Survey Of Serum Thyroglobulin And Anti-Thyroglobulin Concentration In Differentiated Thyroid Cancer – TranThi Doan

Journal of military pharmaco-medicine n o 3-2019 126 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 cross- sectional 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, 1. National Hospital of Endocrinology Correspongding author: Tran Thi Doan (doanbvnt@gmail.com) Date received: 12/12/2018 Date accepted: 13/02/2019 Journal of military pharmaco-medicine n o 3-2019 127 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. SUBJECTS AND METHODS 1. 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. 2. Methods. - Study design: A cross-sectional descriptive study. - Patients were asked for past medical history and present illness. - Patients were examinated to evaluate the thyroid disease status. - Full bood count and some biochemical tests were done. - The MACIS scores of patients were calculated based on metastatic status, age, radical surgery, invasion and tumor size. The MACIS scores were divided into 3 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 Number of patients Percentage (%) Increased 161 95.8 Normal 7 4.2 TG (µg/L) Median (interquartile) 20.03 (10.60 - 47.37) Increased 72 42.9 Normal 96 57.1 Anti-TG (UI/mL) Median (interquartile) 33.75 (20.02 - 84.92) Journal of military pharmaco-medicine n o 3-2019 128 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 Anti-TG (UI/mL) median (interquartile) 26.95 (20 - 51.5) 50.1 (22.4 - 110.7) < 0.001 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. Journal of military pharmaco-medicine n o 3-2019 129 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 N0 (n = 143) N1 (n = 25) p TG (µg/L) median (interquartile) 18.5 (10.2 - 38.64) 51.7 (14.5 - 91.41) < 0.01 Anti-TG (UI/mL) median (interquartile) 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 large- sized 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 Low MACIS (n = 140) Moderate and high MACIS (n = 28) p TG (µg/L) median (interquartile) 18.25 (10.2 - 38.48) 38.41 (13.95 - 77.52) < 0.05 Anti-TG (UI/mL) median (interquartile) 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. Journal of military pharmaco-medicine n o 3-2019 130 TG = 8.883*CRP + 0.042 0 50 100 150 200 0 2 4 6 8 10 12 14 CRP (mg/l) TG (µg /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 0 50 100 150 200 250 0 2 4 6 8 10 12 14 CRP (mg/l) An tiT G (U I/m 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, 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 n o 3-2019 131 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 1. 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. 2. 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