@article{LiPamporakiFliedneretal.2021,
  author    = {Li, Minghao and Pamporaki, Christina and Fliedner, Stephanie M. J. and Timmers, Henri J. L. M. and N{\"o}lting, Svenja and Beuschlein, Felix and Prejbisz, Aleksander and Remde, Hanna and Robledo, Mercedes and Bornstein, Stefan R. and Lenders, Jacques W. M. and Eisenhofer, Graeme and Bechmann, Nicole},
  title     = {Metastatic pheochromocytoma and paraganglioma: signs and symptoms related to catecholamine secretion},
  series = {Discover Oncology},
  volume    = {12},
  journal   = {Discover Oncology},
  issn      = {2730-6011},
  doi       = {10.1007/s12672-021-00404-x},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-309901},
  year      = {2021},
  abstract  = {Background The presence or future development of metastatic pheochromocytomas or paragangliomas (mPPGLs) can be difficult to diagnose or predict at initial presentation. Since production of catecholamines from mPPGLs is different from non-metastatic tumors (non-mPPGLs), this study aimed to clarify whether presenting catecholamine-related signs and symptoms (cSS) might also differ. Methods The study included 249 patients, 43 with mPPGL and 206 with non-mPPGL. Clinical data at the time of biochemical diagnosis (i.e. at entry into the study) were used to generate a cumulative score of cSS for each patient. Results Patients with mPPGL were significantly younger (43.3 ± 14 vs. 48.9 ± 16.1 years) and included a lower proportion of females (39.5\% vs. 60.7\%) than patients with non-mPPGLs. Frequencies of signs and symptoms did not differ between the two groups. Patients with mPPGLs had lower (P < 0.001) urinary excretion of epinephrine (3.5 (IQR, 1.9—6.5) µg/day) than those with non-mPPGLs (19.1 (IQR, 4.3—70.2) µg/day). There was no difference in urinary excretion of norepinephrine. In patients with mPPGLs a high cSS score was associated with high urinary excretion of norepinephrine and normetanephrine. In contrast, in patients with non-mPPGLs, a high cSS was associated with high urinary excretion of epinephrine and metanephrine. Conclusion Although presenting signs and symptoms were associated with production of norepinephrine in patients with mPPGLs and of epinephrine in patients with non-mPPGLs, there were no differences in signs and symptoms between the two groups. Therefore, consideration of signs and symptoms does not appear helpful for distinguishing patients with and without mPPGLs.},
  language  = {en}
}
@article{RogowskiLehmannGeroulaPrejbiszetal.2018,
  author    = {Rogowski-Lehmann, Natalie and Geroula, Aikaterini and Prejbisz, Aleksander and Timmers, Henri J. L. M. and Megerle, Felix and Robledo, Mercedes and Fassnacht, Martin and Fliedner, Stephanie M. J. and Reincke, Martin and Stell, Anthony and Januszewicz, Andrzej and Lenders, Jacques W. M. and Eisenhofer, Graeme and Beuschlein, Felix},
  title     = {Missed clinical clues in patients with pheochromocytoma/paraganglioma discovered by imaging},
  series = {Endocrine Connections},
  volume    = {7},
  journal   = {Endocrine Connections},
  number    = {11},
  doi       = {10.1530/EC-18-0318},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-226481},
  pages     = {1168-1177},
  year      = {2018},
  abstract  = {Background: Pheochromocytomas and paragangliomas (PPGLs) are rare but potentially harmful tumors that can vary in their clinical presentation. Tumors may be found due to signs and symptoms, as part of a hereditary syndrome or following an imaging procedure. Objective: To investigate potential differences in clinical presentation between PPGLs discovered by imaging (iPPGLs), symptomatic cases (sPPGLs) and those diagnosed during follow-up because of earlier disease/known hereditary mutations (fPPGL). Design: Prospective study protocol, which has enrolled patients from six European centers with confirmed PPGLs. Data were analyzed from 235 patients (37 iPPGLs, 36 sPPGLs, 27\% fPPGLs) and compared for tumor volume, biochemical profile, mutation status, presence of metastases and self-reported symptoms. iPPGL patients were diagnosed at a significantly higher age than fPPGLs (P<0.001), found to have larger tumors (P=0.003) and higher metanephrine and normetanephrine levels at diagnosis (P=0.021). Significantly lower than in sPPGL, there was a relevant number of self-reported symptoms in iPPGL (2.9 vs 4.3 symptoms, P< 0.001). In 16.2\% of iPPGL, mutations in susceptibility genes were detected, although this proportion was lower than that in fPPGL (60.9\%) and sPPGL (21.5\%). Patients with PPGLs detected by imaging were older, have higher tumor volume and more excessive hormonal secretion in comparison to those found as part of a surveillance program. Presence of typical symptoms indicates that in a relevant proportion of those patients, the PPGL diagnosis had been delayed. Precis: Pheochromocytoma/paraganglioma discovered by imaging are often symptomatic and carry a significant proportion of germline mutations in susceptibility genes.},
  subject      = {Biochemical-Diagnosis},
  language  = {en}
}
@article{EisenhoferPeitzschKadenetal.2019,
  author    = {Eisenhofer, Graeme and Peitzsch, Mirko and Kaden, Denise and Langton, Katharina and Mangelis, Anastasios and Pamporaki, Christina and Masjkur, Jimmy and Geroula, Aikaterini and Kurlbaum, Max and Deutschbein, Timo and Beuschlein, Felix and Prejbisz, Aleksander and Bornstein, Stefan R. and Lenders, Jacques W. M.},
  title     = {Reference intervals for LC-MS/MS measurements of plasma free, urinary free and urinary acid-hydrolyzed deconjugated normetanephrine, metanephrine and methoxytyramine},
  series = {Clinica Chimica Acta},
  volume    = {490},
  journal   = {Clinica Chimica Acta},
  doi       = {10.1016/j.cca.2018.12.019},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-226598},
  pages     = {46-54},
  year      = {2019},
  abstract  = {Background Plasma or urinary metanephrines are recommended for screening of pheochromocytomas and paragangliomas (PPGLs). Measurements of urinary free rather than deconjugated metanephrines and additional measurements of methoxytyramine represent other developments. For all measurements there is need for reference intervals. Methods Plasma free, urinary free and urinary deconjugated O-methylated catecholamine metabolites were measured by LC-MS/MS in specimens from 590 hypertensives and normotensives. Reference intervals were optimized using data from 2,056 patients tested for PPGLs. Results Multivariate analyses, correcting for age and body surface area, indicated higher plasma and urinary metanephrine in males than females and sex differences in urinary normetanephrine and free methoxytyramine that largely reflected body size variation. There were positive associations of age with plasma metabolites, but negative relationships with urinary free metanephrine and methoxytyramine. Plasma and urinary normetanephrine were higher in hypertensives than normotensives, but differences were small. Optimization of reference intervals using the data from patients tested for PPGLs indicated that age was the most important consideration for plasma normetanephrine and sex most practical for urinary metabolites. Conclusion This study clarifies impacts of demographic and anthropometric variables on catecholamine metabolites, verifies use of age-specific reference intervals for plasma normetanephrine and establishes sex-specific reference intervals for urinary metabolites.},
  language  = {en}
}