2014 Asia-Pacific endocrine conference: optimal … Asia-Pacific endocrine conference: optimal...

2014 Asia-Pacific endocrine conference: optimal management of diabetes and thyroid diseases7 - 8 June 2014 - Manila, Philippines

FINAL PROGRAMME AND ABSTRACT BOOK

Rachel ClarkCEO, EXCEMED

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Dear delegate,

A warm welcome to all attending the conference on “2014 Asia-Pacific endocrine conference: optimal management ofdiabetes and thyroid diseases”.

I would like to inform you that as of 28 April 2014 the name of our Foundation changed to EXCEMED - Excellence inMedical 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-classeducation to thousands of healthcare professionals over the past four decades - as a result, the Foundation has becomesynonymous 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 reflectsthe independent nature of the education we provide; EXCEMED symbolises our enduring mission to support the bestpossible outcomes for patients through the medical education we offer. We take pride in our complete dedication to theprovision of CME - it is our sole focus and our passion.

I wish you an inspiring and successful learning experience here in Manila.

Yours sincerely,

General information

VenueThis live educational conference takes place at the:

New World hotel A. Arnaiz Avenue, Makati CityManila, Philippines

LanguageThe official language of this live educational conference is English.

Scientific secretariatEXCEMED - Excellence in Medical EducationSalita di San Nicola da Tolentino, 1/b00187 Rome, Italy

Senior Programme Manager: Alessia AddessiT: +39 06 420413 591F: +39 06 420413 677E-mail: [email protected]

Specialist Medical Advisor: Davide Mineo

EXCEMED is a Swiss Foundation with headquarters in 14, rue du Rhône, 1204 Geneva, Switzerland

Organising secretariatConnex Asia Consulting 37A Hong Kong Street - Singapore 059676Congress Coordinator: Suzanna TehT +65 9 776 4243 - F +65 6 5333 239E-mail: [email protected]

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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 diseases7 - 8 June 2014 - Manila, Philippines

AimType 2 diabetes mellitus is a growing epidemic in the Asia-Pacific countries, mainly due to the acquisition of a western life-style andthe increasing occurrence of obesity. The complications and comorbidities associated with such conditions are an increasing burdento the healthcare systems and professionals of the region, also because of the lack of standardised guidelines for their care andmanagement appropriate in this setting. Thyroid disorders are very common in the Asia-Pacific region, the main reason being the endemic iodine deficiency in suchpopulation causing goiter and gland dysfunction. Hypothyroidism, thyroid nodules and eventually cancer are common problems forthe 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 disordersby organising a dedicated annual meeting in the 2014, tailored to endocrinologists, diabetologists and general practitioners involvedin managing the care of these important diseases. The aims of this live educational conference are to review the most significantachievements of research in this field, and to share the best practice for the clinical management of such diseases in daily practice.

Learning objectivesAfter attending this live educational conference, participants will have up-to-date knowledge about the research and clinicalmanagement 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 clinicalpractice

• 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 audienceEndocrinologists, diabetologists, general practitioners, and all healthcare professionals from the Asia-Pacific region involved inmanaging either diabetes or thyroid diseases.

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AccreditationEXCEMED (www.excemed.org) is accredited by the European Accreditation Council for Continuing Medical Education (EACCME®) toprovide the following CME activity for medical specialists. The EACCME® is an institution of the European Union of MedicalSpecialists (UEMS), www.uems.net

The CME 2014 Asia-Pacific endocrine conference: optimal management of diabetes and thyroid diseases held on 7-8 June 2014in Manila, Philippines, is designated for a maximum of 9 (nine) hours of European CME credits (ECMEC). Each medical specialistshould claim only those credits that he/she actually spent in the educational activity. EACCME® credits are recognized by theAmerican Medical Association (AMA) towards the Physician's Recognition Award (PRA). To convert EACCME® credit to AMA PRAcategory 1 credit, please contact the AMA.

EXCEMED adheres to the principles of the Good CME Practice Group (gCMEp)

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Scientific organisers

George KahalyDepartment of Medicine IGutenberg University Medical CenterMainz, Germany

Roberto MirasolSt. Luke’s Medical CenterSection of Endocrinology, Diabetes and MetabolismQuezon City, Philippines

This live educational conference is endorsed by MEMS(Malaysian Endocrine & Metabolic Society)

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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 bettertailor our future educational initiatives.

We thank you for participating!

Faculty members

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Su-Ynn ChiaThe Endocrine ClinicMount Elizabeth Medical Centre Mount Elizabeth, Republic of Singapore

Patricia GatbontonDepartment of Medicine Our Lady of Lourdes HospitalManila, Philippines

George KahalyDepartment of Medicine IGutenberg University Medical CenterMainz, Germany

Mohamed MafauzyHealth CampusUniversiti Sains MalaysiaKelantan, Malaysia

Roberto MirasolSt. Luke’s Medical CenterSection of Endocrinology, Diabetes and MetabolismQuezon City, Philippines

Nemencio A. NicodemusUniversity of the PhilippinesCollege of MedicineAteneo School of Medicine & Public HealthEndocrinology, Diabetes & MetabolismManila, Philippines

Rakesh SahayOsmania Medical College & Osmania General HospitalHyderabad & Mediciti HospitalHyderabad, India

Bipin SethiDepartment of EndocrinologyCare HospitalsHyderabad, India

Nanny N.M. SoetedjoEndocrinology and Metabolism Division Internal Medicine DepartmentHasan Sadikin General HospitalFaculty of MedicinePadjadjaran UniversityPadjadjaran, Indonesia

Iris Thiele Isip TanUniversity of the PhilippinesCollege of MedicineManila, Philippines

Paolo VittiDepartment of Endocrinology and MetabolismUniversity of PisaPisa, Italy

Scientificprogramme

Scientific programme

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Chair: R. Mirasol (Philippines)

Real-time survey

09.00 L1: Facing the epidemic of “diabesity” in the Asia-Pacific region todayR. Mirasol (Philippines)

09.30 L2: Metformin as first line therapy in diabetes:hypoglycaemia and beyondM. Mafauzy (Malaysia)

10.00 L3: Second line therapies in diabetes: fromincretins to insulinsN.N.M. Soetedjo (Indonesia)

10.30 Coffee Break

11.00 L4: Tools for improving adherence to treatment indiabetesI. Tan (Philippines)

11.30 RT: Pharmacological management of pre-diabetes:pros and cons

Revisiting real-time survey

12.30 Lunch

Managing diabetes and related disordersSession I

Chair: R. Mirasol (Philippines)

11.00 Real-time survey

13.30 L5: Diabetes and autoimmunity G. Kahaly (Germany)

14.00 L6: CVD in the setting of diabetes: a growingproblem in clinical practice B. Sethi (India)

14.30 L7: Pathophysiology of diabetic neuropathy and itspossible treatmentsR. Mirasol (Philippines)


15.00 Coffee break

Chair: G. Kahaly (Germany)

Real-time survey

15.30 L8: Iodine intake, thyroid function andneurocognitive development: a key relationship N. Nicodemus (Philippines)

16.00 L9: Diagnosis and management of hypothyroidismin its different causesS.Y. Chia (Republic of Singapore)

16.30 L10: Graves’ disease: pathophysiology andmanagementG. Kahaly (Germany)


17.10 End of the first day

Complications and comorbidities associatedwith diabetesSession II

From iodine deficiency and goiter to thyroiddysfunctionSession III

Saturday, 7 June 2014

08.45 Opening welcome and introductionR. Mirasol (Philippines) - G. Kahaly (Germany)

Legend: L : Lecture; RT : Round table; W : Workshop

Sunday, 8 June 2014

Chair: P. Vitti (Italy)08.40

Real-time survey

09.00 L11: Cardiovascular implications of thyroiddysfunctionsG. Kahaly (Germany)

09.30 L12: Thyroid disorders in pregnancy: when and howthe endocrinologist should interveneR. Sahay (India)

10.00 L13: International guidelines for managingdifferentiated thyroid cancersP. Vitti (Italy)


10.30 Coffee break

Thyroid disorders in special conditions andthyroid cancerSession IV

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The workshop session will involve learners in an interactivediscussion, giving them the chance to share opinions and testtheir understanding of different topics and clinical cases.There will be two workshops, one on diabetes and one onthyroid, each lasting 45 minutes. The audience will be dividedinto two groups and each participant will attend bothworkshops in rotation. Take-home messages from thescientific organisers will be delivered at the end of thesession.

11.00 W1: Managing gestational diabetes: from diagnosisto insulin therapyP. Gatbonton (Philippines)

11.30 W2: Dissecting the thyroid nodules: fromultrasound to interventionsP. Vitti (Italy)

12.30 Take-home messages from the workshops byscientific organisersR. Mirasol (Philippines) and G. Kahaly (Germany)


13.00 Closing remarksG. Kahaly (Germany)

13.10 End of the conference and closing lunch

Workshops with clinical case presentations11.00-12.30Session V

Abstracts

L1. Facing the epidemic of “diabesity” in the Asia-Pacificregion today

Diabetes is in epidemic proportions! The number of people diabetes worldwide is believed to be 150 million according to WHO, mostof 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 aconservative estimate. Data has shown the prevalence is rapidly increasing in our countries where significant socioeconomicchanges 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 andSingapore) with body mass index (BMI) values > 23 kg/m2 and European subjects with BMI >25 kg/m2. It also believed that thereis higher visceral fat noted among Asians compared to Caucasians with similar BMI. Adiponectin, a marker of insulin resistance wasalso noted to be low among Asians. There is higher mortality from coronary heart disease (CHD) in migrant South Asians comparedwith 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-glucoseserum insulin concentrations, higher plasma triglyceride. and lower HDL cholesterol concentrations. Mean waist-hip girth ratiosand trunk skinfolds were higher in the South Asian than in the European group. Within each ethnic group waist-hip ratio wascorrelated with glucose intolerance, insulin, blood pressure, and triglyceride. Aside from cardiovascular diseases, nephropathy hasbeen found to occur earlier and more frequently among Asian diabetics. Nephropathy is the single most critical determinant ofoverall 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, andthe progression of many of the complications associated with diabetes can be delayed or even halted. The study by Pan on diabetesprevention among Chinese is one such study. We await the results of the The Acarbose Cardiovascular Evaluation (ACE) clinical trialwill find out if a drug called acarbose can prevent people with coronary heart disease and impaired glucose tolerance (IGT) fromexperiencing, or dying from, further heart attacks and strokes. The ACE trial will also look to see if acarbose, which reduces bloodglucose following a meal, can prevent or delay people progressing from IGT to type 2 diabetes. This is ongoing in Hong Kong andChina.

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Roberto MirasolSt. Luke’s Medical Center, Section of Endocrinology, Diabetes and Metabolism, Quezon City, Philippines

L2. Metformin as first line therapy in diabetes:hypoglycaemia and beyond

Metformin has been in clinical use for more than 55 years and is the recommended first line agent in the treatment for type 2diabetes mellitus. It works mainly through decreasing insulin resistance by decreasing hepatic glucose production and improvinginsulin sensitivity and peripheral glucose uptake. The main advantages of metformin are its’ extensive experience, no hypoglycemiaand weight neutral. Hypoglycemia is a common occurrence in type 2 diabetes mellitus and about 35% of patients reportedhypoglycemia symptoms. Hypoglycemia has also been associated with increased cardiovascular mortality and events. Recurrent orsevere hypoglycemia may predispose to long term cognitive dysfunction and dementia. It may also negatively impact concordancewith prescribed treatment and glycemic control as fear of hypoglycemia may cause patients to stop taking their medication orinsulin.

The United Kingdom Prospective Diabetes Study (UKPDS) is the first study to show that metformin significantly reduced any diabetesrelated 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 cardiovascularoutcomes compared to sulphonylureas. There are several studies which showed that metformin also reduced the risk of cancer andcancer mortality.

In summary, metformin is the recommended agent of first choice in type 2 diabetes mellitus. Hypoglycemia is common in type 2diabetes mellitus and is associated with increase morbidity and mortality and can affect patient compliance to treatment. Metforminhas low risk of hypoglycemia and may also reduce CV events, cancer and deaths.

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Mohamed MafauzyHealth Campus, Universiti Sains Malaysia, Kelantan, Malaysia

L3. Second line therapies in diabetes: from incretins toinsulins

Treatment of type 2 diabetes mellitus is mainly aimed to achieve normal blood glucose levels or at least near normal, hoping toprevent acute and chronic complications. ACCORD's Study showed that the more stringent target of HbA1C in the management oftype 2 DM increased mortality rate due to cardiovascular. However it also proved that this strict target can reduce microvascularcomplications, 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 andinability of drugs to inhibit the decreasing of beta cell pancreatic function. In addition, the presence of other factors that influencethe pathogenesis of type 2 DM such as the role of glucagon and incretin which were considered to play important roles in controllingblood sugar levels. But which one was more superior than others as the cause of difficulty in controlling blood glucose very individualin type 2 DM patients.

In 2012 American Diabetes Association (ADA) and European Association for the Study of Diabetes (EASD) issued a consensus basedon Patients Centered Approach, where the target of HbA1c and selection of blood glucose lowering drugs were very individual. Inthat 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 HbA1Ccannot 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 orthiazolindindione or DPP-IV inhibitors or GLP-1 agonists or basal insulin. Any combinations can be given to type 2 DM, depends onpatients need, this is which we called Patients Centered Approach. No combination is better than others, the good combination isthe one that can delay and prevent complications to our type 2 DM patients.

Keywords: diabetes mellitus, second agent, individual

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Nanny N.M. SoetedjoEndocrinology and Metabolism Division, Department of Internal Medicine, Hasan Sadikin General Hospital - Faculty of Medicine,Padjadjaran University, Bandung-Indonesia

References:1 - Chappel SC, Howles C 1991 Reevaluation of the roles of luteinizing hormone and follicle-stimulating hormone in the ovulatory process. Human Reproduction6 1206-1212.

2 - Filicori M, Cognigni GE, Pocognoli P et al. 2003 Current concepts and novel applications of LH activity in ovarian stimulation. Trends in Endocrinology andMetabolism 14, 267-273.

L4. Tools for improving adherence to treatment in diabetes

There are thousands of mobile apps available and more are being added online every day. Of the many healthcare-related apps, themost popularly downloaded are the apps to track exercise, monitor diet and manage weight. There are also apps that remind itsuser to take medications. The presentation will discuss how these apps can potentially improve adherence to diabetes treatment.

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Iris Thiele Isip TanUniversity of the Philippines, College of Medicine, Manila, Philippines

L5. Diabetes and autoimmunity

Type 1 diabetes is an autoimmune disorder caused by an inflammatory destruction of pancreatic tissue. Several studies revealedcharacteristics 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 andespecially in industrializing nations it is still rapidly increasing nowadays. Type 1 diabetes is frequently accompanied by additionalautoimmune 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 ofthe origin of type 1 diabetes or autoimmune diseases in general has not been found yet. Patients with type 1 diabetes are at a higherrisk for developing additional endocrine autoimmune diseases. Such an autoimmune polyglandular syndrome shows severalcharacteristic features that are different from monoglandular autoimmune diseases suggesting a sub-classification of thesepatients. Recently, genetic research focusing on autoimmune endocrinopathies revealed a multitude of potential autoantigenes thatcan be found in patients with an autoimmune polyglandular syndrome. Therefore the origin and pathogenesis of type 1 diabeteswithin the scope of the autoimmune polyglandular syndrome should be considered to be one of various phenotypes of an endocrineautoimmunity predisposing to different endocrinopathies or autoimmune diseases, respectively.

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George KahalyDepartment of Medicine I, Gutenberg University Medical Center, Mainz, Germany

L6. CVD in the setting of diabetes: a growing problem inclinical practice

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. Theexcess risk attributed to diabetes was initially considered to be equal to that of established myocardial infarction, but this premisehas 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 ormultiple 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 thatits initiation early in the course of disease might be beneficial though the effect is manifest after few years. Interventions later on inthe disease may be neutral or even harmful for CV events. It has also been opined that severe hypoglycemia inherent to intensivetherapies may be responsible for excess CV mortality. Some antihyperglycemic agents have been taken off due to concerns of CVsafety and most new agents are being evaluated for the same or CV benefit. The increased incidence of heart failure with DPP -4inhibitors which conferred no CV benefit in two recent long term CV outcome trials came as a surprise, projected they were as agentswithout 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 withestablished CVD as also for primary prevention when the 10 year ASCVD risk is >7.5%. Moderate intensity statin therapy is suggestedfor others when it is < 7.5% in diabetics aged 40-75 years with LDL levels between 70-199 mg/dl. It does not place emphasis on therole of non HDL-C.

Since the BP lowering arm of ACCORD showed no benefit but some harm in intensely treated patient, the latest JNC8 guidelinesfavor 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/ESCand 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 inexcess of 10yrs or multiple risk factors for CVD.

Notwithstanding these controversies, multiple risk reduction approach addressing weight, smoking cessation, early intensificationof glycemic control, effective blood pressure lowering and LDL reduction are time tested methods to ameliorate/manage CVD. Inestablished cases of CVD the glycemic targets need to be less stringent especially when the agents being administered can causehypoglycemia.

For this increasingly encountered problem there is a need to test the impact of the chosen strategies/cutoffs and evolve theconsensus for choosing the best option for the patients.

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Bipin SethiDepartment of Endocrinology, Care Hospitals, Hyderabad, India



L7. Pathophysiology of diabetic neuropathy and itspossible treatments

Diabetic neuropathies are a family of nerve disorders affecting different parts of the nervous system and presenting as variousclinical manifestations and it remains as one of the most common long-term complication of diabetes. It is important to recognizethis since it can precede foot ulceration, Charcot’s foot and eventually lower extremity amputation and results in a high burden ofcost to the individual and the community. Peripheral neuropathy is characterized by a progressive loss of nerve fibers that predisposea person to painful or insensitive extremities.

Treatment is extremely difficult. Although there are published guidelines (American Academy of Neurology, the AmericanAssociation 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 andopiod - like drugs), treatment can be very daunting to the clinician. We review the most recent meta analysis on this subject bySnedecor et al. in 2014. 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 2013. Only aminority of people achieved acceptably good pain relief with either drug, but it is known that quality of life and function improvedmarkedly with the outcome of at least 50% pain intensity reduction. No other evidence, insufficient evidence or evidence of a lack ofeffect was seen in the other anticonvulsants (2). There is moderate quality evidence for duloxetine a seotonin and noradrenalinereceptor reuptake inhibitor (3). Also a review of Chinese herbal medicines by Chen in 2013 showed that there is no evidence to supportthe objective effectiveness and safety of these Chinese herbal medications for the treatment of painful diabetic neuropathy (4).

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Roberto MirasolSt. Luke’s Medical Center, Section of Endocrinology, Diabetes and Metabolism, Quezon City, Philippines

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):167-184

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 andfibromyalgia - an overview of Cochrane reviews. Cochrane Database of Systematic Reviews 2013, Issue 11. Art. No.: CD010567. DOI:10.1002/14651858.CD010567.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.: CD007115. DOI: 10.1002/14651858.CD007115.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.: CD007796. DOI: 10.1002/14651858.CD007796.pub3.

L8. Iodine intake, thyroid function and neurocognitivedevelopment: a key relationship

A discussion of thyroid function will not be complete without mentioning the role of iodine since this mineral is an essential structuralbackbone of the hormones thyroxine and triiodothyronine. Dietary iodine reaches the circulation as iodide ion. Iodide (I-), is avidlytaken up from blood by thyroid epithelial cells. Once inside the cell, iodide is transported into the lumen of the follicle along withthyroglobulin, where it is incorporatedin the tyrosine residues of the latter. After coupling, thyroid hormones are released from thethyroglobulin 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 thatthe 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 causecretinism in children. Iodine deficiency may manifest as hypothyroidism. The latter has implications in neurodevelopment sincethyroid 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 thyroidhormone status plays a fundamental role. Observational studies have shown a significant association between maternal thyroiddeficiency and cognitive impairment in children. A meta-analysis revealed at 13.5-point difference in IQ between iodine sufficient andiodine deficient children.

Systematic reviews and clinical trials have shown that iodine supplementation improves motor development, visual attention andspatial ability.

Given all these evidence, the European Food Safety Authority (EFSA) panel on Dietetic Products, Nutrition and Allergies (NDA) issueda statement that a cause and effect relationship has been established between the dietary intake of iodine and contribution to normalcognitive development,

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Nemencio A. Nicodemus University of the Philippines, College of Medicine, Ateneo School of Medicine & Public HealthEndocrinology, Diabetes & Metabolism, Manila, Philippines

L9. Diagnosis and management of hypothyroidism in itsdifferent causes

Main objectiveTo present an update on the etiology and types of hypothyroidism as well as its management.

Topic covered by presentationHypothyroidism 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 thyrotropin-releasing hormone or thyroid-stimulating hormone (TSH), or consumptive hypothyroidism from excessive inactivation of thyroidhormone. Subclinical hypothyroidism is present when there is elevated TSH but a normal free thyroxine level. Treatment involvesoral administration of exogenous synthetic thyroid hormone.

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Su-Ynn ChiaThe Endocrine Clinic, Mount Elizabeth Medical Centre, Mount Elizabeth, Republic of Singapore

L10. Graves’ disease: pathophysiology and management

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 offamilial 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), whichis 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, andsmoking makes GO worse. Common symptoms of hyperthyroidism include nervousness or irritability, heat intolerance, rapid andirregular heartbeat, frequent bowel movements or diarrhea, weight loss and goiter. Symptoms of GO include dry, irritated eyes, lightsensitivity, pressure of pain in the eyes, puffy eyelids, bulging eyes, trouble moving the eyes, double vision, and in rare cases visionloss.

GD is an autoimmune thyroid disorder characterized by the infiltration of immune effector cells and thyroid-antigen-specific T cellsinto the thyroid and thyroid stimulating hormone receptor (TSHR) expressing tissues, with the production of autoantibodies to well-defined thyroidal antigens such as thyroid peroxidase, thyroglobulin, and the TSHR. The TSHR expressed on the plasma membraneof thyroid epithelial cells, is central to the regulation of thyroid growth and function. However, it is also expressed on a variety of othertissues, including adipocytes and bone cells. The TSHR is the major autoantigen in the autoimmune hyperthyroidism of GD whereT cells and autoantibodies are directed at the TSHR antigen. Stimulatory autoantibodies in GD activate TSHR on thyroid follicularcells, leading to thyroid hyperplasia and unregulated thyroid hormone production and secretion. The close clinical relationshipbetween Graves’ hyperthyroidism and GO has suggested that immunoreactivity against the TSHR present in both the thyroid andorbit underlies both conditions. Numerous studies did demonstrate that TSHR mRNA and protein are present and expressed as anautoantigen 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 TSHRautoantibodies, and a diffusely enlarged, heterogeneous, hypervascular (increased Doppler flow) thyroid gland confirm diagnosis ofGD. During entire pregnancy of patients with GD circulating anti-TSHR-antibodies can pass to the baby and cause either neonatalautoimmune thyrotoxicosis (functionally stimulating immunoglobulins) or hypothyroidism (blocking autoantibodies). Thehyperthyroidism of GD is treated by reducing thyroid hormone synthesis, using antithyroid drugs, or by reducing the amount ofthyroid tissue with radioiodine treatment or near-total thyroidectomy.

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L11. Cardiovascular implications of thyroid dysfunctions

Thyroid hormone (TH) influences cardiac performance by genomic and non-genomic effects and increases cardiac output byaffecting 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 themyocardium, cardiac growth, myocardial contractility and vascular function. Many of the physiological effects of thyroid hormone aremediated by its genomic nuclear effects. Several important cardiac structural and functional proteins are transcriptionally regulatedby T3, namely, sarcoplasmic reticulum calcium adenosine triphosphatase (ATP-ase) (SERCA2), α myosin heavy chain (α MHC), β1adrenergic receptors, sodium /potassium ATP-ase, voltage-gated potassium channels, malic enzyme and atrial and brain natriuretichormone. Furthermore, TH regulates the transcription of pacemaker-related genes and hyperpolarization-activated cyclicnucleotide-gated channels 3 and 4, and guanine nucleotide regulatory proteins. In addition, T3 modulates the expression ofangiotensin receptors in vascular smooth muscle cells. Other cardiac gene are negatively regulated by T3, i.e., β-myosin heavy chain(βMHC), phospholamban, sodium/calcium exchanger, TRa1 and adenylyl cyclase type V and VI. The non-genomic effects exerted byTH on cardiac myocyte and peripheral vascular resistance are the effects that do not require the binding to nuclear receptors. Theseeffects involve the transport of ions (calcium, sodium and potassium) across the plasma membrane, glucose and amino acidtransport, 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 remarkableincrease 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 increasedrisk of atrial arrhythmias and heart failure. Moreover, autoimmune hyperthyroidism has been linked to autoimmune cardiovascularinvolvement. Pulmonary arterial hypertension, myxomatous cardiac valve disease and autoimmune reversible and irreversibledilated 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 strokevolume. Subclinical hypothyroidism with TSH >10 mU/L is an important risk factor for heart failure and coronary heart diseaseevents and mortality in adults. Replacement doses of L-thyroxine may improve cardiovascular remodeling and function in patientswith overt and subclinical hypothyroidism and therefore significantly decrease the cardiovascular risk factors associated with mildhypothyroidism, foremost in younger patients.

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L12. Thyroid disorders in pregnancy: when and how theendocrinologist should intervene

Abstract not in hand at the time of printing.

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Rakesh SahayOsmania Medical College & Osmania General Hospital, Hyderabad & Mediciti Hospital, Hyderabad, India



L13. International guidelines for managing differentiatedthyroid cancers

Differentiated thyroid cancer (DTC) is the most common endocrine malignancy. In USA, thyroid cancer represents 3.6% of all newcancer 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-nodemetastases 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 ofthyroid 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 theevidence based medicine. The major guidelines showed as the patients risk stratification is a cornerstone for the management ofDTC. Radioiodine (131I) remnant ablation, with low or high activity, and with thyroid hormone withdrawal or recombinant human TSHstimulation, is given post-operatively to destroy any remaining normal or neoplastic thyroid tissue, to increase the sensitivity ofmeasurements 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 lowand 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 recurrentdisease 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 uptakeof metastatic lesion, 131I therapy is suggested. Active therapies with chemotherapy agents (es Tyrosine Kinase Inhibitors) are left tothe patients with a significant (20%) increase in metastatic lesion or with appearance of new lesions.

23

Paolo VittiDepartment of Endocrinology and Metabolism, University of Pisa, Pisa, Italy

Disclosure of faculty relationships

24

EXCEMED adheres to guidelines of the European Accreditation Council for Continuing Medical Education (EACCME®) and all otherprofessional 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 otherproducts (other than those uses indicated in approved product labeling/package insert for the product) may be presented in theprogramme (which may reflect clinical experience, the professional literature or other clinical sources known to the presenter). We askall presenters to provide participants with information about relationships with pharmaceutical or medical equipment companies thatmay have relevance to their lectures. This policy is not intended to exclude faculty who have relationships with such companies; it isonly intended to inform participants of any potential conflicts so that participants may form their own judgements, based on fulldisclosure of the facts. Further, all opinions and recommendations presented during the programme and all programme-relatedmaterials neither imply an endorsement nor a recommendation on the part of EXCEMED. All presentations represent solely theindependent views of the presenters/authors.

The following faculty provided information regarding significant commercial relationships and/or discussions of investigational ornon-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 tobe member of a company advisory board, board of directors or other similar groups: Merck, AstraZeneca.

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 discussionof investigational or non-EMEA/FDA approved (off-label) uses of drugs as of 26 May 2014.

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 arepermitted. There may be presentations discussing investigational uses of various products. These views are the responsibility of the named speakers, and do not representan endorsement or recommendation on the part of EXCEMED. This programme is made possible thanks to educational grants received from: Arseus Medical, BesinsHealthcare, 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.

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