The findings of the present thesis can be summarized in the following conclusions: 1. In Leiden, the so-called ‘founder effect’ resulted in genetic clustering with an extremely high prevalence of... Show moreThe findings of the present thesis can be summarized in the following conclusions: 1. In Leiden, the so-called ‘founder effect’ resulted in genetic clustering with an extremely high prevalence of one single SDHD mutation, the SDHD-c.274G>T (p.Asp92Tyr) mutation. 2. Patients with head-and-neck paragangliomas have a considerable impairment of quality of life. 3. Patients with head-and-neck paragangliomas have serious subjective sleep complaints. 4. Patients with SDHD-associated head-and-neck paragangliomas have an increased risk for development of pheochromocytomas and paragangliomas at other locations and life long, repetitive follow up with protocolized clinical, biochemical and radiological screening is therefore mandatory. 5. The use of [123I]-MIBG for detection of intra- and extra-adrenal paragangliomas combined, revealed a sensitivity and specificity of only 80% and 75%, respectively. The sensitivity is dependent on tumor localization and tumor behavior, with an increase in sensitivity to 92% if (intra-adrenal) pheochromocytomas are investigated separately. 6. The practical clinical implications of non-secreting intra-adrenal paragangliomas are currently uncertain. 7. Patients with SDHD mutations have malignant disease in at least ~2.5% of the cases. 8. Mediastinal paragangliomas are associated with mutations in the succinate dehydrogenase genes (either SDHB or SDHD) and aggressive behavior and might be more prevalent than hitherto appreciated. 9. Although the consequences of missing non-secreting and mediastinal paragangliomas in an SDHD-associated population are currently unclear, their possible presence should be taken into consideration in the development of future screening protocols. 10. In the future, [18F]-FDOPA and/or [18F]-FDA are expected to (at least partly) replace MIBG in diagnostic imaging for pheochromocytoma and paraganglioma. Show less
Celiac disease is an intolerance to dietary gluten in genetically predisposed individuals, leading to alterations of the small bowel mucosa. The treatment consists of a life-long, gluten-free diet.... Show moreCeliac disease is an intolerance to dietary gluten in genetically predisposed individuals, leading to alterations of the small bowel mucosa. The treatment consists of a life-long, gluten-free diet. The aims of this thesis were to measure some of the environmental factors considered to play a role in the prevention of celiac disease. For that purpose breast milk was studied on the presence of glutenpeptides and a food frequency questionnaire was developed and validated to quantify gluten intake in young infants. Furthermore, the current treatment at different ages and the ability to develop gluten tolerance were studied. It became clear that the nutrient intake of adolescents on a gluten-free diet can be ameliorated, and that the rather new naturally gluten-free cereal tef is frequently used by Dutch celiac patients and a wide majority of them can consume tef without clinical symptoms. Therefore tef can be a valuable addition to their diet. Although celiac disease is considered to be a permanent condition, we made an attempt to find patients who have become tolerant to gluten. We found 2 of these exceptional patients and found that one of them had HLA-typing different from HLA-DQ2/DQ8, suggesting that genetic factors may play a role in the development of tolerance. The underlying mechanisms leading to prevention, disease development or tolerance to gluten are complex and need to be further studied. Show less
Prolactinoma are treated with dopamine agonists, which are effective in reducing prolactin and tumor size. Studies reporting clinical and radiological outcome are scarce. The study described in... Show moreProlactinoma are treated with dopamine agonists, which are effective in reducing prolactin and tumor size. Studies reporting clinical and radiological outcome are scarce. The study described in chapter 2, assesses long-term outcome in patients treated with dopamine agonists for macroprolactinoma. An increased risk of cardiac valve disease has been reported in patients treated with cabergoline for Parkinson__s disease. Stimulation of serotonin receptors on cardiac valves by dopamine agonists results in fibrotic changes. The study described in chapter 3, assesses prevalence of valve regurgitation in patients treated for prolactinomas. Many patients with pituitary diseases suffer from decreased quality of life. Although prolactinomas present with emotional disturbances, quality of life has not been assessed in these patients. The study described in chapter 4, assesses quality of life in patients treated for microprolactinomas using four health-related questionnaires. The study described in chapter 5 compares quality of life, adjusted for age and gender, of patients after treatment for different pituitary adenomas. Malignant prolactinoma is rare manifestation, diagnosed at moment metastasis occur. The study described in chapter 6 evaluates history of patient with malignant prolactinoma, and provides an overview of radiological and histological characteristics and treatment of all cases with malignant prolactinomas published in literature. Show less
