Med Oncol (2014) 31:814 DOI 10.1007/s12032-013-0814-2
ORIGINAL PAPER
The relationship between thyroid volume and malignant thyroid disease Ayse Ocak Duran • Cuneyd Anil • Alptekin Gursoy Aslı Nar • Ozden Altundag • Mevlude Inanc • Oktay Bozkurt • Neslihan Bascil Tutuncu
•
Received: 3 November 2013 / Accepted: 6 December 2013 Ó Springer Science+Business Media New York 2013
Abstract The present retrospective study aimed to investigate the relationship between thyroid volume and prevalence of thyroid cancer. We investigated the data of 3,850 patients who underwent fine-needle aspiration biopsy (FNAB). Biopsy results were evaluated as diagnostic or nondiagnostic, and diagnostic results were classified as benign, malignant, and indeterminate. We included 2,672 patients who underwent FNAB firstly in our hospital and evaluated as diagnostic biopsy except subgroup of indeterminate. We obtained cytologic data, levels of serum thyroid-stimulating hormone (TSH), and thyroid volumes of those patients retrospectively. Among 2,672 patients with thyroid nodule, 2,562 (95.9 %) patients had benign cytology and 110 (%4,1) patients had malignant cytology. There was no correlation between the malignancy and gender (p = 0.935), and patients with malignant cytology were younger (52 vs 59, p \ 0.001). Also, TSH levels were higher in patients with malignant than benign cytology (p = 0.017). Median volume of right part, left part, and total thyroid for patients who had malignant cytology was
A. O. Duran (&) M. Inanc O. Bozkurt Department of Medical Oncology, Faculty of Medicine, Erciyes University, Kayseri, Turkey e-mail: [email protected] C. Anil A. Nar N. B. Tutuncu Department of Endocrinology and Metabolism, Faculty of Medicine, Baskent University, Ankara, Turkey A. Gursoy Department of Endocrinology and Metabolism, Guven Hospital, Ankara, Turkey O. Altundag Department of Medical Oncology, Faculty of Medicine, Baskent University, Ankara, Turkey
significantly lower than patients who had benign cytology (8.3, 7.1, 15.9 vs 10.8 ml, 9.0 mml, 20.6 ml, respectively, p B 0.001 for all parameters). The results demonstrated that thyroid cancer prevalence was higher in patients with low thyroid volume. According to our results, thyroid volume should be considered as a risk factor for malignancy in the evaluation of thyroid nodules. Keywords
Thyroid cancer Thyroid volume
Introduction Early diagnosis of thyroid cancer is very important for mortality. Both clinical and sonographic variables have been investigated with regard to their ability to modify nodule cancerous risk [1, 2]. Thyroid ultrasound is a widespread technique that is used as a first-line diagnostic procedure for detecting and characterizing nodular thyroid disease. One of the most difficult challenges in thyroid imaging is the determination of whether a thyroid nodule is benign or malignant. Another hot topic of recent years is the functional, morphological, and pathological changes in the thyroid gland. The assessment of thyroid gland by ultrasound can predict malignant disease. The sonographic findings of microcalcifications, hypoechogenicity, absence of a halo, and irregular nodular margins all increase cancer risk [3]. Thyroid nodule volume can influence risk assessment for malignant disease. However, the relationship between thyroid volume and abnormalities of thyroid gland appears to be remarkable. To date, no study was performed to evaluate thyroid volume and prevalence of thyroid cancer in patients with thyroid nodule. The aim of this study was to investigate the correlation between thyroid volume and prevalence of thyroid cancer.
123
814 Page 2 of 4
Patients and methods In this retrospective study, following approval of the local ethics committee, data of 3,850 patients were reviewed and 2,672 patients, who underwent fine-needle aspiration biopsy (FNAB) between June 2003 and January 2009, were included. The patients with previous pathological diagnosis by operation or FNAB in other medical centers were excluded. Age, gender, cytologic diagnosis, and laboratory findings of the patients were noted. Cytologic classification was performed as benign, malignant, indeterminate/suspected, and inadequate material [4]. Adequacy of material was recognized as presence of at least 10–15 thyroid cells in each group, with at least 6 thyroid cell groups [4]. Materials with inadequate number of thyroid cells due to cystic content, thick smear, or poor technique were deemed as inadequate. Serum thyroid-stimulating hormone (TSH) and thyroid ultrasonography were performed in all participants. The preoperative ultrasound examinations were retrospectively reviewed. Volumes of thyroid glands and nodules were calculated according to the ellipsoid formula: volume (mL) = depth (cm) 9 width (cm) 9 length (cm) 9 p/6. Statistical analysis of the acquired data was carried out with SPSS 17.0 (SSPS Inc, Chicago, USA) for Windows package program. As descriptive statistics, numerical values and percentiles were used for categorical data. The compliance of numerical values to the normal distribution was evaluated with one-sample Kolmogorov–Smirnov test. Since numerical values did not have a normal distribution, median and minimum–maximum values were employed. Intergroup comparisons for categorical values were performed with chi-square test. Moreover, since the relationships between variables expressed by measurement were not compliant with normal distribution, they were evaluated with Mann–Whitney U test. In all evaluations, results with p \ 0.05 within a confidence interval of 95 % were deemed as statistically significant.
Results Among 2,672 patients with thyroid nodule, 2,562 (95.9 %) patients had benign cytology and 110 (%4,1) patients had malignant cytology. In the study population, 2,105 (78.8 %) patients were female and 567 (21.2 %) patients were male. Malign cytology was detected in 87 (%4.1) of women and 23 (%4.1) of men; there was no correlation between the malignancy and gender (p = 0.935, Table 1). Median age for patients who had benign and malignant cytology was 59 and 52, respectively, and there was a statistically significant difference between the groups with regard to age (p \ 0.001, Table 1). Also, TSH levels were
123
Med Oncol (2014) 31:814 Table 1 The relationship of malignancy with age, gender, and TSH Benign Female (n, %)
Malignant
p
2,018 (% 95.9)
87 (% 4.1)
Male (n, %)
544 (% 95.9)
23 (% 4.1)
0.935
Age (years)
59 (15–97)
59 (17–90)
\0.001
TSH (mIU/L)
0.9 (0.01–28.1)
1.2 (0–5.6)
0.017
TSH thyroid-stimulating hormone Table 2 The relationship of thyroid malignancy with thyroid volume Benign
Malignant
Right thyroid volume (ml)
10.8
8.3
Left thyroid volume (ml) Total thyroid volume (ml)
9.0 20.6
7.1 15.9
p B0.001
higher in patients with malignant than benign cytology (1.2 vs 0.9 mIU/L, p = 0.017, Table 2). Median volume of right part, left part, and total thyroid for patients who had malignant cytology was significantly lower than patients who had benign cytology (8.3, 7.1, 15.9 ml vs 10.8 ml, 9.0 mml, 20.6 ml, respectively, p B 0.001 for all parameters).
Discussion Both clinical and sonographic variables have been investigated with regard to their ability to modify nodule cancerous risk [1, 2]. Several clinical features and mechanisms have been suggested to predict malignancy such as age, elevated TSH levels, and insulin resistance (IR) [5, 6]. One of the most difficult challenges in thyroid imaging is the determination of whether a thyroid nodule is benign or malignant. Previous studies suggested that nodule size may assist in cancer risk assessment; however, data are conflicting [3, 7, 8]. According to the knowledge, a relationship between thyroid volume and risk of nodule malignancy was not evaluated up to now. In the current study, we determined a significant correlation between the low thyroid volume and thyroid malignancy among patients diagnosed with thyroid disease by biopsy. Palpable thyroid nodules are relatively common, being reported in 4–7 % of the adult population. Most of these lesions are benign, and thyroid cancer is rare (5 % of all thyroid nodules) [9]. Thyroid cancer presents as a thyroid nodule detected by palpation and more frequently by neck ultrasound. Thyroid ultrasound is a widespread technique that is used as a first-line diagnostic procedure for detecting and characterizing nodular thyroid disease. FNAB is an important technique that recommended as an initial screening tool for the diagnosis of thyroid nodules [10]. Thyroid FNAB diagnosis is ‘‘suspicious for neoplasm,’’ in
Med Oncol (2014) 31:814
the neighborhood of 10 %, warranting surgical resection. Therefore, surgery with its risks and complications is an unnecessary procedure for many patients. We suggested that thyroid volume may predict malignancy in patients with cytologic diagnosis of ‘‘suspicious for neoplasm.’’ Also, up to 7 % of nodules continue to yield nondiagnostic cytology results despite repeated biopsies and may be malignant at the time of surgery [11, 12]. Evaluation of thyroid volume may provide additional information in this regard. FNAC should be performed in any thyroid nodule [1 cm and in those \1 cm if there is any clinical (lymphadenopathy, a history of head and neck irradiation, or a history of thyroid cancer in one or more first-degree relatives) or ultrasonographic (such as hypoechogenicity, microcalcifications, absence of peripheral halo, irregular borders, solid aspect, intranodular blood flow, and shape) suspicion of malignancy [5]. However, some nodules \1 cm lack these warning signs yet eventually cause morbidity and mortality [5]. We suggest the hypothesis that thyroid volume may lead the way in this regard. We suggested that the use of thyroid volume for screening may detect thyroid cancer at an earlier stage and overall survival may be improved. Various sonographic characteristics of a thyroid nodule have been associated with a higher likelihood of malignancy [13, 14]. We think that combination of features, including thyroid volume, has high predictive value for malignancy. Progression of the thyroid cell cycle is dependent on joint activity of TSH and insulin and/or IGF-1, all of which function as co-mitogenic factors [15]. TSH is a major hormone that plays an important role in regulating the growth and differentiation of thyroid cells [16]. High levels of TSH are associated with a increased probability of malignancy [17]. So, serum TSH levels should be evaluated in the initial evaluation of a patient with a thyroid nodule. We found a significant association between serum TSH levels and malign thyroid disease in accordance with studies done so far. Experimental evidences showed that elevated insulin and/ or glucose levels may lead to malignant transformation or tumoral growth by affecting cellular energy metabolism [18]. Elevated insulin levels due to IR lead to increase in IGF-1 level. IGFs are produced by many tissues, and they have receptors on the surface of many cancer cells [15]. Although the proliferative properties of insulin and IGF-1, the impact of these parameters on the total thyroid volume is unclear. Insulin and IGF-1 may stimulate proliferation and differentiation and may cause malignant transformation of thyroid cells without affecting the total volume of thyroid [19]. Although thyroid cancer risk is known to be higher among men, latest epidemiological studies have demonstrated papillary and follicular cancer rates as twofold higher in women
Page 3 of 4 814
[20]. In the current study, malignancy rate was higher among men; however, this rate was not statistically significant. Age \14 or [70 years suggesting increased risk of malignant potential [4]. In our study, the patients with malignancy were younger than benign patients.
Limitations Our study was based on data acquired from a single center. The number of patients may appear adequate with regard to the entire study population; however, the number of malignant patients was relatively low.
Conclusion The results demonstrated that thyroid cancer prevalence was higher in patients with low thyroid volume. We speculated that if we cannot make a decision clearly for thyroid nodule biopsy, thyroid volume may be one of the criteria to be taken into account for this decision. According to our results, thyroid volume should be considered as a risk factor for malignancy in the evaluation of thyroid nodules. Further controlled, prospective, randomized studies on this subject are required to gain more information. Conflict of interest
None.
References 1. Hung W, Anderson KD, Chandra RS, Kapur SP, Patterson K, Randolph JG, August GP. Solitary thyroid nodules in 71 children and adolescents. J Pediatr Surg. 1992;27(11):1407–9. 2. 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(11):4295–301. 3. Frates MC, Benson CB, Doubilet PM, Kunreuther E, Contreras M, Cibas ES, Orcutt J, Moore FD Jr, Larsen PR, Marqusee E, Alexander EK. Prevalence and distribution of carcinoma in patients with solitary and multiple thyroid nodules on sonography. J Clin Endocrinol Metab. 2006;91(9):3411–7. 4. American association of clinical endocrinologists and associazione medici endocrinologi medical guidelines for clinical practice for the diagnosis and management of thyroid nodules. AACE/ AME Task force on Thyroid Nodules. Endocrine Practice. 2006; 12: 63–100. 5. American Thyroid Association (ATA) Guidelines Taskforce on Thyroid Nodules and Differentiated Thyroid Cancer, Cooper DS, Doherty GM, Haugen BR, Kloos RT, Lee SL, Mandel SJ, Mazzaferri EL, McIver B, Pacini F, Schlumberger M, Sherman SI, Steward DL, Tuttle RM. Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid. 2009;19(11):1167–214. 6. Reaven GM. Banting lecture 1988. Role of insulin resistance in human disease. Diabetes. 1988;37(12):1595–607.
123
814 Page 4 of 4 7. Raparia K, Min SK, Mody DR, Anton R, Amrikachi M. Clinical outcomes for ‘‘suspicious’’ category in thyroid fine-needle aspiration biopsy: Patient’s sex and nodule size are possible predictors of malignancy. Arch Pathol Lab Med. 2009;133(5):787–90. 8. Mendelson AA, Tamilia M, Rivera J, Hier MP, Sherman M, Garfield N, Black MJ, Rochon L, Gologan O, Payne RJ. Predictors of malignancy in preoperative nondiagnostic biopsies of the thyroid. J Otolaryngol Head Neck Surg. 2009;38(3):395–400. 9. Thyroid fine needle aspiration (FNA) and cytology. Thyroid. 2003;13:80–86. 10. Pacini F, Castagna MG, Brilli L, Pentheroudakis G, ESMO Guidelines Working Group. Thyroid cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2010;21(5):214–9. 11. de los Santos ET, Keyhani-Rofagha S, Cunningham JJ, Mazzaferri EL. Cystic thyroid nodules: the dilemma of malignant lesions. Arch Intern Med. 1990;150:1422–7. 12. Yeh MW, Demircan O, Ituarte P, Clark OH. Falsenegative fineneedle aspiration cytology results delay treatment and adversely affect outcome in patients with thyroid carcinoma. Thyroid. 2004;14:207–15. 13. Nam-Goong IS, Kim HY, Gong G, Lee HK, Hong SJ, Kim WB, Shong YK. Ultrasonography-guided fine-needle aspiration of thyroid incidentaloma: correlation with pathological findings. Clin Endocrinol (Oxf). 2004;60:21–8.
123
Med Oncol (2014) 31:814 14. Frates MC, Benson CB, Doubilet PM, Kunreuther E, Contreras M, Cibas ES, Orcutt J, Moore FD Jr, Larsen PR, Marqusee E, Alexander EK. Prevalence and distribution of carcinoma in patients with solitary and multiple thyroid nodules on sonography. J Clin Endocrinol Metab. 2006;91:3411–7. 15. Vella V, Sciacca L, Pandini G, Mineo R, Squatrito S, Vigneri R, Belfiore A. The IGF system in thyroid cancer: new concepts. Mol Pathol. 2001;54:121–4. 16. Rapoport B, Chazenbalk GD, Jaume JC, McLachlan SM. The thyrotropin (TSH) receptor: interaction with TSH and autoantibodies. Endocr Rev. 1998;19:673–716. 17. Boelaert K, Horacek J, Holder RL, Watkinson JC, Sheppard MC, Franklyn JA. Serum thyrotropin concentrations a novel predictor of malignancy in thyroid nodules investigated by fine-needle aspiration. J Clin Endocrinol Metab. 2006;91:4295–301. 18. Grote VA, Becker S, Kaaks R. Diabetes mellitus type 2: an independent risk factor for cancer. Exp Clin Endocrinol Diabetes. 2010;118:4–8. 19. Ciampolillo A, De Tullio C, Perlino E, Mairano E. The IGF-I axis in thyroid carcinoma. Curr Pharm Des. 2007;13:729–35. 20. Enewold L, Zhu K, Ron E, Marrogi AJ, Stojadinovic A, Peaples GE, Devesa SS. Rising thyroid cancer incidence in the United States by demographic and tumor characteristics 1980–2005. Cancer Epidemiol Biomarkers. 2009;18:784–91.
ORIGINAL PAPER
The relationship between thyroid volume and malignant thyroid disease Ayse Ocak Duran • Cuneyd Anil • Alptekin Gursoy Aslı Nar • Ozden Altundag • Mevlude Inanc • Oktay Bozkurt • Neslihan Bascil Tutuncu
•
Received: 3 November 2013 / Accepted: 6 December 2013 Ó Springer Science+Business Media New York 2013
Abstract The present retrospective study aimed to investigate the relationship between thyroid volume and prevalence of thyroid cancer. We investigated the data of 3,850 patients who underwent fine-needle aspiration biopsy (FNAB). Biopsy results were evaluated as diagnostic or nondiagnostic, and diagnostic results were classified as benign, malignant, and indeterminate. We included 2,672 patients who underwent FNAB firstly in our hospital and evaluated as diagnostic biopsy except subgroup of indeterminate. We obtained cytologic data, levels of serum thyroid-stimulating hormone (TSH), and thyroid volumes of those patients retrospectively. Among 2,672 patients with thyroid nodule, 2,562 (95.9 %) patients had benign cytology and 110 (%4,1) patients had malignant cytology. There was no correlation between the malignancy and gender (p = 0.935), and patients with malignant cytology were younger (52 vs 59, p \ 0.001). Also, TSH levels were higher in patients with malignant than benign cytology (p = 0.017). Median volume of right part, left part, and total thyroid for patients who had malignant cytology was
A. O. Duran (&) M. Inanc O. Bozkurt Department of Medical Oncology, Faculty of Medicine, Erciyes University, Kayseri, Turkey e-mail: [email protected] C. Anil A. Nar N. B. Tutuncu Department of Endocrinology and Metabolism, Faculty of Medicine, Baskent University, Ankara, Turkey A. Gursoy Department of Endocrinology and Metabolism, Guven Hospital, Ankara, Turkey O. Altundag Department of Medical Oncology, Faculty of Medicine, Baskent University, Ankara, Turkey
significantly lower than patients who had benign cytology (8.3, 7.1, 15.9 vs 10.8 ml, 9.0 mml, 20.6 ml, respectively, p B 0.001 for all parameters). The results demonstrated that thyroid cancer prevalence was higher in patients with low thyroid volume. According to our results, thyroid volume should be considered as a risk factor for malignancy in the evaluation of thyroid nodules. Keywords
Thyroid cancer Thyroid volume
Introduction Early diagnosis of thyroid cancer is very important for mortality. Both clinical and sonographic variables have been investigated with regard to their ability to modify nodule cancerous risk [1, 2]. Thyroid ultrasound is a widespread technique that is used as a first-line diagnostic procedure for detecting and characterizing nodular thyroid disease. One of the most difficult challenges in thyroid imaging is the determination of whether a thyroid nodule is benign or malignant. Another hot topic of recent years is the functional, morphological, and pathological changes in the thyroid gland. The assessment of thyroid gland by ultrasound can predict malignant disease. The sonographic findings of microcalcifications, hypoechogenicity, absence of a halo, and irregular nodular margins all increase cancer risk [3]. Thyroid nodule volume can influence risk assessment for malignant disease. However, the relationship between thyroid volume and abnormalities of thyroid gland appears to be remarkable. To date, no study was performed to evaluate thyroid volume and prevalence of thyroid cancer in patients with thyroid nodule. The aim of this study was to investigate the correlation between thyroid volume and prevalence of thyroid cancer.
123
814 Page 2 of 4
Patients and methods In this retrospective study, following approval of the local ethics committee, data of 3,850 patients were reviewed and 2,672 patients, who underwent fine-needle aspiration biopsy (FNAB) between June 2003 and January 2009, were included. The patients with previous pathological diagnosis by operation or FNAB in other medical centers were excluded. Age, gender, cytologic diagnosis, and laboratory findings of the patients were noted. Cytologic classification was performed as benign, malignant, indeterminate/suspected, and inadequate material [4]. Adequacy of material was recognized as presence of at least 10–15 thyroid cells in each group, with at least 6 thyroid cell groups [4]. Materials with inadequate number of thyroid cells due to cystic content, thick smear, or poor technique were deemed as inadequate. Serum thyroid-stimulating hormone (TSH) and thyroid ultrasonography were performed in all participants. The preoperative ultrasound examinations were retrospectively reviewed. Volumes of thyroid glands and nodules were calculated according to the ellipsoid formula: volume (mL) = depth (cm) 9 width (cm) 9 length (cm) 9 p/6. Statistical analysis of the acquired data was carried out with SPSS 17.0 (SSPS Inc, Chicago, USA) for Windows package program. As descriptive statistics, numerical values and percentiles were used for categorical data. The compliance of numerical values to the normal distribution was evaluated with one-sample Kolmogorov–Smirnov test. Since numerical values did not have a normal distribution, median and minimum–maximum values were employed. Intergroup comparisons for categorical values were performed with chi-square test. Moreover, since the relationships between variables expressed by measurement were not compliant with normal distribution, they were evaluated with Mann–Whitney U test. In all evaluations, results with p \ 0.05 within a confidence interval of 95 % were deemed as statistically significant.
Results Among 2,672 patients with thyroid nodule, 2,562 (95.9 %) patients had benign cytology and 110 (%4,1) patients had malignant cytology. In the study population, 2,105 (78.8 %) patients were female and 567 (21.2 %) patients were male. Malign cytology was detected in 87 (%4.1) of women and 23 (%4.1) of men; there was no correlation between the malignancy and gender (p = 0.935, Table 1). Median age for patients who had benign and malignant cytology was 59 and 52, respectively, and there was a statistically significant difference between the groups with regard to age (p \ 0.001, Table 1). Also, TSH levels were
123
Med Oncol (2014) 31:814 Table 1 The relationship of malignancy with age, gender, and TSH Benign Female (n, %)
Malignant
p
2,018 (% 95.9)
87 (% 4.1)
Male (n, %)
544 (% 95.9)
23 (% 4.1)
0.935
Age (years)
59 (15–97)
59 (17–90)
\0.001
TSH (mIU/L)
0.9 (0.01–28.1)
1.2 (0–5.6)
0.017
TSH thyroid-stimulating hormone Table 2 The relationship of thyroid malignancy with thyroid volume Benign
Malignant
Right thyroid volume (ml)
10.8
8.3
Left thyroid volume (ml) Total thyroid volume (ml)
9.0 20.6
7.1 15.9
p B0.001
higher in patients with malignant than benign cytology (1.2 vs 0.9 mIU/L, p = 0.017, Table 2). Median volume of right part, left part, and total thyroid for patients who had malignant cytology was significantly lower than patients who had benign cytology (8.3, 7.1, 15.9 ml vs 10.8 ml, 9.0 mml, 20.6 ml, respectively, p B 0.001 for all parameters).
Discussion Both clinical and sonographic variables have been investigated with regard to their ability to modify nodule cancerous risk [1, 2]. Several clinical features and mechanisms have been suggested to predict malignancy such as age, elevated TSH levels, and insulin resistance (IR) [5, 6]. One of the most difficult challenges in thyroid imaging is the determination of whether a thyroid nodule is benign or malignant. Previous studies suggested that nodule size may assist in cancer risk assessment; however, data are conflicting [3, 7, 8]. According to the knowledge, a relationship between thyroid volume and risk of nodule malignancy was not evaluated up to now. In the current study, we determined a significant correlation between the low thyroid volume and thyroid malignancy among patients diagnosed with thyroid disease by biopsy. Palpable thyroid nodules are relatively common, being reported in 4–7 % of the adult population. Most of these lesions are benign, and thyroid cancer is rare (5 % of all thyroid nodules) [9]. Thyroid cancer presents as a thyroid nodule detected by palpation and more frequently by neck ultrasound. Thyroid ultrasound is a widespread technique that is used as a first-line diagnostic procedure for detecting and characterizing nodular thyroid disease. FNAB is an important technique that recommended as an initial screening tool for the diagnosis of thyroid nodules [10]. Thyroid FNAB diagnosis is ‘‘suspicious for neoplasm,’’ in
Med Oncol (2014) 31:814
the neighborhood of 10 %, warranting surgical resection. Therefore, surgery with its risks and complications is an unnecessary procedure for many patients. We suggested that thyroid volume may predict malignancy in patients with cytologic diagnosis of ‘‘suspicious for neoplasm.’’ Also, up to 7 % of nodules continue to yield nondiagnostic cytology results despite repeated biopsies and may be malignant at the time of surgery [11, 12]. Evaluation of thyroid volume may provide additional information in this regard. FNAC should be performed in any thyroid nodule [1 cm and in those \1 cm if there is any clinical (lymphadenopathy, a history of head and neck irradiation, or a history of thyroid cancer in one or more first-degree relatives) or ultrasonographic (such as hypoechogenicity, microcalcifications, absence of peripheral halo, irregular borders, solid aspect, intranodular blood flow, and shape) suspicion of malignancy [5]. However, some nodules \1 cm lack these warning signs yet eventually cause morbidity and mortality [5]. We suggest the hypothesis that thyroid volume may lead the way in this regard. We suggested that the use of thyroid volume for screening may detect thyroid cancer at an earlier stage and overall survival may be improved. Various sonographic characteristics of a thyroid nodule have been associated with a higher likelihood of malignancy [13, 14]. We think that combination of features, including thyroid volume, has high predictive value for malignancy. Progression of the thyroid cell cycle is dependent on joint activity of TSH and insulin and/or IGF-1, all of which function as co-mitogenic factors [15]. TSH is a major hormone that plays an important role in regulating the growth and differentiation of thyroid cells [16]. High levels of TSH are associated with a increased probability of malignancy [17]. So, serum TSH levels should be evaluated in the initial evaluation of a patient with a thyroid nodule. We found a significant association between serum TSH levels and malign thyroid disease in accordance with studies done so far. Experimental evidences showed that elevated insulin and/ or glucose levels may lead to malignant transformation or tumoral growth by affecting cellular energy metabolism [18]. Elevated insulin levels due to IR lead to increase in IGF-1 level. IGFs are produced by many tissues, and they have receptors on the surface of many cancer cells [15]. Although the proliferative properties of insulin and IGF-1, the impact of these parameters on the total thyroid volume is unclear. Insulin and IGF-1 may stimulate proliferation and differentiation and may cause malignant transformation of thyroid cells without affecting the total volume of thyroid [19]. Although thyroid cancer risk is known to be higher among men, latest epidemiological studies have demonstrated papillary and follicular cancer rates as twofold higher in women
Page 3 of 4 814
[20]. In the current study, malignancy rate was higher among men; however, this rate was not statistically significant. Age \14 or [70 years suggesting increased risk of malignant potential [4]. In our study, the patients with malignancy were younger than benign patients.
Limitations Our study was based on data acquired from a single center. The number of patients may appear adequate with regard to the entire study population; however, the number of malignant patients was relatively low.
Conclusion The results demonstrated that thyroid cancer prevalence was higher in patients with low thyroid volume. We speculated that if we cannot make a decision clearly for thyroid nodule biopsy, thyroid volume may be one of the criteria to be taken into account for this decision. According to our results, thyroid volume should be considered as a risk factor for malignancy in the evaluation of thyroid nodules. Further controlled, prospective, randomized studies on this subject are required to gain more information. Conflict of interest
None.
References 1. Hung W, Anderson KD, Chandra RS, Kapur SP, Patterson K, Randolph JG, August GP. Solitary thyroid nodules in 71 children and adolescents. J Pediatr Surg. 1992;27(11):1407–9. 2. 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(11):4295–301. 3. Frates MC, Benson CB, Doubilet PM, Kunreuther E, Contreras M, Cibas ES, Orcutt J, Moore FD Jr, Larsen PR, Marqusee E, Alexander EK. Prevalence and distribution of carcinoma in patients with solitary and multiple thyroid nodules on sonography. J Clin Endocrinol Metab. 2006;91(9):3411–7. 4. American association of clinical endocrinologists and associazione medici endocrinologi medical guidelines for clinical practice for the diagnosis and management of thyroid nodules. AACE/ AME Task force on Thyroid Nodules. Endocrine Practice. 2006; 12: 63–100. 5. American Thyroid Association (ATA) Guidelines Taskforce on Thyroid Nodules and Differentiated Thyroid Cancer, Cooper DS, Doherty GM, Haugen BR, Kloos RT, Lee SL, Mandel SJ, Mazzaferri EL, McIver B, Pacini F, Schlumberger M, Sherman SI, Steward DL, Tuttle RM. Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid. 2009;19(11):1167–214. 6. Reaven GM. Banting lecture 1988. Role of insulin resistance in human disease. Diabetes. 1988;37(12):1595–607.
123
814 Page 4 of 4 7. Raparia K, Min SK, Mody DR, Anton R, Amrikachi M. Clinical outcomes for ‘‘suspicious’’ category in thyroid fine-needle aspiration biopsy: Patient’s sex and nodule size are possible predictors of malignancy. Arch Pathol Lab Med. 2009;133(5):787–90. 8. Mendelson AA, Tamilia M, Rivera J, Hier MP, Sherman M, Garfield N, Black MJ, Rochon L, Gologan O, Payne RJ. Predictors of malignancy in preoperative nondiagnostic biopsies of the thyroid. J Otolaryngol Head Neck Surg. 2009;38(3):395–400. 9. Thyroid fine needle aspiration (FNA) and cytology. Thyroid. 2003;13:80–86. 10. Pacini F, Castagna MG, Brilli L, Pentheroudakis G, ESMO Guidelines Working Group. Thyroid cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2010;21(5):214–9. 11. de los Santos ET, Keyhani-Rofagha S, Cunningham JJ, Mazzaferri EL. Cystic thyroid nodules: the dilemma of malignant lesions. Arch Intern Med. 1990;150:1422–7. 12. Yeh MW, Demircan O, Ituarte P, Clark OH. Falsenegative fineneedle aspiration cytology results delay treatment and adversely affect outcome in patients with thyroid carcinoma. Thyroid. 2004;14:207–15. 13. Nam-Goong IS, Kim HY, Gong G, Lee HK, Hong SJ, Kim WB, Shong YK. Ultrasonography-guided fine-needle aspiration of thyroid incidentaloma: correlation with pathological findings. Clin Endocrinol (Oxf). 2004;60:21–8.
123
Med Oncol (2014) 31:814 14. Frates MC, Benson CB, Doubilet PM, Kunreuther E, Contreras M, Cibas ES, Orcutt J, Moore FD Jr, Larsen PR, Marqusee E, Alexander EK. Prevalence and distribution of carcinoma in patients with solitary and multiple thyroid nodules on sonography. J Clin Endocrinol Metab. 2006;91:3411–7. 15. Vella V, Sciacca L, Pandini G, Mineo R, Squatrito S, Vigneri R, Belfiore A. The IGF system in thyroid cancer: new concepts. Mol Pathol. 2001;54:121–4. 16. Rapoport B, Chazenbalk GD, Jaume JC, McLachlan SM. The thyrotropin (TSH) receptor: interaction with TSH and autoantibodies. Endocr Rev. 1998;19:673–716. 17. Boelaert K, Horacek J, Holder RL, Watkinson JC, Sheppard MC, Franklyn JA. Serum thyrotropin concentrations a novel predictor of malignancy in thyroid nodules investigated by fine-needle aspiration. J Clin Endocrinol Metab. 2006;91:4295–301. 18. Grote VA, Becker S, Kaaks R. Diabetes mellitus type 2: an independent risk factor for cancer. Exp Clin Endocrinol Diabetes. 2010;118:4–8. 19. Ciampolillo A, De Tullio C, Perlino E, Mairano E. The IGF-I axis in thyroid carcinoma. Curr Pharm Des. 2007;13:729–35. 20. Enewold L, Zhu K, Ron E, Marrogi AJ, Stojadinovic A, Peaples GE, Devesa SS. Rising thyroid cancer incidence in the United States by demographic and tumor characteristics 1980–2005. Cancer Epidemiol Biomarkers. 2009;18:784–91.
