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  • 1
    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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  • 2
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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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  • 3
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    A Questionnaire Survey of German Thyroidologists on the Use of Thyroid Hormones in Hypothyroid and Euthyroid Patients: The THESIS (Treatment of Hypothyroidism in Europe by Specialists: An International Survey) Collaborative
    Georg Thieme Verlag KG ; 2022
    In:  Experimental and Clinical Endocrinology & Diabetes Vol. 130, No. 09 ( 2022-09), p. 577-586
    Details
    In: Experimental and Clinical Endocrinology & Diabetes, Georg Thieme Verlag KG, Vol. 130, No. 09 ( 2022-09), p. 577-586
    Abstract: Objective To identify the attitudes of German thyroid specialists towards the clinical treatment of hypothyroidism using thyroid hormones (TH). Methods All members of the thyroid section of the German Endocrine Society (DGE) were e-mailed an invitation to participate in a web-based survey about substitution with TH. Results Out of 206 members of the DGE’s thyroid section, 163 (79.1%) responses were received and included in the analysis. Of responding members, 98.6% used levothyroxine (LT4) as the treatment of choice, and 45.4% also prescribed combination therapy with liothyronine (LT4+LT3) in their clinical practice (p 〈 0.001). LT4+LT3 combination was favored in patients with persistent hypothyroidism symptoms despite biochemical euthyroidism on LT4 treatment (p 〈 0.001). Of all respondents, 26.4% never indicated TH therapy for euthyroid patients (p 〈 0.001), while the remainder would consider THs for one or more indications (62.9% for euthyroid infertile women with high anti-thyroid antibody levels (p 〈 0.001), 7.1% in patients with severe hypercholesterolemia, as complementary treatment (p=0.007), and 57.1% in patients with simple goiter (p 〈 0.001)). In conditions that could interfere with LT4 absorption, most respondents still preferred tablets and did not expect a significant difference when switching from one LT4 formulation to another. Conclusion For German thyroid specialists, LT4 is the treatment of choice for hypothyroidism. Combination therapy with LT4+LT3 was considered for patients with persistent symptoms. Even in conditions that could affect bioavailability, German thyroid specialists prefer LT4 tablets rather than other LT4 formulations, such as liquid or soft-gel capsules. The widespread use of thyroid hormone for non-hypothyroid conditions is not consistent with current evidence and needs further study.
    Type of Medium: Online Resource
    ISSN: 0947-7349 , 1439-3646
    URL: Article
    DOI: 10.1055/a-1832-0644
    RVK:
    XA 42403
    Language: English
    Publisher: Georg Thieme Verlag KG
    Publication Date: 2022
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  • 4
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    Analysis of risk factors and prognosis in differentiated thyroid cancer with focus on minimal extrathyroidal extension
    Springer Science and Business Media LLC ; 2021
    In:  BMC Endocrine Disorders Vol. 21, No. 1 ( 2021-12)
    Details
    In: BMC Endocrine Disorders, Springer Science and Business Media LLC, Vol. 21, No. 1 ( 2021-12)
    Abstract: In contrast to all prior AJCC/TNM classifications for differentiated thyroid cancer (DTC) the 8th edition does not take minimal extrathyroidal extension (M-ETE) into consideration for local tumor staging. We therefore aimed to retrospectively assess the specific impact of M-ETE on the outcome of M-ETE patients treated in our clinic. Methods DTC patients with M-ETE and a follow-up time of ≥ 5 years were included and matched with an identical number of patients without M-ETE, but with equal histopathological tumor subtype and size. The frequency of initially metastatic disease among groups was compared using Fisher’s exact test, the recurrence rate by virtue of log-rank test. Fisher’s exact test and multivariate analysis were used to account for the presence of confounding risk factors. Results One hundred sixty patients (80 matching pairs) were eligible. With other confounding risk factors being equal, the prevalence of N1-/M1-disease at initial diagnosis was comparable among groups (M-ETE: 42.5 %; no M-ETE: 32.5 %; p  = 0.25). No differences with regard to the recurrence rate were shown. However, M-ETE patients were treated with external beam radiation therapy more often (16.3 % vs. 1.3 %; p  = 0.004) and received higher median cumulative activities of 131 I (10.0 vs. 8.0 GBq; p   〈  0.001). Discussion Although having played a pivotal role for local tumor staging of DTC for decades M-ETE did not increase the risk for metastases at initial diagnosis and the recurrence rate in our cohort. Patients with M-ETE had undergone intensified treatment, which entails a possible confounding factor that warrants further investigation in randomized controlled trials.
    Type of Medium: Online Resource
    ISSN: 1472-6823
    URL: Article
    DOI: 10.1186/s12902-021-00826-2
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2091323-0
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  • 5
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    Therapeutic Effect of Combined Dabrafenib and Trametinib Treatment of BRAF V600E-Mutated Primary Squamous Cell Carcinoma of the Thyroid: A Case Report
    Bioscientifica ; 2021
    In:  European Thyroid Journal Vol. 10, No. 6 ( 2021), p. 511-516
    Details
    In: European Thyroid Journal, Bioscientifica, Vol. 10, No. 6 ( 2021), p. 511-516
    Abstract: 〈 b 〉 〈 i 〉 Introduction: 〈 /i 〉 〈 /b 〉 Primary squamous cell carcinoma (PSCC) of the thyroid is an exceptionally rare malignancy accounting for & #x3c;1% of all primary thyroid cancers. Therapy is multimodal including surgery, radiotherapy, and chemotherapy but with no consensus for management and therapy. Here, we describe a case of a male patient who presented with a BRAF V600E-mutated PSCC of the thyroid gland showing response to combined dabrafenib and trametinib therapy over a period of & #x3e;12 months. 〈 b 〉 〈 i 〉 Case Presentation: 〈 /i 〉 〈 /b 〉 A 78-year-old male patient presented with a 3-week history of dysphonia and dyspnoea. Laryngoscopy revealed a mechanical obstruction by a right-sided, subglottical mass, which on cervical ultrasound was highly suggestive of anaplastic thyroid carcinoma. Additional workup including esophagogastroduodenoscopy showed compression of the oesophagus but no oesophageal infiltration by the tumour. Immunohistochemistry displayed CK19-positive cells indicating epithelial origin of the tumour. CK5/6 and P40 immunohistochemistry confirmed the morphological impression of squamous cell differentiation while staining with thyroid markers TTF-1 and TPO was negative and PAX8 showed a nuclear positive signal. Based on immunohistopathology, presence of TP53 and BRAF V600E mutations, and exclusion of metastatic squamous cell carcinoma of other origin, the diagnosis of a PSCC of the thyroid was established. As an individualized treatment concept, we decided to advocate combined BRAF V600E targeting by the multikinase inhibitors dabrafenib and trametinib. This led to drastic improvement in patient’s quality of life without severe side effects over a period of & #x3e;12 months. 〈 b 〉 〈 i 〉 Conclusion: 〈 /i 〉 〈 /b 〉 In this case, molecular diagnosis allowed a highly individualized treatment concept with combined dabrafenib and trametinib therapy.
    Type of Medium: Online Resource
    ISSN: 2235-0640 , 2235-0802
    URL: Article
    DOI: 10.1159/000518055
    Language: English
    Publisher: Bioscientifica
    Publication Date: 2021
    detail.hit.zdb_id: 2659767-6
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  • 6
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    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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  • 7
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    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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  • 8
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    Continued Discontinuation of TKI Treatment in Medullary Thyroid Carcinoma – Lessons From Individual Cases With Long-Term Follow-Up
    Frontiers Media SA ; 2021
    In:  Frontiers in Endocrinology Vol. 12 ( 2021-9-29)
    Details
    In: Frontiers in Endocrinology, Frontiers Media SA, Vol. 12 ( 2021-9-29)
    Abstract: The tyrosine kinase inhibitors (TKI) vandetanib and cabozantinib are approved as targeted therapies in advanced medullary thyroid carcinoma (MTC) with symptoms or high tumour burden. Only recently, toxicity in long-time TKI usage was analysed. However, little is known about the impact of TKI discontinuation on MTC disease course after longer-term therapy. Here, we report our experience in a series of 7 MTC patients with vandetanib treatment of up to 87 months followed by discontinuation for concerns of toxicity or due to side-effects. The discontinuation of TKI therapy is a relevant clinical scenario. To our knowledge we present the largest single center series on an important aspect of TKI management. Methods Retrospective analysis of MTC patients with continued discontinuation of vandetanib treatment in a tertiary referral endocrine tumour centre. Analysis included a review of patients’ records for TKI indication, and treatment response as well indications for continued TKI discontinuation and follow-up by clinical assessment, calcitonin and CEA doubling times as well as imaging (ultrasound, CT). Results Seven MTC patients [6 sporadic MTC, 1 Multiple Endocrine Neplasie Type 2a (MEN2a)] with previous vandetanib treatment (median: 41 months; range 7-87 months) and continued TKI discontinuation were identified out of 161 analysed MTC files. TKI treatment was initiated due to high tumour burden and symptoms or RECIST (Response Evaluation Criteria In Solid Tumors) progression in all patients. Two patients (29%) remained stable after discontinuation of vandetanib until now (follow-up of 47 and 61 months). Both patients had been on TKI therapy for 73 and 58 months. Five patients (71%) developed progressive disease after TKI discontinuation. In 2 patients, vandetanib was restarted after 45 and 52 months resulting again in disease control. One patient was enrolled in a new RET kinase inhibitor trial after 45 months of vandetanib discontinuation. Two patients declined restart of treatment due to mental health issues leading to discontinuation of vandetanib in the first place (after 7 and 38 months of treatment) and both patients died of rapidly progressive disease. At time points of tumour progression, calcitonin-doubling time (CDT) was & lt; 2 years in all patients. Conclusion This case series suggests that discontinuation of long-term vandetanib treatment with documented stable disease does not automatically result in rapid disease progression but may be followed by prolonged “TKI free” stable disease in individual patients. Analysis of calcitonin and CDT during discontinuation is indicated as it will unmask tumour progression earlier than imaging. Restart with the same TKI is possible in case of progression.
    Type of Medium: Online Resource
    ISSN: 1664-2392
    URL: Article
    DOI: 10.3389/fendo.2021.718418
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2592084-4
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  • 9
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    Sporadic noninvasive medullary thyroid neoplasm: A desmoplasia-negative unifocal nonmetastatic tumor cured by hemithyroidectomy
    Elsevier BV ; 2023
    In:  Surgery Vol. 174, No. 6 ( 2023-12), p. 1356-1362
    Details
    In: Surgery, Elsevier BV, Vol. 174, No. 6 ( 2023-12), p. 1356-1362
    Type of Medium: Online Resource
    ISSN: 0039-6060
    URL: Article
    DOI: 10.1016/j.surg.2023.09.003
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2023
    detail.hit.zdb_id: 2018278-8
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