Patients' Persistent Symptoms, Clinician Demographics, and Geo-Economic Factors Are Associated with Choice of Therapy for Hypothyroidism by European Thyroid Specialists: The "THESIS" Collaboration.

Background: Hypothyroidism is common, however, aspects of its treatment remain controversial. Our survey aimed at documenting treatment choices of European thyroid specialists and exploring how patients' persistent symptoms, clinician demographics, and geo-economic factors relate to treatment choices. Methods: Seventeen thousand two hundred forty-seven thyroid specialists from 28 countries were invited to participate in an online questionnaire survey. The survey included respondent demographic data and treatment choices for hypothyroid patients with persistent symptoms. Geo-economic data for each country were included in the analyses. Results: The response rate was 32.9% (6058 respondents out of 17,247 invitees). Levothyroxine (LT4) was the initial treatment preferred by the majority (98.3%). Persistent symptoms despite normal serum thyrotropin (TSH) while receiving LT4 treatment were reported to affect up to 10.0% of patients by 75.4% of respondents, while 28.4% reported an increasing such trend in the past 5 years. The principal explanations offered for patients' persistent symptoms were psychosocial factors (77.1%), comorbidities (69.2%), and unrealistic patient expectations (61.0%). Combination treatment with LT4+liothyronine (LT3) was chosen by 40.0% of respondents for patients who complained of persistent symptoms despite a normal TSH. This option was selected more frequently by female thyroid specialists, with high-volume practice, working in countries with high gross national income per capita. Conclusions: The perception of patients' dissatisfaction reported by physicians seems lower than that described by hypothyroid patients in previous surveys. LT4+LT3 treatment is used frequently by thyroid specialists in Europe for persistent hypothyroid-like symptoms even if they generally attribute such symptoms to nonendocrine causes and despite the evidence of nonsuperiority of the combined over the LT4 therapy. Pressure by dissatisfied patients on their physicians for LT3-containing treatments is a likely explanation. The association of the therapeutic choices with the clinician demographic characteristics and geo-economic factors in Europe is a novel information and requires further investigation.

Assessment of Individual and Mixed Effects of Six Minerals on Thyroid Hormones in Chinese Pregnant Women.

The biosynthesis of thyroid hormones is essential for brain and neurological development. It requires iodine as a key component but is also influenced by other nutrients. Evidence for the combined nutrient status in relation to thyroid hormones during pregnancy is limited. We aimed to investigate the joint associations of iodine, selenium, zinc, calcium, magnesium and iron with maternal thyroid functions in 489 pregnant women from Hangzhou, China. Serum levels of six essential minerals and thyroid function parameters were measured during the first antenatal visit. Linear regression, quantile g-computation and Bayesian kernel machine regression were used to explore the individual and joint relationships between the six minerals and thyroid hormones. Linear regression analyses revealed that calcium was positively associated with free triiodothyronine (FT3). Zinc was positively associated with free thyroxine (FT4). Iodine was negatively associated with thyroid-stimulating hormone (TSH) and positively associated with FT3 and FT4. The quantile g-computation and BKMR models indicated that the joint nutrient concentration was negatively associated with TSH and positively associated with FT3 and FT4. Among the six minerals, iodine contributed most to thyroid function. The findings suggested that maintaining the appropriate concentration of minerals, either as individuals or a mixture, is important for thyroid health during pregnancy.

Assessment of the likelihood of hypothyroidism in dogs diagnosed with and treated for hypothyroidism at primary care practices: 102 cases (2016-2021).

BACKGROUND: There is a possibility that an incorrect diagnosis of hypothyroidism could be made in euthyroid dogs, and the prevalence of hypothyroidism in the dog population remains unknown. OBJECTIVES: To retrospectively assess the percentage of dogs diagnosed with, and treated for, hypothyroidism at first opinion practice which are likely to be hypothyroid and require levothyroxine supplementation. ANIMALS: One hundred two client-owned dogs were included in this study. MATERIALS AND METHODS: The computerized databases of 7 first opinion practices were searched to identify dogs treated with levothyroxine supplementation. Three European College of Veterinary Internal Medicine-Companian Animals (ECVIM-CA) diplomates independently assigned 1 of 4 clinical assessments to each case as follows: confirmed or likely hypothyroid, hypothyroidism suspected but not confirmed, hypothyroidism considered unlikely, and no reason to suspect hypothyroidism. They commented as to whether or not they thought levothyroxine supplementation was appropriate. RESULTS: The clinical assessments of "confirmed or likely hypothyroid"; "Hypothyroidism suspected but not confirmed"; "Hypothyroidism considered unlikely"; and "No reason to suspect hypothyroidism" was assigned respectively by Clinician 1 to 38.2%, 5.9%, 3.9%, and 52% of cases, by Clinician 2 to 48%, 22.6%, 22.6%, 6.9% of cases, and by Clinician 3 to 55.9%, 11.8%, 13.7% and 18.6%. Clinician 1, Clinician 2, and Clinician 3 considered levothyroxine supplementation not indicated in 58.8%, 52.9%, and 45.1% of cases, respectively. CONCLUSION: These results support the concern that hypothyroidism might be overly and incorrectly diagnosed in first opinion practice, and that thyroid function testing should be performed only in those dogs with a high pretest probability of the disease.

Longevity, demographic characteristics, and socio-economic status are linked to triiodothyronine levels in the general population.

The hypothalamic-pituitary-thyroid (HPT) axis is fundamental to human biology, exerting central control over energy expenditure and body temperature. However, the consequences of normal physiologic HPT-axis variation in populations without diagnosed thyroid disease are poorly understood. Using nationally representative data from the 2007 to 2012 National Health and Nutrition Examination Survey, we explore relationships with demographic characteristics, longevity, and socio-economic factors. We find much larger variation across age in free T3 than other HPT-axis hormones. T3 and T4 have opposite relationships to mortality: free T3 is inversely related and free T4 is positively related to the likelihood of death. Free T3 and household income are negatively related, particularly at lower incomes. Finally, free T3 among older adults is associated with labor both in terms of unemployment and hours worked. Physiologic TSH/T4 explain only 1.7% of T3 variation, and neither are appreciably correlated to socio-economic outcomes. Taken together, our data suggest an unappreciated complexity of the HPT-axis signaling cascade broadly such that TSH and T4 may not be accurate surrogates of free T3. Furthermore, we find that subclinical variation in the HPT-axis effector hormone T3 is an important and overlooked factor linking socio-economic forces, human biology, and aging.

Real Practice Assessment of Persistent Symptoms After Initiation of Levothyroxine.

OBJECTIVE: Levothyroxine (LT4) is the standard treatment for hypothyroidism. However, certain patients experience persistent symptoms even after achieving euthyroid status with LT4 therapy. We aimed to determine the frequency of persistent or new symptoms in patients with hypothyroidism after initiating LT4. METHODS: This retrospective study included patients with hypothyroidism who started on LT4 between January 2017 and December 2019 at Mayo Clinic in Rochester, Minnesota, USA. Five hundred patient charts were randomly selected for review. Patients with at least 1 documented follow-up encounter after LT4 initiation were evaluated for ≤3 follow-up visits regarding their biochemical status and symptoms. RESULTS: We included 356 patients, a majority of whom were female (66.6%), white (92.3%), and obese (71.9%), with an average age of 59.5 years. At the baseline visit, approximately one-half of the patients (177/356, 47.7%) reported hypothyroid symptoms, with fatigue being the most common symptom. During the follow-up periods, we observed that 17.8% (28/157), 17.9% (19/106), and 19.3% (11/57) of patients had normal thyroid stimulating hormone (TSH) values but persistent symptoms, while 12.3% (19/156), 19.9% (16/107), and 8.9% (5/56) had normal TSH values but new symptoms. Overall, during each respective follow-up period, 26.7% (42/157), 27.3% (29/106), and 28% (16/57) of patients experienced persistent or new symptoms alongside normal TSH values, with fatigue being the most constant symptom. CONCLUSION: Our findings indicate that approximately 1 in every 4 patients with hypothyroidism receiving LT4 therapy and achieving normal TSH levels experience persistent or new hypothyroid symptoms. The cause of these symptoms remains unclear, emphasizing the need for a better understanding of their underlying causes and the development of effective management strategies.

Assessment for bone health in patients with differentiated thyroid carcinoma after postoperative thyroid-stimulating hormone suppression therapy: a new fracture risk assessment algorithm.

Purpose: The fracture risk assessment tool (FRAX) is used to assess the 10-year risk of major site and hip fractures; however, whether this tool can be applied to patients receiving levothyroxine-based thyroid-stimulating hormone (TSH) suppressive therapy for postoperative differentiated thyroid cancer (DTC) patients is yet to be clarified. Methods and design: A total of 64 patients with DTC following thyroidectomy and oral levothyroxine for TSH suppression therapy and 30 gender- and age-matched controls were collected. The fracture risk was compared between the affected groups with different TSH levels. FRAX was used to calculate the fracture risk with and without bone mineral density (BMD). The TSH level was converted to an age-weighted score to estimate the fracture risk of postoperatively differentiated thyroid cancer patients. The sensitivity, specificity, and area under the AUC curve of the traditional FRAX and the new algorithm for osteoporosis diagnosis were compared. The dual-energy X-ray bone mineral density measurement T score was used as the gold standard to diagnose osteoporosis. Results: There were 24 patients in the T ≥ -1-2.5 group, 23 in the -2.5 < T < -1 group, and 17 in the T ≤ -2.5 group. The T score of BMD in the disease group was significantly lower than that in the control group (p < 0.05). The risk of MOF and hip fracture without a T score were significantly different under various TSH levels (p < 0.05). The area under the curve (AUC) of FRAX without BMD for predicting major osteoporotic fractures (PMOF) and major hip fractures (PHF) was 0.694 and 0.683, respectively. The cutoff values were 2.15% and 0.25%, respectively. The AUC of FRAX with BMD for PMOF and PHF was 0.976 and 0.989, respectively, and the cutoff values were 4.15% and 1.1%, respectively. The AUC of FRAX without BMD for PMOF and PHF was 0.708 and 0.72, respectively, and the cutoff values were 5.5% and 1.55%, respectively. Conclusions: FRAX is suitable for postoperative DTC patients after TSH suppressive therapy. In the absence of BMD, TSH weighted by age can improve the specificity of FRAX in the diagnosis of osteoporosis in this population.

Subclinical hypothyroidism in pregnancy - assessment of offspring thyroid status and mitochondrial robustness to stress.

Subclinical hypothyroidism's clinical implications on pregnancy are controversial. Consequently, thyrotropin (TSH) cutoff-values for pregnancy are continuously a subject for debate. In subclinical hypothyroidism, altered levels of thyroid hormones may affect mitochondrial function.Objectives were i) to analyze thyroid hormone levels in offspring of women with and without subclinical hypothyroidism ii) to analyze mitochondrial "robustness" in terms of MTG/TMRM ratio in pregnant women and their offspring in relation to thyroid function and iii) to perform differentiate analyses on different TSH thresholds to determine the importance of cutoff-values to results.Pregnant women were included by blood collections prior to a planned cesarean section, and cord samples were collected after delivery. Thyroid status (analyzed by Siemens Healthcare Diagnostics by an electrochemical luminescent immunoassay based on LOCI-technology) grouped the women and their offspring in euthyroid or subclinical hypothyroid, with groups established from previous recommended third-trimester cutoff-value (TSH > 3.0 mIU/L) and the recently recommended cutoff-value in Denmark (TSH > 3.7 mIU/L). Flow cytometric measurements of mitochondrial function in mononuclear blood cells with the fluorophores TetraMethylRhodamine Methyl Ester (TMRM) and Mitotracker Green (MTG) were used to evaluate mitochondrial robustness as the MTG/TMRM ratio.No significant differences in mitochondrial robustness between euthyroid and subclinical hypothyroid cohorts were observed, irrespective of TSH-cutoff applied. Maternal and cord MTG/TMRM ratios were positively correlated. Cord-TSH was elevated in subclinical hypothyroid offspring, independent of TSH cutoff applied. Cord-TSH was associated with maternal TSH-level, maternal smoking and cord arterial-pH.

Large method differences for free thyroid hormone assays in the hyperthyroid range can affect assessment of hyperthyroid status: Comparison of Abbott Alinity to Roche Cobas, Siemens Centaur and equilibrium dialysis LC-MS/MS.

BACKGROUND: Free T4 (FT4) determination is one of the most commonly performed biochemical tests in endocrinology. Treatment of thyroid dysfunctions is adjusted based on the severity of symptoms and biochemical test results. For Graves' hyperthyroidism, clinical guidelines recommend using FT4 as a (rough) guide to dose antithyroid drugs, together with other clinical information. It is well known that different platforms and methods give different FT4 results; however, large non-linear method differences at high FT4 concentrations are less well recognized. Current clinical guidelines do not make it clear that method differences in the hyperthyroid range can affect recommendations. METHOD: Serum samples from patients with very low (biochemically hypothyroid) to very high (hyperthyroid) concentrations of FT4 and/or free T3 (FT3) were analyzed using Abbott Alinity and compared to concentrations measured using Roche Cobas, Siemens ADVIA Centaur (FT4 only) and an in-house equilibrium dialysis liquid chromatography tandem mass spectrometry (LC-MS/MS) method. RESULTS: Alinity measured markedly lower FT4 and FT3 concentrations compared to the other methods, particularly at high FT4 concentrations. Regression analysis indicated that Alinity FT4 had a non-linear (curved) relationship to FT4 measured by the other methods. The method differences affected guideline-recommended treatments for hyperthyroidism. CONCLUSION: Measured free thyroid hormone concentrations are highly method-dependent, especially at high FT4 concentrations. Clinicians treating hyperthyroid patients should be aware that patients appear much less hyperthyroid from FT4-measurements performed using Alinity compared to Cobas or Centaur. Guideline-recommended antithyroid drug dosages based on FT4 (including multiples of the upper reference range) have to be adjusted to the FT4 method used. FT4 results from different methods should be clearly distinguished (e.g. separate lines) in medical records.

Levothyroxine Treatment Adequacy and Formulation Changes in Patients with Hypothyroidism: A Retrospective Study of Real-World Data from the United States.

Background: The prevalence of hypothyroidism (HT) has increased over time. To assess the effectiveness of treatment, we (1) studied thyrotropin (TSH) levels among patients receiving levothyroxine (LT4) and (2) determined the percentages of patients switching among LT4 formulations. Methods: Data on patients with HT receiving LT4 from the Optum™ Clinical and Claims Database were analyzed from March 2013 through February 2020. Eligible adult patients had ≥1 medical claim with an HT diagnosis and all patients were observed for ≥12 months. Patients included in Objective 1 were indexed on a randomly selected TSH result and had ≥2 results for TSH 1-15 months apart. Patients included in Objective 2 were indexed on a randomly selected LT4 pharmacy claim and had ≥2 LT4 claims ≥1 month apart and ≥1 claim during follow-up. Outcomes were the proportion of patients with low, normal, or high (<0.45, 0.45-4.5, or >4.5 mIU/L, respectively) TSH levels and the proportion of patients switching LT4 formulations, respectively. Data were stratified by age group, sex, and insurance type. All data reported were analyzed using descriptive statistics. Results: Of patients who were in the indexed TSH group, 81.1% [confidence intervals: 80.4-81.8; n/N = 9130/11,259] achieved normal TSH values. When stratified by age group, sex, and insurance type, ≥70% of patients in each of these subgroups exhibited normal mean TSH values at follow-up. For Objective 2 (N = 25,076), 24.9% (N = 6238) of the LT4-indexed group had ≥1 formulation switch in 12 months, of which 67.3% only switched once, and 41.4% (N = 10,370) had ≥1 formulation switch in up to 24 months. A significantly higher proportion of Medicare vs. commercially insured patients had switched formulations (26.2% vs. 23.1%, p < 0.001). Conclusions: Most LT4-treated patients maintain normal TSH levels, which is an improvement vs. previous reports. Continued physician engagement and patient education are advised to further reduce the number of patients who maintain off-target TSH levels. Contrary to clinical recommendations, about 25% of patients receiving LT4 switched formulations within 1 year, with >40% switching within 2 years; among patients who switched, most only switched once.

Hypothyroidism and Somatization: Results from E-Mode Patient Self-Assessment of Thyroid Therapy, a Cross-Sectional, International Online Patient Survey.

Background: Between 10% and 15% of hypothyroid patients experience persistent symptoms despite achieving biochemical euthyroidism. Unexplained persistent symptoms can be a sign of somatization. This is associated with distress and high health care resource use and can be classified as somatic symptom disorder (SSD). Prevalence rates for SSD differ depending on classification criteria and how they are ascertained, varying between 4% and 25%. As this has not been studied in hypothyroid patients before, the aim of this study was to document somatization in people with hypothyroidism and to explore associations with other patient characteristics and outcomes. Methods: Online, multinational cross-sectional survey of individuals with self-reported, treated hypothyroidism, which included the validated Patient Health Questionnaire-15 (PHQ-15) for assessment of somatization. Chi-squared tests with the Bonferroni correction were used to explore outcomes for respondents with a PHQ-15 score ≥10 (probable somatic symptom disorder [pSSD]) versus a PHQ-15 score <10 (absence of SSD). Results: A total of 3915 responses were received, 3516 of which contained the valid PHQ-15 data (89.8%). The median score was 11.3 (range 0-30 [confidence interval 10.9-11.3]). The prevalence of pSSD was 58.6%. Associations were found between pSSD and young age (p < 0.001), women (p < 0.001), not working (p < 0.001), having below average household income (p < 0.001), being treated with levothyroxine (LT4) (rather than combination of LT4 and L-triiodothyronine [LT3], LT3 alone, or desiccated thyroid extract) (p < 0.001), expression of the view that the thyroid medication taken did not control the symptoms of hypothyroidism well (p < 0.001), and with number of comorbidities (p < 0.001). pSSD was associated with respondent attribution of most PHQ-15 symptoms to the hypothyroidism or its treatment (p < 0.001), dissatisfaction with care and treatment of hypothyroidism (p < 0.001), a negative impact of hypothyroidism on daily living (p < 0.001), and with anxiety and low mood/depression (p < 0.001). Conclusions: This study demonstrates a high prevalence of pSSD among people with hypothyroidism and associations between pSSD and negative patient outcomes, including a tendency to attribute persistent symptoms to hypothyroidism or its treatment. SSD may be an important determinant of dissatisfaction with treatment and care among some hypothyroid patients.

Reference intervals for thyroid biomarkers to enhance the assessment of thyroid status in childhood and adolescence.

OBJECTIVES: The determination of assay-dependent upper and lower reference limits (URL, LRL) of free triiodothyronine (FT3), free thyroxine (FT4), and thyroid stimulating hormone (TSH) during childhood and adolescence, is challenging. METHODS: Thyroid hormones were measured via the Abbott Alinity system in 502 euthyroid children partitioned in the following age groups: ≤2, 2.1-10, and 10.1-18 years. The 97.5th and 2.5th percentiles (URL and LRL) were derived according to CLSI EP28- A3c guidelines. Quantile regression models were used to assess: (a) 90% confidence intervals of the URL and LRL, (b) the effect of age on URL and LRL within each age class and on overall age range, (c) the difference between the URLs and LRLs estimated for each age partition with an estimate of the confidence interval divided by the reference interval being derived (CI/RI). RESULTS: The CI/RI for the LRLs are smaller as compared to the URLs, except for FT4 for the 2.1-10 years age group. Considering the CI/RI and the overlap between CIs across the three age groups, one single LRL might be considered for TSH, FT3 and FT4 between 0 and 18 years. However, for the URL, there was a noticeable decrease in the URL over the 3 age groups for all three biomarkers, with there being no overlap in CIs for the URL between the ≤2 vs. the 10.1-19 years age groups. CONCLUSIONS: A common LRL for TSH, FT4 and FT3 for patients aged ≤18 years may be utilized when these biomarkers are measured with the Alinity system. For the URLs the use of age-specific URLs for these biomarkers is recommended.

Association Between Subclinical Thyroid Dysfunction and Fracture Risk.

Importance: Clinical hyperthyroidism accelerates bone resorption without compensatory bone formation, reducing bone density and increasing the risk of fracture. The association between subclinical hyperthyroidism and fracture risk is less clear. Objective: To investigate the association of endogenous subclinical thyroid dysfunction and fracture risk, independent of clinical confounders. Design, Setting, and Participants: This cohort study included 10 946 participants from the Atherosclerosis Risk in Communities Study, an ongoing prospective cohort study of community-dwelling individuals conducted from 1987-1989 through December 31, 2019, in Washington County, Maryland; Forsyth County, North Carolina; Jackson, Mississippi; and the suburbs of Minneapolis, Minnesota. Participants were not taking thyroid medications and had no history of fractures. Exposures: Thyrotropin and free thyroxine levels were measured at visit 2 (1990-1992). Subclinical hyperthyroidism was defined as a thyrotropin level lower than 0.56 mIU/L, subclinical hypothyroidism as a thyrotropin level higher than 5.1 mIU/L, and euthyroidism as a thyrotropin level of 0.56 to 5.1 mIU/L, with normal free thyroxine levels from 0.85 to 1.4 ng/dL. Main Outcomes and Measures: Incident fracture was ascertained using hospitalization discharge codes through 2019 and linkage to inpatient and outpatient Medicare claims through 2018. Results: Of 10 946 participants (54.3% women; mean [SD] age, 57 [5.7] years), 93.0% had euthyroidism, 2.6% had subclinical hyperthyroidism, and 4.4% had subclinical hypothyroidism. During a median follow-up of 21 years (IQR, 13.0-27.3 years), there were 3556 incident fractures (167.1 per 10 000 person-years). The adjusted hazard ratios of fracture were 1.34 (95% CI, 1.09-1.65) for those with subclinical hyperthyroidism and 0.90 (95% CI, 0.77-1.05) for those with subclinical hypothyroidism compared with individuals with euthyroidism. Among those with normal free thyroxine levels, thyrotropin levels in the lower-than-normal range were significantly associated with higher fracture-related hospitalization risk; fracture risk was greater among individuals with thyrotropin concentrations below 0.56 mIU/L. Conclusions and Relevance: This community-based cohort study suggests that subclinical hyperthyroidism was an independent risk factor associated with fracture. The increased risk for fracture among individuals with a thyrotropin level lower than 0.56 mIU/L highlights a potential role for more aggressive screening and monitoring of patients with subclinical hyperthyroidism to prevent bone mineral disease.

The assessment of fetal cardiac output in maternal hypothyroidism under levothyroxine treatment.

OBJECTIVE: In this study, we investigated whether maternal hypothyroidism has a role in the cardiac output (CO) of the fetus or not. METHODS: Pregnant women between 33 and 37 gestational weeks known to have hypothyroidism and using levothyroxine were accepted as the case group. Gestational age-matched healthy euthyroid pregnant women constituted the control group. Fetal echocardiography was performed. Diameters and the velocity waveform of the pulmonary artery (PA) and aortic valves were measured. Velocity time integral (VTI) was also measured from the ventricular outflow tract. CO was calculated using VTI × π (Aortic Valve or Pulmonary Valve diameter/2) 2 × heart rate formula. RESULTS: The aortic and PA annulus were measured larger in the control group. (p = .003, p = .005, respectively). Furthermore, the right and left CO of the case group were lower than the control group. Whereas the mean combined CO (ml/min) of the case group was 674.8 ± 146.2, it was 827.8 ± 167.9 in the control group (p < .001). Additionally, a negative correlation was observed between thyroid-stimulating hormone and aortic VTI (r:-.480; p:.006). CONCLUSION: The findings of our study suggest that the CO of the fetus may be affected by maternal hypothyroidism.

The application of new concepts of the assessment of the thyroid state to pregnant women.

Recently proposed concepts regarding the nature and assessment of the thyroid state have provided a model more consistent with empiric evidence. It now appears likely that there are no such entities as thyroid set points and individual euthyroidism. Rather than there being discrete thyroid states, peripheral organ parameters are associated with thyroid function in a continuous manner. Thyroid hormone levels and, in particular, levels of free thyroxine now appear to be superior to thyrotropin levels as indicators of the thyroid state. Complicating the assessment of the correlations of the thyroid state with pregnancy outcomes are the contribution of the placenta to maternal thyroid function, fetal thyroid development, the multiple potential pathways to any particular outcome, the likely presence of small critical periods of time, the differing genetics of fetal and maternal tissues, and the unreliability of thyroid hormone assays. Nevertheless, there is no apparent reason for there to be a change in pregnancy to the basic principles of thyroid hormone action. The relationships between mild abnormalities of the thyroid state and pregnancy outcomes and the value of treating such mild abnormalities remain uncertain and controversial. The evidence suggests that further investigation of these clinical questions might better be based on thyroid hormone, particularly free thyroxine, levels. In the investigation of borderline low thyroid states, the categories of subclinical hypothyroidism and isolated hypothyroxinemia might both be abandoned with attention being directed to low free thyroxine levels regardless of the thyroid-stimulating hormone (TSH) levels. For these changes to occur, there would ideally be improvements in the assays for free thyroxine in pregnancy. The evidence suggests that, just as in the non-pregnant situation, pregnancy guidelines based on thyrotropin levels may need revision.

Comparative assessment of individual and mixture chronic toxicity of glyphosate and glufosinate ammonium on amphibian tadpoles: A multibiomarker approach.

The aim of the present study was to assess the ecotoxicity of glyphosate and glufosinate ammonium mixtures on amphibian tadpoles and the potential impact of mixture in aquatic ecosystems health. The bonding properties of the mixture based on computational chemistry and an experimental bioassay on morphology, DNA damage and biochemical biomarkers on tadpoles of the common toad Rhinella arenarum were studied. The results of the density functional theory analysis showed trends of the pesticides clustering to form exothermic mixtures, suggesting the likelihood of hot-spots of pesticides in real aquatic systems. In addition, biological effects of individual pesticides and the mixture were studied on tadpoles over 45 days-chronic bioassay. The bioassay consisted of four treatments: a negative control (CO), 2.5 mg L-1 of a glyphosate-based herbicide (GBH), 2.5 mg L-1 of a glufosinate ammonium-based herbicide (GABH) and their 50:50 (% v/v) mixture (GBH-GABH). Morphological abnormality rates were significantly higher in all herbicide treatments with respect to CO at 48 h of exposure. Abdominal edema was the most frequent type of abnormality recorded at 48 h, 10 and 45 days of exposure. DNA damage was recorded in all herbicides treatments. Thyroxin increased only in GABH treatment. Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) significantly increased in GBH treatment, indicating a GBH-neurotoxic effect. Glutathione S-transferase decreased in GABH and GBH-GABH treatments, while catalase decreased in individual GBH and GABH treatments. Overall, teratogenicity, DNA damage, hormonal disruption (T4), and oxidative stress were greater in GABH-treated tadpoles than GBH-treated tadpoles. This study also highlights the robust chemical interaction between the active ingredients of both herbicides, which is reflected on antagonisms in most of analyzed biomarkers, as well as potentiation and additivity in others. Based on our results, the GABH had a higher toxicity than GBH for amphibian tadpoles.

The Impact of Hypothyroidism on Satisfaction with Care and Treatment and Everyday Living: Results from E-Mode Patient Self-Assessment of Thyroid Therapy, a Cross-Sectional, International Online Patient Survey.

Background: Hypothyroid patients often report dissatisfaction and poor quality of life. This survey explored the impact of hypothyroidism on patient satisfaction, everyday living, experiences with health care professionals, and influence of demographic and socioeconomic factors. Methods: Cross-sectional questionnaire survey targeting an international population of hypothyroid patients. Multilevel regression modeling was used for analyses. Results: The total number of responses was 3915 from 68 countries. Satisfaction with care and treatment was not associated with type of treatment for hypothyroidism. Having no confidence and trust in health care professionals was strongly associated with dissatisfaction (p < 0.001). Controlling for all other variables, significant differences were found among satisfaction rates between countries. A weak inverse relationship was found between satisfaction with care and treatment and impact on everyday living (p < 0.001). Respondents taking levothyroxine (LT4) alone were more likely to report a positive impact on everyday living (pooled odds ratio 2.376 [confidence interval: 0.941-5.997]) than respondents taking liothyronine-containing treatments. Conclusions: Low levels of satisfaction with care and treatment for hypothyroidism were strongly associated with lack of confidence and trust and negative experiences with health care professionals. Differences in responses between countries were noted, implying the potential influence of national health care systems, socioeconomic and cultural factors. Contrary to widespread anecdotes in social media, this large-scale survey shows no association between type of treatment for hypothyroidism and patient satisfaction, as well as better outcomes on everyday living associated with LT4, compared with liothyronine-containing treatments.

Novel recombinant human thyroid-stimulating hormone in aiding postoperative assessment of patients with differentiated thyroid cancer-phase I/II study.

PURPOSE: Thyroid hormone withdrawal (THW) inevitably induced hypothyroidism in patients with differentiated thyroid cancer (DTC), and we aimed to evaluate the safety and efficacy of a novel recombinant human thyroid-stimulating hormone (rhTSH, ZGrhTSH) as an alternative of THW in China. METHODS: Totally, 64 DTC patients were enrolled with 24 in the dose-escalation cohort equally grouped into 0.9 mg × 1 day, 0.9 mg × 2 day, 1.8 mg × 1 day, and 1.8 mg × 2 day dosage, and 40 further enrolled into 0.9 mg × 2 day dose-expansion cohort. All patients underwent both ZGrhTSH phase and levothyroxine (L-T4) withdrawal phase for self-comparison in terms of TSH levels, the radioactive iodine (RAI) uptake, stimulated thyroglobulin level, and the quality of life (QoL). RESULTS: In ZGrhTSH phase, no major serious adverse events were observed, and mild symptoms of headache were observed in 6.3%, lethargy in 4.7%, and asthenia in 3.1% of the patients, and mostly resolved spontaneously within 2 days. Concordant RAI uptake was noticed in 89.1% (57/64) of the patients between ZGrhTSH and L-T4 withdrawal phases. The concordant thyroglobulin level with a cut-off of 1 µg/L was noticed in 84.7% (50/59) of the patients without the interference of anti-thyroglobulin antibody. The QoL was far better during ZGrhTSH phase than L-T4 withdrawal phase, with lower Billewicz (- 51.30 ± 4.70 vs. - 39.10 ± 16.61, P < 0.001) and POMS (91.70 ± 16.70 vs. 100.40 ± 22.11, P = 0.011) scores which indicate the lower the better. Serum TSH level rose from basal 0.11 ± 0.12 mU/L to a peak of 122.11 ± 42.44 mU/L 24 h after the last dose of ZGrhTSH. In L-T4 withdrawal phase, a median of 23 days after L-T4 withdrawal was needed, with the mean TSH level of 82.20 ± 31.37 mU/L. The half-life for ZGrhTSH clearance was about 20 h. CONCLUSION: The ZGrhTSH held the promise to be a safe and effective modality in facilitating RAI uptake and serum thyroglobulin stimulation, with better QoL of patients with DTC compared with L-T4 withdrawal.

Assessment of Joint Impact of Iodine, Selenium, and Zinc Status on Women's Third-Trimester Plasma Thyroid Hormone Concentrations.

BACKGROUND: Iodine is essential for synthesizing thyroid hormones, but other micronutrients are also required for optimal thyroid function. However, there is a lack of data on combined micronutrient status in relation to thyroid hormones in pregnancy. OBJECTIVES: We aimed to assess the joint associations of iodine, selenium, and zinc status with plasma concentrations of thyroid hormones and thyroid-stimulating hormone (TSH) in pregnancy. METHODS: We included 531 pregnant women (aged 22-40 y) participating in a Swedish birth cohort who provided blood and spot urine samples in gestational weeks 27-33 (mean: 29). Associations of urinary iodine concentration (UIC), plasma selenium concentration, and plasma zinc concentration (measured by inductively coupled plasma mass spectrometry) with plasma hormone concentrations [total and free thyroxine (tT4, fT4), total and free triiodothyronine (tT3, fT3), and TSH] were explored with Bayesian kernel machine regression (BKMR; n = 516; outliers excluded) and multivariable-adjusted linear regression (n = 531; splined for nonlinear associations). RESULTS: Median (IQR) micronutrient concentrations were 112 µg/L (80-156 µg/L) for UIC, 67 µg/L (58-76 µg/L) for plasma selenium, and 973 µg/L (842-1127 µg/L) for plasma zinc; the former 2 median values were below recommended concentrations (150 µg/L and 70 µg/L, respectively). Mean ± SD TSH concentration was 1.7 ± 0.87 mIU/L, with 98% < 4 mIU/L. BKMR showed a positive trend of joint micronutrient concentrations in relation to TSH. Plasma zinc was most influential for all hormones but tT3, for which plasma selenium was most influential. In adjusted linear regression models, zinc was positively associated with tT4, tT3, and TSH, and <1200 µg/L also with fT4 and fT3. Selenium was inversely associated with fT3, and <85 µg/L with tT3. CONCLUSIONS: Pregnant women's plasma TSH concentrations in the early third trimester increased with increasing joint status of iodine, selenium, and zinc. Zinc and selenium were more influential than iodine for the hormone concentrations. Multiple micronutrients need consideration in future studies of thyroid hormone status.

Frequency, determinants and costs of thyroid function testing in a laboratory serving a large population.

Objective: To assess the rationale and frequency of thyroid function testing and to analyse factors that influence serum thyrotropin (TSH) levels. Patients, design and main outcome measures: Serum TSH levels were evaluated in a hospital laboratory serving a population of 604 000 in 2018. Patients on medications or with conditions affecting thyroid function were excluded. Frequency of thyroid function testing by age and sex was assessed and the relationship between serum TSH with potential predictor variables was analysed using ordinary least square regression analysis allowing for potential non-linearity. Results: Twenty-eight percent of the local population had their thyroid function tested at least once in 2018 with significant differences by sex (28.2% women vs 23.4% men) and by age groups, with less than 2% of <16-year-old people and more than 50% of >80-year-old people being tested. Most of the symptoms commonly attributed to thyroid dysfunction were not higher in the thyroid dysfunction groups. Serum TSH levels were higher in older people particularly after the age of 60 years, in women (by 0.1 mIU/L), during the early hours of the morning, and in winter and spring seasons. There was remarkable uniformity in the frequency of subclinical thyroid dysfunction, as well as substantial cost savings, if TSH reference intervals were recalculated across sexes, age groups, time-periods and seasons. Conclusions: Serum TSH is frequently tested in the population but is not a good discriminant of symptoms attributed to thyroid dysfunction. Furthermore, considering the influence of factors on TSH reference limits could significantly impact patient care and resource utilisation.