Thyrotropin Suppression Therapy Research Articles

Differentiated thyroid cancer: a focus on post-operative thyroid hormone replacement and thyrotropin suppression therapy.

This review focuses on post-operative thyroid hormone replacement and thyrotropin suppression therapy in patients with differentiated thyroid cancer. A clinical review. Differentiated thyroid cancers (DTC), including papillary and follicular thyroid cancers, have an excellent prognosis and their management leverages a unique set of clinical tools arising from homology to the normal thyroid follicular cell. Surgery is the cornerstone of initial management, and post-operative care often requires thyroid hormone replacement therapy, which may be approached with the intent of physiologic normalization or used pharmacologically to suppress TSH as part of a DTC treatment. Management of DTC and approaches to TSH suppression are tailored to an individual's risk of DTC recurrence and are adjusted to a patient's clinical status and comorbidities over time with the goal of mitigating risk and maximizing benefit.

Application and prospect of trabecular bone score in differentiated thyroid cancer patients receiving thyrotropin suppression therapy.

Thyroid-stimulating hormone (TSH) suppression therapy is one of the common treatments for most patients with differentiated thyroid cancer (DTC). Unfortunately, its detrimental effects on bone health are receiving increasing attention. It may increase the risk of osteoporosis and osteoporotic fractures. The trabecular bone score (TBS) is a relatively new gray-scale texture measurement parameter that reflects bone microarchitecture and bone strength and has been shown to independently predict fracture risk. We reviewed for the first time the scientific literature on the use of TBS in DTC patients on TSH suppression therapy and aim to analyze and compare the utility of TBS with bone mass strength (BMD) in the management of skeletal health and prediction of fracture risk. We screened a total of seven relevant publications, four of which were for postmenopausal female patients and three for all female patients. Overall, postmenopausal female patients with DTC had lower TBS and a significant reduction in TBS after receiving TSH suppression therapy, but their BMD did not appear to change significantly. In addition, TBS was also found to be an independent predictor of osteoporotic fracture risk in postmenopausal women with DTC receiving TSH suppression therapy. However, due to limitations in the number of studies and study populations, this evidence is not sufficient to fully demonstrate the adverse effects of TSH suppression therapy on patients’ TBS or BMD and the efficacy of TBS, and subsequent larger and more case-cohort studies are needed to further investigate the relationship and application of TBS to TSH suppression therapy in terms of skeletal health impairment and fracture risk in DTC patients.

Bone-density testing interval and transition to osteoporosis in differentiated thyroid carcinoma patients on TSH suppression therapy.

Thyrotropin (TSH) suppression therapy is a standard treatment after surgery for differentiated thyroid carcinoma (DTC). It may be associated with osteoporosis in postmenopausal women. However, there are no guidelines for bone mineral density (BMD) testing intervals to screen for osteoporosis in these patients. Therefore, we evaluated the timing of repeated BMD testing in DTC patients with TSH suppression according to baseline T-scores. We retrospectively evaluated 658 DTC patients who underwent BMD testing more than twice between January 2007 and January 2020. A 1:3 propensity score matching was conducted to compare the timing of repeated BMD tests between the DTC and non-DTC groups. We stratified the participants into four groups based on their baseline T-scores: normal (-1.00 or higher), mild osteopenia (-1.01 to -1.49), moderate osteopenia (-1.50 to -1.99), and severe osteopenia (-2.00 to -2.49). Additionally, the 10% of patients in each group that transitioned to osteoporosis were analysed. The estimated BMD testing interval for 10% of patients who developed osteoporosis was 85 months for patients with initially mild osteopenia, 65 months for those with moderate osteopenia, and 15 months for those with severe osteopenia in the DTC group. In the non-DTC group, the testing intervals for mild, moderate, and severe osteopenia were 98, 57, and 13 months, respectively. On multivariate analysis, baseline T-score (mild osteopenia: hazard ratio [HR] 5.91, p = .105; moderate osteopenia: HR, 25.27, p = .02; and severe osteopenia: HR, 134.82, p < .001) and duration of TSH suppression (tertile 2: HR, 2.25, p = .005; Tertile 3: 1.78, p = .033) were independent risk factors for osteoporosis in the DTC group. This study provides guidance for the timing of repeated BMD tests in women over 50 years of age with TSH suppression. The rescreening interval for BMD testing can be modified based on the baseline T-score. The appropriate BMD testing intervals in female DTC patients were similar to those in non-DTC females.

Thyrotropin suppression therapy using levothyroxine does not negatively affect breast cancer prognosis

IntroductionBreast cancer (BC) and thyroid dysfunction are common in females, yet the relationship between thyroid hormone and BC is unclear. To search for the connection between thyrotropin and BC, we contradistinguished BC patients with or without synchronous second primary thyroid cancer (TC) with surgery using data from the Surveillance, Epidemiology, and End Results (SEER) database. Theoretically, according to the ATA (American Thyroid Association) guidelines, all TC patients were treated with thyrotropin suppressive therapy only from 2010 to 2015. Materials and MethodsData from BC patients with a synchronous second TC with surgery (BC2TC) and only BC patients (1BC) during 2010–2015 were extracted from the SEER database. Differences in the clinicopathological characteristics between BC2TC and 1BC patients were analyzed by chi-square tests. Comparisons of the disease-specific survival (DSS) and overall survival (OS) curves between these two groups were performed with the log-rank (Mantel-Cox) test. ResultsWithin this dataset, we identified 134 BC2TC patients during the period from 2010 to 2015. Significant differences between the BC2TC and 1BC groups were found only for different ages and TNM (tumor-node-metastasis status) stages. There were no significant differences in DSS between the two cohorts (P = 0.060). The same tendencies in OS or DSS were observed for the different age groups and different TNM groups, even the stage I, N0 (without metastases to lymph nodes), and ER (+) (estrogen receptor (ER)-positive) groups. ConclusionsThere were no remarkable differences in survival between the BC2TC and 1BC groups, and thyrotropin suppression therapy using levothyroxine did not negatively affect BC prognosis.

Invited commentary on “Thyrotropin Suppression therapy Using Levothyroxine Does Not Negatively Affect Breast Cancer Prognosis”

• Data from BC patients with a synchronous second TC with surgery (BC2TC) and only BC patients (1BC) during 2010–2015 were extracted from the SEER database. • Analyzed clinicopathological features amongst 1BC and BC2TC groups and found a significant difference for various age groups and tumor-node-metastasis status. • The present study is a survey and interpretation of data retrieved from the SEER database, and a strong basis for future investigations towards an underlying molecular mechanism.

Incident atrial fibrillation in patients with differentiated thyroid cancer: a meta-analysis.

Differentiated thyroid cancer (DTC) represents the most common form of thyroid neoplasms and is becoming increasingly prevalent. Evidence suggests a possible relationship between DTC diagnosis and subsequent atrial fibrillation (AF). If confirmed, this may present an alarming health risk (AF) in an otherwise condition with a relatively good prognosis (DTC). The aim of this systematic review and meta-analysis is to provide for the first time a pooled estimate of AF incidence in DTC patients in comparison to healthy controls. A detailed search in electronic databases, clinical trial registries and grey literature was performed to identify studies reporting the incidence of AF in DTC patients. Newcastle–Ottawa quality assessment scale was used to assess study quality. We used a random effects (RE) generalized linear mixed model (GLMM) in pooling of individual studies and also calculated a prediction interval for the estimate of a new study. Six observational studies met the eligibility criteria, which included totally 187,754 patients with DTC and 199,770 healthy controls. The median follow-up period was 4.3 to 18.8 years; the incidence rate of AF was 4.86 (95% CI, 3.29 to 7.17, I2 = 96%) cases per 1000 person-years, while the incidence rate ratio was 1.54 (95% CI, 1.44 to 1.65, I2 = 0%, 95% PI, 1.33 to 1.78).This is the first meta-analysis to confirm that patients with DTC are at a high risk for developing AF, which may be attributed to a state of iatrogenic hyperthyroidism due to long-term thyrotropin suppression therapy.

Radioactive iodine treatment of papillary thyroid carcinoma in Japan.

We have a unique history of using radioactive iodine (RAI) therapy and surgical treatment for thyroid cancer in Japan. Less than total thyroidectomy without RAI therapy was the most common management of papillary thyroid carcinoma (PTC) in the past. Limited availability of dedicated facilities for the RAI administration due to the strict regulations and insufficient coverage of the expenses were the major reasons that impacted on the management decisions. Following the publication of the Japanese clinical practice guidelines for thyroid tumors in 2010, the risk-adapted approach has become a standard where the high-risk and selected intermediate-risk PTC patients undergo total thyroidectomy followed by RAI therapy and thyrotropin suppression therapy. We are on the shoulders of pioneers who made every effort to bring the interventions closer to an ideal environment for patients. Armed with the revised clinical practice guidelines 2018 and devised inpatient/outpatient RAI therapy, Japanese physicians are ready to proceed to more rational management that would improve patients' outcomes. Directions for the future include further advancement of relevant clinical research to fill the gaps between current evidence and recommendations in the guidelines, and obtaining approval for high-dose RAI therapy on an outpatient basis to improve its effectiveness in both adjuvant and treatment settings.

Optimal Thyrotropin Suppression Therapy in Low-Risk Thyroid Cancer Patients after Lobectomy.

Background: This study aimed to identify the clinical results after thyrotropin suppression therapy (TST) cessation and evaluated clinical factors associated with successful TST cessation. Methods: Patients who underwent lobectomy due to low-risk papillary thyroid carcinoma (PTC) were included in this study. We compared clinical characteristics and outcomes between patients who succeeded to stop TST and failed to stop TST. Results: A total of 363 patients were included in the study. One hundred and ninety-three patients (53.2%, 193/363) succeeded to stop TST. The independent associated factors for successful TST cessation were the preoperative thyroid-stimulating hormone (TSH) level and the maintenance period of TST. Patients with low TSH level showed a higher success rate for levothyroxine (LT4) cessation than patients with high TSH level (1.79 ± 1.08 and 2.76 ± 1.82 mU/L, p < 0.001). Patients who failed to discontinue TST showed a longer maintenance period of TST than patients who succeeded to discontinue TST (54.09 ± 17.44 and 37.58 ± 17.68 months, p < 0.001). Conclusions: Preoperative TSH level and maintenance period of TST are important factors for successful cessation of TST. If TST cessation is planned for patients who are taking LT4 after lobectomy, a higher success rate of TST cessation is expected with low preoperative TSH level and early cessation of LT4.

Simultaneous Hodgkin lymphoma and BRAF V600E -positive papillary thyroid carcinoma

Rationale:Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy. However, the simultaneous occurrence of PTC and Hodgkin Lymphoma (HL) was rarely reported.Patient concerns:We present a case of simultaneous BRAFV600E-positive PTC and HL in a 17-year-old female.Diagnosis:She was referred to our clinic with a painless lump in her left neck. A highly suspicious thyroid nodule and multiple enlarged lymph nodes in the neck were found by ultrasonography examination. The suspicious nodule was diagnosed as PTC by fine needle aspiration cytology.Interventions:A total thyroidectomy with bilateral lymph node dissection was performed and the microscopic examination revealed a 2-cm PTC with BRAFV600E mutation and HL (mixed cellularity) in the bilateral lymph nodes. PTC was postoperatively considered as T1bN0M0. Levothyroxine (125 μg/d) was administered to the patient for thyrotropin suppression therapy. Then the patient was referred to the Department of Hematology to receive 4 cycles of ABVD followed by 30 Gy involved-site radiotherapy and radioactive iodine (RAI) therapy for thyroid cancer.Outcomes:After two cycles of ABVD, multiple enlarged lymph nodes showed a significant response to the chemotherapy in the patient.Lessons:Simultaneous HL and BRAFV600E-positive PTC is extremely rare. Biopsy of the suspicious lymph nodes should be performed to confirm malignancy metastasizing from PTC or other lesions. Similarly, in HL patients with suspicious thyroid nodule, ultrasound-guided fine needle aspiration of thyroid nodule should be performed to exclude thyroid malignancy.

Sorafenib treatment for papillary thyroid carcinoma with diffuse lung metastases in a child with autism spectrum disorder: a case report

BackgroundPediatric papillary thyroid carcinoma frequently presents with lymph node involvement and distant metastases. Sorafenib, an oral multikinase inhibitor, has been used to treat radioactive iodine (RAI) therapy-refractory thyroid carcinoma in adults; however, pediatric experience is limited. Medical procedures and hospitalization for children with autism spectrum disorder may be challenging.Case presentationAn 11-year-old boy with autism spectrum disorder and moderate intellectual impairment presented with dyspnea on exertion with thyroid carcinoma and diffuses lung metastases. Total thyroidectomy and adjuvant RAI therapy is the standard treatment; however, the latter therapy was impractical because of his respiratory status and challenging behaviors. He was therefore started on sorafenib 200 mg/day (150 mg/m2/day) and this dosage was increased to 400 mg/day (300 mg/m2/day). The adverse effects were mild and tolerable. After administration of medication, his dyspnea improved and surgery was performed. We attempted to administer RAI therapy after surgery; however, we abandoned it because he had difficulty taking care of himself according to isolation room rules. Thyrotropin suppression therapy was therefore started and sorafenib treatment (400 mg/day) resumed. Follow-up imaging showed regression of pulmonary metastases. The metastases have remained stable for over 24 months on continuous sorafenib treatment without serious adverse events.ConclusionWe inevitably used sorafenib as an alternative to standard therapy because of the patient’s specific circumstances. Individualized strategies for pediatric cancer patients with autism spectrum disorder are needed.

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 nodules are a common clinical problem, and differentiated thyroid cancer is becoming increasingly prevalent. Since the American Thyroid Association's (ATA's) guidelines for the management of these disorders were revised in 2009, significant scientific advances have occurred in the field. The aim of these guidelines is to inform clinicians, patients, researchers, and health policy makers on published evidence relating to the diagnosis and management of thyroid nodules and differentiated thyroid cancer. The specific clinical questions addressed in these guidelines were based on prior versions of the guidelines, stakeholder input, and input of task force members. Task force panel members were educated on knowledge synthesis methods, including electronic database searching, review and selection of relevant citations, and critical appraisal of selected studies. Published English language articles on adults were eligible for inclusion. The American College of Physicians Guideline Grading System was used for critical appraisal of evidence and grading strength of recommendations for therapeutic interventions. We developed a similarly formatted system to appraise the quality of such studies and resultant recommendations. The guideline panel had complete editorial independence from the ATA. Competing interests of guideline task force members were regularly updated, managed, and communicated to the ATA and task force members. The revised guidelines for the management of thyroid nodules include recommendations regarding initial evaluation, clinical and ultrasound criteria for fine-needle aspiration biopsy, interpretation of fine-needle aspiration biopsy results, use of molecular markers, and management of benign thyroid nodules. Recommendations regarding the initial management of thyroid cancer include those relating to screening for thyroid cancer, staging and risk assessment, surgical management, radioiodine remnant ablation and therapy, and thyrotropin suppression therapy using levothyroxine. Recommendations related to long-term management of differentiated thyroid cancer include those related to surveillance for recurrent disease using imaging and serum thyroglobulin, thyroid hormone therapy, management of recurrent and metastatic disease, consideration for clinical trials and targeted therapy, as well as directions for future research. We have developed evidence-based recommendations to inform clinical decision-making in the management of thyroid nodules and differentiated thyroid cancer. They represent, in our opinion, contemporary optimal care for patients with these disorders.

Update on the treatment of hypothyroidism.

Differentiated thyroid cancer is a malignancy that is rapidly increasing in frequency. As thyroidectomy plays a central role in the treatment of thyroid cancer, it is incumbent on physicians treating this patient group to be well versed in the intricacies of treating hypothyroidism. Treatment of hypothyroidism may be refined by careful attention to dose selection, monitoring of therapy and achievement of thyrotropin goals that are specific to the individual patient's overall clinical situation. These goals are common not only to patients with a sole diagnosis of hypothyroidism, as discussed in the recent American Thyroid Association Guidelines, but also to patients with hypothyroidism in the setting of thyroid cancer. Several recent studies have illuminated our understanding of the benefits and risks of thyrotropin suppression therapy in patients with differentiated thyroid cancer. Multiple studies of combination therapy with levothyroxine and liothyronine for treating hypothyroidism have not led to a clear conclusion about its benefits over levothyroxine monotherapy. Animal studies have advanced our understanding of the altered serum and tissue milieu that characterizes levothyroxine monotherapy. Crossing the bridge from this translational research into clinical research using sustained release triiodothyronine preparations may ultimately enhance the health of our patients. Continued refinement of our understanding of thyroid status and our ability to flawlessly implement thyroid hormone replacement is an active area of research.

Effect of Thyrotropin Suppression Therapy on Bone in Thyroid Cancer Patients.

The thyroid cancer incidence is rising. Despite current guidelines, controversy exists regarding the degree and duration of thyrotropin suppression therapy. Also, its potential skeletal effects remain a concern to physicians caring for thyroid cancer patients. We conducted a review of published data to evaluate existing studies focusing on the skeletal effects of thyrotropin suppression therapy in thyroid cancer patients. A systematic search of the PubMed, Ovid/Medline, and Cochrane Central Register of Controlled Trials databases was conducted. The retained studies were evaluated for methodological quality, and the study populations were categorized into premenopausal women, postmenopausal women, and men. Twenty-five pertinent studies were included. Seven studies were longitudinal and 18 were cross-sectional. Of the 25 included studies, 13 were assigned an excellent methodological quality score. Three of 5 longitudinal studies and 3 of 13 cross-sectional studies reported decreased bone mineral density (BMD) in premenopausal women; 2 of 4 longitudinal studies and 5 of 13 cross-sectional studies reported decreased BMD in postmenopausal women. The remaining studies showed no effect on BMD. The only longitudinal study of men showed bone mass loss; however, cross-sectional studies of men did not demonstrate a similar effect. Studies to date have yielded conflicting results on the skeletal effects of thyrotropin suppression therapy and a knowledge gap remains, especially for older adults and men. Existing data should be cautiously interpreted because of the variable quality and heterogeneity. Identifying groups at risk of adverse effects from thyrotropin suppression therapy will be instrumental to providing focused and tailored thyroid cancer treatment. The standard treatment for thyroid cancer includes total thyroidectomy with or without radioactive iodine ablation, often followed by thyrotropin suppression therapy. Despite current guidelines, controversy exists regarding the degree and duration of thyrotropin suppression therapy, and discordant results have been reported on its adverse effects on bone. The present review provides physicians with existing data on the skeletal effects of thyrotropin suppression therapy, highlighting the need for further research to identify the groups at risk of adverse skeletal effects. This knowledge will aid in developing tailored thyroid cancer treatment.

The Efficacy of Thyrotropin Suppression Therapy in Treatment of Differentiated Thyroid Cancer after Total Thyroidectomy

Abstract Background: The aim of this prospective study was to assess the effect of the TSH suppression on both disease-free and overall survivals in patients with nonmetastatic differentiated thyroid cancer (DTC) after total thyroidectomy. Patients &amp; Methods: One hundred and forty eight patients with pathologically proved operable differentiated thyroid carcinoma were enrolled in this prospective study. Levothyroxin (L-T4) therapy was started in doses according to treatment groups. Patients were randomly assigned to receive either postoperative TSH suppression therapy in group I (76 patients) or nonsuppression therapy in group II (72 patients). Results: During the period of follow up with a median 54 months, the disease-free survival for patients without TSH suppression therapy did not reach statistically significant difference comparing with those for patients with the suppression therapy (p=0.09). However, the difference was statistically significant for high-risk patients (p=0.04). On comparing both groups there was no statistically significant difference with regard to overall survival (p=0.17). The age of the patients more than 45 years, tumour size more than 4 cm and high-risk group were significant independent predictors for thyroid carcinoma-related relapse in univariate analysis. However, tumour size was the only significant factor in multivariate analysis. Conclusion: Suppressive treatment with L-T4 therapy in patients with differentiated thyroid carcinoma should be individualised and balanced against the adverse effects. TSH suppression is indicated in patients with high-risk disease or recurrent tumour. Normalisation of serum TSH is preferred for long-term treatment of disease-free elderly patients with DTC and comorbidities.

Aortic stiffness and left ventricular function in patients with differentiated thyroid cancer.

The aim of this study was to investigate aortic stiffness and left ventricular (LV) systolic and diastolic function in patients with differentiated thyroid cancer (DTC) on thyroxine (L-T4) therapy and after L-T4 withdrawal to assess the cardiovascular impact of long-term subclinical hyperthyroidism and short-term overt hypothyroidism. Twenty-four patients who had had total thyroidectomy and radioiodine ablation for differentiated thyroid cancer were studied on two occasions: on TSH suppressive L-T4 therapy (sTSH 0.24 ± 0.11 mU/L), and 4 weeks after L-T4 withdrawal (sTSH 89.82 ± 29.36 mU/L). Echocardiography was performed and thyroid function, serum thyroglobulin, lipid parameters, homocystine, C-reactive protein, fibrinogen and von Willebrand factor activity (vWF) were measured. Twenty-two healthy volunteers matched for age and sex served as euthyroid controls. Aortic stiffness was increased both in hypothyroidism (6.04 ± 2.88 cm(2)/dyn/10(3), p < 0.05) and subclinical hyperthyroidism (9.27 ± 4.81 cm(2)/dyn/10(3), p < 0.05) vs. controls (3.92 ± 1.84 cm(2)/dyn/10(3)). Subclinical hyperthyroidism had a more marked effect (p < 0.05). LV dimensions and ejection fractions were similar before and after L-T4 withdrawal. The E'/A' was higher in euthyroid controls (1.34 ± 1.02) as compared to both subclinical hyperthyroidism (1.0 ± 0.14, p < 0.05) and overt hypothyroidism (1.13 ± 0.98, p < 0.05). Change of aortic stiffness correlated with change of free-thyroxine (fT4), vWF and fibrinogen levels in a positive manner. Long-term thyrotropin-suppression therapy has continuous adverse effects on the arterial wall. The degree of TSH suppression in patients with DTC should be kept at the possible minimum, based on individually determined potential benefits and risks of treatment, especially in patients with cardiovascular co-morbidities.

Randomized controlled trial for the effect of postoperative thyrotropin suppression therapy on disease-free survival in patients with papillary thyroid carcinoma and prospective controlled study for influence of the therapy on bone mineral density

Randomized controlled trial for the effect of postoperative thyrotropin suppression therapy on disease-free survival in patients with papillary thyroid carcinoma and prospective controlled study for influence of the therapy on bone mineral density

Does Postoperative Thyrotropin Suppression Therapy Truly Decrease Recurrence in Papillary Thyroid Carcinoma? A Randomized Controlled Trial

Does Postoperative Thyrotropin Suppression Therapy Truly Decrease Recurrence in Papillary Thyroid Carcinoma? A Randomized Controlled Trial

Does Postoperative Thyrotropin Suppression Therapy Truly Decrease Recurrence in Papillary Thyroid Carcinoma? A Randomized Controlled Trial

Does Postoperative Thyrotropin Suppression Therapy Truly Decrease Recurrence in Papillary Thyroid Carcinoma? A Randomized Controlled Trial

Does Postoperative Thyrotropin Suppression Therapy Truly Decrease Recurrence in Papillary Thyroid Carcinoma? A Randomized Controlled Trial

TSH suppression therapy has been used to decrease thyroid cancer recurrence. However, validation of effects through studies providing a high level of evidence has been lacking. This single-center, open-label, randomized controlled trial tested the hypothesis that disease-free survival (DFS) for papillary thyroid carcinoma (PTC) in patients without TSH suppression is not inferior to that in patients with TSH suppression. Participants were randomly assigned to receive postoperative TSH suppression therapy (group A) or not (group B). Before assignment, patients were stratified into groups with low- and high-risk PTC according to the AMES (age, metastasis, extension, size) risk-group classification. For patients assigned to group A, L-T(4) was administered to keep serum TSH levels below 0.01 μU/ml. TSH levels were adjusted to within normal ranges for patients assigned to group B. Recurrence was evaluated by neck ultrasonography and chest computed tomography. Eligible participants were recruited from 1996-2005, with 218 patients assigned to group A and 215 patients to group B. Analysis was performed on an intention-to-treat basis. DFS did not differ significantly between groups. The 95% confidence interval of the hazard ratio for recurrence was 0.85-1.27 according to Cox proportional hazard modeling, within the margin of 2.12 required to declare 10% noninferiority. DFS for patients without TSH suppression was not inferior by more than 10% to DFS for patients with TSH suppression. Thyroid-conserving surgery without TSH suppression should be considered for patients with low-risk PTC to avoid potential adverse effects of TSH suppression.

Management of low-risk papillary thyroid carcinoma: Unique conventional policy in Japan and our efforts to improve the level of evidence

Papillary thyroid carcinoma (PTC) accounts for over 90% of all thyroid cancers in Japan. The majority of patients with PTC are categorized into a low-risk group according to the recent risk-group classification schemes, and they have excellent outcomes. Several management guidelines for thyroid cancers have been published in Western countries. However, the optimal therapeutic options for PTC remain controversial and high-level clinical evidence to resolve the issues is lacking. Moreover, socioeconomic differences in medical care exist; therefore, conventional policies for the treatment of PTC have been different between Japan and other countries. This report reviews the controversy in the treatment of PTC regarding the initial surgery, postoperative adjuvant therapies, and methods of surveillance. This review focuses on the unique policy in Japan preferring to treat patients with low-risk PTC by a less-than-total thyroidectomy without adjuvant therapies rather than a total thyroidectomy with radioactive iodine, in an attempt to maintain patients' quality of life. In addition, the institutional efforts to improve the level of evidence for the management of PTC are introduced, such as a randomized controlled trial for the effect of thyrotropin suppression therapy, a prospective study for selective lymph node dissection based on preoperative ultrasonography, and a prospective nonsurgical observation trial for asymptomatic papillary microcarcinoma.