Introduction In addition to catecholamines, pheochromocytomas and paragangliomas (PPGL) may secrete interleukin-6 (IL-6). IL-6 contributes to the development of unusual symptoms, which may hinder... Show moreIntroduction In addition to catecholamines, pheochromocytomas and paragangliomas (PPGL) may secrete interleukin-6 (IL-6). IL-6 contributes to the development of unusual symptoms, which may hinder the diagnosis. Patients and methods We report the clinical course and subsequent treatment of IL-6 producing PPGL in three patients from a single tertiary referral centre for PPGL patients in the Netherlands. Conclusion PPGL combined with persistent elevated inflammatory markers, either in the presence or absence of pyrexia, raised suspicion of IL-6 overproduction in these three patients. Although surgical resection of the tumour is the only curative treatment option, our case series adds to the accumulating evidence that alpha-blockers might be effective in these patients. Show less
Pheochromocytoma/paraganglioma (PPGL)-induced catecholamine crisis is a rare endocrine emergency leading to life-threatening hemodynamic instability causing end-organ damage or dysfunction. As it... Show morePheochromocytoma/paraganglioma (PPGL)-induced catecholamine crisis is a rare endocrine emergency leading to life-threatening hemodynamic instability causing end-organ damage or dysfunction. As it is associated with a significant mortality rate of approximately 15%, recognizing the signs and symptoms and making the appropriate diagnosis are critical. For this purpose, we report the clinical course of the crisis in four out of a total of six patients with a PPGL crisis from a cohort of 199 PPGL patients of a single tertiary referral center for PPGL patients in the Netherlands diagnosed between 2002 and 2020. Successful treatment of a PPGL crisis demands prompt diagnosis, vigorous pharmacological therapy, and emergency tumor removal if the patient continues to deteriorate. Show less
In this thesis we describe the genetic, biochemical and clinical characteristics of patients with head and neck paragangliomas (HNPGL). In the Netherlands, the majority of SDHx mutation carriers,... Show moreIn this thesis we describe the genetic, biochemical and clinical characteristics of patients with head and neck paragangliomas (HNPGL). In the Netherlands, the majority of SDHx mutation carriers, harbor a mutation in the SDHD gene. Twenty-nine percent of patients with HNPGL have increased urinary excretion of 3-methoxytyramine, indicating dopaminergic activity. Test sensitivity of plasma 3MT measurement equals the measurement of urinary deconjugated 3MT excretion. Only a minority of HNPGL patients have increased plasma chromogranin A levels. Therefore, the practical implications of the measurement of plasma chromogranin A levels are limited in HNPGL patients. Patients screened for pheochromocytomas, because of a hereditary predisposition, present with less signs and symptoms, lower urinary excretion rates of catecholamines, and smaller tumors than patients presenting with symptomatic pheochromocytomas. Despite these differences in biochemical activity and the sizes of the tumors, there is no difference in patients regarding peri-operative complications. Patients with bilateral carotid body tumors are at risk for developing sleep disordered breathing. Sleep disordered breathing is associated with increased carotid body output, which is reflected by increased chemosensitivity. Show less
There is a fundamental difference between mammals and fish in how hypoxia affects the lipid metabolism by means of the stress hormone noradrenaline. In mammals, hypoxia induces an increase in lipid... Show moreThere is a fundamental difference between mammals and fish in how hypoxia affects the lipid metabolism by means of the stress hormone noradrenaline. In mammals, hypoxia induces an increase in lipid metabolism, which can eventually lead to tissue damage due to elevated plasma fatty acid levels, e.g. in case of a heart attack. However, hypoxia is not a normally occurring situation in healthy mammals as opposed to many fish species, because water is a relative poor source of oxygen. In hypoxic fish therefore, noradrenaline mediates a decrease in lipid metabolism, and we believe that this is a general protection mechanism in fish against lipid poisoning. There is a clear difference in the mode of breathing between mammals and fish, namely air- vs. water-breathing. Hence, we hypothesise that this difference is the cause for the opposing effects of noradrenaline. Therefore, we studied the effects of hypoxia on an air-breathing fish, the African catfish. However, physiologically this species reacted the same as other water-breathing fish, namely by means of a reduced lipid metabolism. Additionally, we demonstrated that, despite the opposing effects on the lipid metabolism, the transduction pathways in fish and mammals are very alike, and thus only a minor change has occurred in the course of evolution. This research has aided in a better understanding of the evolutionary changes in lipid metabolism.|Er is een fundamenteel verschil tussen zoogdieren en vissen in hoe het vetmetabolisme onder hypoxie (=zuurstoftekort) wordt veranderd door het stresshormoon noradrenaline. In zoogdieren leidt hypoxie tot een verhoogd vetmetabolisme, wat uiteindelijk zelfs weefselschade kan veroorzaken door te hoge vetzuurgehaltes, b.v. bij een hartaanval. Gezonde zoogdieren komen normaliter niet in zuurstofnood, in tegenstelling tot veel vissoorten, omdat water een relatief arme zuurstofbron is. In hypoxische vissen daalt dan ook het vetmetabolisme door noradrenaline, en wij denken dat dit een beschermingsmechanisme is tegen een vetzuurvergiftiging. Er is een duidelijk verschil in de manier van ademhalen van zoogdieren en vissen, respectievelijk lucht- en waterademhaling, en dit verschil ligt mogelijkerwijs ten grondslag aan deze verschillende effecten van noradrenaline; dit is de centrale hypothese van het onderzoek. Daarom is gekeken naar het effect van zuurstoftekort bij een luchtademhalende vissoort, de Afrikaanse meerval. Deze vis bleek echter fysiologisch hetzelfde te reageren als waterademhalende vissen, namelijk een verlaagd vetmetabolisme. Daarnaast is aangetoond dat, ondanks tegenovergestelde effecten op het vetmetabolisme, de aansturingmechanismen in vissen en zoogdieren vergelijkbaar zijn, en dat er dus maar een minimale verandering in de evolutie heeft plaatsgevonden. Dit onderzoek heeft bijgedragen tot een beter begrip van de evolutionaire veranderingen in het vetmetabolisme. Show less
