Is there an association between thyroid function tests and 18F FDG PET/CT parameters in untreated cancer patients?

Abstract

Objectives: We aimed to investigate the association between the extent of disease, 18F FDG PET/CT parameters (SUVmax and the highest SUVmax) and thyroid function tests (TFT) (TSH, FT4, FT3, FT3/FT4 ratio, AntiTG, and AntiTPO) in untreated cancer patients. Material and Method: One hundred and seventy-nine patients who underwent FDG PET/CT for metabolic characterization and staging in our clinic between May 2020 and November 2020 were included in the study. Patients were divided into two groups as malignant and benign according to histopathology findings. Thyroid function tests were ordered from all patients at the time of PET/CT imaging. The association between the presence of local lymph node metastasis, distant metastases and thyroid function tests as well as the association between PET/CT parameters and thyroid function tests in benign and malignant groups were statistically analyzed. Results: Thyroid function tests did not exhibit a significant difference between patients with malignant and benign disease (p> 0.05). Univariate logistic regression analysis revealed that age, FT4 value, and the FT3/F4 ratio were significant parameters in predicting distant metastases. These parameters were also significant in predicting mortality. Multivariate logistic regression analysis showed that age was an independent prognostic factor predicting mortality. Conclusion: Thyroid function tests are not decisive in differentiating malignant and benign lesions. While no statistically significant correlation was observed between thyroid function tests and PET/CT parameters, univariate analyses revealed that especially FT4 and FT3/FT4 ratio were significant in predicting disease extent and mortality in malignant disease. Age was found to be an independent prognostic factor in predicting mortality.

Keywords

• PET/CT
• SUVmax
• thyroid hormones
• malignancy
• distant metastasis

References

1. St Germain DL, Galton VA, Hernandez A. Minireview: defining the roles of the iodothyronine deiodinases: current concepts and challenges. Endocrinology 2009; 150: 1097-107.
2. Khan SR, Chaker L, Ruiter R, et al. Thyroid function and cancer risk: the Rotterdam study. J Clin Endocrinol Metab 2016; 101: 5030-6.
3. Hellevik AI, Asvold BO, Bjøro T, et al. Thyroid function and cancer risk: a prospective population study. Cancer Epidemiol Biomarkers Prev 2009; 18: 570-4.
4. Dalamaga M, Lekka A, Karmaniolas K, et al. Is thyroid autoimmunity a risk factor for developing primary myelodysplastic syndrome? Cancer Causes Control 2008; 19: 371-8.
5. Davis FB, Mousa SA, O'Connor L, et al. Proangiogenic action of thyroid hormone is fibroblast growth factor-dependent and is initiated at the cell surface. Circ Res 2004; 94: 1500-6.
6. Bergh JJ, Lin HY, Lansing L, et al. Integrin alphaVbeta3 contains a cell surface receptor site for thyroid hormone that is linked to activation of mitogen-activated protein kinase and induction of angiogenesis. Endocrinology 2005; 146: 2864-71.
7. Lin HY, Davis FB, Gordinier JK, Martino LJ, Davis PJ. Thyroid hormone induces activation of mitogen-activated protein kinase in cultured cells. Am J Physiol 1999; 276: 1014-24.
8. Lin HY, Su YF, Hsieh MT, et al. Nuclear monomeric integrin αv in cancer cells is a coactivator regulated by thyroid hormone. FASEB J 2013; 27: 3209-16.

9. Tosovic A, Bondeson AG, Bondeson L, et al. T3 levels in relation to prognostic factors in breast cancer: a population-based prospective cohort study. BMC Cancer 2014; 14: 536.
10. Journy NMY, Bernier MO, Doody MM, et al. Hyperthyroidism, hypothyroidism, and cause-specific mortality in a large cohort of women. Thyroid 2017; 27: 1001-10.
11. Selvaraj N, Bobby Z, Sridhar MG. Is euthyroid sick syndrome a defensive mechanism against oxidative stress? Med Hypotheses 2008; 71: 404-5.
12. Ganesan K, Wadud K. Euthyroid sick syndrome. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022.
13. Kwee TC, Basu S, Saboury B, et al. A new dimension of FDG-PET interpretation: assessment of tumor biology. Eur J Nucl Med Mol Imaging 2011; 38: 1158-70.
14. El-Galaly TC, Gormsen LC, Hutchings M. PET/CT for staging; past, present, and future. Semin Nucl Med 2018; 48: 4-16.
15. Ma CL, Li XD, Sun XR, et al. Using 18F-fluorodeoxyglucose positron emission tomography/ computed tomography to estimate the length of gross tumor and involvement of lymph nodes in esophagogastric junction carcinoma. J Cancer Res Ther 2018; 14: 896-901.
16. Gupta G, Gandhi JS, Sharma A, et al. A study of the pathological outcome of positron emission tomography-computed tomography 2-(18F)-fluro-2-deoxy-D-glucose avid lesion: A 5 years retrospective study. J Cancer Res Ther 2017; 13: 1000-6.
17. Shao M, Zi J, Wen G. 2-fluoro-2-deoxy-D-glucose positron emission tomography versus conventional imaging for the diagnosis of breast cancer and lymph node metastases. J Cancer Res Ther 2018; 14: 661-6.
18. Liao CY, Chen JH, Liang JA, et al. Meta-analysis study of lymph node staging by 18 F-FDG PET/CT scan in non-small cell lung cancer: comparison of TB and non-TB endemic regions. Eur J Radiol 2012; 81: 3518-23.
19. Xia Q, Liu J, Wu C, et al. Prognostic significance of (18)FDG PET/CT in colorectal cancer patients with liver metastases: a meta-analysis. Cancer Imag 2015; 15: 19.
20. Sarker A, Im HJ, Cheon GJ, et al. Prognostic implications of the SUVmax of primary tumors and metastatic lymph node measured by 18F-FDG PET in patients with uterine cervical cancer: a meta-analysis. Clin Nucl Med 2016; 41: 34-40.
21. Im HJ, Pak K, Cheon GJ, et al. Prognostic value o volumetric parameters of 18F-FDG PET in non-small-cell lung cancer: a meta-analysis. Eur J Nucl Med Mol Imaging 2015; 42: 241–51.
22. Pak K, Cheon GJ, Nam HY, et al. Prognostic value of metabolic tumor volume and total lesion glycolysis in head and neck cancer: a systematic review and meta-analysis. J Nucl Med 2014; 55: 884-90.
23. Xie M, Wu K, Liu Y, et al. Predictive value of F-18 FDG PET/CT quantization parameters in diffuse large B cell lymphoma: a meta-analysis with 702 participants. Med Oncol 2015; 32: 446.
24. Sala E, Kataoka M, Pandit-Taskar N, et al. Recurrent ovarian cancer: use of contrast-enhanced CT and PET/CT to accurately localize tumor recurrence and to predict patients survival. Radiology 2010; 257: 125-34.
25. Shani D, Brand DA, Patrick PA. Unrecognized thyroid dysfunction in patients with cancer. Support Care Cancer 2003; 11: 63–5.
26. Ruiter R, Aerts JG V, Hofman A, et al. Thyroid function and cancer risk: the Rotterdam study. J Clin Endocrinol Metab 2016; 101: 5030–6.
27. Kim J, Lee Y, Lee D, et al. The prognostic significance of the lymph node ratio in axillary lymph node positive breast cancer. J Breast Cancer 2011; 78: 204–12.
28. Carter CL, Allen C, Henson DE. Relation of tumor size, lymph node status and survival in 24740 breast cancer cases. Cancer 1989; 63: 18-7.
29. Ittermann T, Haring R, Sauer S, et al. Decreased serum TSH levels are not associated with mortality in the adult northeast German population. Eur J Endocrinol 2010; 162: 579–85.
30. Zhang Y, Chang Y, Ryu S, et al. Thyroid hormones and mortality risk in euthyroid individuals: the Kangbuk Samsung health study. J Clin Endocrinol Metab 2014; 99: 2467–76.
31. Lamprou V, Varvarousis D, Polytarchou K, et al. The role of thyroid hormones in acute coronary syndromes: prognostic value of alterations in thyroid hormones. Clin Cardiol 2017; 40: 528-33.
32. Fragidis S, Sombolos K, Thodis E, et al. Low T3 syndrome and long-term mortality in chronic hemodialysis patients. World J Nephrol 2015; 4: 415-22.
33. Bertoli A, Valentini A, Cianfarani MA, et al. Low FT3: a possible marker of frailty in the elderly. Clin Interv Aging 2017; 12: 335-41.
34. De Alfieri W, Nistico F, Borgogni T, et al. Thyroid hormones as predictors of short and long-term mortality in very old hospitalized patients. J Gerontol A Biol Sci Med Sci 2013; 68: 1122-8.
35. Ratcliffe JG, Stack BH, Burt RW, et al. Thyroid function in lung cancer. Br Med J 1978; 1: 210-2.
36. Pinter M, Haupt L, Hucke F, et al. The impact of thyroid hormones on patients with hepatocellular carcinoma. PLoS One 2017; 12: e0181878.
37. van den Beld AW, Visser TJ, Feelders RA, et al. Thyroid hormone concentrations, disease, physical function, and mortality in elderly men. J Clin Endocrinol Metab 2005; 90: 6403-9.
38. Pasqualetti G, Calsolaro V, Bernardini S, et al. Degree of peripheral thyroxin deiodination, frailty, and long-term survival in hospitalized older patients. J Clin Endocrinol Metab 2018; 103: 1867–76.
39. Warner MH, Beckett GJ. Mechanism behind the non-thyroidal illness syndrome: an update. J Endocrinol 2010; 205: 1–13.
40. Mancini A, Di Segni C, Raimondo S, et al. Thyroid hormones, oxidative stress, and inflammation. Mediators Inflamm 2016; 6757154.
41. De Luca R, Davis PJ, Lin HY, et al. Thyroid hormones interaction with immune response, inflammation and nonthyroidal illness syndrome. Front Cell Dev Biol 2021; 8: 614030.
42. Yasar ZA, Kirakli C, Yilmaz U, et al. Can non-thyroid illness syndrome predict mortality in lung cancer patients? A prospective cohort study. Horm Cancer 2014; 5: 240-6.
43. Gao R, Liang JH, Wang L, et al. Low T3 syndrome is a strong prognostic predictor in diffuse large B cell lymphoma. Br J Haematol 2017; 177: 95-105.
44. Schirripa M, Pasqualetti G, Giampieri R, et al. Prognostic value of thyroid hormone ratios in patients with advanced metastatic colorectal cancer treated with regorafenib: the TOREADOR study. Clin Colorectal Canc 2018; 17: e601–15.
45. Pasqualetti G, Schirripa M, Dochy E, et al. Thyroid hormones ratio is a major prognostic marker in advanced metastatic colorectal cancer: results from the phase III randomised CORRECT trial. Eur J Cancer 2020; 133: 66–73.
46. Maruzzo M, Verzoni E, Vitale MG, et al. Prognostic value of thyroid hormone ratio in patients with advanced metastatic renal cell carcinoma: results from the threefour study (Meet-URO 14). Front Oncol 2021; 11: 787835.
47. Bossoni S, Cossi S, Marengoni A, et al. Low T3 syndrome and outcome in elderly hospitalized geriatric patients. J Endocrinol Invest 2002; 25: 73-4.
48. Tellini U, Pellizzari L, Pravadelli B. Thyroid function in elderly with neoplasms, Minerva Med 1999; 90: 111-21.
49. Hollowell JG, Staehling NW, Flanders WD, et al. Serum TSH, T4, and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). J Clin Endocrinol Metab 2002; 87: 489-99.
50. Dişel U, Beşen A, Karadeniz C, et al. Prevalence of thyroid dysfunction in untreated cancer patients: a cross-sectional study. Med Oncol 2012; 29: 3608-13.