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  • 1
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    Online Resource
    TFF3 -Based Candidate Gene Discrimination of Benign and Malignant Thyroid Tumors in a Region with Borderline Iodine Deficiency
    The Endocrine Society ; 2008
    In:  The Journal of Clinical Endocrinology & Metabolism Vol. 93, No. 4 ( 2008-04-01), p. 1390-1393
    Details
    In: The Journal of Clinical Endocrinology & Metabolism, The Endocrine Society, Vol. 93, No. 4 ( 2008-04-01), p. 1390-1393
    Abstract: Background: With the advent of microarray technology, increasing numbers of marker genes are proposed to distinguish benign and malignant thyroid lesions. However, most markers await confirmation through independent studies. In this paper, we re-evaluate the diagnostic potential of 10 proposed candidate genes in benign and malignant thyroid pathologies in a region with borderline iodine deficiency. Methods: Quantitative real-time PCR was performed for CCND2, PLAB, PCSK2, HGD1, TFF3, B4GALT, LGALS3, ETS1, ADM3, and TG in 150 thyroid specimens, including 52 benign thyroid nodules (28 follicular adenoma and 24 adenomatous nodules), 52 corresponding normal thyroid tissues, 20 follicular carcinomas, 20 papillary carcinomas, and six undifferentiated carcinomas. Results: On a single-gene basis, significant differences in mRNA expression were found for TFF3, PLAB, and ADM3 in benign thyroid nodules and thyroid malignancy. Using two-marker gene sets, we identified 11 combinations, which allowed both a distinction of benign and malignant thyroid nodules and a discrimination of follicular adenoma and carcinoma. However, for cancer prediction, analysis of a minimum of six genes per sample was necessary and allowed correct prediction of a benign thyroid lesion and thyroid cancer with 94% accuracy in the most discriminative set (TFF3/PLAB/TG/ADM3/HGD1/LGALS3). Conclusion: We confirm the applicability of a number of recently proposed marker genes for the distinction of benign and malignant thyroid tumor and suggest that their diagnostic usefulness is independent of the iodide supply. We propose that the most discriminative marker set identified in our validation study together with marker combinations proposed by other investigators should now be evaluated in multicenter trials.
    Type of Medium: Online Resource
    ISSN: 0021-972X , 1945-7197
    URL: Article
    DOI: 10.1210/jc.2006-1255
    RVK:
    XA 10000
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2008
    detail.hit.zdb_id: 2026217-6
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  • 2
    Online Resource
    Online Resource
    Clinical presentation of MEN 2A in index vs. non-index patients
    Springer Science and Business Media LLC ; 2023
    In:  Endocrine Vol. 82, No. 2 ( 2023-07-21), p. 450-455
    Details
    In: Endocrine, Springer Science and Business Media LLC, Vol. 82, No. 2 ( 2023-07-21), p. 450-455
    Type of Medium: Online Resource
    ISSN: 1559-0100
    URL: Article
    DOI: 10.1007/s12020-023-03459-8
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2074043-8
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  • 3
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    Distinct Late-Night Salivary Cortisol Cut-Off Values for the Diagnosis of Hypercortisolism
    Georg Thieme Verlag KG ; 2021
    In:  Hormone and Metabolic Research Vol. 53, No. 10 ( 2021-10), p. 662-671
    Details
    In: Hormone and Metabolic Research, Georg Thieme Verlag KG, Vol. 53, No. 10 ( 2021-10), p. 662-671
    Abstract: Due to high morbidity and mortality of untreated hypercortisolism, a prompt diagnosis is essential. Measurement of late-night salivary cortisol provides a simple and non-invasive method. However, thresholds and reference ranges differ among studies. The goal of this study was to define a threshold of late-night salivary cortisol for the diagnosis of hypercortisolism based on the used assay. Moreover, the influence of different aetiologies of hypercortisolism and individual comorbidities were investigated. Prospective analyses of 217 patients, including 36 patients with proven hypercortisolism were carried out. A sum of 149 patients with suspicion of hypercortisolism but negative endocrine testing and 32 patients with hypercortisolism in remission served as control group. Late-night salivary cortisol was measured using an automated chemiluminescence immunoassay. Cut-off values were calculated by ROC analysis. The calculated cut-off value for the diagnosis of hypercortisolism was 10.1 nmol/l (sensitivity 94%; specificity 84%). Only slightly lower thresholds were obtained in patients with suspected hypercortisolism due to weight gain/obesity (9.1 nmol/l), hypertension or adrenal tumours (both 9.8 nmol/l) or pituitary adenomas (9.5 nmol/l). The late-night salivary cortisol threshold to distinguish between Cushing’s disease and Cushing’s disease in remission was 9.2 nmol/l. The cut-off value for the diagnosis of ectopic ACTH-production was 109.0 nmol/l (sensitivity 50%, specificity 92%). Late-night salivary cortisol is a convenient and reliable parameter for the diagnosis of hypercortisolism. Except for ectopic ACTH-production, thresholds considering different indications for evaluation of hypercortisolism were only slightly different. Therefore, they might only be useful if late-night salivary cortisol results near the established cut-off value are present.
    Type of Medium: Online Resource
    ISSN: 0018-5043 , 1439-4286
    URL: Article
    DOI: 10.1055/a-1608-1720
    RVK:
    XA 46918
    Language: English
    Publisher: Georg Thieme Verlag KG
    Publication Date: 2021
    detail.hit.zdb_id: 2056576-8
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  • 4
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    Predictive Factors for RAI-Refractory Disease and Short Overall Survival in PDTC
    MDPI AG ; 2021
    In:  Cancers Vol. 13, No. 7 ( 2021-04-06), p. 1728-
    Details
    In: Cancers, MDPI AG, Vol. 13, No. 7 ( 2021-04-06), p. 1728-
    Abstract: Background: The clinical phenotype of poorly differentiated thyroid cancer (PDTC) can vary substantially. We aim to evaluate risk factors for radioiodine refractory (RAI-R) disease and reduced overall survival (OS). Methods: We retrospectively screened our institutional database for PDTC patients. For the assessment of RAI-R disease, we included patients who underwent dual imaging with 18F-FDG-PET and 124I-PET/131I scintigraphy that met the internal standard of care. We tested primary size, extrathyroidal extension (ETE), and age 〉 55 years as risk factors for RAI-R disease at initial diagnosis and during the disease course using uni- and multivariate analyses. We tested metabolic tumor volume (MTV), total lesion glycolysis (TLG) on 18F-FDG-PET, and the progression of stimulated thyroglobulin within 4–6 months of initial radioiodine therapy as prognostic markers for OS. Results: Size of primary 〉 40 mm and ETE were significant predictors of RAI-R disease in the course of disease in univariate (81% vs. 27%, p = 0.001; 89% vs. 33%, p 〈 0.001) and multivariate analyses. Primary tumor size was an excellent predictor of RAI-R disease (AUC = 0.90). TLG/MTV 〉 upper quartile and early thyroglobulin progression were significantly associated with shorter median OS (29.0 months vs. 56.9 months, p 〈 0.05; 57.8 months vs. not reached p 〈 0.005, respectively). Discussion: PDTC patients, especially those with additional risk factors, should be assessed for RAI-R disease at initial diagnosis and in the course of disease, allowing for early implementation of multimodal treatment. Primary tumor size 〉 40 mm, ETE, and age 〉 55 are significant risk factors for RAI-R disease. High MTV/TLG is a significant risk factor for premature death and can help identify patients requiring intervention.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers13071728
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2527080-1
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  • 5
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    Online Resource
    Clonidine suppression test for a reliable diagnosis of pheochromocytoma: When to use
    Wiley ; 2022
    In:  Clinical Endocrinology Vol. 97, No. 5 ( 2022-11), p. 541-550
    Details
    In: Clinical Endocrinology, Wiley, Vol. 97, No. 5 ( 2022-11), p. 541-550
    Abstract: In clinical practice, false‐positive results in biochemical testing for suspected pheochromocytoma/paraganglioma (PPGL) are not infrequent and may lead to unnecessary examinations. We aimed to evaluate the role of the clonidine suppression test (CST) in the era of analyses of plasma‐free metanephrines for the diagnosis or exclusion of PPGL in patients with adrenal tumours and/or arterial hypertension. Design and Methods This single‐centre, prospective trial investigated the use of CST in 60 patients with suspected PPGL associated with out‐patient elevations of plasma normetanephrine (NMN) and/or metanephrine (MN), in most cases accompanied with hypertension or an adrenal mass. Measurements of plasma catecholamines and free metanephrines were performed by liquid chromatography with electrochemical detection and tandem mass spectrometry, respectively. Results Forty‐six patients entered final analysis ( n  = 20 with PPGL and n  = 26 with a nonfunctional adrenal mass and/or hypertension). CST reliably excluded false‐positive baseline NMN results with a specificity of 100%. The sensitivity of CST improved from 85% to 94% when tumours with isolated MN increase ( n  = 3) were not considered. In patients with elevated baseline NMN ( n  = 24), CST correctly identified all patients without PPGL. Patients with falsely elevated baseline NMN results ( n  = 7, 26.9%) exhibited increases of baseline NMN up to 1.7‐fold above the upper reference limit. Conclusion CST qualifies as a useful diagnostic tool for differential diagnosis of borderline elevated plasma‐free NMN in patients with suspected PPGL. In this context, CST helps to correctly identify all false‐positive NMN screening results.
    Type of Medium: Online Resource
    ISSN: 0300-0664 , 1365-2265
    URL: Issue
    URL: Article
    DOI: 10.1111/cen.v97.5
    DOI: 10.1111/cen.14724
    RVK:
    XA 10000
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 2004597-9
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  • 6
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    Online Resource
    Anaplastic thyroid cancer—Update 2019
    Springer Science and Business Media LLC ; 2019
    In:  Der Onkologe Vol. 25, No. 7 ( 2019-7), p. 569-572
    Details
    In: Der Onkologe, Springer Science and Business Media LLC, Vol. 25, No. 7 ( 2019-7), p. 569-572
    Type of Medium: Online Resource
    ISSN: 0947-8965 , 1433-0415
    URL: Article
    DOI: 10.1007/s00761-019-0592-3
    Language: German
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2019
    detail.hit.zdb_id: 3120761-3
    detail.hit.zdb_id: 1462966-5
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  • 7
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    The impact of CLAUDIN-1 on follicular thyroid carcinoma aggressiveness
    Bioscientifica ; 2015
    In:  Endocrine-Related Cancer Vol. 22, No. 5 ( 2015-07-28), p. 819-830
    Details
    In: Endocrine-Related Cancer, Bioscientifica, Vol. 22, No. 5 ( 2015-07-28), p. 819-830
    Abstract: CLAUDIN-1 belongs to the family of transmembrane tight junction proteins tightening the paracellular cleft of epithelial cells. In human malignancies, CLAUDIN-1 is often dysregulated and located in subcellular compartments, particularly in the nucleus where it may influence cellular behaviour. Here, we studied CLAUDIN-1 in relation to the biological characteristics of follicular thyroid carcinoma (FTC). CLAUDIN-1 immuno-staining showed loss of membrane expression and increased nuclear CLAUDIN-1 localization in FTC metastases. CLAUDIN-1 function was further investigated in two different follicular thyroid carcinoma cell lines: FTC-133 isolated from a regional lymph node metastasis and FTC-238 derived from a lung metastasis. In both cell lines CLAUDIN-1 expression was demonstrated in the cell nuclei with a significantly higher protein expression in FTC-238 compared to FTC-133 cells. Interestingly, in vitro scratch assay revealed enriched nuclear CLAUDIN-1 expression near the scratch. Furthermore, the increase of the pathogenic character of FTC-133 cells by RASV12 transfection was associated with elevated CLAUDIN-1 expression and enhanced cell migration, invasion and proliferation. Likewise over-expression of nuclear CLAUDIN-1 in FTC-133 cells resulted in increased cell migration and invasion. Conversely, CLAUDIN-1 downregulation in FTC-238 cells by siRNA resulted in decreased cell migration and invasion and was accompanied by reduced phosphoPKC expression. Moreover, activation and inhibition of PKC resulted in CLAUDIN-1 up- and downregulation in FTC cells respectively. These data suggest an impact of CLAUDIN-1 on follicular thyroid carcinoma aggressiveness, which could potentially be influenced by PKC activity.
    Type of Medium: Online Resource
    ISSN: 1351-0088 , 1479-6821
    URL: Article
    DOI: 10.1530/ERC-14-0502
    Language: Unknown
    Publisher: Bioscientifica
    Publication Date: 2015
    detail.hit.zdb_id: 2010895-3
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  • 8
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    Online Resource
    Anaplastic thyroid carcinoma: review of treatment protocols
    Bioscientifica ; 2018
    In:  Endocrine-Related Cancer Vol. 25, No. 3 ( 2018-03), p. R153-R161
    Details
    In: Endocrine-Related Cancer, Bioscientifica, Vol. 25, No. 3 ( 2018-03), p. R153-R161
    Abstract: Anaplastic thyroid carcinoma (ATC) is an orphan disease and in most patients fatal. So far no established treatment is available that prolongs survival. Several large retrospective studies have identified negative prognostic markers, analyzed efficacy of multimodal approaches such as radiotherapy with and without concurrent chemotherapy and chemotherapy protocols. Recently, single case reports have suggested some effectiveness of newer therapies targeting single somatic alterations in ATC. Overall, the conclusions that can be drawn from published retrospective studies and the scarce prospective approaches is that new treatment protocols should be developed including surgery, radiotherapy, chemotherapy and targeted therapy approaches and combinational therapy with immunotherapies. These protocols then need to be evaluated prospectively to improve ATC patients’ outcome in routine care.
    Type of Medium: Online Resource
    ISSN: 1351-0088 , 1479-6821
    URL: Article
    DOI: 10.1530/ERC-17-0435
    Language: Unknown
    Publisher: Bioscientifica
    Publication Date: 2018
    detail.hit.zdb_id: 2010895-3
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  • 9
    Online Resource
    Online Resource
    The Changing Face of Multiple Endocrine Neoplasia 2A: From Symptom-Based to Preventative Medicine
    The Endocrine Society ; 2023
    In:  The Journal of Clinical Endocrinology & Metabolism Vol. 108, No. 9 ( 2023-08-18), p. e734-e742
    Details
    In: The Journal of Clinical Endocrinology & Metabolism, The Endocrine Society, Vol. 108, No. 9 ( 2023-08-18), p. e734-e742
    Abstract: Early genetic association studies yielded too high risk estimates for multiple endocrine neoplasia (MEN2A), suggesting a need for extended surgery. Objective The objective was to delineate temporal changes in MEN2A presentation by birth cohort analyses. Methods Birth cohort analyses (10-year increments; ≤1950 to 2011-2020) of carriers of rearranged during transfection (RET) mutations who underwent surgery for MEN2A. Results Included in this study were 604 carriers (155 index, 445 nonindex, 4 additional patients), with 237 carriers harboring high-risk mutations, 165 carriers moderate–high risk mutations, and 202 carriers low–moderate risk mutations. With increasing recency of birth cohorts, there was a continual decline in index patients from 41-74% to 0% (P & lt; .001) and of medullary thyroid cancer (MTC) from 96-100% to 0-33% (P & lt; .001). Node metastases diminished from 62-70% to 0% (P ≤ .001; high and low–moderate risk mutations), whereas biochemical cure after thyroidectomy surged from 17-33% to 100% (P ≤ .019; high and low–moderate mutations). Surgical interventions for MEN2A-related tumors were performed increasingly earlier, causing median carrier age to fall: from 51-63 to 3-5 years at thyroidectomy (P & lt; .001); from 46-51 to 24-25 years at first adrenalectomy (P ≤ .013; high and moderate–high risk mutations); and from 43.5-66 to 16.5-32 years at parathyroidectomy. MTC diameters were more effectively decreased from 14-32 to 1-4 mm (P ≤ 002) than pheochromocytoma diameters (nonsignificant). Conclusion These insights into MEN2A presentation, adjusted by birth year, illustrate the shift from reactive to preventative medicine, enabling less extensive risk-reducing surgery.
    Type of Medium: Online Resource
    ISSN: 0021-972X , 1945-7197
    URL: Article
    DOI: 10.1210/clinem/dgad156
    RVK:
    XA 10000
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2023
    detail.hit.zdb_id: 2026217-6
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  • 10
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    Online Resource
    Enhancing Radioiodine Incorporation into Radioiodine-Refractory Thyroid Cancer with MAPK Inhibition (ERRITI): A Single-Center Prospective Two-Arm Study
    American Association for Cancer Research (AACR) ; 2022
    In:  Clinical Cancer Research Vol. 28, No. 19 ( 2022-10-03), p. 4194-4202
    Details
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 28, No. 19 ( 2022-10-03), p. 4194-4202
    Abstract: Restoration of iodine incorporation (redifferentiation) by MAPK inhibition was achieved in previously radioiodine-refractory, unresectable thyroid carcinoma (RR-TC). However, results were unsatisfactory in BRAFV600E-mutant (BRAF-MUT) RR-TC. Here we assess safety and efficacy of redifferentiation therapy through genotype-guided MAPK-modulation in patients with BRAF-MUT or wildtype (BRAF-WT) RR-TC. Patients and Methods: In this prospective single-center, two-arm phase II study, patients received trametinib (BRAF-WT) or trametinib + dabrafenib (BRAF-MUT) for 21 ± 3 days. Redifferentiation was assessed by 123I-scintigraphy. In case of restored radioiodine uptake, 124I-guided 131I therapy was performed. Primary endpoint was the redifferentiation rate. Secondary endpoints were treatment response (thyroglobulin, RECIST 1.1) and safety. Parameters predicting successful redifferentiation were assessed using a receiver operating characteristic analysis and Youden J statistic. Results: Redifferentiation was achieved in 7 of 20 (35%) patients, 2 of 6 (33%) in the BRAF-MUT and 5 of 14 (36%) in the BRAF-WT arm. Patients received a mean (range) activity of 300.0 (273.0–421.6) mCi for 131I therapy. Any thyroglobulin decline was seen in 57% (4/7) of the patients, RECIST 1.1 stable/partial response/progressive disease in 71% (5/7)/14% (1/7)/14% (1/7). Peak standardized uptake value (SUVpeak) & lt; 10 on 2[18F]fluoro-2-deoxy-D-glucose (FDG)-PET was associated with successful redifferentiation (P = 0.01). Transient pyrexia (grade 3) and rash (grade 4) were noted in one patient each. Conclusions: Genotype-guided MAPK inhibition was safe and resulted in successful redifferentiation in about one third of patients in each arm. Subsequent 131I therapy led to a thyroglobulin (Tg) decline in more than half of the treated patients. Low tumor glycolytic rate as assessed by FDG-PET is predictive of redifferentiation success. See related commentary by Cabanillas et al., p. 4164
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    URL: Article
    DOI: 10.1158/1078-0432.CCR-22-0437
    RVK:
    XA 36791
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2022
    detail.hit.zdb_id: 1225457-5
    detail.hit.zdb_id: 2036787-9
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