Ratio of Thyrotropin to Thyroglobulin as a Novel Marker for Differentiating Between Benign and Malignant Thyroid Nodules within Different Bethesda Categories

Tam, Abbas Ali

Ratio of Thyrotropin to Thyroglobulin as a Novel Marker for Differentiating Between Benign and Malignant Thyroid Nodules within Different Bethesda Categories

ABBAS ALİ TAM (Ankara Yıldırım Beyazıt University Faculty of Medicine, Department of Endocrinology and Metabolism, Ankara, Turkey)

Turkish Journal of Endocrinology and Metabolism

1 0

Yıl: 2018 Cilt: 22 Sayı: 1 Sayfa Aralığı: 21 - 31 Metin Dili: Türkçe İndeks Tarihi: 29-07-2022

Ratio of Thyrotropin to Thyroglobulin as a Novel Marker for Differentiating Between Benign and Malignant Thyroid Nodules within Different Bethesda Categories

Öz:

Malign ve benign tiroid nodüllerinin ayırımında yeni birprediktif markır olarak tirotropin (TSH) tiroglobulin (Tg) oranınıaraştırmayı amaçladık.Gereç ve Yöntemler: 2007 ve 2014 arasında opere edilenötiroid hastalar retrospektif olarak değerlendirildi. Tiroid hastalığı veya cerrahi öyküsü olanlar ve artmış anti-tiroglobulinantikorları olanlar dışlandı.Histopatolojik olarak benign ve malign gruplar klinikopatolojik özellikler ve serum TSH, Tg,TSH/Tg oranı açısından karşılaştırıldı.Bulgular: 370 (%60.3) benign ve 244 (%39.7) malignhasta vardı.Benign hastalara göre malign hastalarda anlamlıolarak yüksek TSH, TSH/Tg ve total tiroid hacmi ve düşük Tgvardı (her biri için, p<0.001). (%74.2) benign ve 321 (%25.8)malign nodül vardı. Sitopatalojik dağılım şöyleydi; 343(%27.6) nondiagnostik, 637 (%51.2) benign, 121 (%9.7)önemi belirlenemeyen atipi/önemi belirlenemeyen folliküler lezyon (ÖBA/ÖBFL), 39 (%3.1) folliküler neoplazi/follikülerneoplazi şüphesi (FN/FNŞ), 64 (%5.1) malignite şüphesi(MŞ) ve 41 (%3.3) malign. TSH, Tg ve TSH/Tg Bethesdakategorilerinde anlamlı olarak farklıydı (her biri için p<0.001).Median TSH/Tg benignde (0.013) en düşük ve MŞ (0.054)ve malign sitolojilerde (0.086) en yüksekti. ÖBA/ÖBFL,FN/FNŞ ve MŞ kategorilerinde, TSH/Tg oranı malign nodüllerde benign nodüllere göre yüksek bulundu (sırasıyla,p=0.001, p<0.001 ve p=0.003). Regresyon analizindeTSH/Tg; TSH ve Tg'ye göre daha yüksek tanısal performansasahipti (p<0.001).Tartışma: TSH/Tg ameliyat öncesinde benign ve maligntiroid nodüllerinin ayırımında yeni bir marker olarak kullanılabilir. Ayrıca indetermine sitolojisi olan nodüllerde malignite riskinin belirlenmesine ve yönetimine yardımcı olabilir

Anahtar Kelime:

Konular: Endokrinoloji ve Metabolizma

Benign ve Malign Tiroid Nodüllerinin Ayrımında ve Farklı Bethesda Kategorilerinde Yeni bir Belirteç Olarak Tirotropin Tiroglobulin Oranı

Öz:

We aimed to determine whether the ratio of thyrotropin (TSH) to thyroglobulin (Tg) (TSH/Tg) would be able to assist in predicting malignancy in thyroid nodules.Material and Methods: Euthyroid patients operated betweenthe year 2007 and 2014 were retrospectively reviewed. Patientswho previously had thyroid disease or surgery and those with increased levels of anti-thyroglobulin antibodies were excludedfrom this study. Clinicopathological features, as well as serumTSH, Tg, and TSH/Tg were compared between histopathologically benign and malignant groups.Results: Data related to 370 (60.3%) benign and 244 (39.7%)malignant patients were analyzed. The malignant patients exhibited significantly higher TSH, TSH/Tg, and total thyroid volume, anda lower Tg compared to the benign patients (p<0.001 for each).There were 924 (74.2%) benign and 321 (25.8%) malignant nodules. Cytological distribution of the nodules was observed to beas follows: 343 (27.6%) nondiagnostic, 637 (51.2%) benign, 121(9.7%) atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS), 39 (3.1%) follicular neoplasm/suspicious for follicular neoplasm (FN/SFN), 64 (5.1%)suspicious for malignancy (SM), and 41 (3.3%) malignant. TSH,Tg, and TSH/Tg were significantly different in different Bethesdacategories (p<0.001 for each). Median TSH/Tg was the lowest inbenign (0.013), and highest in SM (0.054) and malignant (0.086)cytologies. TSH/Tg was significantly higher in the malignant nodules compared to benign nodules, in AUS/FLUS, FN/SFN, and SMcategories (p=0.001, p<0.001, and p=0.003, respectively). In theregression analysis, TSH/Tg demonstrated higher diagnostic performance compared to TSH and Tg (p<0.001).Discussion: Preoperative TSH/Tg could be used as a novel marker for differentiating between benign and malignant thyroid nodules. It could also assist in the prediction of risk of malignancyand management decisions when the cytology is indeterminate

Anahtar Kelime:

Konular: Endokrinoloji ve Metabolizma

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık

1. Ali SZ. Thyroid cytopathology: Bethesda and beyond. Acta Cytol. 2011;55:4-12.
2. Arul P, Akshatha C, Masilamani S. A study of malignancy rates in different diagnostic categories of the Bethesda system for reporting thyroid cytopathology: an institutional experience. Biomed J. 2015; 38:517-522.
3. Dorange A, Triau S, Mucci-Hennekinne S, Bizon A, Laboureau-Soares S, Illouz F, Rodien P, Rohmer V. An elevated level of TSH might be predictive of differentiated thyroid cancer. Ann Endocrinol (Paris). 2011;72:513-521.
4. Bongiovanni M, Spitale A, Faquin WC, Mazzucchelli L, Baloch ZW. The Bethesda system for reporting thyroid cytopathology: a meta-analysis. Acta Cytol. 2012;56:333-339.
5. Liu X, Medici M, Kwong N, Angell TE, Marqusee E, Kim MI, Larsen PR, Cho NL, Nehs MA, Ruan DT, Gawande A, Moore F Jr, Barletta J, Krane JF, Cibas ES, Yang T, Alexander EK. Bethesda categorization of thyroid nodule cytology and prediction of thyroid cancer type and prognosis. Thyroid. 2016;26:256- 261.
6. Castro MR, Espiritu RP, Bahn RS, Henry MR, Gharib H, Caraballo PJ, Morris JC. Predictors of malignancy in patients with cytologically suspicious thyroid nodules. Thyroid. 2011;21:1191-1198.
7. Jin J, Machekano R, McHenry CR. The utility of preoperative serum thyroid-stimulating hormone level for predicting malignant nodular thyroid disease. Am J Surg. 2010;199:294-297.
8. Boelaert K, Horacek J, Holder RL, Watkinson JC, Sheppard MC, Franklyn JA. Serum thyrotropin concentration as a novel predictor of malignancy in thyroid nodules investigated by fine-needle aspiration. J Clin Endocrinol Metab. 2006;91:4295-4301.
9. Oltmann SC, Leverson G, Lin SH, Schneider DF, Chen H, Sippel RS. Markedly elevated thyroglobulin levels in the preoperative thyroidectomy patient correlates with metastatic burden. J Surg Res. 2014;187:1-5.
10.Zubair Hussain S, Zaman MU, Malik S, Ram N, Asghar A, Rabbani U, Aftab N, Islam N. Preablation stimulated thyroglobulin/TSH ratio as a predictor of successful I (131)remnant ablation in patients with differentiated thyroid cancer following total thyroidectomy. J Thyroid Res. 2014;2014:610273.
11.Petric R, Besic H, Besic N. Preoperative serum thyroglobulin concentration as a predictive factor of malignancy in small follicular and Hürthle cell neoplasms of the thyroid gland. World J Surg Oncol. 2014;12:282.
12.Suh I, Vriens MR, Guerrero MA, Griffin A, Shen WT, Duh QY, Clark OH, Kebebew E. Serum thyroglobulin is a poor diagnostic biomarker of malignancy in follicular and Hürthle-cell neoplasms of the thyroid. Am J Surg. 2010;200:41-46.
13.Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, Pacini F, Randolph GW, Sawka AM, Schlumberger M, Schuff KG, Sherman SI, Sosa JA, Steward DL, Tuttle RM, Wartofsky L. 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. 2016;2016:1-133.
14.Shi L, Li Y, Guan H, Li C, Shi L, Shan Z, Teng W. Usefulness of serum thyrotropin for risk prediction of differentiated thyroid cancers does not apply to microcarcinomas: results of 1,870 Chinese patients with thyroid nodules. Endocr J. 2012;59:973- 980.
15.Moon SS, Lee YS, Lee IK, Kim JG. Serum thyrotropin as a risk factor for thyroid malignancy in euthyroid subjects with thyroid micronodule. Head Neck. 2012;34:949-952.
16.He H, Li W, Liyanarachchi S, Jendrzejewski J, Srinivas M, Davuluri RV, Nagy R, de la Chapelle A. Genetic predisposition to papillary thyroid carcinoma: involvement of FOXE1, TSHR, and a novel lincRNA gene, PTCSC2. J Clin Endocrinol Metab. 2015;100: E164-172.
17.Hoelting T, Tezelman S, Siperstein AE, Duh QY, Clark OH. Thyrotropin stimulates invasion and growth of follicular thyroid cancer cells via PKC- rather than PKA-activation. Biochem Biophys Res Commun. 1993;195:1230-1236.
18.Brabant G, Maenhaut C, Köhrle J, Scheumann G, Dralle H, Hoang-Vu C, Hesch RD, von zur Mühlen A, Vassart G, Dumont JE. Human thyrotropin receptor gene: expression in thyroid tumors and correlation to markers of thyroid differentiation and dedifferentiation. Mol Cell Endocrinol. 1991;82:R7- 12.
19. Jonklaas J, Nsouli-Maktabi H, Soldin SJ. Endogenous thyrotropin and triiodothyronine concentrations in individuals with thyroid cancer. Thyroid. 2008;18:943-952.
20.Haymart MR, Repplinger DJ, Leverson GE, Elson DF, Sippel RS, Jaume JC, Chen H. 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. 2008;93:809-814.
21.Kim KW, Park YJ, Kim EH, Park SY, Park DJ, Ahn SH, Park DJ, Jang HC, Cho BY. Elevated risk of papillary thyroid cancer in Korean patients with Hashimoto’s thyroiditis. Head Neck. 2011;33:691-695.
22.Negro R, Valcavi R, Riganti F, Toulis KA, Colosimo E, Bongiovanni M, Grassi P, Giovanella L, Gardini G, Piana S. Thyrotropin values in patients with micropapillary thyroid cancer versus benign nodular disease. Endocr Pract. 2013;19:651-655.
23.Lin YS, Li TJ, Liang J, Li X, Qiu L, Wang S, Chen Y, Kang Z, Li F. Predictive value of preablation stimulated thyroglobulin and thyroglobulin/thyroid-stimulating hormone ratio in differentiated thyroid cancer. Clin Nucl Med. 2011;36:1102-1105.
24.Guarino E, Tarantini B, Pilli T, Checchi S, Brilli L, Ciuoli C, Di Cairano G, Mazzucato P, Pacini F. Presurgical serum thyroglobulin has no prognostic value in papillary thyroid cancer. Thyroid. 2005;15:1041- 1045.
25.Youn I, Sung JM, Kim EK, Kwak JY. Serum thyroglobulin adds no additional value to ultrasonographic features in a thyroid malignancy. Ultrasound Q. 2014;30:287-290.
26.Lee EK, Chung KW, Min HS, Kim TS, Kim TH, Ryu JS, Jung YS, Kim SK, Lee YJ. Preoperative serum thyroglobulin as a useful predictive marker to differentiate follicular thyroid cancer from benign nodules in indeterminate nodules. J Korean Med Sci. 2012;27:1014-1018.
27.Sands NB, Karls S, Rivera J, Tamilia M, Hier MP, Black MJ, Gologan O, Payne RJ. Preoperative serum thyroglobulin as an adjunct to fine-needle aspiration in predicting well-differentiated thyroid cancer. J Otolaryngol Head Neck Surg. 2010;39: 669-673.
28.Wang L, Li H, Yang Z, Guo Z, Zhang Q. Preoperative serum thyrotropin to thyroglobulin ratio is effective for thyroid nodule evaluation in euthyroid patients. Otolaryngol Head Neck Surg. 2015;153:15-19.
29.Yazici P, Mihmanli M, Bozkurt E, Ozturk FY, Uludag M. Which is the best predictor of thyroid cancer: thyrotropin, thyroglobulin or their ratio? Hormones (Athens). 2016;15:256-263.
30.Cibas ES, Ali SZ. The Bethesda system for reporting thyroid cytopathology. Am J Clin Pathol. 2009;132: 658-665.
31.Liu X, Medici M, Kwong N, Angell TE, Marqusee E, Kim MI, Larsen PR, Cho NL, Nehs MA, Ruan DT, Gawande A, Moore F Jr, Barletta J, Krane JF, Cibas ES, Yang T, Alexander EK. Bethesda categorization of thyroid nodule cytology and prediction of thyroid cancer type and prognosis. Thyroid. 2016;26:256- 261.
32.Chen JC, Pace SC, Chen BA, Khiyami A, McHenry CR. Yield of repeat fine-needle aspiration biopsy and rate of malignancy in patients with atypia or follicular lesion of undetermined significance: the impact of the Bethesda System for Reporting Thyroid Cytopathology. Surgery. 2012;152:1037-1044.

APA	Tam A (2018). Ratio of Thyrotropin to Thyroglobulin as a Novel Marker for Differentiating Between Benign and Malignant Thyroid Nodules within Different Bethesda Categories. , 21 - 31.
Chicago	Tam Abbas Ali Ratio of Thyrotropin to Thyroglobulin as a Novel Marker for Differentiating Between Benign and Malignant Thyroid Nodules within Different Bethesda Categories. (2018): 21 - 31.
MLA	Tam Abbas Ali Ratio of Thyrotropin to Thyroglobulin as a Novel Marker for Differentiating Between Benign and Malignant Thyroid Nodules within Different Bethesda Categories. , 2018, ss.21 - 31.
AMA	Tam A Ratio of Thyrotropin to Thyroglobulin as a Novel Marker for Differentiating Between Benign and Malignant Thyroid Nodules within Different Bethesda Categories. . 2018; 21 - 31.
Vancouver	Tam A Ratio of Thyrotropin to Thyroglobulin as a Novel Marker for Differentiating Between Benign and Malignant Thyroid Nodules within Different Bethesda Categories. . 2018; 21 - 31.
IEEE	Tam A "Ratio of Thyrotropin to Thyroglobulin as a Novel Marker for Differentiating Between Benign and Malignant Thyroid Nodules within Different Bethesda Categories." , ss.21 - 31, 2018.
ISNAD	Tam, Abbas Ali. "Ratio of Thyrotropin to Thyroglobulin as a Novel Marker for Differentiating Between Benign and Malignant Thyroid Nodules within Different Bethesda Categories". (2018), 21-31.

APA	Tam A (2018). Ratio of Thyrotropin to Thyroglobulin as a Novel Marker for Differentiating Between Benign and Malignant Thyroid Nodules within Different Bethesda Categories. Turkish Journal of Endocrinology and Metabolism, 22(1), 21 - 31.
Chicago	Tam Abbas Ali Ratio of Thyrotropin to Thyroglobulin as a Novel Marker for Differentiating Between Benign and Malignant Thyroid Nodules within Different Bethesda Categories. Turkish Journal of Endocrinology and Metabolism 22, no.1 (2018): 21 - 31.
MLA	Tam Abbas Ali Ratio of Thyrotropin to Thyroglobulin as a Novel Marker for Differentiating Between Benign and Malignant Thyroid Nodules within Different Bethesda Categories. Turkish Journal of Endocrinology and Metabolism, vol.22, no.1, 2018, ss.21 - 31.
AMA	Tam A Ratio of Thyrotropin to Thyroglobulin as a Novel Marker for Differentiating Between Benign and Malignant Thyroid Nodules within Different Bethesda Categories. Turkish Journal of Endocrinology and Metabolism. 2018; 22(1): 21 - 31.
Vancouver	Tam A Ratio of Thyrotropin to Thyroglobulin as a Novel Marker for Differentiating Between Benign and Malignant Thyroid Nodules within Different Bethesda Categories. Turkish Journal of Endocrinology and Metabolism. 2018; 22(1): 21 - 31.
IEEE	Tam A "Ratio of Thyrotropin to Thyroglobulin as a Novel Marker for Differentiating Between Benign and Malignant Thyroid Nodules within Different Bethesda Categories." Turkish Journal of Endocrinology and Metabolism, 22, ss.21 - 31, 2018.
ISNAD	Tam, Abbas Ali. "Ratio of Thyrotropin to Thyroglobulin as a Novel Marker for Differentiating Between Benign and Malignant Thyroid Nodules within Different Bethesda Categories". Turkish Journal of Endocrinology and Metabolism 22/1 (2018), 21-31.