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 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.

Type 1 diabetes mellitus associated or not with primary hypothyroidism and women's fertility.

The aim of this study is to evaluate the prevalence of infertility and other reproductive parameters in women with type 1 diabetes mellitus (DM1) with and without primary hypothyroidism (PH). This is a cross-sectional study conducted at Division of Endocrinology. We evaluated 110 female, aged over 18 years, 79 had DM1 and 31 had DM1 plus PH. They were interviewed to obtain data on their gynecological and obstetric history; medical charts were reviewed to determine the characteristics of the diseases and to assess clinical/laboratory data. Infertility was defined as 12 months of unprotected sexual intercourse without conception. We used the chi-square and Mann-Whitney's tests, and logistic regression analysis. The prevalence of infertility in the total sample was 24.5%, no differences were found between groups regarding obstetric outcomes and gynecologic variables. Factors associated with infertility were microvascular complication (OR: 11.36; 95% CI: 2.488-52.632; p = .029), polycystic ovary syndrome (OR: 9.80; 95% CI: 2.247-43.478; p = .016), PH (OR: 3.38; 95% CI: 1.078-10.638; p = .047), and older age at onset of DM1 (OR: 1.12; 95% CI: 1.029-1.215; p = .019). The presence of PH in women with DM1 was a predictive factor for infertility. Women with DM1 showed poorer reproductive outcomes compared to the general population.

Thyroid function during the first year of use of the injectable contraceptive depot medroxyprogesterone acetate.

PURPOSE: The aim of the study was to evaluate thyroid function profile as a possible factor influencing weight and body composition variation in new users of depot medroxyprogesterone acetate (DMPA). MATERIALS AND METHODS: A prospective, non-randomised, comparative study was conducted at the University of Campinas, Brazil. Women aged 18-40 years with a body mass index (BMI) less than 30 kg/m2, normal oral glucose tolerance test, no known diseases, and using no medication, who opted to use DMPA were paired by age (±1 year) and BMI (±1 kg/m2) with women initiating copper intrauterine device (IUD) use. The main outcome measures were thyroid function profile, weight, and body composition, as measured by dual-energy X-ray absorptiometry. We used repeated measures ANOVA to perform comparisons between times and groups. RESULTS: We evaluated 28 DMPA users and 24 IUD users who completed the 12-month follow-up. We observed that FT4 levels were higher at 12 months (compared to baseline) in the DMPA group (p < .0001) and that FT4/FT3 ratio had increased in both groups. Additionally, at 12 months, total body mass had increased around 2 kg and lean mass increased in the DMPA group compared to the IUD group; there was also an increase in weight, BMI, total body mass, and fat mass when compared to baseline. CONCLUSIONS: No changes in thyroid function occurred that could explain the weight increase observed in DMPA users.

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.

Insulin resistance parameters in users of the injectable contraceptive depot medroxyprogesterone acetate during one year of use.

OBJECTIVES: The aim of the study was to assess insulin resistance parameters using successive homeostasis model assessment (HOMA) and clinical evaluations in healthy new users of depot medroxyprogesterone acetate (DMPA). METHODS: A prospective 12-month study was carried out to compare 31 DMPA users with 25 copper intrauterine device (Cu-IUD; TCu380A) users, matched for age (± 1 year) and body mass index (BMI; ± 1 kg/m(2)). Participants met the following criteria: age 18 to 40 years, BMI < 30 kg/m(2), fasting glucose < 5.5 mmol/l, 2-h glucose after a 75 g oral glucose load < 140 mg/dl. BMI, waist circumference, fasting glucose, fasting insulin and HOMA of insulin resistance (HOMA-IR) were evaluated at baseline and after 6 and 12 months of contraceptive use. Insulin resistance was defined as a HOMA-IR value > 2.7. RESULTS: The DMPA group showed significant increases in BMI, waist circumference, fasting insulin and HOMA-IR throughout the observation period in relation to baseline. Significant increases in BMI and waist circumference were observed in the DMPA group at 12 months compared with the Cu-IUD group. Five DMPA users had abnormal HOMA-IR values, three of whom had gained > 5 kg in weight at 12 months. CONCLUSIONS: HOMA-IR represents a useful tool to indicate changes in carbohydrate metabolism in non-obese DMPA users, especially when accompanied by measurement of clinical parameters such as BMI and waist circumference.

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.

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.

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 essential, as well as understanding the mechanisms of tumor progression and the conditions that indicate a worse prognosis. Assessment of the tumor microenvironment can allow us understand how the immune system organizes itself to contain neoplastic progression. Methods: We compared characteristics related to the lymphocytic subpopulations in the thyroid tumor microenvironment and lymph nodes in two groups, with and without lymph node metastatic involvement. Results: Of the 400 cases followed up at a thyroid cancer reference service, 32 were selected, of which, 13 cases did not present lymph node metastasis (N0 group) and 19 had lymph node involvement (N1 group). Clinical data were collected, and immunohistochemical reactions were performed for markers CD4, CD8, FoxP3, CD25, and CD20 in lymph nodes and peritumoral infiltrate. We found that the N1 group had larger tumor sizes, higher risk staging, higher frequency of extrathyroidal extension, shorter disease-free times, and higher expression of CD4+ T lymphocytes in lymph nodes; however, there was no difference in the expression of other markers or in the pattern of lymphocyte distribution in the lymph node. Conclusion: In cervical lymph nodes, the higher frequency of CD4+ T lymphocytes is related to the presence of metastasis. However, there were no differences in lymphocytic subpopulations in the thyroid tumor microenvironment. The absence of changes in unaffected lymph nodes could not predict any tumor behavior.

Lower proportion of intra-thyroidal B lymphocytes CD20+ associated to methimazole and lack of influence of iodide on lymphocyte subpopulations in Graves' disease.

Graves' disease (GD), an autoimmune thyroid disease, is one of the main autoimmune diseases in the general population. It is known that the pathophysiology of this disease may be related to immunological mechanisms dysregulation. These mechanisms can be influenced by GD therapies, such as iodide or antithyroid drugs (ATD). OBJECTIVE: Verify relation between clinical, biochemical and treatment modalities used prior to surgery and histopathological characteristics observed in total thyroidectomy products from patients previously diagnosed with Graves' disease. Furthermore, these data were related to composition of lymphocytic infiltrate in terms of proportions of lymphocytes CD4+, CD8+, CD25+ and CD20+. We aim to contribute to the understanding of the evolution pattern of GD, whose pathophysiology is not yet completely understood. METHODS: Cross-sectional study assessing thyroidectomy products for the presence of lymphocytic infiltrate, as well as the proportion and intensity of CD4+, CD8+, CD25+ and CD20+ markers. We selected 50 patients who underwent total or partial thyroidectomy in a tertiary service between 1996 and 2013 due to GD with histopathological confirmation. The control group (non-autoimmune disease group) consisted of 12 patients with histopathological data compatible with normal perilesional thyroid parenchyma. The intensity of lymphocytic infiltrate and immunohistochemical expression of the markers CD4+ (helper T lymphocytes), CD8+ (cytotoxic T lymphocytes), CD25+ (regulatory T lymphocytes) and CD20+ (B lymphocytes) were retrospectively evaluated and relationship with ultrasound, laboratory and clinical data was assessed. RESULTS: No differences were found in intensity, presence of lymphoid follicles, and expression of CD4+/CD8+/CD25+ in patients with GD who did or did not use ATD or iodide. In the group that did not use ATD, a higher proportion of CD20+ expression was found. The GD group was associated with hyperplastic epithelium and the control group was associated with simple epithelium. There was no difference in ultrasound thyroid volume between the groups. In GD patients with mild lymphocytic infiltrate, higher free thyroxin (FT4) levels were observed than those in patients with no infiltrate or moderate infiltrate. CONCLUSION: We found a lower proportion of intrathyroidal CD20+ B lymphocytes in patients under use of methimazole. However, no difference was observed in intrathyroidal lymphocyte subpopulations related to the short-term use of iodide. The understanding of thyroid autoimmunity, as well as identifying points of pharmacological modulation, are very important for advancement and improvement in treatments for these diseases.

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.

The influence of body mass index and low-grade systemic inflammation on thyroid hormone abnormalities in patients with type 2 diabetes.

Previous reports highlight the role of systemic inflammation in the genesis of non-thyroidal illness syndrome and type 2 diabetes mellitus (T2DM). Our objective was to assess whether body mass index and the low-grade systemic inflammation would be associated with changes in thyroid hormone metabolism in patients with type 2 diabetes. This was a cross-sectional study of 104 subjects; 52 patients with type 2 diabetes and 52 in a control group, paired by age, gender and body mass index. We measured total (T) and free (F) thyroxine (T4) and triiodothyronine (T3), reverse T3 (rT3), the ratios FT3/rT3, FT3/FT4 and FT4/rT3, clinical parameters (age, gender, diabetes duration and complications, body mass index, waist circumference, hypertension, HbA1c), and high sensitivity C-reactive protein. Patients with DM presented lower levels of TT4 (p=0.006), TT3 (p<0.001) and FT3 (p<0.001) and higher of FT4 (p<0.001), waist circumference (p=0.047) and C-reactive protein (p<0.001). Body mass index was inversely correlated with FT4 (p=0.036) and TT3 (p=0.008). C-reactive protein was positively correlated with rT3 (p=0.001) and inversely with FT4/rT3 (p<0.001) and FT3/rT3 (p=0.014). Body mass index was an independent predictor for FT4 (B=-0.011, p=0.029) and TT3 levels (B=-1.118, p=0.003). Inflammation predicted the FT4/rT3 ratio (B=-0.190, p<0.001). C-reactive protein (B=0.235, p<0.001) and body mass index (B=-0.008, p=0.047) were independent predictors for rT3. In conclusion, type 2 diabetes was associated with a low T3 state. Body mass index and the low-grade systemic inflammation are related to the non-thyroidal illness syndrome in these patients, possibly by altering the activity of peripheral deiodinases.

Computed tomography and magnetic resonance imaging approaches to Graves' ophthalmopathy: a narrative review.

Graves' ophthalmopathy (GO) affects up to 50% of patients with Graves' disease (GD) ranging from mild ocular irritation to vision loss. The initial diagnosis is based on clinical findings and laboratory tests. Orbital imaging, such as magnetic resonance imaging (MRI) and computed tomography (CT), is an important tool to assess orbital changes, being also useful for understanding disease progression and surgical planning. In this narrative review, we included 92 studies published from 1979 to 2020 that used either MRI and/or CT to diagnose and investigate GO, proposing new methods and techniques. Most of the methods used still need to be corroborated and validated, and, despite the different methods and approaches for thyroid eye disease (TED) evaluation, there is still a lack of standardization of measurements and outcome reports; therefore, additional studies should be performed to include these methods in clinical practice, facilitating the diagnosis and approach for the treatment of TED.

Ocular Surface Disease Related to the Inflammatory and Non-Inflammatory Phases of Thyroid Eye Disease.

Purpose: This study evaluated the ocular surface disease (OSD), especially dry eye disease (DED) parameters by combining qualitative and quantitative tools, including tear matrix metalloproteinase 9 (MMP-9), in patients with Graves' disease (GD) with and without Thyroid eye disease (TED). Patients and Methods: A total of 17 active TED, 16 inactive TED, 16 GD without ophthalmopathy, and 16 healthy controls were included. All patients were assessed with CAS, ophthalmometry, qualitative tear MMP-9, Ocular Surface Disease Index (OSDI), ocular surface staining, Schirmer test, meibography, tear meniscus height, conjunctival hyperemia, and non-invasive tear film break-up time. Patients were classified into three subtypes of DED: aqueous tear deficiency, meibomian gland dysfunction (MGD) and mixed dry eye. Results: Inactive TED was shown to be an associated factor with DED (odds ratio 14, confidence interval 2.24-87.24, p=0.0047), and presented more DED than healthy controls (87.5% versus 33.3%, p=0.0113). MGD was also more prevalent among these subjects than in healthy control (62.5% versus 6.7%; p=0.0273). No significant differences were found in other ophthalmological parameters, except for more intense conjunctival redness among active TED than GD without ophthalmopathy (p=0.0214). Qualitative MMP-9 test was more frequently positive in both eyes among active TED than in other groups (p < 0.0001). Conclusion: Patients with GD were symptomatic and presented a high prevalence of ocular surface changes and DED, particularly the subgroup with inactive TED. Tear MMP-9 detection was associated with active TED suggesting a relationship between ocular surface changes and the initial inflammatory phase of ophthalmopathy.

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.

Higher systemic inflammatory status and cardiovascular risk associated with Charcot arthropathy unrelated to infection or extremity amputation.

Purpose: People with diabetes and Charcot arthropathy have higher mortality than people with diabetes without this complication. Are the causes of this higher mortality exclusively infectious or of a cardiovascular origin? We aimed to study aspects related to cardiovascular risk and inflammation in a population of people with type 2 diabetes with and without Charcot arthropathy. Methods: A cross-sectional study was performed in people with diabetes and Charcot Eickenholtz III arthropathy, matched for sex and age, with two groups of people with diabetes without Charcot arthropathy with and without peripheral sensory-motor neuropathy, in the absence of active infection. All participants underwent clinical and laboratory evaluation at the time of the interview, and their cardiovascular risk was calculated according to the United Kingdom Prospective Diabetes Study (UKPDS) calculator. Results: We evaluated 69 people with type 2 diabetes (21 with Charcot arthropathy, 24 with diabetic peripheral neuropathy and 24 without this neuropathy), with a mean age between 57 and 61 years and with a diabetes duration of more than 10 years. Patients with Charcot arthropathy had a longer duration of diabetes; more frequency of dyslipidemia; and higher levels of uric acid, microalbuminuria and C-reactive protein than the other two groups. A total of 73.9% of the people evaluated had high or very high cardiovascular risk according to the UKPDS score. Conclusion: The people with type 2 diabetes presenting Charcot arthropathy had greater values of systemic inflammatory parameters, even in the chronic phase of the complication, with a higher risk of mortality unrelated to infections.

Childhood-Onset GH Deficiency versus Adult-Onset GH Deficiency: Relevant Differences Regarding Insulin Sensitivity.

The results of the studies on the pattern of insulin sensitivity (IS) are contradictory in patients with GH deficiency (GHD); however, the interference of the GHD onset stage, childhood or adulthood in the IS has not been assessed by euglycemic hyperinsulinemic clamp (EHC), a gold-standard method for the assessment of insulin sensitivity. In a prospective cross-sectional study, we assessed IS and body composition in 17 adults with hypopituitarism without GH replacement, ten with childhood-onset (COGHD) and seven with adulthood-onset (AOGHD) and compared them to paired control groups. COGHD presented higher IS (p = 0.0395) and a similar percentage of fat mass (PFM) to AOGHD. COGHD showed higher IS than the control group (0.0235), despite a higher PFM (0.0022). No differences were found between AODGH and the control group. In AOGHD and the control group, IS was negatively correlated with PFM (rs: −0.8214, p = 0.0234 and rs: −0.3639, p < 0.0344), while this correlation was not observed with COGHD (rs: −0.1152, p = 0.7514). Despite the higher PFM, patients with COGHD were more sensitive to insulin than paired healthy individuals, while patients with AOGHD showed similar IS compared to controls. The lack of GH early in life could modify the metabolic characteristics of tissues related to the glucose metabolism, inducing beneficial effects on IS that persist into adulthood. Thus, the glycometabolic findings in patients with COGHD seems to be not applicable to AOGHD.

Cardiovascular Autonomic Reflex Tests and 7 Heart Rate Variability Indices for Early Diagnosis of Cardiovascular Autonomic Neuropathy in Type 2 Diabetes Individuals.

BACKGROUND: Cardiovascular autonomic neuropathy (CAN) is a common complication of type 2 Diabetes mellitus (T2D), and prevalence varies according to the methodology used. CAN should be diagnosed in the subclinical stage when an intensive treatment of T2D could avoid the progression to irreversible phases. OBJECTIVE: Determine the prevalence of early involvement (EI) of CAN in T2D individuals comparing two methodologies. METHODS: This was a cross-sectional study that included 183 T2D individuals who were monitored in a Tertiary centre. The diagnosis of CAN was based on the results of four cardiovascular autonomic reflex tests (CARTs: expiration-inspiration index, Valsalva maneuver, orthostatic test, and changes in blood pressure after standing) and of seven heart rate variability (7HRV) indices (CARTs plus the spectral analysis). The findings were validated in an independent cohort comprised of 562 T2D individuals followed in a Primary care setting. RESULTS: With the use of 7HRV, 30.6% and 77.8% of individuals in the Tertiary and in the Primary centers, respectively, were classified as without CAN; 25.1% and 15.3% as EI and 44.3% and 6.9% as definitive CAN, respectively. The use of CARTs decreased the proportion of individuals without CAN in both centers (7.1% and 47%) and increased the frequency of EI (30.6% and 36.6%) and definitive CAN (62.3% and 16.4%), respectively. The concordance between both evaluated methodologies was weak. CONCLUSION: Higher proportions of T2D individuals were diagnosed with EI and with definitive CAN with the use of CARTs.