TY - JOUR A1 - Gelbrich, Götz A1 - Morbach, Caroline A1 - Deutschbein, Timo A1 - Fassnacht, Martin A1 - Störk, Stefan A1 - Heuschmann, Peter U. T1 - The population comparison index: an intuitive measure to calibrate the extent of impairments in patient cohorts in relation to healthy and diseased populations JF - International Journal of Environmental Research and Public Health N2 - We assume that a specific health constraint, e.g., a certain aspect of bodily function or quality of life that is measured by a variable X, is absent (or irrelevant) in a healthy reference population (Ref0), and it is materially present and precisely measured in a diseased reference population (Ref1). We further assume that some amount of this constraint of interest is suspected to be present in a population under study (SP). In order to quantify this issue, we propose the introduction of an intuitive measure, the population comparison index (PCI), that relates the mean value of X in population SP to the mean values of X in populations Ref0 and Ref1. This measure is defined as PCI[X] = (mean[X|SP] − mean[X|Ref0])/(mean[X|Ref1] − mean[X|Ref0]) × 100[%], where mean[X|.] is the average value of X in the respective group of individuals. For interpretation, PCI[X] ≈ 0 indicates that the values of X in the population SP are similar to those in population Ref0, and hence, the impairment measured by X is not materially present in the individuals in population SP. On the other hand, PCI[X] ≈ 100 means that the individuals in SP exhibit values of X comparable to those occurring in Ref1, i.e., the constraint of interest is equally present in populations SP and Ref1. A value of 0 < PCI[X] < 100 indicates that a certain percentage of the constraint is present in SP, and it is more than in Ref0 but less than in Ref1. A value of PCI[X] > 100 means that population SP is even more affected by the constraint than population Ref1. KW - reference data KW - normal values KW - disease severity KW - disease score KW - comparability Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-304933 SN - 1660-4601 VL - 20 IS - 3 ER - TY - JOUR A1 - Kimpel, Otilia A1 - Schindler, Paul A1 - Schmidt-Pennington, Laura A1 - Altieri, Barbara A1 - Megerle, Felix A1 - Haak, Harm A1 - Pittaway, James A1 - Dischinger, Ulrich A1 - Quinkler, Marcus A1 - Mai, Knut A1 - Kroiss, Matthias A1 - Polat, Bülent A1 - Fassnacht, Martin T1 - Efficacy and safety of radiation therapy in advanced adrenocortical carcinoma JF - British Journal of Cancer N2 - Background International guidelines emphasise the role of radiotherapy (RT) for the management of advanced adrenocortical carcinoma (ACC). However, the evidence for this recommendation is very low. Methods We retrospectively analysed all patients who received RT for advanced ACC in five European centres since 2000. Primary endpoint: time to progression of the treated lesion (tTTP). Secondary endpoints: best objective response, progression-free survival (PFS), overall survival (OS), adverse events, and the establishment of predictive factors by Cox analyses. Results In total, 132 tumoural lesions of 80 patients were treated with conventional RT (cRT) of 50–60 Gy (n = 20) or 20–49 Gy (n = 69), stereotactic body RT of 35–50 Gy (SBRT) (n = 36), or brachytherapy of 12–25 Gy (BT) (n = 7). Best objective lesional response was complete (n = 6), partial (n = 52), stable disease (n = 60), progressive disease (n = 14). Median tTTP was 7.6 months (1.0–148.6). In comparison to cRT\(_{20-49Gy}\), tTTP was significantly longer for cRT\(_{50-60Gy}\) (multivariate adjusted HR 0.10; 95% CI 0.03–0.33; p < 0.001) and SBRT (HR 0.31; 95% CI 0.12–0.80; p = 0.016), but not for BT (HR 0.66; 95% CI 0.22–1.99; p = 0.46). Toxicity was generally mild and moderate with three grade 3 events. No convincing predictive factors could be established. Conclusions This largest published study on RT in advanced ACC provides clear evidence that RT is effective in ACC. KW - adrenal tumours KW - adrenocortical carcinoma (ACC) KW - radiotherapy (RT) Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-324411 VL - 128 IS - 4 ER - TY - JOUR A1 - Werner, Rudolf A. A1 - Sayehli, Cyrus A1 - Hänscheid, Heribert A1 - Higuchi, Takahiro A1 - Serfling, Sebastian E. A1 - Fassnacht, Martin A1 - Goebeler, Maria-Elisabeth A1 - Buck, Andreas K. A1 - Kroiss, Matthias T1 - Successful combination of selpercatinib and radioiodine after pretherapeutic dose estimation in RET-altered thyroid carcinoma JF - European Journal of Nuclear Medicine and Molecular Imaging N2 - No abstract available. KW - papillary thyroid carcinoma (PTC) KW - selpercatinib KW - radioiodine KW - combination KW - thyroid carcinoma (TC) Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-324435 VL - 50 IS - 6 ER - TY - JOUR A1 - Kimpel, Otilia A1 - Altieri, Barbara A1 - Dischinger, Ulrich A1 - Fuss, Carmina Teresa A1 - Kurlbaum, Max A1 - Fassnacht, Martin T1 - Early detection of recurrence and progress using serum steroid profiling by LC–MS/MS in patients with adrenocortical carcinoma JF - Metabolites N2 - Serum liquid chromatography–tandem mass spectrometry (LC–MS/MS) steroid profiling is used for the diagnosis of adrenocortical carcinoma (ACC). Guidelines recommend endocrine work-up in addition to radiological imaging for follow-up in ACC, but data on this topic are scarce. Patients were included in this retrospective study if pre-therapeutic hormone values, regular tumour evaluation by imaging, steroid measurements by LC–MS/MS, and details on therapies were available. The utility of steroid profiles in detecting recurrence or disease progression was assessed, whereby “endocrine progress” was defined by an elevation of at least 3 of 13 analysed hormones. Cohort A included 47 patients after R0 resection, of whom 15 experienced recurrence and 32 did not. In cohort B, 52 patients with advanced disease (including 7 patients of cohort A with recurrence) could be evaluated on 74 visits when progressive disease was documented. In 20 of 89 cases with documented disease progression, “endocrine progress” was detectable prior to radiological progress. In these cases, recurrence/progression was detected at a median of 32 days earlier by steroid measurement than by imaging, with 11-deoxycortisol and testosterone being the most sensitive markers. Notably, these patients had significantly larger tumour burden. In conclusion, steroid profiling by LC–MS/MS is of value in detecting recurrent/progressive disease in ACC. KW - adrenal cancer KW - follow-up KW - steroid measurement KW - liquid chromatography–tandem mass spectrometry (LC–MS/MS) Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-355839 SN - 2218-1989 VL - 14 IS - 1 ER - TY - JOUR A1 - Balonov, Ilja A1 - Kurlbaum, Max A1 - Koschker, Ann-Cathrin A1 - Stier, Christine A1 - Fassnacht, Martin A1 - Dischinger, Ulrich T1 - Changes in plasma metabolomic profile following bariatric surgery, lifestyle intervention or diet restriction — insights from human and rat studies JF - International Journal of Molecular Sciences N2 - Although bariatric surgery is known to change the metabolome, it is unclear if this is specific for the intervention or a consequence of the induced bodyweight loss. As the weight loss after Roux-en-Y Gastric Bypass (RYGB) can hardly be mimicked with an evenly effective diet in humans, translational research efforts might be helpful. A group of 188 plasma metabolites of 46 patients from the randomized controlled Würzburg Adipositas Study (WAS) and from RYGB-treated rats (n = 6) as well as body-weight-matched controls (n = 7) were measured using liquid chromatography tandem mass spectrometry. WAS participants were randomized into intensive lifestyle modification (LS, n = 24) or RYGB (OP, n = 22). In patients in the WAS cohort, only bariatric surgery achieved a sustained weight loss (BMI −34.3% (OP) vs. −1.2% (LS), p ≤ 0.01). An explicit shift in the metabolomic profile was found in 57 metabolites in the human cohort and in 62 metabolites in the rodent model. Significantly higher levels of sphingolipids and lecithins were detected in both surgical groups but not in the conservatively treated human and animal groups. RYGB leads to a characteristic metabolomic profile, which differs distinctly from that following non-surgical intervention. Analysis of the human and rat data revealed that RYGB induces specific changes in the metabolome independent of weight loss. KW - metabolomics KW - phosphatidylcholines KW - sphingolipids KW - branched-chain amino acids KW - obesity KW - Roux-en-Y Gastric Bypass KW - rodent model KW - insulin resistance Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-304462 SN - 1422-0067 VL - 24 IS - 3 ER - TY - JOUR A1 - Remde, Hanna A1 - Kranz, Stefanie A1 - Morell, Sarah Maria A1 - Altieri, Barbara A1 - Kroiss, Matthias A1 - Detomas, Mario A1 - Fassnacht, Martin A1 - Deutschbein, Timo T1 - Clinical course of patients with adrenal incidentalomas and cortisol autonomy BT - a German retrospective single center cohort study JF - Frontiers in Endocrinology N2 - 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). KW - adrenal imaging KW - adrenal tumours KW - autonomous cortisol secretion KW - cardiovascular events KW - cardiovascular risk factors KW - dexamethasone suppression test KW - morbidity KW - mortality Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-316793 SN - 1664-2392 VL - 14 ER - TY - JOUR A1 - Hendricks, Anne A1 - Müller, Sophie A1 - Fassnacht, Martin A1 - Germer, Christoph-Thomas A1 - Wiegering, Verena A. A1 - Wiegering, Armin A1 - Reibetanz, Joachim T1 - Impact of lymphadenectomy on the oncologic outcome of patients with adrenocortical carcinoma — a systematic review and meta-analysis JF - Cancers N2 - (1) Background: Locoregional lymphadenectomy (LND) in adrenocortical carcinoma (ACC) may impact oncological outcome, but the findings from individual studies are conflicting. The aim of this systematic review and meta-analysis was to determine the oncological value of LND in ACC by summarizing the available literature. (2) Methods: A systematic search on studies published until December 2020 was performed according to the PRISMA statement. The primary outcome was the impact of lymphadenectomy on overall survival (OS). Two separate meta-analyses were performed for studies including patients with localized ACC (stage I–III) and those including all tumor stages (I–IV). Secondary endpoints included postoperative mortality and length of hospital stay (LOS). (3) Results: 11 publications were identified for inclusion. All studies were retrospective studies, published between 2001–2020, and 5 were included in the meta-analysis. Three studies (N = 807 patients) reported the impact of LND on disease-specific survival in patients with stage I–III ACC and revealed a survival benefit of LND (hazard ratio (HR) = 0.42, 95% confidence interval (95% CI): 0.26–0.68). Based on results of studies including patients with ACC stage I–IV (2 studies, N = 3934 patients), LND was not associated with a survival benefit (HR = 1.00, 95% CI: 0.70–1.42). None of the included studies showed an association between LND and postoperative mortality or LOS. (4) Conclusion: Locoregional lymphadenectomy seems to offer an oncologic benefit in patients undergoing curative-intended surgery for localized ACC (stage I–III). KW - adrenocortical carcinoma KW - adrenal cancer KW - lymphadenectomy KW - lymph node dissection KW - LND KW - LNE KW - review KW - meta-analysis Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-254798 SN - 2072-6694 VL - 14 IS - 2 ER - TY - JOUR A1 - Uttinger, Konstantin L. A1 - Riedmeier, Maria A1 - Reibetanz, Joachim A1 - Meyer, Thomas A1 - Germer, Christoph Thomas A1 - Fassnacht, Martin A1 - Wiegering, Armin A1 - Wiegering, Verena T1 - Adrenalectomies in children and adolescents in Germany – a diagnose related groups based analysis from 2009-2017 JF - Frontiers in Endocrinology N2 - Background Adrenalectomies are rare procedures especially in childhood. So far, no large cohort study on this topic has been published with data on to age distribution, operative procedures, hospital volume and operative outcome. Methods This is a retrospective analysis of anonymized nationwide hospital billing data (DRG data, 2009-2017). All adrenal surgeries (defined by OPS codes) of patients between the age 0 and 21 years in Germany were included. Results A total of 523 patient records were identified. The mean age was 8.6 ± 7.7 years and 262 patients were female (50.1%). The majority of patients were between 0 and 5 years old (52% overall), while 11.1% were between 6 and 11 and 38.8% older than 12 years. The most common diagnoses were malignant neoplasms of the adrenal gland (56%, mostly neuroblastoma) with the majority being younger than 5 years. Benign neoplasms in the adrenal gland (D350) account for 29% of all cases with the majority of affected patients being 12 years or older. 15% were not defined regarding tumor behavior. Overall complication rate was 27% with a clear higher complication rate in resection for malignant neoplasia of the adrenal gland. Bleeding occurrence and transfusions are the main complications, followed by the necessary of relaparotomy. There was an uneven patient distribution between hospital tertiles (low volume, medium and high volume tertile). While 164 patients received surgery in 85 different “low volume” hospitals (0.2 cases per hospital per year), 205 patients received surgery in 8 different “high volume” hospitals (2.8 cases per hospital per year; p<0.001). Patients in high volume centers were significant younger, had more extended resections and more often malignant neoplasia. In multivariable analysis younger age, extended resections and open procedures were independent predictors for occurrence of postoperative complications. Conclusion Overall complication rate of adrenalectomies in the pediatric population in Germany is low, demonstrating good therapeutic quality. Our analysis revealed a very uneven distribution of patient volume among hospitals. KW - pediatric KW - neuroblastoma – diagnosis KW - therapy KW - adrenocortical adenocarcinoma KW - outcome KW - volume KW - adrenalectomia Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-282280 SN - 1664-2392 VL - 13 ER - TY - JOUR A1 - Reibetanz, Joachim A1 - Kelm, Matthias A1 - Uttinger, Konstantin L. A1 - Reuter, Miriam A1 - Schlegel, Nicolas A1 - Hankir, Mohamed A1 - Wiegering, Verena A1 - Germer, Christoph-Thomas A1 - Fassnacht, Martin A1 - Lock, Johan Friso A1 - Wiegering, Armin T1 - Differences in morbidity and mortality between unilateral adrenalectomy for adrenal Cushing’s syndrome and bilateral adrenalectomy for therapy refractory extra-adrenal Cushing’s syndrome JF - Langenbeck’s Archives of Surgery N2 - Purpose In selected cases of severe Cushing’s syndrome due to uncontrolled ACTH secretion, bilateral adrenalectomy appears unavoidable. Compared with unilateral adrenalectomy (for adrenal Cushing’s syndrome), bilateral adrenalectomy has a perceived higher perioperative morbidity. The aim of the current study was to compare both interventions in endogenous Cushing’s syndrome regarding postoperative outcomes. Methods We report a single-center, retrospective cohort study comparing patients with hypercortisolism undergoing bilateral vs. unilateral adrenalectomy during 2008–2021. Patients with adrenal Cushing’s syndrome due to adenoma were compared with patients with ACTH-dependent Cushing’s syndrome (Cushing’s disease and ectopic ACTH production) focusing on postoperative morbidity and mortality as well as long-term survival. Results Of 83 patients with adrenalectomy for hypercortisolism (65.1% female, median age 53 years), the indication for adrenalectomy was due to adrenal Cushing’s syndrome in 60 patients (72.2%; 59 unilateral and one bilateral), and due to hypercortisolism caused by Cushing’s disease (n = 16) or non-pituitary uncontrolled ACTH secretion of unknown origin (n = 7) (27.7% of all adrenalectomies). Compared with unilateral adrenalectomy (n = 59), patients with bilateral adrenalectomy (n = 24) had a higher rate of severe complications (0% vs. 33%; p < 0.001) and delayed recovery (median: 10.2% vs. 79.2%; p < 0.001). Using the MTL30 marker, patients with bilateral adrenalectomy fared worse than patients after unilateral surgery (MTL30 positive: 7.2% vs. 25.0% p < 0.001). Postoperative mortality was increased in patients with bilateral adrenalectomy (0% vs. 8.3%; p = 0.081). Conclusion While unilateral adrenalectomy for adrenal Cushing’s syndrome represents a safe and definitive therapeutic option, bilateral adrenalectomy to control ACTH-dependent extra-adrenal Cushing’s syndrome or Cushing’s disease is a more complicated intervention with a mortality of nearly 10%. KW - Cushing KW - adrenal surgery KW - MTL30 KW - complication Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-323947 VL - 407 IS - 6 ER - TY - JOUR A1 - Lenschow, Christina A1 - Wennmann, Andreas A1 - Hendricks, Anne A1 - Germer, Christoph-Thomas A1 - Fassnacht, Martin A1 - Buck, Andreas A1 - Werner, Rudolf A. A1 - Plassmeier, Lars A1 - Schlegel, Nicolas T1 - Questionable value of [\(^{99m}\)Tc]-sestamibi scintigraphy in patients with pHPT and negative ultrasound JF - Langenbeck’s Archives of Surgery N2 - Purpose A successful focused surgical approach in primary hyperparathyroidism (pHPT) relies on accurate preoperative localization of the parathyroid adenoma (PA). Most often, ultrasound is followed by [\(^{99m}\)Tc]-sestamibi scintigraphy, but the value of this approach is disputed. Here, we evaluated the diagnostic approach in patients with surgically treated pHPT in our center with the aim to further refine preoperative diagnostic procedures. Methods A single-center retrospective analysis of patients with pHPT from 01/2005 to 08/2021 was carried out followed by evaluation of the preoperative imaging modalities to localize PA. The localization of the PA had to be confirmed intraoperatively by the fresh frozen section and significant dropping of the intraoperative parathyroid hormone (PTH) levels. Results From 658 patients diagnosed with pHPT, 30 patients were excluded from the analysis because of surgery for recurrent or persistent disease. Median age of patients was 58.0 (13–93) years and 71% were female. Neck ultrasound was carried out in 91.7% and localized a PA in 76.6%. In 23.4% (135/576) of the patients, preoperative neck ultrasound did not detect a PA. In this group, [\(^{99m}\)Tc]-sestamibi correctly identified PA in only 25.4% of patients. In contrast, in the same cohort, the use of [\(^{11}\)C]-methionine or [\(^{11}\)C]-choline PET resulted in the correct identification of PA in 79.4% of patients (OR 13.23; 95% CI 5.24–33.56). Conclusion [\(^{11}\)C]-Methionine or [\(^{11}\)C]-choline PET/CT are superior second-line imaging methods to select patients for a focused surgical approach when previous ultrasound failed to identify PA. KW - primary hyperparathyroidism KW - parathyroid adenoma KW - [99mTc]-Sestamibi scan KW - [11C]-Methionine KW - [11C]-Choline PET/CT KW - focused surgical approach Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-323926 VL - 407 IS - 8 ER -