- To protect and expand the international leading role of the centre in the personalized treatment of pituitary disorders, along with the leading the translational research position.
- To improve molecular and pathophysiological understanding of hypothalamic and pituitary disease.
- To develop new treatment modalities.
- To expand our international knowledge network and international and national collaboration.with patient-support groups
Research Activities
Present: A large prospective database and bio-bank is initiated for all rare hypothalamic and pituitary patients that are currently being treated in the ACE. The aim is to provide more targeted treatment. In general, we have basic and translation medicine collaboration between pathology, endocrinology, neurosurgery, clinical chemistry and genetics (endocrinology or international). In an international network (LAS) we work together on the genetics and medical outcome in pituitary disease. Collecting long-term data on different kinds of treatment in patients with rare hypothalamic and pituitary disease.
This clinical research that leads often to translation medicine, with the collaboration between mainly endocrinology, neurosurgery and sometimes radiology and pathology. Additional future goals are to share more knowledge about rare hypothalamic and pituitary disease with the medical community and with the public and to address unmet needs in the current treatment strategies.
- To identify novel biomarkers of tissue specific hormone state, for example in growth hormone.
- To assess the interaction between ghrelin and unacylated ghrelin in the different hypothalamic and pituitary disease.
- To develop new treatment modalities or combinations for rare hypothalamic and pituitary disease.
- To assess long-term sequelae of treatment of rare hypothalamic and pituitary disease and to develop a mice model for this.
Collaborations
In an international network (LAS) we work together on the genetics and medical outcome in pituitary disease.
Contributions
Present state:
- Heavily involved at different levels of education at Erasmus MC (Bachelor, Master, Clinical training for medical specialists in Medicine, Postgraduate courses, and facultative courses)
- A leading role in educational activities in the Netherlands and Internationally.
- 6 PhD students are involved in translational and clinical studies.
- Annually we have 1-2 international students and/or fellows. In Erasmus MC, the ACE or members are responsible for:
- Coordination of Bachelor Theme 1.C.3: "The hypothalamus-pituitary-axis"
- The master examination board.
- Organization of the facultative course: "MINOR Oncology"
- Organization of the facultative course: "MINOR Endocrinology"
- Organization of the facultative course: "MINOR Paediatric-oncology"
- Active participation in Clinical Reasoning training of Master 1B.
- Organization Committee of the bi-annual post-graduate course of the Molecular Medicine School, entitled: "Basic and Translational Endocrinology"
- At Clinical Endocrinology Ward, involved in the bedside teaching of clinical residents and fellows.
- Member of the training team and Educational Committee of the Division of Endocrinology Regional/national teaching activities of the ACE involve:
- Biannual regional symposium: Attended by >20 internists, and fellows from surrounding non-academic hospitals
- Medical Advisor of the Dutch Pituitary Patient Society.
- Annual patient information evenings on different aspects of hypothalamic and pituitary disease.
- Participation in Continuing Educational Course for Endocrinologists, Internists and fellows International teaching activities of members of the ACE:
- Educational Board of the European Society of Endocrinology.
- Program organizing committee chair of Annual meeting of Erasmus Endocrinology meeting and are teachers.
- Program organizing committee chair of biannual international meeting in advanced endocrinology
- Active participation in different international guideline committees
Care Activities
The full spectrum of the rare hypothalamic and pituitary disease is covered by this ACE and is a NFU-accredited expertise center, HCP and a Dutch ERN, has an Orphanet status and was awarded a stipend from Erasmus MC zorgpaden II for a reduction in lead time. This ACE provides: Multidisciplinary ternary care of patients with a rare hypothalamic and pituitary disease, including inventions like, optimal hormone assessments, sinus petrosus sampling, and pituitary region surgery. ACE covers all the essential areas for the treatment and diagnostics of rare hypothalamic and pituitary disease within the Erasmus MC except for the genetic testing in case of familial disease.
This is covered by the international coloration the ACE has with the LAS. All patients of the Rotterdam centre for rare hypothalamic and pituitary disease are asked for permission to use their clinical data and/or material for (clinical) research. The ACE has a longstanding world famous track-record for translation, clinical and basic research in this area.
The goal is to develop better markers to predict the effect of current treatments, as well as to develop new therapies, to assess long-term sequelae and to find better biomarker for disease/hormonal activity. National monitoring of the surgery of these patients is done in QRNS by the Dutch Neuro-surgery society. The departments involved are Medicine, Neurosurgery, ENT surgery, Radiotherapy, Pathology, Radiology, Clinical chemistry, and in specific cases Clinical oncology, Nuclear medicine and Paediatrics.
Societal Relevance to Research, Education and Patient Care
The ACE had as spin-off for the development of unacylated ghrelin analogs. These patented drugs are currently tested in phase 1-2 clinical studies by Alize pharma (http://www.alz-pharma.com). Members of the ACE are involved in the development of new master curriculum, and have been furthering in patients' advocacy films (on you tube in Dutch, English, German), development with the advocacy groups brochures, are regular speakers at the annual advocacy groups congress and are part of the advisory board of these advocacy groups.
For the multidisciplinary outpatient clinic a website, protocols and patient information have been developed. Next October, we will celebrate the 10th year anniversary of the HCR, and will install an international advisory board that includes a member from the patient advocacy group. This is on top of our annual meeting for patients with rare hypothalamic and pituitary disease. Activities of members of the ACE: President of the European Society of Endocrinology, Educational Board of the European Society of Endocrinology.
Program organizing committee chair of Annual meeting of Erasmus Endocrinology meeting. Program organizing committee chair of biannual international meeting in advanced endocrinology. Active participation in different international guideline committees. Members of advisory boards of several pharmaceutical companies, as well as the DSM Food Innovation Center.
Viability of Research, Education and Patient Care
The ACE has a balanced structure looking at the age distribution. New talent is stimulated and if possible acquired for the ACE (example S Neggers in 2008). The all PhD students (at this moment 6) have regular presentations at international meetings and publish in the top 10 journals of endocrinology.
Some have started their own research group in their home country, like Prof. Dr. Ferrone and Prof. Dr Pivenello and Dr Gatto. Christian de Bruin is currently working in Cincinnati, USA. A member of the ACE has worked abroad at National Institutes of Health, Bethesda, USA. and have received multiple international prestigious prizes.
Key and relevant publications of the last five years
- Long-term efficacy and safety of pegvisomant in combination with long-acting somatostatin analogs in acromegaly. Neggers SJ, et al. J Clin Endocrinol Metab. 2014 Oct;99(10):3644-52. doi: 10.1210/jc.2014-2032.
- Expert consensus document: A consensus on the medical treatment of acromegaly. Giustina A,et al; Acromegaly Consensus Group. Nat Rev Endocrinol. 2014 Apr;10(4):243-8. doi: 10.1038/nrendo.2014.21.
- Cushing's syndrome. Lacroix A, Feelders RA, Stratakis CA, Nieman LK. Lancet. 2015 Aug 29;386(9996):913-27.
- Pasireotide alone or with cabergoline and ketoconazole in Cushing's disease. Feelders RA, et al; N Engl J Med. 2010 May 13;362(19):1846-8.
- Long-term outcome and MGMT as a predictive marker in 24 patients with atypical pituitary adenomas and pituitary carcinomas given treatment with temozolomide. Bengtsson D, et al; J Clin Endocrinol Metab. 2015 Apr;100(4):1689-98.
- Immunoreactivity score using an anti-sst2A receptor monoclonal antibody strongly predicts the biochemical response to adjuvant treatment with somatostatin analogs in acromegaly. Gatto F, et al; J Clin Endocrinol Metab. 2013 Jan;98(1):E66-71. doi: 10.1210/jc.2012-2609.
- Somatic mosaicism underlies X-linked acrogigantism syndrome in sporadic male subjects. Daly AF, et al; Endocr Relat Cancer. 2016 Apr;23(4):221-33. doi: 10.1530/ERC-16-0082.
- Clinical and genetic characterization of pituitary gigantism: an international collaborative study in 208 patients. Rostomyan L, et al; Endocr Relat Cancer. 2015 Oct;22(5):745-57. doi: 10.1530/ERC-15-0320.
- Pasireotide. Feelders RA, et al; Nat Rev Drug Discov. 2012 Aug;11(8):597-8.
- Preoperative normalization of cortisol levels in Cushing's disease after medical treatment: consequences for somatostatin and dopamine receptor subtype expression and in vitro response to somatostatin analogs and dopamine agonists. van der Pas R, et al; J Clin Endocrinol Metab. 2013 Dec;98(12):E1880-90. doi: 10.1210/jc.2013-1987
PhD theses of the last five years
- Rob van de Pas, basic and clinical aspects of the medical treatment of cushing’s disease
- Aimee Varewijck,insuline receptor and IGF1 receptor bioactivity in health and disease
- Frederico Gato 2015 Novel Molecular Mechanisms of Resistance to Somatostatin Analog Treatment in Pituitary Adenomas
- Karin Blijdorp Determinants & Sequelae of Altered Body Composition in Childhood Cancer Survivors
- Sebastian Neggers New Insights into Medical Treatment of Acromegaly
- Michel Brugts IGF-I Bioactivity in Aging, Health and Disease