Indian Journal of Animal Reproduction 33 (1) : June 2012 REPRODUCTIVE PERFORMANCE DURING PARASITIC LOADS AND ITS CONTROL IN DOES DINESH MAHTO1, L.B.SINGH2, M.P.SINHA3, D.K.SINGH "DRON"4 AND D.K.JHA5 AICRP, on Black Bengal Goat, Department. of ABG, College of Veterinary Science and Animal Husbandry (BAU) Kanke, Ranchi-6 Jharkhand.(India)
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YEAR REPORT 2008 DEPARTMENT OF ENDOCRINOLOGY
University Medical Center Groningen
9700 RB Groningen 9713 GZ Groningen http://www.umcg.net Year Report 2008 – Dept. of Endocrinology, UMCG & University of Groningen, The Netherlands
1. Personnel . 3 2. Developments in 2008 . 4 3. Health care / patient activities . 6 4a. Diabetes mellitus / Diabetes Care . 9 4b. General Endocrinology . 14 5. Teaching . 16 6. Postgraduate education . 17 7. Training for Internal Medicine and Endocrinology . 19 8. Scientific research . 20 9. Activities outside the UMCG . 26 Addendum 1 - Conferences . 27 Addendum 2 - Multidisciplinary teams . 28 Addendum 3 - Publications 2008 . 29 Groningen Metabolism Endocrinology Diabetes Year Report 2008 – Dept. of Endocrinology, UMCG & University of Groningen, The Netherlands 1. Personnel
The members of the Department of Endocrinology and Metabolism are responsible for providing care to
a large and heterogeneous group of patients with endocrine and metabolic diseases and for teaching
and training students, residents in Internal Medicine, fellows training to become an endocrinologist, as
well as scientific research in these fields.
In this year report we will summarize our activities during the year 2008. After its success last years, this
is the 3rd year that our year report appears in English. Reasons for this are our increasing international
contacts and collaborations.
In 2008 the following persons were members of our department:
Mrs. N. Alma - Bierma (Natasja)
Dr. A.P. van Beek (André) Dr. G. van den Berg (Gerrit) Mrs. B.T. de Boer (Berber) Dr. R.P.F. Dullaart (Robin) Mrs. W. van El, MA (Winnie) nurse practitioner Mrs. B. Fokkens (Baukje) Mrs. M.A. Groeneveld (Mariska) research assistant Mrs. B.G. Haandrikman (Bettine) Mrs. I. Hoekstra (Immie) diabetes nurse specialist Mrs. Dr. A.N.A. van der Horst - Schrivers (Anouk) Mrs. K.B.M. Janson (Carla) diabetes nurse specialist Mrs. A.B. Jongbloed (Alied) diabetes nurse specialist Dr. M.N. Kerstens (Michiel) Mrs. dr. M.M. van der Klauw (Melanie) Mrs. G. Kreugel, MSC (Gillian) nursing consultant Mrs. dr. T.P. Links (Thera) internist-endocrinologist Mrs. dr. H. Lutgers (Helen) internist-endocrinologist in training from October 1st Mrs. S.H. Meeuwisse - Pasterkamp (Susanne) internist-endocrinologist in training until February 1st Mrs. Mrs. S.M. Pathuis (Susanne) from August 1 Mrs. I.E. Pop (Inge) Dr. W.J. Sluiter (Wim) biochemist, Mrs. L.G.J. Smit (Linda) diabetes nurse specialist until June1 Drs. F.A.J. Verburg (Erik Jan) internist-endocrinologist in training Prof. dr. B.H.R. Wolffenbuttel (Bruce) internist-endocrinologist Mrs. R. Zuur (Roelie) diabetes nurse specialist Year Report 2008 – Dept. of Endocrinology, UMCG & University of Groningen, The Netherlands
2. Developments in 2008
In 2008 there were several developments within our department.
The discussions within the UMCG have lead to a new organisational structure, effective January 1st,
2007. The Department of Endocrinology has found its place within the organisational cluster of Internal
Medicine and related departments, as part of Sector A. This sector comprises patient care, research
and teaching around the theme of Vascular and Chronic diseases.
Susanne Meeuwisse-Pasterkamp and Erik Jan Verburg finished their training in Endocrinology. Helen
Lutgers started her training as fellow Endocrinology.
The procedure started to nominate dr. Thera Links as professor of Endocrinology, in particular ‘Familial
Endocrine Tumoursyndromes'. It is expected that this will be effected as of April 2009.
Members of the department were involved in several PhD theses, which were defended in 2008.
On October 8, Susan Borggreve defended her thesis entitled 'The role of CETP and HDL metabolism in
Mrs Anouk van der Horst - Schrivers defended her thesis titled ""Prognosis follow up and quality of life in
patients with neuroendocrine tumours" a cooperation with the Department of Oncology and Laboratory
Medicine. Mrs Helen Lutgers defended her thesis ""Skin autofluorescence in diabetes mellitus", a
project in which we collaborated with the Department of General Internal Medicine
Mrs. Winnie van El has won the prestigious EADV award 2008, she was called 'diabetes nurse of the
year'. Winnie deserved this title on the basis of her project "Diabetic patients with chronic renal
Figure 1. Winnie van El Year Report 2008 – Dept. of Endocrinology, UMCG & University of Groningen, The Netherlands
The Health Insurance Companies recognized the Diabetes Rehabilitation program as an outstanding
and innovative program, and agreed to partially reimburse this program.
LifeLines Cohort Study
The LifeLines Cohort Study finished the pilot phase of the project in the fall of 2007. The Medical Ethical
Review Committee of the UMCG approved the final protocol for the main phase of the study, in which
130,000 adult subjects will be included during the upcoming four years. In addition to the pilot location in
the city of Sneek, Friesland, three other location have opened their doors, in the cities of Drachten (in
the province of Friesland), Bedum and Pekela (both province of Groningen). It is expected that in 2009
at least 4 new locations for screening LifeLines participants will open, and the number of research staff
will increase to at least 60. The LifeLines position paper, in which the theoretical background of the
project and details of its data collection have been explained, was published online in October 2007,
and formally appeared in print in the January 2008 issue of the European Journal of Epidemiology.
Year Report 2008 – Dept. of Endocrinology, UMCG & University of Groningen, The Netherlands 3. Health care / patient activities
Clinic Ward E4
The number of patients admitted to our ward E4 was 270, which implies a small increase compared to
2007. Yet this number is lower than in the years 2003-2005, probably related to the fact that we share
the same beds with the Acute Care ward of the Department of Internal Medicine, and a strong demand
for admissions for Internal Medicine reduces the possibilities for our department. The total number of
beds for admission of patients with internal medicine disease is not sufficient, and especially during the
fall and winter months many of our patients have to be admitted on other departments, like Neurology,
Obstetrics and Surgery. With the introduction of new endoscopic techniques, most patients after
pituitary surgery now remain only for 3 - 4 days in the hospital. Only in the case of postoperative issues
like development of diabetes insipidus, which necessitates a longer hospital stay, they are transferred to
the Endocrinology department for treatment.
Those 270 patients stayed in the ward for a total of 1400 days, implicating a stable average stay of 5.4
days. This short admission time is the result of efficient and careful planning of hospital discharge and
outpatient follow-up. Nevertheless, a significant number of patients needed a hospital stay of more than
30 days. Mostly, these were patients with severe diabetic foot problems.
The number of outpatient clinic visit increased further in 2008. The number of patients seen for the first
time has increased by 2%. By the institution of ‘dedicated' clinics for newly referred patients we were
able to reduce the average waiting time for patients to less than two weeks.
Patients are referred by General Practitioners (G.P.'s), or by medical specialists within the UMCG, as
well as colleagues from surrounding hospitals. All referrals are made in writing, and judged on a daily
basis, so that we can give priority to those patients with the highest urgency. If needed, patients can and
will be seen the same day, for instance for patients with newly-diagnosed type 1 diabetes, who have to
start insulin therapy instantaneously. Also, patients who are suspected to have an endocrine tumour, or
who have a thyroid nodule will be seen within a period of 1-2 weeks, in order to start their diagnostic
work-up and treatment as soon as possible.
Also this year we are faced we a 5%' no show' result. This means than on average in one of 20
appointments patients do not show up for their initial or follow-up visit, and this time lost puts other
patients later in the waiting list. For this reason we have continued to make telephone calls to all
patients who do not show up for their appointment, in order to reduce future 'no-shows'.
Table 1. Patient care activities of the department of Endocrinology
admissions clinic visits
Our outpatient care for people with diabetes mellitus is carried out together with our colleagues from the Year Report 2008 – Dept. of Endocrinology, UMCG & University of Groningen, The Netherlands Department of General Internal Medicine. Dr. M.N. Kerstens is the coordinator for diabetes care. Since the beginning of September 2006, diabetes care is offered based on a 'One Stop' principle in the University Diabetes Center, the first dedicated Diabetes Center in the Northern part of The Netherlands, and the first Academic Center in our country. All care providers can be found within the same location, i.e. the first floor of the A-wing of the Triade building (entrance 23). Here a patient can be seen by the internist, diabetes nurse specialist, dietician, podotherapist. There is a facility for making retinal photographs, and for drawing blood for laboratory determinations. In the first quarter of 2009 we will also start clinics by a psychologist. In addition, one floor lower patients can participate in all kinds of sports activities in the Sports and Movement Center. Unfortunately the Information Post of the Dutch Diabetes Patient Association (Diabetesvereniging Nederland) had to close down because of lack of time of volunteers. Figure 2. The Endocrine System
As there are many endocrine glands and metabolic diseases, an endocrinologist takes care of a group
of patients with a large variation of diseases. Several groups of patients are referred to our department
because of specific disease problems. These include:
* thyroid carcinoma
* thyroid dysfunction and goitre
* pituitary tumours
* adrenal diseases (tumours, phaeochromocytoma, disturbances of steroid synthesis)
* endocrine tumour syndromes (MEN1, MEN2, VHL, Neurofibromatosis etc)
* pregnancy in diabetes
* diabetic complications, including diabetic foot problems
* insulin pump therapy.
Year Report 2008 – Dept. of Endocrinology, UMCG & University of Groningen, The Netherlands
There is an extensive collaboration with the endocrinologists working in the hospitals in the four
northern provinces (Friesland, Groningen, Drenthe, Overijssel) of The Netherlands. Some of our
patients come from distant parts of our country, and may travel up to 300 km for their appointment at the
Multidisciplinary patient care
We have multidisciplinary groups of physicians for the care of the above-mentioned patients suffering
from thyroid carcinoma, pituitary diseases, diabetic foot problems, diabetes and pregnancy, as well as
Turner's syndrome. These teams get together on a regular base to discuss patient problems and the
multidisciplinary treatment of complex patients. For diabetic foot patients there is a combined outpatient
clinic once monthly on Thursday afternoon, in addition to the separate clinics held at the Dept of
Orthopaedics, the Dept of (Vascular) Surgery, and the Diabetes Centre. For patients with pituitary
problems, there is a weekly multidisciplinary outpatient clinic on Friday afternoon. For patients with
metabolic diseases, like inborn errors of metabolism or mitochondrial diseases, there is a dedicated
‘metabolic' clinic on Monday morning. Adult patients with Turner's syndrome are periodically checked at
a combined outpatient clinic, staffed by an endocrinologist and a gynaecologist.
Dr. Links is responsible for the Multidisciplinary Thyroid Team, dr. van den Berg and dr. van der Klauw
for the Pituitary Outpatient Clinic, prof. Wolffenbuttel for the Diabetic Foot Collaboration and the
Metabolic Diseases clinic, dr. van den Berg and prof. Links for the Diabetes and Pregnancy Team and
dr. Kerstens and dr. van Beek for the multidisciplinary Turner Team. Also there is intensive interaction
with the Department of Oncology related to the treatment of patients with other endocrine tumours.
All these activities are not possible without the assistance of a dedicated staff of administrative
personnel. These include Monique Gelms, Anita Scholtens, Ada Schaaf, Berber Ellens, Nihaila Sillé and
Fenna Diepenbroek-Beulakker, and also all the ladies responsible for the letters to G.P.'s regarding our
Year Report 2008 – Dept. of Endocrinology, UMCG & University of Groningen, The Netherlands
4a. Diabetes mellitus / Diabetes Care
Integrated diabetes care
The UMCG supports the concepts of the Dutch Diabetes Federation, which are summarized in a
specific Standard of Care for the Treatment of Diabetes. For us, integrated care means:
1. Optimal medical treatment and supportive care.
2. Education and learning to master skills and knowledge, needed for optimal self-management.
3. The process in which the person with diabetes experiences and improves his position in society.
Our care is based on International Guidelines, summarized in the Dutch NDF/CBO guidelines. These
guidelines preferably are based on evidence coming from clinical practice and controlled clinical trials.
In case insufficient evidence exists, we have adopted our diagnostic and treatment protocols on the
basis of the vast experience of our staff. The medical responsibility resides with the physician, but our
Diabetes Management Team includes diabetes nurse specialists, dieticians, a podotherapist, a
psychologist, and a social health worker. We offer integrated diabetes care on two locations of the
UMCG. Our regular outpatient clinic can be found in the Triade building (Entrance 23) at the
Hanzeplein, in the middle of the city of Groningen. The other location harbours the Diabetes
Rehabilitation program, and is situated within the Centre for Rehabilitation Beatrixoord. Together these
locations form the University Diabetes Centre, the only Diabetes Knowledge and Expertise Centre in the
northern part of The Netherlands.
Fig. 3. The Diabetes Center The diabetes nursing staff consists of: mrs. Nella A. Groenewegen, head nurse; mrs. Berber T. de Boer, Carla Janson, Immie Hoekstra, Alied Jongbloed, Susanne Pathuis, Linda Smit and Roelie Zuur, diabetes nurse specialists; Winnie van El, nurse practitioner; Gillian Kreugel, Msc, nursing consultant. There are extensive collaborations between the medical staff of the Endocrinology Department and care providers within the UMCG and outside the UMCG, including regional hospitals, medical specialists, and G.P.'s in the northern part of The Netherlands. Year Report 2008 – Dept. of Endocrinology, UMCG & University of Groningen, The Netherlands Multidisciplinary treatment programs are available for several groups of patients: 1. Patients with limited or no secondary complications
For patients in this category, emphasis is placed on diabetes education, learning how to handle diabetes and how to prevent the development of complications. Patients are seen three times per year by the diabetes nurse specialist, and once or twice by the endocrinologist
2. Patients with long term complications
The care for this patient group is coordinated by the internist-endocrinologist. They follow these patients with a frequency of at least three to four times a year, and all patients will visit the diabetes nurse specialist at least once a year, with support regarding all aspects of care, including intensified diabetes education.
3. Specific patient groups
For specific groups of patients we have an individual and dedicated counselling program.
a. Teenagers & adolescents
Yearly, teenagers of 15 and 16 years old are referred for continuation of their care from the out-patient clinic for children to the out-patient clinic for adults. This year we have a new program to prepare them for the new situation. An information meeting is organised for the teenagers without the parents. During this afternoon, a children's' diabetes nurse specialist, a diabetes nurse specialist of the out-patient clinic for adults and also the internist-endocrinologist are present. During the meeting the teenagers are introduced to each other, the diabetes nurse specialist and the internist-endocrinologist. There is ample time to exchange information on what the teenagers can expect in the new situation and what to do with questions or in case of emergencies. Also, they get a brief tour in the clinic. Follow-up appointments with the endocrinologist and the diabetes nurse are planned. In some cases the teenager comes together with the parents. We have a special afternoon for the transition-group so they can meet each other in the waiting room. In 2008, 24 teenagers have made the transition to the out-patient clinic for adults. In 2009 we will evaluate the new transition process together with the teenagers. b. Pregnancy It is widely known that optimal glycaemic control is necessary to minimise the development of congenital abnormalities or perinatal complications in the newborn babies. This takes a lot of effort. Patients with a wish to become pregnant are offered an intensified outpatient program supported by low-threshold phone, fax or e-mail contact to obtain normal HbA1c levels (HbA1c ≤ 6.5% on at least two occasions) before pregnancy. Folic acid supplementation is started at least two to three months before becoming pregnant. The patients who have become pregnant and patients with gestational diabetes are treated, in a multidisciplinary cooperation, by an internist-endocrinologist, diabetes specialist nurse, gynaecologist, dietician and ophthalmologist. Treatment and follow-up protocols are available, and they have been standardized according to local and (inter)national guidelines. c. Kidney patients Year Report 2008 – Dept. of Endocrinology, UMCG & University of Groningen, The Netherlands
Innovations in diabetes care
Care improvement for diabetic patients with chronic renal failure (CRF)
The aim of the project is to establish a Shared Care model for diabetic patients at different stages of
chronic renal failure (end-stage renal disease or pre-dialysis, renal replacement therapy and post
kidney transplantation). Providing integrated diabetes care with optimal accessibility to CRF patients
with diabetes is the key feature of this model. A nurse practitioner specialized in diabetes care has a
central role in this project.
The project was initiated in 2006 and is currently in the implementation phase. In close collaboration
with the department of Nephrology several changes have been realized in the diabetes care
organization for this high-risk patient group. Examples of these changes are positioning of the nurse
practitioner as the central coordinator for all diabetes related care and consultation and counselling
of the patients during their dialysis sessions. In addition, a counselling program specifically adapted
to kidney transplant patients has recently been started. A program for pre-dialysis patients will be
implemented in the near future.
Other connected activities are:
1. The development of integrated diabetic and nephrological clinical guidelines and of evidence
based nursing guidelines for diabetes care on the dialysis department. The nursing guidelines will be
developed in collaboration with the Dutch Association of Dialysis and Transplantation Nurses
2. Results of the qualitative research ‘Diabetes Self Care and Haemodialysis: Who Cares' have been
presented by the nurse practitioner diabetes at the Dutch Nephrological Days (Veldhoven, April
2006) and at the FEND (Congress of the Federation of European Nurses of Diabetes, (Copenhagen,
Financial support was supplied by AMGEN BV and the office of Medical Technology Assessment of
the UMCG (Innovation Fund). Evaluation of the project will be finished in March 2009.
Fig.4. the Diabetes & Kidney team: from left to right Michiel Kerstens, endocrinologist, Joost Keers, psychologist, Winnie van El, nurse practitioner diabetes, Thera Links, endocrinologist, and Casper Franssen, nephrologist. Year Report 2008 – Dept. of Endocrinology, UMCG & University of Groningen, The Netherlands
4. Group sessions
In 2008 we have started to organise group sessions for patients and their relatives. These sessions comprise three half days. The first day the diabetes nurse gives information about diabetes, insulin administration, hyperglycaemia and hypoglycaemia. The dietician discusses the relationship between life style and nutrition. At the second day self-management, life style and special situations like vacation, sickness and work are the main topics. The podotherapist discusses several aspects of foot care. At the final day the endocrinologist gives information about the complications of diabetes mellitus and their prevention. Also the program at Beatrixoord and the psychosocial effects of diabetes mellitus have a special place in this group session. During the sessions the participants can share their experience, we stimulate to have a interactive program. The participants of the first group session were very enthusiastic, so we will start a second group session in May 2009. Fig. 5. Education materials at the outpatient clinic 5. Newly referred patients
There is an extensive program for patients who are newly referred by their G.P. or by another medical specialist. In this program, sometimes referred to as a 'diabetes carrousel', both the endocrinologist, diabetes nurse specialist and dietician participate. There is considerable attention for improvement of the skills and knowledge, which a person with diabetes needs for optimal self-management. If needed, other specialists like psychologist or podotherapist can be consulted. The patients we care for in our Diabetes Centre come from all around The Netherlands, even from the southern provinces of Limburg and Brabant. However, the majority of them live in one of the four (or five if you include Flevoland) northern provinces: Groningen, Friesland, Drenthe or Overijssel. Their treatment is based on formalized treatment protocols, which include the majority of advices and guidelines issued by the Dutch Diabetes Federation. Our clinical care would be very much facilitated when we would have the availability of an Electronic Patient File.
6. Diabetes Rehabilitation
In the Rehabilitation Centre Beatrixoord, we provide an intensive multidisciplinary diabetes education Year Report 2008 – Dept. of Endocrinology, UMCG & University of Groningen, The Netherlands
and rehabilitation program. Eligible for this program are patients with complex diabetes-related problems, as well as problems related to self-management and acceptance of the disease. Half of the patients come from the outpatient clinic of our own hospital, whereas the other 50% are referrals from internists in the surrounding hospitals in the north of The Netherlands. Some patients even come from provinces like Zeeland and Limburg (figure 3). The program comprises several days of outpatient education in small-sized groups, with focus on practical aspects of diabetes acceptance, self-management and rehabilitation. Patients not only learn to define the problems they have with diabetes management, but also learn to attack them. For instance, the presence of 25 m swimming pool and a dedicated training and gymnastics facility will ensure that all patients can experience effects of exercise and training, and by doing this learn how to adjust their insulin dose and cope with varying blood glucose levels. Long term results of the program are excellent, as described by our psychologist Joost Keers, who defended his thesis on this topic in 2005. Permanent improvement of diabetes control as well as health-related quality of life, but above all improved self-management skills have been the most important achievements. For this reason, the Association of Rehabilitation Physicians and the Dutch Diabetes Federation have rated this program 'a high quality and indispensable asset'. After long negotiations with governmental bodies, we received in 2007 official approval of this program, and subsequently a considerable coverage of the program by health care insurance companies. The following people form the team responsible for the Diabetes Rehabilitation Program: Mrs. Rita Wesselius, team coordinator; Mrs. Linda Faber, mrs. Ingrid Stoelinga, mrs. Madelein Schotman, diabetes nurse specialists; Mrs. Marianne van Dijk, dietician; Mrs. Brigitta Joosen, en Mrs. Renske Bouman, physiotherapists; Mr. Guus van Bochove, movement scientist; Mrs. Heike Mesch, psychologist; Mrs. Tilly Söder and mrs Jannet Waijer, social welfare; Mrs. Franka Waterschoot, ergotherapist. They are supported by Mrs. Janine Kramer and mrs. Elsa Pieterman-Slagter, secretaries; Mrs. Hennie Meijer, assistant. Fig. 6. The team of the Diabetes Rehabilitation program Year Report 2008 – Dept. of Endocrinology, UMCG & University of Groningen, The Netherlands The medical aspects of Diabetes Rehabilitation as well as consultations for General Internal Medicine problems are performed by the medical staff of the Department of Endocrinology. Diabetes care for patients admitted to other wards within the Rehabilitation Centre is supported by the endocrinologist and the diabetes nurse specialists.
An obesity rehabilitation program, which started in 2005, is available for patients with diabetes or metabolic syndrome and complicated obesity. The program aims to change lifestyle patterns by means of an intensive long-term program. Approximately 20 patients have been treated in this year. An internist-endocrinologist, diabetes nurse, dietician, psychologist, physiotherapist are involved in this multidisciplinary program. Experiences in this program are also used for the future development of an obesity treatment centre.
8. The podotherapist
A Diabetes centre can not exist without dedicated people looking after the feet of our patients.
Fig. 7. Please knock. Entry to the office of the podotherapist 4b. General Endocrinology
Turner's syndrome is a genetic anomaly that results from complete or partial absence of one X
chromosome and is the most frequently occurring chromosomal abnormality in females. Adults with
Turner's syndrome have an increased risk of developing multiple co-morbidities such as cardiovascular
diseases, hypothyroidism, diabetes mellitus, osteoporosis, gastrointestinal disorders, hearing loss and
Year Report 2008 – Dept. of Endocrinology, UMCG & University of Groningen, The Netherlands the attendant problems of estrogen deficiency and infertility. Therefore, a multidisciplinary approach is needed for early detection and adequate treatment of the various problems that may affect adult women with this syndrome. In September 2006, a specialized outpatient clinic for patients with Turner's syndrome has been started by the departments of Endocrinology and Gynaecology. In agreement with clinical guidelines that have been issued in recent years, patients visit this facility once a year and are examined at each visit by both the endocrinologist and the gynaecologist. The team is also staffed by social workers experienced with the specific psychosocial problems that Turner patients may be facing. In addition, patients are referred to the Cardiologist and Ear, Nose & Throat specialist for periodic evaluation once every 3 years, or more frequently if indicated. At present, the Turner outpatient-clinic is open to other patients from the northern region. The Department of Endocrinology has a track record for the diagnostics and treatment of (neuro)endocrine tumours, in close collaboration with the Departments of Medical Oncology, Nuclear Medicine and Molecular Imaging, Genetics, Radiology, Pathology, Gastroenterology, Surgical Oncology and Clinical Chemistry, As a consequence, the UMCG is a referral centre for non-hereditary as well as hereditary neuroendocrine tumours (MEN1, MEN2, VHL, NF, paragangliomas). Several innovative PET methods have been used such as 18F-DOPA and 11C-5-HTP for imaging of medullary thyroid cancer, phaeochromocytoma, carcinoids and islet cells tumours and 124I and 11C-methionin for papillary and follicular thyroid cancer. Ongoing research supports these developments in better staging of disease and applying new therapies. The Endocrinology department has participated in several national and international clinical trials with new targeted drugs like imatinib and vandetanib in patients with medullary thyroid cancer. In the spring of 2009 participation in a international multicenter trial with the multikinase inhibitor XL184 for medullary thyroid cancer will start. In February 2009 a national project for screening of pancreatic neuroendocrine tumours in Multiple Endocrine Neoplasia type 1 and Von Hippel-Lindau disease will start employing imaging with endoscopic ultrasound and 11C-5-HTP PET. This project is supported by the Dutch Cancer Society. The VHL Family Alliance from the USA has supported an imaging study for visualizing VEGF producing lesions in Von Hippel-Lindau disease. This project will also start in the spring of 2009. For the diagnostics of catecholamine excess a rapid sensitive and highly selective automated method for plasma free metanephrine and normetanephrine is available on the Department of Clinical Chemistry (prof. dr. I.P. Kema). This quick method enables the routine quantification of catecholamines and their metabolites for daily patient care, but also creates possibilities to perform more in-depth analyses of the biochemical activities of neuroendocrine tumours. Primary aldosteronism is increasingly being recognized as an important secondary cause of hypertension, with an estimated frequency of about 5-10% among hypertensive patients. The diagnostic work-up for primary aldosteronism is relatively complex and requires clinical experience, availability of robust hormone assays for which reference values have been determined locally and expertise with adrenal venous sampling. The UMCG has elaborate experience with all the diagnostic aspects of primary aldosteronism, and is currently one of the main referral centres in the Netherlands for adrenal venous sampling. Personal experience of the radiologists with adrenal venous sampling and application of rapid cortisol measurements during the procedure have resulted in a high success rate of more than 90%. Year Report 2008 – Dept. of Endocrinology, UMCG & University of Groningen, The Netherlands 5. Teaching
The fields of Endocrinology, Diabetes and Metabolism are important parts of the medical curriculum.
Hormones play a pivotal role in the maintenance of all biochemical processes in the human body.
Endocrine diseases can have several consequences for the functioning of organs like the eyes, the
cardiovascular system, kidneys, skeleton and the musculoskeletal system. Therefore, our department
participates in all teaching activities for students in the Bachelors phase of the School for Medical
Sciences, the school for Dentistry and the Life Sciences cluster, and clinical training for the students in
the Masters phase. The lectures are both patient demonstrations as well as theoretical lectures on
endocrine physiology and pathology, including diabetes mellitus, thyroid diseases, Addison's and
Cushing's disease, and pituitary development and pathophysiology.
In addition, staff members act as coach in the medical professionalization program (Year 2) as well as
mentor or tutor for students in the first clinical year (Year 4), when students follow the introduction
period in the clinic. Staff members are also involved in educational research projects for individual
students from the UMCG but also from abroad.
Every year, the department organises a two-week period specifically devoted to Endocrine Pathology.
Students discuss major endocrine diseases based on actual patient cases, and follow patients in the
outpatient clinic. Staff support also has been provided to the yearly ISCOM, International Student
Congress of Medical Sciences by chairing oral and poster sessions
Staff members also participate in the teaching programs of surgeons, urologists, oncologists,
obstetricians and nurse practitioners, as well as specialised programs in the training of nurses.
Year Report 2008 – Dept. of Endocrinology, UMCG & University of Groningen, The Netherlands 6. Postgraduate education
The members of the department of Endocrinology actively participate in all kinds of postgraduate
education activities for general practitioners and medical specialists, like the scientific meetings of the
Dutch Association for Endocrinology (NVE), the Dutch Association for Diabetes Research (NVDO),
Erasmus Endocrinology Course and the Dutch Association of Clinical Chemistry and Laboratory
On January 25, during the Clinical meeting of the Dutch Society for Endocrinology, prof. Wolffenbuttel
gave a presentation on the background and clinical use of rimonabant. On February 14, the department
participated in the organisation of the first national congress on Diabetes and Kidney diseases. The
proceedings of this symposium have been published in the Netherlands Journal of Diabetology
On March 5th dr. Links gave a presentation on progress in thyroid diseases during the Continuum
Endcrinology postgraduate course in Utrecht, and on March 20, prof. Wolffenbuttel discussed insulin
therapy in type 2 diabetes during the National Diabetes Day, organised by the Dutch Diabetes
Federation in Amsterdam. Also in this month, dr. Dullaart gave a presentation on Abnormal Lipid
Metabolism in Endocrine Disease during the National Dutch Symposium on Metabolism.
On October 14, the department participated in the yearly Endocrinology Teaching Evening which is
specially organised for General Practitioners. Topics of the evening were on Diabetes mellitus.
Also in October, dr. Dullaart discussed the Role of HDL-related proteins during the symposium on
Multiple Risk Factors in Cardiovascular Disease, organised by the Giovanni Lorenzini Medical
Foundation in Venice, Italy.
On October 30, prof. Wolffenbuttel gave a presentation during the CODHY (Controversies in Diabetes
and Hypertension) meeting in Barcelona, and on December 12th he spoke on the Dutch meeting for
Physiology on Bone metabolism and related diseases.
Finally, during the yearly Erasmus Postgraduate Course on Endocrinology in Noordwijkerhout, dr. van
Beek gave an invited lecture called Radiotherapy for pituitary adenomas; a underestimated treatment,
while dr. Kerstens discussed Perioperative management of the patient with phaeochromocytoma.
There is intensive collaboration with the company Pronounce, editor of several diabetes-related
journals. One of these activities is the Netherlands Journal of Diabetology, a peer-reviewed journal,
which aims to improve knowledge on diabetes mellitus and its treatment, by special attention for clinical
and scientific developments. The journal publishes original articles, case reports, reviews, book reviews
and brief summaries of important international papers. For more information see www.diabetes.nl .
Another form of collaboration with Pronounce and the Postgraduate Education Institute (Wenckebach
Institute) of the UMCG resulted in an e-learning program for nurses. The E-learning program for nurses
is updated in 2008. By use of this program, nurses working in hospitals but also pharmacy assistants
and other health care providers can learn the latest information on diabetes mellitus, its pathophysiology
and treatment, with this diabetes training program, according to the blended learning possibilities. This
approach uses an electronic education program (Digidiabetes) followed by a practical training, given by
a diabetes nurse specialist. The practical training of three hours was given once in 2008.
In October 2008, the Teaching Course for Diabetes Nurse Specialists started for the first time in
Groningen. This training is carried out in collaboration with the Institute Wenckebach School of Nursing
& SSSV Bunnik. The training is based on the professional profile of diabetes nurse of the EADV. The
course member is nurse with qualification level 4 or 5. The training consists of 5 modules: Health and
Chronic disease; Methodical practice; Education; Quality and expertise; Policy and management
Year Report 2008 – Dept. of Endocrinology, UMCG & University of Groningen, The Netherlands Fig.8. Mrs. Gillian Kreugel (right) and mrs. Alied Jongbloed (left) Year Report 2008 – Dept. of Endocrinology, UMCG & University of Groningen, The Netherlands 7. Training for Internal Medicine and Endocrinology
The Department of Endocrinology participates in the training program MD's becoming internists, and
offers these trainees a 4 months program which consists of outpatient clinics, clinical care for
hospitalised patients and in-clinic consultations for patients with endocrine diseases and diabetes
The Department of Endocrinology is one of the 8 academic training centres for clinical endocrinology in
the Netherlands (AERA: Aandachtsgebied Endocrinologie, Nederlandse Internisten Vereeniging), and is
licensed as a European training centre as well (UEMS). This training to become board-certified
Endocrinologist in The Netherlands consists of a 18 to 24 months' program, during which the
endocrinology fellow is trained in out-patient, clinical and consultative care of patients with all major
endocrinological diseases (thyroid disorders including thyroid carcinoma, adrenal diseases including
congenital adrenal hyperplasia, pituitary diseases, gonadal insufficiency, secondary hypertension
including phaeochromocytoma, disorders in calcium homeostasis and osteoporosis), dyslipidaemias
and premature atherosclerosis, diabetes mellitus, including insulin pump treatment and pregnancies in
patients with diabetes and genetic metabolic diseases. This endocrinology training includes clinical
stays in the Department of Paediatric Endocrinology, Gynaecological Endocrinology and Assisted
Fertility, Nuclear Medicine and Molecular Imaging, and the Laboratory Centre. On a regular basis,
multidisciplinary meetings are organized with respect to care for patients with endocrine diseases and
metabolic disorders, pituitary disorders, thyroid carcinoma and pathology.
At present, dr. R.P.F. Dullaart coordinates the Endocrinology teaching program. All staff members
contribute to the training program. In 2008 two MD's, mrs. Susanne Meeuwisse-Pasterkamp and mr.
Erik-Jan Verburg followed the Endocrinology training program, and mrs. Helen Lutgers started her
training in the 4th quarter of 2008.
In April 2008 two regional study days incorporated in the Internal Medicine training program have been
organized by dr. Dullaart. The topic of this day was ‘Diabetes mellitus'.
Year Report 2008 – Dept. of Endocrinology, UMCG & University of Groningen, The Netherlands 8. Scientific research
The research of the Department of Endocrinology is part of the Kidney Centre and the Cardiovascular
Centre of the Research Institute GUIDE (Groningen University Institute for Drug Exploration). The
mission of GUIDE is to promote and execute innovative drug development research which is based on a
thorough and detailed understanding of the pathophysiology of diseases, and the development of new
(ways of administration of) drugs. New techniques like genomics, proteomics and bioinformatics play a
major role in this development.
Program I: Endocrine tumours and dysfunction
1. Thyroid cancer: diagnosis and treatment
Innovative strategies in differentiated thyroid cancer mrs. A.C.M. Persoon dr. T.P. Links, prof. dr. P.L. Jager prof. dr. B.H.R. Wolffenbuttel Medullary thyroid cancer: distinction and treatment of progressive disease prof. dr. T.P. Links, prof. dr. R.M.W. Hofstra, prof. dr. J.T.M. Plukker Hürthle cell carcinoma and RET/PTC rearrangements mrs. M. de Vries prof. dr. R.M.W. Hofstra, prof. dr. T.P. Links Vascular effects in thyroid cancer patients prof. dr T.P.Links, dr. J. Lefrandt, dr. A.N.A. vd Horst-Schrivers Prognostic factors in differentiated thyroid cancer prof. dr J.T.M.Plukker, prof. dr T.P.Links
2. Pituitary tumors
Long-term effects and quality of life after treatment for pituitary adenoma and Cushing's disease drs. M. Sattler (radiotherapist) dr. A.P. van Beek, dr. A.C.M. van den Bergh prof. dr. J.A. Langendijk, prof. dr. B.H.R. Wolffenbuttel Year Report 2008 – Dept. of Endocrinology, UMCG & University of Groningen, The Netherlands
3. Neuro-endocrine tumours
Imaging in neuroendocrine tumours dr. A.H. Brouwers, prof. dr. T.P.Links prof. dr. T.P. Links, prof. dr. E.G.E. de Vries Disease activity in MEN 1 and VHL Mrs S.van Asselt dr. A.H. Brouwers, prof. dr. T.P.Links prof. dr. T.P. Links, prof. dr. E.G.E. de Vries Optimal treatment of phaeochromocytoma: a multicentre randomized trial Research proposal for ZonMW
Program II: Diabetes / Lipids / Vascular
1. Pathophysiology, genetics and treatment of diabetes and diabetes-related complications
a. The role of endogenous and exogenous AGEs in the development of diabetic complications
b. Genomics and proteomics of diabetic complications
c. Etiology and treatment of type 1 diabetes
d. Genetic predisposition for type 2 diabetes
e. Gene-environment interaction in the development of type 2 diabetes
The role of CETP and HDL metabolism on cardiac risk mrs. S.E. Borggreve prof. dr. B.H.R. Wolffenbuttel, prof. dr. P.E. de Jong, prof. dr. J.L. Hillege co-promotor: dr. R.P.F. Dullaart thesis: Dutch Heart Foundation Lipid transfer proteins: consequences for cellular cholesterol efflux and cardiovascular risk in diabetes mellitus prof. dr. B.H.R. Wolffenbuttel co-promotor: dr. R.P.F. Dullaart, dr. A. van Tol thesis: support: Diabetes Research Foundation (DFN) Towards a personalized risk assessment and therapeutical strategy to prevent and treat macrovascular disease in Type 2 diabetes prof. dr. B.H.R. Wolffenbuttel co-promotor: dr. J.L. Hillebrands, dr. J. Moser, dr. H. van Goor thesis: support: Diabetes Research Foundation (DFN) Year Report 2008 – Dept. of Endocrinology, UMCG & University of Groningen, The Netherlands The projects on genetics of type 2 diabetes are part of the research carried out in the LifeLines Cohort Study, while some of the studies related to diabetic complications are carried out within the String-of-Pearls initiative. "Improving your health by sharing science"
The eight University Medical Centers (UMC's), joined in the Dutch Federation of University Medical Centers (NFU), provide most tertiary care in The Netherlands and thereby treat almost all patients with very specific or relatively rare diseases in the Dutch population. This provides a unique opportunity to combine clinical information and biomaterials on these patients and achieve almost total population coverage. It then becomes a longitudinal patient cohort from which anonymous samples may be drawn for specific research questions, either by academic, governmental or commercial partners. In order to achieve this, patient data and samples must be collected in a uniform fashion and an IT infrastructure must be designed to allow sampling locally and combining data from all eight locations to one anonimised database. In 2006 the NFU submitted a proposal for a project to build a joint infrastructure to collect and access the patient data and biomaterials of at least eight patient categories. In the coming years each of the eight UMC´s will take the initiative to build a joint database and biobank for all patients with a specific diagnosis using uniform definitions and storage circumstances. The following patient cohorts are planned: Inflammatory Bowel Disease, Rheumatoid Arthritis, CVA, hereditary Bowel cancer, Leukemia, Dementia, Diabetes. The data and biomaterials will be collected and stored in each UMC, using the regular electronic patient records to store patient data including imaging data and biobanks to store biomaterial and already completed analyses of the biomaterials. Clinicians from each UMC must agree on uniform definitions for each patient cohort. For that purpose each UMC has adopted one patient cohort and leads its colleagues from the other seven UMC´s to achieve this. Together the UMC´s will build a joint infrastructure to access each of the local data bases to draw a sample, anonymise it and deliver it as a data base to the end user. The patient cohort data will be collected prospectively, but in a number of cases already existing data and biobanks can be included in the database retrospectively if it fits the definitions. A set of rules will be developed to help decide by which criteria and procedures proposals for the use of the data will be accepted and how the resulting proceeds will be used to maintain the infrastructure after the initial funding ends. For more information: www.parelsnoer.org Year Report 2008 – Dept. of Endocrinology, UMCG & University of Groningen, The Netherlands This research programs are carried out by the Department of Endocrinology (dr. R.P.F. Dullaart, dr.
T.P. Links, prof. dr. B.H.R. Wolffenbuttel) in close collaboration with the Dept's of General Internal
Medicine and Nephrology: Dr. S.J.L. Bakker, dr. A.J. Smit, dr. J.C. ter Maaten, prof. dr. R.O.B. Gans,
and with dr. A. van Tol, Department of Cell Biology and Genetics, and mrs. dr. G. Dallinga - Thie,
Department of Internal Medicine, both of the Erasmus Medical Centre Rotterdam.
2. Metabolism, obesity and metabolic syndrome
Thyroid (dys)function, metabolic syndrome and incident cardiovascular disease prof. dr. B.H.R. Wolffenbuttel, prof. Dr. T.P. Links co-promotor: dr. A. Berghout (internist, Rotterdam), dr. S.J.L. Bakker (internist) thesis: Lifestyle modification in obese infertile women: hormonal-metabolic parameters and body-fat distribution mrs. J.G. Dolfing, gynaecologist, W.K.H. Kuchenbecker, gynaecologist dr. A. Hoek, dr. D.H. Schweitzer (internist, Voorburg) prof. dr. B.H.R. Wolffenbuttel, prof. dr. J.A. Land The effects of obesity and weight reduction on inflammatory markers and site-specific adipocyte function in prediabetes prof. dr. B.H.R. Wolffenbuttel co-promotor: dr. A.P. van Beek thesis: 3. Diabetes psychology and quality of care
Diabetes education: effects of self-adopted therapy goals and partner behaviour mrs. M. Schokker prof. dr. T.P. Links, dr. J. Bouma, dr. J.C. Keers prof. dr. M. Hagedoorn, prof. dr. R. Sanderman, prof. dr. B.H.R. Wolffenbuttel What helps patients to keep their medication plan? Compliance vs self-management. dr. J.C. Keers, dr. P. Denig Optimising outpatient diabetes care by integrated treatment and screening for psychosocial problems. (Medical Technology Assessment reseach). prof. dr. T.P. Links, dr. W.J. Sluiter scientific report: 2007 topic: GIANTT: assessing pharmacotherapeutic care for patients with type 2 diabetes prof. dr. F. Haaijer-Ruskamp, prof. dr. B.H.R. Wolffenbuttel Year Report 2008 – Dept. of Endocrinology, UMCG & University of Groningen, The Netherlands ‘Diabetes VerjaarDAG': Implementation of yearly counselling by a diabetes nurse specialist prof. dr. B.H.R. Wolffenbuttel Care improvement for diabetic patients with chronic renal failure (CRF) dr. C.F.M. Franssen (nephrologist), dr. J.C. Keers, dr. M.N. Kerstens, prof. dr. T.P. Links INOBESE, The influence of the needle length on long term glycaemic control in insulin using obese diabetic subjects prof. dr. B.H.R. Wolffenbuttel Mrs. G. Kreugel will present her results in a special poster session at the American
Diabetes Association (ADA). June 5-9, 2009 in New Orleans.
Program III. General endocrinology
Prospective study on the effects of cessation of bisphosphonate treatment in patients with primary osteoporosis. Research proposal to ZonMW
Amiodarone effects and side effects prof. dr. T.P. Links prof. dr. I.C.van Gelder, prof. dr. D.J. van Veldhuizen Year Report 2008 – Dept. of Endocrinology, UMCG & University of Groningen, The Netherlands LifeLines
The risk to develop multifactorial diseases is determined by risk factors that frequently
apply across disorders (universal risk factors). To investigate presently unresolved
issues on etiology of and individual's susceptibility to multifactorial diseases, research
focus should shift from single determinant–outcome relations to effect modification of
universal risk factors.
A study to assess disease risk during life requires phenotype and outcome
measurements in multiple generations with a long-term follow up. The latter will also
enable to separate genetic and environmental factors. Traditionally, representative
individuals (probands) and their first-degree relatives have been included in this type of
research. A three-generation design is an improved approach to investigate
multifactorial diseases. This design has statistical advantages (power and precision,
multiple informants, separation of non-genetic and genetic familial transmission, direct
haplotype assessment, quantify genetic effects), enables unique possibilities to study
social characteristics (socioeconomic mobility, partner preferences, between-generation
similarities), and offers practical benefits (efficiency, lower non-response).
LifeLines is a cohort study to investigate universal risk factors and their modifiers for
multifactorial diseases. It will help to better understand the causes and prognosis of
burden of chronic diseases over lifetime and may ultimately result in optimal tailored
treatment of individual diseases and disease overriding preventive strategies. Specific
research questions will focus on risk factors and modifiers (genetic, environmental and
complex factors) for single and multiple diseases. Rather than co-morbidity, LifeLines
focuses on co-determinants. Secondary aims include the assessment of the prevalence
and incidence of multifactorial diseases and their risk factors in individuals as well as in
families. The burden of disease for the society will be quantified in terms of care
LifeLines is an observational follow-up study in a large representative sample of the
population of the northern provinces of the Netherlands covering three generations.
Firstly, a random sample of persons aged between 25 and 50 years are invited to
participate. Subsequently these probands invite their family members to take part as
well (parents, partner, parents in law, children), resulting in a three-generation study
including 165.000 participants: 45.000 probands, 30.000 partners, 55.000 parents (in
law) and 35.000 children.
The core of the LifeLines project consists of dedicated data collection and biological
sample storage, including genetic samples ("biobank"). All participants receive a number
of questionnaires and a basic medical examination and are followed for many years with
extensive standardized measurements.
Methods of data collection are matched with other ongoing biobank studies (P3G
consortium), which enables combining datasets to construct large study populations.
LifeLines participates in the BBMRI consortium (www.bbmri.eu).
For more information readers are referred to the website www.lifelines.nl.
Year Report 2008 – Dept. of Endocrinology, UMCG & University of Groningen, The Netherlands 9. Activities outside the UMCG
Contacts with patient societies
Our department has extensive contacts with several societies of patients, which results in a continuous
stimulation to further improve patient care. Staff members of the Department give presentations for
regional patient groups. Twice yearly a structured mutual discussion with the Diabetesvereniging
Nederland is organized. From the beginning of 2005, prof. Wolffenbuttel is one of the medical advisors
of the Dutch Association for Addison and Cushing Patients (NVACP, Nederlandse Vereniging voor
Addison en Cushing Patiënten).
Dr. Links is advisor of the foundation "BETER", that supports organization of care for patients with
hereditary endocrine cancer syndromes.
Several members of the department participate in national and international study or research-groups,
amongst others the Dutch Adrenal Collaborative (www.bijniernetwerk.nl)
Dr. A.P. van Beek is representative within The Northern European Neuro-Endocrine Group (NENEG).
Prof. dr. T.P. Links is president of the Dutch national Working Group for Von Hippel Lindau's disease,
member of the Working Group on Thyroid Carcinoma of the Comprehensive Cancer Centre North
Netherlands (IKN), and chairperson of the CBO Guideline Group for Differentiated Thyroid Cancer.
Prof. dr. B.H.R. Wolffenbuttel is Editor-in-chief of the scientific Netherlands Journal of Diabetology, a
peer-reviewed scientific journal in the Dutch language, which appears four times a year. He is also a
member of the Board of the journals International Diabetes Monitor and International Growth Monitor, as
well as Expert Opinion in Pharmacotherapy. He is member of the ZonMW Committee on Prevention.
In 2008 he resigned-after serving for 7 years- as chairman of the Foundation for the Dr. F. Gerritzen
Price, a foundation which every year rewards a price to the best scientific PhD thesis in the field of
Dr. J.C. Keers is member of the Committee on Education and Publicity of the Dutch Diabetes
Mrs. Gillian Kreugel is a member of the ‘Diabetes Expert Network' of the Dutch Diabetes Federation
and a member of ‘Diabetes Network Groningen'. She also serves as a member of the scientific advisory
committee for the third International Injection Technique Seminar
Mrs. Winnie van El participated in the following committees:
- Committee on Education and Publicity of the Dutch Diabetes Federation
- Diabetes Expert Network of the Dutch Diabetes Federation
- The Working Group on Diabetes and Dialysis of the LVDT (Dutch Society for Dialysis and
Year Report 2008 – Dept. of Endocrinology, UMCG & University of Groningen, The Netherlands Addendum 1 - Conferences
Endocrinology Grand Rounds
weekly (Tuesday 9 - 10.30) Endocrine Case Conference weekly (Friday 9 - 10) Internal Medicine Patient Discussion every two weeks (Tuesday 16.45 - 17.30) Thyroid Carcinoma Consultation monthly (Friday 11 – 12.30) Diabetic Foot Rounds weekly clinical rounds (Monday) 1x monthly (Friday) Pituitary Case Conference every two weeks (Tuesday 12 - 13) Multidisciplinary Diabetes Consultation once monthly (Thursday, 16.30 - 17.30) Endocrine Pathology Case Conference once every 2 months (Friday 9 - 10) Vascular Medicine Research meeting every two weeks (Tuesday 16.45 -17.30) Endocrinology Journal Club monthly (Friday 9 - 10.30) Regional Case and Research Conferences 6-8 times a year Year Report 2008 – Dept. of Endocrinology, UMCG & University of Groningen, The Netherlands Addendum 2 - Multidisciplinary teams
Prof. dr. T.P. Links, Endocrinology
Prof. dr. J.T.M. Plukker, dr. L. Jansen, Oncologic Surgery
Dr. A. Brouwer and colleagues, Nuclear Medicine
Dr. F. Burlage, Radiotherapy
Dr. P. C. Jutte, Orthopedics
Dr. M. Coppes, Neurosurgery
Dr. A. Muller Kobold, Clinical Chemistry
Staff members of Endocrinology
Dr. G. van den Berg, Endocrinology
Dr. M.M. van der Klauw, Endocrinology
Dr. E. Hoving, Neurosurgery
Dr. J.W. Pott, Ophthalmology
Dr. A.C.M. van den Bergh, Radiotherapy
Dr. L. Meiners, Neuroradiology
Staff members of Endocrinology
Staff members of the Departments of (Vascular) Surgery, Orthopaedics,
Dermatology, Rehabilitation, Plastic Surgery and Internal Medicine / Endocrinology
Diabetes and Pregnancy
Dr. G. van den Berg, Endocrinology
Prof. Dr. PP van den Berg, Obstetrics/ Gynaecology
Prof. dr. T.P. Links, Endocrinology
Dr. K.M. Sollie, Obstetrics/ Gynaecology
Dr. F.A.J. Verburg, Endocrinology
Dr. M.N. Kerstens, Endocrinology
Dr. A.P. van Beek, Endocrinology
Mrs. dr. A. Hoek, Gynaecology
Mrs. dr. W.M. Bakker- van Waarde, Paediatrics
Mrs. E. Lont, Nursing
Mrs. H.J. Huisinga, Social Support
Mrs. A. Elliot-Pascal, Social Support
Year Report 2008 – Dept. of Endocrinology, UMCG & University of Groningen, The Netherlands Addendum 3 - Publications 2008
PhD Thesis / dissertations
A.N.A. van der Horst – Schrivers: "Prognosis follow up and quality of life in patients with
neuroendocrine tumours"; March 19, 2008
Promotores: Prof. dr. E.G.E. de Vries, Prof. dr. P.H.B. Willemse Copromotores: Dr. A.N.M. Wymenga, Dr. T.P. Links, Dr. I.P. Kema Summary Neuroendocrine tumours (NET) are a group of rare tumours, arising from cells of the neuroendocrine system. To this group belong midgut carcinoid tumours originating from the enterochromaffin cells of the bowel and phaeochromocytomas arising from chromaffin cells in the medulla of the adrenal gland and paraganglia. The aim of this thesis is to evaluate the course and follow-up of patients with NETs focusing on the midgut carcinoid tumours and phaeochromocytomas. Year Report 2008 – Dept. of Endocrinology, UMCG & University of Groningen, The Netherlands L. Vogt: "Strategies to Optimize Renoprotective Therapy in Proteinuric Renal Patients"; April 2,
Promotores: Prof. dr. G.J. Navis, Prof. dr. D. de Zeeuw Copromotores: Dr. R.P.F. Dullaart, Dr. A.J.J. Woittiez Summary (in Dutch): Verhoogde eiwituitscheiding in de urine (proteïnurie) vormt een van de belangrijkste risicofactoren voor nierfunctieachteruitgang in patiënten met chronische nierinsufficiëntie. De mate van proteïnuriereductie door medicamenteuze behandeling blijkt een goede voorspellen voor de mate van nierfunctiebescherming op lange termijn. Toch raken nog steeds patiënten afhankelijk van nierfunctievervangende therapie (dialyse). Vanuit de gedachte dat de laagste proteïnurie de beste nierfunctiebescherming oplevert, staat in dit proefschrift de vraag centraal op welke wijze het doel van een zo laag mogelijke proteïnurie kan worden behaald. Hiertoe zijn verschillende strategieën onderzocht. Deel 1 laat zien dat een specifieke groep bloeddrukverlagende geneesmiddelen, de RAAS-blokkers, een nierfunctiebeschermend effect blijken te hebben dat gerelateerd is aan proteïnuriereductie. Deel 2 laat zien dat het proteïnurieverlagende effect van deze geneesmiddelen sterk kan worden vergroot door de water- en zouthuishouding met een zoutbeperkt dieet en/of een diureticum te beïnvloeden. Ook hogere doseringen van RAAS-blokkers evenals de combinatie van ACE-remmers en AT1-receptorantagonisten kunnen de proteïnurieverlaging sterk verbeteren. Dit proefschrift laat echter zien dat de keerzijde van deze additionele maatregelen het veelvuldige optreden van bijwerkingen vormt. In Deel 3 is de toepassing van geneesmiddelklassen die niet op het RAAS aangrijpen onderzocht. Dit proefschrift toont aan dat COX-2-remmers de proteïnurie verlagen zonder beïnvloeding van de bloeddruk. Nader onderzoek naar de langetermijneffecten van COX-2-remmers lijkt aangewezen. Deel 4 laat zien dat optimale proteïnurieverlaging leidt tot verbetering van het vetspectrum in het bloed en bovendien niet alleen voorspellend is voor de mate van nierfunctiebescherming, maar ook voor het risico op de ontwikkeling van hart- en vaatziekten.
Year Report 2008 – Dept. of Endocrinology, UMCG & University of Groningen, The Netherlands A.C.M. van den Bergh: "Radiation therapy in pituitary adenomas"; September 3, 2008
Promotores: Prof. dr. J.A. Langendijk, Prof. dr. B.H.R. Wolffenbuttel Copromotores: Dr. R.P.F. Dullaart, Dr. J.W.R. Pott Summary (in Dutch): De plaats van radiotherapie bij de behandeling van het hypofyseadenoom, een goedaardige tumor in het hoofd, is wereldwijd niet éénsluidend. De veronderstelde bijwerkingen van de radiotherapie worden als argument aangegrepen om radiotherapie - ondanks zijn gunstige werking - niet toe te passen of uit te stellen. Het Groningse onderzoek bij patiënten met een tumorrest van een niet functionerend hypofyseadenoom laat zien dat direct postoperatief geven van radiotherapie een zéér gunstig effect heeft op het onder controle houden van de tumor en dat het niet geven van radiotherapie een hoge kans op terugkeer van de tumor tot gevolg heeft. Het onthouden van radiotherapie leidt niet tot een verondersteld beter behoud van de hypofysefunctie, het cognitief functioneren, de kwaliteit van leven en de overleving van de patiënt, maar leidt tot meer onzekerheid gezien de hoge kans op terugkeer van de tumor. Tevens wordt radiatie-opticus neuropathie - een plotseling, ernstig onomkeerbaar gezichtsvermogenverlies ten gevolge van schade aan de oogzenuwen door de radiotherapie - zelden of niet waargenomen in de bestraalde patiënten met een niet-functionerend of groeihormoonproducerend hypofyseadenoom in het UMCG en in de door de Groningse onderzoekers gerapporteerde literatuuroverzichten. Nog minder bijwerkingen worden verwacht met toekomstige nog meer geavanceerde radiotherapie. Met Tyrosine positron emissie tomografie (PET), een nieuwe beeldvormingmodaliteit, is de eiwit aanmaak in het hypofyseadenoom zichtbaar te maken, in tegenstelling tot de gehanteerde standaard magnetische resonantie beeldvorming (MRI). Drie jaar na radiotherapie is het postoperatieve tumorvolume gehalveerd, zichtbaar op PET, maar ongewijzigd op MRI, suggererend dat met PET de biologische tumoractiviteit te volgen is. Dit is van nieuwe additionele waarde. De noodzaak van multidisciplinaire samenwerking bij de behandeling van het hypofyseadenoom wordt onderstreept. Year Report 2008 – Dept. of Endocrinology, UMCG & University of Groningen, The Netherlands S.E. Borggreve: "The role of CETP and HDL metabolism in cardiac disease"; October 8, 2008
Promotores: Prof. dr. BHR Wolffenbuttel, Prof. dr. PE de Jong, Prof. dr. JL Hillege Copromotor: dr. R. Dullaart Summary This thesis describes the effects of plasma CETP levels and common CETP polymorphisms, in their relation to HDL metabolism and triglycerides, on cardiac risk in a general western population. The studies of this thesis consist of epidemiological research based on data from PREVEND (Prevention of REnal and Vascular ENDstage Disease) Study, an ongoing population-based project carried out among inhabitants of the city of Groningen, the Netherlands. We have specifically focussed on possible effects of (genetic) variants of CETP on HDL-related compounds such as HDL cholesterol, triglycerides, the cholesteryl ester transfer and cholesterol efflux from vessel walls. The specific aims of this thesis are: - To investigate how circulating CETP and HDL lipids and apolipoproteins relate to cardiac disease. - To verify whether the prognostic significance of plasma CETP levels for cardiac disease and whether this is influenced by different circulating triglyceride levels. - To investigate whether the associations of CETP polymorphisms with HDL cholesterol are modified by different circulating triglyceride levels - To investigate the associations of CETP polymorphisms with incident cardiac disease, HDL cholesterol and cholesterol efflux, and to assess whether the putative associations with cardiac disease and HDL cholesterol are effected by respectively HDL cholesterol and the effect of CETP on lipid transfer. Year Report 2008 – Dept. of Endocrinology, UMCG & University of Groningen, The Netherlands H.L. Lutgers: "Skin autofluorescence in diabetes mellitus"; December 17, 2008
Promotores: Prof. dr. R.O.B. Gans, Prof. dr. H.J.G. Bilo Copromotores: Dr. A.J. Smit, Dr. Ir. R. Graaff, Dr. T.P. Links Summary (in Dutch): AGEs ofwel advanced glycation endproducts zijn onomkeerbaar versuikerde stoffen, die voornamelijk aan eiwitten zijn gekoppeld, en die bij ieder mens stapelen. Bij iemand met diabetes mellitus gaat dit proces echter versneld. AGEs hebben een belangrijke rol bij het ontstaan van chronische complicaties van diabetes en atherosclerose. Tot recent werden weefsel-AGEs via huidbiopten gemeten. Dat is een belastende methode, ongeschikt voor toepassing op grote schaal, of voor herhaalde metingen. Het is vanuit de literatuur bekend dat sommige AGEs fluoresceren. Enkele jaren geleden is de Autofluorescence reader ontwikkeld, dat gebruikmakend van fluorescentieprincipes, niet-invasief autofluorescentie van de huid meet en een maat is voor weefsel-AGEs. Bij type 1, type 2 diabetes patiënten, met en zonder complicaties, werden autofluorescentie metingen gedaan met een monochromator, resulterend in excitatie-emissie maps. Hierbij wordt de huid met licht van een specifieke golflengte beschenen, om verschillende fluorophoren te identificeren. Hieruit bleek dat er geen verschil was in fluorescentiekarakteristieken tussen de onderzochte patiëntgroepen. In 2001 werd in een type 2 diabetes cohort (+/-1000) uit de regio Zwolle, huid autofluorescentie gemeten. Autofluorescentie bleek gerelateerd aan leeftijd, roken, HbA1c en aan microvasculaire en macrovasculaire complicaties. Na een follow-up van 3.5 jaar werden eindpunten verzameld als cardiovasculaire events en mortaliteit. Autofluorescentie blijkt een betere voorspeller t.a.v. mortaliteit en cardiovasculaire events dan HbA1c. Verder is meting van autofluorescentie van aanvullende waarde aan de UKPDS Risk score. Tot slot bleek na een follow-up van 5 jaar de levensverwachting van deze goed gereguleerde type 2 diabetes populatie niet anders dan die van de gemiddelde Nederlander. Year Report 2008 – Dept. of Endocrinology, UMCG & University of Groningen, The Netherlands Publications international
Abma EM, Kluin PM, Dullaart RP. Malignant aldosterone-producing adrenal tumour: reoccurrence with
glucocorticoid excess without hyperaldosteronism. Neth J Med 2008; 66(6): 252-5
Ahmed S, Rienstra M, Crijns HJ, Links TP, Wiesfeld AC, Hillege HL, Bosker HA, Lok DJ, Van
Veldhuisen DJ, Van Gelder IC; CONVERT Investigators. Continuous vs episodic prophylactic treatment
with amiodarone for the prevention of atrial fibrillation: a randomized trial. JAMA 2008; 300(15): 1784-92
Borggreve SE, de Vries R, Dallinga-Thie GM, Wolffenbuttel BHR, Groen AK, van Tol A, Dullaart RPF.
The ability of plasma to stimulate fibroblast cholesterol efflux is associated with the -629C-->A
cholesteryl ester transfer protein promoter polymorphism: role of lecithin: cholesterol acyltransferase
activity. Biochim Biophys Acta 2008; 1781(1-2): 10-5
Bruin de D, de Jong IJ, Arts EG, Nuver J, Dullaart RP, Sluiter WJ, Hoekstra HJ, Sleijfer DT, Gietema JA.
Semen quality in men with disseminated testicular cancer: relation with human chorionic gonadotropin
beta-subunit and pituitary gonadal hormones. Fertil Steril. 2008 Apr 26. [Epub ahead of print]
Dallinga- Thie GM, Dullaart RPF, van Tol A. Derangements of intravascular remodeling of lipoproteins
in Type 2 diabetes mellitus: consequences for atherosclerosis development. Current diabetes reports
2008; 8: 65-70
Dullaart RPF, Groen AK, Dallinga-Thie GM, de Vries R, Sluiter WJ, van Tol A. Fibroblast cholesterol
efflux to plasma from metabolic syndrome subjects is not defective despite low high-density lipoprotein
cholesterol. Eur J Endocrinol 2008; 158(1): 53-60
Dullaart RPF, Borggreve SE, Hillege JL, Dallinga-Thie GM. The association of HDL cholesterol
concentration with the -629C>C CETP promoter polymorphism is not fully explained by its relationship
with plasma cholesteryl ester transfer. Scand J Clin Lab Invest 2008; 68: 99-105
Dullaart RPF, de Vries R, Dallinga-Thie GM, Sluiter WJ, van Tol A. Phospholipid transfer protein activity
is determined by type 2 diabetes mellitus and metabolic syndrome, and is positively associated with
serum transaminases. Clin Endocrinol 2008: 68: 375-381
Dullaart RPF, Schols JL, van der Steege G, Zelissen PMJ, Sluiter WJ, van Beek AP. Glucocorticoid
replacement is associated with hypertriglyceridaemia, elevated glucose and higher non-HDL cholesterol
and may diminish the association of HDL cholesterol with the -629C>A CETP promotor polymorphism in
GH-receiving hypopituitary patients. Clinical Endocrinology 2008; 69: 359-66
Dullaart RP, Perton F, Sluiter WJ, de Vries R, van Tol A. Plasma lecithin: cholesterol acyltransferase
activity is elevated in metabolic syndrome and is an independent marker of increased carotid artery
intima media thickness. Clin Endocrinol Metab 2008; 93(12): 4860-6
Dullaart RPF, Sluiter WJ. Common variations in the CETP gene and the implications for cardiovascular
disease and its treatment: an updated analysis. Pharmacogenomics 2008; 9: 747-763
Fiebrich HB, Brouwers AH, Links TP, de Vries EG. Images in cardiovascular medicine: myocardial
metastases of carcinoid visualized by 18F-dihydroxy-phenyl-alanine positron emission tomography.
Circulation 2008; 118(15): 1602-4
Groen EJ, Roos A, Muntinghe FL, Enting RH, de Vries J, Kleibeuker JH, Witjes MJ, Links TP, van Beek
AP. Extra-intestinal manifestations of familial adenomatous polyposis. Ann Surg Oncol 2008; 15(9):
Heijckmann AC, Drent M, Dumitrescu B, De Vries J, Nieuwenhuijzen Kruseman AC, Wolffenbuttel BHR,
Geusens P, Huijberts MS. Progressive vertebral deformities despite unchanged bone mineral density in
patients with sarcoidosis: a 4-year follow-up study. Osteoporos Int 2008; 19(6): 839-47
Heijckmann AC, Huijberts MS, Schoon EJ, Geusens P, de Vries J, Menheere PP, van der Veer E,
Wolffenbuttel BHR, Stockbrugger RW, Dumitrescu B, Nieuwenhuijzen Kruseman AC. High prevalence
Year Report 2008 – Dept. of Endocrinology, UMCG & University of Groningen, The Netherlands of morphometric vertebral deformities in patients with inflammatory bowel disease. Eur J Gastroenterol Hepatol 2008; 20(8): 740-7 Heijckmann AC, Dumitrescu B, Nieuwenhuijzen Kruseman AC, Geusens P, Wolffenbuttel BHR, De Vries J, Drent M, Huijberts MS. Quantitative ultrasound does not identify patients with an inflammatory disease at risk of vertebral deformities. BMC Musculoskelet Disord. 2008; 9: 72 Horst van der - Schrivers ANA, Slot MH, Willemse PH, Kema IP, De Vries EG, Wymenga AN. Effect of interferon and 5-fluorouracil on serum VEGF levels in neuroendocrine tumours. Acta Oncol 2008; 47(1): 153-5 Horst van der - Schrivers ANA, van Ieperen E, Wymenga AN, Boezen HM, Weijmar-Schultz WC, Kema IP, Meijer WG, de Herder WW, Willemse PH, Links TP, de Vries EG. Sexual Function in Patients with Metastatic Midgut Carcinoid Tumours. Neuroendocrinology 2008 Epub 2008 Nov 26 Koopmans KP, de Groot JW, Plukker JT, de Vries EG, Kema IP, Sluiter WJ, Jager PL, Links TP. 18F-dihydroxyphenylalanine PET in patients with biochemical evidence of medullary thyroid cancer: relation to tumor differentiation. J Nucl Med. 2008; 49(4): 524-31 Koopmans KP, Jager PL, Kema IP, Kerstens MN, Albers F, Dullaart RP. 111In-octreotide is superior to 123I-metaiodobenzylguanidine for scintigraphic detection of head and neck paragangliomas. J Nucl Med 2008; 49(8): 1232-7 Krikken JA, Dallinga-Thie GM, Navis G, Dullaart RPF. Renin-angiotensin- aldosterone responsiveness to low sodium and blood pressure reactivity to angiotensin- II are unrelated to cholesteryl transfer protein mass in healthy subjects. Expert Opinion Ther Targets 2008; 12(11): 1321-8 Meeuwisse-Pasterkamp SH, van der Klauw MM, Wolffenbuttel BHR. Type 2 diabetes mellitus: prevention of macrovascular complications (invited review). Expert Rev Cardiovasc Ther 2008; 6(3): 323-41 Meijer JW, Lange F, Links TP, van der Hoeven JH. Muscle fiber conduction abnormalities in early diabetic polyneuropathy. Clin Neurophysiol 2008; 119(6): 1379-84 Milos IN, Frank-Raue K, Wohllk N, Maia AL, Pusiol E, Patocs A, Robledo M, Biarnes J, Barontini M, Links TP, de Groot JW, Dvorakova S, Peczkowska M, Rybicki LA, Sullivan M, Raue F, Zosin I, Eng C, Neumann HP. Age-related neoplastic risk profiles and penetrance estimations in multiple endocrine neoplasia type 2A caused by germ line RET Cys634Trp (TGC>TGG) mutation. Endocr Relat Cancer 2008; 15(4): 1035-41 Olthof M, Persoon AC, Plukker JT, van der Wal JE, Links TP. Anaplastic Thyroid Carcinoma with Rhabdomyoblastic Differentiation: a case report with a good clinical outcome. Endocr Pathol 2008 Mar 11. [Epub ahead of print] Penning- van Beest FJA, Wolffenbuttel BHR, Herings RMC. Haemoglobin A1c goal attainment in relation to dose in patients with diabetes mellitus taking metformin. A nested, case- control study. Clin Drug Invest 2008; 28(8): 487-93 Phan HT, Jager PL, van der Wal JE, Sluiter WJ, Plukker JT, Dierckx RA, Wolffenbuttel BHR, Links TP. The follow-up of patients with differentiated thyroid cancer and undetectable thyroglobulin (Tg) and Tg antibodies during ablation. Eur J Endocrinol 2008; 158(1): 77-83 Phan HT, Jager PL, Plukker JT, Wolffenbuttel BHR, Dierckx RA, Links TP. Comparison of 11C-methionine PET and 18F-fluorodeoxyglucose PET in differentiated thyroid cancer. Nucl Med Commun 2008; 29(8): 711-6 Phan HT, Jager PL, Paans AM, Plukker JT, Sturkenboom MG, Sluiter WJ, Wolffenbuttel BHR, Dierckx RA, Links TP. The diagnostic value of 124I-PET in patients with differentiated thyroid cancer. Eur J Nucl Med Mol Imaging 2008; 35(5): 958-65 Year Report 2008 – Dept. of Endocrinology, UMCG & University of Groningen, The Netherlands Stolk RP, Rosmalen JG, Postma DS, de Boer RA, Navis G, Slaets JP, Ormel J, Wolffenbuttel BHR.
Universal risk factors for multifactorial diseases: LifeLines: a three-generation population-based study.
Eur J Epidemiol 2008; 23(1): 67-74
Thompson A, Di Angelantonio E, Sarwar N, Erqou S, Saleheen D, Dullaart RP, Keavney B, Ye Z,
Danesh J. Association of cholesteryl ester transfer protein genotypes with CETP mass and activity, lipid
levels, and coronary risk. JAMA 2008; 299(23): 2777-88
Van Beek AP, van den Bergh AC, van den Berg LM, van den Berg G, Keers JC, Langendijk JA,
Wolffenbuttel BHR. Subjective ratings vs. objective measurement of cognitive function: In regard to van
Beek et al (Int J Radiat Oncol Biol Phys 2007;68 : 986-991) - In response to Dr. Klein et al. Int J Radiat
Oncol Biol Phys 2008; 70(3): author reply 962
Vergeer M, Dallinga- Thie GM, Dullaart RPF, van Tol A. Evaluation of phospholipid transfer protein as a
therapeutic target. Future Lipidol 2008; 3(3): 327-35
Voorham J, Haaijer-Ruskamp FM, Stolk RP, Wolffenbuttel BHR, Denig P; Groningen Initiative to
Analyze Type 2 Diabetes Treatment Group. Influence of elevated cardiometabolic risk factor levels on
treatment changes in type 2 diabetes. Diabetes Care 2008; 31(3): 501-3
Voorham J, Denig P, Wolffenbuttel BHR, Haaijer-Ruskamp FM. Cross-sectional versus sequential
quality indicators of risk factor management in patients with type 2 diabetes. Med Care 2008; 46(2):
Vries de MM, Persoon AC, Jager PL, Gravendeel J, Plukker JT, Sluiter WJ, Links TP. Embolization
therapy of bone metastases from epithelial thyroid carcinoma: effect on symptoms and serum
thyroglobulin. Thyroid 2008; 18(12): 1277-84
Wertenbroek MW, Links TP, Prins TR, Plukker JT, van der Jagt EJ, de Jong KP. Radiofrequency
ablation of hepatic metastases from thyroid carcinoma. Thyroid 2008; 18(10): 1105-10
Bangma HR, Smit GP, Kuks JB, Grevink RG, Wolffenbuttel BHR. Two patients with mitochondrial
respiratory chain disease. Ned Tijdschr Geneeskd 2008; 152(42): 2298-301
De Jager CM, Wolffenbuttel BHR. Ernstige diabetische ketoacidose. Ned Tijdschr Diabetol 2008; 6(3):
De Klerk EJ, de Heide LJM, Schaapveld M, Karim- Kos HE, Links TP. Diagnostiek van de
schildkliernodus: een evaluatie van de IKN-richtlijn uit 2000. Ned Tijdschr Oncologie 2008; 5: 98-107
Horst van der - Schrivers ANA, Brouwers AH, Links TP. Functional imaging of neuroendocrine tumours.
Tijdschr Nucleaire Geneeskunde 2008; 30(2):
Koolhaas W, Prak A, Stiekema HM, Kreeftenberg HG, Wolffenbuttel BHR, Jager PL. Efficient and
improved diagnosis of osteoporosis by simultaneous bone density measurement and spinal
morphometry. Ned Tijdschr Geneeskd 2008; 152(16): 938-43
Links TP, Huysmans DAKC, Smit JWA, de Heide LJM, Hamming JF, Kievit J, van Leeuwen M, van Pel
R, de Klerk JMH, van der Wel Y. Richtlijn "gedifferentieerd schildkliercarcinoom". Inclusief de
diagnostiek van de schildkliernodus. Tijdschr Nucleaire Geneeskunde 2008; 30(3):
Wolffenbuttel BHR, van den Berg G, Hoving EW, van der Klauw MM. The natural course of non-
functioning pituitary adenomas. Ned Tijdschr Geneeskd 2008; 152(47): 2537-43
Wolffenbuttel BHR. Epidemiologie en pathofysiologie van diabetische nefropathie. Ned Tijdschr Diabetol
2008; 6(1): 3-11
Year Report 2008 – Dept. of Endocrinology, UMCG & University of Groningen, The Netherlands
Letters to the Editor
Dullaart RP, Kema IP, Kerstens MN. Hypertension due to liquorice and liquorice tea consumption
Ned Tijdschr Geneeskd 2008; 152(7): 407; author reply 407-8
Dullaart RP, Kobold AC, van Tol A. Torcetrapib and coronary events. N Engl J Med 2008; 358(17):
1863; author reply 1863-4
Ross HA, Menheere PP, Thomas CM, Mudde AH, Kouwenberg M, Wolffenbuttel BHR. Interference
from heterophilic antibodies in seven current TSH assays. Ann Clin Biochem 2008; 45(Pt 6): 616. Epub
2008 Sep 9
Several abstracts and (poster) presentations on national and international congresses and symposia.
Year Report 2008 – Dept. of Endocrinology, UMCG & University of Groningen, The Netherlands
B6 UltimateProfessional Balance Charger/Discharger SkyRC Technology Co., Ltd. 2010 TABLE OF CONTENTSIntroduction.02Special features.05Warning and safety notes.09Program flow chart.14Lithium polymer balance charge program connection diagram.16Initial parameter setup (users set up).18Lithium battery (LiIon/LiPo/LiFe) program.21Charging lithium battery in the charge mode.22Charging lithium battery in the balance mode.23Charging lithium battery in the fast charge mode.24Charging lithium battery in the s