, Volume 15, Issue 2, pp 256–263 | Cite as

Which is the best predictor of thyroid cancer: thyrotropin, thyroglobulin or their ratio?

  • Pinar YaziciEmail author
  • Mehmet Mihmanli
  • Emre Bozkurt
  • Feyza Yener Ozturk
  • Mehmet Uludag
Research paper


OBJECTIVE: Since documented incidence of thyroid cancer has been rising over time, in part due to incidental small papillary cancer, several studies have been carried out to investigate the role of possible serum markers of thyroid cancer prior to surgery. DESIGN: Prospective cohort study. AIM: To investigate the role of thyroglobulin (Tg), thyrotropin (TSH) and the TSH:Tg, Tg:TSH ratio in the preoperative diagnosis of thyroid cancer. PATIENTS AND METHODS: Between January 2014 and January 2015, 202 of 242 consecutive patients scheduled for surgical treatment for thyroid disorders at Şişli Etfal Training and Research Hospital, General Surgery Clinic were included in the study. Prospective data collection included demographics, thyroid function tests, Tg levels, fine needle aspiration biopsy (FNAB) results (208 FNABs in 187 patients), surgical procedures and final histopathological examinations. RESULTS: There were 134 patients with benign thyroid diseases and 68 patients with thyroid gland malignancy. Preoperative Tg level was significantly lower in the malignant group (64 ng/mL vs. 20ng/mL, p<0.001, respectively), whereas there was no difference in TSH between groups. TSH:Tg levels were found to be significantly higher in patients with malignant thyroid diseases (0.24±1 vs. 0.87±3.4, p=0.024). Although univariate analysis showed that the TSH:Tg ratio was a predictor for thyroid malignancy (OR 0.001; 95% CI, 0.01–0.125; p=0.007) in conjunction with FNAB, multivariate analysis failed to demonstrate any statistical significance for any factor except FNAB. CONCLUSION: Preoperative assessment of serum Tg and TSH levels appear not to be helpful in identifying patients with thyroid cancer. However, a higher preoperative serum TSH:Tg ratio may hint at an increased risk for thyroid carcinoma. Further studies are needed to elucidate the potential role of preoperative laboratory values of thyroid function.

Key words

Preoperative diagnosis Thyroid cancer Thyroglobulin Thyrotropin 


  1. 1.
    Lee EK, Chung KW, Min HS, et al, 2012 Preoperative serum thyroglobulin as a useful predictive marker to differentiate follicular thyroid cancer from benign nodules in indeterminate nodules. Korean Med Sci 27: 1014–1018.CrossRefGoogle Scholar
  2. 2.
    Sands N, Karls S, Rivera J, et al, 2010 Preoperative serum thyroglobulin as an adjunct to fine-needle aspiration in predicting well-differentiated thyroid cancer. J Otolaryngol Head Neck Surg 39: 669–673.PubMedGoogle Scholar
  3. 3.
    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. J Surg Oncol 105: 351–356.CrossRefGoogle Scholar
  4. 4.
    Rago T, Fiore E, Scutari M, et al, 2010 Male sex, single nodularity, and young age are associated with the risk of finding a papillary thyroid cancer on fine needle aspiration cytology in a large series of patients with nodular thyroid disease. Eur J Endocrinol 162: 763–770.CrossRefGoogle Scholar
  5. 5.
    Sohn SY, Kim HJ, Jang HW, Kim SW, Chung JH, 2014 Lack of association between high serum thyroid-stimulating hormone level and risk of papillary thyroid microcarcinomas. Head Neck 36: 43–46.CrossRefGoogle Scholar
  6. 6.
    McLeod DS, Cooper DS, Ladenson PW, et al, 2014 Prognosis of differentiated thyroid cancer in relation to serum thyrotropin and thyroglobulin antibody status at time of diagnosis. Thyroid 24: 35–42.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    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. Clin Endocrinol (Oxf) 71: 434–439.CrossRefGoogle Scholar
  8. 8.
    Hocevar M, Auersperg M, 1998 Role of serum thyroglobulin in the pre-operative evaluation of follicular thyroid tumors. Eur J Surg Oncol 24: 553–557.CrossRefGoogle Scholar
  9. 9.
    Strazisar B, Petric R, Sesek M, Zgajnar J, Hocevar M, Besic N, 2010 Predictive factors of carcinoma in 279 patients with Hürthle cell neoplasm of the thyroid gland. J Surg Oncol 101: 582–586.CrossRefGoogle Scholar
  10. 10.
    Rinaldi S, Plummer M, Biessy C, et al, 2014 Thyroid-stimulating hormone, thyroglobulin, and thyroid hormones and risk of differentiated thyroid carcinoma: the EPIC study. J Natl Cancer Inst 106: Doi: 10.1093/jnci/dju097Google Scholar
  11. 11.
    Cohen N, Pakdaman MN, Rochon L, Tamilia M, Richard J Payne MD, 2009 Tg:TSH Ratio as a Tumor Marker for Thyroid Cancer. Otolaryngol Head Neck Surg 141: 165CrossRefGoogle Scholar
  12. 12.
    Wang L, Li H, Yang Z, Guo Z, Zhang Q, 2015 Preoperative serum thyrotropin to thyroglobulin ratio is effective for thyroid nodule evaluation in euthyroid patients. Otolaryngol Head Neck Surg 2015: pii: 0194599815579877.Google Scholar
  13. 13.
    Gharib H, Goellner JR, 1993 Fine-needle aspiration biopsy of the thyroid: an appraisal. Ann Intern Med 118: 282–289.CrossRefGoogle Scholar
  14. 14.
    Frates MC, Benson CB, Charboneau JW, et al, 2005 Management of thyroid nodules detected at US: Society of Radiologists in Ultrasound Consensus Conference statement. Radiology 237: 794–800.CrossRefGoogle Scholar
  15. 15.
    Miller B, Burkey S, Lindberg G, Snyder WH 3rd, Nwariaku FE, 2004 Prevalence of malignancy within cytologically indeterminate thyroid nodules. Am J Surg 188: 459–462.CrossRefGoogle Scholar
  16. 16.
    Haigh PI, 2002 Follicular thyroid carcinoma. Current treatment options in oncology 3: 349–354.CrossRefGoogle Scholar
  17. 17.
    Yeh MW, Demircan O, Ituare P, Clark OH, 2004 False negative fine needle aspiration cytology results delay treatment and adversely affect outcome in patients with thyroid carcinoma. Thyroid 14: 207–215.CrossRefGoogle Scholar
  18. 18.
    Sherman SI, 2003 Thyroid carcinoma. Lancet 361: 501–511.CrossRefGoogle Scholar
  19. 19.
    Führer D, 2001 A nuclear receptor in thyroid malignancy: is PAX8/PPAR the holly grail of follicular thyroid cancer. Eur J Endocrinol 144: 453–456.CrossRefGoogle Scholar
  20. 20.
    DeMay RM, 2000 Follicular lesions of the thyroid. W(h)ither follicular carcinoma?. Am J Clin Pathol 114: 681–683.CrossRefGoogle Scholar
  21. 21.
    Gul K, Ozdemir D, Ersoy R, et al, 2009 Comparison of Papillary Thyroid Microcarcinoma and Carcinoma. Turk J Endocrinol Metab 13: 47–51.Google Scholar
  22. 22.
    Xing M, 2005 BRAF mutation in thyroid cancer. Endocr Relat Cancer 12: 245–262.CrossRefPubMedGoogle Scholar
  23. 23.
    Trimboli P, Guidobaldi L, Amendola S, et al, 2015 Galectin-3 and HBME-1 improve the accuracy of core biopsy in indeterminate thyroid nodules. Endocrine 52: 39–45.CrossRefGoogle Scholar
  24. 24.
    Bartolazzi A, D’Alessandria C, Parisella MG, et al, 2008 Thyroid cancer imaging in vivo by targeting the anti-apoptotic molecule galectin-3. PLoS One 2008; 3: e3768.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Cui W, Sang W, Zheng S, Ma Y, Liu X, Zhang W, 2012 Usefulness of cytokeratin-19, galectin-3, and Hector Battifora mesothelial-1 in the diagnosis of benign and malignant thyroid nodules. Clin Lab 58: 673–680.PubMedGoogle Scholar
  26. 26.
    Cooper DS, Doherty GM, Haugen BR, et al, 2009 Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid 19: 1167–1214.CrossRefGoogle Scholar
  27. 27.
    Gharib H, Papini E, Paschke R, et al, AACE/AME/ETA Task Force on Thyroid Nodules, 2010 American Association of Clinical Endocrinologists, Associazione Medici Endocrinologi, and European Thyroid Association medical guidelines for clinical practice for the diagnosis and management of thyroid nodules. Endocr Pract 16: Suppl 1: 1–43.CrossRefGoogle Scholar
  28. 28.
    Suh I, Vriens MR, Guerrero MA, et al, 2010 Serum thyroglobulin is a poor diagnostic biomarker of malignancy in follicular and Hurthle-cell neoplasms of the thyroid. Am J Surg 200: 41–46.CrossRefGoogle Scholar
  29. 29.
    Yalçin S, Ulger BV, Parlak O, Ucar AE, Sarikaya SM, Ozer M, 2011 The role of preoperative serum thyroglobulin and thyroid auto-antibody levels before histopathological diagnosis of thyroid cancers. Turk J Med Sci 41: 487–493.Google Scholar
  30. 30.
    Boelaert K, Horacek J, Holder RL, Watkinson JC, Sheppard MC, Franklyn JA, 2006 Serum thyrotropin concentration as a novel predictor of malignancy in thyroid nodules investigated by fine-needle aspiration. J Clin Endocrinol Metab 91: 4295–4301.CrossRefGoogle Scholar
  31. 31.
    Haymart MR, Repplinger DJ, Leverson GE, et al, 2008 Higher serum thyroid stimulating hormone level in thyroid nodule patients is associated with greater risks of differentiated thyroid cancer and advanced tumor stage. J Clin Endocrinol Metab 93: 809–814.CrossRefGoogle Scholar
  32. 32.
    Jameson JL, Weetman AP, 2001, In Thyroid Cancer. Harrison’s Principles of Internal Medicine, Editors: Braunwald E, Fauci AS, Kasper DL, Hauser SL, Longo DL, Jameson JL (eds) S: 2079–2081.Google Scholar
  33. 33.
    Negro R, Valcavi R, Riganti F, et al, 2013 Thyrotropin values in patients with micropapillary thyroid cancer versus benign nodular disease. Endocr Pract 19: 651–655.CrossRefGoogle Scholar
  34. 34.
    Kim HS, Lee SJ, Park JK, 2011 Association between serum thyroid stimulating hormone level and papillary thyroid microcarcinoma in Korean euthyroid patients. Endocrinol Metab 26: 297–302.CrossRefGoogle Scholar
  35. 35.
    Tuna MM, Basaran MN, Karakilic E, et al, 2014 Diagnostic and Prognostic Value of TSH Levels in Differentiated Thyroid Cancers. Turk Jem 1: 1–4.Google Scholar
  36. 36.
    Haugen BR Md, Alexander EK, Bible KC, et al, 2015 American thyroid association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer. Thyroid 26: 1–133.CrossRefGoogle Scholar
  37. 37.
    Fiore E, Rago T, Provenzale MA, et al, 2009 Lower levels of TSH are associated to a lower risk of papillary thyroid cancer in patients with thyroid nodular disease: thyroid autonomy may play a protective role. Endocr Relat Cancer 16: 1251–1260.CrossRefGoogle Scholar

Copyright information

© Hellenic Endocrine Society 2016

Authors and Affiliations

  • Pinar Yazici
    • 1
    Email author
  • Mehmet Mihmanli
    • 1
  • Emre Bozkurt
    • 1
  • Feyza Yener Ozturk
    • 2
  • Mehmet Uludag
    • 1
  1. 1.General Surgery ClinicIstanbulTurkey
  2. 2.Endocrinology and Metabolism InstituteŞişli Etfal Training and Research HospitalIstanbulTurkey

Personalised recommendations