@article{RemdeKranzMorelletal.2023,
  author    = {Remde, Hanna and Kranz, Stefanie and Morell, Sarah Maria and Altieri, Barbara and Kroiss, Matthias and Detomas, Mario and Fassnacht, Martin and Deutschbein, Timo},
  title     = {Clinical course of patients with adrenal incidentalomas and cortisol autonomy},
  series = {Frontiers in Endocrinology},
  volume    = {14},
  journal   = {Frontiers in Endocrinology},
  issn      = {1664-2392},
  doi       = {10.3389/fendo.2023.1123132},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-316793},
  year      = {2023},
  abstract  = {Background Adrenal incidentalomas with cortisol autonomy are associated with increased cardiovascular morbidity and mortality. Specific data on the clinical and biochemical course of affected patients are lacking. Methods Retrospective study from a tertiary referral centre in Germany. After exclusion of overt hormone excess, malignancy and glucocorticoid medication, patients with adrenal incidentalomas were stratified according to serum cortisol after 1 mg dexamethasone: autonomous cortisol secretion (ACS), >5.0; possible ACS (PACS), 1.9-5.0; non-functioning adenomas (NFA), ≤1.8 µg/dl. Results A total of 260 patients were enrolled (147 women (56.5\%), median follow-up 8.8 (2.0-20.8) years). At initial diagnosis, median age was 59.5 (20-82) years, and median tumour size was 27 (10-116) mm. Bilateral tumours were more prevalent in ACS (30.0\%) and PACS (21.9\%) than in NFA (8.1\%). Over time, 40/124 (32.3\%) patients had a shift of their hormonal secretion pattern (NFA to PACS/ACS, n=15/53; PACS to ACS, n=6/47; ACS to PACS, n=11/24; PACS to NFA, n=8/47). However, none of the patients developed overt Cushing's syndrome. Sixty-one patients underwent adrenalectomy (NFA, 17.9\%; PACS, 24.0\%; ACS, 39.0\%). When non-operated patients with NFA were compared to PACS and ACS at last follow-up, arterial hypertension (65.3\% vs. 81.9\% and 92.0\%; p<0.05), diabetes (23.8\% vs. 35.6\% and 40.0\%; p<0.01), and thromboembolic events (PACS: HR 3.43, 95\%-CI 0.89-13.29; ACS: HR 5.96, 95\%-CI 1.33-26.63; p<0.05) were significantly less frequent, along with a trend towards a higher rate of cardiovascular events in case of cortisol autonomy (PACS: HR 2.23, 95\%-CI 0.94-5.32; ACS: HR 2.60, 95\%-CI 0.87-7.79; p=0.1). Twenty-five (12.6\%) of the non-operated patients died, with higher overall mortality in PACS (HR 2.6, 95\%-CI 1.0-4.7; p=0.083) and ACS (HR 4.7, 95\%-CI 1.6-13.3; p<0.005) compared to NFA. In operated patients, prevalence of arterial hypertension decreased significantly (77.0\% at diagnosis to 61.7\% at last follow-up; p<0.05). The prevalence of cardiovascular events and mortality did not differ significantly between operated and non-operated patients, whereas thromboembolic events were significantly less frequent in the surgical treatment group. Conclusion Our study confirms relevant cardiovascular morbidity in patients with adrenal incidentalomas (especially those with cortisol autonomy). These patients should therefore be monitored carefully, including adequate treatment of typical cardiovascular risk factors. Adrenalectomy was associated with a significantly decreased prevalence of hypertension. However, more than 30\% of patients required reclassification according to repeated dexamethasone suppression tests. Thus, cortisol autonomy should ideally be confirmed before making any relevant treatment decision (e.g. adrenalectomy).},
  language  = {en}
}
@phdthesis{Vogg2023,
  author    = {Vogg, Nora Johanna},
  title     = {Mass spectrometry-based quantification of steroids for the diagnostic workup of adrenal tumors},
  doi       = {10.25972/OPUS-29343},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-293438},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2023},
  abstract  = {Tumors of the adrenal gland belong to the most frequent neoplasms in humans with a prevalence of 3-10 \% in adults. The aim of the diagnostic workup is the identification of potentially hormone-secreting and / or malignant tumors, because most of these tumors will require surgical resection. Malignant adrenocortical carcinomas (ACC) are very rare and associated with a poor prognosis in advanced stages, therefore, an early and accurate diagnosis is crucial. Within this thesis, two liquid chromatography tandem mass spectrometry (LC-MS/MS) methods for the quantification of steroids in different biomaterials were developed to improve the diagnostic workup of adrenal tumors. First, an LC-MS/MS method for the simultaneous quantification of cortisol and dexamethasone in serum samples after dexamethasone suppression test (DST) was developed, validated, and applied to 400 clinical samples. Newly established method-specific threshold concentrations for cortisol and dexamethasone increased DST specificity from 67.5 \% to 92.4 \% while preserving 100 \% sensitivity. Second, an LC-MS/MS method for the quantification of eleven urinary steroids was developed and validated to improve the differentiation between ACC and adrenocortical adenomas (ACA). A decision tree requiring only two steroids was trained for classification and tested based on 24 h urine samples from 268 patients with adrenal tumor. Malignancy was excluded with a negative predictive value of 100 \% in an independent validation cohort of 84 samples of 24-h urine. A newly proposed simplified diagnostic workflow with urinary steroid profiling as first tier test could obviate additional adrenal-specific imaging in 42 of 64 patients with ACA. The new DST method is already in clinical use at the University Hospital W{\"u}rzburg, whereas the classification model based on urinary steroid profiling will require prospective validation in a larger cohort.},
  subject      = {Nebennierentumor},
  language  = {en}
}