| 1. |
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| 2. |
- Al-Majdoub, Mahmoud, et al.
(författare)
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Treatment of Swedish Patients with Graves' Hyperthyroidism Is Associated with Changes in Acylcarnitine Levels
- 2017
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Ingår i: Thyroid : official journal of the American Thyroid Association. - : Mary Ann Liebert Inc. - 1557-9077. ; 27:9, s. 1109-1117
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Hyperthyroidism is associated with alterations in metabolism that are currently only partially understood. The objective of the study was to investigate changes in metabolism associated with reinstatement of euthyroidism in Swedish patients.METHODS: Eighty metabolites in plasma were profiled from 10 subjects with Graves' disease (GD) at baseline and after 9 and 15 months of treatment to reinstate euthyroidism. Thyroid parameters, thyrotropin (TSH), TSH receptor antibodies, free triiodothyronine, and free thyroxine were followed. Main findings were validated in plasma from 20 subjects with GD at baseline and at three, six, and nine months. The study was conducted at the endocrinology clinic in Malmö, Sweden.RESULTS: Euthyroidism was reinstated at three months, and thyroid status did not change further during the 15-month follow-up. This was paralleled by altered levels of 9/19 detected acylcarnitines (p < 0.05 after adjustment for multiple testing). Levels of short-chain acylcarnitines were decreased, intermediate-chain acylcarnitines elevated, and long-chain acylcarnitines unaltered.CONCLUSIONS: GD and treatment of the disease is associated with pronounced acyl chain length-dependent alterations in acylcarnitine levels. These changes may be impacted by ethnicity and or dietary differences.
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| 3. |
- Berg, Gertrud, 1944, et al.
(författare)
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Development of severe thyroid-associated ophthalmopathy in a patient with disseminated thyroid cancer treated with recombinant human thyrotropin/radioiodine and retinoic acid.
- 2005
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Ingår i: Thyroid : official journal of the American Thyroid Association. - : Mary Ann Liebert Inc. - 1050-7256. ; 15:12, s. 1389-94
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Tidskriftsartikel (refereegranskat)abstract
- We present a case in which a patient with disseminated well-differentiated papillary thyroid cancer developed severe thyroid-associated ophthalmopathy. Eight years after initial surgery and ablative radioiodine therapy the patient was found to have multiple pulmonary metastases. The metastases showed poor uptake of radioiodine. An attempt was made to use 13-cis-retinoic acid in order to achieve a redifferentiation of the thyroid cancer cells before recombinant human thyrotropin (rhTSH) stimulated radioiodine therapy. The treatment did not improve the uptake of radioiodine. However, approximately 2 weeks after completion of the treatment the patient experienced discomfort in her eyes and then over the next months she developed a severe ophthalmopathy. The analyses of TSH receptor antibodies and S-thyroglobulin simultaneously showed a pronounced increase. An association between therapy given and severe ophthalmopathy cannot be excluded.
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| 4. |
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| 5. |
- Bullock, Martyn, et al.
(författare)
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ETS Factor ETV5 Activates the Mutant Telomerase Reverse Transcriptase Promoter in Thyroid Cancer
- 2019
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Ingår i: Thyroid. - : MARY ANN LIEBERT, INC. - 1050-7256 .- 1557-9077. ; 29:11, s. 1623-1633
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Tidskriftsartikel (refereegranskat)abstract
- Background: Co-occurrence of TERT (telomerase reverse transcriptase) promoter (TERTp) mutations with BRAF/RAS mutations is associated with significantly more aggressive thyroid cancer. TERTp mutations are hypothesized to generate de novo binding sites for ETS transcription factors, which are themselves activated by BRAF/RAS-stimulated MEK-ERK activity. To date, a detailed study of this mechanism has been limited to only a few cancer types, and we hypothesized that ETS factors involved in TERTp activation could vary between different cancers. Methodology: Here we sought to identify ETS factor(s) required for TERTp activation in thyroid cancer, using a combination of in silico analyses of TCGA data, and experimentation using in vitro thyroid cell models analyzed by quantitative reverse transcription-PCR, immunoprecipitation (IP), chromatin IP, and gene reporter assays. Results: We found that ETV5 was abundantly expressed in papillary thyroid cancers from the TCGA data set, and in thyroid cancer cell line models. Furthermore, ETV5 was found to preferentially bind to the -124 bp(T) TERTp allele and stimulate TERT transcription in thyroid cancer cells devoid of GA binding protein transcription factor (GABP) activity. We also found that ETV5 functionally cooperates with the transcription factor FOXE1 to further enhance TERTp activity, a mechanism that may at least partially explain why FOXE1 represents a significant genetic determinant of thyroid cancer risk. Conclusions: ETS factors that activate mutant TERTp vary between cancer types, and here we show for the first time that ETV5 demonstrates mutant allele-specific affinity for TERTp in thyroid cancer, a property that has previously only been attributable to GABP.
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| 6. |
- Catrina, SB, et al.
(författare)
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A visible cause of hyperthyroidism
- 2004
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Ingår i: Thyroid : official journal of the American Thyroid Association. - : Mary Ann Liebert Inc. - 1050-7256. ; 14:10, s. 866-866
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Tidskriftsartikel (refereegranskat)
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| 7. |
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| 8. |
- Eriksson, Janna, 1992, et al.
(författare)
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The effects of iron and selenium in iodine containing multivitamins on thyroid related compounds during pregnancy in Sweden: a randomized placebo cotrolled trial
- 2017
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Ingår i: 87th Annual Meeting of the American Thyroid Association. Thyroid, 27(S1), poster 71. - : Mary Ann Liebert Inc. - 1050-7256 .- 1557-9077.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Multivitamins with iodine are advocated to pregnant women to avoid iodine deficiency, as iodine may be beneficial for brain development in the child. Multivitamins also contain iron and selenium that may affect thyroid hormone metabolism. Iron is included in the tyreoperoxidase enzyme promoting the coupling of iodine to thyroglobulin (Tg) and selenium is incorporated in deiodinases that regulates levels of thyroxine (T4) and triiodothyronine (T3). There is no previous studies on the effects of iodine containing multivitamins on iron and selenium levels in pregnant women and the relation to thyroid hormone levels. This was a randomized, double-blinded controlled trial of 200 pregnant women, who were randomized to multivitamins containing 150 lg iodine, 12 mg iron and 50 lg selenium/day or multivitamins without iodine, iron and selenium in pregnancy week 7–12 until delivery, besides iron supplements on usual routines. Thyroid hormones, Tg, selenium (ref 0.7– 1.2 lmol/L) and iron measurements (ferritin (ref 15–150 mg/L), transferrin saturation (ref 0.1–0.5)) were collected in the third trimester. Urinary iodine concentration confirmed mild ID in the control group with a Tg increase. In the third trimester, 139 patients were left for sampling. In the active group (n = 67) median (interquartile range (IQR)) selenium levels were 0.72 (0.16) vs 0.61 (0.14) in the control group (n = 72), p < 0.001. Low selenium values were noted in 70.0% of participants and it was more common in the control group (81.9%), p < 0.001. Median (IQR) Tg levels was higher in those with low selenium 30.0 (30.5) than in those with normal selenium 20.5 (21.5), p = 0.037. Thyroid hormones did not differ between active/control groups or low/normal selenium groups, but FT3/FT4 ratio was higher in the low selenium group than in the normal selenium group (0.35 (0.08) vs 0.33 (0.08)), p= 0.025. Ferritin in the active group was 22.0 (21.0) and 20.0 (21.5) in the control group, p = 0.393 and transferrin saturation 0.20 (0.11) and 0.18 (0.18), p = 0.802, respectively. Multivitamins used during pregnancy to increase iodine levels also increase selenium levels where effects on thyroid metabolism needs further evaluation.
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| 9. |
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| 10. |
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| 11. |
- Forrest, D, et al.
(författare)
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Functions of thyroid hormone receptors in mice
- 2000
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Ingår i: Thyroid : official journal of the American Thyroid Association. - : Mary Ann Liebert Inc. - 1050-7256. ; 10:1, s. 41-52
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Tidskriftsartikel (refereegranskat)
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| 12. |
- Giesecke, Peter, et al.
(författare)
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Increased Cardiovascular Mortality and Morbidity in Patients Treated for Toxic Nodular Goiter Compared to Graves' Disease and Nontoxic Goiter
- 2017
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Ingår i: Thyroid. - : Mary Ann Liebert. - 1050-7256 .- 1557-9077. ; 27:7, s. 878-885
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Previous research has suggested an increased risk of death and cardiovascular disease in patients treated for hyperthyroidism. However, studies on this subject are heterogeneous, often based on old data, or have not considered the impact that treatment for hyperthyroidism might have on cardiovascular risk. It is also unclear whether long-term prognosis differs between Graves' disease and toxic nodular goiter. The aim of this study was to use a very large cohort built on recent data to assess whether improvements in cardiovascular care might have changed the prognosis over time. The study also investigated the impact of different etiologies of hyperthyroidism.METHODS: This was an observational register study for the period 1976-2012, with subjects followed for a median period of 18.4 years. Study patients were Stockholm residents treated for Graves' disease or toxic nodular goiter with either radioactive iodine or surgery (N = 12,239). This group was compared to Stockholm residents treated for nontoxic goiter (N = 3685), with adjustments made for age, sex, comorbidities, and time of treatment. Comparisons were also made to the general population of Stockholm. Outcomes were assessed in terms of all-cause and cardiovascular mortality as well as cardiovascular morbidity.RESULTS: The hazard ratios (HR) for all-cause mortality and for cardiovascular mortality were 1.27 [confidence interval (CI) 1.20-1.35] and 1.29 [CI 1.17-1.42], respectively, for hyperthyroid patients compared to those with nontoxic goiter. For cardiovascular morbidity, the HR was 1.12 [CI 1.06-1.18]. Patients aged ≥45 years who were treated for toxic nodular goiter were generally at greater risk than others, and those included from the year 1990 and onwards were at greater risk than those included earlier. Increased all-cause mortality, as well as cardiovascular mortality and morbidity, were also seen in comparisons with the general population.CONCLUSIONS: This is the first large study to indicate that the long-term risk of death and cardiovascular disease in hyperthyroid subjects is due to the hyperthyroidism itself and not an effect of confounding introduced by its treatment. Much of the excess risk is confined to individuals treated for toxic nodular goiter. Despite advances in cardiovascular care during recent decades, hyperthyroidism is still a diagnosis associated with increased cardiovascular morbidity and mortality.
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| 13. |
- Grodski, S, et al.
(författare)
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Surgery versus radioiodine therapy as definitive management for Graves' disease: The role of patient preference
- 2007
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Ingår i: Thyroid. - : Mary Ann Liebert Inc. - 1050-7256 .- 1557-9077. ; 17:2, s. 157-160
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 14. |
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| 15. |
- Hallengren, Bengt, et al.
(författare)
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Pregnant Women on Thyroxine Substitution Are Often Dysregulated in Early Pregnancy.
- 2009
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Ingår i: Thyroid. - : Mary Ann Liebert Inc. - 1557-9077 .- 1050-7256. ; 19, s. 391-394
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Tidskriftsartikel (refereegranskat)abstract
- Background: Thyroid hormones are important for normal fetal development. Maternal hypothyroidism during early pregnancy is associated with impaired neuropsychological development of children and other adverse outcomes. The primary aim of this prospective study was to determine whether thyroxine-treated pregnant women with hypothyroidism are adequately thyroxine substituted in early pregnancy. A secondary aim was to determine if fetal loss differed between females with thyrotropin (TSH) values within and outside the reference range at their first TSH test, scheduled for 1-2 weeks after verification of pregnancy. Methods: This was a prospective open-labeled study. During the years 1997-2002, 119 consecutive pregnancies in 101 females with thyroid diseases were followed at the Department of Endocrinology, Malmö University Hospital. At the first visit, 63 patients, median age 30 years (range 17-45 years), were on thyroxine substitution therapy for hypothyroidism. In these patients 83% were in their first trimester at the time of the initial test. Results: Of the 63 patients on thyroxine substitution for hypothyroidism 32 (51%; Group A) patients had serum TSH values within the reference range at their initial test and 31 (49%; Group B) had serum TSH values outside the reference range. Twelve (19%) had TSH values of <0.40 mIU/L and 19 (30%) had TSH values of >4.0 mIU/l. The fetal loss was 2 of 32 (6%) in Group A compared to 9 of 31 (29%) in Group B (p < 0.05). Conclusions: In 49% of pregnant women on thyroxine substitution, serum TSH values were outside the reference range when first tested, generally in the first trimester. Fetal loss was significantly greater in pregnant women with abnormal TSH values compared to those with normal TSH values. Thyroid function in pregnant women on thyroxine substitution should be monitored early in pregnancy and carefully followed during pregnancy. The thyroxine dose should be increased as needed early in pregnancy to avoid hypothyroidism.
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| 16. |
- Hansson, Marie, 1979, et al.
(författare)
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Iodine content and distribution in extratumoral and tumor thyroid tissue analyzed with X-ray fluorescence and time-of-flight secondary ion mass spectrometry.
- 2008
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Ingår i: Thyroid : official journal of the American Thyroid Association. - : Mary Ann Liebert Inc. - 1557-9077. ; 18:11, s. 1215-20
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The thyroid's ability to enrich and store iodine has implications for thyroid cancer genesis, progression, and treatment. The study objective was to investigate thyroid iodine content (TIC) in tumoral and extratumoral tissue in patients with papillary thyroid cancer (PTC) as opposed to thyroid healthy controls using two different techniques: X-ray fluorescence (XRF) and time-of-flight secondary ion mass spectrometry (TOF-SIMS). METHODS: Tissue samples from 10 patients with normal thyroids and 7 patients with PTC were collected. TIC was quantified with XRF, and the iodine stores were located on a histological level with TOF-SIMS. RESULTS: Mean TIC in controls was 0.6 mg/mL (range 0.3-1.2 mg/mL). For the cancer patients, the mean TIC was 0.8 mg/mL (range 0.2-2.3 mg/mL) in extratumoral thyroid tissue, but no iodine was detected in the tumors. TOF-SIMS investigation of the PTC patients showed significantly higher TIC in extratumoral tissue than in tumoral tissue. Iodine in the extratumoral tissue was predominantly located in the follicle lumen with a variation in concentration among follicles. CONCLUSIONS: XRF and TOF-SIMS are two complementary methods for obtaining insight into content and localization of iodine in the thyroid. XRF can be used in vitro or in vivo on a large number of samples or patients, respectively. TOF-SIMS on the other hand provides detailed images of the iodine location. The combined information from the two methods is of value for further studies on iodine metabolism in thyroid malignancy.
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| 17. |
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| 18. |
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| 19. |
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| 20. |
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| 21. |
- Holmberg, M., et al.
(författare)
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Treatment outcome 6-10 years after diagnosis of hyperthyroidism in 2916 patients : a longitudinal evaluation of a swedish incidence cohort
- 2018
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Ingår i: Thyroid. - : Mary Ann Liebert. - 1050-7256 .- 1557-9077. ; :S1
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Treatment of Graves’ disease (GD) and toxic nodular goiter (TNG) has the objectives to cure hyperthyroidism, prevent recurrent disease and preserve thyroid function. Treatment efficacies and long-termout comes of antithyroid drugs (ATD), radioactive iodine (RAI) or surgery varies in the literature. We report outcome of treatment, cure rate and risk factors for relapse for GD and TNG in an unselected cohort. A prospective incidence-cohort of de novo diagnosed GD and TNG patients (n = 2916) from 2003-05, were invited to a follow-up 6 - 10 years after diagnosis. Questionnaires were sent to 2430 patients regarding treatments, cure rate, recurrence, quality of life, demographic data, comorbidities and life-style factors. Patients were treated according to clinical routine with ATD, RAI or surgery. Of those included, 1186 (83.3%) had GD and 237 (16.7%) had TNG. In GD patients, 351 (45.3%), 264 (81.5%), and 52 (96.3%) were cured by ATD, RAI or surgery respectively as first line treatment. Of those, 77.0%, 15.4% and 3.8% respectively were without levothyr-oxine supplementation at follow-up at 8 – 0.9 years. Including all treatment modalities, 851 (71.8%) of GD patients were cured within one treatment period. At follow-up, 278 (23%) of GD patients had been operated. In TNG patients, RAI cured 88.6% and surgery 92.9%, whereof 52/154 (33.8%) and 3/15 (20%) had no levothyroxine supplementation post RAI and surgery, respectively.The proportion that did not feel fully recovered at follow-up was 25.3% of GD and 18.1% of the TNG patients. Overall, treatment of hyperthyroidism results in preserved thyroid function only in 35.3% and 44.7% of GD and TNG cases, respectively. As many as 23.4% of the GD patients end up with surgery although only 4.6% choose it from the beginning. Our treatment tradition cures 71.8% of GD patients and 78.1% of TNG patients within one treatment period. The high number of patients who do not feel recovered 6 -10 years after hyperthyroidism in GD and TNG is are minder of the chronic nature of hyperthyroidism.
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| 22. |
- Ittermann, T., et al.
(författare)
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Standardized Map of Iodine Status in Europe
- 2020
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Ingår i: Thyroid. - : Mary Ann Liebert Inc. - 1050-7256 .- 1557-9077. ; 30:9
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Tidskriftsartikel (refereegranskat)abstract
- Background:Knowledge about the population's iodine status is important, because it allows adjustment of iodine supply and prevention of iodine deficiency. The validity and comparability of iodine-related population studies can be improved by standardization, which was one of the goals of the EUthyroid project. The aim of this study was to establish the first standardized map of iodine status in Europe by using standardized urinary iodine concentration (UIC) data. Materials and Methods:We established a gold-standard laboratory in Helsinki measuring UIC by inductively coupled plasma mass spectrometry. A total of 40 studies from 23 European countries provided 75 urine samples covering the whole range of concentrations. Conversion formulas for UIC derived from the gold-standard values were established by linear regression models and were used to postharmonize the studies by standardizing the UIC data of the individual studies. Results:In comparison with the EUthyroid gold-standard, mean UIC measurements were higher in 11 laboratories and lower in 10 laboratories. The mean differences ranged from -36.6% to 49.5%. Of the 40 postharmonized studies providing data for the standardization, 16 were conducted in schoolchildren, 13 in adults, and 11 in pregnant women. Median standardized UIC was <100 mu g/L in 1 out of 16 (6.3%) studies in schoolchildren, while in adults 7 out of 13 (53.8%) studies had a median standardized UIC <100 mu g/L. Seven out of 11 (63.6%) studies in pregnant women revealed a median UIC Conclusions:We demonstrate that iodine deficiency is still present in Europe, using standardized data from a large number of studies. Adults and pregnant women, particularly, are at risk for iodine deficiency, which calls for action. For instance, a more uniform European legislation on iodine fortification is warranted to ensure that noniodized salt is replaced by iodized salt more often. In addition, further efforts should be put on harmonizing iodine-related studies and iodine measurements to improve the validity and comparability of results.
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| 23. |
- Khamisi, Selwan, et al.
(författare)
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Fracture Incidence in Graves' Disease: A Population-Based Study.
- 2023
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Ingår i: Thyroid : official journal of the American Thyroid Association. - : Mary Ann Liebert. - 1557-9077 .- 1050-7256. ; 33:11, s. 1349-1357
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Tidskriftsartikel (refereegranskat)abstract
- Background: Population-based studies have indicated an increase in bone turnover in hyperthyroidism with a subsequent decrease in bone mineral density and an increased risk of fractures, especially in postmenopausal women. However, heterogeneity between studies prevents a definitive conclusion. Graves' disease (GD) is an autoimmune disease, and it is the most common cause of hyperthyroidism. The aim of this study was to investigate fracture risk in patients with GD. Methods: A total of 2134 patients with incident GD and 21,261 age, sex- and county-matched controls were included 16-18 years after diagnosis in a retrospective cohort study. Drug and patient national registries in Sweden were used to assess the risk of developing skeletal complications. Up to 10 years of age, sex- and county-matched controls per patient were selected from databases from the National Board of Health and Welfare and Statistics Sweden. Cox proportional hazards models were fitted to estimate hazard ratios (HR) and confidence intervals [CI]. Results: There were no significant differences in fracture rates between GD and controls but after adjustment for comorbidities, the data showed higher vertebral fracture rates in male GD patients aged >52 years compared to male controls, HR=2.83 [CI 1.05-7.64]. The rates of osteoporosis treatments as well as treatment with corticosteroids were higher in patients with GD. However, HR for the association between GD and fractures remained largely unchanged after adjustment for osteoporosis treatments and treatments with corticosteroids. Conclusions: There were no significant differences in total fracture rate between GD and the general population. However, men older than 52 years had a higher vertebral fracture rate. This study also shows that patients with treated GD receive more osteoporosis treatments compared to the general population.
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| 24. |
- Kitahara, Cari M., et al.
(författare)
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Anthropometric Factors and Thyroid Cancer Risk by Histological Subtype : Pooled Analysis of 22 Prospective Studies
- 2016
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Ingår i: Thyroid. - : MARY ANN LIEBERT, INC. - 1050-7256 .- 1557-9077. ; 26:2, s. 306-318
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Tidskriftsartikel (refereegranskat)abstract
- Background: Greater height and body mass index (BMI) have been associated with an increased risk of thyroid cancer, particularly papillary carcinoma, the most common and least aggressive subtype. Few studies have evaluated these associations in relation to other, more aggressive histologic types or thyroid cancer-specific mortality. Methods: This large pooled analysis of 22 prospective studies (833,176 men and 1,260,871 women) investigated thyroid cancer incidence associated with greater height, BMI at baseline and young adulthood, and adulthood BMI gain (difference between young-adult and baseline BMI), overall and separately by sex and histological subtype using multivariable Cox proportional hazards regression models. Associations with thyroid cancer mortality were investigated in a subset of cohorts (578,922 men and 774,373 women) that contributed cause of death information. Results: During follow-up, 2996 incident thyroid cancers and 104 thyroid cancer deaths were identified. All anthropometric factors were positively associated with thyroid cancer incidence: hazard ratios (HR) [confidence intervals (CIs)] for height (per 5cm)=1.07 [1.04-1.10], BMI (per 5kg/m(2))=1.06 [1.02-1.10], waist circumference (per 5cm)=1.03 [1.01-1.05], young-adult BMI (per 5kg/m(2))=1.13 [1.02-1.25], and adulthood BMI gain (per 5kg/m(2))=1.07 [1.00-1.15]. Associations for baseline BMI and waist circumference were attenuated after mutual adjustment. Baseline BMI was more strongly associated with risk in men compared with women (p=0.04). Positive associations were observed for papillary, follicular, and anaplastic, but not medullary, thyroid carcinomas. Similar, but stronger, associations were observed for thyroid cancer mortality. Conclusion: The results suggest that greater height and excess adiposity throughout adulthood are associated with higher incidence of most major types of thyroid cancer, including the least common but most aggressive form, anaplastic carcinoma, and higher thyroid cancer mortality. Potential underlying biological mechanisms should be explored in future studies.
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| 25. |
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| 26. |
- Lantz, Mikael, et al.
(författare)
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Thyrostimulin (a TSH-like Hormone) Expression in Orbital and Thyroid Tissue.
- 2007
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Ingår i: Thyroid. - : Mary Ann Liebert Inc. - 1557-9077 .- 1050-7256. ; 17:2, s. 113-118
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate gene expression of thyrostimulin in orbital and thyroid tissue from patients with and without Graves' disease. Design: Real-time reverse transcriptase polymerase chain reaction (RT-PCR) was used for detection of thyrostimulin gene expression in intraorbital adipose tissue from patients with severe ophthalmopathy and thyroid healthy controls in addition to thyrostimulin expression in normal thyroid tissue, multinodular goiter tissue, and Graves' thyroid tissue. Main Outcome: In intraorbital tissue, thyrostimulin expression was identified in both patients and controls with fluorescence intensities varying between 0.23 and 0.88 in patients and 0.29 and 8.9 in controls before treatment with DNase. The signal of thyrostimulin was weak or absent in intraorbital adipose tissue from patients with ophthalmopathy and thyroid healthy controls after treatment of samples with DNase. This was in contrast to the expression of the thyroid-stimulating hormone (TSH) receptor and the housekeeping gene cyclophilin A that were detected both before and after DNase treatment. Similar results were found when analyzing human and rat thyroid tissue. Conclusions: Neither did we demonstrate gene expression of thyrostimulin in intraorbital adipose tissue or in thyroid tissue, nor could we confirm earlier findings in rat thyroid tissue. Whether thyrostimulin is a regulator of thyroid function has to be further investigated in future studies.
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| 27. |
- Lee, Jia-Jing, et al.
(författare)
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Molecular cytogenetic profiles of novel and established human anaplastic thyroid carcinoma models
- 2007
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Ingår i: Thyroid. - : Mary Ann Liebert Inc. - 1050-7256 .- 1557-9077. ; 17:4, s. 289-301
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 28. |
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| 29. |
- Levie, Deborah, et al.
(författare)
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The Association of Maternal Iodine Status in Early Pregnancy with Thyroid Function in the Swedish Environmental Longitudinal, Mother and Child, Asthma and Allergy Study
- 2019
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Ingår i: Thyroid. - : Mary Ann Liebert. - 1050-7256 .- 1557-9077. ; 29:11, s. 1660-1668
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Tidskriftsartikel (refereegranskat)abstract
- Background: Severe maternal iodine deficiency can impact fetal brain development through effects on maternal and/or fetal thyroid hormone availability. The effects of mild-to-moderate iodine deficiency on thyroid function are less clear. The aim was to investigate the association of maternal urinary iodine concentration corrected for creatinine (UI/Creat) with thyroid function and autoantibodies in a mild-to-moderate iodine-deficient pregnant population. Methods: This study was embedded within the Swedish Environmental Longitudinal, Mother and child, Asthma and allergy (SELMA) study. Clinical reference ranges were determined by the 2.5th and 97.5th population-based percentile cutoffs. The associations of UI/Creat with thyrotropin (TSH), free thyroxine (fT4), free triiodothyronine (fT3), total T4 (TT4), and total T3 (TT3) were studied using multivariable linear regression in thyroid peroxidase antibody (TPOAb)-negative women. The association of UI/Creat with TPOAb and thyroglobulin antibody (TgAb) positivity was analyzed using multivariable logistic regression. Results: Urinary iodine and thyroid function were measured at a median (95% range) gestational age of 10 (6-14) weeks in 2009 women. The median (95% range) UI/Creat was 85 mu g/g (36-386) and the UI/Creat was below 150 mu g/g in 80.1% of women. Reference ranges did not differ substantially by UI/Creat. A lower UI/Creat was associated with a lower TSH (p = 0.027), a higher TT4 (p = 0.032), and with a corresponding trend toward slightly higher fT4 (p = 0.081), fT3 (p = 0.079), and TT3 (p = 0.10). UI/Creat was not associated with the fT4/fT3 (p = 0.94) or TT4/TT3 ratios (p = 0.63). Women with a UI/Creat of 150-249 mu g/g had the lowest prevalence of TPOAb positivity (6.1%), while women with a UI/Creat of <150 mu g/g had a higher prevalence (11.0%, odds ratio [OR] confidence interval [95% CI] 1.84 [1.07-3.20], p = 0.029). Women with a UI/Creat >= 500 mu g/g showed the highest prevalence and a higher risk of TPOAb positivity, however, only a small proportion of women had such a UI/Creat (12.5%, OR, [95% CI] 2.36 [0.54-10.43], p = 0.26). Conclusions: We could not identify any meaningful differences in thyroid function reference ranges. Lower iodine availability was associated with a slightly lower TSH and a higher TT4. Women with adequate iodine intake had the lowest risk of TPOAb positivity.
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| 30. |
- Lietzow, J., et al.
(författare)
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Comparative Analysis of the Effects of Long-Term 3,5-diiodothyronine Treatment on the Murine Hepatic Proteome and Transcriptome Under Conditions of Normal Diet and High-Fat Diet
- 2021
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Ingår i: Thyroid. - : Mary Ann Liebert Inc. - 1050-7256 .- 1557-9077. ; 31:7, s. 1135-1146
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Tidskriftsartikel (refereegranskat)abstract
- Background: The thyroid hormone (TH) metabolite 3,5-diiodothyronine (3,5-T2) is considered as a potential drug for treatment of nonalcoholic fatty liver disease (NAFLD) based on its prominent antisteatotic effects in murine models of obesity without the detrimental thyromimetic side effects known for classical TH. To expand our understanding of its mode of action, we comprehensively characterized the effects of 3,5-T2 on hepatic gene expression in a diet-induced murine model of obesity by a combined liver proteome and transcriptome analysis. Materials and Methods: Male C57BL/6 mice fed high-fat diet (HFD) to induce NAFLD or standard diet (SD) as control were treated with 2.5 mu g/g body weight 3,5-T2 or saline for 4 weeks. We performed mass spectrometry analyses and integrated those proteome data with earlier published microarray-based transcriptome data from the same animals. In addition, concentrations of several sex steroids in serum and different tissues were determined by gas chromatography-tandem mass spectrometry. Results: We observed limited concordance between transcripts and proteins exhibiting differential abundance under 3,5-T2 treatment, which was only partially explainable by methodological reasons and might, therefore, reflect noncanonical post-transcriptional events. The treatment affected the levels of more and partially different proteins under HFD as compared with SD, demonstrating response modulation by the hepatic lipid load. The hepatic physiological signatures of 3,5-T2 treatment inferable from the omics data comprised the reduction of oxidative stress and alteration of apolipoprotein profiles, both due to decreased liver fat content. In addition, induction of several classical TH target genes and genes involved in the biosynthesis of cholesterol, bile acids (BAs), and male sex steroids was observed. The latter finding was supported by hepatic sex steroid measurements. Conclusion: While confirming the beneficial hepatic liver fat reduction by 3,5-T2 treatment, our data suggest that besides the well-known induction of fatty acid oxidation the stimulation of cholesterol- and BA synthesis with subsequent excretion of the latter through bile might represent a further important mechanism in this context. The obvious intensified male sex steroid exposition of the liver in 3,5-T2-treated HFD animals can be predicted to cause enhanced hepatic "masculinization," with not yet clear but potentially detrimental physiological consequences.
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| 31. |
- Lindberg, Bengt, et al.
(författare)
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Comparison of some different methods for analysis of thyroid autoantibodies: Importance of thyroglobulin autoantibodies
- 2001
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Ingår i: Thyroid. - : Mary Ann Liebert Inc. - 1557-9077 .- 1050-7256. ; 11:3, s. 265-269
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Tidskriftsartikel (refereegranskat)abstract
- Blood samples from 141 children and adolescents were used to evaluate differences between commercial kits and radioimmunoassay (RIA) methods for detecting thyroid autoantibodies. Thyroglobulin autoantibodies (Tg-Ab) were analyzed with a hemagglutination kit and a RIA; thyroid peroxidase autoantibodies (TPO-Ab) were measured with a gelagglutination assay and a RIA. The result; of the antibody tests were compared with thyroid function tests (triiodothyronine [T-3] thyroxine [T-4], thyrotropin [TSH]) and with the results of ultrasound of the thyroid in antibody-positive patients. The correlation of antibody levels between the two methods was higher for TPO-Ab than for Tg-Ab. Moderate to high levels of TPO-Ab correlated to elevated TSH levels. Auto immune thyroiditis (AIT) was found in 6 of the 141 children. The RIA-based thyroglobulin assay was the only test that identified autoantibodies in all 6 cases. in contrast, the hemagglutination kit thyroglobulin assay failed to identify 4 of the 6 AIT cases.
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| 32. |
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| 33. |
- Ludvigsson, Jonas F., et al.
(författare)
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Risk of Thyroid Cancer in a Nationwide Cohort of Patients with Biopsy-Verified Celiac Disease
- 2013
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Ingår i: Thyroid. - : Mary Ann Liebert Inc. - 1050-7256 .- 1557-9077. ; 23:8, s. 971-976
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 34. |
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| 35. |
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| 36. |
- Nagataki, Shigenobu, et al.
(författare)
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Epidemiology and primary prevention of thyroid cancer.
- 2002
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Ingår i: Thyroid : official journal of the American Thyroid Association. - : Mary Ann Liebert Inc. - 1050-7256. ; 12:10, s. 889-96
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this review is to provide an account of our present knowledge about the epidemiology of nonmedullary thyroid carcinoma, to discuss the effects of environment, lifestyle and radiation on the risk of developing thyroid cancer, and to discuss aspects on primary prevention of the disease. In areas not associated with nuclear fallout, the annual incidence of thyroid cancer ranges between 2.0-3.8 cases per 100,000 in women and 1.2-2.6 per 100,000 in men, women of childbearing age being at highest risk. Low figures are found in some European countries (Denmark, Holland, Slovakia) and high figures are found in Iceland and Hawaii. Differences in iodine intake may be one factor explaining the geographic variation, high iodine intake being associated with a slightly increased risk of developing thyroid cancer. In general, lifestyle factors have only a small effect on the risk of thyroid cancer, a possible protective effect of tobacco smoking has been recently reported. Because of the (small) increase in risk of thyroid cancer associated with iodination programs, these should be supervised, so that the population does not receive excess iodine. The thyroid gland is highly sensitive to radiation-induced oncogenesis. This is verified by numerous reports from survivors after Hiroshima and Nagasaki, the Nevada, Novaja Semlja and Marshal Island atmospheric tests, and the Chernobyl plant accident, as well as by investigations of earlier medical use of radiation for benign diseases in childhood. These reports are summarized in the review. There appears to be a dose-response relation for the risk of developing cancer after exposure to radioactive radioiodine. The thyroid gland of children is especially vulnerable to the carcinogenic action of ionizing radiation. Thus, the incidence of thyroid cancer in children in the Belarus area was less than 1 case per million per year before the Chernobyl accident, increasing to a peak exceeding 100 per million per year in certain areas after the accident. It is a social obligation of scientists to inform the public and politicians of these risks. All nuclear power plants should have a program in operation for stockpiling potassium iodide for distribution within 1-2 days after an accident.
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| 37. |
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| 38. |
- Okoye, Chukwuma, et al.
(författare)
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The Free Triiodothyronine/Free Thyroxine Ratio Is Associated with Frailty in Older Adults : A Longitudinal Multisetting Study
- 2023
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Ingår i: Thyroid. - : Mary Ann Liebert Inc. - 1050-7256 .- 1557-9077. ; 33:2, s. 169-176
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Tidskriftsartikel (refereegranskat)abstract
- Background: Various models have been proposed to predict frailty, including those based on clinical criteria and phenotypes. However, a simple biomarker associated with frailty has been not yet identified. The aim of this study is to evaluate the relationship between free triiodothyronine (fT3)/free thyroxine (fT4) ratio value and the degree of frailty among three different cohorts of older individuals: (1) acutely ill hospitalized patients, (2) nursing-home (NH) residents, and (3) home-dwelling centenarians.Methods: We performed a secondary analysis of de-identified patient-level data from two prospective observational studies on acutely hospitalized older patients (Geriatric Acute Unit [GAU]), and home-dwelling centenarians (CENT), and a retrospective-prospective observational study on older NH residents. Demographic characteristics, along with a 30-items Frailty Index (FI) and serum thyrotropin, fT3 and fT4 measurements were obtained.Results: Six hundred fifteen individuals (aged 86.4 ± 8.9 years; 55.1% females) were included in the study, including 298 (48.5%) GAU, 250 (40.6%) NH, and 67 (10.9%) CENT. A significant inverse relationship between fT3/fT4 ratio and FI values was observed (ρs = −0.17 [confidence interval; CI: −0.092 to 0.252], p < 0.001), and this was confirmed by logistic multivariate analysis (β = −0.44, odds ratio [OR]: 0.64 [CI: 0.47–0.87], p < 0.001) (after adjustment for age, sex, and cohorts). Moreover, a progressively decreased mortality risk was associated with rising fT3/fT4 ratio (OR 0.60 [CI: 0.44–0.80] β = −0.51, p < 0.001].Conclusions: The fT3/fT4 ratio value was inversely correlated with frailty degree and mortality risk in a large cohort of older individuals, including centenarians, regardless of their sex and clinical condition. fT3/fT4 ratio value could represent an easily measured independent biochemical marker of frailty degree in older people.
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| 39. |
- Patyra, K., et al.
(författare)
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Congenital Hypothyroidism and Hyperthyroidism Alters Adrenal Gene Expression, Development, and Function
- 2022
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Ingår i: Thyroid. - : Mary Ann Liebert Inc. - 1050-7256 .- 1557-9077. ; 32:4, s. 459-471
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Tidskriftsartikel (refereegranskat)abstract
- Background: The human adrenal cortex undergoes several rapid remodeling steps during its lifetime. In rodents, similar remodeling occurs postnatally in the "X-zone" layer through unknown mechanisms. Furthermore, little is known regarding the impact of thyroid hormone (TH) on adrenal glands in humans.Methods: To investigate the impact of TH on adrenal pathophysiology, we created two genetic murine models mimicking human nonautoimmune hypothyroidism and hyperthyroidism. Moreover, we analyzed serum thyrotropin (TSH) and steroid hormone concentrations in patients diagnosed with congenital hypothyroidism and premature adrenarche (PA).Results: We found that TH receptor beta-mediated hypertrophy of the X-zone significantly elevated the adrenal weights of hyperthyroid women. In the hypothyroid model, the X-zone was poorly developed in both sexes. Moreover, large reciprocal changes in the expression levels of genes that regulate adrenal cortical function were observed with both models. Unexpectedly, up- and downregulation of several genes involved in catecholamine synthesis were detected in the adrenal glands of the hypothyroid and hyperthyroid models, respectively. Furthermore, TSH and adrenal steroid concentrations correlated positively in pediatric patients with congenital hypothyroidism and PA.Conclusions: Our results revealed that congenital hypothyroidism and hyperthyroidism functionally affect adrenal gland development and related steroidogenic activity, as well as the adrenal medulla.
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| 40. |
- Planck, Tereza, et al.
(författare)
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ASSOCIATION OF BTG2, CYR61, ZFP36, AND SCD GENE POLYMORPHISMS WITH GRAVES' DISEASE AND OPHTHALMOPATHY.
- 2014
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Ingår i: Thyroid. - : Mary Ann Liebert Inc. - 1557-9077 .- 1050-7256. ; 24:7, s. 1156-1161
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Tidskriftsartikel (refereegranskat)abstract
- Background: Environmental and genetic factors predispose an individual to the development of Graves' disease (GD). In an expression study of intraorbital tissue, adipocyte-related immediate early genes (IEGs) and immunomodulatory genes were found to be overexpressed in patients with Graves' ophthalmopathy (GO). We hypothesized that genetic variations in these genes could be associated with GD and/or GO. Methods: A total of 98 single nucleotide polymorphisms (SNPs) in twelve genes were genotyped in 594 GD patients with (n=267) or without (n=327) GO and 1147 sex- and ethnicity-matched controls from Malmö, Sweden. Results: Ten SNPs in four genes (BTG family, member 2 [BTG2], cysteine-rich, angiogenic inducer, 61 [CYR61], zinc finger protein 36, C3H type, homolog mouse [ZFP36], and stearoyl-coenzyme A desaturase [SCD]) showed an association with GD and/or GO. SNPs rs12136280 (OR 1.29, p=0.002), rs6663606 (OR 1.26, p=0.004), and rs17534202 (OR 1.21, p=0.02) in BTG2 and rs3753793 (OR 1.21, p=0.03) in CYR61 were associated with GD. An association with GO was shown for SNPs rs3753793 (OR 1.45, p=0.008), rs6682848 (OR 1.55, p=0.03), rs12756618 (OR 1.77, p=0.049), and rs1378228 (OR 1.29, p=0.049) in CYR61, rs1057745 (OR 1.56, p=0.03) and rs11083522 (OR 1.32, p=0.04) in ZFP36, and rs1393491 (OR 1.38, p=0,048) in SCD. Smoking and CYR61 rs12756618 interacted to increase the risk of GO. Conclusions: We found associations of SNPs in IEGs and SCD with GD and/or GO; however, confirmation in a different population is required.
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| 41. |
- Planck, Tereza, et al.
(författare)
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COX-2 and SCD, markers of inflammation and adipogenesis, are related to disease activity in Graves' ophthalmopathy
- 2007
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Ingår i: Thyroid. - : Mary Ann Liebert Inc. - 1557-9077 .- 1050-7256. ; 17:6, s. 511-517
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Tidskriftsartikel (refereegranskat)abstract
- Context: Inflammation and adipogenesis are two parallel processes with increased activity in severe Graves' ophthalmopathy. Objective: The aim of this work was to define target genes for therapeutic intervention in adipogenesis and inflammation in Graves' ophthalmopathy. Design: Orbital tissue was obtained from patients with ophthalmopathy in acute or chronic phase undergoing orbital surgery to study gene expression followed by the study of potential intervention mechanisms in preadipocytes. Setting: Clinic of Endocrinology, University Hospital, Malmo, Sweden. Participants: Patients in acute severe or in chronic phase of ophthalmopathy. Interventions: Lateral orbital decompression in acute phase and restorative surgery in chronic phase. In vitro treatment of preadipocytes with rosiglitazone and diclofenac. Main outcome measure: Gene expression in intraorbital tissue or preadipocytes and differentiation of preadipocytes. Results: A marker of adipose tissue, stearoyl-coenzyme A desaturase (SCD), and the proinflammatory gene, cyclooxygenase-2 (COX-2), were overexpressed in patients in active phase compared to the chronic phase of ophthalmopathy. In growth-arrested preadipocytes stimulated with rosiglitazone, COX-2 expression increased temporarily within 1 hour and decreased to undetectable levels after 48 hours. In contrast, SCD and peroxisome proliferator-activated receptor-gamma (PPAR-gamma) expression increased continuously from day 2 to day 7 during adipogenesis. Diclofenac, an inhibitor of cyclooxygenases with antagonistic effects on PPAR-gamma, reduced the number of mature adipocytes by approximately 50%. Conclusion: We conclude that inflammation and adipogenesis decrease with a decrease in activity of ophthalmopathy and that the nonsteroidal antiinflammatory drug diclofenac inhibits adipogenesis. This may represent a putative future treatment of endocrine ophthalmopathy.
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| 42. |
- Planck, Tereza, et al.
(författare)
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Gene Expression in Graves' Ophthalmopathy and Arm Lymphedema: Similarities and Differences.
- 2011
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Ingår i: Thyroid. - : Mary Ann Liebert Inc. - 1557-9077 .- 1050-7256. ; 21, s. 663-674
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Tidskriftsartikel (refereegranskat)abstract
- Background: Graves' ophthalmopathy (GO) and lymphedema share some pathogenetic mechanisms, such as edema, inflammation, and adipogenesis. The aim of this study was to examine similarities and differences between chronic GO and chronic lymphedema. Methods: Intraorbital adipose tissue was collected from patients with active (n = 10) or chronic GO (n = 10) and thyroid-healthy controls (n = 10). Arm subcutaneous adipose tissue was obtained from patients with chronic arm lymphedema (n = 10), where the unaffected arm served as a control. Gene expression was studied using microarray and real-time polymerase chain reaction. Results: The following genes were significantly upregulated (p < 0.05) in lymphedema but not in GO and have functions in wound healing, fibrosis, fat metabolism, inflammation, differentiation, development, adhesion, and the cytoskeleton: ATP-binding cassette, sub-family G (WHITE), member 1 (ABCG1), actin, alpha 2, smooth muscle, aorta (ACTA2), secreted frizzled-related protein 2 (SFRP2), tenascin C (TNC), pentraxin-related gene, rapidly induced by IL-1 beta (PTX3), and carboxypeptidase X (M14 family), member 1 (CPMX1). In chronic GO, but not in lymphedema, adipocyte-related immediate early genes known to be overexpressed in patients with active GO were upregulated but at a lower level than previously shown for the active phase. Genes of the Wnt pathway, such as secreted frizzled-related protein 1, 2, and 3, were up- and downregulated in both chronic GO and lymphedema. Parathyroid hormone-like hormone (PTHLH) was downregulated (p = 0.01) and apolipoprotein L domain containing 1 (APOLD1) was upregulated (p = 0.05) in both active and chronic GO. Conclusions: There are more differences than similarities between chronic ophthalmopathy and chronic lymphedema, but both conditions exhibit less inflammation and adipogenesis compared to the active phases. In lymphedema, fibrosis dominates. PTHLH, which can inhibit adipogenesis, is downregulated both in active and chronic ophthalmopathy, indicating the possibility of an increased risk of adipogenesis.
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| 43. |
- Planck, Tereza, et al.
(författare)
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Liothyronine Use in Hypothyroidism and its Effects on Cancer and Mortality
- 2021
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Ingår i: Thyroid. - : Mary Ann Liebert Inc. - 1050-7256 .- 1557-9077. ; 31:5, s. 732-739
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Tidskriftsartikel (refereegranskat)abstract
- Background: The prescription of liothyronine (LT3) to treat hypothyroidism is increasing worldwide; however, the long-term safety of LT3 use has yet to be determined. Previous studies have suggested a possible association between LT3 use and breast cancer. The aim of this study was to examine the effects of LT3 use on cancer incidence and mortality. Methods: Our sample included the full adult population of individuals living in Sweden with at least three purchases of thyroid hormone therapy between July 2005 and December 2017. Individual-level data on drug purchases were linked to registry data on cancer incidence and mortality. There were 575,461 individuals with at least three purchases, of which 11,147 had made at least three purchases of LT3, including combinations of levothyroxine (LT4) and LT3. Individuals were followed for a median follow-up time of 8.1 years. We applied Cox regression with a time-varying exposure variable, comparing LT3 users (individuals with at least three cumulative purchases of LT3) with LT4-only users (the rest). Outcomes included breast cancer incidence, any cancer incidence, all-cause mortality, any cancer mortality, and breast cancer mortality. We adjusted for age, sex, previous thyroid cancer, previous other cancer, use of antithyroid preparations, use of sex hormones, and dose in multivariate analyses. Results: Multivariate analyses produced a hazard ratio of 0.93 (95% confidence interval [0.75-1.15]) for breast cancer incidence (only females), 0.97 (0.87-1.08) for any cancer incidence, 0.69 (0.61-0.77) for all-cause mortality, 0.78 (0.62-0.98) for any cancer mortality, and 0.91 (0.50-1.66) for breast cancer mortality (only females). Conclusions: In this large, Swedish, long-term registry-based study, the use of LT3 did not lead to increased breast cancer incidence, any cancer incidence, all-cause mortality, any cancer mortality, or breast cancer mortality compared with LT4 use. Somewhat surprisingly, there was evidence of lower mortality in LT3 users in models adjusting for dose, potentially an artifact of underlying associations between dose and health status/diagnosis.
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| 44. |
- Planck, Tereza, et al.
(författare)
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Smoking induces overexpression of immediate early genes in active Graves' ophthalmopathy.
- 2014
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Ingår i: Thyroid. - : Mary Ann Liebert Inc. - 1557-9077 .- 1050-7256. ; 24:10, s. 1524-1532
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cigarette smoking is a risk factor for the development of Graves' ophthalmopathy (GO). In a previous study of gene expression in intraorbital fat, adipocyte-related immediate early genes (IEGs) were overexpressed in patients with GO compared to controls. We investigated whether IEGs are upregulated by smoking and examined other pathways that may be affected by smoking. Methods: Gene expression in intraorbital fat was studied in smokers (n=8) and non-smokers (n=8) with severe active GO as well as in subcutaneous fat in thyroid-healthy smokers (n=5) and non-smokers (n=5) using microarray and real-time PCR. Results: With microarray, eight IEGs were upregulated more than 1.5-fold in smokers compared to non-smokers with GO. Five were chosen for confirmation and were also overexpressed with real-time PCR. Interleukin-1 beta /IL-1B/ (2.3-fold) and interleukin-6 /IL-6/ (2.4-fold) were upregulated both with microarray and with real-time PCR in smokers with GO compared to non-smokers. Major histocompatibility complex, class II, DR beta 1 /HLA-DRB1/ was upregulated with microarray (2.1-fold) and with borderline significance with real-time PCR. None of these genes were upregulated in smokers compared to non-smokers in subcutaneous fat. Conclusions: IEGs, IL-1B, and IL-6 were overexpressed in smokers with severe active GO compared to non-smokers suggesting that smoking activates pathways associated with adipogenesis and inflammation. This study underlines the importance of IEGs in the pathogenesis of GO and provides evidence for possible novel therapeutic interventions in GO. The mechanisms activated by smoking may be shared with other conditions such as rheumatoid arthritis.
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| 45. |
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| 46. |
- Roswall, Pernilla, et al.
(författare)
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2-methoxyestradiol induces apoptosis in cultured human anaplastic thyroid carcinoma cells
- 2006
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Ingår i: Thyroid. - 1050-7256 .- 1557-9077. ; 16:2, s. 143-50
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 47. |
- Roy, Abhik, et al.
(författare)
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Prevalence of Celiac Disease in Patients with Autoimmune Thyroid Disease : A Meta-Analysis
- 2016
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Ingår i: Thyroid. - : Mary Ann Liebert Inc. - 1050-7256 .- 1557-9077. ; 26:7, s. 880-890
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 48. |
- Schagdarsurengin, Undraga, et al.
(författare)
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CpG island methylation of tumor-related promoters occurs preferentially in undifferentiated carcinoma.
- 2006
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Ingår i: Thyroid. - : Mary Ann Liebert Inc. - 1050-7256 .- 1557-9077. ; 16:7, s. 633-42
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To understand the role of epigenetic inactivation of tumor-related genes in the pathogenesis of thyroid cancer, we investigated the methylation profile of distinct thyroid neoplasms.DESIGN: We analyzed the methylation pattern of 17 gene promoters in nine thyroid cancer cell lines and in 38 primary thyroid carcinomas (13 papillary thyroid carcinoma [PTC], 10 follicular thyroid carcinoma [FTC], 9 undifferentiated thyroid carcinoma [UTC], 6 medullary thyroid carcinoma [MTC]), 12 goiters, and 10 follicular adenomas (FA) by methylation- specific polymerase chain reaction (PCR). Epigenetic inactivation was validated by expression analysis.MAIN OUTCOME: Twelve of these genes (RASSF1A, p16(INK4A), TSHR, MGMT, DAPK, ERalpha, ERbeta, RARbeta, PTEN, CD26, SLC5A8, and UCHL1) were frequently methylated in UTC (15%-86%) and thyroid cancer cell lines (25%-100%). In the more aggressive UTC, the mean methylation index (MI = 0.44) was the highest compared to other thyroid alterations PTC (MI = 0.29, p = 0.123), FTC (MI = 0.15, p = 0.005), MTC (MI = 0.13; p = 0.017), FA (MI = 0.27; p = 0.075) and goiters (MI = 0.23; p = 0.024). Methylation of TSHR, MGMT, UCHL1, and p16 occurred preferentially in UTC and this inactivation was reverted by a demethylating agent.CONCLUSIONS: Our results show that hypermethylation of several tumor-related gene promoters is a frequent event in UTC. The hypermethylation status may be reversed by DNA demethylating agents. Their clinical value remains to be investigated.
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| 49. |
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| 50. |
- Simanainen, J., et al.
(författare)
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Analysis of mutations in exon 1 of the human thyrotropin receptor gene : high frequency of the D36H and P52T polymorphic variants
- 1999
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Ingår i: Thyroid. - 1050-7256 .- 1557-9077. ; 9:1, s. 7-11
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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