Thyrotoxicosis does not protect against incidental papillary thyroid cancer Jessica Preece, MBBS, BMedSc,a Simon Grodski, MBBS, FRACS,a Meei Yeung, MBBS, BMedSc, FRACS,a Michael Bailey, PhD, MSc, BSc,b and Jonathan Serpell, MBBS, MD, MEd, FRACS, FACS,a Melbourne, Australia
Background. Thyroid cancer is the 10th most commonly diagnosed cancer in Australia, and many studies have linked thyroid-stimulating hormone (TSH) and papillary thyroid cancer (PTC). Low TSH is thought to be protective against thyroid cancer. Our aim was to evaluate the relationship between thyrotoxicosis, in particular Graves’ disease, and the incidence of incidental PTC. Methods. After ethics approval, a review of the thyroid database at Monash University Endocrine Surgery Unit was performed. Data was obtained for the period September 1994 to August 2012 and identified those patients who underwent total thyroidectomy (n = 1,898). Those patients with known or suspected malignancy were excluded from the study (n = 390). The remaining patients (n = 1,508) were divided into 3 groups: Graves’ disease (n = 250), toxic multinodular goiter (MNG; n = 295), and nontoxic MNG (n = 963) based on indication for surgery and thyroid status. Data were analyzed for the presence of malignancy in each group. Results. Of the 1,508 patients included in the study, 96 (6.4%) had thyroid cancer, and the incidence of PTC was similar between the 3 groups. There were 16 cases (6.4%) in the Graves’ group, 48 cases (5%) in the nontoxic MNG group, and 20 cases (6.8%) in the toxic MNG group (P = .41). Conclusion. The incidence of malignancy, particularly PTC, is similar in patients with Graves’ disease, toxic MNG, and nontoxic MNG. This study demonstrates no protective effect of thyrotoxicosis on the incidence of incidental thyroid cancer. (Surgery 2014;156:1153-6.) From the Endocrine Surgery Unit,a The Alfred Hospital, and the Department of Epidemiology and Preventative Medicine,b Monash University, Melbourne, Australia
THYROID CANCER is the 10th most commonly diagnosed cancer in Australia with 2,420 cases diagnosed in 2012, and it has been predicted that this number will continue to increase.1 This rising incidence of thyroid cancer may be in part related to the increased diagnosis of micropapillary carcinomas (tumor size < 10 mm) secondary to the increased use of ultrasonography and increased sampling by pathologists.2-4 Autopsy studies have shown a prevalence of papillary microcarcinoma of between 1.0% and 36%.5 The prevalence of hyperthyroidism in the adult population is thought to be approximately 1%, with Graves’ disease, toxic multinodular goiter (MNG) and toxic adenomas accounting for the most common causes.6 Many studies have linked thyroid-stimulating hormone (TSH) and papillary Accepted for publication April 14, 2014. Reprint requests: Jonathan W. Serpell, MBBS, MD, MEd, FRACS, FRCS, The Alfred, Commercial Road, Prahran, VIC 3181, Australia. E-mail: [email protected]. 0039-6060/$ - see front matter Ó 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.surg.2014.04.025
thyroid cancer (PTC), with a general consensus that a low TSH may be protective against thyroid cancer.7,8 In theory, the presence of thyrotoxicosis with a suppressed TSH should lead to a lesser incidence of PTC than in euthyroid patients. In addition, the presence of thyroiditis is known to lead to an increased risk of malignancy with studies at our own institution confirming the incidence of incidental PTC is increased in patients with Hashimoto’s thyroiditis.9 Our aim was to evaluate the relationship between thyrotoxicosis, in particular Graves’ disease, and the incidence of incidental PTC. We hypothesized that owing to the presence of thyroiditis, there would be a greater incidence of PTC in patients with Graves’ disease compared with those patients with toxic and nontoxic MNG, and that low TSH may not be protective against the development of PTC. METHODS After approval by the hospital research and ethics committee, a review of the thyroid database of the Monash University Endocrine Surgery Unit SURGERY 1153
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was performed. Data were obtained for the period September 1994 to August 2012. We identified those patients who underwent total thyroidectomy (n = 1,898), including patient demographics, thyroid status (thyrotoxic, euthyroid, or hypothyroid), and results of fine needle aspiration (FNA) cytology and histopathology. Thyrotoxicosis was defined by the combination of suppressed TSH and increased T4/T3 levels and included patients on anti-thyroid medication with treated thyrotoxicosis. Patients with known or suspected malignancy with a positive FNA for malignancy or patients where the indication for operation was malignancy were excluded (n = 390). The remaining patients (n = 1,508) with presumed benign disease were divided into 3 groups: Graves’ disease (n = 250), toxic MNG (n = 295), and nontoxic MNG (n = 963) based on indications for operation and thyroid status. The data were then analyzed for the presence of malignancy in each group. Statistical analysis was performed using SAS Version 9.3 (SAS Institute Inc, Cary, NC). Group comparisons were made using Chi-square tests for equal proportion and reported as n (%), and comparisons of continuously normally distributed variables were made using student t-tests and reported as mean values ± standard deviation. Kruskal-Wallis 1-way variance analysis was used to compare tumor size between the groups. To ensure observed differences in malignancy rates were not owing to imbalances between groups, multivariate logistic regression was performed adjusting for baseline imbalances. Continuous data are expressed as mean values ± standard deviation.
P < .0001). No FNAC results were malignant (Bethesda 6) or suspicious for malignancy (Bethesda 5) in keeping with the selection criteria. In the Graves’ disease group, 16 patients (6.4%) had malignancy, including 3 with macro PTC (>10 mm) and 13 with micro PTC (
Background. Thyroid cancer is the 10th most commonly diagnosed cancer in Australia, and many studies have linked thyroid-stimulating hormone (TSH) and papillary thyroid cancer (PTC). Low TSH is thought to be protective against thyroid cancer. Our aim was to evaluate the relationship between thyrotoxicosis, in particular Graves’ disease, and the incidence of incidental PTC. Methods. After ethics approval, a review of the thyroid database at Monash University Endocrine Surgery Unit was performed. Data was obtained for the period September 1994 to August 2012 and identified those patients who underwent total thyroidectomy (n = 1,898). Those patients with known or suspected malignancy were excluded from the study (n = 390). The remaining patients (n = 1,508) were divided into 3 groups: Graves’ disease (n = 250), toxic multinodular goiter (MNG; n = 295), and nontoxic MNG (n = 963) based on indication for surgery and thyroid status. Data were analyzed for the presence of malignancy in each group. Results. Of the 1,508 patients included in the study, 96 (6.4%) had thyroid cancer, and the incidence of PTC was similar between the 3 groups. There were 16 cases (6.4%) in the Graves’ group, 48 cases (5%) in the nontoxic MNG group, and 20 cases (6.8%) in the toxic MNG group (P = .41). Conclusion. The incidence of malignancy, particularly PTC, is similar in patients with Graves’ disease, toxic MNG, and nontoxic MNG. This study demonstrates no protective effect of thyrotoxicosis on the incidence of incidental thyroid cancer. (Surgery 2014;156:1153-6.) From the Endocrine Surgery Unit,a The Alfred Hospital, and the Department of Epidemiology and Preventative Medicine,b Monash University, Melbourne, Australia
THYROID CANCER is the 10th most commonly diagnosed cancer in Australia with 2,420 cases diagnosed in 2012, and it has been predicted that this number will continue to increase.1 This rising incidence of thyroid cancer may be in part related to the increased diagnosis of micropapillary carcinomas (tumor size < 10 mm) secondary to the increased use of ultrasonography and increased sampling by pathologists.2-4 Autopsy studies have shown a prevalence of papillary microcarcinoma of between 1.0% and 36%.5 The prevalence of hyperthyroidism in the adult population is thought to be approximately 1%, with Graves’ disease, toxic multinodular goiter (MNG) and toxic adenomas accounting for the most common causes.6 Many studies have linked thyroid-stimulating hormone (TSH) and papillary Accepted for publication April 14, 2014. Reprint requests: Jonathan W. Serpell, MBBS, MD, MEd, FRACS, FRCS, The Alfred, Commercial Road, Prahran, VIC 3181, Australia. E-mail: [email protected]. 0039-6060/$ - see front matter Ó 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.surg.2014.04.025
thyroid cancer (PTC), with a general consensus that a low TSH may be protective against thyroid cancer.7,8 In theory, the presence of thyrotoxicosis with a suppressed TSH should lead to a lesser incidence of PTC than in euthyroid patients. In addition, the presence of thyroiditis is known to lead to an increased risk of malignancy with studies at our own institution confirming the incidence of incidental PTC is increased in patients with Hashimoto’s thyroiditis.9 Our aim was to evaluate the relationship between thyrotoxicosis, in particular Graves’ disease, and the incidence of incidental PTC. We hypothesized that owing to the presence of thyroiditis, there would be a greater incidence of PTC in patients with Graves’ disease compared with those patients with toxic and nontoxic MNG, and that low TSH may not be protective against the development of PTC. METHODS After approval by the hospital research and ethics committee, a review of the thyroid database of the Monash University Endocrine Surgery Unit SURGERY 1153
1154 Preece et al
Surgery November 2014
was performed. Data were obtained for the period September 1994 to August 2012. We identified those patients who underwent total thyroidectomy (n = 1,898), including patient demographics, thyroid status (thyrotoxic, euthyroid, or hypothyroid), and results of fine needle aspiration (FNA) cytology and histopathology. Thyrotoxicosis was defined by the combination of suppressed TSH and increased T4/T3 levels and included patients on anti-thyroid medication with treated thyrotoxicosis. Patients with known or suspected malignancy with a positive FNA for malignancy or patients where the indication for operation was malignancy were excluded (n = 390). The remaining patients (n = 1,508) with presumed benign disease were divided into 3 groups: Graves’ disease (n = 250), toxic MNG (n = 295), and nontoxic MNG (n = 963) based on indications for operation and thyroid status. The data were then analyzed for the presence of malignancy in each group. Statistical analysis was performed using SAS Version 9.3 (SAS Institute Inc, Cary, NC). Group comparisons were made using Chi-square tests for equal proportion and reported as n (%), and comparisons of continuously normally distributed variables were made using student t-tests and reported as mean values ± standard deviation. Kruskal-Wallis 1-way variance analysis was used to compare tumor size between the groups. To ensure observed differences in malignancy rates were not owing to imbalances between groups, multivariate logistic regression was performed adjusting for baseline imbalances. Continuous data are expressed as mean values ± standard deviation.
P < .0001). No FNAC results were malignant (Bethesda 6) or suspicious for malignancy (Bethesda 5) in keeping with the selection criteria. In the Graves’ disease group, 16 patients (6.4%) had malignancy, including 3 with macro PTC (>10 mm) and 13 with micro PTC (
