Predominance of CD4+ T cells in metastatic cervical lymph nodes in papillary thyroid carcinoma.

BACKGROUND: Papillary thyroid carcinoma has become increasingly prevalent over the years. Avoiding unnecessary treatments and the risk of complications is fundamental, as well as understanding the mechanisms of tumor progression and conditions that indicate a worse prognosis. The evaluation of the tumor microenvironment can allow the understanding of how the immune system organizes itself to contain the neoplastic advance. METHODS: We compared characteristics related to the lymphocytic subpopulations in the thyroid tumor microenvironment and in the lymph nodes in two groups, with and without lymph node involvement. RESULTS: From four hundred cases followed up at a reference service in thyroid cancer, we selected thirty-two, of which thirteen cases did not present lymph node metastasis (N0 group) and nineteen had lymph node involvement (N1 group). Clinical data were collected, and immunohistochemical reactions were performed for CD4, CD8, FoxP3, CD25 and CD20 markers in lymph nodes and peritumoral infiltrate. We found that the N1 group had a larger tumor size, higher risk staging, higher frequency of extrathyroidal extension, shorter disease-free time and higher expression of CD4+ T lymphocytes in the lymph nodes; however, there was no difference in the expression of other markers or in the pattern of lymphocytic distribution in the lymph node. CONCLUSION: In cervical lymph nodes, the higher frequency of T CD4+ lymphocytes, would be related to the presence of metastasis, while there were no differences in lymphocytic subpopulations in thyroid tumor microenvironment. The absence of changes in unaffected lymph nodes could not predict any tumor behavior.

Cardiac Autonomic Neuropathy in Graves' Disease: Smoking and Age as Predictive Factors.

OBJECTIVES: Hypermetabolic state in Graves' disease (GD) has a great impact on heart homeostasis, acting directly on the heart muscle and modulating the autonomic nervous system. To characterize cardiac autonomic neuropathy (CAN) as a possible complication in patients with GD. METHODS: We evaluated euthyroid GD patients and a control group of healthy euthyroid people. CAN was assessed using autonomic tests of cardiovascular reflex and heart rate variability: respiratory, Valsalva, orthostatic and orthostatic hypotension tests, high frequency, low frequency, and very low-frequency bands. Transthoracic echocardiography was performed in GD patients. RESULTS: Sixty GD patients and 50 people in control group were assessed. CAN was diagnosed in 20% of GD and 14% in the control group. Among GD, 13.3% presented incipient, and 6.7% established CAN, while in the control group, it was verified incipient in 8% and established in 6% (P = .7479). All GD patients with CAN presented an alteration in the deep breathing test. Age and smoking were evidenced as factors associated with the presence of CAN, while higher TRAb values at diagnosis decreased the chance of CAN. CONCLUSIONS: The prevalence of CAN in euthyroid GD patients was 20%. Changes in the cardiac autonomic nervous system were identified, pointing to the importance of evaluating this complication in these patients. Smoking was a predictive factor for CAN, increasing its relationship with conditions that aggravate GD.

Impact of age on tumor characteristics and treatment outcomes in pediatric Differentiated Thyroid Carcinoma.

PURPOSE: There is a tendency to use data generated for adults in the management of pediatric Differentiated Thyroid Carcinoma, neglecting the clinical peculiarities of this condition in childhood. This study aimed to assess and compare the clinical-epidemiological characteristics and their significance in the evolution of thyroid carcinoma diagnosed in childhood across different age groups. METHODS: Seventy-seven patients diagnosed with Differentiated Thyroid Carcinoma (DTC) up to 21 years old were selected and divided into different age groups: up to 10 years, 11 to 18 years, and 19 to 21 years old. Clinical-epidemiological data and their influence in the disease progression were analyzed and compared across age groups. RESULTS: Patients diagnosed below 10 years of age were associated with tumors showing extrathyroidal extension, metastasis in regional lymph nodes, higher levels of stimulated thyroglobulin in the diagnostic iodine-131 whole-body scan (WBS), and under TSH suppression in the last assessment. Additionally, pulmonary metastasis were associated in both diagnostic and post-radioiodine dose WBSs in these younger patients. Analysis of findings in the post-radioiodine therapy WBS revealed significant differences between all age groups (p = 0.0029). The time of diagnosis was identified as a factor associated with an excellent response in subgroups up to 18 years and up to 21 years. No factors associated with dynamic responses over the 1st, 3rd and 5th years of follow-up and the persistence/recurrence of the disease were identified in the subgroup up to 18 years. In the subgroup up to 21 years, having an incomplete structural response in the 3rd year of follow-up increased the chances of recurrent or persistent response by 5.5 times, and by 32.6 times if found in the 5th year of follow-up. CONCLUSIONS: Younger patients exhibited more aggressive tumor characteristics and underwent more rigorous treatment. However, treatment response and disease status in the last assessment, whether free or recurrent/persistence, were similar when comparing the age groups of 11 to 18 and 19 to 21 years. Nonetheless, responses obtained in the 3rd and 5th years post-treatment emerged as factors associated with the persistence/recurrence of the disease in the last assessment in the age group up to 21 years but not in patients diagnosed up to 18 years, a relevant distinction considering the tumor behavior in defining the pediatric age range in thyroid cancer.

Impact of the number of intermediate risk factors on outcome of papillary thyroid cancer.

PURPOSE: The 2015 American Thyroid Association risk stratification system (2015-RSS) is used to assess the tumor recurrence rate and guide the initial treatment. At the current moment, patients with one or multiple intermediate risk factors (IRF) have the same treatment. This study was conducted to evaluate the impact of the number of IRF characteristics on tumor persistence or recurrence rates. METHODS: Patients with intermediate risk papillary thyroid cancer (PTC) were selected and analyzed, furthermore, they were divided into two subgroups, one with 1-2 IRF and another with ≥3 IRF. Those data were analyzed in relation to response to therapy at the end of the first year and in last appointment, time to reach non evidence of disease (NED) state and time in NED state. RESULTS: A total of 257 patients were evaluated. Extrathyroidal invasion, vascular invasion, the total number of IRF and the subgroup of ≥3 IRF were associated with non-excellent response in last consultation; IRF lymph node metastasis was associated with non-excellent response in the first year and in last appointment and prolonged time in NED state; vascular invasion was associated with a shorter time in NED state; total number of IRF and aggressive histology were related to delay in the achievement of NED state. CONCLUSIONS: Higher number of IRF was a predictive factor of non-excellent response in the last visit and was associated with longer time to reach the NED state. Those data suggest a benefit from closer follow-up and more intensive treatment in these patients.

PD-L1 and MCL-1 markers and the relationship with prognostic characteristics of differentiated thyroid carcinoma.

OBJECTIVES: MCL-1 and PD-L1 proteins are related to carcinogenesis mechanisms in differentiated thyroid carcinoma(DTC). Tumor antigens stimulate the expression of PD-1 in immune cells, which binds to PD-L1 of tumor cells, inducing immune escape from the tumor. MCL-1, an anti-apoptotic member of the BCL-2 family, is necessary for the survival of T and B lymphocytes and has a high oncogenic potential. We aim to evaluate the clinical utility and relevance of MCL-1 and PD-L1 in the long-term prognosis of DTC. METHODS: 120 DTC patients after total thyroidectomy and radioiodine therapy followed for a minimum of 2 years were included. Demographic features, tumor histopathology, persistence/recurrence risk, factors associated with outcome, initial response to therapy, persistence or disease-free at the follow-up were related to MCL-1 and PD-L1 immunohistochemical expression and BRAFV600E mutation. RESULTS: 100(83.3%) were women, 46.64 ± 16.73 years old at diagnosis; 37(30.8%) patients were at high, 45(37.5%) of intermediate and 38(31.7%) of low disease recurrence/persistence risk. At the end of follow-up of 124.86 ± 65.36 months, 48(42.5%) had persistent disease. 103(85.8%) patients had papillary thyroid carcinoma (PTC), 17(14.2%) follicular thyroid carcinoma (FTC). In PTC, moderate/strong PD-L1 and MCL-1 expressions were associated to BRAFV600E (p=0.0467; p=0.0044). PD-L1 was also associated with tall cell subtype (p=0.0274). In FTC, weak PD-L1 expression was associated to the largest nodule diameter (p=0.0100). Strong/moderate PD-L1 expression was associated to T2 and the weak expression with T3 in TNM classification (p=0.0490). Moderate MCL-1 expression was associated to smoking (p=0.0350). CONCLUSIONS: PDL-1, marker of progression of tumor cells and MCL-1, anti-apoptotic marker, were associated with PTC carrying BRAFV600E mutation, while PDL-1 was associated with more aggressive PTC subtype. MCL-1 and PD-L1 could be useful in composing a panel to assess the prognosis of PTC patients. On the other hand, both markers seemed to have lower relevance to FTC patients.

Impact of the use of illicit and licit substances and anxiety disorders on the academic performance of medical students: a pilot study.

BACKGROUND: Medical students have a considerable prevalence of anxiety and substance use disorders. Our aim was to assess the presence of anxiety disorders and the use of alcohol and licit and illicit substances, and their influence on the academic performance of medical students. METHODS: This is a cross-sectional, non-experimental pilot study, with quantitative analyses, in which 67 medical students at the Federal University of Rondonópolis, Mato Grosso, Brazil (UFR), were evaluated through the application of non-invasive anxiety assessment instruments, screening for involvement with tobacco, alcohol and other substances, related to school performance coefficient, between June 2019 and March 2020. RESULTS: Worse academic performance was associated with frequent use of tobacco and its derivatives (p = 0.0022), marijuana (p = 0.0020), hypnotics and sedatives (p = 0.0138). Also, the performance was negatively correlated with the use of tobacco (p = 0.0004), alcoholic beverages (p = 0.0261), cannabis (p = 0.0075), sedatives (p = 0.0116) and trait anxiety (p = 0.0036). Greater trait anxiety intensity was associated with previous use of tobacco (p = 0.0276), marijuana (p = 0.0466), amphetamines/ecstasy (p = 0.0151), and hypnotics/sedatives (p = 0.0103). State anxiety was positively correlated with heavy alcohol use (p = 0.0434). Higher state anxiety intensity was related to needing intervention due to the use of amphetamines/ecstasy (p = 0.00379). Students from the intermediate classes of the course (3rd and 4th years) had a higher frequency and intensity of use of tobacco and its derivatives (p = 0.0133), amphetamines or ecstasy (p = 0.0006), and inhalants (p = 0.0256). CONCLUSIONS: Worse academic performance in medical students was correlated with licit and illicit substances use and anxiety disorders. Mid-course students had a higher frequency and intensity of substance use.

Usefulness of pre-thyroidectomy neutrophil-lymphocyte, platelet-lymphocyte, and monocyte-lymphocyte ratios for discriminating lymph node and distant metastases in differentiated thyroid cancer.

OBJECTIVE: This study aimed to analyze the relationship of neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and monocyte-lymphocyte ratio (MLR) with clinicopathological characteristics of patients with differentiated thyroid cancer (DTC). METHODS: This retrospective study included 390 patients with DTC who had complete blood cell counts available at the time of surgery. NLR, PLR, and MLR were calculated, and the risk of cancer-related death, structural recurrence, and response to therapy were assessed using the eighth edition of the tumor-node-metastasis classification, American Thyroid Association (ATA) Risk Stratification System, and ATA Response to Therapy Reclassification, respectively. RESULTS: PLR was higher in patients with distant metastasis than in those without (133.15±43.95 versus 119.24±45.69, p=0.0345) and lower in patients with disease-free status (117.72±44.70 versus 131.07±47.85, p=0.0089) than in those who experienced persistent disease or death. Patients aged ≥55 years had a higher MLR than those aged <55 years (0.26±0.10 versus 0.24±0.12, p=0.0379). Higher MLR (odds ratio [OR]: 8.775, 95% confidence interval [CI]: 1.532-50.273, p=0.0147), intermediate ATA risk (OR: 4.892, 95% CI: 2.492-9.605, p≤0.0001), and high ATA risk (OR: 5.998, 95% CI: 3.126-11.505, p≤0.0001) were risk factors associated with active disease. NLR was not significantly different among the studied variables. Receiver operating characteristic curve cut-off values for NLR, PLR, and MLR were able to differentiate distant metastasis from lymph node metastasis (NLR>1.93: 73.3% sensitivity and 58.7% specificity, PLR>124.34: 86.7% sensitivity and 69.2% specificity, MLR>0.21: 80% sensitivity and 45.2% specificity). CONCLUSION: Cut-off values of NLR, PLR, and MLR differentiated distant metastasis from lymph node metastasis with good sensitivity and accuracy. PLR was associated with disease-free status and it was higher in DTC patients with distant metastasis, persistent disease, and disease-related death. MLR was a risk factor for active disease.

Usefulness of pre-thyroidectomy neutrophil-lymphocyte, platelet-lymphocyte, and monocyte-lymphocyte ratios for discriminating lymph node and distant metastases in differentiated thyroid cancer

OBJECTIVE: This study aimed to analyze the relationship of neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and monocyte-lymphocyte ratio (MLR) with clinicopathological characteristics of patients with differentiated thyroid cancer (DTC). METHODS: This retrospective study included 390 patients with DTC who had complete blood cell counts available at the time of surgery. NLR, PLR, and MLR were calculated, and the risk of cancer-related death, structural recurrence, and response to therapy were assessed using the eighth edition of the tumor-node-metastasis classification, American Thyroid Association (ATA) Risk Stratification System, and ATA Response to Therapy Reclassification, respectively. RESULTS: PLR was higher in patients with distant metastasis than in those without (133.15±43.95 versus 119.24±45.69, p=0.0345) and lower in patients with disease-free status (117.72±44.70 versus 131.07±47.85, p=0.0089) than in those who experienced persistent disease or death. Patients aged ≥55 years had a higher MLR than those aged <55 years (0.26±0.10 versus 0.24±0.12, p=0.0379). Higher MLR (odds ratio [OR]: 8.775, 95% confidence interval [CI]: 1.532-50.273, p=0.0147), intermediate ATA risk (OR: 4.892, 95% CI: 2.492-9.605, p≤0.0001), and high ATA risk (OR: 5.998, 95% CI: 3.126-11.505, p≤0.0001) were risk factors associated with active disease. NLR was not significantly different among the studied variables. Receiver operating characteristic curve cut-off values for NLR, PLR, and MLR were able to differentiate distant metastasis from lymph node metastasis (NLR>1.93: 73.3% sensitivity and 58.7% specificity, PLR>124.34: 86.7% sensitivity and 69.2% specificity, MLR>0.21: 80% sensitivity and 45.2% specificity). CONCLUSION: Cut-off values of NLR, PLR, and MLR differentiated distant metastasis from lymph node metastasis with good sensitivity and accuracy. PLR was associated with disease-free status and it was higher in DTC patients with distant metastasis, persistent disease, and disease-related death. MLR was a risk factor for active disease.

Fixed 30 mCi 131I-iodine therapy without recombinant human thyroid-stimulating hormone stimulation as an attractive therapeutic alternative in nontoxic nodular goiter.

OBJECTIVE: To analyze outcomes of patients with compressive nontoxic multinodular goiter after 131I-iodine 30 mCi treatment without previous use of recombinant human thyroid-stimulating hormone or methimazole. METHODS: We evaluated fixed-dose radioiodine therapy outcomes in patients with nontoxic multinodular goiter who did not accept thyroidectomy as a therapeutic option. Laboratory thyroid function and thyroid volume estimated by ultrasound were assessed before and one year after radioiodine therapy. RESULTS: Twenty euthyroid female patients received 30 mCi of 131I-iodine without recombinant human thyroid-stimulating hormone or methimazole pretreatment. Median thyroid volume and Tc-99m sodium pertechnetate thyroid uptake before radioiodine therapy were 68.05 cm (31.3-295.3) and 0.5% (0.1%-1.2%), respectively. One year after radioiodine therapy, thyroid volume decreased to 55.4 cm (19.8-149.9), and merely 4 patients (20%) developed hypothyroidism. Thyroid volume decreased significantly after radioiodine therapy, presenting a variation of -21.1 cm (-161.3 to -0.8) and -30.61% (-73.88 to -1.02), both with P < 0.0001. Thyroid volume variation was positively correlated with thyroid uptake in Spearman's correlation (r = 0.4730; P = 0.0352). The group satisfied with radioiodine therapy (85%, n = 17) showed a significant reduction in thyroid volume, -25.8 cm (-161.3 to -6.2) and -36.74% (-73.88 to -9.95). The dissatisfied group (15%, n = 3) showed -1.0 cm (-2.0 to -0.8) and -1.67% (-3.38 to -1.02) in thyroid volume, P = 0.0081. Patients that complained about dysphagia presented a lower percentage of thyroid volume decrease after radioiodine therapy, -21.97% (-70.12 to -1.02, P = 0.0430). CONCLUSIONS: A substantial reduction in thyroid volume associated with a low incidence of hypothyroidism and a high satisfaction rate support the use of conventional radioiodine therapy with a fixed dose of 30 mCi. This therapy is an attractive and cheaper therapeutic alternative in selected patients with nontoxic multinodular goiter.

Head-to-head comparison of F-18 FDG PET/CT in radioidine refractory thyroid cancer patients with elevated versus suppressed TSH levels a pilot study.

INTRODUCTION: To perform a head-to-head comparison of the uptake pattern of F-18 fluorodeoxyglucose in positron emission computed tomography (FDG PET/CT) in radioiodine refractory thyroid carcinomas (RAIR) in the same patient under elevated TSH levels (eTSH) and suppressed TSH levels (sTSH). METHODS: FDG PET/CT studies were performed under two conditions: levothyroxine intake (sTSH) and 30 days after hormonal withdrawal (eTSH). SUVmax values and the number of lesions detected (local recurrence and metastases in cervical and distant lymph nodes, lungs and bone) where blindly evaluated. Blood serum TSH and Tg levels were obtained prior to both studies. FDG PET/CT imaging, neck ultrasound, biopsy and follow-up were considered the reference standard. RESULTS: Fifteen patients performed both eTSH and sTSH FDG PET/CT studies. Both were positive for metastases in 80% of the patients. eTSH FDG PET/CT studies did not reveal increased uptake (p = 0.0640) and did not demonstrate a higher number of lesions (p = 0.320) when compared to sTSH FDG PET/CT studies. There was no change in the clinical management of these patients. CONCLUSIONS: eTSH FDG PET/CT in patients with RAIR did not show more metastases in comparison to sTSH FDG PET/CT and there was no impact in clinical management of patients. Elevating TSH levels (whether by hormonal withdrawal or recombinant TSH) in patients being submitted to FDG PET/CT may not be necessary.

Interplay between Body Size Measures and Thyroid Cancer Aggressiveness: A Retrospective Analysis.

Considering controversial data about the relationship between body size and prognosis of differentiated thyroid cancer (DTC), the current study aimed to assess the influence of body weight, body mass index (BMI), and body surface area (BSA) on DTC. We conducted a retrospective analysis of patients' records from the Thyroid Cancer Unit, assessing body size measures, clinical and laboratory prognostic factors, and disease evolution. 337 patients, aged 45.95 ± 13.04 years old, with BMI of 27.87 ± 5.13 kg/m2 and BSA of 1.74 ± 0.18 m2 were enrolled. After 9.5 ± 6.9 years of follow-up, 87.29% of patients were disease-free and 12.71% had persistent disease; no patient had deceased. Patients aged <45 years old with extrathyroidal invasion tumor had greater baseline body weight and BSA than those without extrathyroidal invasion (median 79.5 kg versus 67 kg and 1.85 m2 versus 1.74 m2). Women with poorly differentiated tumor and patients aged ≥45 years old with distant metastasis presented greater weight loss during follow-up compared to patients without such characteristics (median -2 kg versus +1.5 kg and -3 kg versus +1 kg, respectively). The relationship between body size and DTC evolution was not observed. In conclusion, higher weight and BSA were associated with a greater chance of extrathyroidal tumor invasion in younger patients. Specific subgroups of patients with aggressive disease presented higher weight loss. Young patients with higher BSA should be carefully treated due to possible worse prognosis related to increased incidence of extrathyroid invasion. Findings related to tumor aggressiveness and weight loss in specific groups deserve further mechanistic studies.

Panhypopituitarism Without GH Replacement: About Insulin Sensitivity, CRP Levels, and Metabolic Syndrome.

A complete deficiency of anterior pituitary hormones from several etiologies characterizes Panhypopituitarism (PH). Despite advances in treatment, patients with PH maintain high rates of morbidity and mortality, a reason to investigate some insulin sensitivity, metabolic and inflammatory parameters that could be related to the increase of these indicators. This was a cross-sectional study comprising 41 PH patients under hormonal replacement, except for growth hormone, and 37 individuals in a control group (CG) with similar age, gender and body mass index (BMI). We assessed clinical data as age, sex, BMI, waist circumference, waist/hip ratio (WHR), history of hypertension, diabetes mellitus and dyslipidemia as well as fasting glycaemia, insulin, HOMA-IR, HbA1c, high-sensitivity CRP (hs-CRP), and lipid profile. PH patients presents lower values of glycaemia, insulin, HOMA-IR (0.88 vs 2.1) and WHR, but higher levels of hs-CRP (0.38 vs 0.16mg/dl) when compared with the CG. Although the occurrence of dyslipidemia was higher in patients with PH, the frequency of metabolic syndrome was similar between the groups. In multivariate linear regression analysis, the PH group independently predicted lower HOMA-IR and WHR values. In conclusion, this study demonstrated that patients with PH without GH replacement have lower HOMA-IR and WHR values and higher levels of hs-CRP than a CG paired by age, gender and BMI. The diagnosis of dyslipidemia was more frequent in patients with PH, but the occurrence of MS was similar to CG. Further studies are needed to confirm our findings and to better understand the metabolic characteristics of patients with PH.

Vitamin D in Hashimoto's thyroiditis and its relationship with thyroid function and inflammatory status.

Several studies have shown the correlation between vitamin D [25(OH)D] deficiency and thyroid autoimmunity and reducing of thyroid autoantibodies in patients with normal levels of vitamin D combining with thyroid hormone replacement. However, other authors not agree with this association. It is still unclear whether the low 25(OH)D levels are the result of HT disease or a part of its cause. We studied 88 patients with HT regarding vitamin D status and thyroid autoimmunity markers as well as the relationship with cytokines produced by Th1, Th2, and Th17 cells compared with a control group of 71 euthyroid healthy subjects. The present study demonstrated that vitamin D concentrations were similar in patients HT and the control group. The reduction of free T4 levels was a predictor of vitamin D insufficiency for Hashimoto's thyroiditis, but not for the control group. Lower concentrations of TNF-α was a predictor of lower levels of vitamin D. Differences in the association between HT and vitamin D insufficiency remain unresolved in the literature. The thyroid hormone status would play a role in the maintenance of vitamin D sufficiency, and its immunomodulatory role would influence the presence of autoimmune thyroid disease. The positive correlation between free T4 and vitamin D concentrations suggests that adequate levothyroxine replacement in HT would be an essential factor in maintaining vitamin D at sufficient levels.

Reduced insulin sensitivity in differentiated thyroid cancer patients with suppressed TSH.

OBJECTIVE: TSH-suppression is a therapy for thyroid cancer management, but it may lead to adverse effects, which should be balanced with its benefits. Previous studies evaluating the consequences of TSH suppression on insulin sensitivity have only been done with indirect techniques, and results were controversial. Therefore, we aimed to assess insulin sensitivity in patients with thyroid cancer and suppressed thyroid-stimulating hormone (TSH) with the most appropriate direct method (hyperinsulinemic-euglycemic clamp) in order to get a more conclusive response about the topic. METHODS: A group of 20 non-obese and non-diabetic thyroid cancer patients with suppressed TSH underwent a hyperinsulinemic-euglycemic clamp to evaluate insulin sensitivity. Their results were compared to the results of a sex and body mass index (BMI) -paired control group composed of 20 healthy volunteers. RESULTS: Patients were all female, aged 36.8 ± 10.2 years-old, with mean TSH 0.1 ± 0.1 µIU/mL and mean BMI 26.2 ± 3.3 kg/m2. Insulin sensitivity, determined by the insulin-stimulated glucose uptake (M-value), was lower in the patients group (4.2 ± 1.6 mg/min*kg versus 5.8 ± 1.7, age-adjusted p-value = 0.0205). CONCLUSION: This study shows for the first time that subclinical thyrotoxicosis in patients with thyroid cancer is associated with insulin resistance, as measured by hyperinsulinemic-euglycemic clamp technique. Such finding may be taken into consideration by clinicians when balancing risks and benefits of TSH-suppression therapy in thyroid cancer patients.

Relation of thyroid hormone abnormalities with subclinical inflammatory activity in patients with type 1 and type 2 diabetes mellitus.

Thyroid hormone (TH) abnormalities are common in patients with diabetes mellitus (DM). These thyroid hormone abnormalities have been associated with inflammatory activity in several conditions but this link remains unclear in DM. We assessed the influence of subclinical inflammation in TH metabolism in euthyroid diabetic patients. Cross-sectional study involving 258 subjects divided in 4 groups: 70 patients with T2DM and 55 patients with T1DM and two control groups of 70 and 63 non-diabetic individuals, respectively. Groups were paired by age, sex, and body mass index (BMI). We evaluated the association between clinical and hormonal variables [thyrotropin, reverse T3 (rT3), total and free thyroxine (T4), and triiodothyronine (T3)] with the inflammation markers C-reactive protein (hs-CRP), serum amyloid A (SAA), and interleukin-6 (IL-6). Serum T3 and free T3 were lower in patients with diabetes (all P < 0.001) compared to the control groups. Interleukin-6 showed positive correlations with rT3 in both groups (P < 0.05). IL-6 was independently associated to FT3/rT3 (B = -0.193; 95% CI -0.31; -0.076; P = 0.002) and FT4/rT3 (B = -0.107; 95% CI -0.207; -0.006; P = 0.039) in the T1DM group. In the T2DM group, SAA (B = 0.18; 95% CI 0.089; 0.271; P < 0.001) and hs-CRP (B = -0.069; 95% CI -0.132; -0.007; P = 0.03) predicted FT3 levels. SAA (B = -0.16; 95% CI -0.26; -0.061; P = 0.002) and IL6 (B = 0.123; 95% CI 0.005; 0.241; P = 0.041) were related to FT4/FT3. In DM, differences in TH levels compared to non-diabetic individuals were related to increased subclinical inflammatory activity and BMI. Altered deiodinase activity was probably involved. These findings were independent of sex, age, BMI, and HbA1c levels.

Low BMI and low TSH value as risk factors related to lower bone mineral density in postmenospausal women under levothyroxine therapy for differentiated thyroid carcinoma.

OBJECTIVE: Treatment of differentiated thyroid carcinoma (DTC) includes suppression of TSH with levothyroxine therapy, which may negatively influence bone mineral density (BMD), but the effects are controversial. We aimed to evaluate the relationship between TSH-suppressive therapy and BMD in postmenopausal women with DTC. METHODOLOGY: Cross-sectional study that assessed BMD by densitometry and risk factors for decreased BMD in 109 postmenopausal women under TSH-suppressive therapy for DTC, compared to an age-matched euthyroid women control group. Conditions that might have affected BMD were exclusion criteria. RESULTS: Patients were 58.4 ± 8.3 years-old, mean serum TSH was 0.21 ± 0.28µIU/ml. In BMD evaluation, T-scores were -1.09 ± 1.43 SD (lumbar spine) and -0.12 ± 1.18 SD (total femur). No significant differences were found between lumbar or femoral T-scores of patients and control group. Multivariate logistic regression analysis evidenced that low BMI and low mean TSH levels (assessed in the year of BMD measurement) were factors significantly related to lower lumbar and spinal BMD. CONCLUSION: Although low TSH levels and low BMI were correlated with lower BMD, it was not observed an increased prevalence of osteopenia or osteoporosis in this cohort of post-menopausal women under levothyroxine treatment for DTC, when compared to age-matched control women. Nevertheless, such risk factors should be carefully observed in individual patients at high risk of decrease in BMD.

Factors related to mortality in patients with papillary and follicular thyroid cancer in long-term follow-up.

PURPOSE: Differentiated thyroid cancer (DTC) includes papillary thyroid cancer (PTC) and follicular thyroid cancer (FTC). They have different biological behavior but are frequently analyzed together in studies. We aimed to identify factors associated with mortality in those two different cancer subtypes. METHODS: Case series study, with clinical-pathological analysis of the characteristics of 424 patients with PTC and 89 patients with FTC, correlating them to survival rates in a single institution. RESULTS: Patients were followed from 1983 to 2011. Mean follow-up time was 9.4 years for FTC (range 1-36.6 years) and 6.8 years for PTC (range 1.1-30.7 years). Mean age at diagnosis was 51.2 ± 15.5 for FTC and 41 ± 14.7 years for PTC. 50.62% of FTC nodules sized 1.1-4 cm and 20% of PTC sized ≤1 cm. Cox multiple regression analysis evidenced distant metastasis at diagnosis (p = 0.0038; relative risk (RR) 41.247, 95% confidence interval (CI) 3.317-512.986), lymph node metastasis at diagnosis (p = 0.0081; RR 50.98, 95% CI 2.783-934.026) and vascular/lymphatic invasion (p = 0.0039; RR 40.424, 95% CI 3.287-497.177) as factors related to mortality in FTC patients. For PTC, the factors were distant metastasis at diagnosis (p < 0.0001; RR 32.5, 95% CI 6.676-158.543) and degree of differentiation (poor versus well differentiated, p = 0.003; RR 10.4, 95% CI 2.218-49.487). CONCLUSION: The common factor that influenced mortality for FTC and PTC patients was distant metastasis at diagnosis, increasing mortality rate by 41 times in FTC and 30 times in PTC patients. The different factors influencing mortality for different DTC types highlight the importance of analyzing them separately.

Follicular thyroid carcinoma metastasis to the internal jugular vein demonstrated by 131I SPECT/CT.

Cervical uptake detected by 131I whole body scintigraphy (131I-WBS) may be due to thyroid remnants or loco-regional metastases. We describe a patient with follicular carcinoma submitted to total thyroidectomy. 131I-WBS showed left cervical linear uptake and focal areas of uptake in the abdomen and pelvis. SPECT/CT images demonstrated a potential thrombus in the left jugular vein (confirmed by doppler neck ultrasound and MRI) as well as bone metastases. The patient was submitted to thrombectomy and histopathology confirmed metastasis of follicular carcinoma.

Risk factors associated with benign and malignant thyroid nodules in autoimmune thyroid diseases.

Objectives. Assess the prevalence of thyroid nodules and predictors of malignant origin in patients with autoimmune thyroid diseases. Patients and Methods. Retrospective study including 275 patients, 198 with Graves' disease and 77 with Hashimoto's thyroiditis. Clinical and demographical data, ultrasonographical nodule characteristics, total thyroid volume and histological characteristics were recorded. Results. Graves' disease: the prevalence of thyroid nodules and thyroid carcinoma were 27.78% and 5.05%, respectively. Older age (OR = 1.054; 95% CI = 1.029-1.080) and larger thyroid volumes (OR = 1.013; 95% CI = 1.003-1.022) increased the chance of nodules. Younger age (OR = 1.073; 95% CI = 1.020-1.128) and larger thyroid volume (OR = 1.018; 95% CI = 1.005-1.030) predicted thyroid carcinoma. Hashimoto's thyroiditis: the prevalence of thyroid nodules and carcinomas were 50.7% and 7.8%, respectively. Nodules were predicted by thyroid volume (OR = 1.030; 95% CI = 1.001-1.062). We found higher number of nodules in patients with thyroid carcinoma than in those with benign nodules (3 versus 2; P = 0.03). Patients with Hashimoto's thyroiditis presented nodules more frequently than patients with Graves' disease (50.65% versus 27.28%; P < 0.001), while the prevalence of carcinoma was similar (P = 0.751). Conclusions. Larger goiter was associated with carcinoma in Graves' disease and Hashimoto's thyroiditis. Younger patients presented higher risk of papillary thyroid carcinoma in Graves' disease. The prevalence of carcinoma was similar in both conditions.

Thyroid nodule management: clinical, ultrasound and cytopathological parameters for predicting malignancy.

Although fine-needle aspiration cytology is considered to be the reference method for evaluating thyroid nodules, the results are inaccurate in approximately 10-30% of cases. Several studies have attempted to predict the risk of malignancy in thyroid nodules based on age, nodularity, thyrotropin values, thyroid autoimmune disease, hot/cold nodule status, and ultrasound parameters. However, no consensus has been found, and none of these parameters has significantly affected patient management. The management of indeterminate thyroid nodules and re-biopsies of nodules with initially benign cytological results remain important and controversial topics of discussion. The Bethesda cytological system and several studies on the use of molecular markers to predict malignancy from cytological samples of thyroid nodules need further clarification. More in-depth discussions among and continuous education of the specialists involved in treating thyroid disease are necessary to improve the management of these patients. This review aims to examine the clinical, laboratory, ultrasound, and scintigraphic parameters that can be used for thyroid nodule management.