Werner & Ingbar's the thyroid , Werner & Ingbar's the thyroid , کتابخانه دیجیتال جندی شاپور اهواز

Background: It has been advocated to apply individualized strategies to evaluate thyroid nodules due to the growing awareness that the pathogenesis of thyroid cancer is not uniform. Molecular markers in fine needle biopsies (FNBs) may be helpful for the diagnosis and management decisions. Unlike the detection of BRAF mutations, the clinical utility of rat sarcoma viral oncogene homolog (RAS) mutations has not been fully elucidated. This study aimed at presenting a real-world performance of RAS mutations in identifying thyroid malignancies, at investigating the nature of thyroid tumors carrying RAS mutations, and at providing an additional reference for interpreting how to utilize the presence of RAS mutations in the decision-making process of thyroid nodule management. Methods: Between February 2015 and December 2017, 1400 sequential thyroid biopsies were performed at Boston Medical Center. Of these, 546 FNBs were evaluated for RAS mutations by using a ThyroSeq next-generation sequencing panel. Nodules carrying RAS mutations were prospectively followed, and medical records were collected. Results: ThyroSeq successfully provided molecular information in 504 nodules; 173 with molecular alteration(s); and 80 positive for mutations in the Kirsten-, Neuroblastoma-, or Harvey-RAS genes. RAS gene mutations constituted up to 46.2% of the total molecular alterations found in the study. Fifty-six of the 80 RAS-positive nodules underwent surgery, 33 (58.9%) were confirmed to be benign, 7 (12.5%) were noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP), and 16 (28.6%) were thyroid carcinomas. The positive predictive value, negative predictive value, and accuracy of RAS mutations for identifying malignancies among cytologically indeterminate nodules were 25.5%, 89.7%, and 54.0% when NIFTP was not counted as cancer. A combination of RAS and other mutations increased the risk of malignancy. Twelve histopathologically proved RAS-only-positive malignant nodules all showed low-risk features and favorable prognosis. RAS isoforms added little assistance for predicting a malignancy and the response to therapy in our series. Conclusions:RAS mutations represent the most frequently detected genetic alterations in our series. RAS mutations, when occurring alone, are not helpful markers to identify malignancy among Bethesda III/IV cytologies, but may predict favorable behavior, and hence should be considered to guide initial management.

Objective: Iodine is a necessary nutrient for the synthesis of thyroid hormones and essential in human development. Being naturally deficient in iodine, Armenia launched a national universal salt iodization (USI) strategy in 2004. Although high rates of goiter continued to be reported, iodine status has not been studied since 2005. Therefore, this study sought to assess the current situation of population iodine nutrition in Armenia. Methods: We used a selective cross-sectional model to recruit three groups: school-age children (SAC), pregnant women (PW), and nonpregnant women of reproductive age (WRA) from each province. We collected casual urine and table salt samples from each participant, which were analyzed for iodine concentration. A repeat urine sample was collected in a subset of participants to adjust the results for within-person variation in iodine concentration. Group-wise urinary iodine concentrations (UICs) were compared with international reference criteria for iodine status. Results: Urine samples were collected from 1,125 participants from 13 different towns in Armenia; a total of 1,078 participants were included in the final analysis: 361 SAC (mean age, 10.5 years, 46.6% female), 356 PW (mean age, 26.1 years), and 361 WRA (mean age, 35.5 years). Population and geographically weighted median UIC were: SAC, 242 μg/L ([25th percentile] 203 to [75th percentile] 289 μg/L); PW, 226 μg/L (209 to 247 μg/L); WRA, 311 μg/L (244 to 371 μg/L). A total of 1,041 table salt samples were sufficient for laboratory analysis: 973 (93.4%) of the salt iodine measurements were within the national standard range of 40 ± 15 mg/kg. Conclusion: The results of household salt sampling indicated a successful USI strategy. While the present study did not achieve a truly representative sample of Armenia's population, the UIC results support the conclusion that iodine deficiency has not recurred and is not an underlying factor for any remaining high goiter prevalence in Armenia. Abbreviations: PW = pregnant women; SAC = school-age children; SI = salt iodine; UIC = urinary iodine concentration; USI = universal salt iodization; WHO = World Health Organization; WRA = women of reproductive age.

IntroductionEpoprostenol, a synthetic prostaglandin I2 (PGI(2)) analog, has been the mainstay of treatment for severe pulmonary arterial hypertension (PAH) for the last two decades. Treprostinil, another synthetic prostaglandin analog, and selexipag, an oral selective Inositol Phosphate (IP) prostacyclin receptor agonist, have also been approved for treatment of PAH. Prostacyclin and its analogs cause a variety of side effects in patients with PAH; however, thyroid dysfunction is rarely reported.MethodsAfter treating an index case of thyroid dysfunction occurring after initiation of epoprostenol, we reviewed our databases of PAH patients treated with epoprostenol, treprostinil or selexipag to identify the occurrence of this association.ResultsWe identified six cases of thyroid dysfunction in our cohort: five after initiation of an intravenous prostacyclin (epoprostenol) and one after initiation of an oral prostacyclin receptor agonist (selexipag). Four of the patients presented with hyperthyroidism and two with a large autoimmune goiter. Graves' disease was seen in three patients, Hashimoto's disease in two patients and thyrotoxicosis in one patient.ConclusionTherapy with medications targeting the prostacyclin pathway is a potential risk factor for the development of symptomatic thyroid disease.

BACKGROUND As iodine is a requisite micronutrient for infant brain development, infants are at risk for iodine deficiency during the weaning period when their diet transitions from milk (breast-milk, infant formula, or follow-on formula) to solid food. Dietary iodine intake during this weaning period is likely minimal, as the iodine content of commercial baby food is not regulated, and the addition of salt to baby food is not recommended. This study reports the current status of iodine nutrition among weaning infants in the United States. METHODS Subjects (n = 60; 50% Caucasian, 30% black) were infants <12 months of age who were fed any combination of formula and/or baby food. Samples of all formula and food consumed in the previous 24 hours and a spot urine sample from each infant were obtained for the measurement of iodine. The estimated quantities of ingested formula and baby food were summed from a food diary recorded by the infants' parents. RESULTS The mean age of the infants was 6.3 ± 3.5 months. The median urinary iodine concentration (UIC) was 117 μg/L (range 26.9-1302.8 μg/L). Estimated daily iodine intake obtained from the measured iodine content in infant formula/foods was 89 μg (range 0-288 μg). There was a positive correlation between the infants' UIC and the iodine content in the consumed foods (r = 0.4, p < 0.001). CONCLUSIONS Although the median UIC of infants fed a combination of infant formula and baby food would meet the criteria for iodine sufficiency in a larger sample, those consuming the lowest quartile of iodine-containing nutritional sources had a median UIC <100 μg/L.

was enriched with 'I-labeled T4 for 8 or more days, labeled T3 and tetraiodothyroacetic acid (Tetrac or TA4) were found in the serum to the extent of approximately 2-5% of total radioactivity, as assessed by unidimensional paper chromatography. The same results were obtained with a specially purified lot of radioactive T4 containing less than 0.1% T3 as a contaminant. The identities of the 'I-labeled T3 and TA4 were verified by two-dimensional chromatography as well as by specific patterns of binding in serum. The labeled T3 isolated was bound by albumin and by T4-binding globulin (TBG), but not by T4-binding prealbumin (TBPA); in contrast the labeled TA4 was bound by albumin and TBPA, but not by TBG. To exclude the possibility that the conversion of T4 to T3 was a peculiarity of the oral route of administraThis work was presented in part at the 51st Annual Meeting of the Endocrine Society, 28 June 1969, at the Americana Hotel, New York. Received for publication 7 November 1969 and in revised form 22 December 1969. tion, the sera of two additional patients were obtained 48 hr after 7-day courses of daily intravenous injections of a mixture of stable and 'I-labeled T4. Both stable and labeled T3 were likewise found in these sera. In contrast to earlier experiments in humans in which 'I-labeled T3 was not definitively demonstrated in serum after a single intravenous injection of 'I-labeled T4, the present findings are taken to provide conclusive evidence of the extrathyroidal conversion of T4 to T3 in man. These results raise once again the question of the extent to which the metabolic effect of T4 is mediated through the peripheral generation of T3.

Iodine is important for thyroid hormone synthesis, and iodine deficiency in pregnancy may impair fetal neurological development. As perchlorate and thiocyanate inhibit sodium-iodide symporter reducing the transport of iodine from circulation into the thyroid follicular cells, environmental exposure to these substances in pregnancy may impair maternal thyroid hormone synthesis. We aimed to explore the impact of perchlorate and thiocyanate exposure on thyroid status in a cohort of pregnant mothers from South West England.

Objective: We sought to assess the universal salt iodization (USI) strategy in Armenia by characterizing dietary iodine intake from naturally occurring iodine, salt-derived iodine in processed foods and salt-derived iodine in household-prepared foods.Design: Using a cross-sectional cluster survey model, we collected urine samples which were analysed for iodine and sodium concentrations (UIC and UNaC) and household salt samples which were analysed for iodine concentration (SI). SI and UNaC data were used as explanatory variables in multiple linear regression analyses with UIC as dependent variable, and the regression parameters were used to estimate the iodine intake sources attributable to native iodine and iodine from salt in processed foods and household salt.Setting: Armenia is naturally iodine deficient; in 2004, the government mandated a USI strategy.Subjects: We recruited school-age children (SAC), pregnant women (PW) and non-pregnant women of reproductive age (WRA).Results: From thirteen sites covering all provinces, sufficient urine and table salt samples were obtained from 312 SAC, 311 PW and 332 WRA. Findings revealed significant differences between groups: contribution of native iodine ranged from 81% in PW to 46% in SAC, while household salt-derived iodine contributed from 19% in SAC to 1% in PW.Conclusions: Differences between groups may reflect differences in diet. In all groups, household and processed food salt constituted a significant part of total iodine intake, highlighting the success and importance of USI in ensuring iodine sufficiency. There appears to be leeway to reduce salt intake without adversely affecting the iodine status of the population in Armenia.

Background: Prenatal exposure to per- and polyfluoroalkyl substances (PFASs) may disrupt maternal and neonatal thyroid function, which is critical for growth and neurodevelopment.Objectives: To examine associations of prenatal exposure to multiple PFASs with maternal and neonatal thyroid function.Methods: We studied 732 pregnant women and 480 neonates in Project Viva, a longitudinal pre-birth cohort in Boston, MA. We quantified six PFASs including perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS), and maternal thyroid hormones [thyroxine (T4), Free T4 Index (FT4I), thyroid stimulating hormone (TSH)] in plasma collected at a median 9.6 weeks gestation and neonatal T4 levels from post-partum heel sticks. We estimated associations of concentrations of single PFASs with thyroid hormone levels using covariate-adjusted linear regression models and assessed effects of exposure to multiple PFASs using multi-pollutant regression models.Results: PFASs were moderately to strongly correlated (rs: 0.19–0.74). In single-pollutant models, PFASs were not associated with maternal T4 or TSH, but PFOA, PFOS, perfluorohexane sulfonate (PFHxS), and 2-(N-methyl-perfluorooctane sulfonamido) acetate were inversely associated with maternal FT4I [e.g., -1.87% (95% CI: -3.40, -0.31) per interquartile (IQR) increase in PFOA]. Prenatal PFOS, PFOA, and PFHxS were inversely associated with T4 levels in male neonates [e.g. PFHxS, -0.46 µg/dL (95% CI: -0.83, -0.10)]. In multi-pollutant models, PFOA was suggestively inversely associated with maternal FT4I [-1.62% (-3.77, 0.57)]; in neonatal models, PFHxS [-0.36 (-0.75, 0.03)] and PFOA [-0.70 (-1.79, 0.37)] were suggestively inversely associated with T4 levels in males.Conclusions: Prenatal exposure to PFASs was inversely associated with maternal FT4I and T4 in male neonates, with evidence for confounding by PFAS coexposure. These results support the hypothesis that exposure to PFASs may influence maternal and neonatal thyroid function.

Objective:To conduct a more robust examination of perchlorate exposure on iodide uptake inhibition (IUI) using pooled data from four clinical studies of perchlorate exposure.Methods:To establish a response threshold for IUI, data were analyzed using segmented linear regression and benchmark dose (BMD) analysis.Results:Segmented linear regression applied to data for 69 subjects representing nine doses identified a breakpoint corresponding to a change in the slope of the dose-response relationship of 3.0mg/d perchlorate. The estimated BMD for a 20% decrease in iodine uptake was 2.3mg/d, with a lower 95% confidence interval limit of 1.6mg/d.Conclusions:A threshold dose for IUI from perchlorate exposure of 1.6 to 3.0mg/d (0.021 to 0.038mg/kgd) was estimated using two modeling approaches. These estimates are slightly higher than the lowest observed effect level of 0.02mg/kgd from the Greer Study.

BACKGROUND:Prenatal exposure to some per- and polyfluoroalkyl substances (PFASs) may disrupt maternal and neonatal thyroid function, which is critical for normal growth and neurodevelopment. OBJECTIVES:We examined associations of PFAS exposure during early pregnancy with maternal and neonatal thyroid hormone levels. METHODS:We studied 732 mothers and 480 neonates in Project Viva, a longitudinal prebirth cohort in Boston, Massachusetts. We quantified six PFASs, including perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), and maternal thyroid hormones [thyroxine (T4), Free T4 Index (FT4I), thyroid stimulating hormone (TSH)] in plasma samples collected at a median 9.6 wk gestation and neonatal T4 levels from postpartum heel sticks. We estimated associations of PFAS concentrations with thyroid hormone levels using covariate-adjusted linear regression models and explored effect measure modification by maternal thyroid peroxidase antibody (TPOAb) status and infant sex. RESULTS:PFAS concentrations were not associated with maternal T4, but PFOA, perfluorohexane sulfonate (PFHxS), and 2-(N-methyl-perfluorooctane sulfonamido) acetate (MeFOSAA) were inversely associated with maternal FT4I [e.g., -1.87% (95% confidence interval (CI): -3.40, -0.31) per interquartile (IQR) increase in PFOA]. PFAS concentrations [PFOA, PFOS, and perfluorononanoate (PFNA)] were inversely associated with TSH levels in TPOAb-positive women only. Prenatal PFOS, PFOA, and PFHxS concentrations were inversely associated with T4 levels in male [e.g., PFHxS, quartile 4 vs.1: -2.51μg/dL (95% CI: -3.99, -1.04 )], but not female neonates [0.40μg/dL (95% CI: -0.98, 1.79)]. CONCLUSIONS:In this study, prenatal exposure to some PFASs during early pregnancy was inversely associated with maternal FT4I and neonatal T4 in male infants. These results support the hypothesis that prenatal exposure to PFASs influences thyroid function in both mothers and infants. https://doi.org/10.1289/EHP2534.

Author(s): Seger, Christian D; He, Xuemei; Braverman, Lewis E; Yeh, Michael W; Bernet, Victor J; Singh, Ravinder J; Rhee, Connie M; Leung, Angela M

Context:Iodine deficiency is the leading cause of preventable neurodevelopmental delay in children worldwide and a possible public health concern in Haiti. Objective:To determine the prevalence of iodine deficiency in Haitian young children and its influence by environmental factors. Design:Cross-sectional study, March through June 2015. Setting:Community churches in 3 geographical regions in Haiti. Participants:299 healthy Haitian children aged 9 months to 6 years; one-third each enrolled in a coastal, mountainous, and urban region. Main Outcome Measures:Urinary iodide, serum thyrotropin (TSH), goiter assessment, and urinary perchlorate and thiocyanate. Results:Mean age was 3.3±1.6 years, with 51% female, median family income USD 30/week, and 16% malnutrition. Median urinary iodide levels were normal in coastal (145 μg/L, interquartile range [IQR] 97 to 241) and urban regions (187 μg/L, IQR 92 to 316), but revealed mild iodine deficiency in a mountainous region (89 μg/L, IQR 56 to 129), P < 0.0001. Grade 1 goiters were palpated in 2 children, but TSH values were normal. Urinary thiocyanate and perchlorate concentrations were not elevated. Predictors of higher urinary iodide included higher urinary thiocyanate and perchlorate, breastfeeding, and not living in a mountainous region. Conclusions:Areas of mild iodine deficiency persist in Haiti's mountainous regions. Exposure to two well-understood environmental thyroid function disruptors is limited.

Fallahi et al ( 1. Fallahi P. Ferrari S.M. Antonelli A. In patients with subclinical hypothyroidism while in therapy with tablet LT4, the liquid LT4 formulation is more effective in restoring euthyroidism. Endocr Pract. 2017; 23: 170-174 Abstract Full Text Full Text PDF PubMed Scopus (22) Google Scholar ) have performed an interesting observational, prospective study assessing the ability of comparable levothyroxine doses of tablet and liquid preparations in lowering serum thyroid-stimulating hormone (TSH) concentration in patients with subclinical hypothyroidism who are not ingesting potentially interfering medications and do not have gastrointestinal disorders that might potentially interfere with levothyroxine absorption. The authors ( 1. Fallahi P. Ferrari S.M. Antonelli A. In patients with subclinical hypothyroidism while in therapy with tablet LT4, the liquid LT4 formulation is more effective in restoring euthyroidism. Endocr Pract. 2017; 23: 170-174 Abstract Full Text Full Text PDF PubMed Scopus (22) Google Scholar ) studied hypothyroid individuals who were taking stable levothyroxine doses and had serum TSH concentrations ≤3 μU/mL on at least two separate determinations within 2 years prior to the study or serum TSH level at least 4 μU/mL or higher (assessed within 1 month prior to the study) in conjunction with normal serum free thyroxine (FT4) and free triiodothyronine (FT3) on two different occasions. They ( 1. Fallahi P. Ferrari S.M. Antonelli A. In patients with subclinical hypothyroidism while in therapy with tablet LT4, the liquid LT4 formulation is more effective in restoring euthyroidism. Endocr Pract. 2017; 23: 170-174 Abstract Full Text Full Text PDF PubMed Scopus (22) Google Scholar ) appropriately excluded patients who had Helicobacter pylori or atrophic gastritis, previous gastric or intestinal surgery, or bariatric surgery. Fallahi et al ( 1. Fallahi P. Ferrari S.M. Antonelli A. In patients with subclinical hypothyroidism while in therapy with tablet LT4, the liquid LT4 formulation is more effective in restoring euthyroidism. Endocr Pract. 2017; 23: 170-174 Abstract Full Text Full Text PDF PubMed Scopus (22) Google Scholar ) did an excellent job of examining and detailing the inclusion and exclusion criteria, even investigating unexplained anemia or dyspepsia and also performed serum antibody measurements to help exclude undiagnosed celiac disease and measured H. pylori antigen in feces. Patients taking medications that are known to interfere with levothyroxine absorption were also excluded.