Review 247
Preoperative Measurement of Serum Thyroglobulin to Predict Malignancy in Thyroid Nodules: A Systematic Review
Authors
P. Trimboli1, 2, G. Treglia1, L. Giovanella1, 3
Affiliations
1
Key words ▶ thyroid cancer ● ▶ cytology ● ▶ thyroglobulin ● ▶ Thy 3 ●
Abstract
Bibliography DOI http://dx.doi.org/ 10.1055/s-0034-1395517 Published online: November 10, 2014 Horm Metab Res 2015; 47: 247–252 © Georg Thieme Verlag KG Stuttgart · New York ISSN 0018-5043 Correspondence P. Trimboli, MD Department of Nuclear Medicine and PET/CT Center Oncology Institute of Southern Switzerland Via Ospedale 12 6500 Bellinzona Switzerland Tel.: + 41/91/811 86 72 Fax: + 41/91/811 82 50 [email protected]
▼
Several articles have assessed the role of preoperative serum thyroglobulin (Tg) as predictor of malignancy of thyroid nodules, with particular focus on nodules with indeterminate cytology. However, the role of serum Tg as diagnostic marker remains unclear. The aim of the study was to perform a systematic review to add more evidence-based data on this topic. A comprehensive literature search was conducted to find relevant published articles on this topic. MeSH terms were: “thyroglobulin” and “predict * ”. In order to include only recent serum Tg assay methods, we analyzed the timeframe between 2001 and July 31st, 2014. To expand our search, references of the retrieved articles were also screened. Thirteen studies, including 3 580 patients, were analyzed. Nine out of these studies reported data on
Introduction
▼
Thyroglobulin (Tg) is a large glycoprotein that is stored in follicles in healthy thyroid tissue as colloid where it acts as a substrate for thyroid hormones synthesis. It is exclusively produced by normal or well-differentiated malignant thyrocytes. Then, its tissue-specific origin makes it eminently suitable as a serum tumor indicator in patients followed-up for differentiated thyroid carcinoma (DTC) after thyroid removal and remnants ablation [1]. Vice versa, routinely Tg measurement for initial evaluation of thyroid nodules is not recommended because Tg value may be skewed in many thyroid diseases and is considered as a low sensitive and nonspecific test in detecting thyroid cancer [1]. In the last years, the technical performance of Tg assays has been significantly improved. As a consequence, its determination has been ascribed as a potential predictor of malignancy in patients with thyroid
thyroid nodules with prior indeterminate cytology. Preoperative serum Tg levels demonstrated suboptimal accuracy in discriminating malignant from benign nodules due to a significant overlap of values between these groups. However, most articles demonstrated a statistically significant difference in mean or median serum Tg between patients with cancer and benign lesions correlated to final histology. Furthermore, most studies reported Tg as independent predictor of malignancy. According to the most recent literature, the preoperative measurement of Tg alone fails to discriminate thyroid cancers from benign lesions. However, our data show that Tg is an independent predictor of malignancy; as a consequence, the presurgical determination of Tg should be considered in patients with thyroid nodules, especially when cytology is indeterminate.
nodules; specifically, Tg might be useful in those lesions with indeterminate fine-needle aspiration cytology (FNAC) report [1]. Thyroid indeterminate lesions occur for 15–20 % of thyroid cytologies and are assessed as Thy 3, Class 3, or Category III–IV according to British Thyroid Association [2], American Association Clinical Endocrinologists/Associazione Medici Endocrinologi/European Thyroid Association [3], or Bethesda System for Reporting Thyroid Cytopathology [4], respectively. Only one in 4 of these nodules is a cancer [5]. However, malignant tumors, mainly represented by follicular carcinoma or follicular variant of papillary carcinoma, may not be discriminated from benign neoplasms (i. e., follicular adenoma and nodular adenomatous goiter), and the histological validation after surgery is traditionally required [2–4]. Thus, identification of predictors of malignancy is one of the most critical challenges in thyroidology. Many molecular, cytologic/morphologic and
Trimboli P et al. Thyroglobulin as Predictor of Thyroid Malignancy … Horm Metab Res 2015; 47: 247–252
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
received 19.08.2014 accepted 22.10.2014
Department of Nuclear Medicine and Thyroid Center, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland Section of Endocrinology and Diabetology, Ospedale Israelitico, Rome, Italy 3 Department of Clinical Chemistry and Laboratory Medicine, Ente Ospedaliero Cantonale, Bellinzona, Switzerland 2
248 Review imaging studies focusing on potential predictors have been conducted [6–9]; among them, several articles investigated the preoperative measurement of serum Tg, with controversial findings. To date, no systematic analysis of the literature on this topic has been conducted. We have now performed a systematic review of the literature to provide more robust estimates of the use of serum Tg as a risk factor in patients with thyroid nodules, with particular focus on thyroid lesions with prior indeterminate FNAC report.
Data extraction
For each included study, information was collected concerning basic study (authors, journals and year of publication, country of origin, study design), patient characteristics (number, mean age, gender), method of Tg assay used, preoperative serum Tg values in malignant and benign lesions, and diagnostic accuracy data on Tg in predicting malignancy.
Results
▼
This systematic review was performed according to the “Preferred Reporting Items for Systematic Reviews and Meta-Analyses” (PRISMA) statement which describes an evidence-based minimum set of items that have to be reported in systematic reviews [10].
Search strategy
A comprehensive literature search of PubMed/MEDLINE and Scopus databases was conducted to find relevant published articles on the use of serum Tg as predictor of thyroid malignancy. We used a search algorithm that was based on a combination of the terms: “thyroglobulin” and “predict * ”. In order to include only recent serum Tg assay methods the timeframe was from 2001 up to July 31st, 2014. To expand our search, references of the retrieved articles were also screened for additional studies.
Study selection
Studies or subsets in studies reporting data about the use of serum Tg as predictor of thyroid malignancy were eligible for inclusion. The exclusion criteria were: a) articles not within the field of interest of this review; b) review articles, editorials or letters, comments, conference proceedings; c) case reports or case series; and d) articles not in English language. Three researchers independently reviewed the titles and abstracts of the retrieved articles, applying the above mentioned criteria. Articles were rejected if they were clearly ineligible. The same 3 researchers then independently reviewed the full-text version of the remaining articles to determine their eligibility for inclusion. Disagreements were resolved in a consensus meeting.
The literature search revealed 480 articles. Reviewing their titles and abstracts, 470 articles were excluded according to the above criteria, and 10 full-text papers were assessed as eligible [11–20]; 3 additional studies were found by screening the references of these 10 articles [21–23]. Finally, 13 studies [11–23] comprising 3 580 patients were included in the present systematic review and their characteristics are summarized in ● ▶ Table 1, 2. Regarding the geographical distribution of the 13 articles, about a half of them (n = 7) originated by European research groups while the remaining ones originated by authors from Asia (n = 3) or Northern America (n = 3). Most of the studies were retrospective and single-center. Mean patients age ranged from 44 to 58 years, and female gender was more prevalent. Overall, the inclusion criteria and the characteristics of patients enrolled in the ▶ Table 1). selected studies were quite different ( ● Remarkably, many articles reported a series of thyroid nodules with indeterminate FNAC report, including patients with follicular [13–18, 20] or Hürthle cell [17, 21, 23] cytology. The remaining articles enrolled series of thyroid lesions regardless of their FNAC results [11, 12, 19, 22]. Different methods of Tg assay and several Tg cutoff values were used, contributing to the heterogeneity of the studies ▶ Table 2). Common exclusion criteria among the selected stud( ● ies were patients with positive Tg-antibodies (TgAb) or performing serum Tg assay just after FNAC, due to the potential interference of TgAb and FNAC on Tg serum levels [24]. Most of the studies, specifically those articles with larger sample size, demonstrated a statistically significant difference in mean [13, 18, 21, 22] or median [11, 14–16, 21] preoperative serum Tg values between patients with malignant and benign lesions at final histology. Nevertheless, a significant overlap in preoperative
Table 1 Basic study and patient characteristics. Authors
Year
Country
Study design
Patients (n)
Selection of series by FNAB
Malignancies
Rinaldi et al. [11]
2014
Prospective
1 124
No
Scheffler et al. [12] Lee et al. [13] Zimny et al. [14] Petric et al. [15] Lee et al. [16] Suh et al. [17] Sands et al. [18] Strazisar et al. [21] Kuru et al. [19] Besic et al. [20]
2014 2013 2012 2012 2012 2010 2010 2010 2009 2008
Europe (multicentric) Canada Korea Germany Slovenia Korea USA Canada Slovenia Turkey Slovenia
Retrospective Retrospective Retrospective Retrospective Retrospective Retrospective Retrospective Retrospective Prospective Retrospective
173 97 119 388 164 39 68 279 571 327
No Follicular neoplasms Follicular neoplasms Follicular neoplasms Follicular neoplasms Follicular or Hürthle neoplasms Follicular neoplasms Follicular or Hürthle neoplasms No Follicular neoplasms
Guarino et al. [22] Sugino et al. [23]
2005 2001
Italy Japan
Retrospective Retrospective
105 126
No Follicular or Hürthle neoplasms
357 (262 PC, 58 FC, 37 not specified) 84 (78 PC and 6 FC) 47 (31 PC and 16 FC) 21 (14 PC, 6 FC, 1 not specified) 127 (89 PC, 33 FC, 3 HC, 2 AC) 76 (41 PC and 35 FC) 16 (5 PC, 8 FC, 3 HC) 41 (FC or PC, not detailed) 71 (18 PC, 8 FC, 45 HC) 83 (76 PC, 5 FC, 2 MC) 119 (histologic types not detailed) 71 (all PC) 22 (histologic types not detailed)
NR: Not reported; PC: Papillary carcinoma; FC: Follicular carcinoma; HC: Hürthle cell carcinoma; AC: Anaplastic carcinoma; MC: Medullary carcinoma; PG: Paraganglioma; FNAB: Fine needle aspiration biopsy; Tg: Thyroglobulin
Trimboli P et al. Thyroglobulin as Predictor of Thyroid Malignancy … Horm Metab Res 2015; 47: 247–252
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
▼
Methods
DYNO immunoradiometric test and IRMA LIASON test IRMA immunoradiometric assay Brahms
Chemiluminescent immunoassay using the Nichols Advantage platform and DPC Immulite 2000 NR
DYNO test immunoradiometric test and IRMA LIASON test
Cobas Immunoassay Systems
Petric et al. [15]
Suh et al. [17]
Strazisar et al. [21]
Kuru et al. [19]
Sands et al. [18]
Lee et al. [16]
Immunoradiometric assays SELCO Tg, TgCTK, or RIASON
Trimboli P et al. Thyroglobulin as Predictor of Thyroid Malignancy … Horm Metab Res 2015; 47: 247–252
569 ng/ml (mean) 121 ng/ml (median in goiter) 125 ng/ ml (median in adenoma) 90 ng/ml (median)
53 ng/ml (mean)
116.3 ng/ml (median)
15.4 ng/ml (median)
172 ng/ml (median)
NR
malignancy
78 ng/ml
1 000 ng/ml
75 ng/ml
NR
187.5 ng/ml
300 ng/ml
300 ng/ml
75 ng/ml
NR
NR
71.1 %
31 %
61 %
NR
48.5 %
50.4 %
21 %
75 %
ROC cirve: 43 % sensitivity for 90 % specificity and 80 % sensitivity for 42 % specificity NR
Sensitivity
Speci-
49 %
86 %
65 %
NR
91.5 %
69.3 %
95 %
76 %
NR
ficity
19.1 %
43.1 %
81 %
NR
NR
44.4 %
44.4 %
75 %
NR
NR
PPV
90.9 %
78.5 %
71 %
NR
NR
74.2 %
85.2 %
76 %
NR
NR
NPV
Among patients with follicular cell cytology, preoperative serum Tg was significantly higher in thyroid carcinoma compared to benign lesions at final histology (p = 0.007) Predictive values of Tg + FNAB were higher compared to those of FNAB only (p = 0.015) Among patients with Hürthle cell cytology, preoperative serum Tg was significantly higher in patients with malignant compared to those with benign lesions (p = 0.007). Preoperative serum Tg > 1 000 ng/ml was an independent predictor of malignancy in Hürthle cell cytology (OR: 2.11; p = 0.0001) Preoperative serum Tg > 78 ng/ml was an independent predictor of malignancy (OR: 2; p = 0.019)
There was no significant difference in preoperative serum Tg level between malignant and benign histology groups in patients with follicular or Hürthle cell cytology at FNAB (p = 0.54)
Among patients with follicular cell cytology, preoperative serum Tg was significantly higher in FC compared to benign lesions or PC at final histology (p
Preoperative Measurement of Serum Thyroglobulin to Predict Malignancy in Thyroid Nodules: A Systematic Review
Authors
P. Trimboli1, 2, G. Treglia1, L. Giovanella1, 3
Affiliations
1
Key words ▶ thyroid cancer ● ▶ cytology ● ▶ thyroglobulin ● ▶ Thy 3 ●
Abstract
Bibliography DOI http://dx.doi.org/ 10.1055/s-0034-1395517 Published online: November 10, 2014 Horm Metab Res 2015; 47: 247–252 © Georg Thieme Verlag KG Stuttgart · New York ISSN 0018-5043 Correspondence P. Trimboli, MD Department of Nuclear Medicine and PET/CT Center Oncology Institute of Southern Switzerland Via Ospedale 12 6500 Bellinzona Switzerland Tel.: + 41/91/811 86 72 Fax: + 41/91/811 82 50 [email protected]
▼
Several articles have assessed the role of preoperative serum thyroglobulin (Tg) as predictor of malignancy of thyroid nodules, with particular focus on nodules with indeterminate cytology. However, the role of serum Tg as diagnostic marker remains unclear. The aim of the study was to perform a systematic review to add more evidence-based data on this topic. A comprehensive literature search was conducted to find relevant published articles on this topic. MeSH terms were: “thyroglobulin” and “predict * ”. In order to include only recent serum Tg assay methods, we analyzed the timeframe between 2001 and July 31st, 2014. To expand our search, references of the retrieved articles were also screened. Thirteen studies, including 3 580 patients, were analyzed. Nine out of these studies reported data on
Introduction
▼
Thyroglobulin (Tg) is a large glycoprotein that is stored in follicles in healthy thyroid tissue as colloid where it acts as a substrate for thyroid hormones synthesis. It is exclusively produced by normal or well-differentiated malignant thyrocytes. Then, its tissue-specific origin makes it eminently suitable as a serum tumor indicator in patients followed-up for differentiated thyroid carcinoma (DTC) after thyroid removal and remnants ablation [1]. Vice versa, routinely Tg measurement for initial evaluation of thyroid nodules is not recommended because Tg value may be skewed in many thyroid diseases and is considered as a low sensitive and nonspecific test in detecting thyroid cancer [1]. In the last years, the technical performance of Tg assays has been significantly improved. As a consequence, its determination has been ascribed as a potential predictor of malignancy in patients with thyroid
thyroid nodules with prior indeterminate cytology. Preoperative serum Tg levels demonstrated suboptimal accuracy in discriminating malignant from benign nodules due to a significant overlap of values between these groups. However, most articles demonstrated a statistically significant difference in mean or median serum Tg between patients with cancer and benign lesions correlated to final histology. Furthermore, most studies reported Tg as independent predictor of malignancy. According to the most recent literature, the preoperative measurement of Tg alone fails to discriminate thyroid cancers from benign lesions. However, our data show that Tg is an independent predictor of malignancy; as a consequence, the presurgical determination of Tg should be considered in patients with thyroid nodules, especially when cytology is indeterminate.
nodules; specifically, Tg might be useful in those lesions with indeterminate fine-needle aspiration cytology (FNAC) report [1]. Thyroid indeterminate lesions occur for 15–20 % of thyroid cytologies and are assessed as Thy 3, Class 3, or Category III–IV according to British Thyroid Association [2], American Association Clinical Endocrinologists/Associazione Medici Endocrinologi/European Thyroid Association [3], or Bethesda System for Reporting Thyroid Cytopathology [4], respectively. Only one in 4 of these nodules is a cancer [5]. However, malignant tumors, mainly represented by follicular carcinoma or follicular variant of papillary carcinoma, may not be discriminated from benign neoplasms (i. e., follicular adenoma and nodular adenomatous goiter), and the histological validation after surgery is traditionally required [2–4]. Thus, identification of predictors of malignancy is one of the most critical challenges in thyroidology. Many molecular, cytologic/morphologic and
Trimboli P et al. Thyroglobulin as Predictor of Thyroid Malignancy … Horm Metab Res 2015; 47: 247–252
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
received 19.08.2014 accepted 22.10.2014
Department of Nuclear Medicine and Thyroid Center, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland Section of Endocrinology and Diabetology, Ospedale Israelitico, Rome, Italy 3 Department of Clinical Chemistry and Laboratory Medicine, Ente Ospedaliero Cantonale, Bellinzona, Switzerland 2
248 Review imaging studies focusing on potential predictors have been conducted [6–9]; among them, several articles investigated the preoperative measurement of serum Tg, with controversial findings. To date, no systematic analysis of the literature on this topic has been conducted. We have now performed a systematic review of the literature to provide more robust estimates of the use of serum Tg as a risk factor in patients with thyroid nodules, with particular focus on thyroid lesions with prior indeterminate FNAC report.
Data extraction
For each included study, information was collected concerning basic study (authors, journals and year of publication, country of origin, study design), patient characteristics (number, mean age, gender), method of Tg assay used, preoperative serum Tg values in malignant and benign lesions, and diagnostic accuracy data on Tg in predicting malignancy.
Results
▼
This systematic review was performed according to the “Preferred Reporting Items for Systematic Reviews and Meta-Analyses” (PRISMA) statement which describes an evidence-based minimum set of items that have to be reported in systematic reviews [10].
Search strategy
A comprehensive literature search of PubMed/MEDLINE and Scopus databases was conducted to find relevant published articles on the use of serum Tg as predictor of thyroid malignancy. We used a search algorithm that was based on a combination of the terms: “thyroglobulin” and “predict * ”. In order to include only recent serum Tg assay methods the timeframe was from 2001 up to July 31st, 2014. To expand our search, references of the retrieved articles were also screened for additional studies.
Study selection
Studies or subsets in studies reporting data about the use of serum Tg as predictor of thyroid malignancy were eligible for inclusion. The exclusion criteria were: a) articles not within the field of interest of this review; b) review articles, editorials or letters, comments, conference proceedings; c) case reports or case series; and d) articles not in English language. Three researchers independently reviewed the titles and abstracts of the retrieved articles, applying the above mentioned criteria. Articles were rejected if they were clearly ineligible. The same 3 researchers then independently reviewed the full-text version of the remaining articles to determine their eligibility for inclusion. Disagreements were resolved in a consensus meeting.
The literature search revealed 480 articles. Reviewing their titles and abstracts, 470 articles were excluded according to the above criteria, and 10 full-text papers were assessed as eligible [11–20]; 3 additional studies were found by screening the references of these 10 articles [21–23]. Finally, 13 studies [11–23] comprising 3 580 patients were included in the present systematic review and their characteristics are summarized in ● ▶ Table 1, 2. Regarding the geographical distribution of the 13 articles, about a half of them (n = 7) originated by European research groups while the remaining ones originated by authors from Asia (n = 3) or Northern America (n = 3). Most of the studies were retrospective and single-center. Mean patients age ranged from 44 to 58 years, and female gender was more prevalent. Overall, the inclusion criteria and the characteristics of patients enrolled in the ▶ Table 1). selected studies were quite different ( ● Remarkably, many articles reported a series of thyroid nodules with indeterminate FNAC report, including patients with follicular [13–18, 20] or Hürthle cell [17, 21, 23] cytology. The remaining articles enrolled series of thyroid lesions regardless of their FNAC results [11, 12, 19, 22]. Different methods of Tg assay and several Tg cutoff values were used, contributing to the heterogeneity of the studies ▶ Table 2). Common exclusion criteria among the selected stud( ● ies were patients with positive Tg-antibodies (TgAb) or performing serum Tg assay just after FNAC, due to the potential interference of TgAb and FNAC on Tg serum levels [24]. Most of the studies, specifically those articles with larger sample size, demonstrated a statistically significant difference in mean [13, 18, 21, 22] or median [11, 14–16, 21] preoperative serum Tg values between patients with malignant and benign lesions at final histology. Nevertheless, a significant overlap in preoperative
Table 1 Basic study and patient characteristics. Authors
Year
Country
Study design
Patients (n)
Selection of series by FNAB
Malignancies
Rinaldi et al. [11]
2014
Prospective
1 124
No
Scheffler et al. [12] Lee et al. [13] Zimny et al. [14] Petric et al. [15] Lee et al. [16] Suh et al. [17] Sands et al. [18] Strazisar et al. [21] Kuru et al. [19] Besic et al. [20]
2014 2013 2012 2012 2012 2010 2010 2010 2009 2008
Europe (multicentric) Canada Korea Germany Slovenia Korea USA Canada Slovenia Turkey Slovenia
Retrospective Retrospective Retrospective Retrospective Retrospective Retrospective Retrospective Retrospective Prospective Retrospective
173 97 119 388 164 39 68 279 571 327
No Follicular neoplasms Follicular neoplasms Follicular neoplasms Follicular neoplasms Follicular or Hürthle neoplasms Follicular neoplasms Follicular or Hürthle neoplasms No Follicular neoplasms
Guarino et al. [22] Sugino et al. [23]
2005 2001
Italy Japan
Retrospective Retrospective
105 126
No Follicular or Hürthle neoplasms
357 (262 PC, 58 FC, 37 not specified) 84 (78 PC and 6 FC) 47 (31 PC and 16 FC) 21 (14 PC, 6 FC, 1 not specified) 127 (89 PC, 33 FC, 3 HC, 2 AC) 76 (41 PC and 35 FC) 16 (5 PC, 8 FC, 3 HC) 41 (FC or PC, not detailed) 71 (18 PC, 8 FC, 45 HC) 83 (76 PC, 5 FC, 2 MC) 119 (histologic types not detailed) 71 (all PC) 22 (histologic types not detailed)
NR: Not reported; PC: Papillary carcinoma; FC: Follicular carcinoma; HC: Hürthle cell carcinoma; AC: Anaplastic carcinoma; MC: Medullary carcinoma; PG: Paraganglioma; FNAB: Fine needle aspiration biopsy; Tg: Thyroglobulin
Trimboli P et al. Thyroglobulin as Predictor of Thyroid Malignancy … Horm Metab Res 2015; 47: 247–252
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
▼
Methods
DYNO immunoradiometric test and IRMA LIASON test IRMA immunoradiometric assay Brahms
Chemiluminescent immunoassay using the Nichols Advantage platform and DPC Immulite 2000 NR
DYNO test immunoradiometric test and IRMA LIASON test
Cobas Immunoassay Systems
Petric et al. [15]
Suh et al. [17]
Strazisar et al. [21]
Kuru et al. [19]
Sands et al. [18]
Lee et al. [16]
Immunoradiometric assays SELCO Tg, TgCTK, or RIASON
Trimboli P et al. Thyroglobulin as Predictor of Thyroid Malignancy … Horm Metab Res 2015; 47: 247–252
569 ng/ml (mean) 121 ng/ml (median in goiter) 125 ng/ ml (median in adenoma) 90 ng/ml (median)
53 ng/ml (mean)
116.3 ng/ml (median)
15.4 ng/ml (median)
172 ng/ml (median)
NR
malignancy
78 ng/ml
1 000 ng/ml
75 ng/ml
NR
187.5 ng/ml
300 ng/ml
300 ng/ml
75 ng/ml
NR
NR
71.1 %
31 %
61 %
NR
48.5 %
50.4 %
21 %
75 %
ROC cirve: 43 % sensitivity for 90 % specificity and 80 % sensitivity for 42 % specificity NR
Sensitivity
Speci-
49 %
86 %
65 %
NR
91.5 %
69.3 %
95 %
76 %
NR
ficity
19.1 %
43.1 %
81 %
NR
NR
44.4 %
44.4 %
75 %
NR
NR
PPV
90.9 %
78.5 %
71 %
NR
NR
74.2 %
85.2 %
76 %
NR
NR
NPV
Among patients with follicular cell cytology, preoperative serum Tg was significantly higher in thyroid carcinoma compared to benign lesions at final histology (p = 0.007) Predictive values of Tg + FNAB were higher compared to those of FNAB only (p = 0.015) Among patients with Hürthle cell cytology, preoperative serum Tg was significantly higher in patients with malignant compared to those with benign lesions (p = 0.007). Preoperative serum Tg > 1 000 ng/ml was an independent predictor of malignancy in Hürthle cell cytology (OR: 2.11; p = 0.0001) Preoperative serum Tg > 78 ng/ml was an independent predictor of malignancy (OR: 2; p = 0.019)
There was no significant difference in preoperative serum Tg level between malignant and benign histology groups in patients with follicular or Hürthle cell cytology at FNAB (p = 0.54)
Among patients with follicular cell cytology, preoperative serum Tg was significantly higher in FC compared to benign lesions or PC at final histology (p
