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Background: Studies report a wide spectrum of 124I positron emission tomography (PET)/computed tomography (CT) sensitivity and specificity in the detection of differentiated thyroid cancer (DTC) le...

Myxedema coma and thyroid storm are among the most common endocrine emergencies presenting to general hospitals. Myxedema coma represents the most extreme, life threatening expression of severe hypothyroidism with subjects presenting with deteriorating mental status, hypothermia, and multiple organ system abnormalities. It typically appears in patients with pre-existing hypothyroidism via a common pathway of respiratory decompensation with CO2 narcosis leading to coma. Without early and appropriate therapy, there is often a fatal outcome. It is a clinical diagnosis based on history and physical findings at presentation and not on any objective thyroid laboratory tests. Clinically based scoring systems have been proposed to aid in the diagnosis. While a relatively rare syndrome, the typical patient is an elderly woman (thyroid hypofunction being much more common in women) who may or may not have a history of previously diagnosed or treated thyroid dysfunction. Thyrotoxic storm or thyroid crisis also is a rare condition and it too reflects a clinical diagnosis. Diagnosis is based upon the appearance of severe hyperthyroidism accompanied by elements of systemic decompensation. Based upon the prospect of high mortality without aggressive treatment, therapy must be initiated as early as possible in a critical care setting. There are no clues to diagnosis based upon laboratory tests alone, but several scoring systems have been developed to aid in diagnosis. The usual clinical signs and symptoms of hyperthyroidism will be present along with more exaggerated clinical manifestations affecting the cardiovascular, gastrointestinal, and central nervous systems. A multi-pronged treatment approach has been recommended and has been associated with improved outcomes.

Myxoedema coma is a rare but life-threatening condition resulting from severe thyroid hormone deficiency. Despite having a low incidence, the mortality rate may be as high as 30–60%. The prompt recognition of clinical presentation and precipitating events allows earlier diagnosis and treatment reducing the probability of an adverse outcome. The risk of myxoedema coma is greatest in hypothyroid older patients exposed to a precipitating event such as infection or a systemic superimposed illness. The effect of thyroid hormone deficiency on multiple systems (cardiovascular, respiratory, gastrointestinal, renal, neuropsychiatric, haematologic and thermoregulatory) often blurs the diagnosis resulting in treatment delay. Proper treatment includes thyroid hormone administration and a multifaceted approach to the multiple metabolic derangements in order to optimize survival.

Thyroid storm is a rare presentation of exaggerated manifestations of thyrotoxicosis and represents a complex endocrine emergency with a high mortality rate. Multiple organs are affected leading to multisystemic decompensation. To facilitate early diagnosis, a scoring system has been developed based on thermoregulation dysfunction, central nervous system alteration, gastrointestinal symptoms, cardiovascular involvement, and presence of precipitating event. Treatment delay increases the likelihood of irreversible progression and ultimate demise. Hence, when the diagnosis is likely but indefinite, treatment for thyrotoxic storm should be initiated. Management is based on four main strategies directed to reducing thyroid gland hormone production and release, managing the effects of circulating thyroid hormone in the periphery, addressing the systemic decompensation and the precipitating event.

Background: Biotin has been reported to interfere with several commonly used laboratory assays resulting in misleading values and possible erroneous diagnosis and treatment. This report describes a prospective study of possible biotin interference in thyroid-related laboratory assays, with a comparison of different commonly used assay platforms. Materials and Methods: Thirteen adult subjects (mean age 45 ± 13 years old) were administered biotin 10 mg/day for eight days. Blood specimens were collected at three time points on day 1 and on day 8 (baseline, two, and five hours after biotin ingestion). Thyrotropin (TSH), free triiodothyronine (fT3), free thyroxine (fT4), total triiodothyronine (TT3), total thyroxine (TT4), thyroxine binding globulin (TBG), and thyroglobulin (Tg) levels were analyzed with four different platforms: Abbott Architect, Roche Cobas 6000, Siemens IMMULITE 2000, and liquid chromatography with tandem mass spectrometry (LC-MS/MS). TSH, fT3, fT4, TT3, and TT4 were measured with Abbott Architect and Roche Cobas 6000. fT3, fT4, TT3, and TT4 were also measured by LC-MS/MS. Tg was measured by Siemens IMMULITE 2000. TBG was assessed with Siemens IMMULITE 2000. Results: Significant changes in TSH, fT4, and TT3 measurements were observed after biotin exposure when the Roche Cobas 6000 platform was used. Biotin intake resulted in a falsely lower Tg level when measurements were performed with Siemens IMMULITE 2000. At the time points examined, maximal biotin interference was observed two hours after biotin exposure both on day 1 and day 8. Conclusions: A daily dose of 10 mg was shown to interfere with specific assays for TSH, fT4, TT3, and Tg. Physicians must be aware of the potential risk of erroneous test results in subjects taking biotin supplements. Altered test results for TSH and Tg can be particularly problematic in patients requiring careful titration of levothyroxine therapy such as those with thyroid cancer.

Management of metastatic radioiodine refractory differentiated thyroid cancer (DTC) can be a therapeutic challenge. Generally, little is known about the paired molecular profile of the primary tumor and the metastases and whether they harbor the same genetic abnormalities. The present study compared the molecular profile of paired tumor specimens (primary tumor/metastatic sites) from patients with radioiodine refractory DTC in order to gain insight into a possible basis for resistance to radioiodine. Twelve patients with radioiodine refractory metastases were studied; median age at diagnosis of 61 years (range, 25–82). Nine patients had papillary TC (PTC), one had follicular TC (FTC), and two had Hürthle cell TC (HTC). Distant metastases were present in the lungs (n = 10), bones (n = 4), and liver (n = 1). The molecular profiling of paired tumors was performed with a panel of 592 genes for Next Generation Sequencing, RNA-sequencing, and immunohistochemistry. Digital microfluidic PCR was used to investigate TERT promoter mutations. The genetic landscape of all paired sites comprised BRAF, NRAS, HRAS, TP53, ATM, MUTYH, POLE, and NTRK genes, including BRAF and NTRK fusions. BRAF V600E was the most common point mutation in the paired specimens (5/12). TERT promoter mutation C228T was detected in one case. PD-L1 expression at metastatic sites was highly positive (95%) for one patient with HTC. All specimens were stable for microsatellite instability testing, and the tumor mutation burden was low to intermediate. Therefore, the molecular profile of DTC primary and metastatic lesions can show heterogeneity, which may help explain some altered responses to therapeutic intervention.

Simple Summary Targeting the metabolism of cancers is a promising strategy for treatment. In the current study we examine the role of COX4, an enzyme of the mitochondria, in thyroid cancer. The experiments were performed in immortalized cell lines and tissue sample from human thyroid cancers. We examined several types of thyroid cancers, and we found out that the role of COX4 was more pronounced in medullary thyroid cancer. As a result, we believe that COX4 should be studied further as a therapeutic target in medullary thyroid cancer. Abstract The nuclear-encoded subunit 4 of cytochrome c oxidase (COX4) plays a role in regulation of oxidative phosphorylation and contributes to cancer progression. We sought to determine the role of COX4 in differentiated (DTC) and medullary (MTC) thyroid cancers. We examined the expression of COX4 in human thyroid tumors by immunostaining and used shRNA-mediated knockdown of COX4 to evaluate its functional contributions in thyroid cancer cell lines. In human thyroid tissue, the expression of COX4 was higher in cancers than in either normal thyroid (p = 0.0001) or adenomas (p = 0.001). The level of COX4 expression correlated with tumor size (p = 0.04) and lymph-node metastases (p = 0.024) in patients with MTCs. COX4 silencing had no effects on cell signaling activation and mitochondrial respiration in DTC cell lines (FTC133 and BCPAP). In MTC-derived TT cells, COX4 silencing inhibited p70S6K/pS6 and p-ERK signaling, and was associated with decreased oxygen consumption and ATP production. Treatment with potassium cyanide had minimal effects on FTC133 and BCPAP, but inhibited mitochondrial respiration and induced apoptosis in MTC-derived TT cells. Our data demonstrated that metastatic MTCs are characterized by increased expression of COX4, and MTC-derived TT cells are vulnerable to COX4 silencing. These data suggest that COX4 can be considered as a novel molecular target for the treatment of MTC.

The detection of rare mutational targets in plasma (liquid biopsy) has emerged as a promising tool for the assessment of patients with cancer. We determined the presence of cell-free DNA containing the BRAFV600E mutations (cfBRAFV600E) in plasma samples from 57 patients with papillary thyroid cancer (PTC) with somatic BRAFV600E mutation-positive primary tumors using microfluidic digital PCR, and co-amplification at lower denaturation temperature (COLD) PCR. Mutant cfBRAFV600E alleles were detected in 24/57 (42.1%) of the examined patients. The presence of cfBRAFV600E was significantly associated with tumor size (p = 0.03), multifocal patterns of growth (p = 0.03), the presence of extrathyroidal gross extension (p = 0.02) and the presence of pulmonary micrometastases (p = 0.04). In patients with low-, intermediate- and high-risk PTCs, cfBRAFV600E was detected in 4/19 (21.0%), 8/22 (36.3%) and 12/16 (75.0%) of cases, respectively. Patients with detectable cfBRAFV600E were characterized by a 4.68 times higher likelihood of non-excellent response to therapy, as compared to patients without detectable cfBRAFV600E (OR (odds ratios), 4.68, 95% CI (confidence intervals)) 1.26&ndash, 17.32, p = 0.02). In summary, the combination of digital polymerase chain reaction (dPCR) with COLD-PCR enables the detection of BRAFV600E in the liquid biopsy from patients with PTCs and could prove useful for the identification of patients with PTC at an increased risk for a structurally or biochemically incomplete or indeterminate response to treatment.

Background: The identification of somatic mutations and gene fusions is crucial for guiding therapeutic decisions in patients with thyroid cancer. Microfluidic digital PCR is currently considered as a technique of choice for highly sensitive detection of gene mutations/fusion. We recently demonstrated that dPCR is a useful tool for detection of BRAFV600E and TERT promoter mutations in thyroid tumors. Objectives: This study aimed to determine the analytic and clinical validity of dPCR for detection of RAS mutations and RET/PTC fusions in thyroid cancer tissue. Material and Methods: Thyroid tissues from 75 patients with PTCs (58 classical PTC (CPTC) and 17 follicular variant (FVPTC) were used for DNA and RNA extraction. The rare mutation SNP genotyping assays which were multiplexed for detection of mutant and wild type NRASQ61; as well as RET/PTC1 and RET/PTC3 were synthesized by Thermo Fisher Scientific. Digital PCR was performed using a QuantStudio 3D Digital PCR platform. QuantStudio Software was used for relative and quantitative data analysis. Results: NRASQ61 was detected in 0/58 CPTC and in 6/17 (35%) FVPTC. The ratios of mutant/total varying from 11.7% to 61.5%. Among patients with FVPTC there were no significant associations between the presence of NRASQ61 and patient’s age, sex, multifocal growth, extra-thyroidal invasion and lymph node metastases. The ratios mutant/total correlated with tumor size in patients harboring NRASQ61. In 23 cases, RET/PTC1 and RET/PTC3 transcripts were examined. RET/PTC1 and RET/PTC3 transcripts were detected in 3 and 1 case, respectively. RET/PTCs were detected in CPTC, but not in FVPTC. RET/PTC positive tumors were characterized by multi-focal patterns of growth, presence of extra-thyroidal invasion, and presence of lymph node metastases (4 of 4 cases with RET/PTC). There were not RET/PTCs positive tumors harboring simultaneously anomalies in RAS oncogene. Conclusions: Microfluidic digital PCR allows specific, sensitive and rapid detection of RAS mutations and RET/PTC fusions in thyroid tissue samples. Implementation of dPCR-based assays may facilitate analysis of thyroid tumors and support research in patients with thyroid cancer.

We discuss the study of Samuels et al., focusing on the effect that levothyroxine treatment has on energy expenditure and body composition in subclinical hypothyroidism.

The detection of recurrent disease in differentiated thyroid cancer (DTC) patients with elevated or rising serum thyroglobulin (Tg) levels and multiple negative conventional imaging studies can be challenging, especially when 18F-FDG PET/CT scan is also negative. We report a patient and review the literature on the diagnostic use of 99mTc-sestamibi scans to identify the source of elevated or rising Tg in patients with negative conventional imaging including negative 18F-FDG PET/CT scans. A 73-year-old woman was referred for widely-invasive metastatic follicular thyroid cancer with bone metastasis to her left mandible. She had a total thyroidectomy, left mandibular resection, and 131I therapy of 145 mCi (5.4 GBq) and her subsequent unstimulated serum Tg level was 29 ng/ml (TgAb negative). At six months’ follow-up, her stimulated Tg was 527 ng/ml (TSH 188 mIU/L, TgAb negative). All imaging studies performed within the prior 12 months were reported as negative for recurrence or metastasis; this included neck ultrasound, diagnostic radioiodine scan, chest CT and, 18F-FDG PET/CT. The patient was injected with 24.6 mCi (910 MBq) of 99mTc-sestamibi intravenously, and whole-body and SPECT/CT images were acquired. The 99mTc-sestamibi whole-body posterior image demonstrated abnormal focal uptake in the right posterior calvarium and corresponded to an occipital lytic bone lesion on the SPECT/CT. The patient underwent surgical resection of the skull metastasis, and pathology confirmed metastatic follicular thyroid cancer. Five months post-surgery, the suppressed Tg was markedly reduced and remained stable at ~3.2 ng/ml. With the knowledge of the DTC recurrence location, the two sets of 18F-FDG images were re-evaluated. The more thorough and targeted interpretation underscored the importance of structured image reporting. The current literature on the utility of 99mTc-sestamibi scans when radioiodine, 18F-FDG PET/CT, and other imaging studies are negative is sparse and inconsistent. 99mTc-sestamibi may have a role in thyroid cancer localization when physical exam, neck ultrasound, radioiodine scan, chest/abdomen CT, and 18F-FDG PET/CT does not identify the source of elevated Tg levels in DTC.

We examined the utility of microfluidic digital PCR (dPCR) for detection of BRAF and TERT mutations in thyroid tumors. DNA extracted from 100 thyroid tumors (10 follicular adenomas, 10 follicular cancers, 5 medullary cancers, and 75 papillary thyroid cancer (PTC) were used for detection of BRAF and TERT mutations. Digital PCRs were performed using rare mutation SNP genotyping assays on QuantStudio 3D platform. In PTCs, BRAFV600E was detected by dPCR and Sanger sequencing in 42/75 (56%) and in 37/75 (49%), respectively. BRAFV600E was not detected in other tumors. The ratio of mutant/total BRAF alleles varied from 4.7% to 47.5%. These ratios were higher in classical PTCs (27.1%) as compared to follicular variant PTCs (9.4%) p = 0.001. In PTCs with and without metastases, the ratios of mutant/total BRAF alleles were 27.6% and 18.4%, respectively, (p = 0.03). In metastatic lesions percentages of mutant/total BRAF alleles were similar to those detected in primary tumors. TERTC228T and TERTC250T were found in two and one cases, respectively, and these tumors concomitantly harbored BRAFV600E. These tumors exhibited gross extra-thyroidal extension, metastases to lymph nodes, and pulmonary metastases (one case). Our results showed that dPCR allows quantitative assessment of druggable targets in PTCs and could be helpful in a molecular-based stratification of prognosis in patients with thyroid cancer.

Background: Initiation of thyroid hormone replacement (THR) after a total thyroidectomy has traditionally relied on the weight of the patient, regardless of the patient's body mass index (BMI). Cur...

Background:Identification of somatic mutations is crucial for guiding therapeutic decisions in patients with thyroid cancer. Droplet digital PCR (ddPCR) is a sensitive and particularly useful method of nucleic acid detection for quantification of gene mutations. This study aimed to determine the analytic and clinical validity of BRAF ddPCR mutational testing in thyroid cancer tissue. Material and Methods: Initially we examined a training cohort of 30 patients with thyroid cancer that had been previously tested for BRAF mutation with Sanger sequencing and included 15 BRAF positive and 15 BRAF negative subjects. A second group included 65 samples from 18 patients with thyroid cancer. Samples were obtained from central and invasive areas of tumors, normal thyroid tissue and lymph node metastasis. The DNA was extracted using Thermo Fisher Scientific King Fisher Duo Prime Purification System, and DNA concentration was measured by NanoDrop. Digital PCR was performed using a QuantStudio 3D Digital PCR platform. QuantStudio Software was used for relative and quantitative data analysis. Results: In the training set, BRAF mutations were detected in 15/15 BRAF-positive thyroid cancers and in 0/15 BRAF- negative tumors. Analysis of tissue samples from the second group of patients demonstrated detection of wild type BRAF alleles in normal thyroid as well as in thyroid cancer tissue. In contrast, BRAFV600 mutant alleles were detected only in thyroid cancer tissue samples (13/18 (72%) examined patients). In cancer samples, the ratios of mutant/total BRAF alleles ranged from 1.47% to 42.8% (average 24.6%). Quantification of BRAF mutant alleles did not reveal differences between male and female patients or patient age. The ratios of mutant/total BRAF did not correlate with tumor size, and were not different in central and invasive areas of the thyroid tumors. Metastases at the time of surgery were detected in 2/5 patients with BRAF-negative tumors, and in 6/13 patients with BRAF-positive tumors. The ratios of mutant/total BRAF alleles were higher in cancers presenting with metastases at the time of surgery (average 26.6%) compared to tumors without metastases (average 19.6%). However, these differences were not statistically significant. The quantifications of mutant BRAF alleles in metastatic lesions showed that the ratios of mutant/total BRAF were similar to corresponding primary tumors in 3 cases, and were decreased in 3 cases. Conclusion: Overall, droplet digital PCR allows specific, sensitive and rapid detection of BRAF mutations in thyroid tissue samples. Quantitative evaluation of BRAF mutations offers an opportunity for additional assessment of prognosis and potential response to treatment with tyrosine kinase inhibitors. Further research on implementation of ddPCR-based assays of thyroid tumors may provide important insights to the management of patients with thyroid cancer.

Background: Although thyroid cancer is considered to have generally a good prognosis, approximately 2000 patients a year die as a consequence of progressive disease. Understanding the conditions arising from thyroid cancer progression and directly contributing to death could improve and personalize therapeutic and palliative treatment in patients with aggressive disease. Material and methods: Information from 586 deceased patients with thyroid cancer treated in MedStar facilities from 1986 to 2018 were obtained from MedStar Cancer Registries. Data from patients coded with cancer related death were extracted and analysis of clinical and pathological data was performed. Charts were reviewed to obtain information regarding the precipitating cause of death. Results: A pool of 71 patients with thyroid cancer related cause of death was obtained, of whom 35 were female (49%) and 36 male (51%). Histopathology analysis revealed 23 (32%) papillary thyroid cancer, 14 (20%) follicular variant papillary cancer, 11 (15%) follicular thyroid cancer, 3 (4%) poorly differentiated, 13 (18%) anaplastic, 3 (4%) medullary thyroid cancer and 1 (1%) squamous cell carcinoma. Staging was possible for 42 patients: (31% stage I, 7% STAGE II, 5% STAGE III, 57% STAGE IV). As initial management, 50% of the patients had total thyroidectomy, 13 % subtotal, 10% lobectomy and 24% did not undergo surgery. 78% of the differentiated thyroid carcinoma (DTC) patients had been treated with I-131 therapy and 34% of all the patients received external beam radiation therapy. For patients with DTC, age at diagnosis (mean ± 2 SD) was 55 ± 15 years old, and the mean age at the time of death was 64.86 ± 10 years old with a mean survival after diagnosis of 9.5 years. For anaplastic thyroid cancer, mean age at diagnosis was 76.6 ± 8.5 years old and mean age at the moment of death was 77.39 ± 13 years old with a mean survival of 0.77 years. The precipitating cause of death was identifiable in 24 patients. The main precipitating event was respiratory insufficiency (50%) mainly triggered by pneumonia, followed by upper airway obstruction (17%) and stroke and/or brain hemorrhage (17%). Other causes included septic shock (13%) (mainly related to gastrointestinal obstruction or perforation) and multiple organ failure in (4%). At the time of death 69% of patients had lung metastasis, 54% bone metastasis, 59% brain metastasis, 15% liver metastasis, 10% muscle metastasis, 8% peritoneum metastasis and 8% other locations (eye, adrenal, kidney). Conclusion: Death from thyroid cancer does occur, and death in patients originally considered as Stage 1 raises question of the utility of the existing thyroid cancer staging system. The spectrum of causes of death in these patients (respiratory insufficiency, airway obstruction, brain hemorrhage and stroke) provides insight into potential end of life planning and management in patients with progressive thyroid cancer.

International audience; Branched chain amino acids (BCAA) are essential elements of the human diet, which display increased plasma levels in obesity and regained particular interest as potential biomarkers for development of diabetes. To define determinants of insulin resistance (IR) we investigated 73 genes involved in BCAA metabolism or regulation by fine-scale haplotype mapping in two European populations with metabolic syndrome. French and Romanians (n = 465) were genotyped for SNPs (Affymetrix) and enriched by imputation (BEAGLE 4.1) at 1000 genome project density. Initial association hits detected by sliding window were refined (HAPLOVIEW 3.1 and PHASE 2.1) and correlated to homeostasis model assessment (HOMAIR) index, in vivo insulin sensitivity (SI) and BCAA plasma levels (ANOVA). Four genomic regions were associated with IR located downstream of MUT, AACS, SLC6A15 and PRKCA genes (P between 9.3 and 3.7 x 10-5). Inferred haplotypes up to 13 SNPs length were associated with IR (e.g. MUT gene with P < 4.9 x 10-5; Bonferroni 1.3 x 10-3) and synergistic to HOMAIR. SNPs in the same regions were also associated with one order of magnitude lower P values (e.g. rs20167284 in the MUT gene with P < 1.27 x 10-4) and replicated in Mediterranean samples (n = 832). In French, influential haplotypes (OR > 2.0) were correlated with in vivo insulin sensitivity (1/SI) except for SLC6A15 gene. Association of these genes with BCAA levels was variable, but influential haplotypes confirmed implication of MUT from BCAA metabolism as well as a role of regulatory genes (AACS and PRKCA) and suggested potential changes in transcriptional activity. These data drive attention towards new regulatory regions involved in IR in relation with BCAA and show the ability of haplotypes in phased DNA to detect signals complimentary to SNPs, which may be useful in designing genetic markers for clinical applications in ethnic populations.

This article presents an overview of the use of radioactive iodine (131-I) in the treatment of patients with differentiated thyroid cancer. Topics reviewed include definitions; staging; the 2 principal methods for selection of 131-I dosage; the indications for ablation, adjuvant treatment, and treatment; the recommendations for the use of 131-I contained in the guidelines of the American Thyroid Association and the Society of Nuclear Medicine and Molecular Imaging; the dosage recommendations and selection of dosage approach for 131-I by these organizations; the use of recombinant human thyrotropin for radioiodine ablation, adjuvant therapy, or treatment; and the MedStar Washington Hospital Center approach.

Objectives. It has been already confirmed that retinal neurodegeneration has a predictive value in the development of microvascular alterations in diabetic retinopathy. However, no data are available on the association between neuroretinal dysfunction and peripheral motor unit loss. Our study, therefore, was aimed at investigating the hypothesis that retinal neurodegeneration could be considered an early marker of diabetic peripheral neuropathy (DPN). Methods. 20 T1DM patients with no symptoms/signs of peripheral polyneuropathy, without DR or with very mild nonproliferative DR, and 14 healthy controls (C) age- and gender-matched were enrolled. The following electrophysiological tests were performed: standard nerve conduction studies (NCS) and incremental motor unit number estimation (MUNE) from the abductor hallux (AH) and abductor digiti minimi (ADM). Neuroretinal function was studied by multifocal electroretinogram (MfERG) recordings, measuring response amplitude density (RAD) and implicit time (IT) from rings and sectors of superior (S)/inferior (I)/temporal (T)/nasal (N) macular sectors up to 10 degrees of foveal eccentricity. Results. MfERG RADs from rings and sectors were significantly reduced in T1DM (p<0.05) vs. C. ADM MUNE and AH MUNE were significantly decreased in T1DM (p=0.039 and p<0.0001, respectively) vs. C. A positive correlation between mean MfERG RADs from the central 5 degrees of the four (S, I, T, and N) macular sectors and lower limb motor unit number (r=0.50, p=0.041; r=0.64, p=0.005; r=0.64, p=0.006; and r=0.61, p=0.010, respectively) was observed in T1DM patients. No abnormalities of NCS were found in any subject. Conclusions. The motor unit loss on the one hand and neuroretinal dysfunction on the other hand are already present in T1DM patients without DPN. The relationship between neuroretinal dysfunction and motor unit decline supports the hypothesis that neuroretina may represent a potential “window” to track the early neurogenic damage in diabetes.

Aims An increased rate of cerebrovascular complications in patients with metabolic syndrome (MetS) has been reported. Previous studies demonstrated an association between glycemic variability (GV) and cerebrovascular reactivity (CRV) in MetS, thus suggesting a putative role of GV on cerebrovascular events. Although the pathophysiological mechanism linking GV to damage is still to be elucidated, evidence suggests oxidative stress plays a crucial role. Since functional variants in glutathione S-transferases (GST) genes modulate the cellular detoxification processes, the aim of this study was to elucidate the involvement of GSTs in MetS and investigating the correlation with GV, arterial stiffness, and sympatho-vagal (SV) balance. Methods A hundred metabolic syndrome patients without diabetes underwent GST gene polymorphism analysis and a sub-sample 36 patients were randomly selected to investigate the correlation between GST gene polymorphisms and GV, and sympatho-vagal (SV) balance and arterial stiffness. Results GSTM1 showed a significant association with several GV, arterial stiffness, and SV balance indexes. In particular, the GSTM1 deletion positively correlates with lower values of these indexes when compared to the presence of the gene. Conclusions Therefore, we suggested a global influence of GSTM1 deletion on the GV, arterial stiffness, and SV balance pathways in MetS patients, probably also interacting with AMP-activated protein kinase (AMPK) regulation. Our novel findings indicate GSTM1 could be a risk locus in MetS development and shed light novel scenarios on the role of glucose fluctuations in neurological impairments.

The detection of recurrent disease in differentiated thyroid cancer (DTC) patients with elevated or rising serum thyroglobulin (Tg) levels and multiple negative conventional imaging studies can be challenging, especially whenA 73-year-old woman was referred for widely-invasive metastatic follicular thyroid cancer with bone metastasis to her left mandible. She had a total thyroidectomy, left mandibular resection, andThe

Background Unlike virtually all other cancer types, thyroid cancer is unique in that patient age is a key component in its staging. Pathologists and clinicians worldwide have accepted an age cutoff of 45 years for staging; in 2018, this advances to age 55 years in the eighth edition of the American Joint Commission on Cancer staging system. Evidence acquisition Clinical and basic research studies, reviews, and previous editions of consensus statements regarding thyroid cancer staging were reviewed, with particular focus on the influence of age in thyroid cancer prognosis. Purpose This perspective briefly reviews the basis for this practice and challenges it as no more appropriate than for other malignancies. Evidence synthesis The majority of findings report an association of age with thyroid cancer survival but do not support a specific age cutoff; rather, they suggest that outcome is affected by age as a continuous variable. Conceivably, other factors interact with age on a continuous basis over time, affecting prognosis. When identified, these factors could alter our current concept of the importance of an age cutoff in staging. Conclusions Among all cancers, age has an important role in only thyroid cancer staging. The consideration of age as a continuous variable and the search for age-associated prognostic variables could elucidate a more accurate staging system.