Does autoimmune thyroid disorder act as a predisposing factor in the development of oral lichen planus?

Considering previous data from our clinic, as had consistently demonstrated a significant number of OLP patients also reporting thyroid disease (Hashimoto's thyroiditis, in particular), the present study investigated the prevalence of OLP in patients with autoimmune thyroid disease, including Hashimoto's thyroiditis and Graves' disease.

Laser Ablation of Benign Thyroid Nodules: A Prospective Pilot Study With a Preliminary Analysis of the Employed Energy.

BACKGROUND AND OBJECTIVES: To assess the effectiveness of ultrasound (US)-guided laser ablation of benign thyroid nodules (TNs) under different amounts of applied energy. STUDY DESIGN/MATERIALS AND METHODS: Thirty-four euthyroid patients with 5-18 ml TNs were enrolled: 21 (laser ablation) and 13 (clinical follow up) patients with a mean age of 56.2 ± 12.0 and 54.7 ± 14.7 years, respectively. The laser ablation protocol used a 1.064 mm wavelength diode laser source; 3.5 W output power; 1,100-1,500 J and 5-8 min/illumination; and one or two fibers/session. Clinical, laboratory, and US data were obtained immediately before treatment and at 6 and 12 months follow-up and were analyzed by Student's t test and Fisher's exact test. Low- and high-energy subgroups were subsequently defined, and the receiver operating characteristic (ROC) curves were calculated. RESULTS: Laser ablation follow-up showed an overall nodule volume reduction of more than 50%; improvement of symptoms and cosmetic complaints (P = 0.001); and stable laboratory data compared with the baseline and control groups. Minor complications were 9.5% ( n = 2). One or two fibers/session resulted in a similar nodule volume reduction among 10-18 ml nodules. Analysis of the applied energy suggested a 398.8 J/ml inferior cutoff (ROC curve: 0.889 sensitivity; 0.545 specificity) for the high-energy subgroup ( n = 14, mean 599.9 ± 136.5 J/ml) to reduce the nodule volume over time (-55.1% vs. -58.4%, P = 0.55). The low-energy subgroup ( n = 7, mean 240.2 ± 74.6 J/ml) did not show a persistent volume reduction ( P < 0.05) from the 6- to 12-month follow-ups (-56.6% vs. -53.7%). CONCLUSIONS: Laser ablation of benign TNs achieved technique efficacy at 12 months posttreatment, with clinical improvement and few minor side effects. A single fiber in a single session with a high deployed energy (>398.8 J/ml) may be associated with improved results, a finding to be confirmed with a larger series. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

Color Duplex Doppler US can Follow up the Response of Radioiodine in Graves' Disease by Evaluating the Thyroid Volume and Peak Systolic Velocity.

PURPOSE: The objective of this study was to prove the efficacy of Doppler ultrasonography (US-Doppler) in the follow-up of patients with GD treated with radioactive iodine. METHODS: 97 patients (77 female and 20 male) with a mean age of 42 years (SD ±â€Š15) and with prior diagnosis of GD were treated with radioiodine. In total, 88.5 % achieved euthyroidism or hypothyroidism after treatment. The study was documented before treatment and one, three, and six months after treatment with radioactive iodine (131I) by a single investigator. The volume, echogenicity, echotexture and vascularization of the glands as well as the peak systolic velocity (PSV) of the inferior thyroid arteries were evaluated and compared with the laboratory data. RESULTS: Thyroid volume and PSV had a statistically significant correlation with hormone levels (p < 0.05). The mean pre-dose therapeutic thyroid volume was 43.01 ±â€Š3.88 cm3 and was 11.58 ±â€Š11.26 cm3 6 months after treatment. The mean PSV before 131I was 90.06 ±â€Š44.13 cm/s and decreased significantly over time (p < 0.001). Six months after the therapeutic dose, the mean PSV was 32.95 ±â€Š16.36 cm/s. However, the subjective parameters did not have a significant correlation with the normalization of the thyroid hormones. CONCLUSION: Doppler US was useful for monitoring the therapeutic response of GD patients after treatment with radioiodine by evaluating the thyroid volume and peak systolic velocity.

Prevalence of DICER1 variants in large multinodular goiter: thyroid function, clinical and imaging characteristics.

Objective: Mutations in DICER1 are found in differentiated thyroid carcinoma (DTC) and in multinodular goiter (MNG) at a younger age with other tumors, which characterizes DICER1 syndrome. DICER1 is one driver to DTC; however, it is also found in benign nodules. We speculated that patients with mutations in DICER1 may present long-lasting MNG. Our aim was to investigate the frequency of DICER1 variants in patients with MNG. Subjects and methods: Patients who submitted to total thyroidectomy due to large MNG with symptoms were evaluated. DICER1 hotspots were sequenced from thyroid nodule samples. To confirm somatic mutation, DNA from peripheral blood was also analyzed. Results: Among 715 patients, 154 were evaluated with 56.2 ± 12.3 years old (28-79) and the thyroid volume was 115.7 ± 108 mL (16.2-730). We found 11% with six DICER1 variations in a homo or heterozygous state. Only rs12018992 was a somatic DICER1 variant. All remaining variants were synonymous and likely benign, according to the ClinVar database. The rs12018992 was previously described in an adolescent with DTC, measuring 13 mm. There were no significant differences according to gender, familial history of goiter, age, thyroid volume, TSH and TI-RADS classification between DICER1 carriers. Free T4 were lower in patients with DICER1 polymorphisms (13.77 ± 1.8 vs. 15.44 ± 2.4 pmol/L, p = 0.008), regardless of TSH levels. Conclusion: We conclude that germline DICER1 variants can be found in 11% of large goiters but no second-hit somatic mutation was found. DICER1 is one driver to thyroid lesion and a second-hit event seems unnecessary in the MNG development.

Thyroid disturbance related to chronic hepatitis C infection: role of CXCL10.

Association between autoimmune thyroid diseases (AITD) and hepatitis C is controversial, but may occur or worsen during alpha-interferon treatment. The mechanism responsible for autoimmune diseases in infected patients has not been fully elucidated. This study aims to evaluate the frequency of AITD in chronic hepatitis C and the association of chemokine (CXC motif) ligand 10 (CXCL10) and AITD. One hundred and three patients with chronic hepatitis C and 96 controls were prospectively selected to clinical, hormonal, thyroid autoimmunity and ultrasound exams, besides thyroxine-binding globulin (TBG) and CXCL10 measurements and hepatic biopsies. The frequency of AITD among infected subjects was similar to controls. TT3 and TT4 distributions were right shifted, as was TBG, which correlated to both of them. Thyroid heterogeneity and hypoechogenicity were associated with AITD. Increased vascularization was more prevalent in chronic hepatitis C.CXCL10 was higher in infected patients (p=0.007) but was not related to thyroid dysfunction. Increase in CXCL10 levels were consistent with hepatic necroinflammatory activity (p=0.011). In summary, no association was found between chronic hepatitis C and AITD. Infected subjects had higher TT3 and TT4 which were correlated to TBG. Increased CXCL10 was not associated to thyroid dysfunction in HCV-infected population.

Correlations of CTLA-4 gene polymorphisms and hepatitis C chronic infection.

BACKGROUND: Cytotoxic T lymphocyte-associated factor 4 (CTLA-4) functions as a negative regulator of T cell-mediated immune response. Molecular changes associated to CTLA-4 gene polymorphisms could reduce its ability to suppress and control lymphocyte proliferation. AIMS: To evaluate the frequency of CTLA-4 gene polymorphisms in chronic hepatitis C virus (HCV) infected patients and correlate to clinical and histological findings. METHODS: We evaluated 112 HCV-infected subjects prospectively selected and 183 healthy controls. Clinical and liver histological data were analysed. -318C > T, A49G and CT60 CTLA-4 single-nucleotide polymorphisms (SNPs) were studied by PCR-RFLP and AT(n) polymorphism by DNA fragment analysis by capillary electrophoresis in automatic sequencer. RESULTS: Eight AT repetitions in 3'UTR region were more frequent in HCV-infected subjects. We found a positive association of -318C and + 49G with HCV genotype 3 (P = 0.008, OR 9.13, P = 0.004, OR 2.49 respectively) and an inverse association of both alleles with HCV genotype 1 (P = 0.020, OR 0.19, P = 0.002, OR 0.38 respectively). Allele + 49G was also associated to aminotransferases quotients > 3 (qALT, P = 0.034, qAST, P = 0.041). Allele G of CT60 SNP was also associated with qAST > 3 (P = 0.012). Increased number of AT repetitions was positively associated to severe necroinflammatory activity scores in liver biopsies (P = 0.045, OR 4.62). CONCLUSION: CTLA-4 gene polymorphisms were associated to HCV-infection. Eight AT repetitions were more prevalent in HCV-infected subjects. -318C and + 49G alleles were associated to genotypes 1 and 3 infections and increased number of AT repetitions in 3'UTR region favoured severe necroinflammatory activity scores in liver biopsies.

Is there a role for diagnostic scans in the management of intermediate-risk thyroid cancer?

Radioiodine (RAI) is selectively recommended for intermediate-risk differentiated thyroid carcinomas (DTC). The information gleaned from pretherapy stimulated thyroglobulin levels (sTg) and diagnostic 131I whole-body scans (DxWBS) to guide therapy remains controversial. The present study aimed at evaluating the impact of preablation sTg and DxWBS in the management of intermediate-risk DTC. A retrospective analysis of 301 intermediate-risk DTC patients submitted to total thyroidectomy and RAI therapy was performed. Pretherapy sTg and DxWBS and post-therapy WBS (RxWBS) findings were analyzed and compared to outcomes. Fifty-two patients (17.3%) had metastases diagnosed by DxWBS and/or RxWBS. The DxWBS identified 10.6% of patients with functioning metastases, including unexpected distant metastases. If combined with SPECT-CT, DxWBS detected RAI-avid metastases more frequently, particularly lymph node metastases (13.1% vs 4.2% planar WBS, P = 0.015). The DxWBS findings modified patient management in 8.3%. A pretherapy sTg <1 ng/mL was associated with a low false-negative rate for the presence of metastases (5.2%), and its performance in excluding metastasis was improved by a negative DxWBS (2.7% of patients with both negative exams had metastases in RxWBS). A sTg <1 ng/mL predicted statistically significant lower rates of recurrent/persistent disease and biochemical/structural incomplete responses. In conclusion, preablation sTg and DxWBS contribute to the detection of unknown or persistent metastatic disease in intermediate-risk DTC patients. A sTg <1 ng/mL in combination with a negative DxWBS is highly suggestive of the absence of remaining malignant disease, and one may consider deferring RAI ablation if both exams are negative. A stunning effect is rarely observed and it does not impair proper treatment of metastases.

Etiology of congenital hypothyroidism using thyroglobulin and ultrasound combination.

Methods currently employed to establish the etiology of congenital hypothyroidism include thyroid ultrasound and scintigraphic exams. Thyroglobulin is a protein almost exclusively secreted by thyroid tissue and indirectly reflects the amount of follicular cells. Even though thyroglobulin is easy to measure, it has been not frequently used because of discordant results to distinguish mainly athyreosis and ectopy (dysgenesis). Knowing the differences in inheritance and prognosis of thyroid dysgenesis and dyshormonogenesis, it is important to define the etiology of CH, combining tools that are easy, fast and available in most medical centers. Our objective was to evaluate and compare color Doppler ultrasound and serum thyroglobulin with radionuclide scan to define the etiology of congenital hypothyroidism. We evaluated 38 children above 3 years-old off-treatment that performed serum thyroglobulin by immunofluorometric assay, color Doppler ultrasound and radionuclide study. On color Doppler ultrasound, 11 patients had athyreosis, 5 ectopic glands, being 1 associated to hemiagenesis. Twenty one had topic thyroid (3 goiters, 10 normal, 8 hypoplastic). Hemiagenesis and cystic lesion were not revealed by radionuclide scan. We observed substantial agreement between color Doppler ultrasound and radionuclide scan (kappa=0.745, p<0.0001). Serum thyroglobulin in athyreosis ranged from <1.0 to 18.7 micro g/L. Patients with ectopic glands showed wider thyroglobulin range (4.5 to 123 micro g/L, median 28.4 micro g/L). Only one patient showed thyroglobulin deficiency. By using color Doppler ultrasound and serum thyroglobulin levels as valuable combined tools, we established the etiology of congenital hypothyroidism limiting excessive and harmful exams in children, like radionuclide scan.

Molecular profile of Hürthle cell carcinomas: recurrent mutations in the Wnt/ß-catenin pathway.

OBJECTIVE: Genomic alterations in Hürthle cell carcinomas (HCC) include chromosomal losses, mitochondrial DNA mutations, and changes in the expression profile of the PI3K-AKT-mTOR and Wnt/ß-catenin pathways. This study aimed at characterizing the mutational profile of HCC. METHODS: Next-generation sequencing (NGS) of 40 HCC using a 102-gene panel including, among others, the MAPK, PI3K-AKT-mTOR, Wnt/ß-catenin, and Notch pathways. HCC was widely invasive in 57.5%, and lymph node and distant metastases were diagnosed in 5% and 7.5% of cases. During follow-up, 10% of patients presented with persistent/recurrent disease, but there were no cancer-related deaths. RESULTS: Genetic alterations were identified in 47.5% of HCC and comprised 190 single-nucleotide variants and 5 insertions/deletions. The Wnt/ß-catenin pathway was most frequently affected (30%), followed by MAPK (27.5%) and PI3K-AKT-mTOR (25%). FAT1 and APC were the most frequently mutated genes and present in 17.5%. RAS mutations were present in 12.5% but no BRAF mutation was found. There was no association between the mutational profile and clinicopathological features. CONCLUSIONS: This series of HCC presents a wide range of mutations in the Wnt/ß-catenin, MAPK and PI3K-AKT-mTOR pathways. The recurrent involvement of Wnt/ß-catenin pathway, particularly mutations in APC and FAT1, are of particular interest. The data suggest that mutated FAT1 may represent a potential novel driver in HCC tumorigenesis and that the Wnt/ß-catenin pathway plays a critical role in this distinct thyroid malignancy.

Is There a Difference Between Minimal and Gross Extension into the Strap Muscles for the Risk of Recurrence in Papillary Thyroid Carcinomas?

Background: The morbidity of papillary thyroid carcinoma (PTC) is primarily related to locoregional recurrences and distant metastases. The definition of minimal extrathyroidal extension (mETE) has been recently revised. The presence of mETE does not impact mortality and is generally not considered to be a predictor for the risk of recurrence. This study aimed at comparing the risk of recurrence and the response to therapy of PTC with mETE and gross extrathyroidal extension (ETE) into the strap muscles (gETE) with low- and intermediate-risk PTC without ETE (low risk w/o ETE and intermediate risk w/o ETE, respectively) to further characterize the impact of ETE on outcomes. Methods: A total of 596 PTCs were analyzed according to the degree of ETE as well as other predictors of recurrence. Four groups of patients were compared, low risk w/o ETE (n = 251), intermediate risk w/o ETE (n = 89), mETE (n = 191), and gETE (n = 65), to determine the risk of recurrence and the response to treatment. Cox proportional hazards models were used to investigate associations between groups and disease-free survival (DFS). Results: The risk of recurrence was 3% in low risk w/o ETE PTC, 14% in intermediate risk w/o ETE, 14% in mETE, and 25% in gETE. The recurrence risk was increased by the presence of ETE (odds ratio [OR] = 2.86, 95% confidence interval [CI] 1.36-5.85, p = 0.005) and lymph node metastases (OR = 2.44 [95% CI 1.25-4.76], p = 0.009). Patients with low-risk carcinomas w/o ETE experienced longer DFS than those with mETE (hazard ratio = 0.08 [95% CI 0.02-0.28], p < 0.001), but no significant difference was observed between intermediate risk w/o ETE, mETE, and gETE. In terms of the response to therapy, patients with gETE had higher rates of biochemical and/or structural incomplete responses within the first year of treatment (OR = 2.68 [95% CI 1.31-5.45], p = 0.007) and at the final follow-up evaluation (OR = 4.35 [95% CI 1.99-9.51], p < 0.001) compared with those with mETE. An analysis of the subgroups of microcarcinomas without lymph node metastases revealed no significant difference in DFS or the response to therapy between the low risk w/o ETE and mETE PTC groups. Conclusions: The results of this study suggest that both mETE and gETE are independent risk factors for the risk of recurrence in PTC. Although gETE has a more pronounced impact on the recurrence risk and is associated with a worse response to therapy, mETE may not be associated with a low risk of recurrence. This observation suggests that patients with PTC and mETE may, in part, have an intermediate risk of recurrence and need to be followed accordingly.

Prevalence of DICER1 variants in large multinodular goiter: thyroid function, clinical and imaging characteristics

ABSTRACT Objective: Mutations in DICER1 are found in differentiated thyroid carcinoma (DTC) and in multinodular goiter (MNG) at a younger age with other tumors, which characterizes DICER1 syndrome. DICER1 is one driver to DTC; however, it is also found in benign nodules. We speculated that patients with mutations in DICER1 may present long-lasting MNG. Our aim was to investigate the frequency of DICER1 variants in patients with MNG. Subjects and methods: Patients who submitted to total thyroidectomy due to large MNG with symptoms were evaluated. DICER1 hotspots were sequenced from thyroid nodule samples. To confirm somatic mutation, DNA from peripheral blood was also analyzed. Results: Among 715 patients, 154 were evaluated with 56.2 ± 12.3 years old (28-79) and the thyroid volume was 115.7 ± 108 mL (16.2-730). We found 11% with six DICER1 variations in a homo or heterozygous state. Only rs12018992 was a somatic DICER1 variant. All remaining variants were synonymous and likely benign, according to the ClinVar database. The rs12018992 was previously described in an adolescent with DTC, measuring 13 mm. There were no significant differences according to gender, familial history of goiter, age, thyroid volume, TSH and TI-RADS classification between DICER1 carriers. Free T4 were lower in patients with DICER1 polymorphisms (13.77 ± 1.8 vs. 15.44 ± 2.4 pmol/L, p = 0.008), regardless of TSH levels. Conclusions: We conclude that germline DICER1 variants can be found in 11% of large goiters but no second-hit somatic mutation was found. DICER1 is one driver to thyroid lesion and a second-hit event seems unnecessary in the MNG development.

Diagnostic performance of thyroid ultrasound in Hürthle cell carcinomas.

OBJECTIVE: Hürthle cell carcinomas (HCCs) of the thyroid have been recently reclassified as a separate entity due to their distinct clinical and molecular profiles. Few studies have assessed the ability of preoperative characteristics in differentiating HCCs from Hürthle cell adenomas (HCAs) due to the low prevalence of both lesions. This study aimed to compare the preoperative features of HCCs and HCAs and evaluate the diagnostic performance of ultrasound in distinguishing between both. SUBJETCS AND METHODS: Retrospective study including 101 patients (52 HCCs and 49 HCAs) who underwent thyroid surgery from 2000 to 2016. Clinical, ultrasonographic, and histological data were reviewed. Diagnostic performance of suspicious sonographic features was analyzed in 51 cases (24 HCCs and 27 HCAs). RESULTS: Hürthle cell neoplasms were predominant in females. Subjects ≥ 55 years represented 58% of the cases of HCCs and 53% of those of HCAs. Carcinomas were significantly larger (p < 0.001), and a tumor size ≥ 4 cm significantly increased the risk of malignancy (odds ratio 3.67). Other clinical, cytologic, and sonographic data were similar between HCCs and HCAs. Among the HCCs, the lesions were purely solid in 54.2%, hypoechoic in 37.5%, and had coarse calcifications in 12.5%, microcalcifications in 8.3%, irregular contours in 4.2%, and a taller-than-wide shape in 16.7%. Predominantly/exclusive intranodular vascularization was observed in 52.6%. Overall, 58% of the HCCs were classified as TI-RADS 4 or 5 compared with 48% of the HCAs. TI-RADS 4 or 5 had a specificity of only 51.8% and a positive likelihood ratio of 1.21. CONCLUSIONS: Apart from the lesion size, no other preoperative feature adequately distinguished HCCs from HCAs. Sonographic characteristics raising suspicion for malignancy, which are mostly present in papillary carcinomas, were infrequent in HCCs. New tools must be developed to improve preoperative diagnosis and deferral of surgery in cases of adenomas.

Factitious thyrotoxicosis induced by mesotherapy: a case report.

CONTEXT: Mesotherapy consists of cutaneous injections of a mixture of compounds and has recently been used for cosmetic purposes to reduce local fat and cellulite. To date, several reports have described only local adverse events related to this therapy. We describe the first report of a female patient who developed thyrotoxicosis due to cosmetic mesotherapy with triiodothyroacetic acid in its formulation. Apart from mechanical rupture of the epidermal barrier, a disturbance of type III deiodinase activity or skin fibroblast paracrine function and vascular alterations related to simultaneously injected vasoactive compounds were observed. These findings could be related to thyroid hormone metabolite absorption and systemic consequences in the reported case. CONCLUSION: We describe factitious thyrotoxicosis induced by mesotherapy, to raise awareness of a systemic adverse effect resulting from this widespread cosmetic practice.

High prevalence of pituitary magnetic resonance abnormalities and gene mutations in a cohort of Brazilian children with growth hormone deficiency and response to treatment.

Data were retrospectively collected from 69 Brazilian patients (45 boys) with growth hormone deficiency (GHD) who received exogenous growth hormone (GH) for a median duration of 4 years (range 1-13 years). Forty-two patients had multiple pituitary hormone deficiencies and 27 had isolated GHD. Peak GH was < 7 ng/ml (IRMA) or < 3.2 ng/ml (IFMA) after two stimulation tests. Therapy was started at median age of 10.0 years (range 2.2-21.6 years), bone age of 5.8 years (0.5-13.5 years) and height standard deviation score -4.4 (range -9.3 to -1.6). MRI revealed pituitary abnormalities in 87% of patients. Homozygous mutations in PROP-1, GHRH-R, GH-1 or HESX-1 genes were found in 12 patients. Mean height velocities were 3.3 pretreatment and 10.3, 7.8, 7.4 and 6.4 cm/yr, respectively, during 1-4 years of treatment with GH. In conclusion, the high prevalence (96%) of genetic and/or pituitary abnormalities probably reflects the stringent diagnostic criteria used, and GH replacement resulted in significant catch-up growth.

Safety and Efficacy of Low-Level Laser Therapy in Autoimmune Thyroiditis: Long-Term Follow-Up Study.

INTRODUCTION: A randomized clinical trial (RCT) was performed to evaluate the efficacy of low-level laser therapy (LLLT) for hypothyroidism induced by chronic autoimmune thyroiditis (CAT). OBJECTIVE: The objective was to assess the safety and actions of LLLT 6 years after completion of the RCT. MATERIALS AND METHODS: Forty-three participants were invited to participate in this study 6 years after completion of the RCT. Twenty-five were subjected to LLLT (group L), and 18 were subjected to placebo (group P). Primary outcome measure: frequency of thyroid nodules, which were subjected to fine-needle aspiration biopsy. Secondary outcome measures: dose of levothyroxine required to treat hypothyroidism, thyroid peroxidase antibodies (anti-TPO), and anti-thyroglobulin antibodies (anti-Tg). RESULTS: In group L, a nodule was observed in three patients, who all had a Bethesda II classification. In group P, a nodule was also observed in three patients, with two classified as Bethesda II and one as Bethesda III. The levothyroxine dose required by group L was significantly lower than that required by group P (P = 0.002). The anti-TPO and anti-Tg levels did not differ between the groups. CONCLUSION: LLLT, by the methods described, has been shown to be safe for the treatment of hypothyroidism resulting from CAT. This trial is registered with ClinicalTrials.gov Identifier: NCT02240563.

Oncogenic mutations in KEAP1 disturbing inhibitory Nrf2-Keap1 interaction: Activation of antioxidative pathway in papillary thyroid carcinoma.

BACKGROUND: Nuclear factor erythroid 2-like 2 (NFE2L2) encodes Nrf2, transcription factor of antioxidative genes. In the presence of reactive oxygen species, Keap1 (Kelch-ECH-associating protein-1) inhibitor complex undergoes conformational changes disrupting Keap1-Nrf2 binding and Nrf2 translocates into nucleus. We evaluated the presence of mutations in NFE2L2 and KEAP1 in papillary thyroid carcinomas (PTCs) and correlated them with clinical presentation. METHODS: Coding regions of NFE2L2 and KEAP1 were sequenced in 131 patients with PTC. Clinical and histopathological features were analyzed. Immunohistochemical analysis of Nrf2 expression was performed in mutated carcinomas. RESULTS: Although no mutations were found in NFE2L2, missense mutations in KEAP1 were observed in 6 patients with PTC (4.6%). Immunohistochemistry showed increased Nrf2 expression in nuclei of all mutated carcinomas, which presented poor prognostic features in histopathology. CONCLUSION: We identified mutations in KEAP1 associated with Nrf2 overexpression in PTC. Mutations favored disruption of inhibitory interaction Nrf2-Keap1 to enable increased antioxidant Nrf2 activity, possibly with prognostic consequences.

High prevalence of iodine deficiency in pregnant women living in adequate iodine area.

OBJECTIVES: Iodine deficiency during pregnancy is associated with obstetric and neonatal adverse outcomes. Serum thyroglobulin (sTg) and thyroid volume (TV) are optional tools to urinary iodine concentration (UIC) for defining iodine status. This cross-sectional study aims to evaluate the iodine status of pregnant women living in iodine-adequate area by spot UIC and correlation with sTg, TV and thyroid function. METHODS: Two hundred and seventy-three pregnant women were evaluated at three trimesters. All had no previous thyroid disease, no iodine supplementation and negative thyroperoxidase and thyroglobulin antibodies. Thyroid function and sTg were measured using electrochemiluminescence immunoassays. TV was determined by ultrasonography; UIC was determined using a modified Sandell-Kolthoff method. RESULTS: Median UIC was 146 µg/L, being 52% iodine deficient and only 4% excessive. TSH values were 1.50 ± 0.92, 1.50 ± 0.92 and 1.91 ± 0.96 mIU/L, respectively, in each trimester (P = 0.001). sTg did not change significantly during trimesters with median 11.2 ng/mL and only 3.3% had above 40 ng/mL. Mean TV was 9.3 ± 3.4 mL, which positively correlated with body mass index, but not with sTg. Only 4.5% presented with goitre.When pregnant women were categorized as iodine deficient (UIC < 150 µg/L), adequate (≥150 and <250 µg/L) and excessive (≥250 µg/L), sTg, thyroid hormones and TV at each trimester showed no statistical differences. CONCLUSIONS: Iodine deficiency was detected frequently in pregnant women living in iodine-adequate area. sTg concentration and TV did not correlate to UIC. Our observation also demonstrated that the Brazilian salt-iodization programme prevents deficiency, but does not maintain iodine status within adequate and recommended ranges for pregnant women.

Potential role of sorafenib as neoadjuvant therapy in unresectable papillary thyroid cancer.

Total thyroidectomy, radioiodine (RAI) therapy, and TSH suppression are the mainstay treatment for differentiated thyroid carcinomas (DTCs). Treatments for metastatic disease include surgery, external-beam radiotherapy, RAI, and kinase inhibitors for progressive iodine-refractory disease. Unresectable locoregional disease remains a challenge, as standard therapy with RAI becomes unfeasible. We report a case of a young patient who presented with unresectable papillary thyroid carcinoma (PTC), and treatment with sorafenib allowed total thyroidectomy and RAI therapy. A 20-year-old male presented with severe respiratory distress due to an enlarging cervical mass. Imaging studies revealed an enlarged multinodular thyroid gland, extensive cervical adenopathy, severe tracheal stenosis, and pulmonary micronodules. He required an urgent surgical intervention and underwent tracheostomy and partial left neck dissection, as the disease was deemed unresectable; pathology revealed PTC. Treatment with sorafenib was initiated, resulting in significant tumor reduction allowing near total thyroidectomy and bilateral neck dissection. Postoperatively, the patient underwent radiotherapy for residual tracheal lesion, followed by RAI therapy for avid cervical and pulmonary disease. The patient's disease remains stable 4 years after diagnosis. Sorafenib has been approved for progressive RAI-refractory metastatic DTCs. In this case report, we describe a patient with locally advanced PTC in whom treatment with sorafenib provided sufficient tumor reduction to allow thyroidectomy and RAI therapy, suggesting a potential role of sorafenib as an induction therapy of unresectable DTC.

The End-Diastolic Velocity of Thyroid Arteries Is Strongly Correlated with the Peak Systolic Velocity and Gland Volume in Patients with Autoimmune Thyroiditis.

BACKGROUND: The end-diastolic velocity (EDV) of thyroid arteries reflects peripheral blood flow resistance. OBJECTIVE: The aim was to evaluate EDV correlations with other Doppler sonography parameters and with clinical and biochemical variables in a sample of patients with hypothyroidism caused by chronic autoimmune thyroiditis (CAT). METHODS: A sample of 48 CAT hypothyroid patients receiving treatment with stable doses of levothyroxine was selected. The participants underwent clinical evaluation and measurement of serum thyrotropin (TSH), total triiodothyronine (T3), total thyroxine (T4), free T4, thyroid peroxidase antibodies (anti-TPO), and antithyroglobulin antibodies (anti-Tg) and Doppler sonography. RESULTS: The EDV of the inferior thyroid arteries (ITA-EDV) was strongly and positively correlated with the peak systolic velocity of the inferior thyroid arteries (ITA-PSV, r = 0.919), thyroid volume (r = 0.711), and thyroid visual vascularization pattern (TVP, r = 0.687). There was no correlation between ITA-EDV and the clinical variables, hormones, anti-TPO, or anti-Tg. CONCLUSION: The strong correlation of ITA-EDV with ITA-PSV, TVP, and volume suggests that increased vascularization in CAT may be associated with a reduction in thyroid blood flow resistance, possibly due to an angiogenesis-induced increase in the total vascular cross-sectional area of the parenchyma.