Risk of Lymphoma and Leukemia in Thyroid Cancer Patients: A Retrospective Cohort Study in Germany.

Thyroid cancer is the ninth most common cancer worldwide. While differentiated thyroid cancer (DTC) has a high survival rate, concerns arise regarding optimal treatment strategies and potential long-term risks, including second primary malignancies (SPMs), associated with therapies such as radioiodine (RAI). The aim of the present study was to investigate the association between thyroid cancer and the incidence of subsequent lymphoma and leukemia in Germany. This retrospective cohort study used the IQVIA TM Disease Analyzer database and included adults with a first documented diagnosis of thyroid cancer between January 2005 and December 2021 as well as propensity score matched individuals without thyroid cancer in 1284 general practices. Univariate Cox regression models were performed to examine the association between thyroid cancer and the incidence of subsequent lymphoma and leukemia. A total of 4232 thyroid cancer patients (mean age: 54.2 years; 73.6% female) and 21 160 controls (mean age: 54.2 years; 72.6% female) were available for analyses. Thyroid cancer was significantly associated with a higher lymphoma incidence (HR: 3.35, 95% CI: 2.04-5.52), especially in men (HR: 5.37) and those aged 61-70 years. Leukemia incidence was not significantly associated with thyroid cancer (HR: 1.79, 95% CI: 0.91-3.53), although associations were notable in younger age groups. Thyroid cancer is positively associated with a risk of subsequent lymphoma, highlighting the need for vigilant surveillance and tailored treatment strategies. While the association with leukemia is less pronounced, close surveillance remains critical, especially in younger patients.

Thyroglobulin Antibodies and Tumor Epitope-Specific Cellular Immunity in Papillary Thyroid Cancer.

Papillary thyroid carcinoma (PTC) is characterized by T cell infiltration and frequently by the presence of anti-thyroglobulin antibodies (TgAbs). The role of cellular immunity and of TbAbs in this context is a matter of debate. The aim of our study was to correlate the presence of TgAbs, tumor epitope-specific T cells and the clinical outcome of PTC patients. We studied n=183 consecutive patients with a diagnosis of PTC which were treated with total thyroidectomy plus 131I ablation. During a follow-up of in mean 97 months, most of the PTC patients had no signs of tumor relapse (n=157 patients). In contrast, one patient had serum Tg levels above the detection limit and<1 ng/ml, two patients Tg serum levels≥1 ng/ml and<2 ng/ml and n=23 patients had Tg serum levels≥2 ng/ml. Morphological signs of tumor recurrence were seen in 14 patients; all of these patients had serum Tg levels≥2 ng/ml. Importantly, with the exception of one patient, all TgAb positive PTC patients (n=27) had no signs of tumor recurrence as the serum Tg levels were below the assays functional sensitivities. Tetramer analyses revealed a higher number of tumor epitope-specific CD8+T cells in TgAb positive patients compared to TgAb negative PTC patients. In summary, we show that the occurrence of TgAbs may have an impact on the clinical outcome in PTC patients. This might be due to a tumor epitope-specific cellular immunity in PTC patients.

Chronic Fatigue and Dysautonomia following COVID-19 Vaccination Is Distinguished from Normal Vaccination Response by Altered Blood Markers.

SARS-CoV-2 mRNA vaccination can entail chronic fatigue/dysautonomia tentatively termed post-acute COVID-19 vaccination syndrome (PACVS). We explored receptor autoantibodies and interleukin-6 (IL-6) as somatic correlates of PACVS. Blood markers determined before and six months after first-time SARS-CoV-2 vaccination of healthy controls (N = 89; 71 females; mean/median age: 39/49 years) were compared with corresponding values of PACVS-affected persons (N = 191; 159 females; mean/median age: 40/39 years) exhibiting chronic fatigue/dysautonomia (≥three symptoms for ≥five months after the last SARS-CoV-2 mRNA vaccination) not due to SARS-CoV-2 infection and/or confounding diseases/medications. Normal vaccination response encompassed decreases in 11 receptor antibodies (by 25-50%, p < 0.0001), increases in two receptor antibodies (by 15-25%, p < 0.0001) and normal IL-6. In PACVS, serological vaccination-response appeared significantly (p < 0.0001) altered, allowing discrimination from normal post-vaccination state (sensitivity = 90%, p < 0.0001) by increased Angiotensin II type 1 receptor antibodies (cut-off ≤ 10.7 U/mL, ROC-AUC = 0.824 ± 0.027), decreased alpha-2B adrenergic receptor antibodies (cut-off ≥ 25.2 U/mL, ROC-AUC = 0.828 ± 0.025) and increased IL-6 (cut-off ≤ 2.3 pg/mL, ROC-AUC = 0.850 ± 0.022). PACVS is thus indicated as a somatic syndrome delineated/detectable by diagnostic blood markers.

The Role of Alternative Lymph Node Classification Systems in Gastroenteropancreatic Neuroendocrine Neoplasms (GEP-NEN): Superiority of a LODDS Scheme Over N Category in Pancreatic NEN (pNEN).

Lymph node (LN) involvement in gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN) has been reported to have prognostic and therapeutic implications. Numerous novel LN classifications exist; however, no comparison of their prognostic performance for GEP-NEN has been done yet. Using a nationwide cohort from the German Neuroendocrine Tumor (NET) Registry, the prognostic and discriminatory power of different LN ratio (LNR) and log odds of metastatic LN (LODDS) classifications were investigated using multivariate Cox regression and C-statistics in 671 patients with resected GEP-NEN. An increase in positive LN (pLN), LNR, and LODDS was associated with advanced tumor stages, distant metastases, and hormonal functionality. However, none of the alternative LN classifications studied showed discriminatory superiority in predicting prognosis over the currently used N category. Interestingly, in a subgroup analysis, one LODDS classification was identified that might be most appropriate for patients with pancreatic NEN (pNEN). On this basis, a nomogram was constructed to estimate the prognosis of pNEN patients after surgery. In conclusion, a more accurate classification of LN status may allow a more precise prediction of overall survival and provide the basis for individualized strategies for postoperative treatment and surveillance especially for patients with pNEN.

Effects of diesel exhaust particles on the health and survival of the buff-tailed bumblebee Bombus terrestris after acute and chronic oral exposure.

The diesel-powered transportation sector is a major producer of environmental pollution in the form of micro- and nanoscale diesel exhaust particles (DEP). Pollinators, such as wild bees, may inhale DEP or ingest it orally through plant nectar. However, if these insects are adversely affected by DEP is largely unknown. To investigate potential health threats of DEP to pollinators, we exposed individuals of Bombus terrestris to different concentrations of DEP. We analysed the polycyclic aromatic hydrocarbons (PAH) content of DEP since these are known to elicit adverse effects on invertebrates. We investigated the dose-dependent effects of those well-characterized DEP on survival and fat body content, as a proxy for the insects' health condition, in acute and chronic oral exposure experiments. Acute oral exposure to DEP showed no dose-dependent effects on survival or fat body content of B. terrestris. However, we could show dose-dependent effects after chronic oral exposure with high doses of DEP where significantly increased mortality was observed. Further, there was no dose-dependent effect of DEP on the fat body content after exposure. Our results give insights into how the accumulation of high concentrations of DEP e.g., near heavily trafficked sites, can influence insect pollinators' health and survival.

Contrast medium free selective adrenal vein sampling in the management of primary aldosteronism.

BACKGROUND: To analyze contrast free adrenal vein sampling (AVS) for differentiating unilateral from bilateral disease in patients diagnosed with hypertension due to primary aldosteronism (PA). METHODS: Consecutive patients with PA and subsequent contrast medium free AVS between April 2015 and March 2020 were retrospectively included. Cross-sectional imaging (CSI), AVS and clinical data were analyzed regarding diagnostic performance. In addition, patients with lateralisation receiving adrenalectomy were compared to a control group treated with mineralocorticoid antagonists. RESULTS: In total 186 patients with AVS were included. The success rate for bilateral catheterization was 88% (median effective dose 2.8 mSv). CSI had an accuracy of 60% (CI: 0.52-0.67) in the detection of lateralization compared to AVS. Patients with bilateral adrenal hyperplasia and those with aldosterone-producing adenoma did not differ in systolic blood pressure (sBP) (p = 0.63) or number of antihypertensive drugs (NAD) (p = 0.11). After adrenalectomy, 28 patients were cured (51%; sBP ≤130 mmHg, NAD = 0), 18 were improved (33%; decrease of sBP ≥20 mmHg and NAD), and 8 were unchanged (15%). Serum renin increased significantly after treatment (p < 0.01). CONCLUSION: Contrast medium free AVS is a reliable procedure in the diagnostic management of patients with PA with high technical success rate. The accordance between CSI and results from AVS was only moderate indicating the central role of AVS in the diagnostic work-up of patients with PA. Patients with predominant disease diagnosed with AVS had a high cure rate and/or significant improvement after adrenalectomy.

A Revised Version of the TNM Classification Leads to Optimized Predictive Performance in Patients with Adrenocortical Carcinoma.

The prognostic stratification of the current AJCC/UICC TNM classification for adrenocortical carcinoma (ACC) has been validated in only a few studies. In this study, it was hypothesized that redefining the T category cut-off would result in a significant improvement in estimated stage-related survival. In 935 patients with ACC from the SEER database, optimal cut-off values based on tumor size were first determined to redefine T1 and T2 categories. Cox proportional hazards regression analysis and receiver operating characteristics (ROC) were then used to determine the prognostic value of the revised version. A new cut-off value of 9.5 cm tumor size was established to differentiate between T1 and T2 tumors, leading to a revised TNM classification. As a result, a more homogeneous distribution of patients with ACC across all stages was observed. Notably, the predictive value of the newly proposed TNM classification in the ROC analysis exceeded that of the 7th and 8th editions of the AJCC/UICC classification system. Finally, the prognostic superiority of the revised TNM classification was confirmed in a multivariate Cox proportional hazards regression model. In conclusion, the present study demonstrates that updating the current staging system with revised T1 and T2 categories significantly improves the prediction of cancer-specific survival (CSS) in patients with ACC.

Novel ideas for the high luminosity phase of the LHC.

Without doubt, the High Luminosity Large Hadron Collider (HL-LHC) is one of the major projects in particle physics at the high energy frontier in the upcoming decades. Planned to come into operation mid-2027 it will substantially increase the amount of proton-proton collisions at 14 TeV delivered to the LHC experiments with a planned integrated luminosity of 3000 fb - 1 for both ATLAS and CMS experiments, 50 fb - 1 for LHCb, and 5 fb - 1 for ALICE. The delivery of Pb-Pb and p-Pb collisions with integrated luminosities of 13  nb - 1 and 50  nb - 1 is foreseen, yielding an increase by a factor of up to twenty compared to the currently available data of Run-1 and Run-2.

BRAFV600E and BRAF-WT Specific Antitumor Immunity in Papillary Thyroid Cancer.

One feature of papillary thyroid cancer (PTC) is the frequently present somatic BRAFV600E mutation. PTCs are also characterized by a lymphocytic infiltration, which may correlate with an improved clinical outcome. The objective of the study was the characterization of BRAFV600E specific anti-immunity in PTC patients and correlation analyses with the clinical outcome. Fourteen HLA A2 positive PTC patients were included into the study of whom tumor tissue samples were also available. Of those, 8 PTC patients revealed a somatic BRAFV600E mutation. All PTC patients were also MHC class II typed. Tetramer analyses for detection of MHC class I and MHC class II-restricted, BRAFV600E epitope-specific T cells using unstimulated and peptide-stimulated T cells were performed; correlation analyses between MHC phenotypes, T cell immunity, and the clinical course were performed. In regard to unstimulated T cells, a significantly higher amount of BRAFV600E epitope specific T cells was detected compared to a control tetramer. Importantly, after overnight peptide stimulation a significantly higher number of BRAFV600E positive and BRAF WT epitope-specific T cells could be seen. In regard to the clinical course, however, no significant differences were seen, neither in the context of the initial tumor size, nor in the context of lymph node metastases or peripheral metastastic spread. In conclusion, we clearly demonstrated a BRAF-specific tumor immunity in PTC-patients which is, however, independent of a BRAFV600E status of the PTC patients.

Treatment of RET-Positive Advanced Medullary Thyroid Cancer with Multi-Tyrosine Kinase Inhibitors-A Retrospective Multi-Center Registry Analysis.

BACKGROUND: RET (rearranged during transfection) variants are the most prevalent oncogenic events in medullary thyroid cancer (MTC). In advanced disease, multi-tyrosine kinase inhibitors (MKIs) cabozantinib and vandetanib are the approved standard treatment irrespective of RET status. The actual outcome of patients with RET-positive MTC treated with MKIs is ill described. METHODS: We here retrospectively determined the RET oncogene variant status with a targeted DNA Custom Panel in a prospectively collected cohort of 48 patients with advanced MTC treated with vandetanib and/or cabozantinib at four German referral centers. Progression-free survival (PFS) and overall survival (OS) probabilities were estimated using the Kaplan-Meier method. RESULTS: In total, 44/48 (92%) patients had germline or somatic RET variants. The M918T variant was found in 29/44 (66%) cases. In total, 2/32 (6%) patients with a somatic RET variant had further somatic variants, while in 1/32 (3%) patient with a germline RET variant, additional variants were found. Only 1/48 (2%) patient had a pathogenic HRAS variant, and no variants were found in 3 cases. In first-line treatment, the median OS was 53 (95% CI (95% confidence interval), 32-NR (not reached); n = 36), and the median PFS was 21 months (12-39; n = 33) in RET-positive MTC patients. In second-line treatment, the median OS was 18 (13-79; n = 22), and the median PFS was 3.5 months (2-14; n = 22) in RET-positive cases. CONCLUSIONS: RET variants were highly prevalent in patients with advanced MTC. The treatment results in RET-positive cases were similar to those reported in unselected cohorts.

Primary thyroid gland myxofibrosarcoma: a case report and review of the literature.

BACKGROUND: Myxofibrosarcoma is a common soft tissue sarcoma of the extremities, which occurs very rarely in the thyroid gland. CASE PRESENTATION: We report the case of a 61-year-old male who presented with a swelling of the left side of the neck and a newly emerged hoarseness. Ultrasound depicted a hypoechoic thyroid nodule with microcalcifications that was highly suspicious for malignancy. He underwent a left hemithyroidectomy. Histopathological examination and immunohistochemical studies revealed a myxofibrosarcoma of the thyroid gland. CONCLUSION: Myxofibrosarcoma of the thyroid gland is extremely rare. The diagnosis is based on histopathological features. Radical surgery achieving tumor-free resection margins remains the only chance for cure. However, the role of radiotherapy and/or chemotherapy is still under debate. Due to their high tendency for locoregional recurrence, a close follow-up after surgery is mandatory.

Beyond microplastics: Water soluble synthetic polymers exert sublethal adverse effects in the freshwater cladoceran Daphnia magna.

Plastic pollution is considered one of the causes of global change. However, water soluble synthetic polymers (WSSPs) have been neglected so far, although they are used in several industrial, dietary, domestic and biomedical products. Moreover, they are applied in wastewater treatment plants (WWTPs) as flocculants and coagulant agents. Hence, their presence in the aquatic environment as well as their uptake by aquatic organisms is probable, whereas no data are available regarding their potential adverse effects. Here we show in the freshwater key species D. magna exposed to five different WSSPs life history changes along with an altered level of reactive oxygen species, although acute mortality was not observed. Since daphnids act as keystone species in lake ecosystems by controlling phytoplankton biomass, even sublethal effects such as WSSPs induced changes in life history may result in cascading effects, from lower to higher trophic levels, which in turn could affect the whole food web.

In-depth characterization revealed polymer type and chemical content specific effects of microplastic on Dreissena bugensis.

In aquatic ecosystems, filter feeders like mussels are particularly vulnerable to microplastics (MP). However, little is known about how the polymer type and the associated properties (like additives or remaining monomers) of MP impact organisms, as the predominant type of MP used for effect studies on the organismic level are micron grade polystyrene spheres, without considering their chemical composition. Therefore, we exposed the freshwater mussel Dreissena bugensis (D. bugensis) to in-depth characterized fragments in the same concentration and size range (20-120 µm): recycled polyethylene terephthalate from drinking bottles, polyamide, polystyrene, polylactic acid, and mussel shell fragments as natural particle control. Real-time valvometry, used to study behavioral responses via the movement of the mussels' valves, showed that mussels cannot distinguish between natural and MP particles, and therefore do not cease their filtration, as when exposed to dissolved pollutants. This unintentional ingestion led to polymer type-dependent adverse effects (activity of antioxidant enzymes and proteomic alterations), related to chemicals and residual monomers found in MP. Overall, recycled PET elicited the strongest negative effects, likely caused by anthranilamide, anthranilonitrile and butylated hydroxytoluene, contained in the fragments, which are toxic to aquatic organisms. As PET is among the most abundant MP in the environment, sublethal effects may gradually manifest at the population level, leading to irreversible ecosystem changes.

Shape, size, and polymer dependent effects of microplastics on Daphnia magna.

The effects of microplastic (MP) pollution on organisms are gaining increasing attention. To date, a variety of polymers of different shapes and sizes are used in ecotoxicology. Although polystyrene (PS) is the predominant polymer type used in effect studies, it is still unclear whether the observed effects derive from the polymer itself or from a certain particle shape and size. To elucidate whether the effects are polymer specific, we conducted a systematic study on Daphnia magna by comparing various PS-MPs to nonplastic control particles with similar properties. In chronic exposure experiments, we used PS beads (6 µm; 20 µm), fibers (Ø 3 µm, length: 75.5 µm), and fragments (5.7 µm; 17.7 µm) in two different size classes and two different concentrations (500 and 5000 particles ml-1) and in-house-produced control particles of comparable size, shape, concentration and, if possible, density. Although most PS properties did not elicit effects on the tested endpoints, we observed sublethal effects on D. magna life history and morphology for small PS beads and fragments. Interestingly, no adverse effects were detected for any of the control particles. Hence, the observed effects are polymer-specific, related to the size and shape of the polymer, and do not result from particle exposure per se.

Prognostic Performance of Alternative Lymph Node Classification Systems for Patients with Medullary Thyroid Cancer: A Single Center Cohort Study.

BACKGROUND: Lymph node ratio (LNR) and the log odds of positive lymph nodes (LODDS) have been proposed as alternative lymph node (LN) classification schemes. Various cut-off values have been defined for each system, with the question of the most appropriate for patients with medullary thyroid cancer (MTC) still remaining open. We aimed to retrospectively compare the predictive impact of different LN classification systems and to define the most appropriate set of cut-off values regarding accurate evaluation of overall survival (OS) in patients with MTC. METHODS: 182 patients with MTC who were operated on between 1985 and 2018 were extracted from our medical database. Cox proportional hazards regression models and C-statistics were performed to assess the discriminative power of 28 LNR and 28 LODDS classifications and compare them with the N category according to the 8th edition of the AJCC/UICC TNM classification in terms of discriminative power. Regression models were adjusted for age, sex, T category, focality, and genetic predisposition. RESULTS: High LNR and LODDS are associated with advanced T categories, distant metastasis, sporadic disease, and male gender. In addition, among 56 alternative LN classifications, only one LNR and one LODDS classification were independently associated with OS, regardless of the presence of metastatic disease. The C-statistic demonstrated comparable results for all classification systems showing no clear superiority over the N category. CONCLUSION: Two distinct alternative LN classification systems demonstrated a better prognostic performance in MTC patients than the N category. However, larger scale studies are needed to further verify our findings.

[Graves' Disease]. / Morbus Basedow.

DIAGNOSIS: The diagnosis of Graves' disease is mainly based on ultrasonography and laboratory diagnostics. This includes the determination of the TSH value and the peripheral thyroid hormones. TSH receptor antibody (TRAb) measurement is highly sensitive and specific for the detection of Graves' disease (GD) and helps to distinguish from autoimmune thyroiditis (AIT). However, as recent studies show, some may AIT patients may also reveal TRAb. THERAPY: Current guidelines recommend primarily the use of thiamazol/carbimazole in GD. Due to the comparatively higher hepatotoxicity, propylthiouracil is not recommended as first line therapy. In case of relapse during 12 up to 18 months of antithyroid drug therapy or after a frustrating attempt at cessation, definitive therapy should be considered. Alternatively, in accordance with the current recommendations of the European Thyroid Association, drug therapy may be continued for up to 12 months after initial diagnosis. PREGNANCY: The treatment of active GD during pregnancy is problematic due to diaplacental crossing of peripheral thyroid hormones, TSH receptor stimulating antibodies and antithyroid drugs. According to current guidelines, PTU is recommended during the first 16 weeks of pregnancy, whereas for the 2nd and 3 rd trimester no special recommendations are given. After that, you can choose which antithyroid drug might be used. The aim of antithyroid drug therapy during pregnancy is to achieve a suppressed TSH value together with normal or slightly increased fT4 while using lowest effective dose of antithyroid drug. IMMUNE CHECKPOINT INHIBITORS (ICI): The most common endocrine side effect with this therapy is thyroid dysfunction. Hyperthyroidism; occur most frequently in combination therapy (CTLA-4 / anti-PD-1 therapy) ICI mainly causes destructive thyroiditis with lymphocytic infiltration; GD is absolutely rare in this context and only few cases are described.

FGF-Receptors and PD-L1 in Anaplastic and Poorly Differentiated Thyroid Cancer: Evaluation of the Preclinical Rationale.

Background: Treatment options for poorly differentiated (PDTC) and anaplastic (ATC) thyroid carcinoma are unsatisfactory and prognosis is generally poor. Lenvatinib (LEN), a multi-tyrosine kinase inhibitor targeting fibroblast growth factor receptors (FGFR) 1-4 is approved for advanced radioiodine refractory thyroid carcinoma, but response to single agent is poor in ATC. Recent reports of combining LEN with PD-1 inhibitor pembrolizumab (PEM) are promising. Materials and Methods: Primary ATC (n=93) and PDTC (n=47) tissue samples diagnosed 1997-2019 at five German tertiary care centers were assessed for PD-L1 expression by immunohistochemistry using Tumor Proportion Score (TPS). FGFR 1-4 mRNA was quantified in 31 ATC and 14 PDTC with RNAscope in-situ hybridization. Normal thyroid tissue (NT) and papillary thyroid carcinoma (PTC) served as controls. Disease specific survival (DSS) was the primary outcome variable. Results: PD-L1 TPS≥50% was observed in 42% of ATC and 26% of PDTC specimens. Mean PD-L1 expression was significantly higher in ATC (TPS 30%) than in PDTC (5%; p<0.01) and NT (0%, p<0.001). 53% of PDTC samples had PD-L1 expression ≤5%. FGFR mRNA expression was generally low in all samples but combined FGFR1-4 expression was significantly higher in PDTC and ATC compared to NT (each p<0.001). No impact of PD-L1 and FGFR 1-4 expression was observed on DSS. Conclusion: High tumoral expression of PD-L1 in a large proportion of ATCs and a subgroup of PDTCs provides a rationale for immune checkpoint inhibition. FGFR expression is low thyroid tumor cells. The clinically observed synergism of PEM with LEN may be caused by immune modulation.

Real-World Efficacy and Safety of Multi-Tyrosine Kinase Inhibitors in Radioiodine Refractory Thyroid Cancer.

Background: The management of patients with locally advanced or metastatic differentiated thyroid cancer (DTC) that is refractory to radioiodine (RAI) remains a therapeutic challenge. The multi-tyrosine kinase inhibitors (TKIs) sorafenib and lenvatinib have been approved based on phase 3 clinical trials. Patients and Methods: We aimed at describing the efficacy and safety of TKI treatment of RAI-refractory DTC in a real-world setting at six German referral centers. One hundred and one patients with locally advanced or metastatic RAI-refractory DTC treated with sorafenib, lenvatinib, and/or pazopanib were included. Progression-free survival (PFS) and overall survival (OS) probabilities were estimated by using the Kaplan-Meier method. Results: Ninety-seven of 101 patients had progressive disease before TKI initiation. The median PFS for first-line treatment with sorafenib (n = 33), lenvatinib (n = 53), and pazopanib (n = 15) was 9 (95% confidence interval 5.2-12.8), 12 (4.4-19.6), and 12 months (4.4-19.6), respectively. The median OS for first-line treatment was 37 (10-64) for sorafenib, 47 (15.5-78.5) for lenvatinib, and 34 months (20.2-47.8) for pazopanib. Serious complications (e.g., hemorrhage, acute coronary syndrome, and thrombosis/venous thromboembolism) occurred in 16 out of 75 (21%) patients taking lenvatinib, in 3 out of 42 (7%) patients taking sorafenib, and in 3 out of 24 (13%) patients taking pazopanib. Conclusions: Sorafenib, lenvatinib, and pazopanib are effective treatment options in the majority of patients with RAI-refractory DTC. The PFS and six-month survival rate in patients treated with lenvatinib und pazopanib appear to compare favorably with sorafenib in the first-line treatment setting. However, a more advanced disease stage at treatment initiation in sorafenib- and pazopanib-treated patients in the era before TKI-approval and the retrospective nature of this study precludes a direct comparison of TKIs.

DHEAS and Differential Blood Counts as Indirect Signs of Glucocorticoid Excess in Adrenal Non-Producing Adenomas.

The majority of incidentally discovered adrenal tumors are later characterized as non-producing adrenocortical adenomas (NPA). We asked whether laboratory abnormalities in parameters that reflect glucocorticoid action can be found in patients with NPA despite their nature of being clinically unapparent. Since glucocorticoids are potent immunosuppressants we studied blood counts and differential blood counts along with corticotropin and dehydroepiandrostenedione sulfate (DHEAS) blood concentrations, as well as cortisol values before and after an overnight 1 mg dexamethasone suppression test. We compared the results of normal individuals, of patients with adrenal adenomas and normal hormone profiles and with subclinical autonomous glucocorticoid hypersecretion, as well as overt cortisol excess. We found that almost all indices of the blood counts were significantly different between the patients groups. In particular, patients with adrenal non-producing adenomas already showed signs of glucocorticoid excess, including relative lymphocytopenia, lowered DHEAS, and ACTH concentrations than control individuals. We also found that the extent of lymphocytopenia correlated with the concentrations of DHEAS and ACTH, and DHEAS correlated well with ACTH. We conclude that the basal ACTH and DHEAS values along with the differential blood counts give good information on the extent of glucocorticoid excess and that silent adrenal adenomas seem to oversecrete glucocorticoids at concentrations that already alter these parameters.