Advertisement

Anti-Thyroid Antibodies and TSH as Potential Markers of Thyroid Carcinoma and Aggressive Behavior in Patients with Indeterminate Fine-Needle Aspiration Cytology

  • Mohammadmehdi Adhami
  • Peter Michail
  • Apoorva Rao
  • Chhavi R. Bhatt
  • Simon Grodski
  • Jonathan W. Serpell
  • James C. LeeEmail author
Original Scientific Report

Abstract

Background

Indeterminate fine-needle aspiration cytology (FNAC) imposes challenges in the management of thyroid nodules. This study aimed to examine whether preoperative anti-thyroid antibodies (Abs) and TSH are indicators of thyroid malignancy and aggressive behavior in patients with indeterminate FNAC.

Methods

This was a retrospective study of thyroidectomy patients from 2008 to 2016. We analyzed Abs and TSH levels, FNAC, and histopathology. Serum antibody levels were categorized as ‘Undetectable’, ‘In-range’ if detectable but within normal range, and ‘Elevated’ if above upper limit of normal. ‘Detectable’ levels referred to ‘In-range’ and ‘Elevated’ combined.

Results

There were 531 patients included. Of 402 patients with preoperative FNAC, 104 (25.9%) had indeterminate cytology (Bethesda III–V). Of these, 39 (37.5%) were malignant and 65 (62.5%) benign on histopathology. In the setting of indeterminate FNAC, an increased risk of malignancy was associated with ‘Elevated’ thyroglobulin antibodies (TgAb) (OR 7.25, 95% CI 1.13–77.15, P = 0.01) and ‘Elevated’ thyroid peroxidase antibodies (TPOAb) (OR 6.79, 95% CI 1.23–45.88, P = 0.008). Similarly, while still ‘In-range’, TSH ≥ 1 mIU/L was associated with an increased risk of malignancy (OR 3.23, 95% CI 1.14–9.33, P = 0.01). In all patients with malignancy, the mean tumor size was 8 mm larger in those with TSH ≥ 1 mIU/L (P = 0.03); furthermore, in PTC patients, ‘Detectable’ TgAb conferred a 4 × risk of lymph node metastasis (95% CI 1.03–13.77, P = 0.02).

Conclusion

In this cohort, in indeterminate FNAC patients, Abs and TSH were associated with an increased risk of malignancy. Additionally, TgAb and TSH were potential markers of aggressive biology. As such, they may be diagnostic and prognostic adjuncts.

Notes

Acknowledgements

We would like to acknowledge all the surgeons who have contributed cases to the Monash University Endocrine Surgery Unit (MUESU) database.

Funding

No grants or funding received for this project.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

Study approved by Alfred Health Human Research Ethics Committee (Project No: 185/19).

References

  1. 1.
    Parsa AA, Gharib H (2018) Chapter 1, Epidemiology of thyroid nodules. In: Gharib H (ed) Thyroid nodules - diagnosis and management. Humana Press, Cham, p 7Google Scholar
  2. 2.
    Haugen BR, Alexander EK, Bible KC et al (2016) 2015 American thyroid association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: the American thyroid association guidelines task force on thyroid nodules and differentiated thyroid cancer. Thyroid 26(1):1–133CrossRefGoogle Scholar
  3. 3.
    Keutgen XM, Filicori F, Fahey TJ (2013) Molecular diagnosis for indeterminate thyroid nodules on fine needle aspiration: advances and limitations. Expert Rev Mol Diagn 13(6):613–623CrossRefGoogle Scholar
  4. 4.
    Cibas ES, Ali SZ (2009) The Bethesda system for reporting thyroid cytopathology. Am J Clin Pathol 132(5):658–665CrossRefGoogle Scholar
  5. 5.
    Jooya A, Saliba J, Blackburn A et al (2016) The role of repeat fine needle aspiration in the management of indeterminate thyroid nodules. J Otolaryngol Head Neck Surg 45(1):51CrossRefGoogle Scholar
  6. 6.
    Schneider DF, Cherney Stafford LM, Brys N et al (2017) Gauging the extent of thyroidectomy for indeterminate thyroid nodules: an oncologic perspective. Endocr Pract 23(4):442–450CrossRefGoogle Scholar
  7. 7.
    Uhliarova B, Hajtman A (2018) Hashimoto's thyroiditis: an independent risk factor for papillary carcinoma. Braz J Otorhinolaryngol 84(6):729–735CrossRefGoogle Scholar
  8. 8.
    Seifman MA, Grodski SF, Bailey M et al (2011) Surgery in the setting of Hashimoto's thyroiditis. ANZ J Surg 81(7–8):519–523CrossRefGoogle Scholar
  9. 9.
    Korniluk A, Koper O, Kemona H et al (2017) From inflammation to cancer. Ir J Med Sci 186(1):57–62CrossRefGoogle Scholar
  10. 10.
    Besler E, Citgez B, Aygun N et al (2019) The relationship of clinicopathological factors of the tumor with preoperative TSH level in papillary thyroid cancers. Eurasian J Med 51(1):8–11CrossRefGoogle Scholar
  11. 11.
    Hu N, Li ZM, Liu JF et al (2016) An overall and dose-response meta-analysis for thyrotropin and thyroid cancer risk by histological type. Oncotarget 7(30):47750–47759Google Scholar
  12. 12.
    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(3):809–814CrossRefGoogle Scholar
  13. 13.
    Kim KW, Park YJ, Kim EH et al (2011) Elevated risk of papillary thyroid cancer in Korean patients with Hashimoto's thyroiditis. Head Neck 33(5):691–695CrossRefGoogle Scholar
  14. 14.
    Muzza M, Degl'Innocenti D, Colombo C et al (2010) The tight relationship between papillary thyroid cancer, autoimmunity and inflammation: clinical and molecular studies. Clin Endocrinol (Oxf) 72(5):702–708CrossRefGoogle Scholar
  15. 15.
    Hosseini S, Payne RJ, Zawawi F et al (2016) Can preoperative thyroglobulin antibody levels be used as a marker for well differentiated thyroid cancer? J Otolaryngol Head Neck Surg 45(1):31CrossRefGoogle Scholar
  16. 16.
    Azizi G, Keller JM, Lewis M et al (2014) Association of Hashimoto's thyroiditis with thyroid cancer. Endocr Relat Cancer 21(6):845–852CrossRefGoogle Scholar
  17. 17.
    Repplinger D, Bargren A, Zhang YW et al (2008) Is Hashimoto's thyroiditis a risk factor for papillary thyroid cancer? J Surg Res 150(1):49–52CrossRefGoogle Scholar
  18. 18.
    Zhang Y, Dai J, Wu T et al (2014) The study of the coexistence of Hashimoto's thyroiditis with papillary thyroid carcinoma. J Cancer Res Clin Oncol 140(6):1021–1026CrossRefGoogle Scholar
  19. 19.
    Anil C, Goksel S, Gursoy A (2010) Hashimoto's thyroiditis is not associated with increased risk of thyroid cancer in patients with thyroid nodules: a single-center prospective study. Thyroid 20(6):601–606CrossRefGoogle Scholar
  20. 20.
    Matesa-Anic D, Matesa N, Dabelic N et al (2009) Coexistence of papillary carcinoma and Hashimoto's thyroiditis. Acta Clin Croat 48(1):9–12Google Scholar
  21. 21.
    Castagna MG, Belardini V, Memmo S et al (2014) Nodules in autoimmune thyroiditis are associated with increased risk of thyroid cancer in surgical series but not in cytological series: evidence for selection bias. J Clin Endocrinol Metab 99(9):3193–3198CrossRefGoogle Scholar
  22. 22.
    Selek A, Cetinarslan B, Tarkun I et al (2017) Thyroid autoimmunity: is really associated with papillary thyroid carcinoma? Eur Arch Otorhinolaryngol 274(3):1677–1681CrossRefGoogle Scholar
  23. 23.
    Mantovani A, Allavena P, Sica A et al (2008) Cancer-related inflammation. Nature 454(7203):436–444CrossRefGoogle Scholar
  24. 24.
    Allavena P, Garlanda C, Borrello MG et al (2008) Pathways connecting inflammation and cancer. Curr Opin Genet Dev 18(1):3–10CrossRefGoogle Scholar
  25. 25.
    Coussens LM, Werb Z (2002) Inflammation and cancer. Nature 420(6917):860–867CrossRefGoogle Scholar
  26. 26.
    Guarino V, Castellone MD, Avilla E et al (2010) Thyroid cancer and inflammation. Mol Cell Endocrinol 321(1):94–102CrossRefGoogle Scholar
  27. 27.
    Larson SD, Jackson LN, Riall TS et al (2007) Increased incidence of well-differentiated thyroid cancer associated with Hashimoto thyroiditis and the role of the PI3k/Akt pathway. J Am Coll Surg 204(5):764–773 (discussion 73–5) CrossRefGoogle Scholar
  28. 28.
    Kang DY, Kim KH, Kim JM et al (2007) High prevalence of RET, RAS, and ERK expression in Hashimoto's thyroiditis and in papillary thyroid carcinoma in the Korean population. Thyroid 17(11):1031–1038CrossRefGoogle Scholar
  29. 29.
    Unger P, Ewart M, Wang BY et al (2003) Expression of p63 in papillary thyroid carcinoma and in Hashimoto's thyroiditis: a pathobiologic link? Hum Pathol 34(8):764–769CrossRefGoogle Scholar
  30. 30.
    Arif S, Blanes A, Diaz-Cano SJ (2002) Hashimoto's thyroiditis shares features with early papillary thyroid carcinoma. Histopathology 41(4):357–362CrossRefGoogle Scholar
  31. 31.
    Vasileiadis I, Boutzios G, Charitoudis G et al (2014) Thyroglobulin antibodies could be a potential predictive marker for papillary thyroid carcinoma. Ann Surg Oncol 21(8):2725–2732CrossRefGoogle Scholar
  32. 32.
    Ahn D, Heo SJ, Park JH et al (2011) Clinical relationship between Hashimoto's thyroiditis and papillary thyroid cancer. Acta Oncol 50(8):1228–1234CrossRefGoogle Scholar
  33. 33.
    Song E, Oh HS, Jeon MJ et al (2019) The value of preoperative antithyroidperoxidase antibody as a novel predictor of recurrence in papillary thyroid carcinoma. Int J Cancer 144(6):1414–1420Google Scholar
  34. 34.
    Kimura H, Yamashita S, Namba H et al (1992) Interleukin-1 inhibits human thyroid carcinoma cell growth. J Clin Endocrinol Metab 75(2):596–602Google Scholar
  35. 35.
    Cunha LL, Morari EC, Guihen AC et al (2012) Infiltration of a mixture of immune cells may be related to good prognosis in patients with differentiated thyroid carcinoma. Clin Endocrinol (Oxf) 77(6):918–925CrossRefGoogle Scholar
  36. 36.
    Lucas SD, Karlsson-Parra A, Nilsson B et al (1996) Tumor-specific deposition of immunoglobulin G and complement in papillary thyroid carcinoma. Hum Pathol 27(12):1329–1335CrossRefGoogle Scholar
  37. 37.
    Singh B, Shaha AR, Trivedi H et al (1999) Coexistent Hashimoto's thyroiditis with papillary thyroid carcinoma: impact on presentation, management, and outcome. Surgery 126(6):1070–1077CrossRefGoogle Scholar
  38. 38.
    Rowe CW, Paul JW, Gedye C et al (2017) Targeting the TSH receptor in thyroid cancer. Endocr Relat Cancer 24(6):R191–R202CrossRefGoogle Scholar
  39. 39.
    Boelaert K, Horacek J, Holder RL et al (2006) Serum thyrotropin concentration as a novel predictor of malignancy in thyroid nodules investigated by fine-needle aspiration. J Clin Endocrinol Metab 91(11):4295–4301CrossRefGoogle Scholar
  40. 40.
    Golbert L, de Cristo AP, Faccin CS et al (2017) Serum TSH levels as a predictor of malignancy in thyroid nodules: a prospective study. PLoS ONE 12(11):e0188123CrossRefGoogle Scholar
  41. 41.
    Boi F, Minerba L, Lai ML et al (2013) Both thyroid autoimmunity and increased serum TSH are independent risk factors for malignancy in patients with thyroid nodules. J Endocrinol Invest 36(5):313–320Google Scholar
  42. 42.
    Hegedus L, Hansen JM, Karstrup S (1983) High-incidence of normal thyroid-gland volume in patients with Graves-disease. Clin Endocrinol (Oxf) 19(5):603–607CrossRefGoogle Scholar
  43. 43.
    Beck-Peccoz P, Persani L, Mannavola D et al (2009) Pituitary tumours: TSH-secreting adenomas. Best Pract Res Clin Endocrinol Metab 23(5):597–606CrossRefGoogle Scholar
  44. 44.
    Kim D, Park JW (2013) Clinical implications of preoperative thyrotropin serum concentrations in patients who underwent thyroidectomy for nonfunctioning nodule(s). J Korean Surg Soc 85(1):15–19CrossRefGoogle Scholar
  45. 45.
    Carayon P, Thomas-Morvan C, Castanas E et al (1980) Human thyroid cancer: membrane thyrotropin binding and adenylate cyclase activity. J Clin Endocrinol Metab 51(4):915–920CrossRefGoogle Scholar
  46. 46.
    Abe Y, Ichikawa Y, Muraki T et al (1981) Thyrotropin (TSH) receptor and adenylate cyclase activity in human thyroid tumors: absence of high affinity receptor and loss of TSH responsiveness in undifferentiated thyroid carcinoma. J Clin Endocrinol Metab 52(1):23–28CrossRefGoogle Scholar
  47. 47.
    McGriff NJ, Csako G, Gourgiotis L et al (2002) Effects of thyroid hormone suppression therapy on aciverse clinical outcomes in thyroia cancer. Ann Med 34(7–8):554–564CrossRefGoogle Scholar

Copyright information

© Société Internationale de Chirurgie 2019

Authors and Affiliations

  • Mohammadmehdi Adhami
    • 1
  • Peter Michail
    • 1
  • Apoorva Rao
    • 1
  • Chhavi R. Bhatt
    • 1
  • Simon Grodski
    • 1
    • 2
    • 3
  • Jonathan W. Serpell
    • 1
    • 2
  • James C. Lee
    • 1
    • 2
    • 3
    Email author
  1. 1.Department of General Surgery, Monash University Endocrine Surgery UnitThe Alfred HospitalMelbourneAustralia
  2. 2.Department of SurgeryMonash UniversityMelbourneAustralia
  3. 3.Department of SurgeryMonash HealthMelbourneAustralia

Personalised recommendations