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Objectives: To evaluate serum thyroglobulin and anti-thyroglobulin concentration and its relation with some features of differentiated thyroid cancer patients. Subjects and methods: A crosssectional study was implemented on 168 differentiated thyroid cancer patients. All patients had been quantified serum thyroglobulin and anti- thyroglobulin by radioimmunoassay methods. Results: The mean serum thyroglobulin and anti- thyroglobulin concentration was 20.03 µg/L and 33.75 UI/mL, respectively.
Journal of military pharmaco-medicine no3-2019 SURVEY OF SERUM THYROGLOBULIN AND ANTI-THYROGLOBULIN CONCENTRATION IN DIFFERENTIATED THYROID CANCER Tran Thi Doan1; Nguyen Vinh Quang1 SUMMARY Objectives: To evaluate serum thyroglobulin and anti-thyroglobulin concentration and its relation with some features of differentiated thyroid cancer patients Subjects and methods: A crosssectional study was implemented on 168 differentiated thyroid cancer patients All patients had been quantified serum thyroglobulin and anti- thyroglobulin by radioimmunoassay methods Results: The mean serum thyroglobulin and anti- thyroglobulin concentration was 20.03 µg/L and 33.75 UI/mL, respectively There were 95.8% of patients who had increasing serum thyroglobulin concentration and 42.9% of patients who had increasing serum anti-thyroglobulin concentration The proportion of patients with both increasing serum thyroglobulin and anti-thyroglobulin concentration was 41.1% In group of patients with age ≥ 40 years old, ≥ T2, N1 and medium and high MACIS scores, serum thyroglobulin and anti-thyroglobulin concentration was significantly higher than those without above features, p < 0.01 There was a significant positive correlation between serum thyroglobulin, anti-thyroglobulin concentration and serum CRP concentration (p < 0.05) Conclusions: Increasing serum thyroglobulin and anti-thyroglobulin concentration was common and related to some characteristics of patients with differentiated thyroid cancer * Keywords: Differentiated thyroid cancer; Serum thyroglobulin; Anti-thyroglobulin; Nodal metastasis INTRODUCTION Thyroid cancer is rare compared to other types of cancer In the United States, in 2016, the number of patients with thyroid cancer revealed nearly 64,000 patients which was equivalent to 1/4 of breast cancer patients and 1/2 of colon cancer patients In Vietnam, thyroid cancer accounts for only 1% of all types of cancer, but it is the most common cancer in all types of endocrine cancers [1, 2] The incidence of this disease in female is higher than in male (3 times) In patients with thyroid cancer, depending on the type of cancer, we can detect the changing of some blood biomarkers such as thyroglobulin (TG) and anti-TG TG is synthesized by thyroid follicular cells and may be a marker for specific thyroid cancer such as papillary and follicular thyroid cancer TG, which is used as a marker to evaluate the efficacy of thyroid cancer treatment and the recurrence of differentiated thyroid cancer, is often tested along with anti-TG antibodies TG is usuallyTG is usually prescribed prior to surgery and periodically after thyroid surgery to evaluate the therapeutic effect This also helps to determine whether surgery has completely removed the cancerous tissue or left cancerous tissue For these reasons, National Hospital of Endocrinology Correspongding author: Tran Thi Doan (doanbvnt@gmail.com) Date received: 12/12/2018 Date accepted: 13/02/2019 126 Journal of military pharmaco-medicine no3-2019 we conducted this study with the aims: Evaluation of serum TG, anti-TG concentration and its relation with some features of differentiated thyroid cancer patients - Patients were asked for past medical history and present illness SUBJECTS AND METHODS Subjects The study was conducted on 168 differentiated thyroid cancer patients who were treated at National Hospital of Endocrinology from March 2014 to March 2016 * Inclusion criteria: - Patients who were diagnosed with differentiated thyroid cancer by small needle aspiration - Age ≥ 18 years old - Agreed to participate in the research * Exclusion criteria: - Patients had acute diseases such as pneumonia, fever… - Patients did not agree to participate in the study Methods - Study design: A cross-sectional descriptive study - Full bood count and some biochemical tests were done - Patients were examinated to evaluate the thyroid disease status - The MACIS scores of patients were calculated based on metastatic status, age, radical surgery, invasion and tumor size The MACIS scores were divided into subgroups: low, moderate, high - Patients had been quantified serum TG and anti-TG by the following technique: All patients were taken blood in the early morning After that, serum separation was performed Finally, serum TG and anti-TG were quantified by radioimmunoassay method The unit of TG and anti-TG was μg/L and UI/mL respectively Diagnosis of increasing or decreasing serum TG and anti-TG were based on the laboratory reference ranges (TG > 5.0 μg/L and anti-TG > 40 UI/mL) - Data was processed by SPSS software version 22.0 RESULTS AND DISCUSSIONS The study group had an average age of 41.25 years old and 87.5% of females There were 13.1% of patients on stage I, 69.6% on stage II and 17.3% on stage III of thyroid cancer According to the MACIS prediction, 83.3% of patients had low risk, 13.1% were at moderate risk and 3.6% at high risk Table 1: Characteristics of serum TG and anti-TG concentrations in patients with thyroid carcinoma (n = 168) Indices TG (µg/L) Number of patients Percentage (%) Increased 161 95.8 Normal 4.2 Median (interquartile) Anti-TG (UI/mL) 20.03 (10.60 - 47.37) Increased 72 42.9 Normal 96 57.1 Median (interquartile) 33.75 (20.02 - 84.92) 127 Journal of military pharmaco-medicine no3-2019 Mean values of both TG and anti-TG concentrations were within the normal range However, up to 95.8% of patients had elevated TG concentration, the remaining 4.2% of patients had TG concentration in normal range Meanwhile, 42.9% of patients had increased anti-TG concentration, the remaining 57.1% of patients had anti-TG concentration in normal range Our results were consistent with Mai Trong Khoa’s [1] and Li C’s findings [9] Indrasena B.S’s [6] findings also highlighted the use of TG as a marker for thyroid cancer In patients with thyroid cancer, there was a proliferation of cancer cells, so TG level usually increased in serum The use of TG as a screening and diagnostic tool for thyroid cancer was shown The sensitivity and specificity of this test were 70% and 80%, respectively for follicular thyroid cancer Table 2: The proportion of patients with increased TG and anti-TG concentration (n = 168) Features Number of patients Percentage (%) Increased TG 161 95.8 Increased anti-TG 72 42.9 Increased both TG and anti-TG 69 41.1 Up to 41.1% of the patients had both increased TG and anti-TG concentration Although TG is a marker for diagnosis, prognosis and evaluation of treatment response of thyroid cancer, especially papillary and follicular cancer, however, if TG and anti-TG levels are not determined, which will sometimes lead to a misjudgment of the patient's condition It has been found that, in the presence of anti-TG in the patient's blood, some patients have low artificial TG levels This may be due to the association between TG and anti-TG In fact, this compound is often not quantified, so it is not known how accurate the concentration of TG and anti-TG is High levels of anti-TG will reduce TG levels However, in our study, we still had 41.1% of patients with both TG and anti-TG elevations Thus, in patients with differentiated thyroid cancer, there was a simultaneous increase in these biomarkers which showed that both TG and anti-TG played an independent roles in thyroid cancer [10] Table 3: Relation between TG, anti-TG and ages Indices < 40 years old (n = 82) ≥ 40 years old (n = 86) p TG (µg/L) median (interquartile) 17.75 (9.89 - 25.91) 32.46 (12.97 - 78.65) < 0.01 26.95 (20 - 51.5) 50.1 (22.4 - 110.7) < 0.001 Anti-TG (UI/mL) median (interquartile) Our results indicated that TG and anti-TG levels were significantly different between the older and younger groups (p < 0.001), which may be related to the severity of patients with thyroid cancer Our results were in contrast with Mai Trong Khoa’s findings [1] This might due to the selected sample characteristics in our study differrent from those of above authors 128 Journal of military pharmaco-medicine no3-2019 Table 4: Relation between TG, anti-TG and the characteristics of thyroid mass on ultrasound Indices T1 (n = 22) T2-4 (n = 146) p TG (µg/L) median (interquartile) 12.5 (7.33 - 15.51) 23.93 (11.28 - 51.18) < 0.01 Anti-TG (UI/mL) median (interquartile) 22.7 (14.85 - 36.02) 37.65 (21.47 - 99.36) < 0.001 Patients with T2-4 thyroid tumors had higher TG and anti-TG levels than patients with T1 thyroid tumors with p < 0.01 Lee EK et al (2012) [7] also assessed the relationship between tumor size, tumor characteristics and concentration of some biological markers in 88 patients with thyroid disease, 35 patients with thyroid tumor and 41 patients with papillary thyroid tumor The results showed that patients with thyroid cancer had a larger tumor size than patients with benign tumors In addition, serum TG levels were related to the size of the tumor mass [10] Table 5: Relation between TG, anti-TG and the nodal characteristics on ultrasound Indices TG (µg/L) median (interquartile) Anti-TG (UI/mL) median (interquartile) N0 (n = 143) N1 (n = 25) p 18.5 (10.2 - 38.64) 51.7 (14.5 - 91.41) < 0.01 31 (20 - 72.7) 101.59 (28.3 - 131.85) < 0.01 Group of patients with N1 had higher TG and anti-TG levels than patients with N0 nodal characteristics (p < 0.01) Characteristics of lymph node metastasis are that thyroid cancer tissue will metastasize and proliferate in lymphoid tissue [5] With largesized lymph nodes, the result indicates that a large number of thyroid epithelial cells appear, so does an increased secretion of biomarkers such as TG and anti-TG into the blood The levels of TG and anti-TG in lymph node metastasis patients are higher than those without lymph node metastases Table 6: Relation between TG, anti-TG and the MACIS prediction Indices TG (µg/L) median (interquartile) Anti-TG (UI/mL) median (interquartile) Low MACIS (n = 140) Moderate and high MACIS (n = 28) p 18.25 (10.2 - 38.48) 38.41 (13.95 - 77.52) < 0.05 31 (20 - 76.75) 69.5 (26.12 - 110) < 0.05 Thyroid cancer patients with moderate and high MACIS score had higher TG and anti-TG levels than those with low MACIS score (p < 0.05) The correlation with the MACIS score also confirmed the association of increased TG and anti-TG with tumor size, metastasis status and the age of thyroid cancer patients 129 Journal of military pharmaco-medicine no3-2019 TG = 8.883*CRP + 0.042 200 TG (µg/l) 150 100 50 0 10 12 14 CRP (mg/l) Chart 1: Correlation between TG and CRP (n = 168) TG had a moderate possitive correlation with serum CRP (r = 0.596, p < 0.001) AntiTG = 14.103* CRP + 1.47 AntiTG (UI/ml) 250 200 150 100 50 0 10 12 14 CRP (mg/l) Chart 2: Correlation between anti-TG and CRP (n = 168) Anti-TG had a moderate possitive correlation with serum CRP (r = 0.693, p < 0.001) The association between inflammation and cancer was also reported in Lee S et al’s study in 2011 [8] They compared hs-CRP levels in 80,781 patients, of whom 729 were diagnosed with primary cancer The results revealed that the mean hs-CRP level of cancer patients was 2.9 mg/L, 130 which was significantly higher than that of non-cancer patients (1.4 mg/L) Inflammation is also considered as a risk factor for thyroid cancer [3, 4] Pro-inflammatory cytokines that arise in chronic inflammation are thought to trigger or promote cancer or may affect Journal of military pharmaco-medicine no3-2019 the progression of this disease In thyroid cancer, histologic studies had confirmed the penetration of white blood cell components such as CD8+, CD4+, regulated T cells into tumor tissue CONCLUSIONS Study on serum TG and anti-TG concentration in 168 patients with differentiated thyroid cancer, we had some comments: - The median serum TG and anti-TG concentration was 20.03 µg/L and 33.75 UI/mL, respectively There was 95.8% of patients who had increasing serum TG concentration and 42.9% of patients who had increasing serum anti-TG concentration The proportion of patients with both increasing serum TG and anti-TG concentration was 41.1% - In group of patients ≥ 40 years old, ≥ T2, N1 and medium and high MACIS scores, serum TG and anti-TG concentration was significantly higher than those wthout above features (p < 0.01) There was a significant positive correlation between serum TG, anti-TG concentration and serum CRP concentration (p < 0.05) REFFERENCES Mai Trong Khoa Quantification of serum thyroglobulin in patients with thyroid cancer treated with radioactive iodine-I131 Journal of Practical Medicine Ministry of Health 2013, 869 (5), pp.101-104 Ministry of Health Treatment of thyroid cancer by I131 Guidelines for the Diagnosis and Treatment of Diseases with Nuclear Medicine 2014, pp.13-21 Fugazzola L, Colombo C, Perrino M, Muzza M Papillary thyroid carcinoma and inflammation Front Endocrin 2011, 2, p.88 https://doi.org/10.3389/fendo.2011.00088 Ghoshal A, Garmo H, Arthur R et al Thyroid cancer risk in the Swedish AMORIS study: The role of inflammatory biomarkers in serum Oncotarget 2017 Dec 4, (1), pp.774-782 Holmes B.J, Sokoll L.J, Li Q.K Measurement of fine-needle aspiration thyroglobulin levels increases the detection of metastatic papillary thyroid carcinoma in cystic neck lesions Cancer Cytopathol 2014, 122, pp.521-526 Indrasena B.S Use of thyroglobulin as a tumour marker World J Biol Chem 2017, Feb 26, (1), pp.81-85 Lee E.K, Chung K.W, Min H.S et al Preoperative serum thyroglobulin as a useful predictive marker to differentiate thyroid cancer from benign nodules in indeterminate nodules J Korean Med Sci 2012, Sep, 27 (9), pp.1014-1018 Lee S, Choe J.W, Kim H.K, Sung J High-sensitivity C-reactive protein and cancer J Epidemiol 2011, 21 (3), pp.161-168 Li C, Yu W, Fan J et al Thyroid functional parameters and correlative autoantibodies as prognostic factors for differentiated thyroid cancers Oncotarget 2016, Aug 2, (31), pp.49930-49938 10 Martins-Costa M.C, Maciel RMB, Kasamatsu T.S et al Clinical impact of thyroglobulin (Tg) and Tg autoantibody (TgAb) measurements in needle washouts of neck lymph node biopsies in the management of patients with papillary thyroid carcinoma Arch Endocrinol Metab 2017, Mar-Apr, 61 (2), pp.108-114 131 ... patients with both increasing serum TG and anti- TG concentration was 41.1% - In group of patients ≥ 40 years old, ≥ T2, N1 and medium and high MACIS scores, serum TG and anti- TG concentration was... cells into tumor tissue CONCLUSIONS Study on serum TG and anti- TG concentration in 168 patients with differentiated thyroid cancer, we had some comments: - The median serum TG and anti- TG concentration. .. TG concentration, the remaining 4.2% of patients had TG concentration in normal range Meanwhile, 42.9% of patients had increased anti- TG concentration, the remaining 57.1% of patients had anti- TG