The association between serum concentration of thyroid hormones and thyroid cancer: a cohort study

in Endocrine-Related Cancer
Authors:
Tae-Hwan KimDepartment of Otorhinolaryngology-Head and Neck Surgery, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea

Search for other papers by Tae-Hwan Kim in
Current site
Google Scholar
PubMed
Close
https://orcid.org/0000-0003-3835-144X
,
Mi Yeon LeeDivision of Biostatistics, Department of R&D Management, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea

Search for other papers by Mi Yeon Lee in
Current site
Google Scholar
PubMed
Close
https://orcid.org/0000-0003-2119-9226
,
Sung Min JinDepartment of Otorhinolaryngology-Head and Neck Surgery, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea

Search for other papers by Sung Min Jin in
Current site
Google Scholar
PubMed
Close
, and
Sang Hyuk LeeDepartment of Otorhinolaryngology-Head and Neck Surgery, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea

Search for other papers by Sang Hyuk Lee in
Current site
Google Scholar
PubMed
Close
https://orcid.org/0000-0003-4412-3486

Correspondence should be addressed to S H Lee: entlsh@hanmail.net
Restricted access

USD  $0.01
USD  $0.01

USD  $0.01
USD  $0.01

USD  $0.01
USD  $0.01

USD  $0.01
USD  $0.01

USD  $0.01
USD  $0.01

USD  $0.01
USD  $0.01

USD  $0.01
USD  $0.01

USD  $0.01
USD  $0.01

The impact of serum thyroid hormone levels on thyroid cancer risk is unclear. Some studies reported that elevated thyroid-stimulating hormone (TSH) is associated with higher risk for incidence of thyroid cancer, but other studies reported no relationship. We conducted a large cohort study in 164,596 South Korean men and women who were free of thyroid cancer at baseline and underwent health examination with hormone levels of thyroid function. A parametric proportional hazard model was used to evaluate the adjusted hazard ratio (HR) and 95% CI. During 2,277,749.78 person-years of follow-up, 1280 incident thyroid cancers were identified (men = 593, women = 687). Among men, the multivariable-adjusted HR (95% CI) for thyroid cancer comparing low levels of TSH with normal levels of TSH was 2.95 (1.67–5.23), whereas the corresponding HR (95% CI) in women was 1.5 (0.88–2.55). High levels of free T4 and free T3 were also associated with incident thyroid cancer in both men and women. In clinical implication, overt hyperthyroidism is associated with thyroid cancer in both men and women. Within the euthyroid range, the highest tertile of TSH was associated with a lower risk of thyroid cancer than the lowest TSH tertile and the highest FT4 tertile was associated with a higher risk of thyroid cancer than the lowest FT4 tertile in both men and women. Our finding indicates that low levels of TSH and high levels of FT4, even within the normal range, were associated with an increased risk of incident thyroid cancer.

 

  • Collapse
  • Expand

Society for Endocrinology logo

  • Belfiore A, Garofalo MR, Giuffrida D, Runello F, Filetti S, Fiumara A, Ippolito O & Vigneri R 1990 Increased aggressiveness of thyroid cancer in patients with Graves’ disease. Journal of Clinical Endocrinology and Metabolism 70 830835. (https://doi.org/10.1210/jcem-70-4-830)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Brandt F 2013 Morbidity before and after the diagnosis of hyperthyroidism: a nationwide register-based study. PLoS ONE 8 e66711. (https://doi.org/10.1371/journal.pone.0066711)

    • Search Google Scholar
    • Export Citation
  • Chen AY, Jemal A & Ward EM 2009 Increasing incidence of differentiated thyroid cancer in the United States, 1988–2005. Cancer 115 38013807. (https://doi.org/10.1002/cncr.24416)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Filetti S, Belfiore A, Amir SM, Daniels GH, Ippolito O, Vigneri R & Ingbar SH 1988 The role of thyroid-stimulating antibodies of Graves’ disease in differentiated thyroid cancer. New England Journal of Medicine 318 753759. (https://doi.org/10.1056/NEJM198803243181206)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Fiore E, Rago T, Provenzale MA, Scutari M, Ugolini C, Basolo F, Di Coscio G, Berti P, Grasso L & Elisei R et al.2009 Lower levels of TSH are associated with a lower risk of papillary thyroid cancer in patients with thyroid nodular disease: thyroid autonomy may play a protective role. Endocrine-Related Cancer 16 12511260. (https://doi.org/10.1677/ERC-09-0036)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Gerschpacher M, Göbl C, Anderwald C, Gessl A & Krebs M 2010 Thyrotropin serum concentrations in patients with papillary thyroid microcancers. Thyroid 20 389392. (https://doi.org/10.1089/thy.2009.0139)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Gul K, Ozdemir D, Dirikoc A, Oguz A, Tuzun D, Baser H, Ersoy R & Cakir B 2010 Are endogenously lower serum thyroid hormones new predictors for thyroid malignancy in addition to higher serum thyrotropin? Endocrine 37 253260. (https://doi.org/10.1007/s12020-010-9316-6)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Haymart MR, Repplinger DJ, Leverson GE, Elson DF, Sippel RS, Jaume JC & Chen H 2008 Higher serum thyroid stimulating hormone level in thyroid nodule patients is associated with greater risks of differentiated thyroid cancer and advanced tumor stage. Journal of Clinical Endocrinology and Metabolism 93 809814. (https://doi.org/10.1210/jc.2007-2215)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Haymart MR, Glinberg SL, Liu J, Sippel RS, Jaume JC & Chen H 2009 Higher serum TSH in thyroid cancer patients occurs independent of age and correlates with extrathyroidal extension. Clinical Endocrinology 71 434439. (https://doi.org/10.1111/j.1365-2265.2008.03489.x)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Hercbergs A, Mousa SA, Leinung M, Lin HY & Davis PJ 2018 Thyroid hormone in the clinic and breast cancer. Hormones and Cancer 9 139143. (https://doi.org/10.1007/s12672-018-0326-9)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Huang H, Rusiecki J, Zhao N, Chen Y, Ma S, Yu H, Ward MH, Udelsman R & Zhang Y 2017 Thyroid-stimulating hormone, thyroid hormones, and risk of papillary thyroid cancer: a nested case-control study. Cancer Epidemiology, Biomarkers and Prevention 26 12091218. (https://doi.org/10.1158/1055-9965.EPI-16-0845)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Imaizumi M, Usa T, Tominaga T, Neriishi K, Akahoshi M, Nakashima E, Ashizawa K, Hida A, Soda M & Fujiwara S et al.2006 Radiation dose-response relationships for thyroid nodules and autoimmune thyroid diseases in Hiroshima and Nagasaki atomic bomb survivors 55–58 years after radiation exposure. JAMA 295 10111022. (https://doi.org/10.1001/jama.295.9.1011)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Iribarren C, Haselkorn T, Tekawa IS & Friedman GD 2001 Cohort study of thyroid cancer in a San Francisco Bay area population. International Journal of Cancer 93 745750. (https://doi.org/10.1002/ijc.1377)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Ishikawa N, Eguchi K, Otsubo T, Ueki Y, Fukuda T, Tezuka H, Matsunaga M, Kawabe Y, Shimomura C & Izumi M 1987 Reduction in the suppressor-inducer T cell subset and increase in the helper T cell subset in thyroid tissue from patients with Graves’ disease. Journal of Clinical Endocrinology and Metabolism 65 1723. (https://doi.org/10.1210/jcem-65-1-17)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Jonklaas J, Sarlis NJ, Litofsky D, Ain KB, Bigos ST, Brierley JD, Cooper DS, Haugen BR, Ladenson PW & Magner J et al.2006 Outcomes of patients with differentiated thyroid carcinoma following initial therapy. Thyroid 16 12291242. (https://doi.org/10.1089/thy.2006.16.1229)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Jonklaas J, Nsouli-Maktabi H & Soldin SJ 2008 Endogenous thyrotropin and triiodothyronine concentrations in individuals with thyroid cancer. Thyroid 18 943952. (https://doi.org/10.1089/thy.2008.0061)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Kim KW, Park YJ, Kim EH, Park SY, Park DJ, Ahn SH, Park DJ, Jang HC & Cho BY 2011 Elevated risk of papillary thyroid cancer in Korean patients with Hashimoto’s thyroiditis. Head and Neck 33 691695. (https://doi.org/10.1002/hed.21518)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Kitahara CM, Platz EA, Freeman LE, Hsing AW, Linet MS, Park Y, Schairer C, Schatzkin A, Shikany JM & Berrington de Gonzalez A 2011 Obesity and thyroid cancer risk among U.S. men and women: a pooled analysis of five prospective studies. Cancer Epidemiology, Biomarkers and Prevention 20 464472. (https://doi.org/10.1158/1055-9965.EPI-10-1220)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Kitahara CM, K Rmendiné Farkas D, Jørgensen JOL, Cronin-Fenton D & Sørensen HT 2018 Benign thyroid diseases and risk of thyroid cancer: a nationwide cohort study. Journal of Clinical Endocrinology and Metabolism 103 22162224. (https://doi.org/10.1210/jc.2017-02599)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Laurberg P, Knudsen N, Andersen S, Carle A, Pedersen IB & Karmisholt J 2012 Thyroid function and obesity. European Thyroid Journal 1 159167. (https://doi.org/10.1159/000342994)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Mazzaferri EL 1990 Thyroid cancer and Graves’ disease. Journal of Clinical Endocrinology and Metabolism 70 826829. (https://doi.org/10.1210/jcem-70-4-826)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Mazzaferri EL 1999 An overview of the management of papillary and follicular thyroid carcinoma. Thyroid 9 421427. (https://doi.org/10.1089/thy.1999.9.421)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • McLeod DS 2014 Thyrotropin in the development and management of differentiated thyroid cancer. Endocrinology and Metabolism Clinics of North America 43 367383. (https://doi.org/10.1016/j.ecl.2014.02.012)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • McLeod DS, Watters KF, Carpenter AD, Ladenson PW, Cooper DS & Ding EL 2012 Thyrotropin and thyroid cancer diagnosis: a systematic review and dose-response meta-analysis. Journal of Clinical Endocrinology and Metabolism 97 26822692. (https://doi.org/10.1210/jc.2012-1083)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Moon SS, Lee YS, Lee IK & Kim JG 2012 Serum thyrotropin as a risk factor for thyroid malignancy in euthyroid subjects with thyroid micronodule. Head and Neck 34 949952. (https://doi.org/10.1002/hed.21828)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Morshed SA, Latif R & Davies TF 2009 Characterization of thyrotropin receptor antibody-induced signaling cascades. Endocrinology 150 519529. (https://doi.org/10.1210/en.2008-0878)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Petric R, Perhavec A, Gazic B & Besic N 2012 Preoperative serum thyroglobulin concentration is an independent predictive factor of malignancy in follicular neoplasms of the thyroid gland. Journal of Surgical Oncology 105 351356. (https://doi.org/10.1002/jso.22030)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Pinto M, Soares P & Ribatti D 2011 Thyroid hormone as a regulator of tumor induced angiogenesis. Cancer Letters 301 119126. (https://doi.org/10.1016/j.canlet.2010.11.011)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Polyzos SA, Kita M, Efstathiadou Z, Poulakos P, Slavakis A, Sofianou D, Flaris N, Leontsini M, Kourtis A & Avramidis A 2008 Serum thyrotropin concentration as a biochemical predictor of thyroid malignancy in patients presenting with thyroid nodules. Journal of Cancer Research and Clinical Oncology 134 953960. (https://doi.org/10.1007/s00432-008-0373-7)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Rinaldi S, Plummer M, Biessy C, Tsilidis KK, Ostergaard JN, Overvad K, Tjonneland A, Halkjaer J, Boutron-Ruault MC & Clavel-Chapelon F et al.2014 Thyroid-stimulating hormone, thyroglobulin, and thyroid hormones and risk of differentiated thyroid carcinoma: the EPIC study. Journal of the National Cancer Institute 106 dju097. (https://doi.org/10.1093/jnci/dju097)

    • Search Google Scholar
    • Export Citation
  • Ron E, Doody MM, Becker DV, Brill AB, Curtis RE, Goldman MB, Harris BS, Hoffman DA, McConahey WM & Maxon HR et al.1998 Cooperative Thyrotoxicosis Therapy Follow-Up Study Group: cancer mortality following treatment for adult hyperthyroidism. JAMA 280 347355. (https://doi.org/10.1001/jama.280.4.347)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Senosain MF, Zou Y, Novitskaya T, Vasiukov G, Balar AB, Rowe DJ, Doxie DB, Lehman JM, Eisenberg R & Maldonado F et al.2021 HLA-DR cancer cells expression correlates with T cell infiltration and is enriched in lung adenocarcinoma with indolent behavior. Scientific Reports 11 14424. (https://doi.org/10.1038/s41598-021-93807-3)

    • Search Google Scholar
    • Export Citation
  • Tran TV, Kitahara CM, de Vathaire F, Boutron-Ruault MC & Journy N 2020 Thyroid dysfunction and cancer incidence: a systematic review and meta-analysis. Endocrine-Related Cancer 27 245259. (https://doi.org/10.1530/ERC-19-0417)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • VanderWeele TJ & Ding P 2017 Sensitivity analysis in observational research: introducing the E-value. Annals of Internal Medicine 167 268274. (https://doi.org/10.7326/M16-2607)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Wartofsky L 2010 Increasing world incidence of thyroid cancer: increased detection or higher radiation exposure? Hormones 9 103108. (https://doi.org/10.14310/horm.2002.1260)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Ye ZQ, Gu DN, Hu HY, Zhou YL, Hu XQ & Zhang XH 2013 Hashimoto’s thyroiditis, microcalcification and raised thyrotropin levels within normal range are associated with thyroid cancer. World Journal of Surgical Oncology 11 56. (https://doi.org/10.1186/1477-7819-11-56)

    • Crossref
    • Search Google Scholar
    • Export Citation