) L12: Thyroid disorders in pregnancy: when and how the endocrinologist should intervene R. Sahay (India) L13: International guidelines for managing differentiated thyroid cancers P. Vitti (Italy) Revisiting real-time survey Coffee break Workshops with clinical case presentations Session V The workshop session will involve learners in an interactive discussion, giving them the chance to share opinions and test their understanding of different topics and clinical cases. There will be two workshops, one on diabetes and one on thyroid, each lasting 45 minutes. The audience will be divided into two groups and each participant will attend both workshops in rotation. Take-home messages from the scientific organisers will be delivered at the end of the session W1: Managing gestational diabetes: from diagnosis to insulin therapy P. Gatbonton (Philippines) W2: Dissecting the thyroid nodules: from ultrasound to interventions P. Vitti (Italy) Take-home messages from the workshops by scientific organisers R. Mirasol (Philippines) and G. Kahaly (Germany) Revisiting real-time survey Closing remarks G. Kahaly (Germany) End of the conference and closing lunch 9

12 Abstracts

13 L1. Facing the epidemic of diabesity in the Asia-Pacific region today Roberto Mirasol St. Luke s Medical Center, Section of Endocrinology, Diabetes and Metabolism, Quezon City, Philippines Diabetes is in epidemic proportions! The number of people diabetes worldwide is believed to be 150 million according to WHO, most of it in this part of the world- the Asia Pacific region. By 2025 the number is expected to increase to over 300 million but this is a conservative estimate. Data has shown the prevalence is rapidly increasing in our countries where significant socioeconomic changes are occurring. The direct and indirect costs could greatly affect the healthcare budget of our countries. There is a large body of data showing that there are pathophysiological differences when comparing diabetes among Caucasians vs. Asians. Acceleration of cardiovascular risks has been demonstrated to be similar between Chinese communities (Hong Kong and Singapore) with body mass index (BMI) values > 23 kg/m2 and European subjects with BMI >25 kg/m2. It also believed that there is higher visceral fat noted among Asians compared to Caucasians with similar BMI. Adiponectin, a marker of insulin resistance was also noted to be low among Asians. There is higher mortality from coronary heart disease (CHD) in migrant South Asians compared with other populations and is due to metabolic disturbances related to insulin resistance. In comparison with the European group, the South Asian group had a higher prevalence of diabetes (19% vs 4%), higher blood pressures, higher fasting and post-glucose serum insulin concentrations, higher plasma triglyceride. and lower HDL cholesterol concentrations. Mean waist-hip girth ratios and trunk skinfolds were higher in the South Asian than in the European group. Within each ethnic group waist-hip ratio was correlated with glucose intolerance, insulin, blood pressure, and triglyceride. Aside from cardiovascular diseases, nephropathy has been found to occur earlier and more frequently among Asian diabetics. Nephropathy is the single most critical determinant of overall prognosis and this is particularly true in the Asia- Pacific region. Can we do something about it? Fortunately, there is now robust evidence that diabetes can be prevented in people at high risk, and the progression of many of the complications associated with diabetes can be delayed or even halted. The study by Pan on diabetes prevention among Chinese is one such study. We await the results of the The Acarbose Cardiovascular Evaluation (ACE) clinical trial will find out if a drug called acarbose can prevent people with coronary heart disease and impaired glucose tolerance (IGT) from experiencing, or dying from, further heart attacks and strokes. The ACE trial will also look to see if acarbose, which reduces blood glucose following a meal, can prevent or delay people progressing from IGT to type 2 diabetes. This is ongoing in Hong Kong and China. 11

14 L2. Metformin as first line therapy in diabetes: hypoglycaemia and beyond Mohamed Mafauzy Health Campus, Universiti Sains Malaysia, Kelantan, Malaysia Metformin has been in clinical use for more than 55 years and is the recommended first line agent in the treatment for type 2 diabetes mellitus. It works mainly through decreasing insulin resistance by decreasing hepatic glucose production and improving insulin sensitivity and peripheral glucose uptake. The main advantages of metformin are its extensive experience, no hypoglycemia and weight neutral. Hypoglycemia is a common occurrence in type 2 diabetes mellitus and about 35% of patients reported hypoglycemia symptoms. Hypoglycemia has also been associated with increased cardiovascular mortality and events. Recurrent or severe hypoglycemia may predispose to long term cognitive dysfunction and dementia. It may also negatively impact concordance with prescribed treatment and glycemic control as fear of hypoglycemia may cause patients to stop taking their medication or insulin. The United Kingdom Prospective Diabetes Study (UKPDS) is the first study to show that metformin significantly reduced any diabetes related endpoint and in the post-trial monitoring, there was also a significant reduction in myocardial infarction and mortality. Several observational studies had also shown that metformin treatment significantly reduced mortality and adverse cardiovascular outcomes compared to sulphonylureas. There are several studies which showed that metformin also reduced the risk of cancer and cancer mortality. In summary, metformin is the recommended agent of first choice in type 2 diabetes mellitus. Hypoglycemia is common in type 2 diabetes mellitus and is associated with increase morbidity and mortality and can affect patient compliance to treatment. Metformin has low risk of hypoglycemia and may also reduce CV events, cancer and deaths. 12

15 L3. Second line therapies in diabetes: from incretins to insulins Nanny N.M. Soetedjo Endocrinology and Metabolism Division, Department of Internal Medicine, Hasan Sadikin General Hospital - Faculty of Medicine, Padjadjaran University, Bandung-Indonesia Treatment of type 2 diabetes mellitus is mainly aimed to achieve normal blood glucose levels or at least near normal, hoping to prevent acute and chronic complications. ACCORD's Study showed that the more stringent target of HbA1C in the management of type 2 DM increased mortality rate due to cardiovascular. However it also proved that this strict target can reduce microvascular complications, especially nephropathy (microalbuminuria). Not only pharmacologic factors but also non-pharmacologic explained why controlling blood glucose cannot be done perfectly. Among them, poor adherence to lifestyle and not consuming the drugs regularly were the ones. There were also limitations and inability of drugs to inhibit the decreasing of beta cell pancreatic function. In addition, the presence of other factors that influence the pathogenesis of type 2 DM such as the role of glucagon and incretin which were considered to play important roles in controlling blood sugar levels. But which one was more superior than others as the cause of difficulty in controlling blood glucose very individual in type 2 DM patients. In 2012 American Diabetes Association (ADA) and European Association for the Study of Diabetes (EASD) issued a consensus based on Patients Centered Approach, where the target of HbA1c and selection of blood glucose lowering drugs were very individual. In that consensus, metformin was the first choice as type 2 DM treatment, followed by healthy lifestyle. In general the target of HbA1c 7.0 %, but in specific groups can be more stringent ( 6.5 %) or even more loose ( 8.0 %). If after 3 months with metformin HbA1C cannot achieved, we have to add second agent. Choosing the second agent was depend on aged, risk of hypoglycemia, weight gain, the ability in decreasing rate of HbA1C and the most important was the costs. Metformin can be combined with sulfonylurea or thiazolindindione or DPP-IV inhibitors or GLP-1 agonists or basal insulin. Any combinations can be given to type 2 DM, depends on patients need, this is which we called Patients Centered Approach. No combination is better than others, the good combination is the one that can delay and prevent complications to our type 2 DM patients. Keywords: diabetes mellitus, second agent, individual References: 1 - Chappel SC, Howles C 1991 Reevaluation of the roles of luteinizing hormone and follicle-stimulating hormone in the ovulatory process. Human Reproduction Filicori M, Cognigni GE, Pocognoli P et al Current concepts and novel applications of LH activity in ovarian stimulation. Trends in Endocrinology and Metabolism 14,

16 L4. Tools for improving adherence to treatment in diabetes Iris Thiele Isip Tan University of the Philippines, College of Medicine, Manila, Philippines There are thousands of mobile apps available and more are being added online every day. Of the many healthcare-related apps, the most popularly downloaded are the apps to track exercise, monitor diet and manage weight. There are also apps that remind its user to take medications. The presentation will discuss how these apps can potentially improve adherence to diabetes treatment. 14

17 L5. Diabetes and autoimmunity George Kahaly Department of Medicine I, Gutenberg University Medical Center, Mainz, Germany Type 1 diabetes is an autoimmune disorder caused by an inflammatory destruction of pancreatic tissue. Several studies revealed characteristics of the pathologic process and found susceptibility genes for type 1 diabetes or autoimmune diseases, respectively. Over the past years, the annual incidence of type 1 diabetes mellitus has constantly increased in most parts of the world and especially in industrializing nations it is still rapidly increasing nowadays. Type 1 diabetes is frequently accompanied by additional autoimmune endocrine and non-endocrine diseases and a familial clustering can be found, which suggests a genetic predisposition. Currently, there are several various hypotheses pertaining to the cause of pancreatic autoimmunity, but a complete explanation of the origin of type 1 diabetes or autoimmune diseases in general has not been found yet. Patients with type 1 diabetes are at a higher risk for developing additional endocrine autoimmune diseases. Such an autoimmune polyglandular syndrome shows several characteristic features that are different from monoglandular autoimmune diseases suggesting a sub-classification of these patients. Recently, genetic research focusing on autoimmune endocrinopathies revealed a multitude of potential autoantigenes that can be found in patients with an autoimmune polyglandular syndrome. Therefore the origin and pathogenesis of type 1 diabetes within the scope of the autoimmune polyglandular syndrome should be considered to be one of various phenotypes of an endocrine autoimmunity predisposing to different endocrinopathies or autoimmune diseases, respectively. 15

18 L6. CVD in the setting of diabetes: a growing problem in clinical practice Bipin Sethi Department of Endocrinology, Care Hospitals, Hyderabad, India The prevalence of diabetes mellitus is increasing globally and with that increases the burden of its complications. Cardiovascular disease is the leading cause of death and in diabetes this accounts for higher mortality especially in women. The excess risk attributed to diabetes was initially considered to be equal to that of established myocardial infarction, but this premise has been contested and was an aberration due to the longer duration of diabetes or age. The issue of screening for CVD is controversial and should be limited to individuals with symptoms, resting EKG abnormalities or multiple risk factors. The emphasis is on CVD prevention with focus on glycemia, lipids, hypertension, procoagulant stage and adoption of healthy life style. None of these interventions is without controversy about their relative role, timing, overall safety and intensity/target. Though the role of antihyperglycemic strategies is not as well tested as the antihypertensive or lipid lowering drugs, it is clear that its initiation early in the course of disease might be beneficial though the effect is manifest after few years. Interventions later on in the disease may be neutral or even harmful for CV events. It has also been opined that severe hypoglycemia inherent to intensive therapies may be responsible for excess CV mortality. Some antihyperglycemic agents have been taken off due to concerns of CV safety and most new agents are being evaluated for the same or CV benefit. The increased incidence of heart failure with DPP -4 inhibitors which conferred no CV benefit in two recent long term CV outcome trials came as a surprise, projected they were as agents without hypoglycemia and some other theoretical benefits. The new ACC-AHC guidelines recommend the use of high intensity statin with the intention of >50% lowering of LDL in patients with established CVD as also for primary prevention when the 10 year ASCVD risk is >7.5%. Moderate intensity statin therapy is suggested for others when it is < 7.5% in diabetics aged years with LDL levels between mg/dl. It does not place emphasis on the role of non HDL-C. Since the BP lowering arm of ACCORD showed no benefit but some harm in intensely treated patient, the latest JNC8 guidelines favor the target to 140/90 mm Hg for diabetics. This cutoff is based on safety but has been a subject of intense debate. The ESH/ESC and ADA targets are at 140/85 mm 140/80 mm Hg respectively. Given the propensity for promoting bleeding, the role of aspirin in primary prevention is limited to those who have 10yr CVD risk in excess of 10yrs or multiple risk factors for CVD. Notwithstanding these controversies, multiple risk reduction approach addressing weight, smoking cessation, early intensification of glycemic control, effective blood pressure lowering and LDL reduction are time tested methods to ameliorate/manage CVD. In established cases of CVD the glycemic targets need to be less stringent especially when the agents being administered can cause hypoglycemia. For this increasingly encountered problem there is a need to test the impact of the chosen strategies/cutoffs and evolve the consensus for choosing the best option for the patients. References: 1 - Chappel SC, Howles C 1991 Reevaluation of the roles of luteinizing hormone and follicle-stimulating hormone in the ovulatory process. Human Reproduction Filicori M, Cognigni GE, Pocognoli P et al Current concepts and novel applications of LH activity in ovarian stimulation. Trends in Endocrinology and Metabolism 14,

19 L7. Pathophysiology of diabetic neuropathy and its possible treatments Roberto Mirasol St. Luke s Medical Center, Section of Endocrinology, Diabetes and Metabolism, Quezon City, Philippines Diabetic neuropathies are a family of nerve disorders affecting different parts of the nervous system and presenting as various clinical manifestations and it remains as one of the most common long-term complication of diabetes. It is important to recognize this since it can precede foot ulceration, Charcot s foot and eventually lower extremity amputation and results in a high burden of cost to the individual and the community. Peripheral neuropathy is characterized by a progressive loss of nerve fibers that predispose a person to painful or insensitive extremities. Treatment is extremely difficult. Although there are published guidelines (American Academy of Neurology, the American Association of Neuromuscular and Electrodiagnostic Medicine, and the American Academy of Physical Medicine and Rehabilitation, American Diabetes Association) and there are available treatment options (tricyclic antidepressants, anticonvulsants, opiod and opiod - like drugs), treatment can be very daunting to the clinician. We review the most recent meta analysis on this subject by Snedecor et al. in Data from 58 studies including 29 interventions and 11,883 patients were analyzed and will be reviewed (1). Among the anticonvulsants, only gabapentin and pregabalin are effective. According to a review made by Wiffen in Only a minority of people achieved acceptably good pain relief with either drug, but it is known that quality of life and function improved markedly with the outcome of at least 50% pain intensity reduction. No other evidence, insufficient evidence or evidence of a lack of effect was seen in the other anticonvulsants (2). There is moderate quality evidence for duloxetine a seotonin and noradrenaline receptor reuptake inhibitor (3). Also a review of Chinese herbal medicines by Chen in 2013 showed that there is no evidence to support the objective effectiveness and safety of these Chinese herbal medications for the treatment of painful diabetic neuropathy (4). References: 1. Snedecor SJ, et al. Systematic review and meta-analysis of pharmacological therapies for painful diabetic peripheral neuropathy, Pain Prac, 2014 Feb; 14 (2): Wiffen PJ, Derry S, Moore RA, Aldington D, Cole P, Rice ASC, Lunn MPT, Hamunen K, Haanpaa M, Kalso EA. Antiepileptic drugs for neuropathic pain and fibromyalgia - an overview of Cochrane reviews. Cochrane Database of Systematic Reviews 2013, Issue 11. Art. No.: CD DOI: / CD pub2. 3. Lunn MPT, Hughes RAC, Wiffen PJ. Duloxetine for treating painful neuropathy, chronic pain or fibromyalgia. Cochrane Database of Systematic Reviews 2014, Issue 1. Art. No.: CD DOI: / CD pub3. 4. Chen W, Zhang Y, Li X, Yang G, Liu JP. Chinese herbal medicine for diabetic peripheral neuropathy. Cochrane Database of Systematic Reviews 2013, Issue 10. Art. No.: CD DOI: / CD pub3. 17

20 L8. Iodine intake, thyroid function and neurocognitive development: a key relationship Nemencio A. Nicodemus University of the Philippines, College of Medicine, Ateneo School of Medicine & Public Health Endocrinology, Diabetes & Metabolism, Manila, Philippines A discussion of thyroid function will not be complete without mentioning the role of iodine since this mineral is an essential structural backbone of the hormones thyroxine and triiodothyronine. Dietary iodine reaches the circulation as iodide ion. Iodide (I-), is avidly taken up from blood by thyroid epithelial cells. Once inside the cell, iodide is transported into the lumen of the follicle along with thyroglobulin, where it is incorporatedin the tyrosine residues of the latter. After coupling, thyroid hormones are released from the thyroglobulin via proteolysis. Since the main sources of iodine in the serum come from the food rich in iodine, dietary iodine intake affects thyroid function in that the rate of iodine uptake and incorporation into thyroglobulin is influenced by the amount of iodide available: Low iodide levels increase iodine transport into follicular cells High iodide levels decrease iodine transport into follicular cells Thus, adequate dietary iodine is required for normal thyroid function. Neurocognitive development and iodine intake has been well studied. It is well established that severe iodine deficiency can cause cretinism in children. Iodine deficiency may manifest as hypothyroidism. The latter has implications in neurodevelopment since thyroid hormones play an important role in neuronal cell differentiation, maturation, migration, myelination and neurotransmission. Since neurocognitive development starts during infancy and continues through adolescence and adulthood, maternal thyroid hormone status plays a fundamental role. Observational studies have shown a significant association between maternal thyroid deficiency and cognitive impairment in children. A meta-analysis revealed at 13.5-point difference in IQ between iodine sufficient and iodine deficient children. Systematic reviews and clinical trials have shown that iodine supplementation improves motor development, visual attention and spatial ability. Given all these evidence, the European Food Safety Authority (EFSA) panel on Dietetic Products, Nutrition and Allergies (NDA) issued a statement that a cause and effect relationship has been established between the dietary intake of iodine and contribution to normal cognitive development, 18

21 L9. Diagnosis and management of hypothyroidism in its different causes Su-Ynn Chia The Endocrine Clinic, Mount Elizabeth Medical Centre, Mount Elizabeth, Republic of Singapore Main objective To present an update on the etiology and types of hypothyroidism as well as its management. Topic covered by presentation Hypothyroidism is the result of inadequate production of thyroid hormone or inadequate action of thyroid hormone in target tissues. Primary hypothyroidism is the most common cause of hypothyroidism, but rarer causes include central deficiency of thyrotropinreleasing hormone or thyroid-stimulating hormone (TSH), or consumptive hypothyroidism from excessive inactivation of thyroid hormone. Subclinical hypothyroidism is present when there is elevated TSH but a normal free thyroxine level. Treatment involves oral administration of exogenous synthetic thyroid hormone. 19

22 L10. Graves disease: pathophysiology and management George Kahaly Department of Medicine I, Gutenberg University Medical Center, Mainz, Germany Graves disease (GD) is the most common cause of hyperthyroidism. GD occurs more often in women than in men with a female: male ratio of 5:1 and a population prevalence of 1-2%. A genetic determinant to the susceptibility to GD is suspected because of familial clustering of the disease, a high sibling recurrence risk, the familial occurrence of thyroid autoantibodies, and the 30% concordance in disease status between identical twins. About 30-50% of subjects with GD develop Graves orbitopathy (GO), which is usually of mild to moderate severity. This eye disorder usually lasts 1 to 2 years and often improves on its own. GO can occur before, at the same time as, or after other symptoms of hyperthyroidism develop. GO is severe in 5% of people who have the disorder, and smoking makes GO worse. Common symptoms of hyperthyroidism include nervousness or irritability, heat intolerance, rapid and irregular heartbeat, frequent bowel movements or diarrhea, weight loss and goiter. Symptoms of GO include dry, irritated eyes, light sensitivity, pressure of pain in the eyes, puffy eyelids, bulging eyes, trouble moving the eyes, double vision, and in rare cases vision loss. GD is an autoimmune thyroid disorder characterized by the infiltration of immune effector cells and thyroid-antigen-specific T cells into the thyroid and thyroid stimulating hormone receptor (TSHR) expressing tissues, with the production of autoantibodies to welldefined thyroidal antigens such as thyroid peroxidase, thyroglobulin, and the TSHR. The TSHR expressed on the plasma membrane of thyroid epithelial cells, is central to the regulation of thyroid growth and function. However, it is also expressed on a variety of other tissues, including adipocytes and bone cells. The TSHR is the major autoantigen in the autoimmune hyperthyroidism of GD where T cells and autoantibodies are directed at the TSHR antigen. Stimulatory autoantibodies in GD activate TSHR on thyroid follicular cells, leading to thyroid hyperplasia and unregulated thyroid hormone production and secretion. The close clinical relationship between Graves hyperthyroidism and GO has suggested that immunoreactivity against the TSHR present in both the thyroid and orbit underlies both conditions. Numerous studies did demonstrate that TSHR mrna and protein are present and expressed as an autoantigen in affected orbital tissues of patients with GO. Below-normal levels of baseline serum TSH, normal to elevated levels of T4, elevated levels of T3, elevated levels of TSHR autoantibodies, and a diffusely enlarged, heterogeneous, hypervascular (increased Doppler flow) thyroid gland confirm diagnosis of GD. During entire pregnancy of patients with GD circulating anti-tshr-antibodies can pass to the baby and cause either neonatal autoimmune thyrotoxicosis (functionally stimulating immunoglobulins) or hypothyroidism (blocking autoantibodies). The hyperthyroidism of GD is treated by reducing thyroid hormone synthesis, using antithyroid drugs, or by reducing the amount of thyroid tissue with radioiodine treatment or near-total thyroidectomy. 20

23 L11. Cardiovascular implications of thyroid dysfunctions George Kahaly Department of Medicine I, Gutenberg University Medical Center, Mainz, Germany Thyroid hormone (TH) influences cardiac performance by genomic and non-genomic effects and increases cardiac output by affecting stroke volume and heart rate. Triiodothyronine (T3) is essential to preserve cardiac morphology and function in adult life. The heart is particularly vulnerable to the reduction in T3 levels because T3 controls the inotropic and lusitropic properties of the myocardium, cardiac growth, myocardial contractility and vascular function. Many of the physiological effects of thyroid hormone are mediated by its genomic nuclear effects. Several important cardiac structural and functional proteins are transcriptionally regulated by T3, namely, sarcoplasmic reticulum calcium adenosine triphosphatase (ATP-ase) (SERCA2), α myosin heavy chain (α MHC), β1 adrenergic receptors, sodium /potassium ATP-ase, voltage-gated potassium channels, malic enzyme and atrial and brain natriuretic hormone. Furthermore, TH regulates the transcription of pacemaker-related genes and hyperpolarization-activated cyclic nucleotide-gated channels 3 and 4, and guanine nucleotide regulatory proteins. In addition, T3 modulates the expression of angiotensin receptors in vascular smooth muscle cells. Other cardiac gene are negatively regulated by T3, i.e., β-myosin heavy chain (β MHC), phospholamban, sodium/calcium exchanger, TRa1 and adenylyl cyclase type V and VI. The non-genomic effects exerted by TH on cardiac myocyte and peripheral vascular resistance are the effects that do not require the binding to nuclear receptors. These effects involve the transport of ions (calcium, sodium and potassium) across the plasma membrane, glucose and amino acid transport, mitochondrial function and a variety of intracellular signaling pathways. Pertaining to the clinical phenotype, short-term hyperthyroidism is characterized by a high cardiac output state with a remarkable increase in heart rate and cardiac preload and a reduction in peripheral vascular resistance, resulting in a hyperdynamic circulation. However, patients with untreated overt and subclinical hyperthyroidism are at increased risk of cardiac death due to the increased risk of atrial arrhythmias and heart failure. Moreover, autoimmune hyperthyroidism has been linked to autoimmune cardiovascular involvement. Pulmonary arterial hypertension, myxomatous cardiac valve disease and autoimmune reversible and irreversible dilated cardiomyopathy have been reported in patients with Graves disease. In comparison, short-term hypothyroidism is characterized by a low cardiac output due to the decreased heart rate and stroke volume. Subclinical hypothyroidism with TSH >10 mu/l is an important risk factor for heart failure and coronary heart disease events and mortality in adults. Replacement doses of L-thyroxine may improve cardiovascular remodeling and function in patients with overt and subclinical hypothyroidism and therefore significantly decrease the cardiovascular risk factors associated with mild hypothyroidism, foremost in younger patients. 21

24 L12. Thyroid disorders in pregnancy: when and how the endocrinologist should intervene Rakesh Sahay Osmania Medical College & Osmania General Hospital, Hyderabad & Mediciti Hospital, Hyderabad, India Abstract not in hand at the time of printing. References: 1 - Chappel SC, Howles C 1991 Reevaluation of the roles of luteinizing hormone and follicle-stimulating hormone in the ovulatory process. Human Reproduction Filicori M, Cognigni GE, Pocognoli P et al Current concepts and novel applications of LH activity in ovarian stimulation. Trends in Endocrinology and Metabolism 14,

25 L13. International guidelines for managing differentiated thyroid cancers Paolo Vitti Department of Endocrinology and Metabolism, University of Pisa, Pisa, Italy Differentiated thyroid cancer (DTC) is the most common endocrine malignancy. In USA, thyroid cancer represents 3.6% of all new cancer cases and it s the fastest increasing cancer in women since 1990s. It has a lower mortality and accounts for less than 0.3% af all cancer deaths. Most DTC present as asymptomatic thyroid nodules, but the first sign of the disease is occasionally lymph-node metastases or, in rare cases, lung or bone metastases. The primary treatment for DTC is the total or near total thyroidectomy although there is still some controversy about the extent of thyroid surgery. Therefore, the thyroid gland and affected cervical lymph-nodes should be resected. During the years, the way to manage DTC is changed, and nowadays many of the treatments for this disease are based on the evidence based medicine. The major guidelines showed as the patients risk stratification is a cornerstone for the management of DTC. Radioiodine ( 131 I) remnant ablation, with low or high activity, and with thyroid hormone withdrawal or recombinant human TSH stimulation, is given post-operatively to destroy any remaining normal or neoplastic thyroid tissue, to increase the sensitivity of measurements of serum thyroglobulin (Tg) and for the detection of persistent or recurrent disease. According to recent papers radioiodine remnant ablation is suggesting for the high risk patients, is not suggested for the very low and low risk patients, while for the intermediate risk is recommended the selective use based upon the clinical expert opinions. The goals of follow-up after initial therapy are to maintain an adequate thyroxine therapy and to detect persistent or recurrent disease by serum Tg measurement and neck ultrasound. DTC is usually a type of cancer that is often cured after initial treatments (surgery and radioiodine) and also in case of biochemical or structural disease show a slow growth; so, in case of radioiodine uptake of metastatic lesion, 131 I therapy is suggested. Active therapies with chemotherapy agents (es Tyrosine Kinase Inhibitors) are left to the patients with a significant (20%) increase in metastatic lesion or with appearance of new lesions. 23

26 Disclosure of faculty relationships EXCEMED adheres to guidelines of the European Accreditation Council for Continuing Medical Education (EACCME ) and all other professional organizations, as applicable, which state that programmes awarding continuing education credits must be balanced, independent, objective, and scientifically rigorous. Investigative and other uses for pharmaceutical agents, medical devices, and other products (other than those uses indicated in approved product labeling/package insert for the product) may be presented in the programme (which may reflect clinical experience, the professional literature or other clinical sources known to the presenter). We ask all presenters to provide participants with information about relationships with pharmaceutical or medical equipment companies that may have relevance to their lectures. This policy is not intended to exclude faculty who have relationships with such companies; it is only intended to inform participants of any potential conflicts so that participants may form their own judgements, based on full disclosure of the facts. Further, all opinions and recommendations presented during the programme and all programme-related materials neither imply an endorsement nor a recommendation on the part of EXCEMED. All presentations represent solely the independent views of the presenters/authors. The following faculty provided information regarding significant commercial relationships and/or discussions of investigational or non-emea/fda approved (off-label) uses of drugs: Su-Ynn Chia Declared no potential conflict of interest. George Kahaly Declared no potential conflict of interest. Mohamed Mafauzy Declared no potential conflict of interest. Roberto Mirasol Declared to be member of a company advisory board, board of directors or other similar groups: Merck, Merck Sharpe and Dohme. Nemencio A. Nicodemus Declared receipt of honoraria or consultation fees from Novartis, Merck, Eli Lilly. He declared also to be member of a company advisory board, board of directors or other similar groups: Merck, Astra Zeneca. Rakesh Sahay Declared receipt of honoraria or consultation fees from Sanofi, Novo Nordisk, Eli Lilly, Astra Zeneca, Abbott, BMS. Bipin Sethi Declared no potential conflict of interest. Nanny N.M. Soetedjo Declared no potential conflict of interest. The following faculty have provided no information regarding significant relationship with commercial supporters and/or discussion of investigational or non-emea/fda approved (off-label) uses of drugs as of 26 May Patricia Gatbonton Iris Thiele Isip Tan Paolo Vitti All EXCEMED programmes are organized solely to promote the exchange and dissemination of scientific and medical information. No forms of promotional activities are permitted. There may be presentations discussing investigational uses of various products. These views are the responsibility of the named speakers, and do not represent an endorsement or recommendation on the part of EXCEMED. This programme is made possible thanks to educational grants received from: Arseus Medical, Besins Healthcare, Bristol-Myers Squibb, Celgene, Centre d Esclerosi Multiple de Catalunya (Vall d Hebron University Hospital), Centre Hépato-Biliaire (Hôpital Paul Brousse), Croissance Conseil, Cryo-Save, Datanalysis, Dos33, Esaote, Ferring, Fondazione Humanitas, Fundación IVI, GE Healthcare, GlaxoSmithKline Pharmaceuticals, IPSEN, Italfarmaco, Johnson & Johnson Medical, K.I.T.E., Karl Storz, Lumenis, Merck Serono Group, PregLem, Richard Wolf Endoscopie, Sanofi-Aventis, Stallergenes, Stopler, Teva Pharma, Toshiba Medical Systems, Université Catholique de Louvain (UCL), University of Catania. 24

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32 Improving the patient's life through medical education EXCEMED - Excellence in Medical Education Headquarters 14, Rue du Rhône Geneva, Switzerland Representative Office Salita di San Nicola da Tolentino 1/b Rome, Italy T F Copyright EXCEMED, All rights reserved.