A Horizontal and Longitudinal Study on the Changes of Aging Thyroid Function in Elderly Male Population.

OBJECTIVES: There are few follow-up studies on thyroid function in the same group for many years. Therefore, the purpose of this study was to retrospectively analyze the changes of thyroid function in a group of people for 8 years and to explore the changes of thyroid function in elderly men with normal thyroid function with age. METHODS: Reviewing the records of elderly men who underwent physical examination in the Beijing Hospital physical examination center from 2013 to 2020, 354 subjects were included in the study. According to age, they are divided into 4 groups. The differences in thyrotropin (TSH), anti-triiodothyronine (rT3), free triiodothyronine (FT3), and free thyroid hormone (FT4) among different age groups in initial time (2013) were compared. Longitudinal comparison of changes of thyroid function in the same age group for 8 years was compared too. RESULTS: At the initial time, age was negatively correlated with FT3 (r = 0.349, p < 0.001), positively correlated with rT3 and TSH (r = 0.182, p < 0.001, r = 0.212, p < 0.001), but not correlated with FT4. The results of eight years of analysis show that, for TSH, during the whole follow-up period, the TSH of the >80 years group was higher than that of the <60 years and 60-69 years groups, and the difference was statistically significant. The 70-79 age group was higher than the <60 years group at different time points, except for the age group <60 years. The other three groups showed an increasing trend with age, especially in the group of ≥80 years. For FT3, in 2013, the age ≥80 years group was significantly lower than that of the 70-79 years, 60-69 years, and <60 years old groups (p < 0.05). The analysis results at different time points in each age group showed a downward trend and then an upward trend. For FT4, there was no significant difference in FT4 among different age groups in 2013. Still, during the follow-up period, the age group ≥80 was lower than other age groups in 2019 and lower than the <60 years groups in 2014, 2015, 2019, and 2020, and the difference was statistically significant. The change rule of FT4 with the increase of age was not clear. For rT3, during the whole follow-up period, the rT3 of the >80 years group was higher than that of the <60 years and 60-69 years groups, and the difference was statistically significant. The analysis results at different time points in each age group showed a trend of rising first, then falling, and finally rising. After 2017, the rT3 of the 70-79 years and ≥80 years groups increased with age. CONCLUSIONS: The thyroid function index of elderly men changes with age. In transverse analysis, the value of TSH is the highest, and FT3 is the lowest in the group ≥80 years old. There are differences between the changes in the longitudinal analysis and the results of the horizontal analysis. Therefore, the law of thyroid function changing with age in different individuals is not the same as that of the same individual with age, which should be paid more attention in medical research and clinical diagnosis and treatment.

Free triiodothyronine to free thyroxine ratio as a marker of poor prognosis in euthyroid patients with acute coronary syndrome and diabetes after percutaneous coronary intervention.

Objectives: In recent years, the free triiodothyronine/free thyroxine (FT3/FT4) ratio, a new comprehensive index for evaluating thyroid function, which could reflect thyroid function more stably and truly than serum thyroid hormone level, has been demonstrated to correlate with the risks of diabetes and cardiovascular disease in euthyroid adults. However, the correlation between thyroid hormone sensitivity and long-term prognosis in euthyroid patients with acute coronary syndrome (ACS) and diabetes after percutaneous coronary intervention (PCI) remains unclear. Methods: A total of 1,786 euthyroid patients with ACS who successfully underwent PCI at Beijing Anzhen Hospital from August 2021 to April 2022 were included in our study, which was divided into three groups according to tertiles of thyroid hormone sensitivity index. Cox regression, Kaplan-Meier, and receiver operating characteristic analyses were applied to analyze the associations between the FT3/FT4 ratio with ACS and diabetes after PCI. Results: Our analysis indicated that a lower level of FT3/FT4 ratio in euthyroid patients with acute coronary syndrome (ACS) and diabetes after PCI showed significantly higher incidences of major adverse cardiac and cerebrovascular events (MACCE) when compared with a higher level of FT3/FT4 ratio. After adjusting for other covariates, patients with a lower level of FT3/FT4 ratio were negatively associated with the risk of MACCE than those with a higher level of FT3/FT4 ratio (adjusted OR =1.61, 95% CI 1.05-2.47, P = 0.028). In subgroup analyses, individuals were stratified by age, sex, BMI, ACS type, hypertension, and dyslipidemia, showing that there were no significant interactions between the FT3/FT4 ratio and all subgroups for MACCE. In addition, the FT3/FT4 ratio performed better on ROC analyses for cardiac death prediction [area under the curve (AUC), 0.738]. Conclusion: A reduced level of FT3/FT4 ratio was a potential marker of poor prognosis in euthyroid patients with ACS and diabetes after PCI.

Higher serum free thyroxine levels are associated with increased risk of hip fractures in older men.

Overt and subclinical hyperthyroidism are associated with an increased fracture risk, but whether thyroid hormones are associated with fracture risk in individuals with normal thyroid-stimulating hormone (TSH) has mostly been investigated in women. Therefore, we investigated if serum levels of free thyroxine (FT4) or TSH are associated with fracture risk in Swedish men. We followed (median 12.2 yr) elderly men (n = 1825; mean age 75, range 69-81 yr) participating in the Gothenburg and Malmö subcohorts of the prospective, population-based MrOS-Sweden study. The statistical analyses included Cox proportional hazards regression. Men receiving levothyroxine treatment were excluded. In our total cohort, serum FT4 (per SD increase) was associated with increased risk of major osteoporotic fractures (MOFs; n = 479; fully adjusted hazard ratio [HR] 1.14, 95% CI, 1.05-1.24) and hip fractures (n = 207; HR 1.18, 95% CI, 1.04-1.33). Also, in men with normal TSH (n = 1658), FT4 (per SD increase) was significantly associated with increased risk of MOF and hip fractures. Furthermore, men in the highest FT4 quartile had a 1.5-fold increase in hip fracture risk compared with men in the three lower FT4 quartiles, both in the total population and in men with normal TSH (fully adjusted: HR 1.45, 95% CI, 1.04-2.02 and HR 1.51, 95% CI, 1.07-2.12, respectively). In contrast, the risk of MOF was not statistically different in the highest FT4 quartile compared with the three lower FT4 quartiles. Finally, serum TSH was not associated with fracture risk after full adjustment for covariates. In conclusion, serum FT4, but not serum TSH, is a predictor of hip fracture risk in elderly Swedish men. Additionally, there was an association between FT4 (per SD increase) and the risk of MOF.

Urinary haloacetic acid concentrations and thyroid function among women: Results from the TREE study.

BACKGROUND: Disinfection byproducts (DBPs) have been shown to impair thyroid function in experimental models. However, epidemiological evidence is scarce. METHODS: This study included 1190 women undergoing assisted reproductive technology (ART) treatment from the Tongji Reproductive and Environmental (TREE) cohort from December 2018 to August 2021. Serum thyrotropin (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) were measured as indicators of thyroid function. FT4/FT3 and TSH/FT4 ratios were calculated as markers of thyroid hormone homeostasis. Dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA), the two most abundant HAAs, in urine were detected to assess individual DBP exposures. RESULTS: After adjusting for relevant covariates, positive associations were observed between urinary TCAA concentrations and serum TSH and TSH/FT4 levels (e.g., percent change = 5.82 %, 95 % CI: 0.70 %, 11.21 % for TSH), whereas inverse associations were found for serum FT3 and FT4 (e.g., percent change = -1.29 %, 95 % CI: -2.49 %, -0.07 % for FT3). There also was a negative association between urinary DCAA concentration and serum FT4/FT3 (percent change = -2.49 %, 95 % CI: -4.71 %, -0.23 %). These associations were further confirmed in the restricted cubic spline and generalized additive models with linear or U-shaped dose-response relationships. CONCLUSION: Urinary HAAs were associated with altered thyroid hormone homeostasis among women undergoing ART treatment.

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.

Promoting Choosing Wisely Thyroid Function Test Guidelines in a Large Pediatric Hospital System.

BACKGROUND: Free thyroxine (fT4) is often ordered when not indicated. The goal of the current study was to use quality improvement tools to identify and implement an optimal approach to reduce inappropriate fT4 testing throughout a large pediatric hospital system. METHODS: After reviewing evidence-based guidelines and best practices, a thyroid-stimulating hormone with reflex to fT4 test and an outpatient thyroid order panel with clinical decision support at order entry, along with several rounds of provider education and feedback, were implemented. Outpatient and inpatient order sets and system preference lists were reviewed with subject matter experts and revised when appropriate. Tracking metrics were identified. Automated monthly run charts and statistical process control charts were created using data retrieved from the electronic health record. Charts established baseline data, balancing measure data, monitored the impact of interventions, and identified future interventions. RESULTS: Over a 44-month period, among nonendocrinology providers, a reduction in fT4 and thyroid-stimulating hormone co-orders from 67% to 15% and an increase in reflex fT4 tests from 0% to 77% was obtained in inpatient and outpatient settings. Direct cost savings as a result of performing 5179 fewer fT4 tests over 3 years was determined to be $45 800. CONCLUSIONS: After implementation of a reflex fT4 test, a novel order panel with clinical decision support, provider education, and changes to ordering modes, a large and sustainable reduction in fT4 tests that was associated with significant cost savings was achieved among nonendocrinology providers.

A National Laboratory Perspective: The Impact of the Covid-19 Pandemic on the Management of Patients With Non-Communicable Disease in South Africa: Impact of COVID-19 on patients with noncommunicable diseases.

OBJECTIVE: The aim of this study was to determine the impact of the COVID-19 pandemic on test requests for the diagnosis and routine care of patients with various non-communicable diseases (NCD) across South Africa (SA). METHODS: A retrospective audit of laboratory test requests received from hospital outpatient departments and primary healthcare facilities across SA was performed. The following analytes were studied: glycated hemoglobin (HbA1c), lipids profiles, thyroid-stimulating hormone (TSH), and thyroxine (fT4), as well as triiodothyronine (fT3), serum protein electrophoresis (SPE), serum free light chains (SFLC), and prostate specific antigen (PSA); these tests were used as a proxy of NCD detection and follow-up. Requests received during the 3 waves of the pandemic were compared to requests received within the same period during 2017 - 2019. RESULTS: During the first wave, requests for all analytes were reduced, with the biggest reduction observed for SPE (- 37%); TSH (- 29%); fT4 (- 28%); and HbA1c (- 25%). Requests received from urban facilities showed a larger decrease compared to those from rural facilities. During the third wave there was an increase in requests for all analytes; the biggest increase observed was for fT3 (21%) and HbA1c (18%). CONCLUSIONS: The COVID-19 pandemic had a significant impact on the South African population receiving care in the public healthcare sector.

Trends and Components of Thyroid Status Evaluation in Commercially Insured Adults in the United States, 2006-2020.

CONTEXT: Thyroid-stimulating hormone (TSH) is one of the most ordered laboratory tests. OBJECTIVE: Determine trends of TSH testing rates and components of thyroid function testing. METHODS: This was a retrospective analysis of adults 18-64 years old without evidence of thyroid disease with at least 365 days of continuous enrollment between 2006 and 2020 in the IBM MarketScan Claims Database. The main outcome measures were trends of TSH tests/1000 eligible patient-months stratified by age, sex, and region and composition of thyroid function testing. RESULTS: Among 67 353 280 patients meeting eligibility criteria, we identified 25 606 518 TSH tests and 15 138 211 patients with ≥1 TSH test. Patients contributing an episode of TSH testing were most commonly 45-54 years old (29.8%) and female (63.6%). TSH testing rates remained consistent throughout the study period with 11.4 and 11.7 TSH tests/1000 person-months in the first and last study months, respectively (mean 12.2 TSH tests/1000 person-months). TSH testing rates dropped sharply in the spring of 2020 (4.2 TSH tests/1000 person-months). Females showed a nearly 2-fold higher rate of TSH testing than males (16.1 TSH tests/1000 person-months vs 8.6 TSH tests/1000 person-months). TSH testing rates increased with age (8.2 TSH tests/1000 person-months among individuals 18-34 years old vs 15.4 TSH tests/1000 person-months among individuals 55-64 years old). No difference in TSH testing rates was noted between regions. Thyroid function testing episodes included only TSH in most cases (70.8%). CONCLUSION: TSH testing rates among commercially insured individuals without known thyroid disease appears stable over time, with higher frequency in females and with increasing age.

Thyroid function tests during nonthyroidal illness syndrome and recovery in acutely ill dogs.

BACKGROUND: Nonthyroidal illness syndrome (NTIS) can result in thyroid function test alterations that mimic hypothyroidism. The duration of NTIS-induced changes in dogs is not well-described. OBJECTIVES: Document alterations in thyroid function tests during NTIS and recovery, and the time necessary for their resolution. ANIMALS: From 103 dogs sampled, 25 euthyroid dogs with acute, resolvable illness having a low serum total thyroxine (TT4) concentration on admission were analyzed. METHODS: Prospective observational study. Serum TT4 concentration was measured in 103 dogs within 4 hours of admission. If below the reference interval (RI), subsequent serum samples were obtained every 24 hours from admission until discharge (acute phase) and at 2 weeks and 4 weeks after discharge (recovery phase). Serum samples were submitted for batch measurement of serum TT4, free thyroxine (fT4), total 3,5,3'-triiodothyronine (TT3), and thyroid-stimulating hormone (TSH) concentrations. RESULTS: In the cohort of dogs analyzed, serum TT4, TT3, and fT4 concentrations were below the RI in 100%, 80%, and 16% at admission; 20%, 80%, and 0% at discharge; 4%, 8%, and 0% at 2 weeks; and 0%, 0%, and 0% at 4 weeks, respectively. Serum TSH concentration was within the RI in 100% at admission and discharge, and above the RI in 4% and 12% at 2 weeks and 4 weeks, respectively. CONCLUSIONS AND CLINICAL IMPORTANCE: Naturally occurring NTIS in dogs induces alterations in thyroid function tests during acute illness and recovery. Measurement of serum TT4 concentration 2 to 4 weeks after discharge or serum fT4 concentration by ED during illness is recommended for accurate assessment of thyroid function in acutely ill dogs.

The impact of quetiapine monotherapy or in combination with lithium on the thyroid function in patients with bipolar depression: A retrospective study.

OBJECTIVE: This study aims to investigate whether quetiapine monotherapy or in combination with lithium significantly disturbs thyroid function in depressed patients with bipolar disorder (BD), and whether difference exists in the post-treatment thyroid function between the two therapies. METHODS: Based on the electric medical records, outpatients and inpatients with a current depressive episode of BD from January 2016 to December 2022 were screened. All patients were treated with quetiapine monotherapy or in combination with lithium. In addition to the demographic data and depression scale, thyroid profiles including total thyroxine (TT4), total triiodothyronine (TT3), free thyroxine (FT4), free triiodothyronine (FT3), thyroid-stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb), and antithyroglobulin antibody (TGAb) were recorded, analyzed, and compared before and after the treatment. RESULTS: Totally, 73 eligible patients were enrolled, including 53 in the monotherapy group (MG) and 20 in the combined therapy group (CG). No significant differences in thyroid profiles were detected between the two groups at the baseline (p > 0.05). After one-month treatment, in the MG, serum levels of TT4, TT3, FT4, and FT3 reduced significantly (p < 0.05), while TSH, TPOAb, and TGAb increased significantly (p < 0.05). In the CG, serum levels of TT4, TT3, and FT4 reduced and TSH increased following one-month treatment (p < 0.05), with no significant change in FT3, TPOAb, or TGAb (p > 0.05). After one-month treatment, no difference of TT4, TT3, FT4, FT3, and TSH was found between the two groups (p > 0.05). CONCLUSION: Both quetiapine monotherapy and a combined therapy with lithium significantly disturbed thyroid function in patients with bipolar depression, while quetiapine monotherapy seems to be associated with immune dysregulation in the thyroid.

Isolated central hypothyroidism: Underlying pathophysiology and relation to antidepressant and antipsychotic medications-A multi-centre South Wales study.

OBJECTIVE: Isolated biochemical central hypothyroidism is a presentation we are experiencing more frequently as endocrinologists, with variation in levels of investigation between physicians. We therefore conducted research to investigate the final diagnosis and clinical outcome of patients across multiple hospitals in South Wales with biochemical isolated central hypothyroidism; namely to establish whether this isolated biochemical picture was clinically significant. We also analysed whether there is an association between this biochemical picture and treatment with antidepressant and antipsychotic medications, and how common this is. DESIGN: We performed a retrospective observational study of patients across nine different hospitals in South Wales. We analysed patients referred to endocrinology at each site over a 6-year period with unexplained isolated biochemical central hypothyroidism. MATERIALS AND METHODOLOGY: 1022 individual patients' thyroid function test results were identified from our biochemical database using our inclusion criteria. After exclusion criteria were applied, 71 patients' results were analysed as to the final pathophysiology of their central hypothyroidism. RESULT: Of the 71 patients included in the study, none were found to have any clinically significant pathology on pituitary imaging. On reviewing their medications, 46/71 (65%) were found to be taking psychotropic medications. CONCLUSIONS: Our study strongly suggests isolated central hypothyroidism, in the absence of other pituitary hormone dysfunction or visual field defect, does not require further investigation, saving resources as well as sparing patients unnecessary anxiety. It also strongly supports a relationship between patients taking psychotropic medications and biochemical isolated central hypothyroidism, an association only described in a very limited amount of literature before this, and further supporting our previous single-centre study findings. The mechanism behind this is likely to be the suppression of thyrotropin secretion via antagonism of the dopamine-serotoninergic pathway. In our opinion, patients found to have isolated biochemical central hypothyroidism who are taking psychotropic medications can therefore be regarded to have a recognised cause for this biochemical finding and do not require further radiological investigation.

TSH and FT4 Reference Interval Recommendations and Prevalence of Gestational Thyroid Dysfunction: Quantification of Current Diagnostic Approaches.

CONTEXT: Guidelines recommend use of population- and trimester-specific thyroid-stimulating hormone (TSH) and free thyroxine (FT4) reference intervals (RIs) in pregnancy. Since these are often unavailable, clinicians frequently rely on alternative diagnostic strategies. We sought to quantify the diagnostic consequences of current recommendations. METHODS: We included cohorts participating in the Consortium on Thyroid and Pregnancy. Different approaches were used to define RIs: a TSH fixed upper limit of 4.0 mU/L (fixed limit approach), a fixed subtraction from the upper limit for TSH of 0.5 mU/L (subtraction approach) and using nonpregnancy RIs. Outcome measures were sensitivity and false discovery rate (FDR) of women for whom levothyroxine treatment was indicated and those for whom treatment would be considered according to international guidelines. RESULTS: The study population comprised 52 496 participants from 18 cohorts. Compared with the use of trimester-specific RIs, alternative approaches had a low sensitivity (0.63-0.82) and high FDR (0.11-0.35) to detect women with a treatment indication or consideration. Sensitivity and FDR to detect a treatment indication in the first trimester were similar between the fixed limit, subtraction, and nonpregnancy approach (0.77-0.11 vs 0.74-0.16 vs 0.60-0.11). The diagnostic performance to detect overt hypothyroidism, isolated hypothyroxinemia, and (sub)clinical hyperthyroidism mainly varied between FT4 RI approaches, while the diagnostic performance to detect subclinical hypothyroidism varied between the applied TSH RI approaches. CONCLUSION: Alternative approaches to define RIs for TSH and FT4 in pregnancy result in considerable overdiagnosis and underdiagnosis compared with population- and trimester-specific RIs. Additional strategies need to be explored to optimize identification of thyroid dysfunction during pregnancy.

The Combined Effect of Immune Checkpoint Inhibitors and Tyrosine Kinase Inhibitors on Thyroid Function.

Background: Recent successes with immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs) for the treatment of solid malignancies have paved the way for a new era of combined therapy. A common side effect seen with each of these classes of treatment is thyroid dysfunction, with rates estimated at 30-40% for TKI and 10-20% for ICI. However, little is known about the effect of combined ICI+TKI therapy on thyroid function. Therefore, this study evaluated the incidence, clinical features, and risk factors for developing thyroid abnormalities during ICI+TKI therapy and the relationship to cancer outcomes. Methods: We conducted a retrospective cohort study of patients treated with combination ICI+TKI cancer therapy at City of Hope Comprehensive Cancer Center from 2017 to 2023 who had pretreatment normal thyrotropin (TSH) levels. Primary analyses assessed the frequency, timing, and severity of thyroid function test abnormalities during ICI+TKI cancer therapy, and the requirement for thyroid hormone replacement. Secondary analyses evaluated risk factors for the development of thyroid dysfunction, including sex and drug regimen, and the association with cancer progression-free survival or overall survival. Univariable and multivariable models were used. Results: There were 106 patients who received ICI+TKI therapy with a median age of 63.5 years and a median follow-up of 12.8 months (interquartile range [IQR] 5.9-20.9). Notably, 63.2% (67/106) developed thyroid function abnormalities during ICI+TKI therapy, including 11 (10.4%) with hyperthyroidism, 42 (39.6%) with subclinical hypothyroidism (SCHypo), and 14 (13.2%) with overt hypothyroidism. The onset of thyroid dysfunction occurred at a median of 7 weeks (IQR 3.1-9.0) after start of ICI+TKI treatment for hyperthyroidism, 8.0 weeks (IQR 3.0-19.0) for SCHypo, and 8.1 weeks (IQR 5.9-9.1) for overt or worsening hypothyroidism. Hyperthyroidism resolved to hypothyroidism or normal TSH without intervention in all subjects, suggesting thyroiditis, and hypothyroidism was readily treated with thyroid hormone replacement. Conclusions: Thyroid dysfunction is a frequent adverse event in individuals treated with combination ICI+TKI therapy, with our data suggesting a rapid onset and higher incidence than previously seen with ICI or TKI therapy alone. Therefore, close monitoring of thyroid function during initial therapy and multidisciplinary care with endocrinology are recommended to facilitate early detection and initiation of thyroid hormone replacement in these patients.

Anaemia-based screening for resistance to thyroid hormone alpha in children.

BACKGROUND: The hypothyroid phenotype associated with resistance to thyroid hormone alpha (RTH-α) is associated with a diverse clinical picture. On the other hand, thyroid-stimulating hormone (TSH) levels are normal. Free triiodothyronine (fT3) and free thyroxine (fT4) levels can also be normal; however, normo- or macrocytic anaemia is usually present in reported cases. Diagnosis is challenging and there is limited data regarding screening methods. OBJECTIVE: The study aimed to assess the efficiency of a screening strategy for RTH-α. SUBJECTS AND METHODS: Out of a total of 6540 children evaluated at the outpatient clinics of paediatric neurology over 2 years and who underwent complete blood count and thyroid function tests, 432 were found to have anaemia. Within this group, we identified 42 children without an underlying specific neurological aetiology who exhibited normo- or macrocytic anaemia, normal TSH levels, fT3 levels in the upper half of the normal range or high, and fT4 levels in the lower half of the normal range or low. We excluded one patient who had already been diagnosed with RTH-α and nine patients could not be reached. Subsequently, clinical evaluation, biochemical assessment, and THRA sequencing analysis were conducted on 32 children. The findings were compared with those of the known RTH-α patients in our unit. RESULTS: The median age of the patients was 5.7 (5.1-7.4) years, and 22 of them were males (69%). The main reasons for assessment in paediatric neurology clinics were autism spectrum disorder (n = 12, 38%), epilepsy (n = 11, 34%), and delay in developmental stages (n = 8, 25%). Constipation was present in five of the cases (16%), while the closure of the anterior fontanelle and tooth eruption were delayed in two cases (6%) and one case (3%), respectively. The median length/height and weight standard deviation (SD) scores were 0.3 [(-0.8)-(1.1)] and -0.1 [(-0.8)-(0.3)], respectively. The median fT3, fT4, and TSH levels were 4.6 (4.2-5.0) pg/mL, 0.9 (0.8-1.0) ng/dL, and 2.2 (1.8-3.1) uIU/mL, respectively. Thirteen of the patients (41%) had high fT3 levels, while none of them had low fT4 levels. The normo- or macrocytic anaemia rate was 47% (normocytic/macrocytic, n = 8/7) at the time of reassessment. Serum creatine kinase (CK) was elevated in five patients (16%; one had anaemia). None of the subjects had a pathological variant in THRA. Known RTH-α patients had significantly lower median height SD score, higher rates of delayed tooth eruption and closure of the anterior fontanelle, lower haemoglobin levels, and higher mean corpuscular volume (MCV) and CK levels as compared to those found without RTH-α. CONCLUSIONS: This approach found one known patient with RTH-α but did not reveal any new cases. Notably, normo- or macrocytic anaemia did not persist in nearly half of the screened patients. A screening strategy that takes clinical findings and prominent laboratory features suggestive of RTH-α into account could lower unnecessary genetic analysis of THRA in patients presenting with neurological problems.

Interference against a newly labeled substance with ruthenium sulfonate complexes showing discrepant thyroid function test results.

We report here two patients exhibiting a combination of falsely elevated serum levels of free thyroxine (FT4), free triiodothyronine (FT3), and thyrotropin receptor antibodies (TRAb), measured using Elecsys assay kits (Roche Diagnostics GmbH). The first patient was a 74-year-old man misdiagnosed with Graves' disease and treated with methimazole. The second patient was a 48-year-old woman whose serum FT4 and FT3 concentrations were found to be high during a blood test. These patients denied taking biotin or any other supplements. Further detailed examination, including a heterophilic blocking tube test, revealed the presence of serum antibodies. The abnormal reactions were observed only using the improved assay kits using ruthenium (Ru) sulfonate instead of Ru as a chemiluminescent agent. Therefore, serum antibodies to the Ru sulfonate complex caused the pseudo-high levels of FT4, FT3, and TRAb. To our knowledge, this is the first report showing that antibodies to the Ru sulfonate complex in the electrochemiluminescence immunoassay can cause falsely elevated levels of the combination, leading to discrepant thyroid function test results. We emphasize that in cases of abnormal test results, alternative assay methods should be considered for further examination; unusual test results should not be impulsively interpreted, even when using revised assay kits.

Low levels of free triiodothyronine are associated with risk of cognitive impairment in older euthyroid adults.

Accumulated evidence showed that thyroid diseases induced cognitive decline. However, the relationship between thyroid hormones (THs) and cognition in older euthyroid people is still unclear. Our study aimed to estimate the association between THs within the euthyroid range and cognition in community-dwelling older adults in China. Data were extracted from a cohort study on the health status of rural older adults from the Guizhou province in China (HSRO). Serum thyroid-stimulating hormone (TSH), free thyroxine (FT4), and free triiodothyronine (FT3) were measured using the electrochemiluminescence immunoassay. Cognitive function was evaluated by the Mini-Mental State Examination (MMSE). Linear regression and a binary logistic regression model were used to explore the relationship between THs and cognition in euthyroidism (TSH level of 0.27 ~ 4.20mIU/L). A total of 957 euthyroidism individuals were included in this study, with a mean (SD) age of 71.34 (6.35) years. In individuals with euthyroidism, serum TSH and FT3 levels were positively associated with cognition (TSH:ß = 0.06, 95% CI 0.01 ~ 0.11, P = 0.03; FT3:ß = 0.07, 95% CI 0.01 ~ 0.12, P = 0.01); and serum FT3 and TSH levels were significantly associated with cognitive domains (P < 0.05). Further, euthyroid individuals in the lowest serum FT3(OR = 1.96; 95% CI 1.27 ~ 3.03) quartile had a twofold increased risk of cognitive impairment compared to those in the highest quartile after adjusting for potential confounding factors. These findings suggested that low levels of FT3 could be an independent risk factor for cognitive impairment in older euthyroid adults. Additionally, a positive linear association exists between serum FT3 levels and cognitive domains (such as immediate memory, language, and attention). Further studies are needed to determine the underlying mechanisms and the community significance of these findings.

Prevalence of thyroid dysfunction among Iranian older adults: a cross-sectional study.

There is limited data on the prevalence of thyroid dysfunction in the older population. This study aimed to determine the prevalence of thyroid dysfunction among a sample of Iranian older adults. A cross-sectional analysis of older adults who aged 60 years and over was conducted. A total of 363 subjects were randomly selected from Birjand longitudinal aging study (BLAS) cohort study. Serum thyroid-stimulating hormone (TSH) level, total thyroxine (T4) and total triiodothyronine (T3) were measured by the enzyme-linked immunosorbent assay (ELISA). Based on thyroid function tests and history of taking medicines used to treat thyroid disorders, participants were classified into the following groups: euthyroid, overt/subclinical hypothyroidism, and overt/subclinical hyperthyroidism. Subsequently, the crude and World Health Organization (WHO) age-standardized prevalence were estimated for different thyroid function categories. A total of 171 men and 192 women, aged 60-94 years, were randomly selected. The crude prevalence of total hypothyroidism was 22.31% (subclinical [18.46%], overt [3.86%]), and that of hyperthyroidism was 1.66% (subclinical [1.38%], overt [0.28%]). The crude prevalence of total thyroid dysfunction was, therefore, 23.97%. A female preponderance was noticed in both total (P-value = 0.035) and overt (P-value = 0.035) hypothyroidism. An increasing trend with age was noticed in the prevalence of total hypothyroidism (P-value = 0.049). Age-standardized prevalence of total hypothyroidism and hyperthyroidism was 26.63% (95% confidence interval [CI] 20.58-33.69%) and 1.11% (95% CI 0.49-2.51%), respectively. A considerable proportion of our study population demonstrated evidence of thyroid dysfunction, particularly subclinical hypothyroidism. Our findings highlight the importance of further investigation of thyroid disorders among older Iranian adults.