Risk Factors for Developing Hyponatremia in Thyroid Cancer Patients Undergoing Radioactive Iodine Therapy

Background

Due to the alarming increase in the incidence of thyroid cancer worldwide, more patients are receiving postoperative radioactive iodine (RAI) therapy and these patients are given a low-iodine diet along with levothyroxine withdrawal to induce a hypothyroid state to maximize the uptake of RAI by thyroid tissues. Recently, the reported cases of patients suffering from life-threatening severe hyponatremia following postoperative RAI therapy have increased. This study aimed to systematically assess risk factors for developing hyponatremia following RAI therapy in post-thyroidectomy patients.

Methods

We reviewed the medical records of all thyroid cancer patients who underwent thyroidectomy and postoperative RAI therapy from July 2009 to February 2012. Demographic and biochemical parameters including serum sodium and thyroid function tests were assessed along with medication history.

Results

A total of 2229 patients (47.0±11.0 years, female 76.3%) were enrolled in the analysis. Three hundred seven patients (13.8%) of all patients developed hyponatremia; 44 patients (2.0%) developed moderate to severe hyponatremia (serum Na⁺≤130 mEq/L) and another 263 (11.8%) patients showed mild hyponatremia (130 mEq/L<serum Na⁺≤135 mEq/L). In univariate analysis, old age, female sex, presence of hypertension, presence of diabetes, use of thiazide diuretics, use of angiotensin receptor blocker or angiotensin-converting enzyme inhibitors, lung metastasis, and hyponatremia and lower estimated glomerular filtration rate at the start of RAI therapy were significantly associated with hyponatremia in patients undergoing RAI therapy after total thyroidectomy. Multivariate analysis showed that old age, female sex, use of thiazide diuretics, and hyponatremia at the initiation of RAI therapy were independent risk factors for the development of hyponatremia.

Conclusion

Our data suggest that age greater than 60 years, female sex, use of thiazide, and hyponatremia at the initiation of RAI therapy are important risk factors for developing hyponatremia following RAI therapy in post-thyroidectomy patients.     

Renal Function and Plasma Renin activity as Potential Factors Causing Hyperkalemia in Patients with Thyroid Carcinoma Undergoing Thyroid Hormone Withdrawal For Radioactive Iodine Therapy

Objective: Hypothyroidism is not commonly considered a cause of hyperkalemia. We previously reported that hyperkalemia was observed mainly in elderly patients treated with renin-angiotensin-aldosterone system (RAS) inhibitors when levothyroxine treatment was withdrawn for the thyroidectomized patients with thyroid carcinoma to undergo radioactive iodine treatment. Here, we investigated whether acute hypothyroidism causes hyperkalemia in patients who were not treated with RAS inhibitors. We also investigated factors influencing potassium metabolism in hypothyroid patients.Methods: We conducted a single-center, prospective cohort study of 46 Japanese patients with thyroid carcinoma undergoing levothyroxine withdrawal prior to radioiodine therapy. All patients were normokalemic before levothyroxine withdrawal. Blood samples were analyzed 3 times: before, and at 3 and 4 weeks after levothyroxine withdrawal. We investigated factors that may be associated with the elevation of serum potassium levels from a euthyroid state to a hypothyroid state.Results: None of the patients developed symptomatic hyperkalemia. The mean serum potassium level was significantly higher at 4 weeks after levothyroxine withdrawal compared to baseline. The serum sodium levels, the estimated glomerular filtration rate (eGFR), and the plasma renin activity (PRA) decreased significantly as hypothyroidism advanced. In contrast, the plasma levels of adrenocorticotropic hormone, cortisol, aldosterone, and antidiuretic hormone were not changed, while serum thyroid hormone decreased. At 4 weeks after their levothyroxine withdrawal, the patients' serum potassium values were significantly correlated with the eGFR and the PRA.Conclusion: Acute hypothyroidism can cause a significant increase in the serum potassium level, which may be associated with a decreased eGFR and decreased circulating RAS.Abbreviations: ACTH = adrenocorticotropic hormone; ADH = antidiuretic hormone; ATPase = adenosine triphosphatase; eGFR = estimated glomerular filtration rate; HbA1c = glycated hemoglobin; K⁺ = potassium; Na⁺ = sodium; PRA = plasma renin activity; RAS = renin-angiotensin-aldosterone system; T4 = thyroxine; TSH = thyroid-stimulating hormone     

Hyperkalemia Develops in Some Thyroidectomized Patients Undergoing Thyroid Hormone Withdrawal in Preparation for Radioactive Iodine Ablation for Thyroid Carcinoma

Objective: Hyponatremia is observed in hypothyroidism, but it is not known if hypo- or hyperkalemia is associated with hypothyroidism. To study these questions, we determined serum potassium (K⁺) levels in thyroidectomized patients undergoing levothyroxine withdrawal before radioactive iodine (RAI) therapy for thyroid carcinoma.Methods: We retrospectively studied the records of 108 patients who had undergone total thyroidectomy for thyroid carcinoma followed by levothyroxine withdrawal and then ablation with RAI at Nagasaki University Hospital from 2009–2013. Blood samples were analyzed for serum K⁺ concentrations when patients were euthyroid just before levothyroxine withdrawal and hypothyroid 21 days after levothyroxine withdrawal. We determined the proportion of patients who developed hyperkalemia (K⁺ ≥5 mEq/L) and hypokalemia (K⁺ ≤3.5 mEq/L).Results: Five (4.6%) patients developed hyperkalemia and 2 (1.9%) patients developed hypokalemia after levothyroxine withdrawal. The mean serum K⁺ level after levothyroxine withdrawal was significantly higher than before levothyroxine withdrawal (4.23 ± 0.50 mEq/L vs. 4.09 ± 0.34 mEq/L; P<.001). After levothyroxine withdrawal, serum K⁺ values were significantly correlated with age, serum sodium and creatinine levels, and the estimated glomerular filtration rate but not with serum free thyroxine or thyroid-stimulating hormone concentrations. The finding of an elevated serum K⁺ of >0.5 mEq/L after levothyroxine withdrawal was more prevalent with age >60 years (odds ratio [OR], 4.66; P = .026) and with the use of angiotensin-II receptor blockers or angiotensin-converting enzyme inhibitors (OR, 3.53; P = .033) in a multivariate analysis.Conclusion: Hyperkalemia develops in a small percentage of hypothyroid patients after thyroid hormone withdrawal, especially in patients over 60 years of age who are using antihypertensive agents that inhibit the reninangiotensin- aldosterone system.Abbreviations: ACE-I = angiotensin-converting enzyme inhibitor ARB = angiotensin-II receptor blocker Cr = creatinine eGFR = estimated glomerular filtration rate Eu-K⁺ = serum level of K⁺ in the euthyroid state Hypo-K⁺ = serum level of K⁺ in the hypothyroid state K⁺ = potassium Na⁺ = sodium ?K⁺ = Hypo-K⁺ value minus Eu-K⁺ value RAI = radioactive iodine TSH = thyroid-stimulating hormone     

Could Urinary Iodine Be an Effective Predictive Factor for Thyroid Cancer After High Dose Radioactive Iodine Therapy?

ObjectiveThe study aimed to investigate whether urinary iodine concentration (UIC) and urinary iodine to creatinine ratio (UICR) measurements can act as markers for the curative effect of radioactive iodine (RAI) therapy.MethodsA total of 337 patients who underwent RAI therapy between May 2018 and March 2020 were recruited. According to the levels of UIC or UICR, patients were divided into 6 groups: group A, UIC levels of <100 μg/L; group B, UIC levels ranging from 100 to 200 μg/L; group C, UIC levels of ≥200 μg/L; group D, UICR levels of <100 μg/g; group E, UICR levels ranging from 100 to 200 μg/g; and group F, UICR levels of ≥200 μg/g. Treatment and follow-up were defined according to the criteria used in the 2015 ATA guidelines.ResultsWhen dividing the 337 patients into 3 groups according to UIC levels, 50.7%, 22.6%, and 26.7% of patients were in the A, B, and C groups, respectively. Based on the UICR levels, 58.1%, 29.4%, and 12.5% of patients were in the D, E, and F groups, respectively. There was a significant positive correlation between UIC and UICR levels and iodine-131 uptake rates (P < .001). The excellent response rate was not significantly different between the UIC groups (P = .997) and the UICR groups (P = .634). In logistic regression analysis, UIC and UICR levels were not confirmed to be independent factors predicting the excellent response status, but an age of ≥55 years (OR = 0.373; P = .007) and Tg levels of ≥10 ng/mL (OR = 18.972; P = .001) were confirmed to be independent factors predicting the excellent response status at the end of follow-up.ConclusionThe UIC or UICR levels before RAI therapy did not compromise the therapeutic response to iodine-131.     

Thyroid Function in Patients Treated with Radioactive Iodine for Thyrotoxicosis

A series of 105 patients treated at least two years earlier with radioactive iodine for thyrotoxicosis have been surveyed. Eighty-five patients (81%) were euthyroid clinically and on the basis of routine thyroid function tests. Of the euthyroid patients 46 (54%) had normal thyroid-stimulating hormone (TSH) levels and 39 (46%) had raised TSH levels. There was no difference in serum triiodothyronine levels between these two groups but the serum protein bound iodine and serum thyroxine, though still well within the normal range, were significantly lower in the group with raised TSH levels. The serum cholesterol was also significantly higher in this latter group.Most of the euthyroid patients were seen again a year later. None had become hypothyroid and neither those with normal nor those with raised TSH levels showed any evidence of a decline in the level of serum thyroxine.It is concluded that raised serum TSH levels in patients treated with iodine-131 are not necessarily indicative of hypothyroidism. There is no indication that patients who have this abnormality become overtly hypothyroid over a 12-month follow up.     

Management of Patients With Low-Risk Papillary Thyroid Carcinoma

ObjectiveTo define a rational, cost-effective, simple approach to managing most patients with papillary thyroid cancer (PTC) who are at low-risk of either cause-specific mortality or tumor recurrence.MethodsTaking advantage of the collective experience of a cohort of 2512 patients with PTC who had initial definitive treatment at the Mayo Clinic in Rochester, Minnesota, between 1940 and 2000, a 5-step approach to the management of low-risk PTC has been devised. This program is based on appropriate preoperative ultrasound localization of neck disease and potentially curative surgery consisting of near-total or total thyroidectomy, with appropriate neck nodal exploration and resection.ResultsThe emphasis of the present program is on the extent of initial surgery, where optimal care is ascribed to a near-total thyroidectomy with curative intent and appropriate neck nodal resection as predicated by appropriate preoperative ultrasonography evaluation of regional lymph nodes. Radioiodine remnant ablation (RRA) is not applicable to patients with PTC who are defined on the day of definitive initial surgery to be at low risk as defined by a metastasis, age, completeness of resection, invasion, and size (MACIS) score of less than 6.ConclusionThe outlook for patients with low-risk PTC is very optimistic, with rates at 30 postoperative years of only 1% for cause-specific mortality and less than 15% for tumor recurrence at any site. The long-term results obtained by potentially curative bilateral resection, appropriate regional lymph nodal excision, and selective use of RRA are excellent. Realistically improving these acceptably low rates for cause-specific mortality and tumor recurrence may be difficult. (Endocr Pract. 2007;13:521-533)     

Papillary Hyperplastic Nodule: Pitfall in the Cytopathologic Diagnosis of Papillary Thyroid Carcinoma

ObjectiveTo identify the pitfalls of overdiagnosing papillary formation as papillary thyroid carcinoma (PTC) in thyroid cytology specimens.MethodsPatients with papillary hyperplastic nodules who had preoperative fine-needle aspiration biopsy (FNAB) were selected for this study. All patients had been diagnosed as having either PTC or lesions suggestive of PTC on preoperative FNAB. Pathology reports, surgical reports, and cytopathology slides were reviewed and analyzed for demographic data, nature of surgery, and pathologic features.ResultsSix women and 2 men with a mean age of 49 years (range, 16-79 years) were included. The lesion size ranged from 1.0 to 3.5 cm. Four patients were diagnosed as having PTC and 4 as having lesions suspicious for PTC. FNAB specimens were available for review in 6 cases. Surgical pathology slides were reviewed in all cases. When cytologic material was evaluated for the morphologic features that led to the misdiagnosis of PTC by comparing it with FNAB specimens of classic variant of PTC, the specimens from these patients showed follicular cells arranged in short, nonbranching papillae in a background of watery colloid and macrophages. The follicular cells were round and demonstrated oncocytic change with nuclear enlargement, prominent central nucleoli, nuclear chromatin clearing, and intranuclear grooves.ConclusionsCaution should be exercised rendering the diagnosis of PTC on FNAB samples when a thyroid lesion shows papillary configurations and oncocytic cells and if convincing nuclear features of PTC are not present. Furthermore, some morphologic features on thyroid aspiration can help differentiate these cases from true PTC. (Endocr Pract. 2008;14:863-868)     

敲低EDAG抑制乳头状甲状腺癌细胞的增殖

为研究EDAG在人乳头状甲状腺癌病人组织中的表达及在乳头状甲状腺癌细胞中的作用,利用免疫组化检测31例乳头状甲状腺癌癌组织及癌旁组织中EDAG蛋白的表达,并进行数据分析.包装EDAG敲低慢病毒颗粒,感染乳头状甲状腺癌细胞系K1,建立EDAG敲低稳定细胞株,检测EDAG敲低对细胞增殖、克隆形成、周期和凋亡的影响. 结果显示,EDAG蛋白在乳头状甲状腺癌癌组织中异常高表达,而在对应癌旁组织极低表达或不表达.建立稳定敲低EDAG的K1细胞株,敲低效果达到约96%,敲低EDAG后细胞增殖变缓,倍增时间由18.49±0.19 h变为19.47±0.11 h,且克隆形成能力下降,G0/G1期比例升高,无血清培养时凋亡增多.本文报道了EDAG在乳头状甲状腺癌病人中高表达,且敲低甲状腺癌细胞系K1中内源EDAG抑制细胞增殖,降低细胞克隆形成能力,G0/G1期增多,凋亡升高,提示EDAG异常高表达可能在甲状腺癌发生发展中具有重要作用.     

The Impact of Thyroid Cancer and Post-Surgical Radioactive Iodine Treatment on the Lives of Thyroid Cancer Survivors: A Qualitative Study

Background

Adjuvant treatment with radioactive iodine (RAI) is often considered in the treatment of well-differentiated thyroid carcinoma (WDTC). We explored the recollections of thyroid cancer survivors on the diagnosis of WDTC, adjuvant radioactive iodine (RAI) treatment, and decision-making related to RAI treatment. Participants provided recommendations for healthcare providers on counseling future patients on adjuvant RAI treatment.

Methods

We conducted three focus group sessions, including WDTC survivors recruited from two Canadian academic hospitals. Participants had a prior history of WDTC that was completely resected at primary surgery and had been offered adjuvant RAI treatment. Open-ended questions were used to generate discussion in the groups. Saturation of major themes was achieved among the groups.

Findings

There were 16 participants in the study, twelve of whom were women (75%). All but one participant had received RAI treatment (94%). Participants reported that a thyroid cancer diagnosis was life-changing, resulting in feelings of fear and uncertainty. Some participants felt dismissed as not having a serious disease. Some participants reported receiving conflicting messages from healthcare providers on the appropriateness of adjuvant RAI treatment or insufficient information. If RAI-related side effects occurred, their presence was not legitimized by some healthcare providers.

Conclusions

The diagnosis and treatment of thyroid cancer significantly impacts the lives of survivors. Fear and uncertainty related to a cancer diagnosis, feelings of the diagnosis being dismissed as not serious, conflicting messages about adjuvant RAI treatment, and treatment-related side effects, have been raised as important concerns by thyroid cancer survivors.     

Complete Blood Counts are Frequently Abnormal 1 Year after Dosimetry-Guided Radioactive Iodine Therapy for Metastatic Thyroid Cancer

ObjectiveRadioactive iodine (RAI) has been associated with hematologic abnormalities. Previous research has shown that even a single dose of RAI can cause changes in the peripheral complete blood count (CBC). It is unclear if the use of dosimetry guidance would prevent the effects of high doses of RAI on bone marrow suppression.MethodsCBC at baseline was compared to a CBC obtained 1 year after the last RAI treatment in 50 thyroid cancer patients that received ≥ 250 mCi RAI during the course of their disease. Cumulative dose, number of treatments, patients’ age, and the use of external beam radiation therapy (EBRT) were considered in the analysis.ResultsWe observed a small but statistically significant decrease in hemoglobin (Hb), hematocrit (Hct), and platelet (Plt) counts at 1 year in 50 patients who had received ≥ 250 mCi RAI. We did not find a significant change in white blood cell count (WBC). Approximately 60% of patients who developed anemia had concomitant WBC and Plt abnormalities. RAI dose, number of treatments, and age at diagnosis did not confer a higher risk of bone marrow suppression.ConclusionHigh cumulative activities of RAI administered under dosimetric guidance are associated with a small but statistically significant decreases in Hb, Hct, and Plt counts. The clinical implications of these changes, if any, are unclear. The benefits obtained with high doses of RAI, when indicated, are likely to outweigh the minimal hematologic risks observed in the present study. (Endocr Pract. 2014;20:213-220)     

Molecular Analysis of Structural Abnormalities in Papillary Thyroid Carcinoma Genome

Rearrangements of the protooncogene RET (RET/PTC) and somatic mutations of the gene BRAF are the most common events in the etiopathogenesis of papillary thyroid carcinoma (PTC). The rates of RET/PTC rearrangements and BRAF mutations in different nodular formations of the thyroid gland (TG) have been estimated. Comparative expression analysis of the extracellular (EC) and tyrosine kinase (TK) domains of RET has shown that 14% (12 out of 85) of PTC cases are RET/PTC-positive, including one RFP/RET-, two RET/PTC3-, and seven RET/PTC1-positive tumors, as well as two unidentified chimeric RET/PTC oncogenes. The standard T1796A transversion in the gene BRAF has been found in 60% (55 out of 91) PTC cases with the use of amplification refractory mutation system–polymerase chain reaction (ARMS–PCR). Somatic mutation G1753A and deletion del1800_1811 have been identified in PTC for the first time. The absence of the BRAF mutations in RET/PTC-positive tumors allows these two genetic defects to be regarded as alternative mechanisms of the RAS–RAF–MEK–ERK mitogen-activated protein (MAP) kinase cascade activation in PTCs. In none of the three follicular thyroid carcinomas (FTCs), 11 follicular thyroid adenomas (FTAs), and 13 nodular goiters have either BRAF mutations or RET/PTC rearrangements been found. Thus, the RET/PTC chimeric oncogenes and BRAF somatic mutations are specific markers of PTC and can be used for the preoperative diagnosis of these tumors.     

乳头状甲状腺癌中线粒体DNA突变的研究

该文探究了线粒体DNA(mtDNA)突变与甲状腺癌的发生发展的相关性,评估了mtDNA拷贝数对甲状腺癌的诊断价值。根据对结节性甲状腺肿、滤泡状甲状腺腺瘤和乳头状甲状腺癌3组病人的mtDNA全基因测序和单倍型分型结果,统计3组病人mtDNA突变率及单倍型的差异,分析乳头状甲状腺癌病人的mtDNA突变率与临床资料的联系,最后通过荧光定量PCR检测3组病人的组织和血液样本中mtDNA的拷贝数。结果显示,乳头状甲状腺癌患者mtDNA的复合体I亚基编码区和tRNA编码区的突变率明显高于结节性甲状腺肿,在乳头状甲状腺癌患者中线粒体单体型M相对于单体型N有更低的淋巴结转移率,荧光定量PCR结果显示,甲状腺腺瘤和甲状腺癌组织中的mtDNA拷贝数明显高于结节性甲状腺肿,而在血液标本中,两者的mtDNA拷贝数均低于结节性甲状腺肿。这些结果表明,mtDNA拷贝数的变化和复合体I亚基编码区的突变可能作为甲状腺癌诊断的生物指标,而线粒体单体型N可能可以作为乳头状甲状腺癌恶性变化的预警指标。     

HABP2 G534E Variant in Papillary Thyroid Carcinoma

The main nonmedullary form of thyroid cancer is papillary thyroid carcinoma (PTC) that accounts for 80–90% of all thyroid malignancies. Only 3–10% of PTC patients have a positive family history of PTC yet the familiality is one of the highest of all cancers as measured by case control studies. A handful of genes have been implicated accounting for a small fraction of this genetic predisposition. It was therefore of considerable interest that a mutation in the HABP2 gene was recently implicated in familial PTC. The present work was undertaken to examine the extent of HABP2 variant involvement in PTC. The HABP2 G534E variant (rs7080536) was genotyped in blood DNA from 179 PTC families (one affected individual per family), 1160 sporadic PTC cases and 1395 controls. RNA expression of HABP2 was tested by qPCR in RNA extracted from tumor and normal thyroid tissue from individuals that are homozygous wild-type or heterozygous for the variant. The variant was found to be present in 6.1% familial cases, 8.0% sporadic cases (2 individuals were homozygous for the variant) and 8.7% controls. The variant did not segregate with PTC in one large and 6 smaller families in which it occurred. In keeping with data from the literature and databases the expression of HABP2 was highest in the liver, much lower in 3 other tested tissues (breast, kidney, brain) but not found in thyroid. Given these results showing lack of any involvement we suggest that the putative role of variant HABP2 in PTC should be carefully scrutinized.     

DcR3在甲状腺乳头状癌中的表达及临床意义

应用RT-PCR、Westem blot、免疫组化分别检测甲状腺乳头状癌组织与癌旁正常甲状腺组织标本中DcR3mRNA及蛋白的表达情况,探讨DcR3在甲状腺乳头状癌组织中的表达及,临床意义。RT-PCR检测显示,甲状腺乳头状癌中DcR3 mRNA的表达明显高于正常甲状腺组织（P〈0．05）：Western blot提示,DcR3蛋白在甲状腺乳头状癌中表达比正常甲状腺组织高（P〈0．05）;免疫组化显示,DcR3蛋白在甲状腺乳头状癌中高表达（P〈0．05）。DcR3mRNA及蛋白质在甲状腺乳头状癌及正常甲状腺组织间的表达差异有统计学意义（P〈0．05）。DcR3基因及蛋白在甲状腺乳头状癌中高表达,提示DcR3可能促进了甲状腺乳头状癌的发生发展。     

Expression and Biologic Significance of Adiponectin Receptors in Papillary Thyroid Carcinoma

Obesity is associated with a higher incidence of thyroid cancer. Adiponectin is one of the most abundant adipokines with a pleiotropic role in metabolism and in the development and progression of cancer. It has been shown that circulating adiponectin level is inversely associated with the risk of thyroid cancer. This study aimed to investigate the possible association between the expression of adiponectin receptors (AdipoR1 and AdipoR2) and clinicopathological variables in papillary thyroid cancer. We found that protein levels of AdipoR1 and AdipoR2 were increased in some thyroid cancer specimens compared with adjacent normal thyroid tissues. Thyroid cancer cells expressed AdipoR1 and AdipoR2, which were attenuated by histone deacetylase inhibitors valproic acid and trichostatin A. Adiponectin stimulated AMP-activated protein kinase phosphorylation in thyroid cancer cells. We further determined the expression of AdipoR1 and AdipoR2 by immunohistochemical staining in primary tumor samples and metastatic lymph nodes. AdipoR1 was expressed in 27 % of primary tumors and AdipoR2 in 47 %. Negative expression of both adiponectin receptors was significantly associated with extrathyroidal invasion, multicentricity, and higher TNM stage. There was a trend toward decreased disease-free survival in patients with negative tumor expression of AdipoR1 and AdipoR2 (log-rank P = 0.051). Collectively, overexpression of adiponectin receptors was observed in some tumor tissues of papillary thyroid cancer and was associated with a better prognosis.     

BRAF Mutation Analysis of Fine-Needle Aspiration Biopsies of Papillary Thyroid Carcinoma: Impact on Diagnosis and Prognosis

Objective: The BRAF V600E mutation has been associated with aggressive disease in papillary thyroid carcinoma (PTC). Molecular testing has been proposed as a useful adjunct to cytology in the diagnosis of malignancy and for tailoring clinical management. The aims of our study were to evaluate the BRAF mutational status using archived fine-needle aspiration biopsy (FNAB) material from patients with long-term follow-up and to correlate it with the original cytology diagnosis, clinicopathological stage at surgery, and prognosis. Study Design: FNAB material from 52 cases of PTC, with a mean follow-up of 8.4 years, was used in this study. DNA was extracted from archival cytology slides. Mutation analysis was performed by standard sequencing and locked nucleic acid-PCR/sequencing. Results: The BRAF V600E mutation was present in 46% of cases, but it was absent in all FNABs diagnosed originally as atypical and in 14 of 17 suspicious cases. Recurrence was significantly more frequent (p = 0.006) in cases with BRAF mutations and 54% of these cases presented with stage 2 or higher. Conclusion: The BRAF V600E mutation is associated with a higher pathological stage at surgery and a higher rate of recurrence. BRAF mutation analysis did not provide a significant increase in the accuracy of thyroid FNABs diagnosed as suspicious or atypical in our institution.