Mendelian randomization to investigate the link between TSH and thyroid cancer

2021 ◽  
Author(s):  
Jonathan M Fussey ◽  
Robin N Beaumont ◽  
Andrew R Wood ◽  
Bijay Vaidya ◽  
Joel Smith ◽  
...  

Evidence from observational studies suggests a positive association between serum thyroid stimulating hormone (TSH) levels and differentiated thyroid carcinoma. However, the cause-effect relationship is poorly understood and these studies are susceptible to bias and confounding. Using Mendelian randomization (MR) methodology, this study aimed to investigate the causal role of TSH in both benign thyroid nodules and thyroid cancer in up to 451,025 UK Biobank. Hospital Episode Statistics and Cancer Registry databases were used to identify 462 patients with differentiated thyroid carcinoma and 2031 patients with benign nodular thyroid disease. MR methods using genetic variants associated with serum TSH were used to test causal relationships between TSH and the two disease outcomes. We observed evidence of an inverse association between TSH levels and both thyroid cancer and benign nodular thyroid disease. Two-sample MR suggested that a one standard deviation higher genetically instrumented TSH (approximately 0.8 mlU/L) resulted in an 80% reduction of risk of benign nodular disease (OR 0.2; 95% CI 0.10 – 0.41) and a 50% reduction of risk of thyroid cancer (OR 0.50; 95% CI 0.27 – 0.92). In keeping with other recently published studies, our results refute a causal role for TSH in both benign nodular thyroid disease and thyroid cancer, with increasing genetically instrumented TSH resulting in a lower risk of both diseases.

2020 ◽  
Vol 27 (10) ◽  
pp. 551-559 ◽  
Author(s):  
Jonathan M Fussey ◽  
Robin N Beaumont ◽  
Andrew R Wood ◽  
Bijay Vaidya ◽  
Joel Smith ◽  
...  

Evidence from observational studies suggest a positive association between serum thyroid-stimulating hormone (TSH) levels and differentiated thyroid carcinoma. However, the cause–effect relationship is poorly understood and these studies are susceptible to bias and confounding. This study aimed to investigate the causal role of TSH in both benign thyroid nodules and thyroid cancer in up to 451,025 UK Biobank participants, using a genetic technique, known as Mendelian randomization (MR). Hospital Episode Statistics and Cancer Registry databases were used to identify 462 patients with differentiated thyroid carcinoma and 2031 patients with benign nodular thyroid disease. MR methods using genetic variants associated with serum TSH were used to test causal relationships between TSH and the two disease outcomes. Mendelian randomization provided evidence of a causal link between TSH and both thyroid cancer and benign nodular thyroid disease. Two-sample MR suggested that a 1 s.d. higher genetically instrumented TSH (approximately 0.8 mIU/L) resulted in 4.96-fold higher odds of benign nodular disease (95% CI 2.46–9.99) and 2.00-fold higher odds of thyroid cancer (95% CI 1.09–3.70). Our results thus support a causal role for TSH in both benign nodular thyroid disease and thyroid cancer.


2019 ◽  
Vol 24 (01) ◽  
pp. e73-e79
Author(s):  
Bambang Udji Djoko Rianto ◽  
Anton Sony Wibowo ◽  
Camelia Herdini

Abstract Introduction Papillary and follicular thyroid carcinoma are common head and neck cancers. This cancer expresses a thyroid stimulating hormone (TSH) receptor that plays a role as a cancer stimulant substance. This hormone has a diagnostic value in the management of thyroid carcinoma. Objective The present study aimed to determine the difference in TSH levels between differentiated thyroid carcinoma and benign thyroid enlargement. Methods The present research design was a case-control study. The subjects were patients with thyroid enlargement who underwent thyroidectomies at the Dr. Sardjito General Hospital, Yogyakarta, Indonesia. Thyroid stimulating hormone levels were measured before the thyroidectomies. The inclusion criteria for the case group were: 1) differentiated thyroid carcinoma, and 2) complete data; while the inclusion criteria for the control group were: 1) benign thyroid enlargement, and 2) complete data. The exclusion criteria for both groups were: 1) patients suffering from thyroid hormone disorders requiring therapy before thyroidectomy surgery, 2) patients receiving thyroid suppression therapy before the thyroidectomy was performed, and 3) patients suffering from severe chronic diseases such as renal insufficiency, and severe liver disease. Results There were 40 post-thyroidectomy case group patients and 40 post-thyroidectomy control group patients. There were statistically significant differences in TSH levels between the groups with differentiated thyroid carcinoma and benign thyroid enlargement (p = 0.001; odds ratio [OR] = 8.42; 95% confidence interval [CI]: 3.19–36.50). Conclusion Based on these results, it can be concluded that there were significant differences in TSH levels between the groups with differentiated thyroid carcinoma and benign thyroid enlargement.


2019 ◽  
Vol 35 (5) ◽  
Author(s):  
Sumera Batool ◽  
Muhammad Shakir Afridi ◽  
Adeel Akbar Khoja ◽  
Najmul Islam

Background and Objective: As the thyroid cancer incidence is increasing, the search for its risk factor is becoming more important. Serum thyroid stimulating hormone (TSH) levels being a growth factor for normal thyroid tissue, is also considered as growth promotor of cancer cells. In our study we aimed for pre-operative serum TSH levels of Differentiated thyroid cancers (DTC) done before their first surgery and determined its association with advanced disease in terms of stage, multifocal disease, lymph node involvement and distant metastasis. Methods: We have conducted a retrospective review of thyroid cancers from 1st January 2008 to 31st December 2017. Out of 281, 142 cases were included according to inclusion criteria. We noted the demographic details of participants, their histopathological diagnosis and serum TSH levels done before first surgery from the medical records. We calculated the stage of tumor through modified American Joint Committee (AJCC) staging system. Results: Out of 147 participants, 89.4% had papillary carcinoma or its variants whereas 10.6% reported follicular carcinoma. The mean pre-op TSH level of the patients included was 2.04 ± 1.79. In addition to the descriptive analysis, the univariate regression analysis revealed that the association of serum TSH levels was found to be statistically insignificant with advanced stage of thyroid cancer, multifocal disease, lymph node metastasis and distant metastasis respectively. Conclusion: The serum TSH levels before surgery was not associated with poor prognosis of differentiated thyroid cancer with respect to higher staging, multifocal disease, lymphatic or distant metastasis. doi: https://doi.org/10.12669/pjms.35.5.704 How to cite this:Batool S, Afridi MS, Khoja A, Islam N. Pre-operative serum TSH levels: A risk factor for advanced metastatic differentiated thyroid carcinoma. Pak J Med Sci. 2019;35(5):---------. doi: https://doi.org/10.12669/pjms.35.5.704 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


2011 ◽  
Vol 121 (12) ◽  
pp. 441-447 ◽  
Author(s):  
Elwira Przybylik-Mazurek ◽  
Dorota Pach ◽  
Sylwia Kuźniarz-Rymarz ◽  
Marta Tracz-Bujnowicz ◽  
Krystyna Szafraniec ◽  
...  

2018 ◽  
Vol 3 (2) ◽  
pp. 359-371 ◽  
Author(s):  
Cristiane J Gomes-Lima ◽  
Di Wu ◽  
Sarika N Rao ◽  
Sree Punukollu ◽  
Rama Hritani ◽  
...  

Abstract Background and Objective The brain is an unusual site for distant metastases of differentiated thyroid carcinoma (DTC). The aim of this study was to document the prevalence of brain metastases from DTC at our institutions and to analyze the current therapies and the outcomes of these patients. Methods We performed a retrospective chart review of patients with DTC and secondary neoplasia of the brain. Results From 2002 to 2016, 9514 cases of thyroid cancer were evaluated across our institutions and 24 patients met our inclusion criteria, corresponding to a prevalence of 0.3% of patients with DTC. Fourteen (58.3%) were female and 10 (41.7%) were male. Fifteen patients had papillary thyroid cancer (PTC) (62.5%). Brain metastases were diagnosed 0 to 37 years (mean ± SD, 10.6 ± 10.4 years) after the initial diagnosis of thyroid cancer. Patients undergoing surgery had a median survival time longer than those that did not undergo surgery (27.3 months vs 6.8 months; P = 0.15). Patients who underwent stereotactic radiosurgery (SRS) had a median survival time longer than those that did not receive SRS (52.5 months vs 6.7 months; P = 0.11). Twelve patients (50%) were treated with tyrosine kinase inhibitors (TKIs), and they had a better survival than those who have not used a TKI (median survival time, 27.2 months vs 4.7 months; P < 0.05). Conclusion The prevalence of brain metastases of DTC in our institutions was 0.3% over 15 years. The median survival time after diagnosis of brain metastases was 19 months. In our study population, the use of TKI improved the survival rates.


2019 ◽  
Vol 8 (8) ◽  
pp. 1106 ◽  
Author(s):  
Young Ki Lee ◽  
Hokyou Lee ◽  
Seunghee Han ◽  
Hyein Jung ◽  
Dong Yeob Shin ◽  
...  

Less-intense TSH suppression strategies can be used for differentiated thyroid cancer (DTC) patients with a low recurrence risk, but their metabolic outcomes are not well known. We aimed to evaluate changes in the serum cholesterol levels and the risk of hypercholesterolemia according to postoperative TSH levels in 1092 female DTC patients receiving levothyroxine after total thyroidectomy. The preoperative-to-follow-up change in total cholesterol (TC) levels in the TSH level <0.03, 0.03–0.3, 0.3–2, and 2–5 mIU/L groups was −3.69 mg/dL (p = 0.006), +0.13 mg/dL (p = 0.926), +12.46 mg/dL (p < 0.001), and +16.46 mg/dL (p < 0.001), respectively. When compared with TSH levels of 0.03–0.3 mIU/L, those of 0.3–2 mIU/L were found to be associated with hypercholesterolemia (adjusted odds ratio (AOR) = 1.86 and 5.08 for TC 200–240 and ≥240 vs. <200 mg/dL) and hyper-low-density lipoprotein (LDL)-cholesterolemia (AOR = 2.76 for LDL-cholesterol ≥160 vs. <130 mg/dL). Additionally, TSH levels of 2–5 mIU/dL were associated with hypercholesterolemia (AOR = 2.85 and 6.95 for TC 200–240 and ≥240 vs. <200 mg/dL) and hyper-LDL-cholesterolemia (AOR = 2.08 and 4.17 for LDL-cholesterol 130–159 and ≥160 mg/dL vs. <130 mg/dL). In patients with normal TSH level maintenance following thyroidectomy, TC levels markedly increased, resulting in an increased hypercholesterolemia prevalence. Metabolic derangement risk due to insufficient levothyroxine replacement should be considered in the adoption of less-intense TSH suppression strategies, postoperatively, in DTC patients.


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