Shortened telomere length in peripheral blood leukocytes is associated with cumulative radioactive iodine doses in patients with differentiated thyroid carcinoma.

BACKGROUND: Telomere length is associated with cancer risk and cancer aggressiveness. Radioactive iodine (RAI) therapy for thyroid cancer has raised concerns for second primary malignancy (SPM) in patients with high cumulative doses. The association between RAI dose and peripheral blood leukocyte telomere length was examined. METHODS: A total of 425 patients were included who underwent total thyroidectomy and were followed up for at least 1 year with or without RAI treatment. The relative telomere length (RTL) of the patients was assessed via a quantitative polymerase chain reaction amplification method. RAI doses were divided into five groups on the basis of cumulative dose, and a comparison was made among these groups. RESULTS: The number of patients with RAI treatment was 287 (67.5%), and the cumulative RAI dose was 3.33 GBq (range, 1.11-131.35 GBq). The mean RTL was significantly shorter in the highest RAI group (>22.2 GBq) compared to both the no-RAI and lower dose groups. The association between RAI dose and RTL was positive in the lower RAI group (1.1-3.7 GBq) and negative in the highest RAI group in both univariate and multivariate analyses. We observed 59 (13.9%) SPMs and 20 (4.7%) mortalities, and RTL did not show a significant risk effect for all-cause, thyroid cancer-specific, or SPM-specific mortality. CONCLUSIONS: In patients with thyroid cancer who underwent total thyroidectomy, peripheral blood leukocyte telomere length exhibited a significant association with cumulative RAI dose higher than 22.2 GBq. These results suggest the possibility of telomere length shortening in patients who undergo high-dose RAI treatment.

Surgical Outcomes in Patients With Low-risk Papillary Thyroid Microcarcinoma From MAeSTro Study: Immediate Operation Versus Delayed Operation After Active SurveillanceA Multicenter Prospective Cohort Study.

OBJECTIVE: To investigate surgical, and clinical outcomes in patients with low-risk papillary thyroid microcarcinoma (PTMC) according to treatment options [immediate operation (IOP) vs delayed operation after active surveillance (AS) (DOP)]. BACKGROUND: AS has been adopted as an alternative to immediate surgery in patients with low-risk PTMC. Although some patients undergo surgery during AS, there is little information on surgical, and clinical outcomes after delayed operation after AS. METHODS: A multicenter prospective cohort study including 1177 patients was conducted at 3 tertiary hospitals in Korea from June 2016 to January 2020. Patients with low-risk PTMC were enrolled. The participants were self-assigned into AS or IOP, and during AS, the patients underwent surgery if there were signs of disease progression or if the patient's choice changed. RESULTS: A total of 516 patients underwent operation; 384 (74.4%) in the IOP group and 132 (25.6%) in the DOP group. Compared with the IOP group, the DOP group was significantly associated with a larger tumor size ( P =0.002), higher rates of lymphatic invasion ( P =0.002), and multifocality ( P =0.008). However, the rates of total thyroidectomy, postoperative hypoparathyroidism and vocal cord palsy did not differ significantly between the groups ( P = 0.283, P =0.184, and P =0.284, respectively). Of the 132 patients in the DOP group, disease progression was present in 39 (29.5%) patients. The DOP group with disease progression had a significantly higher rate of lymph node metastasis ( P =0.021) and radioiodine therapy ( P =0.025) than the DOP group without disease progression. CONCLUSIONS: These results suggest that AS might be considered an alternative treatment option for patients with low-risk PTMC regarding the extent of thyroidectomy and postoperative complications in the DOP group. To assess oncologic outcomes, long-term follow-up will be needed. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02938702.

Skeletal effects of combined bisphosphonates treatment and parathyroidectomy in osteoporotic patients with primary hyperparathyroidism.

INTRODUCTION: Bone loss caused by primary hyperparathyroidism (PHPT) is an indication for parathyroidectomy (PTX). However, whether adding bisphosphonates would be superior to PTX alone to increase bone mass remains unclear. We thus aimed to compare the skeletal effects of the combination treatment of bisphosphonates and PTX with PTX alone. MATERIALS AND METHODS: In this retrospective analysis, bone mineral density (BMD) changes after 1 year of combination treatment and PTX alone were compared. We also analyzed the correlation between changes in serum biochemical parameters and BMD after 1 year of treatment in both groups. RESULTS: The baseline characteristics of patients treated with PTX alone (n = 24) and combination treatment (n = 26) were comparable. BMD significantly increased after 1 year of treatment in both groups (all p < 0.001), and the increase in BMD at the femur neck was higher in the PTX alone group than in the combination group (p = 0.011). There was a decreasing trend in serum alkaline phosphatase (ALP) levels in PTX alone compared to the combination treatment group (p = 0.053). In the study cohort, lower BMD and higher ALP levels at baseline were associated with higher 1-year BMD changes at all sites. Interestingly, a significant association was found between changes in ALP and BMD at the femur neck in the PTX alone group (p = 0.003), but abolished in the combination group (p = 0.946). CONCLUSIONS: There is no additional benefit of BMD in combination treatment with bisphosphonates and PTX over PTX alone in osteoporotic patients with PHPT. Combined bisphosphonate treatment might interfere with the increase in bone mass caused by PTX.

Functional Voice and Swallowing Outcome Analysis After Thyroid Lobectomy: Transoral Endoscopic Vestibular Versus Open Approach.

BACKGROUND: The transoral endoscopic thyroidectomy vestibular approach (TOETVA) is a scarless remote-access thyroidectomy technique. This study compared subjective and objective voice outcomes and swallowing outcomes of patients who underwent thyroid lobectomy using the TOETVA versus conventional open thyroidectomy (OT). METHODS: In addition to questionnaires, acoustic and aerodynamic analyses were performed to compare subjective and objective voice outcomes of the two groups. Swallowing outcome analyses were conducted using Swallowing Impairment Index-6 (SIS-6) scores. Assessments were performed preoperatively and 3 and 6 months after surgery. Propensity score matching was performed to compare the outcomes of the two groups. RESULTS: One hundred and two patients were included in this study (52 TOETVA and 50 OT). Excluding two patients who had vocal cord palsy and open conversion in the TOETVA group, 100 patients completed 3-month postoperative surveys. There were no significant differences between the groups in VAS, GRBAS, or VHI-10 scores at the preoperative and 3- and 6-month assessments. For both groups, there were no significant changes in acoustic or aerodynamic parameters during the 3-6-month postoperative period. The TOETVA group had lower SIS-6 scores at the postoperative 6-month assessment, but the SIS-6 scores after 12 months were similar between groups before and after propensity score matching. CONCLUSIONS: Following TOETVA lobectomy, there were no significant changes in voice outcomes 3 and 6 months after surgery, and the outcomes were comparable with those of OT. The TOETVA group also had swallowing outcomes that were comparable with the OT group.

Prognostic effects of TERT promoter mutations are enhanced by coexistence with BRAF or RAS mutations and strengthen the risk prediction by the ATA or TNM staging system in differentiated thyroid cancer patients.

BACKGROUND: Recent reports suggest that mutations in the promoter of the gene encoding telomerase reverse transcriptase (TERT) affect thyroid cancer outcomes. METHODS: In all, 551 patients with differentiated thyroid cancer (DTC) enrolled in this study. The median follow-up duration was 4.8 years (interquartile range, 3.4-10.6 years). RESULTS: TERT promoter mutations were detected in 25 DTCs (4.5%): 2.8% in neither BRAF-mutated nor RAS-mutated tumors, 4.8% in BRAF-mutated tumors, and 11.3% in RAS-mutated tumors. Moreover, they were frequently observed in American Thyroid Association (ATA) high-risk and TNM stage III/IV groups (9.1% and 12.9%, respectively). The coexistence of BRAF or RAS with TERT promoter mutations increased aggressive clinicopathologic features, recurrence (hazard ratio [HR] for BRAF, 4.64; 95% confidence interval [CI], 1.42-15.18; HR for RAS, 5.36; 95% CI, 1.20-24.02), and mortality (HR for BRAF, 15.13; 95% CI, 1.55-148.23; HR for RAS, 14.75; 95% CI, 1.30-167.00), even after adjustments for the age at diagnosis and sex, although the significance was lost after additional adjustments for pathologic characteristics. Furthermore, TERT promoter mutations significantly increased the risk of both recurrence and mortality in the ATA high-risk (HR for recurrence, 5.79; 95% CI, 2.07-16.18; HR for mortality, 16.16; 95% CI, 2.10-124.15) and TNM stage III/IV groups (HR for recurrence, 3.60; 95% CI, 1.19-10.85; HR for mortality, 9.06; 95% CI, 2.09-39.26). CONCLUSIONS: The coexistence of BRAF or RAS mutations enhanced the prognostic effects of TERT promoter mutations. Furthermore, TERT promoter mutations strengthened the predictions of mortality and recurrence by the ATA and TNM staging systems, particularly for high-risk patients with DTC. Cancer 2016;122:1370-1379. © 2016 American Cancer Society.

Recombinant human thyrotropin-stimulated thyroglobulin level at the time of radioactive iodine ablation is an independent prognostic marker of differentiated thyroid carcinoma in the setting of prophylactic central neck dissection.

OBJECTIVE: We investigated the value of the stimulated thyroglobulin (Tg) level at the time of recombinant human thyrotropin (rhTSH)-aided remnant ablation for predicting disease status 1 year later in patients with DTC who underwent total thyroidectomy with central neck dissection (CND). DESIGN, SETTING, AND PARTICIPANT: This was a prospective observational study of 253 consecutive patients with DTC who underwent rhTSH-aided RAI ablation after total thyroidectomy and prophylactic CND. Patients with evidence of initial distant metastasis or positive Tg antibodies were excluded. MAJOR OUTCOME MEASURE: We compared rhTSH-stimulated Tg level at RAI ablation according to the disease status at 1 year and evaluated optimal cut-off value of rhTSH-stimulated Tg. Binary logistic regression analysis was performed to investigate the independent predictive factors for disease status 1 year after ablation. RESULTS: Among study participants, 228 (90·1%) were considered disease free at 1 year after remnant ablation. Patients with persistent or recurrent disease were more likely to be aged ≥45 years, and to have N1b stage, TNM stage III or IV, and higher rhTSH-stimulated Tg level at RAI ablation. The optimal cut-off of rhTSH-stimulated Tg for predicting persistent or recurrent disease was 1·79 ng/ml, with a negative predictive value of 99·5%. A serum rhTSH-stimulated Tg level ≥1·79 at the time of ablation was independently associated with persistent or recurrent disease 1 year later. N1b stage tended to be associated with persistent or recurrent disease. CONCLUSION: A low stimulated serum Tg level at rhTSH-aided RAI ablation may be a favourable prognostic marker in the setting of prophylactic CND.

Postoperative biochemical remission of serum calcitonin is the best predictive factor for recurrence-free survival of medullary thyroid cancer: a large-scale retrospective analysis over 30 years.

CONTEXT: The increase in thyroid screening in the general population may lead to earlier detection of medullary thyroid carcinoma (MTC). OBJECTIVE: We aimed to evaluate secular trends in clinicopathological characteristics and long-term prognosis of MTC and its prognostic factors. DESIGN: This was a retrospective analysis from 1982 to 2012. PATIENTS: Three hundred and thirty-one patients with MTC were included and grouped based on the year of diagnosis (1982-2000, 2001-2005, 2006-2010 and 2011-2012). MEASUREMENTS: These included recurrence and mortality as well as biochemical remission (BCR) of serum calcitonin. RESULTS: Mean tumour size (from 2·5 cm to 1·7 cm, P < 0·001) and percentage of extrathyroidal extension (from 52·0% to 26·0%, P = 0·026) decreased. The percentage of patients achieving BCR within six postoperative months (po-BCR) increased with time (from 39·6% to 76·1%, P < 0·001). The 5-year overall recurrence rate significantly decreased in 2006-2012 compared to 1982-2005 (10% vs 18%, respectively, P = 0·031), although the 5-year survival rate did not improve (92% vs 92%, P = 0·929). Failure to achieve po-BCR was the strongest predictive factor associated with recurrence (hazard ratio [HR] = 58·04, 95% CI 7·14-472·11; P < 0·001). Male gender (HR = 3·18, 95% CI 1·18-8·56; P = 0·022), tumour size >2 cm (HR = 18·33, 95% CI 2·35-143·06; P = 0·006) and distant metastasis (HR = 4·00, 95% CI 1·31-12·21; P = 0·015) were significant prognostic factors for mortality. CONCLUSIONS: Clinicopathological characteristics and recurrence of MTC improved with time. Po-BCR was the best predictive factor for recurrence-free survival.

The risk of second primary malignancy is increased in differentiated thyroid cancer patients with a cumulative (131)I dose over 37 GBq.

BACKGROUND: The aim of this study was to investigate the risk factors for second primary malignancy (SPM) diagnosed after differentiated thyroid cancer (DTC). METHODS: A total of 2468 DTC patients who underwent thyroidectomy were reviewed. SPM was defined as a non-thyroidal malignancy, diagnosed at least 1 year after the diagnosis of thyroid cancer. Patients were divided into five groups according to cumulative (131)I dose: very high-activity (≥ 37.0 GBq), high-activity (22.3-36.9 GBq), intermediate-activity (5.56-22.2 GBq), low-activity (1.1-5.55 GBq) and no RAI. RESULTS: Among the 2468 patients, 61 (2.5%) had SPMs during 7.0 (1.0-33.0) years of median follow-up. Age above 40 years, male sex and very high-activity RAI were independent risk factors for the development of SPM. SPM-related mortality was highest in the very high-activity group, while DTC-related mortality was highest in the high-activity group. The overall mortality both from SPM and DTC was highest in the high-activity group. CONCLUSION: A cumulative (131)I dose <37.0 GBq did not increase the risk of SPM. A cumulative (131) I dose ≥ 37.0 GBq increased the risk of SPM and SPM-related mortality and decreased the DTC-specific mortality, resulting in a similar all-cause mortality compared with the low-activity RAI group. Using repeated high-dose RAI for treating RAI-responsive but persistent DTC patients needs careful consideration of the individual benefits from RAI vs the risk of developing SPM.

Loss of ERß expression in papillary thyroid carcinoma is associated with recurrence in young female.

OBJECTIVES: We investigated the expression of oestrogen receptors (ERs) in papillary thyroid cancers (PTCs) and evaluated their prognostic role. METHODS: We enrolled 81 female patients who underwent thyroid surgery and had a confirmed diagnosis of PTC between 01 January 1995 and 31 December 1996. Data on clinicopathologic parameters were obtained from patients' medical records. Tissue paraffin blocks of these 81 patients were collected for immunohistochemistry for ERα and ERß. RESULTS: ERα expression was observed in only eight patients (9·9%). In contrast, ERß expression was positive in 36 (44·4%) patients. Total thyroidectomy (84·4% vs 61·1%, P = 0·017) and cervical lymph node metastasis (62·2% vs 22·2%, P = 0·000) were more frequent in the ERß-negative group than in the ERß-positive group. Among younger female patients (<45 years), the ERß-negative group showed a tendency towards more frequent recurrent or persistent disease than the ERß-positive group (42·3% vs 13·6%, P = 0·029). In contrast, the ERα-positive group showed more recurrent or persistent disease than the ERα-negative group in older female patients (100% vs 24·1%, P = 0·024). In multivariate analysis, ERß negativity, extrathyroidal invasion and radioactive iodine treatment were risk factors for recurrence in young female patients. CONCLUSION: Loss of ERß expression was associated with recurrence in young female PTC patients. This finding suggests that oestrogen might play a protective role in the progression of PTC via ERß, especially in young female patients.

Clinical Outcome of Remnant Thyroid Ablation with Low Dose Radioiodine in Korean Patients with Low to Intermediate-risk Thyroid Cancer.

Radioiodine activity required for remnant thyroid ablation is of great concern, to avoid unnecessary exposure to radiation and minimize adverse effects. We investigated clinical outcomes of remnant thyroid ablation with a low radioiodine activity in Korean patients with low to intermediate-risk thyroid cancer. For remnant thyroid ablation, 176 patients received radioiodine of 1.1 GBq, under a standard thyroid hormone withdrawal and a low iodine diet protocol. Serum levels of thyroid stimulating hormone stimulated thyroglobulin (off-Tg) and thyroglobulin-antibody (Tg-Ab), and a post-therapy whole body scan (RxWBS) were evaluated. Completion of remnant ablation was considered when there was no visible uptake on RxWBS and undetectable off-Tg (<1.0 ng/mL). Various factors including age, off-Tg, and histopathology were analyzed to predict ablation success rates. Of 176 patients, 68.8% (n = 121) who achieved successful remnant ablation were classified into Group A, and the remaining 55 were classified into Group B. Group A presented with significantly lower off-Tg at the first radioiodine administration (pre-ablative Tg) than those of Group B (1.2 ± 2.3 ng/mL vs. 6.2 ± 15.2 ng/mL, P = 0.027). Pre-ablative Tg was the only significant factor related with ablation success rates. Diagnostic performances of pre-ablative Tg < 10.0 ng/mL were sensitivity of 99.1%, specificity of 14.0%, positive predictive value of 71.1%, and negative predictive value of 87.5%, respectively. Single administration of low radioiodine activity could be sufficient for remnant thyroid ablation in patients with low to intermediate-risk thyroid cancer. Pre-ablative Tg with cutoff value of 10.0 ng/mL is a promising factor to predict successful remnant ablation.

The role of ultrasound findings in the management of thyroid nodules with atypia or follicular lesions of undetermined significance.

BACKGROUND: Atypia or follicular lesions of undetermined significance (AUS/FLUS) is a broad cytological category in the Bethesda system for classifying thyroid cytology. This study investigated the diagnostic accuracy of ultrasound (US) analysis of thyroid nodules with AUS/FLUS. PATIENTS AND METHODS: Of 5062 subjects with nodules subjected to fine-needle aspiration cytology (FNACs) at our institution from January 2010 through May 2012, 383 met the Bethesda criteria for AUS/FLUS. After excluding subjects who had a history of thyroid cancer, who only underwent repeat FNA or who underwent no further examinations, we selected 249 subjects who had subsequently undergone a core-needle biopsy and/or surgery. Of these, 100 were found to have malignant nodules (40·2%), 122 had benign nodules (49%), and 27 had nodules with indeterminate status (10·8%). We compared specific US parameters, including size, location, content, shape, margin, echogenicity, echotexture and calcification across these subject groups. RESULTS: Multivariate analysis revealed that malignancy was associated with taller-than-wide shape (TDW) (OR = 8·43, P = 0·002), ill-defined margin (OR = 3·23, P = 0·002) and marked hypoechogenicity. (OR = 3·61, P = 0·001). The specificity and positive predictive values of TDW were 98% and 90·6%,respectively. The specificity and positive predictive values of 'TDW and marked hypoechogenicity' were both 100%. CONCLUSION: US findings play a complementary role in the diagnosis of thyroid nodules with AUS/FLUS. In case of highly suspicious US findings such as 'TDW and marked hypoechogenicity', could be very helpful in the diagnosis of malignancy.

Plasma FGF21 levels are increased in patients with hypothyroidism independently of lipid profile.

Thyroid hormone is a potent regulator of metabolic and energy homeostasis implicated in various metabolic diseases. Fibroblast growth factor 21(FGF21) is a systemic metabolic regulator known to modulate various biological functions similar to the actions of thyroid hormone. We investigated the differences in plasma FGF21 concentrations in patients with varying thyroid function. Ninety drug-naïve subjects who underwent thyroid evaluation at Seoul National University Bundang Hospital were enrolled and classified into euthyroid, subclinical hypothyroid, and overtly hypothyroid groups. Biochemical markers and plasma FGF21 levels were measured and analyzed. The mean age of the subjects was 42.6 ± 9.1 years. The mean body mass index (BMI), waist circumference, and fasting glucose concentrations were similar between groups. Overtly hypothyroid subjects exhibited significantly higher concentrations of total cholesterol, triglyceride, and LDL-cholesterol than the other groups (p<0.01). Mean plasma FGF21 concentrations in euthyroid, subclinical hypothyroid and overtly hypothyroid groups were 43.2 ± 39.2 pg/mL, 63.6 ± 73.6 pg/mL, and 101.5 ± 74.9 pg/mL, respectively (p<0.01 between groups). Plasma FGF21 concentrations remained significantly higher in overtly hypothyroid subjects after adjusting for serum triglyceride concentrations (p<0.005). Multivariate analysis revealed a significant positive linear relationship between serum TSH concentrations and plasma FGF21 concentrations (ß = 0.192, p = 0.002) and a significant negative linear relationship between free T4 and plasma FGF21 concentrations (ß = -0.382, p = 0.037) after adjusting for gender, BMI and serum concentrations of triglycerides and glucose. Plasma FGF21 levels were significantly increased in patients with hypothyroidism independently of BMI, or lipid or glucose metabolism.

Diagnosis and Management of Thyroid Disease during Pregnancy and Postpartum: 2023 Revised Korean Thyroid Association Guidelines.

Thyroid hormone plays a critical role in fetal growth and development, and thyroid dysfunction during pregnancy is associated with several adverse outcomes, such as miscarriage and preterm birth. In this review, we introduce and explain three major changes in the revised Korean Thyroid Association (KTA) guidelines for the diagnosis and management of thyroid disease during pregnancy: first, the normal range of thyroid-stimulating hormone (TSH) during pregnancy; second, the treatment of subclinical hypothyroidism; and third, the management of euthyroid pregnant women with positive thyroid autoantibodies. The revised KTA guidelines adopt 4.0 mIU/L as the upper limit of TSH in the first trimester. A TSH level between 4.0 and 10.0 mIU/L, combined with free thyroxine (T4) within the normal range, is defined as subclinical hypothyroidism, and a TSH level over 10 mIU/L is defined as overt hypothyroidism regardless of the free T4 level. Levothyroxine treatment is recommended when the TSH level is higher than 4 mIU/L in subclinical hypothyroidism, regardless of thyroid peroxidase antibody positivity. However, thyroid hormone therapy to prevent miscarriage is not recommended in thyroid autoantibody-positive women with normal thyroid function.

Prevalence, Treatment Status, and Comorbidities of Hyperthyroidism in Korea from 2003 to 2018: A Nationwide Population Study.

BACKGRUOUND: This study aimed to investigate the changes of incidence and treatment of choice for hyperthyroidism from 2003 to 2018 and explore the treatment-related complications and concomitant comorbidities in South Korea using data from the National Health Insurance Service. METHODS: This is a retrospective observational study. Hyperthyroidism was defined as a case having two or more diagnostic codes of thyrotoxicosis, with antithyroid drug intake for more than 6 months. RESULTS: The average age-standardized incidence of hyperthyroidism from 2003 to 2018 was 42.23 and 105.13 per 100,000 men and women, respectively. In 2003 to 2004, hyperthyroidism was most often diagnosed in patients in their 50s, but in 2017 to 2018, people were most often diagnosed in their 60s. During the entire period, about 93.7% of hyperthyroidism patients were prescribed with antithyroid drugs, and meanwhile, the annual rates of ablation therapy decrease from 7.68% in 2008 to 4.56% in 2018. Antithyroid drug-related adverse events, mainly agranulocytosis and acute hepatitis, as well as complications of hyperthyroidism such as atrial fibrillation or flutter, osteoporosis, and fractures, occurred more often in younger patients. CONCLUSION: In Korea, hyperthyroidism occurred about 2.5 times more in women than in men, and antithyroid drugs were most preferred as the first-line treatment. Compared to the general population, hyperthyroid patients may have a higher risk of atrial fibrillation or flutter, osteoporosis, and fractures at a younger age.

Serum thyroglobulin level measured after thyroxine withdrawal is useful to predict further recurrence in whole body scan-negative papillary thyroid cancer patients after reoperation.

The best treatment option for recurrent papillary thyroid carcinoma (PTC) is reoperation when the recurrent lesion is locoregional. The prognostic significance of serum thyroglobulin (Tg) levels before reoperation and the association between the outcome of reoperation and Tg level remain unclear. Our study aimed to determine the outcomes of patients who underwent reoperation and their association with serum Tg levels. We retrospectively studied 79 patients with PTC with locoregional recurrence whose whole-body scan results were negative for any recurrence but whose serum Tg levels were detectable after first-line treatment. All the patients underwent reoperation and follow-up examinations, which involved serial serum Tg measurements after thyroxine withdrawal (T4-off Tg), neck ultrasonography, chest computed tomography, and/or fluorodeoxyglucose-positron emission tomography, to detect further recurrence. During the median follow-up duration of 89 months (range, 38-332 months), 30 patients (38.0%) experienced a second recurrence even after the reoperation. Among all patients, only 12 whose Tg levels decreased postoperatively to undetectable levels showed no recurrence. Most recurrences were detected in the patients with high T4-off Tg levels after the reoperation (T4-off Tg level (ng/mL), number of patients with recurrence, %: <1, 0/12, 0%; 1-10, 9/31, 33.3%; >10, 16/22, 72.7%; P < 0.001). In conclusion, recurrence occurred in 38.0% of the patients even after the reoperation. The postoperative T4-off Tg level was a good indicator of recurrence after the reoperation. Therefore, patients who experience recurrence should undergo follow-up examinations that involve routine measurements of T4-off Tg levels, especially when postreoperative values exceed 10 ng/mL.

Risk of Adverse Pregnancy Outcomes in Young Women with Thyroid Cancer: A Systematic Review and Meta-Analysis.

This meta-analysis investigated whether thyroidectomy or radioactive iodine treatment (RAIT) in patients with differentiated thyroid cancer (DTC) was associated with an increase in adverse pregnancy outcomes, such as miscarriage, preterm delivery, and congenital malformations. A total of 22 articles (5 case-control and 17 case series studies) from 1262 studies identified through a literature search in the PubMed and EMBASE databases from inception up to 13 September 2021 were included. In patients with DTC who underwent thyroidectomy, the event rates for miscarriage, preterm labor, and congenital anomalies were 0.07 (95% confidence interval [CI], 0.05-0.11; 17 studies), 0.07 (95% CI, 0.05-0.09; 14 studies), and 0.03 (95% CI, 0.02-0.06; 17 studies), respectively. These results are similar to those previously reported in the general population. The risk of miscarriage or abortion was increased in patients with DTC when compared with controls without DTC (odds ratio [OR], 1.80; 95% CI, 1.28-2.53; I2 = 33%; 3 studies), while the OR values for preterm labor and the presence of congenital anomalies were 1.22 (95% CI, 0.90-1.66; I2 = 62%; five studies) and 0.73 (95% CI, 0.39-1.38; I2 = 0%; two studies) respectively, which showed no statistical significance. A subgroup analysis of patients with DTC according to RAIT revealed that the risk of miscarriage, preterm labor, or congenital anomalies was not increased in the RAIT group when compared with patients without RAIT. The results of this meta-analysis suggest that thyroid cancer treatment, including RAIT, is not associated with an increased risk of adverse pregnancy outcomes, including miscarriage, preterm labor, and congenital anomalies.

Effect of Cigarette Smoking on Thyroid Cancer: Meta-Analysis.

BACKGROUND: Although smoking is generally carcinogenic, its effect on thyroid cancers is still subject to controversy. The purpose of this study was to summarize the role of smoking in relation to thyroid cancer occurrence. METHODS: We performed a meta-analysis of 24 eligible studies: 21 case-control studies and three prospective cohort studies. The summary odds ratio (OR) and 95% confidence interval (CI) of all studies were acquired based on random effect model. Further subgroup analyses were conducted according to gender, histological type of thyroid cancer, and smoking status of patients for the case-control studies. RESULTS: The summary effect size indicated a negative association of smoking for thyroid cancer (OR, 0.798; 95% CI, 0.681 to 0.935). From the subgroup analyses for the case-control studies, reduced risk of thyroid cancer was observed in both men (OR, 0.734; 95% CI, 0.553 to 0.974) and women (OR, 0.792; 95% CI, 0.700 to 0.897). The protective effect of smoking was observed in studies in which thyroid cancer was limited to differentiated thyroid cancers (DTCs) (OR, 0.798; 95% CI, 0.706 to 0.902). CONCLUSION: Our results suggests that smoking may have a protective effect on thyroid cancer, especially on DTCs. Further studies with larger sample sizes should be conducted in elucidating the dose and time dependent effect of smoking on thyroid cancer with specific focus on the types of thyroid cancers.

Assessment of Inter-Institutional Post-Operative Hypoparathyroidism Status Using a Common Data Model.

Post-thyroidectomy hypoparathyroidism may result in various transient or permanent symptoms, ranging from tingling sensation to severe breathing difficulties. Its incidence varies among surgeons and institutions, making it difficult to determine its actual incidence and associated factors. This study attempted to estimate the incidence of post-operative hypoparathyroidism in patients at two tertiary institutions that share a common data model, the Observational Health Data Sciences and Informatics. This study used the Common Data Model to extract explicitly specified encoding and relationships among concepts using standardized vocabularies. The EDI-codes of various thyroid disorders and thyroid operations were extracted from two separate tertiary hospitals between January 2013 and December 2018. Patients were grouped into no evidence of/transient/permanent hypoparathyroidism groups to analyze the likelihood of hypoparathyroidism occurrence related to operation types and diagnosis. Of the 4848 eligible patients at the two institutions who underwent thyroidectomy, 1370 (28.26%) experienced transient hypoparathyroidism and 251 (5.18%) experienced persistent hypoparathyroidism. Univariate logistic regression analysis predicted that, relative to total bilateral thyroidectomy, radical tumor resection was associated with a 48% greater likelihood of transient hypoparathyroidism and a 102% greater likelihood of persistent hypoparathyroidism. Moreover, multivariate logistic analysis found that radical tumor resection was associated with a 50% greater likelihood of transient hypoparathyroidism and a 97% greater likelihood of persistent hypoparathyroidism than total bilateral thyroidectomy. These findings, by integrating and analyzing two databases, suggest that this analysis could be expanded to include other large databases that share the same Observational Health Data Sciences and Informatics protocol.

Clinicopathological Characteristics and Recurrence-Free Survival of Rare Variants of Papillary Thyroid Carcinomas in Korea: A Retrospective Study.

BACKGROUND: We aimed to evaluate the clinicopathological features and biological behaviors of Korean thyroid cancer patients with rare variants of papillary thyroid carcinoma (PTC) to address the ambiguity regarding the prognostic consequences of these variants. METHODS: We retrospectively reviewed the medical records of 5,496 patients who underwent thyroid surgery for PTC, between January and December 2012, in nine tertiary hospitals. Rare PTC variants included tall cell (TCV), columnar cell (CCV), diffuse sclerosing (DSV), cribriform-morular (CMV), solid (SV), hobnail, and Warthin-like variants. Recurrence-free survival (RFS) was defined as the time from the date of thyroidectomy until recurrence. RESULTS: Rare variants accounted for 1.1% (n=63) of the PTC patients; with 0.9% TCV, 0.02% CCV, 0.1% DSV, 0.1% CMV, and 0.1% SV. The mean age of patients and primary tumor size were 42.1±13.1 years and 1.3±0.9 cm, respectively. Extrathyroidal extension and cervical lymph node metastasis were observed in 38 (60.3%) and 37 (58.7%) patients, respectively. Ultrasonographic findings revealed typical malignant features in most cases. During a median follow-up of 7 years, 6.3% of patients experienced a locoregional recurrence. The 5-year RFS rates were 71.4% in patients with DSV or SV, 95.9% for TCV, or CCV, and 100% for other variants. DSV emerged an independent risk factor associated with shorter RFS. CONCLUSION: In this multicenter Korean cohort, rare variants accounted for 1.1% of all PTC cases, with TCV being the most frequent subtype. DSV emerged as a significant prognostic factor for RFS.

A Multicenter, Randomized, Controlled Trial for Assessing the Usefulness of Suppressing Thyroid Stimulating Hormone Target Levels after Thyroid Lobectomy in Low to Intermediate Risk Thyroid Cancer Patients (MASTER): A Study Protocol.

BACKGROUND: Postoperative thyroid stimulating hormone (TSH) suppression therapy is recommended for patients with intermediate- and high-risk differentiated thyroid cancer to prevent the recurrence of thyroid cancer. With the recent increase in small thyroid cancer cases, the extent of resection during surgery has generally decreased. Therefore, questions have been raised about the efficacy and long-term side effects of TSH suppression therapy in patients who have undergone a lobectomy. METHODS: This is a multicenter, prospective, randomized, controlled clinical trial in which 2,986 patients with papillary thyroid cancer are randomized into a high-TSH group (intervention) and a low-TSH group (control) after having undergone a lobectomy. The principle of treatment includes a TSH-lowering regimen aimed at TSH levels between 0.3 and 1.99 µIU/mL in the low-TSH group. The high-TSH group targets TSH levels between 2.0 and 7.99 µIU/mL. The dose of levothyroxine will be adjusted at each visit to maintain the target TSH level. The primary outcome is recurrence-free survival, as assessed by neck ultrasound every 6 to 12 months. Secondary endpoints include disease-free survival, overall survival, success rate in reaching the TSH target range, the proportion of patients with major cardiovascular diseases or bone metabolic disease, the quality of life, and medical costs. The follow-up period is 5 years. CONCLUSION: The results of this trial will contribute to establishing the optimal indication for TSH suppression therapy in low-risk papillary thyroid cancer patients by evaluating the benefit and harm of lowering TSH levels in terms of recurrence, metabolic complications, costs, and quality of life.