Resting Energy Expenditure and Cold-induced Thermogenesis in Patients With Overt Hyperthyroidism.

CONTEXT: Thyroid hormone (TH) is crucial for the adaptation to cold. OBJECTIVE: To evaluate the effect of hyperthyroidism on resting energy expenditure (REE), cold-induced thermogenesis (CIT) and changes in body composition and weight. METHODS: This was a prospective cohort study at the endocrine outpatient clinic of a tertiary referral center. Eighteen patients with overt hyperthyroidism were included. We measured REE during hyperthyroidism, after restoring euthyroid TH levels and after 3 months of normal thyroid function. In 14 of the 18 patients, energy expenditure (EE) was measured before and after a mild cold exposure of 2 hours and CIT was the difference between EEcold and EEwarm. Skin temperatures at 8 positions were recorded during the study visits. Body composition was assessed by dual X-ray absorption. RESULTS: Free thyroxine (fT4) and free triiodothyronine (fT3) decreased significantly over time (fT4, P = .0003; fT3, P = .0001). REE corrected for lean body mass (LBM) decreased from 42 ±â€…6.7 kcal/24 hour/kg LBM in the hyperthyroid to 33 ±â€…4.4 kcal/24 hour/kg LBM (-21%, P < .0001 vs hyperthyroid) in the euthyroid state and 3 months later to 33 ±â€…5.2 kcal/24 hour/kg LBM (-21%, P = .0022 vs hyperthyroid, overall P < .0001). fT4 (P = .0001) and fT3 (P < 0.0001) were predictors of REE. CIT did not change from the hyperthyroid to the euthyroid state (P = .96). Hyperthyroidism led to increased skin temperature at warm ambient conditions but did not alter core body temperature, nor skin temperature after cold exposure. Weight regain and body composition were not influenced by REE and CIT during the hyperthyroid state. CONCLUSION: CIT is not increased in patients with overt hyperthyroidism.

Interplay Between Thyroid Hormone Status and Pulmonary Hypertension in Graves' Disease: Relevance of the Assessment in Thyrotoxic and Euthyroid Patients.

Background: Graves' disease (GD) is the most common cause of hyperthyroidism and can cause cardiac changes, such as pulmonary hypertension. Methods: This is a prospective study in which we obtained demographic, clinical, laboratory data and characteristics of the GD, in addition to investigating cardiorespiratory function, focusing on the detection of pulmonary hypertension. Patients were separated into two groups: thyrotoxicosis and euthyroidism. Ninety patients with GD of both sexes, over 18 years of age, were included. The cardiorespiratory assessment included an echocardiographic evaluation, a questionnaire of specific symptoms, spirometry and a six-minute walk test. Results: The hyperthyroid group included 42 patients (47.73%) and the euthyroid group 46 patients (52.27%); 78 were women (86.67%). The prevalence of pulmonary hypertension between the hyperthyroidism (48.57%) and the euthyroidism (29.41%) groups was not different. Free thyroxine levels (FT4) (OR 1.266), higher left atrium volume (OR 1.113) and right ventricle diameter were associated with pulmonary hypertension. A direct correlation between FT4 with forced vital capacity (FVC) and forced expiratory volume in the first second (FEV1), as also an inverse correlation between initial oxygen saturation (SpO2) with diagnostic time and drop SpO2 with the ratio between the diastolic velocity E of the mitral flow and the diastolic velocity of the mitral ring (E/e') were observed in the euthyroid group. An inverse correlation between FT4 levels with walked distance as % of predicted value, and a direct correlation between E/e' ratio and walked distance as % of predicted value were observed in the hyperthyroid group. Conclusion: We emphasize the importance of a cardiorespiratory reassessment in GD, even after a long-term control of the thyrotoxic state, as we demonstrate that about 30% of these patients remain with PH and are subject to specific treatment.

Pitfalls in the assessment of gestational transient thyrotoxicosis.

Gestational transient thyrotoxicosis (GTT) is associated with direct stimulation of the maternal thyroid gland by human chorionic gonadotropin (hCG). It is characterized by slightly higher thyroid hormone and lower thyroid-stimulating hormone (TSH) levels in early pregnancy and mild or no symptoms. While GTT must be distinguished from Graves' disease (GD), which is associated with maternal and fetal complications, treated GD and new-onset GD in pregnancy are occasionally challenging to distinguish. Evaluating serum hCG levels and TSH receptor antibody (TRAb) titers can help, but the results are not irrefutable due to pregnancy-related immunosuppression. Moreover, GTT can follow unusual clinical courses in relation to some pregnancy complications. Excessive hCG production can cause severe GTT symptoms in patients with hyperemesis gravidarum, trophoblastic disease, or multiple pregnancies. Thyrotoxicosis can emerge beyond the second trimester in patients with gestational diabetes mellitus and mirror syndrome, because of delayed elevations in the hCG levels. Detailed knowledge about GTT is necessary for correct diagnoses and its appropriate management. This review focuses on the diagnosis of GTT, and, particularly, its differentiation from GD, and unusual clinical conditions associated with GTT that require comprehensive management.

Assessment of biotin interference in thyroid function tests.

The aim of the study was to systematically characterize the interference of biotin on thyroid function tests and biotin washout periods.Ten healthy adults were recruited with administration of 5 and 10 mg/d biotin for 7 days. Analyte concentrations of thyroid function tests were measured at baseline prior to starting biotin and from 2 hours to 2 days after withdrawal of 5 and 10 mg/d biotin. The outcomes were compared the baseline with the several points after taking biotin at Roche cobas e602, Beckman UniCel DxI 800, and Abbott Architect 2000 immunoassay platforms, respectively.Ingesting 5 or 10 mg/d of biotin for 7 days could produce positive or negative interference among the thyroid function tests at Roche cobas e602 and Beckman UniCel DxI 800 systems, but no interference on Abbott Architect 2000. Interference duration of 5 mg/d biotin for Roche cobas e602 and Beckman UniCel DxI 800 of thyroid function tests lasted for 8 hours, while 10 mg/d biotin interfered with Roche cobas e602 or Beckman UniCel DxI 800 for 1 day or 2 days.This study provides valuable guidance on biotin washout periods at doses common in over-the-counter supplements necessary to avoid false assay results.Trial registration: ChiCTR1800020472.

UCP2, SHBG, Leptin, and T3 Levels are Associated with Resting Energy Expenditure in Obese Women.

OBJECTIVE: The aim of this study was to investigate the association of Sex Hormone Binding Globulin (SHBG) with leptin, Triidothyronine (T3), and Uncoupling Protein 2 (UCP2) in obese women with low and normal Resting Energy Expenditure (REE) and to determine the role of these factors in the regulation of REE in obese women. METHOD: A total 49 subjects (25-50 years old) were selected. Anthropometric and body composition parameters and resting energy expenditure were measured. Fasting circulating leptin, T3, SHBG and UCP2 levels were measured. Subjects were divided into three groups: Group І (BMI>30 and low resting energy expenditure, 16 subjects), group II (BMI>30 and normal resting energy expenditure, 17 subjects), and group ІІІ (control group, 16 non-obese subjects). RESULT: It was found that obese subjects who had higher SHBG and leptin levels were at risk for high levels of UCP2. A significant association was found between T3 and REE. Obese subjects with higher concentrations of UCP2 and SHBG had decreased resting energy expenditure. A significant association was observed between SHBG and leptin in group І (r=0.90, p<0.0001) and group ІІ (r=0.83, p<0.0001). Moreover, a significant association was found between T3 and SHBG in group І (r=-0.69, P=0.003). CONCLUSION: Changes of the UCP2, leptin, and thyroid hormone (T3) levels may be related to SHBG levels. Thus, lower leptin and T3 levels may decrease SHBG in obese women. Therefore, lower SHBG, leptin, T3 and UCP2 levels may decrease the REE level in obese women.

A critical evaluation of thyroid hormone measurements in OECD test guideline studies: Is there any added value?

Recently several OECD test guidelines were updated to include thyroid hormone measurements for assessing endocrine disruptor potency, which led to an imperative need to align interpretation of these results by the different stakeholders. We therefore evaluated 124 repro screening studies, which showed in 38% of the studies a statistical significant finding for T4 in at least one treatment group, probably due to disturbances of normal homeostasis causing high variation. Consequently, for a thorough evaluation it is extremely important to take the historical control range into account. In conclusion, the current testing approach is not providing specific information needed to assess endocrine disruption, as too often a statistical significant finding is noted and as down-stream adverse effects are not evaluated. Therefore, major modifications are urgently needed. Instead of extending the in vivo experiments, it should be investigated if in vitro assessments will provide more relevant information on human endocrine disruptor potential.

The study protocol for a randomized, controlled trial of acupuncture versus a sham procedure versus standard care alone for the treatment of delirium in acutely hospitalized older adults with a medical illness.

BACKGROUND: Many hospitalized older adults experience delirium, but treatment options are limited. Acupuncture has been shown to improve cognitive function and reduce agitation in dementia. We hypothesize that acupuncture, when compared with a sham intervention, will reduce the duration and severity of delirium, normalize delirium biomarkers, and improve clinical outcomes related to delirium in acutely hospitalized older adults with a medical illness. METHODS: This three-arm, prospective, randomized, clinical trial will evaluate adults aged over 65 years who are acutely hospitalized to an internal-medicine ward and diagnosed with delirium or subsyndromal delirium. The 288 patients (96 in each of three groups) will be randomly allocated to receive either daily true acupuncture with usual care, a daily sham procedure with usual care, or usual care only in a 1:1:1 distribution for up to one week or until the patient is delirium-free for over 48 h. Other delirium and clinical interventions will remain unchanged. Delirium will be diagnosed using DSM-5 criteria and its severity will be assessed using the long Confusion Assessment Method Severity (CAM-S) tool. OUTCOMES: The primary study outcome will be the daily CAM-S score over 7 days between the three groups. Secondary outcomes will include time to first resolution of the delirium (over 7 days), the proportion of days spent delirium-free, daily antipsychotic use, daily pain scores, sleep quality, morning serum cortisol and T3 levels, and midnight urinary cortisol/creatinine ratio, all determined twice a week, and delirium-related complications. Hospital mortality, duration of hospital stay and functional status at discharge will also be compared between the three groups. Adverse events potentially related to acupuncture will be evaluated daily. The cost-effectiveness of acupuncture will be estimated. CONCLUSION: This novel randomized study will evaluate both the specific and the non-specific effects of acupuncture on delirium, and related outcomes, and its safety. Potential mechanism(s) of action for acupuncture in reducing delirium will be explored and healthcare-related costs estimated. Positive study results may prove pivotal in facilitating a multimodal, non-pharmacologic, integrative approach to delirium treatment among older, medical inpatients.

Assessment of the Relationship Between Genetic Determinants of Thyroid Function and Atrial Fibrillation: A Mendelian Randomization Study.

Importance: Increased free thyroxine (FT4) and decreased thyrotropin are associated with increased risk of atrial fibrillation (AF) in observational studies, but direct involvement is unclear. Objective: To evaluate the potential direct involvement of thyroid traits on AF. Design, Setting, and Participants: Study-level mendelian randomization (MR) included 11 studies, and summary-level MR included 55 114 AF cases and 482 295 referents, all of European ancestry. Exposures: Genomewide significant variants were used as instruments for standardized FT4 and thyrotropin levels within the reference range, standardized triiodothyronine (FT3):FT4 ratio, hypothyroidism, standardized thyroid peroxidase antibody levels, and hyperthyroidism. Mendelian randomization used genetic risk scores in study-level analysis or individual single-nucleotide polymorphisms in 2-sample MR for the summary-level data. Main Outcomes and Measures: Prevalent and incident AF. Results: The study-level analysis included 7679 individuals with AF and 49 233 referents (mean age [standard error], 62 [3] years; 15 859 men [29.7%]). In study-level random-effects meta-analysis, the pooled hazard ratio of FT4 levels (nanograms per deciliter) for incident AF was 1.55 (95% CI, 1.09-2.20; P = .02; I2 = 76%) and the pooled odds ratio (OR) for prevalent AF was 2.80 (95% CI, 1.41-5.54; P = .003; I2 = 64%) in multivariable-adjusted analyses. The FT4 genetic risk score was associated with an increase in FT4 by 0.082 SD (standard error, 0.007; P < .001) but not with incident AF (risk ratio, 0.84; 95% CI, 0.62-1.14; P = .27) or prevalent AF (OR, 1.32; 95% CI, 0.64-2.73; P = .46). Similarly, in summary-level inverse-variance weighted random-effects MR, gene-based FT4 within the reference range was not associated with AF (OR, 1.01; 95% CI, 0.89-1.14; P = .88). However, gene-based increased FT3:FT4 ratio, increased thyrotropin within the reference range, and hypothyroidism were associated with AF with inverse-variance weighted random-effects OR of 1.33 (95% CI, 1.08-1.63; P = .006), 0.88 (95% CI, 0.84-0.92; P < .001), and 0.94 (95% CI, 0.90-0.99; P = .009), respectively, and robust to tests of horizontal pleiotropy. However, the subset of hypothyroidism single-nucleotide polymorphisms involved in autoimmunity and thyroid peroxidase antibodies levels were not associated with AF. Gene-based hyperthyroidism was associated with AF with MR-Egger OR of 1.31 (95% CI, 1.05-1.63; P = .02) with evidence of horizontal pleiotropy (P = .045). Conclusions and Relevance: Genetically increased FT3:FT4 ratio and hyperthyroidism, but not FT4 within the reference range, were associated with increased AF, and increased thyrotropin within the reference range and hypothyroidism were associated with decreased AF, supporting a pathway involving the pituitary-thyroid-cardiac axis.

Assessment of hair cortisol in euthyroid, hypothyroid, and subclinical hypothyroid subjects.

PURPOSE: Hypothyroidism is associated with an increase in serum cortisol level while the long-term activity of hypothalamic-pituitary-adrenal (HPA) axis in hypothyroid, and subclinical hypothyroid (SCH) subjects has not been studied. This study aimed to assess the hair cortisol levels as a long-term activity of HPA axis in hypothyroid, SCH and a group of healthy adult subjects. Also, it aimed to examine the correlation of hair cortisol levels with hypothalamic-pituitary-thyroid (HPT) axis and anthropometric measures. METHODS: We prospectively evaluated a group of normal, SCH and hypothyroid subjects. Serum TSH, FT4, and FT3 were measured as a component of the HPT axis. Hair samples were collected, prepared, followed by extraction of hair cortisol and measurement in pg/mg of hair. Hair cortisol levels were compared in normal, SCH and hypothyroid groups and correlated with HPT axis and anthropometric data. RESULTS: A total of 65 healthy volunteers were analyzed, and the mean hair cortisol level was reported to be 17.38 pg/mg of hair. Hair cortisol level was slightly higher in the SCH subjects, 18.19 pg/mg of hair; however the difference was not significant. Compared to the euthyroid subject, a significantly higher hair cortisol level was recorded in the hypothyroid subjects, 24.17 pg/mg hair, p < .05. Hair cortisol was significantly and positively associated with each of the serum TSH, age, weight and BMI (p < .05). CONCLUSIONS: Overt hypothyroidism but not SCH is significantly associated with higher hair cortisol levels compared to normal subjects, and a significant relation between hair cortisol with HPT axis was found. Also, weight and BMI were positively correlated with hair cortisol level.

The relationship between resting energy expenditure and thyroid hormones in response to short-term weight loss in severe obesity.

BACKGROUND: Regulating thermogenesis is a major task of thyroid hormones (THs), and involves TH-responsive energetic processes at the central and peripheral level. In severe obesity, little is known on the relationship between THs and resting energy expenditure (REE) before and after weight loss. METHODS: We enrolled 100 euthyroid subjects with severe obesity who were equally distributed between genders. Each was examined before and after completion of a 4-wk inpatient multidisciplinary dieting program and subjected to measurement of thyroid function, REE, fat-free mass (FFM, kg) and percent fat mass (FM). RESULTS: Baseline REE was lower than predicted in 70 obese patients, and overall associated with BMI, FFM and FM but not thyroid-related parameters. By the study end, both BMI and REE decreased (5.5% and 4.1%, p<0.001 vs. baseline) and their percent changes were significantly associated (p<0.05), while no association related percent changes of REE and FFM or FM. Individually, REE decreased in 66 and increased in 34 patients irrespective of gender, BMI and body composition. Weight loss significantly impacted TSH (-6.3%), FT3 (-3.3%) and FT4 levels (3.9%; p<0.001 for all). By the study end, a significant correlation became evident between REE and FT4 (r = 0.42, p<0.001) as well as FT3 (r = 0.24, p<0.05). In stepwise multivariable regression analysis, however, neither THs nor body composition entered the regression equation for REE response to weight loss. CONCLUSIONS: In severe obesity, short-term weight loss discloses a positive relationship between REE and THs.

The effect of aggression I: The increases of metabolic cost and mobilization of fat reserves in male striped hamsters.

Aggression can benefit individuals by enhancing their dominance and thereby their ability to acquire and retain resources that increase survival or fitness. Engaging in aggressive behavior costs energy and how animals manage their energy budget to accommodate aggression remains unclear. We conducted three experiments to examine changes in physiological, behavioral and hormonal markers indicative of energy budget in male striped hamsters subject to resident-intruder aggression tests. Body temperature, metabolic rate and serum corticosterone levels significantly increased in resident hamsters immediately after the introduction of intruders. Energy intake did not change, but the metabolic rate of residents increased by 16.1% after 42-days of repeated encounters with intruders. Residents had significantly decreased body fat content and serum thyroxine (T4) levels, and a considerably elevated tri-iodothyronine (T3)/T4 ratio compared to a control group that had no intruders. Attack latency considerably shortened, and the number of attack bouts and total duration of attacks, significantly increased in residents on day 42 compared to day 1 of experiments. These findings may suggest that the conversion of T4 to T3 is involved in defensive aggression behavior. The mobilization of fat reserves resulting in lean body mass is probably common response to the increased metabolic cost of aggression in small mammals. Aggressive behavior, which is important for the successful acquisition and defense of resources, may be of significance for adaptation and evolution of metabolic rate.

Analysis of current thyroid function test ordering practices.

RATIONALE: Current guidelines recommend thyroid stimulating hormone (TSH) alone as the best test to detect and monitor thyroid dysfunction, yet free thyroxine (FT4) and free triiodothyronine (FT3) are commonly ordered when not clinically indicated. Excessive testing can lead to added economic burden in an era of rising healthcare costs, while rarely contributing to the evaluation or management of thyroid disease. OBJECTIVE: To evaluate our institution's practice in ordering thyroid function tests (TFTs) and to identify strategies to reduce inappropriate FT4 and FT3 testing. METHODS: A record of all TFTs obtained in the San Antonio Military Health System during a 3-month period was extracted from the electronic medical record. The TFTs of interest were TSH, FT4, thyroid panel (TSH + FT4), FT3, total thyroxine (T4), and total triiodothyronine (T3). These were categorized based on the presence or absence of hypothyroidism. RESULTS: Between August 1 and October 31, 2016, there were 38 214 individual TFTs ordered via 28 597 total laboratory requests; 11 486 of these requests were in patients with a history of hypothyroidism. The number (percent) of laboratory requests fell into these patterns: TSH alone 14 919 (52.14%), TSH + FT4 7641 (26.72%), FT3 alone 3039 (10.63%), FT4 alone 1219 (4.26%), TSH + FT4 + FT3 783 (2.74%), and others 996 (3.48%); 36.0% of TFTs ordered were free thyroid hormones. Projected out to a year, using Department of Defense laboratory costs, $317 429 worth of TFTs would be ordered, with free thyroid hormone testing accounting for $107 720. CONCLUSION: Inappropriate ordering of free thyroid hormone tests is common. In an era of rising healthcare costs, inappropriate thyroid function testing is an ideal target for efforts to reduce laboratory overutilization, which in our system, could save up to $120 000 per year. Further evaluation is needed to determine strategies that can reduce excessive thyroid hormone testing.

Adoption of TSH Reflex algorithm in an Italian clinical laboratory.

BACKGROUND: TSH Reflex is an automated diagnostic algorithm which follows the rule "If ... then", in which the initial determination of TSH is followed by the determination of fT4, and possibly of fT3, if TSH is not within the reference limits. The aim of our study was to evaluate the results of the introduction and implementation of the test "TSH Reflex", which started in late 2013 in the hospital of Grosseto, comparing the requests of thyroid hormones for external patients, in 2012, 2014 and 2015. METHODS: In our study we analyzed the number of thyroid tests prescribed in 2012, 2014 and 2015 and we calculated the increase in prescription of "TSH Reflex" from 2014 to 2015; the prescriptive appropriateness, after the introduction of the "TSH Reflex", through the ratios TSH/FT4, TSH/FT3 and the ratio "TSH Reflex"/TSH. Finally we calculated the total spending for the reagents in 2012, 2014 and 2015 and the consequent savings in euros (the costs of the reagents did not change during that time). RESULTS: Requests for TSH decreased by 4.6% in 2014, compared to 2012 and by 5.4% in 2015 compared to 2014, with a 9.8% reduction in 2015 compared to 2012. The requests for FT4 decreased by 11.5%, comparing 2014 with 2012, by 5.3% comparing 2015 with 2014, with a 16.2% reduction in 2015 compared to 2012. The requests for FT3 decreased by 13.3% in 2014 compared to 2012 and by 8.4% in 2015 compared to 2014, with a 20.6% reduction in 2015 compared to 2012. The appropriateness, evaluated the indicator TSH/FT4, increased by 7.6%, comparing 2014 with 2012, and remained unchanged in 2015. In 2012 71,134 euros were spent, 63,998 euros in 2014, 60,055 euros in 2015, resulting in a saving of € 11,079 in 2015 compared to 2012. The spending for "TSH Reflex" should be subtracted (1,964 Euros in 2015) from the previous savings. CONCLUSIONS: The improvement of the efficiency and the prescriptive appropriateness was better in 2014, the first year of implementation of the "TSH Reflex". The overall assessment suggests that the 2014 results are attributable to the letters that general practitioners received in December 2013, with a temporary increase of the use of the test. We need further analyses with the same indicators in order to assess the possibility of additional improvements in the future.

Assessment of thyroid function in intensive care unit patients by liquid chromatography tandem mass spectrometry methods.

OBJECTIVES: Patients with non-thyroidal illness syndrome have many abnormalities in thyroid hormone tests. Such patients have medical comorbidities associated with low serum proteins and are on multiple medications that interfere with thyroid hormone measurement by immunoassay platforms. It is unknown if these thyroid hormone measurements reflect physiologic conditions or if they are artifacts of testing methodology. METHODS: Fifty patients were selected from the intensive care unit (ICU) from our institution. Total and free thyroid hormones in plasma were measured by gold standard liquid chromatography-tandem mass spectrometry (LC-MSMS). The results were compared to the Roche Cobas 6000. Patient medical comorbidities and binding protein levels were assessed. RESULTS: Concentrations of total 3,5,5'-triidothyronine (TT3) and total thyroxine (TT4) were significantly more likely to be low by LC-MSMS compared to immunoassay. Free 3,5,5'-triidothyronine (FT3) levels were similar by immunoassay and LC-MSMS. However, FT4 concentrations were mildly elevated for many patients when measured by ultrafiltration LC-MSMS (19/50, 38%) compared to 1/50 (2%) when measured by immunoassay (p=0.0001). Decreased albumin and thyroxine binding globulin were common and patients were on an average of 11.7±5.0 medications, all factors known to interfere with results found on immunoassays. CONCLUSIONS: Marked discrepancies in thyroid hormone measurement were noted between reference LC-MSMS and a common immunoassay platform. It is hypothesized that T4 binding to low affinity albumin is displaced by several drugs, raising concentrations of FT4 by LC-MSMS compared to immunoassay, and that the immunoassay values are falsely decreased due to low binding proteins in our patient population.

An assessment of exposure and effects of persistent organic pollutants in an urban Cooper's hawk (Accipiter cooperii) population.

Among the stressors confronting urban wildlife, chemical contaminants pose a particular problem for high trophic feeding species. Previous data from fortuitous carcass collections revealed surprisingly high levels of persistent organic pollutants in raptor species, including the Cooper's hawk (Accipiter cooperii), from urbanized areas of southwestern British Columbia, Canada. Thus, in 2012 and 2013, we followed up on that finding by measuring POPs in blood samples from 21 adult and 15 nestling Cooper's hawks in Vancouver, a large urban area in southwestern Canada. Reproductive success and circulating thyroid hormones were measured to assess possible toxicological effects. Model comparisons showed concentrations of polychlorinated biphenyls (ΣPCBs) were positively influenced by the level of urbanization. Total thyroxin (TT4) was negatively associated with increases in ΣPCBs. Total triiodothyronine (TT3) was negatively associated with ΣPCBs and polybrominated diphenyl ethers (ΣPBDEs). The legacy insecticide, dieldrin, appeared to have some negative influence on reproductive success. There is some evidence of biochemical perturbation by PBDEs and lingering impact of legacy POPs which have not been used for at least 40 years, but overall Cooper's hawks have successfully populated this urban environment.

Development of Standard Reference Materials to support assessment of iodine status for nutritional and public health purposes.

The use of urinary iodine as an indicator of iodine status relies in part on the accuracy of the analytical measurement of iodine in urine. Likewise, the use of dietary iodine intake as an indicator of iodine status relies in part on the accuracy of the analytical measurement of iodine in dietary sources, including foods and dietary supplements. Similarly, the use of specific serum biomarkers of thyroid function to screen for both iodine deficiency and iodine excess relies in part on the accuracy of the analytical measurement of those biomarkers. The National Institute of Standards and Technology has been working with the NIH Office of Dietary Supplements for several years to develop higher-order reference measurement procedures and Standard Reference Materials to support the validation of new routine analytical methods for iodine in foods and dietary supplements, for urinary iodine, and for several serum biomarkers of thyroid function including thyroid-stimulating hormone, thyroglobulin, total and free thyroxine, and total and free triiodothyronine. These materials and methods have the potential to improve the assessment of iodine status and thyroid function in observational studies and clinical trials, thereby promoting public health efforts related to iodine nutrition.

Neurotoxicant exposure during pregnancy is a confounder for assessment of iodine supplementation on neurodevelopment outcome.

CONTEXT: The developing brain is vulnerable to iodine deficiency (ID) and environmental neuro-toxicants. OBJECTIVES: To assess neurocognitive development of children whose mothers have received (or not) iodine supplementation during pregnancy, in an area of borderline ID, while assessing in utero exposure to environmental neuro-toxicants. DESIGN/PATIENTS: Among 86 children born from normal euthyroid women who participated in our prospective interventional study on iodine supplementation (150 µg/day) started early in pregnancy, 44 (19 with iodine supplementation, 25 controls) were assessed at two years using the Bayley test. Information on parents' education and habits (smoking), and on child development was recorded. Thyroid tests at each trimester of pregnancy and on cord blood (CB) were available, as well as milk concentrations of selected environmental compounds known for their neurotoxicity, including heavy metals and PCBs. RESULTS: There was no difference in Bayley tests for children born to mothers with and without iodine supplementation, but sample size was small. Language and Social-Emotional Scales were negatively correlated with TBG at all times tested, while PCB 118 correlated negatively with all Language scales. Among maternal and CB thyroid tests, only CB thyroglobulin, the best marker of iodine status, correlated (negatively) with neurodevelopment scales (Motor and Expressive Language). CONCLUSIONS: This pilot study suggests that PCB118 has a negative impact on neurocognitive development, possibly mitigating the benefit of iodine supplementation in an area of borderline ID. We propose that exposure to environmental neurotoxicants should be taken into account when designing studies on the benefit of iodine supplementation in pregnancy. The potential interactions between TBG, environmental neurotoxicants and brain development warrant further studies.

ANIMAL PHYSIOLOGY. Exceptionally low daily energy expenditure in the bamboo-eating giant panda.

The carnivoran giant panda has a specialized bamboo diet, to which its alimentary tract is poorly adapted. Measurements of daily energy expenditure across five captive and three wild pandas averaged 5.2 megajoules (MJ)/day, only 37.7% of the predicted value (13.8 MJ/day). For the wild pandas, the mean was 6.2 MJ/day, or 45% of the mammalian expectation. Pandas achieve this exceptionally low expenditure in part by reduced sizes of several vital organs and low physical activity. In addition, circulating levels of thyroid hormones thyroxine (T4) and triiodothyronine (T3) averaged 46.9 and 64%, respectively, of the levels expected for a eutherian mammal of comparable size. A giant panda-unique mutation in the DUOX2 gene, critical for thyroid hormone synthesis, might explain these low thyroid hormone levels. A combination of morphological, behavioral, physiological, and genetic adaptations, leading to low energy expenditure, likely enables giant pandas to survive on a bamboo diet.

Association between Adult Stature and Energy Expenditure in Low-Income Women from Northeastern Brazil.

BACKGROUND: Perinatal undernutrition may lead to important metabolic adaptations in adult life, short stature being the most visible. The present study aimed to evaluate the association between stature and total energy expenditure of low-income women. METHOD: Women aged 19-45 years from low-income communities in Maceió-AL were recruited. A sample of 67 volunteers was selected and divided into either short stature (≤ 152.4 cm; n = 34) or non-short stature (≥ 158.7 cm; n = 33) group. Data on socioeconomic status, anthropometric variables, and hormonal profiles was collected. Total energy expenditure and body composition were assessed by the doubly labeled water technique with multiple points over 14 days. In addition, physical activity levels were measured with triaxial accelerometers and dietary intake data were collected using three 24-hour food records. RESULTS: The mean subject age was 30.94 years. Women of short stature had lower body weight and lean body mass compared to non-short women, but there were no differences in thyroid hormone concentrations or daily energy intake between the two groups. Short-stature women showed lower total energy expenditure (P = 0.01) and a significantly higher physical activity level (P = 0.01) compared to non-short women. However, the difference in total energy expenditure was no longer significant after statistical adjustment for age, lean body mass, and triiodothyronine concentrations. CONCLUSION: Women with short stature present the same energy intake, but lower total energy expenditure than non-short women, even with a higher physical activity level, which suggests that they are more prone to weight gain.

No role for tri-iodothyronine (T3) testing in the assessment of levothyroxine (T4) over-replacement in hypothyroid patients.

Tri-iodothyronine (T3) is a sensitive marker of endogenous hyperthyroidism. In levothyroxine (T4)-induced hyperthyroidism, there is no reason for T3 to be elevated, but this test is often requested in over-treated hypothyroid patients. This study investigated how informative T3 levels are in these patients. Our hypothesis is that T3 measurement would not add anything to the assessment of T4 over-replacement in primary hypothyroidism. Over a 15-week period, consecutive thyroid function test requests in patients on levothyroxine had T3 levels measured if thyroid-stimulating hormone (TSH) was below the reference range (RR; <0.27 miu/L) and free T4 was within or above the RR (12-22 pmol/L). Those with fully suppressed TSH (<0.02 mu/L) and high free T4 (>27 pmol/L) were defined as being over-replaced, while those with low, but measurable TSH and a normal free T4 were defined as unlikely to be over- replaced (control group). Receiver operating characteristic (ROC) curve analysis was used to assess the discriminant power of T3 to detect over-replacement. Of the 542 patients examined, 33 were included in the over-replaced group and 236 patients in the control group. A total of 273 patients were excluded for not fulfilling the criteria for either of these groups. In the over-replaced group, none had a raised T3. The most discriminant T3 level, using ROC curve analysis, was 1.6 nmol/L (RR=1.3-2.6 nmol/L), with a corresponding sensitivity and specificity of 58% and 71%, respectively (P=0.16). T3 levels bear little relation to thyroid status in patients on levothyroxine replacement, and normal levels can be seen in over-replaced patients. Measurement of T3 in this situation is of doubtful clinical value. WHAT'S ALREADY KNOWN ABOUT THIS TOPIC?: Thyroid function tests are the way that adequacy of levothyroxine replacement is determined. Where the test is available, T3 is often requested together with T4 and TSH by clinicians. The question is whether T3 measurement adds any further information. WHAT DOES THIS ARTICLE ADD?: The presented data supports the position that T3 measurement does not add anything to the interpretation of thyroid hormone levels in subjects with hypothyroidism on levothyroxine replacement therapy. Unnecessary testing could be avoided if this were more widely appreciated. In addition, over-replacement, with its attendant risks, would be more readily recognised and not wrongly excluded on the basis of a falsely reassuring normal T3 result.