Comprehensive guidance on the diagnosis and management of primary mesenchymal tumours of the thyroid gland.

Most primary thyroid tumours are of epithelial origin. Primary thyroid mesenchymal tumours are rare but are being increasingly detected. A vast majority of thyroid mesenchymal tumours occur between the fourth and seventh decades of life, presenting as progressively enlarging thyroid nodules that often yield non-diagnostic results or spindle cells on fine needle aspiration biopsy. Surgery is the preferred mode of treatment, with adjuvant chemoradiotherapy used for malignant thyroid mesenchymal tumours. Benign thyroid mesenchymal tumours have excellent prognosis, whereas the outcome of malignant thyroid mesenchymal tumours is variable. Each thyroid mesenchymal tumour is characterised by its unique histopathology and immunohistochemistry. Because of the rarity and aggressive nature of malignant thyroid mesenchymal tumours, a multidisciplinary team-based approach should ideally be used in the management of these tumours. Comprehensive guidelines on the management of thyroid mesenchymal tumours are currently lacking. In this Review, we provide a detailed description of thyroid mesenchymal tumours, their clinical characteristics and tumour behaviour, and provide recommendations for the optimal management of these tumours.

Poor patient compliance with instructions for continuous sialogogues after 131 I therapy.

OBJECTIVES: To analyze the role of patient compliance as a factor in evaluating the effectiveness of continuous sialogogues to prevent salivary side effects from 131 I therapy in differentiated thyroid cancer patients. METHODS: Differentiated thyroid cancer patients who were clinically scheduled for an 131 I therapy at MedStar Washington Hospital Center between 2012 and 2013 were given instructions for continuous sialogogues per standard clinical protocol. The prospective survey was given at multiple time points. RESULTS: Ninety-nine patients consented to participate of whom 94 participants had complete data. The mean prescribed 131 I activity was 121 ± 50 mCi (4.5 ± 1.9 GBq), range 27.5-288 mCi (1.0-10.7 GBq ). Overall, only 10% (9/94) of patients were compliant with continuous sialogogues. Even though all patients took sialogogues on the first day of post-therapy, 17% of participants did not continuously take sialogogues during the first day, 60% during the first night, and 72% on the second day despite rigorous instructions to continue for two days. CONCLUSION: Despite repetitive instructions to use sialogogues continuously, most patients (90%) were not compliant. In future studies, strict monitoring and evaluation of patient compliance will be crucial when assessing the effect of continuous versus intermittent or delayed initiation of sialogogues.

Therapeutic advances in anaplastic thyroid cancer: a current perspective.

Thyroid cancer incidence is increasing at an alarming rate, almost tripling every decade. In 2017, it was the fifth most common cancer in women. Although the majority of thyroid tumors are curable, about 2-3% of thyroid cancers are refractory to standard treatments. These undifferentiated, highly aggressive and mostly chemo-resistant tumors are phenotypically-termed anaplastic thyroid cancer (ATC). ATCs are resistant to standard therapies and are extremely difficult to manage. In this review, we provide the information related to current and recently emerged first-line systemic therapy (Dabrafenib and Trametinib) along with promising therapeutics which are in clinical trials and may be incorporated into clinical practice in the future. Different categories of promising therapeutics such as Aurora kinase inhibitors, multi-kinase inhibitors, epigenetic modulators, gene therapy using oncolytic viruses, apoptosis-inducing agents, and immunotherapy are reviewed. Combination treatment options that showed synergistic and antagonistic effects are also discussed. We highlight ongoing clinical trials in ATC and discuss how personalized medicine is crucial to design the second line of treatment. Besides using conventional combination therapy, embracing a personalized approach based on advanced genomics and proteomics assessment will be crucial to developing a tailored treatment plan to improve the chances of clinical success.

18F-FDG-PET SUV AS A PROGNOSTIC MARKER OF INCREASING SIZE IN THYROID CANCER TUMORS.

OBJECTIVE: Positron emission tomography/computed tomography (PET/CT) scans with 2-[fluorine-18] fluoro-2-deoxy-D-glucose (18F-FDG) are used in high-risk thyroid cancer patients to identify metastasis. The prognostic significance of increases in standardized uptake values (SUVs) has not been clearly defined. This pilot study investigated the correlation between SUV increases and subsequent changes in individual lesion size. METHODS: A retrospective chart review of patients with histologically confirmed thyroid cancer who were monitored with serial 18F-FDG-PET/CT scans from 2008 to 2013 was performed. Forty-seven patients were selected for analysis. A mixed-effects statistical model was used after data normalization. RESULTS: For a 10% increase in SUV, a 6% increase in tumor area was observed (P<.0001). Analysis on cube root-transformed data from serial scans was significant in 4 of 5 groups: scans 1 to 2 (P = .0001), scans 2 to 3 (P = .0005), scans 3 to 4 (P = .008), scans 4 to 5 (P = .66), and overall (P<.0001). After exclusion of outliers, for a 10% increase in SUV, the expected percentage increases in area on subsequent scans were found to be 3.4% (P = .0006), 2.6% (P = .005), 4% (P = .074), and 4.1% (P = .27) for the second, third, fourth, and fifth scans, respectively. The association was similarly significant in cases with a ≥25% increase in SUV. Secondary analysis showed a significant association of SUV with thyroglobulin (Tg) level (P = .035) but not with thyroid-stimulating hormone (TSH) level (P = .85). CONCLUSIONS: A significant positive correlation was noted between the increase in lesional SUV and subsequent increase in lesion area. An increase in lesional SUV in subsequent scans may portend tumor growth and could prompt consideration for earlier or more aggressive intervention. ABBREVIATIONS: DTC = differentiated thyroid cancer EORTC = European Organization for Research and Treatment of Cancer 18F-FDG = 2-[fluorine-18] fluoro-2-deoxy-D-glucose FNA = fine-needle aspiration MTC = medullary thyroid cancer PET/CT = positron emission tomography/computed tomography PVE = partial volume effect RAI = radioactive iodine SUV = standardized uptake value Tg = thyroglobulin TSH = thyroid-stimulating hormone.

Single-dose T3 administration: kinetics and effects on biochemical and physiological parameters.

BACKGROUND: As changes in thyroid stimulating hormone (TSH), thyroid hormones, and vital signs after administration of a single dose of liothyronine have typically only been documented for 24 hours, we documented these parameters more than 96 hours. METHODS: Blood samples were obtained for 4 days after administration of 50-mcg liothyronine to 12 healthy euthyroid participants. Concentrations of total and free triiodothyronine, free and total thyroxine, and TSH were measured. Vital signs were documented. RESULTS: Triiodothyronine concentrations peaked at 2.5 hours after liothyronine administration. Heart rate (HR) increased by 5 hours after liothyronine administration, subsequently reaching a value higher than baseline (P = 0.009). Suppression of TSH concentrations began at 2 hours. The nadir TSH value at 12 hours was significantly different from baseline (P < 0.001) and remained lower than the baseline value for 2-3 days. CONCLUSIONS: A single dose of liothyronine has both short-term and long-term effects. There is clearly a different lag time between the serum concentrations of triiodothyronine and its effects on the heart and pituitary, respectively. The increase in serum triiodothyronine concentration occurred within hours and was then followed by an increase in HR. The increased HR was transient and was followed by a reduction in TSH concentration. The suppression of TSH was delayed but was more sustained. Thus, sustained TSH reduction beyond 24 hours was achieved by a single dose of liothyronine that produced only brief increases in serum triiodothyronine levels and transient increases in HR.

3,3'-Diiodothyronine concentrations in hospitalized or thyroidectomized patients: results from a pilot study.

OBJECTIVE: To determine if various medical conditions affect the serum concentrations of 3,3'-diiodothyronine (3,3'-T2). METHODS: A total of 100 patients who were recruited from a group of inpatients and outpatients with a diverse range of medical conditions, donated a single blood sample that was assayed for thyroid hormone derivatives using liquid-chromatography tandem mass spectrometry (LC-MS/MS). The associations between 3,3'-T2 concentrations and physiologic data and medical conditions were assessed. RESULTS: Higher quartiles of 3,3'-T2 concentrations (quartile 1: 2.01-7.48, quartile 2: 7.74-12.4, quartile 3: 12.5-17, quartile 4: 17.9-45.8 pg/mL) were associated with decreasing occurrence of critical illness (58%, 11%, 0%, 8%), stroke (29%, 7.7%, 4%, 0%), critical care unit hospitalization (75%, 39%, 8.3 %, 12%), and inpatient status (83%, 42%, 8%, 12%) (all P<.001). The same quartiles were associated with increasing frequency of thyroidectomy (4%, 12%, 17%, 60%). In multivariate analyses, after adjustment for age and sex, inpatient status was associated with decreasing concentrations of 3,3'-T2 (46% decrease for inpatients with 95% confidence interval [CI] 32-57%, P<.0001). Thyroidectomy was associated with increasing concentrations of 3,3'-T2 (29% increase (CI 0.5-66%, P = .049). CONCLUSION: We observed associations between inpatient status and reduced 3,3'-T2 concentrations. This appears to be a global change associated with illness, rather than an association with specific medical conditions. We also observed higher 3,3'-T2 concentrations in athyreotic outpatients receiving thyroid-stimulating hormone (TSH) suppression therapy. This demonstrates that there is production of 3,3'-T2 from levothyroxine (LT4) in extrathyroidal tissues. Conversion of thyroxine (T4) to 3,3'-T2 via both triiodothyronine (T3) and reverse triiodothyronine (rT3) pathways may prevent excessive T3 concentrations in such patients.

A diagnostic scoring system for myxedema coma.

OBJECTIVE: To develop diagnostic criteria for myxedema coma (MC), a decompensated state of extreme hypothyroidism with a high mortality rate if untreated, in order to facilitate its early recognition and treatment. METHODS: The frequencies of characteristics associated with MC were assessed retrospectively in patients from our institutions in order to derive a semiquantitative diagnostic point scale that was further applied on selected patients whose data were retrieved from the literature. Logistic regression analysis was used to test the predictive power of the score. Receiver operating characteristic (ROC) curve analysis was performed to test the discriminative power of the score. RESULTS: Of the 21 patients examined, 7 were reclassified as not having MC (non-MC), and they were used as controls. The scoring system included a composite of alterations of thermoregulatory, central nervous, cardiovascular, gastrointestinal, and metabolic systems, and presence or absence of a precipitating event. All 14 of our MC patients had a score of ≥60, whereas 6 of 7 non-MC patients had scores of 25 to 50. A total of 16 of 22 MC patients whose data were retrieved from the literature had a score ≥60, and 6 of 22 of these patients scored between 45 and 55. The odds ratio per each score unit increase as a continuum was 1.09 (95% confidence interval [CI], 1.01 to 1.16; P = .019); a score of 60 identified coma, with an odds ratio of 1.22. The area under the ROC curve was 0.88 (95% CI, 0.65 to 1.00), and the score of 60 had 100% sensitivity and 85.71% specificity. CONCLUSION: A score ≥60 in the proposed scoring system is potentially diagnostic for MC, whereas scores between 45 and 59 could classify patients at risk for MC.

A Rare Case of Persistent Multifocal Cribriform-Morular Thyroid Carcinoma.

Background/Objective: Cribriform-morular thyroid carcinoma (CMTC) was considered a variant of papillary thyroid carcinoma (PTC) but is a separate entity in the 2022 World Health Organization classification. CMTC has an association with familial adenomatous polyposis (FAP). Our objective is to report a case of CMTC who was subsequently diagnosed with FAP, to highlight these associated entities and implications for management. Case Report: A 15-year-old female with a history of iron-deficiency anemia and alpha-gal syndrome presented with several years of goiter and dysphagia. She also noted unintentional weight loss, abdominal pain, melena and hematochezia, and symptomatic anemia. Physical examination was significant for multiple thyroid nodules. Laboratory results revealed normal thyroid function and iron deficiency. Multiple nodules were visualized on thyroid ultrasound, and fine needle aspiration biopsy was consistent with PTC. Total thyroidectomy was performed with a revised diagnosis of multifocal CMTC, with administration of adjuvant radioactive iodine due to persistent disease. Genetic testing confirmed FAP and she was referred for upper endoscopy, colonoscopy, and an evaluation for colectomy. Discussion: There are no best practice guidelines for management of CMTC. Management of CMTC is guided by FAP status; sporadic cases can be managed with hemithyroidectomy, while FAP-associated cases are better managed with total thyroidectomy. Recurrence is usually managed with surgical resection. The decision to treat with adjuvant radioactive iodine is often extrapolated from management of classic PTC. Conclusion: Thyroid carcinoma in the setting of extensive family history of colorectal carcinoma should arouse suspicion for CMTC. Patients with CMTC should receive a referral for colonoscopy and genetic testing for FAP.

Redifferentiation of Differentiated Thyroid Cancer: Clinical Insights from a Narrative Review of Literature.

Background: Patients who have metastatic differentiated thyroid cancer (mDTC) frequently have negative diagnostic and/or post-therapy radioiodine scans. As a result, 131I therapy is frequently no longer considered a therapeutic option for these patients. However, with the knowledge of genomic alterations of patients with mDTC, the use of selected agents in specific patient groups may be used with the intention to re-establish 131I uptake (i.e., redifferentiation) and additional 131I therapy. The objectives of this narrative review are to present definitions of related terminology, a brief overview of the molecular mechanisms of redifferentiating agents, and a narrative review of the literature for redifferentiation in patients who have radioiodine refractory mDTC. Summary: We searched multiple electronic databases and reviewed the relevant English-language literature reported after 2010. Fourteen articles were included in this narrative review. Conclusions: Preliminary data suggest that select agents may offer potential for re-establishing 131I uptake in selected patients with radioiodine refractory mDTC (e.g., negative diagnostic and/or post-therapy radioiodine scans). These agents may also enhance uptake (e.g., uptake enhancement) in patients who have 131I uptake in mDTC on a diagnostic and/or post-therapy radioiodine scan. As a result, this may facilitate higher absorbed dose delivered (Gy (rad]) per 131I activity administered [GBq (mCi)]. This in turn may increase the likelihood of a better therapeutic effect for the planned administered 131I activity or a reduction in the originally planned administered 131I activity, while achieving the same intended therapeutic effect with potentially less untoward effects. Further studies are warranted to confirm these preliminary observations and to confirm acceptable subsequent 131I therapy responses after redifferentiation and/or uptake enhancement.

Characteristics, staging and outcomes of differentiated thyroid cancer in patients with and without Graves' disease.

Background: The incidence of thyroid cancer has increased over the last three decades with studies showing incidence of thyroid cancer is higher among patients with Graves' Disease (GD) when compared to Toxic multinodular goiter.1 We conducted a retrospective study to further investigate characteristics and outcomes in patients with thyroid cancer and GD. Methods: We retrospectively reviewed 62 patients with a diagnosis of Differentiated Thyroid Cancer (DTC). We compared age at diagnosis, type, size of tumor, radioactive iodine (RAI) use, and DTC recurrence amongst patients with GD, non-GD patients. We used Chi-square to test for independence among categorical variables at a nominal level of 0.05; comparison was based on t-test. Results: Out of 62 patients, 29 patients had GD and DTC (47%). 94% had papillary thyroid cancer. Patients with GD were diagnosed with DTC at a younger age (mean 46 years) in comparison to patients without GD (mean 53 years). There was no difference in the type of DTC. Patients with GD had significantly smaller tumor size (mean size 1.035 cm; p value = 0.002), more Stage 1 and 2 compared to patients without GD (p-value = 0.009). Both groups of patients had similar rates of recurrence on follow up and RAI use. Conclusion: We found patients with GD had smaller tumor size, early-stage DTC when compared to patients without GD and potentially favorable prognosis. More data is needed to understand whether this is due to pathogenesis like Graves antibodies promoting tumor formation or merely earlier detection of DTC in GD.

Improved sexual function after parathyroidectomy in women with primary hyperparathyroidism.

BACKGROUND: The study aimed to evaluate whether women with primary hyperparathyroidism (PHPT) experience improvement in their sexual function after parathyroidectomy. METHODS: Women with PHPT or benign thyroid nodules (controls) undergoing surgery were administered the validated Parathyroidectomy Assessment Score (PAS), Patient-Reported Outcomes Measurement Information System-29 (PROMIS-29) and Female Sexual Function Index (FSFI) pre-operatively, at 3 months and 6 months postoperatively. RESULTS: Of the 26 PHPT and 18 control patients, PHPT patients were older (53.1 vs 45.3 years, p â€‹= â€‹0.008). Post-operatively, both PHPT (pre-op 2.4 vs 3-month 3.0 vs 6-month 2.4, p â€‹= â€‹0.022) and control patients (pre-operative 2.4 vs 3-month 3.3 vs 6-month 3.6, p â€‹= â€‹0.032) reported increased desire for sexual activities. In addition, PHPT patients experienced increased arousal (pre-operative 2.7 vs 3-month 3.9 vs 6-month 3.6, p â€‹= â€‹0.047) and satisfaction (pre-operative 3.0 vs 3-month 4.8 vs 6-month 4.0, p â€‹= â€‹0.006). CONCLUSIONS: The current study indicates that women with PHPT may experience improved sexual function after parathyroidectomy.

Efficacy of machine learning to identify clinical factors influencing levothyroxine dosage after total thyroidectomy.

BACKGROUND: We employed Machine Learning (ML) to evaluate potential additional clinical factors influencing replacement dosage requirements of levothyroxine. METHOD: This was a retrospective study of patients who underwent total or completion thyroidectomy with benign pathology. Patients who achieved an euthyroid state were included in three different ML models. RESULTS: Of the 487 patients included, mean age was 54.1 ± 14.1 years, 86.0% were females, 39.0% were White, 53.0% Black, 2.7% Hispanic, 1.4% Asian, and 3.9% Other. The Extreme Gradient Boosting (XGBoost) model achieved the highest accuracy at 61.0% in predicting adequate dosage compared to 47.0% based on 1.6 mcg/kg/day (p < 0.05). The Poisson regression indicated non-Caucasian race (p < 0.05), routine alcohol use (estimate = 0.03, p = 0.02), and osteoarthritis (estimate = -0.10, p < 0.001) in addition to known factors such as age (estimate = -0.003, p < 0.001), sex (female, estimate = -0.06, p < 0.001), and weight (estimate = 0.01, p < 0.001) were associated with the dosing of levothyroxine. CONCLUSIONS: Along with weight, sex, age, and BMI, ML algorithms indicated that race, ethnicity, lifestyle and comorbidity factors also may impact levothyroxine dosing in post-thyroidectomy patients with benign conditions.

Efficacy of Levothyroxine Sodium Soft Gelatin Capsules in Thyroidectomized Patients Taking Proton Pump Inhibitors: An Open-Label Study.

Background: Treatment with proton pump inhibitors (PPIs) and antacids affects the gastrointestinal absorption of levothyroxine sodium (LT4) tablets. Patients with hypothyroidism taking LT4 and PPIs or antacids, thus, require appropriate monitoring. The objective of this study was to determine whether a soft gelatin capsule of LT4 (Tirosint®) would obviate the effect of PPIs on LT4 absorption. The objective was achieved by assessing the effects of a switch from a conventional LT4 tablet form to the same dose as soft capsules in thyroidectomized patients on treatment with LT4 and PPIs. Methods: Patients with history of hypothyroidism due to total thyroidectomy on stable treatment with LT4 tablets, and with gastrointestinal disease treated with PPIs, were switched to a 12-week treatment with Tirosint at the same dose of the LT4 tablets, while maintaining treatment with PPIs. Serum thyrotropin (TSH) levels were the primary endpoint of the study. Secondary efficacy endpoints were: serum levels of free thyroxine (fT4), total thyroxine (TT4), free triiodothyronine (fT3), total triiodothyronine (TT3), creatine-phosphokinase (CPK), sex-hormone binding globulin, ferritin, angiotensin converting enzyme, and a lipid panel. Results: Forty-seven patients (36 females and 11 males, mean age 55.4 years) were enrolled and 45 of them completed the study (2 patients withdrew consent). During treatment with Tirosint, mean TSH levels demonstrated a statistically significant decrease (mean changes from baseline: -0.32 mIU/L at week 6 and -0.68 mIU/L at week 12) and concomitant increases in thyroid hormone (TH) levels from baseline to week 12, which were statistically significant for fT3 and TT3 (mean changes from baseline: 0.26 pmol/L and 0.10 nmol/L, respectively). Significant decreases of serum low-density lipoprotein, total cholesterol, and CPK levels were observed at week 12. No signs/symptoms arose during the study that could be specifically correlated to either hypo- or hyperthyroidism. Conclusions: In thyroidectomized patients taking PPIs and replacement LT4, a switch from conventional LT4 tablets to LT4 soft capsules at the same dose was associated with a significant decrease in TSH and increase in TH, indicating that LT4 absorption may be less affected by PPIs when given in the form of soft capsules. Clinical Trial Registration: NCT03094416.

Sex Differences in Differentiated Thyroid Cancer.

Background: Sex dimorphism strongly impacts tumor biology, with most cancers having a male predominance. Uniquely, thyroid cancer (TC) is the only nonreproductive cancer with striking female predominance with three- to four-fold higher incidence among females, although males generally have more aggressive disease. The molecular basis for this observation is not known, and current approaches in treatment and surveillance are not sex specific. Summary: Although TC has overall good prognosis, 6-20% of patients develop regional or distant metastasis, one third of whom are not responsive to conventional treatment approaches and suffer a 10-year survival rate of only 10%. More efficacious treatment strategies are needed for these aggressive TCs, as tyrosine kinase inhibitors and immunotherapy have major toxicities without demonstrable overall survival benefit. Emerging evidence indicates a role of sex hormones, genetics, and the immune system in modulation of both risk for TC and its progression in a sex-specific manner. Conclusion: Greater understanding of the molecular mechanisms underlying sex differences in TC pathogenesis could provide insights into the development of sex-specific, targeted, and effective strategies for prevention, diagnosis, and management. This review summarizes emerging evidence for the importance of sex in the pathogenesis, progression, and response to treatment in differentiated TC with emphasis on the role of sex hormones, genetics, and the immune system.

Lipid Profile Changes Associated with SGLT-2 Inhibitors and GLP-1 Agonists in Diabetes and Metabolic Syndrome.

The introduction of sodium glucose transporter-2 inhibitors and glucagon-like peptide-1 receptor agonists in type 2 diabetes mellitus treatment has shown an unexpectedly significant improvement in heart disease outcome trials. Although they have very different modes of action, a portion of the salutary cardiovascular disease improvement may be related to their impact on diabetic dyslipidemia. As discussed in this focused review, the sodium glucose transporter-2 inhibitors as a class show a mild increase in low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol levels, while triglycerides (TG) decrease inconsistently. In particular, the rise in LDL appears to be related to the less atherogenic, large buoyant LDL particles. The glucagon-like peptide-1 receptor agonists show more of an impact on weight loss and improvement in the underlying low HDL and high TG dyslipidemia. The effect of sodium glucose transporter-2 inhibitors and glucagon-like peptide 1 receptor agonists when used in combination remains largely unknown. Also unexplored is difference in effect of these medications among various ethnicities and metabolic syndrome.

Clinical Factors Predictive of Lymph Node Metastasis in Thyroid Cancer Patients: A Multivariate Analysis.

BACKGROUND: Early-stage thyroid cancers have excellent survival. However, lymph node metastases (LNM) confer a worse prognosis and are not always known preoperatively. Therefore, investigation on the clinical and histological factors predictive of LNM in thyroid cancers was conducted to tailor the extent of surgery and radioactive iodine therapy. STUDY DESIGN: Multivariate logistic regressions were performed based on retrospective data from thyroid cancer patients seen between 2013 and 2020 at a single institution. RESULTS: Among 913 patients, mean age was 49.4 years, 76.5% were female, 58.3% were White, 21.2% were Black, and 27.9% had LNM. In the multivariate analyses in which the outcome was LNM, White (odds ratio [OR] 1.74, 95% CI 0.98 to 3.15, p = 0.064) and Hispanic patients (OR 2.36, 95% CI 0.97 to 5.77, p = 0.059) trended toward higher risk of LNM compared to Black patients, whereas age (OR 0.98, 95% CI 0.97 to 1.00, p = 0.008) showed protective effect. Tumor size (OR 1.04, 95% CI 1.01 to 1.07, p = 0.007), extrathyroidal extension (OR 2.46, 95% CI 1.53 to 3.97, p < 0.001), lymphovascular invasion (OR 6.30, 95% CI 3.68 to 11.14, p < 0.001), and multifocality (OR 1.47, 95% CI 1.01 to 2.12, p = 0.042) were associated with higher risk of LNM. In another model with outcome as >5 LNM, tumor size (OR 1.07, 95% CI 1.03 to 1.11, p = 0.001), age (OR 0.95, 95% CI 0.93 to 0.97, p < 0.001), extrathyroidal extension (OR 3.20, 95% CI 1.83 to 5.61, p < 0.001), and lymphovascular invasion (OR 6.82, 95% CI 3.87 to 12.17, p < 0.001) remained significant predictors. CONCLUSION: Our analyses demonstrated and confirmed that age, tumor size, extrathyroidal extension, and lymphovascular invasion are independent predictors of significant LNM, thereby conferring higher risk of recurrence. Risk of LNM based on these patient characteristics should be considered when planning an operative approach.