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  • 1. Grodski, S
    et al.
    Stålberg, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Robinson, BG
    Delbridge, L
    Surgery versus radioiodine therapy as definitive management for Graves' disease: The role of patient preference2007In: Thyroid, ISSN 1050-7256, E-ISSN 1557-9077, Vol. 17, no 2, p. 157-160Article in journal (Refereed)
    Abstract [en]

    Background: Thyroidectomy is an option for the definitive management of Graves' disease. The aim of this study was to examine the role of patient preference for selecting surgery as definitive treatment. Patients and Methods: This is a retrospective cohort study comprising all patients (n = 63) presenting to a single surgeon for surgical management of Graves' disease over 3 years. Documented reasons for surgery were compared with accepted indications, as well as patients' perceptions as assessed by questionnaire. Results: The most frequent absolute indication was the presence of a large goiter (n = 8; 13%) or associated thyroid nodule (n = 6; 10%). Ophthalmopathy, a relative indication, comprised the largest single group overall (n = 18; 29%); however, a significant number of patients (n = 17; 27%) elected surgery in the absence of a recognized indication. There was strong concordance (73%) between the recorded indication and the patients' survey response. Overall, there was a high level of satisfaction with surgery with 88% of respondents giving a satisfaction score of 7 or greater on a visual analog scale (VAS) (0–10). Conclusions: One-third of all patients electing surgery as definitive management do so in the absence of a specific indication. Overall, there is a high level of satisfaction with the decision for surgery as definitive management of Graves' disease.

  • 2. Lee, Jia-Jing
    et al.
    Foukakis, Theodoros
    Hashemi, Jamileh
    Grimelius, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Heldin, Nils-Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Wallin, Göran
    Rudduck, Christina
    Lui, Weng-Onn
    Höög, Anders
    Larsson, Catharina
    Molecular cytogenetic profiles of novel and established human anaplastic thyroid carcinoma models2007In: Thyroid, ISSN 1050-7256, E-ISSN 1557-9077, Vol. 17, no 4, p. 289-301Article in journal (Refereed)
    Abstract [en]

    In this study we present two novel anaplastic thyroid carcinoma (ATC) lines (HTh 104 and HTh 112) and further characterize six frequently used ATC lines (HTh 7, HTh 74, HTh 83, C 643, KAT-4, and SW 1736). Three of the lines carried a heterozygous BRAF mutation V600E, which is in line with reports of BRAF mutations in primary ATC and papillary thyroid cancer. Several nonrandom breakpoints were identified by spectral karyotyping (SKY) and G-banding in these lines including the novel 1p36 and 17q24-25 as well as 3p21-22 and 15q26 that are also implicated in well-differentiated thyroid cancers. Comparative genomic hybridization showed frequent gain of 20q, including the UBCH10 gene in 20q13.12, which was further confirmed by array-comparative genomic hybridization and fluorescence in situ hybridization analyses. Our results concur with previous studies in both primary tumors and cell lines, indicating that gain of chromosome 20 is important in the pathogenesis of ATC and/or progression of differentiated thyroid cancers to ATC.

  • 3. Ludvigsson, Jonas F.
    et al.
    Lebwohl, Benjamin
    Kämpe, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Autoimmunity.
    Murray, Joseph A.
    Green, Peter H.
    Ekbom, Anders
    Risk of Thyroid Cancer in a Nationwide Cohort of Patients with Biopsy-Verified Celiac Disease2013In: Thyroid, ISSN 1050-7256, E-ISSN 1557-9077, Vol. 23, no 8, p. 971-976Article in journal (Refereed)
    Abstract [en]

    Background: In earlier studies based on selected populations, the relative risk for thyroid cancer in celiac disease has varied between 0.6 and 22.5. We aimed to test this relationship in a population-based setting. Methods: We collected small intestinal biopsy report data performed in 1969-2008 from all 28 Swedish pathology departments. 29,074 individuals with celiac disease (villous atrophy; Marsh histopathology stage III) were matched for sex, age, calendar year, and county to 144,440 reference individuals from the Swedish general population. Through Cox regression, we then estimated hazard ratios (HRs) and confidence intervals (CIs) for any thyroid cancer and papillary thyroid cancer (defined according to relevant pathology codes in the Swedish Cancer Register) in patients with celiac disease. Results: During follow-up, any thyroid cancer developed in seven patients with celiac disease (expected = 12) and papillary thyroid cancer developed in five patients (expected = 7). Celiac disease was not associated with an increased risk of any thyroid cancer (HR 0.6 [CI 0.3-1.3]) or of papillary thyroid cancer (HR 0.7 [CI 0.3-1.8]). All cases of thyroid cancer in celiac disease occurred in female patients. Risk estimates were similar before and after the year 2000 and independent of age at celiac diagnosis (<= 24 years vs. >= 25 years). Conclusions: We conclude that, in the Swedish population, there is no increased risk of thyroid cancer in patients with celiac disease. This differs from what has been reported in smaller studies in Italy and the United States.

  • 4.
    Roswall, Pernilla
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Bu, Shizhong
    Rubin, Kristofer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Landström, Maréne
    Ludwiginstitutet för Cancerforskning.
    Heldin, Nils-Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    2-methoxyestradiol induces apoptosis in cultured human anaplastic thyroid carcinoma cells2006In: Thyroid, ISSN 1050-7256, E-ISSN 1557-9077, Vol. 16, no 2, p. 143-50Article in journal (Refereed)
    Abstract [en]

    Anaplastic thyroid carcinoma (ATC) is one of the most malignant tumors in humans, and currently there is no effective treatment. In the present study we investigated the effect of an endogenous estrogen metabolite, 2-methoxyestradiol (2-ME), on the growth of human ATC cells. 2-ME treatment had a strong growth inhibitory effect on five human ATC cell lines (HTh7, HTh 74, HTh83, C643, and SW1736), but showed no effect on one cell line (KAT-4). Cell cycle analysis of the growth-inhibited cells showed that 2-ME induced a G2/M-arrest, followed by an increased fraction of cells in sub-G1. Analysis of internucleosomal DNA laddering as well as DNA fragmentation in a terminal deoxynucleotide transferase-mediated dUTP nick-end labeling (TUNEL) assay demonstrated a high number of cells undergoing apoptosis after 2-ME treatment. An increased activation of caspase-3 and caspase-8 by 2-ME was observed, and inhibition of caspase-3 decreased the apoptotic effect. Addition of 2-ME increased activity of p38 mitogen-activated protein kinase (MAPK) in the sensitive HTh7 as well as the refractory KAT-4 cells, however, activation of stress-activated protein kinase/c-jun aminoterminal kinase (SAPK/JNK) was seen only in the HTh7 cells. Inhibitors of p38 MAPK and SAPK/JNK significantly attenuated the 2-ME effect. Taken together, our data demonstrate an antiproliferative and apoptotic effect of 2-ME on ATC cells involving activation of MAPKs.

  • 5.
    Roy, Abhik
    et al.
    Columbia Univ Coll Phys & Surg, Dept Med, Celiac Dis Ctr, New York, NY USA..
    Laszkowska, Monika
    Columbia Univ Coll Phys & Surg, Dept Med, Celiac Dis Ctr, New York, NY USA..
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Lebwohl, Benjamin
    Columbia Univ Coll Phys & Surg, Dept Med, Celiac Dis Ctr, New York, NY USA..
    Green, Peter H. R.
    Columbia Univ Coll Phys & Surg, Dept Med, Celiac Dis Ctr, New York, NY USA..
    Kämpe, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Autoimmunity. Karolinska Inst, Karolinska Univ Hosp, Dept Med Solna, S-17177 Stockholm, Sweden..
    Ludvigsson, Jonas F.
    Columbia Univ Coll Phys & Surg, Dept Med, Celiac Dis Ctr, New York, NY USA.;Karolinska Inst, Karolinska Univ Hosp, Dept Med Epidemiol & Biostat, S-17177 Stockholm, Sweden.;Orebro Univ Hosp, Dept Paediat, Orebro, Sweden.;Univ Nottingham, Sch Med, Div Epidemiol & Publ Hlth, Nottingham, England..
    Prevalence of Celiac Disease in Patients with Autoimmune Thyroid Disease: A Meta-Analysis2016In: Thyroid, ISSN 1050-7256, E-ISSN 1557-9077, Vol. 26, no 7, p. 880-890Article in journal (Refereed)
    Abstract [en]

    Background: Several screening studies have indicated an increased prevalence of celiac disease (CD) among individuals with autoimmune thyroid disease (ATD), but estimates have varied substantially. Objective: The aim of this study was to examine the prevalence of CD in patients with ATD. Method: A systematic review was conducted of articles published in PubMed Medline or EMBASE until September 2015. Non-English papers with English-language abstracts were also included, as were research abstracts without full text available when relevant data were included in the abstract. Search terms included "celiac disease'' combined with "hypothyroidism'' or "hyperthyroidism'' or "thyroid disease.'' Fixed-effects inverse variance-weighted models were used. Meta-regression was used to examine heterogeneity in subgroups. Results: A pooled analysis, based on 6024 ATD patients, found a prevalence of biopsy-confirmed CD of 1.6% [ confidence interval (CI) 1.3-1.9%]. Heterogeneity was large (I-2 = 70.7%). The prevalence was higher in children with ATD (6.2% [ CI 4.0-8.4%]) than it was in adults (2.7%) or in studies examining both adults and children (1.0%). CD was also more prevalent in hyperthyroidism (2.6% [ CI 0.7-4.4%]) than it was in hypothyroidism (1.4% [ CI 1.0-1.9%]). Conclusions: About 1/62 patients with ATD have biopsy-verified CD. It is argued that patients with ATD should be screened for CD, given this increased prevalence.

  • 6.
    Simanainen, J.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Kinch, Amelie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Westermark, Kerstin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Winsa, Brita
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Bengtsson, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Schuppert, F.
    Westermark, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Heldin, N. E.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Analysis of mutations in exon 1 of the human thyrotropin receptor gene: high frequency of the D36H and P52T polymorphic variants1999In: Thyroid, ISSN 1050-7256, E-ISSN 1557-9077, Vol. 9, no 1, p. 7-11Article in journal (Refereed)
    Abstract [en]

    The aim of the present study was to investigate the N-terminal part (the translated part of exon 1) of the human thyrotropin receptor (TSHR) for the presence of mutations. Patients with Graves' disease (n = 160) and healthy controls (blood donors; n = 140) were screened using single-stranded conformational polymorphism (SSCP) in combination with restriction enzyme digestion for the two previously known mutations in this part of the receptor, viz. D36H and P52T TSHR-variants. We did not find any novel mutation in this region. However, D36H and P52T variants were found both in the TSHR of Graves' patients and in the healthy controls. The overall frequency of the D36H-receptor variant was 5.0% (15/300) and of the P52T-receptor, 7.3% (22/300). There was no major difference in the frequency for either of the TSHR alleles between the 2 groups. Thus, these 2 polymorphic variants of the TSHR seem to occur in a relatively high frequency in the population.

  • 7.
    Sjölin, Gabriel
    et al.
    Orebro Univ, Fac Med & Hlth, Dept Surg, SE-70185 Orebro, Sweden.
    Holmberg, Mats
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Gothenburg, Sweden;Karolinska Univ Hosp, ANOVA, Stockholm, Sweden.
    Törring, Ove
    Karolinska Inst, Inst Clin Sci & Educ, Stockholm, Sweden;Soder Sjukhuset, Dept Internal Med, Div Endocrinol, Stockholm, Sweden.
    Byström, Kristina
    Orebro Univ, Dept Med, Orebro, Sweden;Univ Hosp, Orebro, Sweden.
    Khamisi, Selwan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    de Laval, Dorota
    Blekinge Hosp, Dept Med, Karlskrona, Sweden.
    Abraham-Nordling, Mirna
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.
    Calissendorff, Jan
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden;Karolinska Univ Hosp, Dept Endocrinol Metab & Diabet, Stockholm, Sweden.
    Lantz, Mikael
    Skane Univ Hosp, Dept Endocrinol, Malmo, Sweden;Lund Univ, Dept Clin Sci, Lund, Sweden.
    Hallengren, Bengt
    Skane Univ Hosp, Dept Endocrinol, Malmo, Sweden;Lund Univ, Dept Clin Sci, Lund, Sweden.
    Filipsson Nyström, Helena
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Gothenburg, Sweden;Sahlgrens Univ Hosp, Dept Endocrinol, Gothenburg, Sweden.
    Wallin, Göran
    Orebro Univ, Fac Med & Hlth, Dept Surg, SE-70185 Orebro, Sweden;Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.
    The Long-Term Outcome of Treatment for Graves' Hyperthyroidism2019In: Thyroid, ISSN 1050-7256, E-ISSN 1557-9077, Vol. 29, no 11, p. 1545-1557Article in journal (Refereed)
    Abstract [en]

    Background: The treatment efficacy of antithyroid drug (ATD) therapy, radioactive iodine (I-131), or surgery for Graves' hyperthyroidism is well described. However, there are a few reports on the long-term total outcome of each treatment modality regarding how many require levothyroxine supplementation, the need of thyroid ablation, or the individual patient's estimation of their recovery. Methods: We conducted a pragmatic trial to determine the effectiveness and adverse outcome in a patient cohort newly diagnosed with Graves' hyperthyroidism between 2003 and 2005 (n = 2430). The patients were invited to participate in a longitudinal study spanning 8 +/- 0.9 years (mean +/- standard deviation) after diagnosis. We were able to follow 1186 (60%) patients who had been treated with ATD, I-131, or surgery. We determined the mode of treatment, remission rate, recurrence, quality of life, demographic data, comorbidities, and lifestyle factors through questionnaires and a review of the individual's medical history records. Results: At follow-up, the remission rate after first-line treatment choice with ATD was 45.3% (351/774), with I-131 therapy 81.5% (324/264), and with surgery 96.3% (52/54). Among those patients who had a second course of ATD, 29.4% achieved remission (vs. the 45.3% after the first course of ATD). The total number of patients who had undergone ablative treatment was 64.3% (763/1186), of whom 23% (278/1186) had received surgery, 43% (505/1186) had received I-131 therapy, including 2% (20/1186) who had received both surgery and I-131. Patients who received ATD as first-line treatment and possibly additional ATD had 49.7% risk (385/774) of having undergone ablative treatment at follow-up. Levothyroxine replacement was needed in 23% (81/351) of the initially ATD treated in remission, in 77.3% (204/264) of the I-131 treated, and in 96.2% (50/52) of the surgically treated patients. Taken together after 6-10 years, and all treatment considered, normal thyroid hormone status without thyroxine supplementation was only achieved in 35.7% (423/1186) of all patients and in only 40.3% of those initially treated with ATD. The proportion of patients that did not feel fully recovered at follow-up was 25.3%. Conclusion: A patient selecting ATD therapy as the initial approach in the treatment of Graves' hyperthyroidism should be informed that they have only a 50.3% chance of ultimately avoiding ablative treatment and only a 40% chance of eventually being euthyroid without thyroid medication. Surprisingly, 1 in 4 patients did not feel fully recovered after 6-10 years. The treatment for Graves' hyperthyroidism, thus, has unexpected long-term consequences for many patients.

  • 8.
    Törring, Ove
    et al.
    Karolinska Inst, Dept Clin Sci & Educ, Stockholm, Sweden; Söderdsjukhuset, Dept Internal Med, Div Endocrinol, Stockholm, Sweden.
    Watt, Torquil
    Rigshosp, Dept Med Endocrinol, Copenhagen, Denmark; Copenhagen Univ Hosp, Internal Med Herlev Gentofte Hosp, Copenhagen, Denmark.
    Sjölin, Gabriel
    Örebro Univ, Fac Med & Hlth, Dept Surg, Örebro, Sweden.
    Byström, Kristina
    Univ Hosp, Dept Med, Örebro, Sweden; Örebro Univ, Örebro, Sweden.
    Abraham-Nordling, Mirna
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.
    Calissendorff, Jan
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden; Karolinska Univ Hosp, Dept Endocrinol Metab & Diabet, Stockholm, Sweden.
    Cramon, Per Karkov
    Rigshosp, Dept Med Endocrinol, Copenhagen, Denmark; Copenhagen Univ Hosp, Internal Med Herlev Gentofte Hosp, Copenhagen, Denmark.
    Nystrom, Helena Filipsson
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Gothenburg, Sweden; Sahlgrens Univ Hosp, Dept Endocrinol, Gothenburg, Sweden.
    Hallengren, Bengt
    Skåne Univ Hosp, Dept Endocrinol, Malmö, Sweden; Lund Univ, Dept Clin Sci, Malmö, Sweden.
    Holmberg, Mats
    Karolinska Univ Hosp, ANOVA, Stockholm, Sweden; Univ Gothenburg, Sahlgrenska Acad, Inst Med, Gothenburg, Sweden.
    Khamisi, Selwan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism. Uppsala Univ, Inst Internal Med, Uppsala, Sweden.
    Lantz, Mikael
    Skåne Univ Hosp, Dept Endocrinol, Malmö, Sweden; Lund Univ, Dept Clin Sci, Malmö, Sweden.
    Wallin, Goran
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden; Örebro Univ, Fac Med & Hlth, Dept Surg, Örebro, Sweden.
    Impaired Quality of Life After Radioiodine Therapy Compared to Antithyroid Drugs or Surgical Treatment for Graves' Hyperthyroidism: A Long-Term Follow-Up with the Thyroid-Related Patient-Reported Outcome Questionnaire and 36-Item Short Form Health Status Survey2019In: Thyroid, ISSN 1050-7256, E-ISSN 1557-9077, Vol. 29, no 3, p. 322-331Article in journal (Refereed)
    Abstract [en]

    Background: Hyperthyroidism is known to have a significant impact on quality of life (QoL), at least in the short term. The purpose of the present study was to assess QoL in patients 6–10 years after treatment for Graves' disease (GD) with radioiodine (RAI) compared to those treated with thyroidectomy or antithyroid drugs (ATD) as assessed with both thyroid-specific Thyroid-Related Patient-Reported Outcome (ThyPRO) questionnaire and general (36-item Short Form Health Status) QoL survey.

    Methods: The study evaluated 1186 GD patients in a sub-cohort from an incidence study 2003–2005 who had been treated according to routine clinical practice at seven participating centers. Patients were included if they had returned the ThyPRO (n = 975) and/or the 36-item Short Form Health Status survey questionnaire (n = 964) and informed consent at follow-up. Scores from ThyPRO were compared to scores from a general population sample (n = 712) using multiple linear regression adjusting for age and sex as well as multiple testing. Treatment-related QoL outcome for ATD, RAI, and surgery were compared, including adjustment for the number of treatments received, sex, age, and comorbidity.

    Results: Regardless of treatment modality, patients with GD had worse thyroid-related QoL 6–10 years after diagnosis compared to the general population. Patients treated with RAI had worse thyroid-related and general QoL than patients treated with ATD or thyroidectomy on the majority of QoL scales. Sensitivity analyses supported the relative negative comparative effects of RAI treatment on QoL in patients with hyperthyroidism.

    Conclusions: GD is associated with a lower QoL many years after treatment compared to the general population. In a previous small randomized controlled trial, no difference was found in patient satisfaction years after ATD, RAI, or surgery. Now, it is reported that in a large non-randomized cohort, patients who received RAI had adverse scores on ThyPRO and 36-item Short Form Health Status survey. These findings in a Swedish population are limited by comparison to normative data from Denmark, older age, and possibly a more prolonged course in those patients who received RAI, and a lack of information regarding thyroid status at the time of evaluation. The way RAI may adversely affect QoL is unknown, but since the results may be important for future considerations regarding treatment options for GD, they need to be substantiated in further studies.

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