Top reference center for optimal care of children with growth disorders, with a leading role in clinical, fundamental and translational research in focus areas Prader Willi Syndrome, SGA, Silver Russell Syndrome, non-acquired growth hormone (GH)-IGF-I pathway disorders and GH resistance, in collaboration with partners in Erasmus MC and national and international researchers.
Includes the NFU accredited Dutch Expert Center for Prader Willi Syndrome (PWS) and Expert Center for Rare Growth Disorders, and EU Rare Growth Disorder Network in the European Rare Endocrine Network (Endo ERN)
Research Activities
Project leader of 5 large Dutch multicenter studies in collaboration with 11-18 Dutch Universities and large hospitals, together with pediatricians, clinical geneticists, orthopedic surgeons, endocrinologists, medical psychologists, basic genetic scientists, a.o.,
- fundamental, translational and clinical research One of the project leaders of the EU project ''SAGHE'' on long-term safety of GH treatment, a collaborative project including 8 scientific institutes in 6 countries (24.000 childhood-GH-treated adults)
- epidemiological and clinical research Project leader of several genetic, laboratory and clinical studies in children with either a severe growth disorder with unknown etiology, growth hormone deficiency or non-acquired combined pituitary hormone deficiency, in collaboration with all Dutch Universities and large centers, Dutch Growth Research Foundation and with University of Madrid and Leipzig
- fundamental, translational and clinical research Project leader of a collaborative study in children with PWS, together with University of Toulouse, Stockholm, London and Essen
- fundamental, translational and clinical. EU application in preparation, with endocrinologists, clinical geneticists, basic genetic scientists. ZonMw project (Seenez), national study in Dutch growth hormone deficient adolescents, including Free University MC, Erasmus MC, UMC Amsterdam and all Dutch University Hospitals/6 large Dutch hospitals, in collaboration with pediatric endocrinologists and biostatisticians
Collaborations
One of the project leaders of the EU project ‘’SAGHE’’ on long-term safety of GH treatment, a collaborative project including 8 scientific institutes in 6 countries. Project leader of several genetic, laboratory and clinical studies in children with either a severe growth disorder with unknown etiology, growth hormone deficiency or non-acquired combined pituitary hormone deficiency, in collaboration with all Dutch Universities and large centers, Dutch Growth Research Foundation and with University of Madrid and Leipzig. Project leader of a collaborative study in children with PWS, together with University of Toulouse, Stockholm, London and Essen
Contributions
Our ACE is involved in the education of Ba and MSc students, specialists in training, pediatric nurses, PhDs and postgraduate training. We developed a dedicated e-learning program with different levels, which is used in Erasmus MC to support the education of Ba and MSc students, pediatricians in training and PhDs. It is also used in the postgraduate training by our ACE.
The e-learning program has been approved by the European Society of Pediatric Endocrinology (ESPE) and is now worldwide available for (fellow) pediatric endocrinologists via ESPE website. We also designed a serious game allowing medical students, physician assistants, nurses, general practitioners, internists and endocrinologists to improve their endocrine knowledge. Because the game can be played at different levels, it is suitable for different audiences. For endocrinologists, for example, this game can replace a workshop during a conference. Our serious game provides an innovative way of learning, where knowledge is combined with humor and excitement; an ideal way to reach the target audience. We did not receive a formal feedback such as SET Q, visitation of audit report. Our ACE has on average one international student and one international PhD student (recently Spain, UK, Brasil, Latvia, now request from Chili)
Care Activities
Our ACE provides highly specialized care to children with severe and very rare growth disorders, care that cannot be provided by non-academic hospitals. Ninety-five percent of patients are referred by pediatricians outside Erasmus MC and only 3% via pediatric specialists in Erasmus MC. Most patients belong to the NFU accredited 1) Expertise Center Rare Growth Disorders and 2) Expertise Center for Prader Willi Syndrome.
Many patients receive care in multidisciplinary outpatient clinics. Clinical care pathways are defined. Majority of patients receive very expensive biosynthetic growth hormone treatment, which can only be prescribed by academic pediatric-endocrinologists. Our ACE is the largest and most experienced Dutch center for severe and rare growth disorders, also having the largest scientific output from clinical research in this field.
Research results of the ACE contribute to innovation and better (academic) care, worldwide. Unfortunately we cannot insert and thus not show the right (rare) diagnoses via the DBC registration system because there is only one very unspecified code ''short stature/ growth retardation''. This code is also used by general pediatricians for low care patients in regional hospitals. Also, we had not been aware of the important issue of the referring physician, so there is a great backlog. As a result, the hospital system does not show that our ACE gives more than 80% academic care according to the ROBIJN criteria.
We are working to solve the problem, in collaboration with Hong Xiong, Dept of Portfolio. We have implemented the Value Based Health Care for some disorders, will continue with others. The two Rare Disorder Expertise Centers have been reviewed by NFU, but the ACE has not been formally audited.
Societal Relevance to Research, Education and Patient Care
Results of the many studies performed by our ACE are translated into clinical practice for patients and population health. Our ACE leads many scientific publications, develops of (inter)national guidelines, masterclasses and symposia for health care workers and for patients. Provides presentations during congresses, educational materials, newsletters for patients and updates on our websites www.groeienco.nl and www.praderwillisyndroom.nl.
Our ACE has developed the curriculum 'Growth disorders'' for Ba and MSc students and the innovative e-learning program on growth disorders which is nowadays used in Erasmus MC and worldwide. Our ACE is one of the world leading research centers for growth disorders, focused on pathophysiologic mechanisms and (epi)genetic research, innovative medicines, phase 2 and 3 multicenter clinical trials, long-term effects and cost-effectiveness. Based on our research data, the FDA and EMA have registered growth hormone treatment for patients with renal insufficiency, Turner syndrome and short stature after SGA birth.
Our research and subsequent clinical care regimen in children with PWS has changed the natural (morbid) course of PWS. Based on our recent data an application for GH registration for PWS adults will be filed. Our ACE contributes, mostly as leader, to (inter)national guidelines and development of care standards
Viability of Research, Education and Patient Care
Knowledge sharing in ACE occurs via
- Research meeting (1h/wk), with all researchers and (fellow) pediatric-endocrinologists- to discuss results, clinical implications and updates (guidelines and/or websites, newsletters), new initiatives and news from congresses/symposia, and via
- Clinical care meeting (2h/wk), with (fellow) pediatric-endocrinologists, pediatricians and biochemists in training, PhD fellows, head of Endocrine laboratory, clinical geneticist (1x/mo).
Also:
- 1x/2 mo meeting with the pediatricians of 18 hospitals of our regional network and
- 1x/3 months with pediatric-endocrinologists and fellows of South-West Netherlands and 1x/3 months with Dutch Advisory Board on GH therapy - to discuss difficult cases, give updates from our research and literature, discuss clinical implications of new insights.
During last 10 years, ACE generated 25 PhD doctorates (promotor Prof. A.C.S. Hokken-Koelega). All of them had >6 papers in high-ranking peer-reviewed international-journals, presented their data in >6 international congresses; 50% had international working experience (6 mo-2 yrs). Nineteen PhDs started an international career.
On average 8 PhD fellows working in the ACE. Monitoring/review 1-2 wkly by research teams, PhD fellows and supervisor, and annual reports. Bibliometric analysis not available. No doubt ACE belongs to world-top, based on 20 years of research. Hokken: 2012 ESPE Award for Scientific leadership
Key and relevant publications of the last five years
- Smeets CC, …, Hokken-Koelega AC. Long-term results of GH treatment in Silver-Russell Syndrome (SRS). J Clin Endo Metab. 2016 April;
- Van der Steen M, …, Hokken-Koelega AC. Puberty and pubertal growth in GH-treated SGA children J Clin Endo Metab. 2016 Mar 10:jc20161317.
- Van der Steen M,., Hokken-Koelega AC. Insulin Sensitivity and β-Cell Function in SGA Treated With GH and GnRHa. J Clin Endo Metab.2016; 101:705-13.
- Van der Steen M, … Hokken-Koelega AC. Metabolic Health in Short Children Born Small for Gestational Age. J Clin Endo Metab. 2015; 100:3725-34.
- Bakker NE, .. Hokken-Koelega AC. IGF-1 Levels, Complex Formation, and IGF Bioactivity in GH-treated PWS children. J Clin Endo Metab. 2015;100:3041-9.
- Bakker NE, .. Hokken-Koelega AC. Bone mineral density in PWS children and adolescents - 9 yrs longitudinally. J Clin Endo Metab. 2015;100:1609-18.
- Allen DB, . Hokken-Koelega AC,.. Thorner M. GH safety workshop position paper on GH therapy in children and adults. Eur J Endo 2015;174:1-9;174:1-9.
- Renes JS, .., Hokken-Koelega. Bloom syndrome in short children born small for gestational age: a challenging diagnosis. J Clin Endo Metab. 2013;98:3932-8
- Del Blanco DG, de Graaff LC, .., Hokken-Koelega AC. A novel OTX2 mutation in CPHD and underdeveloped left optic nerve. Eur J Endo. 2012;167:441-52.
- Sävendahl L, .., Hokken-Koelega AC, Long-term mortality and causes of death in isolated GHD, ISS and SGA patients treated with GH in childhood – in Belgium, Netherlands and Sweden in EU SAGhE study.J Clin Endo Metab 2012;97: 213-7
PhD theses of the last five years
- L. Breij Infant growth and later body composition and metab health 22-4-2016
- N. Bakker GH treatment in children and adolescents with PWS 19-6-2015
- S. Lo Psychiatric disorders and effects of GH in PWS 21-4-2015
- J. Renes New insights in factors influencing growth in SGA 6-12-2013
- F. de Steenwinkel Growth in children of mothers with RA 18-12-2013
- P. Breukhoven Growth of term vs preterm SGA children 23-12-2012
- E. Siemensma PWS gonadal function, cognition & GH effects 20-11-2012
- A .Lem Short adolescents born SGA: BMD, QoL, gonads, growth 9-11-2012
- G. Kerkhof Early growth patterns and adult health profile 19-6-2012
- D. Gorbenko CPHD: Genotypes & Molecular mechanisms 13-12-2011