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Incidence and Risk Factors of Thyroid Malignancy in Patients with Toxic Nodular Goiter

Incidence and Risk Factors of Thyroid Malignancy in Patients with Toxic Nodular Goiter Hindawi International Journal of Surgical Oncology Volume 2022, Article ID 1054297, 5 pages https://doi.org/10.1155/2022/1054297 Research Article Incidence and Risk Factors of Thyroid Malignancy in Patients with Toxic Nodular Goiter 1 1 1 Tarek Zaghloul Mohamed , Ahmed Abd El Aal Sultan , Mohamed Tag El-Din , 1 1 1 Ahmed A. Elfattah Mostafa , Mohammed A. Nafea , Abd-Elfattah Kalmoush , 1 2 1 Mohammed Shaaban Nassar, Mohamad Adel Abdalgaleel, Ahmed M. Hegab , 1 1 Ayman Helmy Ibrahim , and Mohamad Baheeg General Surgery, Faculty of Medicine, Al-Azhar University, Cairo, Egypt Surgical Oncology, Faculty of Medicine, Al-Azhar University, Cairo, Egypt Correspondence should be addressed to Ahmed Abd El Aal Sultan; dr.ahmedsultan@azhar.edu.eg Received 25 March 2022; Accepted 12 May 2022; Published 23 May 2022 Academic Editor: C. H. Yip Copyright © 2022 Tarek Zaghloul Mohamed et al. �is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background. Although hyperfunctioning thyroid disorders were thought to be protective against malignancy, some recent studies reported a high incidence of incidentally discovered cancer in patients with hyperfunctioning benign thyroid disorders. We performed this study to estimate the incidence and predictors of malignant thyroid disease in patients with toxic nodular goiter (TNG). Patients and Methods. �e data of 98 patients diagnosed with TNG were reviewed (including toxic multinodular goiter SMNG and single toxic nodule STN). �e collected data included patients age, gender, systemic comorbidities, family history of thyroid malignancy, previous neck radiation, type of disease (multinodular or single), size of the dominant nodule by the US, operative time, and detection of signiŽcant lymph nodes during operation. Based on the histopathological analysis, the cases were allocated into benign and malignant groups. Results. Malignancy was detected in 21 patients (21.43%). Although age distribution was comparable between the two groups, males showed a signiŽcant increase in association with malignancy. Medical comorbidities and family history of cancer did not di–er between the two groups. However, TMNG showed a statistically higher prevalence in the malignant group. Operative data, including operative time and lymph node detection, were comparable between the two groups. On regression analysis, both male gender and TMNG were signiŽcant predictors of malignancy. Conclusion. �e presence of thyroid hyperfunction is not a protective factor against malignancy, as malignancy was detected in about 1/5 of cases. Male gender and TMNG were signiŽcant risk factors of malignancy in such patients. Graves’ disease, toxic multinodular goiter (TMNG), and 1. Introduction single toxic nodule (STN) are the most common etiologies of �e incidence of thyroid dysfunction is increasing around hyperthyroidism [3, 4]. the world, as approximately they represent 30–40% of pa- �e increased levels of thyroid-stimulating hormone (TSH) were reported to increase the risk of thyroid ma- tients visiting endocrine clinics, making it one of the most common endocrine disorders [1, 2]. According to a previous lignancy, even within normal ranges. Additionally, it is Egyptian epidemiological study, about 30% of patients at- associated with more advanced nodular thyroid disease [5]. tending the endocrine clinic had thyroid dysfunction, from TSH stimulates the proliferation of both normal and well- whom 19.2% had hyperthyroidism, and 15.8% had sub- di–erentiated neoplastic thyroid tissues. Based on the pre- clinical hyperthyroidism [2]. vious belief, suppression of this hormone is one of the 2 International Journal of Surgical Oncology management plans for patients with well-differentiated )e collected data included the patient’s age, gender, thyroid malignancy [6]. systemic comorbidities, family history of thyroid malig- nancy, previous neck radiation, type of disease (multi- Patients with primary toxic goiter express decreased levels of TSH. As a result, they are less likely to harbour nodular or single), size of the dominant nodule by the US, malignant disease due to inhibition of the related oncogenes operative time, and detection of significant lymph nodes [7]. Based on these data, the presence of hyperfunctioning during operation. thyroid disorder was thought to be protective against ma- lignancy [4]. 2.1. Statistical Analysis. )e Statistical Package for the Social Older studies reported a very low incidence of thyroid Sciences (SPSS 26, IBM/SPSS Inc., Chicago, IL) software was cancer in patients with hyperfunctioning thyroid nodules used to analyse the collected data. Frequencies and per- (3–5%) [8]. Even the American )yroid Association does centages (%) or mean values with standard deviations (SD) not recommend cytological evaluation for such nodules due were used to report basic demographic statistics (SD). )e to low malignancy risk [3]. Nevertheless, recent evidence has chi-square test was used to compare two independent sets of proved increased incidence of thyroid malignancy in toxic qualitative data. To compare quantitative data, the inde- goiter patients (12–18%), which confirms that this incidence pendent-samples t-test and the Mann–Whitney U test were has been underestimated in the past [4, 9]. utilised. Risk variables for the binary categorical outcome Herein, we performed this study to estimate the inci- were examined using univariate and multivariate logistic dence and predictors of malignant thyroid disease in pa- regression. A p value of 0.05 or less was used to determine tients with toxic nodular goiter (TNG). the statistical significance. 2. Patients and Methods 3. Results )is is a retrospective study that was performed at the General Surgery Department, Al-Azhar University Hospi- )e mean age of the cases included in the study was 47.13 tals. We retrospectively reviewed the data of consecutive 98 years in the benign group and 48.67 years in the malignant adult patients diagnosed with TNG who underwent surgical group, with no significant difference between the two intervention during the period between January 2018 and groups. Although the female gender was predominant in the December 2020. TNG was defined when the patient had two groups, males showed a significant increase in associ- thyroid nodule (single or multiple), decreased serum TSH, ation with malignancy (p � 0.023). with normal or increased T3 or T4 [4]. )e prevalence of systemic comorbidities, including All of the included cases were subjected to history taking, diabetes, hypertension, and chronic liver disease, showed no clinical examination, and routine preoperative laboratory significant difference between the study groups. Likewise, investigations (including TSH, T3, and T4). Additionally, positive family history of thyroid cancer was reported only in neck ultrasonography (US) was ordered for all cases, and the one case (1.3%) in the benign group, and that was statistically detected nodules were classified according to the British comparable to the malignant one. )yroid Association (BTA) classification [10]. We included We included two types of TNG: TMNG and STN. )e only patients who were classified as U2 according to the former had a statistically larger prevalence in the malignant previous classification and did not require preoperative fine- group, as it was found in 57.14 percent of cases in the benign needle aspiration cytology (FNAC). Contrarily, patients with and 80.95 percent of cases in the malignant group U3 (intermediate), U4 (suspicious), or U5 (malignant) were (p � 0.046). On the other hand, the size of the dominant excluded from the study. Also, we excluded patients with nodule, measured by the US, did not show significant dif- Graves’ disease or previous history of neck radiation. Only ferences between the two groups (p � 0.303). )e previous cases diagnosed with single nodule were subjected to thyroid data are shown in Table 1. scan to confirm hyperfunction. When it comes to the operative data, operative time was After explaining the benefits, details, and potential statistically comparable between the two groups (87.17 vs problems of surgery, we obtained signed informed per- 93.29 in the benign and malignant groups;p � 0.204). No mission from all patients prior to surgical intervention. All significant lymph nodes were detected on surgical explo- cases underwent total thyroidectomy following normaliza- ration in neither of the two groups. Table 2 illustrates these tion of their thyroid profile, according to our management data. protocol. )e surgical specimen was sent to the histopa- On regression analysis to detect risk factors of malig- thology laboratory for analysis. Incidental thyroid cancer nancy in TNG patients, both male gender and TMNG were was established when discovered on histopathological significant predictors of malignancy in patients with TNG in analysis in patients lacking the clinical features of malig- univariate and multivariate analyses, as shown in Table 3. nancy [11]. In our department, routine thyroid evaluation included analysis of all dominant nodules and obtaining one representative section from every one cm of the remaining 3.1. CI: Confidence Interval. Regarding the detected malig- thyroid tissue. Based on the final histopathological report, nancies in our study, 9 patients were diagnosed with pap- we classified the included patients into two groups; benign illary cancer (42.86%) and 7 patients had the follicular and malignant. variant of papillary cancer (33.33%), while the remaining five International Journal of Surgical Oncology 3 Table 1: Preoperative data. Benign group Malignant group Variable p value (n � 77) (n � 21) Age (year) 47.13± 11.94 48.67± 10.66 0.594 Gender Male 12 (15.58%) 8 (38.1%) 0.023 Female 65 (84.42%) 13 (61.90%) Comorbidities Diabetes mellitus 9 (11.69%) 3 (14.29%) 0.748 Hypertension 9 (11.69%) 4 (19.05%) 0.378 Chronic liver disease 2 (2.6%) 0 (0%) 0.456 Family history of cancer thyroid 1 (1.3%) 0 (0%) 0.600 Preoperative diagnosis TMNG 44 (57.14%) 17 (80.95%) 0.046 STN 33 (42.86%) 4 (19.05%) Size of the dominant nodule (mm) by the US 32.29± 12.93 35.67± 14.43 0.303 Table 2: Operative findings. Variable Benign group (n � 77) Malignant group (n � 21) p value Operative time 87.17± 19.30 93.29± 19.90 0.204 Detected lymph nodes 0 (0%) 0 (0%) 1 Table 3: Regression analysis to detect risk factors of malignancy in TNG. Multivariate analysis Variables Univariate analysis OR 95% CI for OR p value Age 0.590 Male gender 0.028 2.713 1.207–8.423 0.043 Diabetes 0.748 Hypertension 0.383 Chronic liver disease 0.999 Family history of cancer thyroid 0.999 TMNG 0.001 3.530 1.642–11.965 0.022 Size of the nodules 0.301 OR: odds ratio. reported that the rate of thyroid malignancy in their 164 cases had the follicular type (23.81%) (data not shown in tables). patients was 18.3% (30 patients) [4]. Moreover, Tam et al. reported an incidence rate of 19.2%, as 14 patients had malignancy out of the included 73 cases [6]. 4. Discussion Other studies reported a lower incidence of the same Historically, the hyperthyroid state observed in patients with parameter. Giles et al. reported an incidence rate of 12%, TNG was presumed to be “protective” against malignant whereas Cerci et al. reported that malignancy was detected in thyroid neoplasms [12]. However, there is a current debate 11 out of 124 patients with TMNG (incidence � 9%) [14]. in the existing literature [6], as some studies reported very Kang et al. included cases with TMNG and STN like us, and low incidence [8], while others reported a high incidence of they detected malignancy in five out of the included 181 malignancy in TNG patients [4]. According to a recent cases, with an incidence rate of 2.7% [8]. A previous study also emphasized that hyperfunc- meta-analysis published in 2021, hot nodules had a lower risk of cancer than cold nodules. Nonetheless, the rate of tioning nodules in the pediatric population have a higher malignancy risk, reaching up to 29% [15]. )is was not malignancy in hot nodules was higher than anticipated [13]. )is study was conducted to estimate the incidence and observed in our study as all of our cases were adults (>18 risk factors of malignant thyroid disease in patients with years). TNG. We included a total of 98 patients diagnosed with Apparently, there is some heterogenicity regarding the TNG. After histopathological examination of the surgical incidence between different studies, and this could be specimen, 21 patients appeared to harbour thyroid malig- explained by different patient selection criteria, aetiology of nancy, with an incidence rate of 21.43%. hyperthyroidism, the operation performed (total or hemi- )is is consistent with a number of recent studies that thyroidectomy), or the extent of histopathological exami- have found an incidence rate similar to ours. Smith et al. nation [16, 17]. 4 International Journal of Surgical Oncology Mirfakhraee et al., the authors reported that papillary In the current study, patient age was not a significant risk factor for malignancy, as it had mean values of 47.13 and neoplasm was the most common malignancy detected in patients with hyperfunctioning thyroid nodules as it was 48.67 years in the benign and malignant groups, respectively, with no significant difference in statistical analysis. Tam et al. present in 57.1% of malignant cases [20]. On the other hand, confirmed our findings regarding age, as it was statistically Als et al. reported that follicular neoplasm was the most comparable between benign and malignant groups common type, as it was detected in 15 out of 19 patients with (p � 0.416). )e included patients had median values of 49 TNG (79%) [21]. )is contradicts the previous findings. and 50 years in the benign and malignant groups, respec- Whether being papillary or follicular, the high incidence tively [6]. Other authors confirmed the previous findings of malignancy in toxic thyroid patients should alert the surgical community towards changing our management regarding age (p � 0.382) [18]. In our study, the male gender was a significant predictor plan for such cases. Patients who have SNG with docu- mented risk factors of malignancy should be scheduled for of malignancy on both univariate and multivariate analyses. Males represented 15.58% and 38.1% of the included cases in surgery to catch malignancy at early stages, and we suggest that patients should potentially need preoperative FNA for the benign and malignant groups, respectively. In line with our findings, another study reported that the male gender dominate nodules to rule-out malignancy, which will change could be a risk factor for malignancy in such cases. Males the timing of surgery to catch malignancy at early stages, and represented 27% of patients in the malignant group, com- protect patients with papillary thyroid carcinoma from neck pared to only 11% in the benign group (p � 0.03) [4]. LNs dissection, as reported by Hisham Omran et.al. that Contrarily, another study negated any significant impact of total thyroidectomy without prophylactic central LN dis- gender on the incidence of cancer, as males represented 44% section in early papillary thyroid cancer with no statistical difference as regard to postoperative recurrence especially and 50% of patients in the benign and malignant groups, respectively (p � 0.77) [6]. with presence of postoperative radioactive ablation [22]. Our study has some limitations such as being retro- Our findings showed that positive family history of thyroid cancer did not have a significant impact on har- spective in nature, conducted in a single-centre, and the relatively small sample size. Hence, more studies including bouring malignancy in patients with TNG. Another study also confirmed the previous findings regarding positive more patients from different surgical centres should be family history of thyroid cancer [4]. conducted to establish a risk stratification system for these In the current study, TMNG was a significant risk factor patients. for thyroid malignancy on univariate and multivariate an- alyses. It was present in 57.14% and 80.95% of patients in the 5. Conclusion benign and malignant groups, respectively. Another study confirmed our findings regarding TMNG, as the incidence According to the previous results, the presence of thyroid of malignancy in patients with TMNG was 21%, compared hyperfunction is not a protective factor against malignancy, to only 4.5% in patients with STN (p � 0.04) [4]. Some as malignancy was detected in about 1/5 of these cases. Male authors have also reported an increased risk of cancer in gender and TMNG were significant risk factors of malig- patients with thyroiditis [19], but we did not include such nancy in such patients. Patients who have SNG with patients in our study. documented risk factors of malignancy should be scheduled In the current study, the size of the dominant thyroid early for surgery to catch malignancy at early stages, which nodule was not a significant risk factor of malignancy, as it will affect the need for further surgery in the setting of had comparable mean values between the benign and ma- thyroid malignancy. So, we suggest that patients should lignant groups (p � 0.303). Likewise, Tam et al. reported potentially need preoperative FNA for dominate nodules comparable nodule diameters between the benign and even in the presence toxicity to rule-out malignancy, which malignant groups (p � 0.413). It had median values of 41.5 will change the timing of surgery to catch malignancy at and 35 mm in the benign and malignant groups, respectively early stages. [6]. In our study, operative parameters including duration of Data Availability surgery and detection of significant lymph nodes showed no significant difference between the two groups. )is is )e data used to support the findings of this study are in- probably that these cases had early-stage cancers that were cluded in the manuscript. not associated with lymph node metastasis or any other operative difficulty that might prolong operative time. Conflicts of Interest When analyzing malignant specimens detected in the current study, 9 patients were diagnosed with papillary )e authors declare no conflicts of interest. cancer (42.86%) and 7 patients had the follicular variant of papillary cancer (33.33%), while the remaining five cases had References the follicular type (23.81%). Smith et al. also reported that most of the accidently discovered cases had papillary cancer [1] B. Tsegaye and W. Ergete, “Histopathologic pattern of thyroid (73%), while the remaining cases had the follicular variant of disease,” East African Medical Journal, vol. 80, no. 10, papillary carcinoma [4]. In the study conducted by pp. 525–528, 2004. International Journal of Surgical Oncology 5 [2] N. M. Rashad and G. M. Samir, “Prevalence, risks, and Otolaryngology—Head & Neck Surgery, vol. 47, no. 1, p. 6, comorbidity of thyroid dysfunction: a cross-sectional epide- 2018. [18] H. Baser, O. Topaloglu, M. C. Bilginer et al., “Are cytologic miological study,” Egyptian Journal of Internal Medicine, and histopathologic features of hot thyroid nodules different vol. 31, no. 4, pp. 635–641, 2019. from cold thyroid nodules?” Diagnostic Cytopathology, vol. 47, [3] B. R. Haugen, E. K. Alexander, K. C. Bible et al., “2015 no. 9, pp. 898–903, 2019. 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Provenzale et al., “Lower levels of TSH vol. 37, Article ID 100411, 2021. are associated with a lower risk of papillary thyroid cancer in patients with thyroid nodular disease: thyroid autonomy may play a protective role,” Endocrine-Related Cancer, vol. 16, no. 4, pp. 1251–1260, 2009. [8] A. S. Kang, C. S. Grant, G. B. )ompson, and J. A. van Heerden, “Current treatment of nodular goiter with hyperthyroidism (Plummer’s disease): surgery versus radio- iodine,” Surgery, vol. 132, no. 6, pp. 916–923, 2002. [9] Y. Giles (Senyurek), T. Fatih, B. Harika, K. Yersu, T. Tarik, and T. Serdar, “)e risk factors for malignancy in surgically treated patients for graves’ disease, toxic multinodular goiter, and toxic adenoma,” Surgery, vol. 144, no. 6, pp. 1028–1037, [10] C. Xie, P. Cox, N. Taylor, and S. LaPorte, “Ultrasonography of thyroid nodules: a pictorial review,” Insights Imaging, vol. 7, no. 1, pp. 77–86, 2016. [11] K. C. Choong and C. R. McHenry, “)yroid cancer in patients with toxic nodular goiter—is the incidence increasing?” American Journal of Surgery, vol. 209, no. 6, pp. 974–976, [12] J. E. Sokal, “Incidence of malignancy in toxic and nontoxic nodular goiter,” Journal of the American Medical Association, vol. 154, no. 16, pp. 1321–1325, 1954. [13] L. W. Lau, S. Ghaznavi, A. D. Frolkis et al., “Malignancy risk of hyperfunctioning thyroid nodules compared with non-toxic nodules: systematic review and a meta-analysis,” +yroid Research, vol. 14, no. 1, p. 3, 2021. [14] C. Cerci, S. S. Cerci, E. Eroglu et al., “)yroid cancer in toxic and non-toxic multinodular goiter,” Journal of Postgraduate Medicine, vol. 53, no. 3, pp. 157–160, 2007. [15] M. Niedziela, D. Breborowicz, E. Trejster, and E. Korman, “Hot nodules in children and adolescents in western Poland from 1996 to 2000: clinical analysis of 31 patients,” Journal of Pediatric Endocrinology & Metabolism, vol. 15, no. 6, pp. 823–830, 2002. [16] K. Pazaitou-Panayiotou, K. Michalakis, and R. Paschke, “)yroid cancer in patients with hyperthyroidism,” Hormone and Metabolic Research, vol. 44, no. 04, pp. 255–262, 2012. [17] F. Medas, E. Erdas, G. L. Canu et al., “Does hyperthyroidism worsen prognosis of thyroid carcinoma? a retrospective analysis on 2820 consecutive thyroidectomies,” Journal of http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png International Journal of Surgical Oncology Hindawi Publishing Corporation

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Abstract

Hindawi International Journal of Surgical Oncology Volume 2022, Article ID 1054297, 5 pages https://doi.org/10.1155/2022/1054297 Research Article Incidence and Risk Factors of Thyroid Malignancy in Patients with Toxic Nodular Goiter 1 1 1 Tarek Zaghloul Mohamed , Ahmed Abd El Aal Sultan , Mohamed Tag El-Din , 1 1 1 Ahmed A. Elfattah Mostafa , Mohammed A. Nafea , Abd-Elfattah Kalmoush , 1 2 1 Mohammed Shaaban Nassar, Mohamad Adel Abdalgaleel, Ahmed M. Hegab , 1 1 Ayman Helmy Ibrahim , and Mohamad Baheeg General Surgery, Faculty of Medicine, Al-Azhar University, Cairo, Egypt Surgical Oncology, Faculty of Medicine, Al-Azhar University, Cairo, Egypt Correspondence should be addressed to Ahmed Abd El Aal Sultan; dr.ahmedsultan@azhar.edu.eg Received 25 March 2022; Accepted 12 May 2022; Published 23 May 2022 Academic Editor: C. H. Yip Copyright © 2022 Tarek Zaghloul Mohamed et al. �is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background. Although hyperfunctioning thyroid disorders were thought to be protective against malignancy, some recent studies reported a high incidence of incidentally discovered cancer in patients with hyperfunctioning benign thyroid disorders. We performed this study to estimate the incidence and predictors of malignant thyroid disease in patients with toxic nodular goiter (TNG). Patients and Methods. �e data of 98 patients diagnosed with TNG were reviewed (including toxic multinodular goiter SMNG and single toxic nodule STN). �e collected data included patients age, gender, systemic comorbidities, family history of thyroid malignancy, previous neck radiation, type of disease (multinodular or single), size of the dominant nodule by the US, operative time, and detection of signiŽcant lymph nodes during operation. Based on the histopathological analysis, the cases were allocated into benign and malignant groups. Results. Malignancy was detected in 21 patients (21.43%). Although age distribution was comparable between the two groups, males showed a signiŽcant increase in association with malignancy. Medical comorbidities and family history of cancer did not di–er between the two groups. However, TMNG showed a statistically higher prevalence in the malignant group. Operative data, including operative time and lymph node detection, were comparable between the two groups. On regression analysis, both male gender and TMNG were signiŽcant predictors of malignancy. Conclusion. �e presence of thyroid hyperfunction is not a protective factor against malignancy, as malignancy was detected in about 1/5 of cases. Male gender and TMNG were signiŽcant risk factors of malignancy in such patients. Graves’ disease, toxic multinodular goiter (TMNG), and 1. Introduction single toxic nodule (STN) are the most common etiologies of �e incidence of thyroid dysfunction is increasing around hyperthyroidism [3, 4]. the world, as approximately they represent 30–40% of pa- �e increased levels of thyroid-stimulating hormone (TSH) were reported to increase the risk of thyroid ma- tients visiting endocrine clinics, making it one of the most common endocrine disorders [1, 2]. According to a previous lignancy, even within normal ranges. Additionally, it is Egyptian epidemiological study, about 30% of patients at- associated with more advanced nodular thyroid disease [5]. tending the endocrine clinic had thyroid dysfunction, from TSH stimulates the proliferation of both normal and well- whom 19.2% had hyperthyroidism, and 15.8% had sub- di–erentiated neoplastic thyroid tissues. Based on the pre- clinical hyperthyroidism [2]. vious belief, suppression of this hormone is one of the 2 International Journal of Surgical Oncology management plans for patients with well-differentiated )e collected data included the patient’s age, gender, thyroid malignancy [6]. systemic comorbidities, family history of thyroid malig- nancy, previous neck radiation, type of disease (multi- Patients with primary toxic goiter express decreased levels of TSH. As a result, they are less likely to harbour nodular or single), size of the dominant nodule by the US, malignant disease due to inhibition of the related oncogenes operative time, and detection of significant lymph nodes [7]. Based on these data, the presence of hyperfunctioning during operation. thyroid disorder was thought to be protective against ma- lignancy [4]. 2.1. Statistical Analysis. )e Statistical Package for the Social Older studies reported a very low incidence of thyroid Sciences (SPSS 26, IBM/SPSS Inc., Chicago, IL) software was cancer in patients with hyperfunctioning thyroid nodules used to analyse the collected data. Frequencies and per- (3–5%) [8]. Even the American )yroid Association does centages (%) or mean values with standard deviations (SD) not recommend cytological evaluation for such nodules due were used to report basic demographic statistics (SD). )e to low malignancy risk [3]. Nevertheless, recent evidence has chi-square test was used to compare two independent sets of proved increased incidence of thyroid malignancy in toxic qualitative data. To compare quantitative data, the inde- goiter patients (12–18%), which confirms that this incidence pendent-samples t-test and the Mann–Whitney U test were has been underestimated in the past [4, 9]. utilised. Risk variables for the binary categorical outcome Herein, we performed this study to estimate the inci- were examined using univariate and multivariate logistic dence and predictors of malignant thyroid disease in pa- regression. A p value of 0.05 or less was used to determine tients with toxic nodular goiter (TNG). the statistical significance. 2. Patients and Methods 3. Results )is is a retrospective study that was performed at the General Surgery Department, Al-Azhar University Hospi- )e mean age of the cases included in the study was 47.13 tals. We retrospectively reviewed the data of consecutive 98 years in the benign group and 48.67 years in the malignant adult patients diagnosed with TNG who underwent surgical group, with no significant difference between the two intervention during the period between January 2018 and groups. Although the female gender was predominant in the December 2020. TNG was defined when the patient had two groups, males showed a significant increase in associ- thyroid nodule (single or multiple), decreased serum TSH, ation with malignancy (p � 0.023). with normal or increased T3 or T4 [4]. )e prevalence of systemic comorbidities, including All of the included cases were subjected to history taking, diabetes, hypertension, and chronic liver disease, showed no clinical examination, and routine preoperative laboratory significant difference between the study groups. Likewise, investigations (including TSH, T3, and T4). Additionally, positive family history of thyroid cancer was reported only in neck ultrasonography (US) was ordered for all cases, and the one case (1.3%) in the benign group, and that was statistically detected nodules were classified according to the British comparable to the malignant one. )yroid Association (BTA) classification [10]. We included We included two types of TNG: TMNG and STN. )e only patients who were classified as U2 according to the former had a statistically larger prevalence in the malignant previous classification and did not require preoperative fine- group, as it was found in 57.14 percent of cases in the benign needle aspiration cytology (FNAC). Contrarily, patients with and 80.95 percent of cases in the malignant group U3 (intermediate), U4 (suspicious), or U5 (malignant) were (p � 0.046). On the other hand, the size of the dominant excluded from the study. Also, we excluded patients with nodule, measured by the US, did not show significant dif- Graves’ disease or previous history of neck radiation. Only ferences between the two groups (p � 0.303). )e previous cases diagnosed with single nodule were subjected to thyroid data are shown in Table 1. scan to confirm hyperfunction. When it comes to the operative data, operative time was After explaining the benefits, details, and potential statistically comparable between the two groups (87.17 vs problems of surgery, we obtained signed informed per- 93.29 in the benign and malignant groups;p � 0.204). No mission from all patients prior to surgical intervention. All significant lymph nodes were detected on surgical explo- cases underwent total thyroidectomy following normaliza- ration in neither of the two groups. Table 2 illustrates these tion of their thyroid profile, according to our management data. protocol. )e surgical specimen was sent to the histopa- On regression analysis to detect risk factors of malig- thology laboratory for analysis. Incidental thyroid cancer nancy in TNG patients, both male gender and TMNG were was established when discovered on histopathological significant predictors of malignancy in patients with TNG in analysis in patients lacking the clinical features of malig- univariate and multivariate analyses, as shown in Table 3. nancy [11]. In our department, routine thyroid evaluation included analysis of all dominant nodules and obtaining one representative section from every one cm of the remaining 3.1. CI: Confidence Interval. Regarding the detected malig- thyroid tissue. Based on the final histopathological report, nancies in our study, 9 patients were diagnosed with pap- we classified the included patients into two groups; benign illary cancer (42.86%) and 7 patients had the follicular and malignant. variant of papillary cancer (33.33%), while the remaining five International Journal of Surgical Oncology 3 Table 1: Preoperative data. Benign group Malignant group Variable p value (n � 77) (n � 21) Age (year) 47.13± 11.94 48.67± 10.66 0.594 Gender Male 12 (15.58%) 8 (38.1%) 0.023 Female 65 (84.42%) 13 (61.90%) Comorbidities Diabetes mellitus 9 (11.69%) 3 (14.29%) 0.748 Hypertension 9 (11.69%) 4 (19.05%) 0.378 Chronic liver disease 2 (2.6%) 0 (0%) 0.456 Family history of cancer thyroid 1 (1.3%) 0 (0%) 0.600 Preoperative diagnosis TMNG 44 (57.14%) 17 (80.95%) 0.046 STN 33 (42.86%) 4 (19.05%) Size of the dominant nodule (mm) by the US 32.29± 12.93 35.67± 14.43 0.303 Table 2: Operative findings. Variable Benign group (n � 77) Malignant group (n � 21) p value Operative time 87.17± 19.30 93.29± 19.90 0.204 Detected lymph nodes 0 (0%) 0 (0%) 1 Table 3: Regression analysis to detect risk factors of malignancy in TNG. Multivariate analysis Variables Univariate analysis OR 95% CI for OR p value Age 0.590 Male gender 0.028 2.713 1.207–8.423 0.043 Diabetes 0.748 Hypertension 0.383 Chronic liver disease 0.999 Family history of cancer thyroid 0.999 TMNG 0.001 3.530 1.642–11.965 0.022 Size of the nodules 0.301 OR: odds ratio. reported that the rate of thyroid malignancy in their 164 cases had the follicular type (23.81%) (data not shown in tables). patients was 18.3% (30 patients) [4]. Moreover, Tam et al. reported an incidence rate of 19.2%, as 14 patients had malignancy out of the included 73 cases [6]. 4. Discussion Other studies reported a lower incidence of the same Historically, the hyperthyroid state observed in patients with parameter. Giles et al. reported an incidence rate of 12%, TNG was presumed to be “protective” against malignant whereas Cerci et al. reported that malignancy was detected in thyroid neoplasms [12]. However, there is a current debate 11 out of 124 patients with TMNG (incidence � 9%) [14]. in the existing literature [6], as some studies reported very Kang et al. included cases with TMNG and STN like us, and low incidence [8], while others reported a high incidence of they detected malignancy in five out of the included 181 malignancy in TNG patients [4]. According to a recent cases, with an incidence rate of 2.7% [8]. A previous study also emphasized that hyperfunc- meta-analysis published in 2021, hot nodules had a lower risk of cancer than cold nodules. Nonetheless, the rate of tioning nodules in the pediatric population have a higher malignancy risk, reaching up to 29% [15]. )is was not malignancy in hot nodules was higher than anticipated [13]. )is study was conducted to estimate the incidence and observed in our study as all of our cases were adults (>18 risk factors of malignant thyroid disease in patients with years). TNG. We included a total of 98 patients diagnosed with Apparently, there is some heterogenicity regarding the TNG. After histopathological examination of the surgical incidence between different studies, and this could be specimen, 21 patients appeared to harbour thyroid malig- explained by different patient selection criteria, aetiology of nancy, with an incidence rate of 21.43%. hyperthyroidism, the operation performed (total or hemi- )is is consistent with a number of recent studies that thyroidectomy), or the extent of histopathological exami- have found an incidence rate similar to ours. Smith et al. nation [16, 17]. 4 International Journal of Surgical Oncology Mirfakhraee et al., the authors reported that papillary In the current study, patient age was not a significant risk factor for malignancy, as it had mean values of 47.13 and neoplasm was the most common malignancy detected in patients with hyperfunctioning thyroid nodules as it was 48.67 years in the benign and malignant groups, respectively, with no significant difference in statistical analysis. Tam et al. present in 57.1% of malignant cases [20]. On the other hand, confirmed our findings regarding age, as it was statistically Als et al. reported that follicular neoplasm was the most comparable between benign and malignant groups common type, as it was detected in 15 out of 19 patients with (p � 0.416). )e included patients had median values of 49 TNG (79%) [21]. )is contradicts the previous findings. and 50 years in the benign and malignant groups, respec- Whether being papillary or follicular, the high incidence tively [6]. Other authors confirmed the previous findings of malignancy in toxic thyroid patients should alert the surgical community towards changing our management regarding age (p � 0.382) [18]. In our study, the male gender was a significant predictor plan for such cases. Patients who have SNG with docu- mented risk factors of malignancy should be scheduled for of malignancy on both univariate and multivariate analyses. Males represented 15.58% and 38.1% of the included cases in surgery to catch malignancy at early stages, and we suggest that patients should potentially need preoperative FNA for the benign and malignant groups, respectively. In line with our findings, another study reported that the male gender dominate nodules to rule-out malignancy, which will change could be a risk factor for malignancy in such cases. Males the timing of surgery to catch malignancy at early stages, and represented 27% of patients in the malignant group, com- protect patients with papillary thyroid carcinoma from neck pared to only 11% in the benign group (p � 0.03) [4]. LNs dissection, as reported by Hisham Omran et.al. that Contrarily, another study negated any significant impact of total thyroidectomy without prophylactic central LN dis- gender on the incidence of cancer, as males represented 44% section in early papillary thyroid cancer with no statistical difference as regard to postoperative recurrence especially and 50% of patients in the benign and malignant groups, respectively (p � 0.77) [6]. with presence of postoperative radioactive ablation [22]. Our study has some limitations such as being retro- Our findings showed that positive family history of thyroid cancer did not have a significant impact on har- spective in nature, conducted in a single-centre, and the relatively small sample size. Hence, more studies including bouring malignancy in patients with TNG. Another study also confirmed the previous findings regarding positive more patients from different surgical centres should be family history of thyroid cancer [4]. conducted to establish a risk stratification system for these In the current study, TMNG was a significant risk factor patients. for thyroid malignancy on univariate and multivariate an- alyses. It was present in 57.14% and 80.95% of patients in the 5. Conclusion benign and malignant groups, respectively. Another study confirmed our findings regarding TMNG, as the incidence According to the previous results, the presence of thyroid of malignancy in patients with TMNG was 21%, compared hyperfunction is not a protective factor against malignancy, to only 4.5% in patients with STN (p � 0.04) [4]. Some as malignancy was detected in about 1/5 of these cases. Male authors have also reported an increased risk of cancer in gender and TMNG were significant risk factors of malig- patients with thyroiditis [19], but we did not include such nancy in such patients. Patients who have SNG with patients in our study. documented risk factors of malignancy should be scheduled In the current study, the size of the dominant thyroid early for surgery to catch malignancy at early stages, which nodule was not a significant risk factor of malignancy, as it will affect the need for further surgery in the setting of had comparable mean values between the benign and ma- thyroid malignancy. So, we suggest that patients should lignant groups (p � 0.303). Likewise, Tam et al. reported potentially need preoperative FNA for dominate nodules comparable nodule diameters between the benign and even in the presence toxicity to rule-out malignancy, which malignant groups (p � 0.413). 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Journal

International Journal of Surgical OncologyHindawi Publishing Corporation

Published: May 23, 2022

References