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Background: Long-term management of patients with hypothyroidism on thyroxine replacement requires thyroid function test (TFT) monitoring once every six–12 months as recommended by clinical practice guidelines. This study determined their thyroid function status during two-year follow-up visits in primary care, and the factors influencing their thyroid status, and assessed the optimal interval for TFTs. Methods: A retrospective cohort study was conducted on adults with a clinical diagnosis code for hypothyroidism in their electronic health records taken from a group of polyclinics in Singapore between July 2017 and June 2020. The follow-up thyroid status was categorized as under-replacement (TSH ≥ 3.70mIU/L), over-replacement (TSH ≤ 0.65mIU/L) or euthyroid (TSH 0.65–3.70mIU/L). The patients' demographic, clinical and TFT data were analyzed using appropriate statistical tests during the two-year follow-up. Stepwise logistic regression analysis identified the factors associated with suboptimal thyroid control. Kaplan–Meier analysis was used to compare their thyroid function status in association with the interval between TFT monitoring. Results: Data from 5,749 eligible subjects (mean age 62.1 ± 13.29 years; 79% female; 79.7% Chinese) were analyzed. After a two-year follow-up, 61.9% (n = 3558) of all subjects were euthyroid, with 29.5% (n = 1694) being under-replaced and 8.6% (n = 497) over-replaced. However, thyroid status did not differ significantly with the various dose regimen (daily, segmented, or alternate days) (p = 0.193). Stepwise logistic regression showed that thyroxine under-replacement was significantly associated with the male gender (AOR = 1.25,95%CI = 1.03–1.51,p = 0.02) and obesity (AOR = 1.34,95%CI = 1.08–1.66,p = 0.008). Every unit (μg/kg body weight) increase in the mean daily thyroxine dose was associated with 2.72 times greater odds of over-replacement. When comparing thyroid function monitoring at intervals of 13-24 months, monitoring at shorter intervals (≤ 12 months) was less likely to detect thyroxine under-replacement (AOR = 0.57,95%CI = 0.44–0.74,p < 0.001) and over-replacement (AOR = 0.62,95%CI = 0.41–0.97,p = 0.033). Among the 3,312 adults who were euthyroid at baseline, 22.2%, 41.7% and 59.6% had suboptimal thyroid control at 6, 12 and 24 months respectively (Kaplan–Meier analysis). Conclusion: Around six in ten patients were euthyroid with thyroxine replacement for hypothyroidism in primary care over two years. Thyroxine under-replacement was associated with male gender and obesity. The proportion of euthyroid patients developing abnormal thyroid function doubled with TFTs at six, 12 and 24-month intervals. [ABSTRACT FROM AUTHOR]

Abstract Background Long-term management of patients with hypothyroidism on thyroxine replacement requires thyroid function test (TFT) monitoring once every six–12 months as recommended by clinical practice guidelines. This study determined their thyroid function status during two-year follow-up visits in primary care, and the factors influencing their thyroid status, and assessed the optimal interval for TFTs. Methods A retrospective cohort study was conducted on adults with a clinical diagnosis code for hypothyroidism in their electronic health records taken from a group of polyclinics in Singapore between July 2017 and June 2020. The follow-up thyroid status was categorized as under-replacement (TSH ≥ 3.70mIU/L), over-replacement (TSH ≤ 0.65mIU/L) or euthyroid (TSH 0.65–3.70mIU/L). The patients’ demographic, clinical and TFT data were analyzed using appropriate statistical tests during the two-year follow-up. Stepwise logistic regression analysis identified the factors associated with suboptimal thyroid control. Kaplan–Meier analysis was used to compare their thyroid function status in association with the interval between TFT monitoring. Results Data from 5,749 eligible subjects (mean age 62.1 ± 13.29 years; 79% female; 79.7% Chinese) were analyzed. After a two-year follow-up, 61.9% (n = 3558) of all subjects were euthyroid, with 29.5% (n = 1694) being under-replaced and 8.6% (n = 497) over-replaced. However, thyroid status did not differ significantly with the various dose regimen (daily, segmented, or alternate days) (p = 0.193). Stepwise logistic regression showed that thyroxine under-replacement was significantly associated with the male gender (AOR = 1.25,95%CI = 1.03–1.51,p = 0.02) and obesity (AOR = 1.34,95%CI = 1.08–1.66,p = 0.008). Every unit (μg/kg body weight) increase in the mean daily thyroxine dose was associated with 2.72 times greater odds of over-replacement. When comparing thyroid function monitoring at intervals of 13-24 months, monitoring at shorter intervals (≤ 12 months) was less likely to detect thyroxine under-replacement (AOR = 0.57,95%CI = 0.44–0.74,p

The presence of latent fibrin clots is a recognised pre-analytical factor that causes inaccurate immunoassay results. This report details a case of a patient with Graves' disease and congenital dysfibrinogenemia (CD) that had serum thyroid function test results (TFTs) that were not in keeping with clinical signs or symptoms. Analysis of plasma samples taken from the patient was shown to provide more accurate results than those obtained using serum samples. Further cases of patients with CD, all sharing the same genetic mutation of fibrinogen, and discordant TFTs are described, where TFTs measurement in serum samples proved to be unreliable. Despite evidence of fibrin effecting immunoassays, this is the first report of its kind linking CD to erroneous immunoassay results. The mechanism is postulated to be related to atypical forms of fibrinogen resulting in latent fibrin in serum samples blocking the antigen binding site and leading to incorrect results. Congenital dysfibrinogenemia is asymptomatic in most patients and therefore abnormal, albeit inaccurate, TFTs may be the first finding. Recognition of CD as a cause of discordant results is important when interpreting TFTs to avoid unnecessary investigations and inappropriate clinical interventions to those with the disorder and potentially identify undiagnosed cases. [ABSTRACT FROM AUTHOR]

Background Establishing local trimester-specific reference intervals for gestational TSH and free T4 (FT4) is often not feasible, necessitating alternative strategies. We aimed to systematically quantify the diagnostic performance of standardized modifications of center-specific nonpregnancy reference intervals as compared to trimester-specific reference intervals. Methods We included prospective cohorts participating in the Consortium on Thyroid and Pregnancy. After relevant exclusions, reference intervals were calculated per cohort in thyroperoxidase antibody-negative women. Modifications to the nonpregnancy reference intervals included an absolute modification (per.1 mU/L TSH or 1 pmol/L free T4), relative modification (in steps of 5%) and fixed limits (upper TSH limit between 3.0 and 4.5 mU/L and lower FT4 limit 5-15 pmol/L). We compared (sub)clinical hypothyroidism prevalence, sensitivity, and positive predictive value (PPV) of these methodologies with population-based trimester-specific reference intervals. Results The final study population comprised 52 496 participants in 18 cohorts. Optimal modifications of standard reference intervals to diagnose gestational overt hypothyroidism were −5% for the upper limit of TSH and +5% for the lower limit of FT4 (sensitivity,.70, CI, 0.47-0.86; PPV, 0.64, CI, 0.54-0.74). For subclinical hypothyroidism, these were −20% for the upper limit of TSH and −15% for the lower limit of FT4 (sensitivity, 0.91; CI, 0.67-0.98; PPV, 0.71, CI, 0.58-0.80). Absolute and fixed modifications yielded similar results. CIs were wide, limiting generalizability. Conclusion We could not identify modifications of nonpregnancy TSH and FT4 reference intervals that would enable centers to adequately approximate trimester-specific reference intervals. Future efforts should be turned toward studying the meaningfulness of trimester-specific reference intervals and risk-based decision limits. [ABSTRACT FROM AUTHOR]

Introduction: Initial surge of thyroid-stimulating hormone (TSH) in neonates increases free and total triiodothyronine (T3) and tetraiodothyronine (T4) in 24–36 hours following birth, and the effect then gradually wanes off. As somatic and intellectual development is dependent on normal thyroid function especially in infancy, normative data in these children may be of immense value to diagnose hypothyroidism in this subset of infants. Comprehensive normative values of thyroid function parameters in preterm neonates are scarcely available. The objective of this study was to determine the normative value of thyroid function parameters in preterm neonates. Methods: Preterm neonates (n = 102) born at 34 and 35 weeks of gestation of euthyroid mothers from an iodine-sufficient population were evaluated for T3, T4, free thyroxine (FT4) and TSH during 3–7 days after birth and again after 1 month. The expected date of delivery (EDD) and Ballard score were used to identify the duration of gestation. Results: The mean gestational age was 34.7 ± 0.41 weeks. The mean (± SD) for T3 (ng/dl), T4 (μg/dl), FT4 (ng/ml) and TSH (μIU/ml) on days 3–7 following birth was as follows: 156 ± 44.6, 12.8 ± 3.7, 1.50 ± 0.54 and 7.13 ± 6.04, respectively. Around 4 weeks of age, values changed to 104 ± 38.4, 12.1 ± 4.02, 1.46 ± 0.42 and 3.25 ± 2.85, respectively. All parameters changed significantly around 4 weeks, except FT4. None of the parameters were correlated with gestational age or body weight at birth. Normative values for each parameter in percentiles were generated. Conclusion: This study generated the normative values of the thyroid function test during the first week and after around 4 weeks of life for premature neonates (born at 34–35 weeks).

MacroTSH still interferes with TSH assays. We present here a case report illustrating the difficulties that can arise in such conditions and attempt to discuss the steps involved in diagnosis.

Context Apalutamide (APT) is a nonsteroidal antiandrogen medication used to treat metastatic castrate-sensitive and nonmetastatic castrate-resistant prostate cancer. Early clinical trials of APT identified thyroid dysfunction as a common adverse effect of therapy, but the clinical presentation and management of APT-induced hypothyroidism has not been studied. Objective The objective of our study is to elucidate the clinical presentation and treatment approach of APT-associated thyroid dysfunction in prostate cancer patients. Methods We report a case series of 16 patients with APT-associated thyroid dysfunction during prostate cancer treatment at 2 academic medical centers. Patient clinical parameters, thyroid function laboratory data, and thyroid hormone requirements over the course of APT treatment were analyzed. Results Among the 16 patients in our case series with APT-associated hypothyroidism, 3 had no prior thyroid disease and 13 had preexisting hypothyroidism. The patterns of thyroid dysfunction included overt and subclinical hypothyroidism. The median time from APT initiation to thyroid function test abnormality was 19 weeks, but occurred in some cases as early as 2 to 4 weeks. Hypothyroidism was effectively managed with thyroid hormone replacement using levothyroxine (LT4), though some patients with preexisting hypothyroidism required a 2- to 3-fold dose increase while on APT to achieve a euthyroid state. In the subset of patients who completed or stopped APT therapy, thyrotropin levels fell at a median of 11 weeks post APT therapy and thyroid hormone requirements decreased to near pre-APT levels. Conclusion APT-associated thyroid dysfunction presents as new or worsening hypothyroidism and should prompt initiation or increase in thyroid hormone replacement. Monitoring of thyroid function tests is recommended every 1 to 2 months for all patients on APT and 2 to 3 months after completion of APT. [ABSTRACT FROM AUTHOR]

Background: International guidelines recommend targeted screening to identify gestational thyroid dysfunction. However, currently used risk factors have questionable discriminative ability. We quantified the risk for thyroid function test abnormalities for a subset of risk factors currently used in international guidelines. Methods: We included prospective cohort studies with data on gestational maternal thyroid function and potential risk factors (maternal age, body mass index [BMI], parity, smoking status, pregnancy through in vitro fertilization, twin pregnancy, gestational age, maternal education, and thyroid peroxidase antibody [TPOAb] or thyroglobulin antibody [TgAb] positivity). Exclusion criteria were pre-existing thyroid disease and use of thyroid interfering medication. We analyzed individual participant data using mixed-effects regression models. Primary outcomes were overt and subclinical hypothyroidism and a treatment indication (defined as overt hypothyroidism, subclinical hypothyroidism with thyrotropin >10 mU/L, or subclinical hypothyroidism with TPOAb positivity). Results: The study population comprised 65,559 participants in 25 cohorts. The screening rate in cohorts using risk factors currently recommended (age >30 years, parity ≥2, BMI ≥40) was 58%, with a detection rate for overt and subclinical hypothyroidism of 59%. The absolute risk for overt or subclinical hypothyroidism varied <2% over the full range of age and BMI and for any parity. Receiver operating characteristic curves, fitted using maternal age, BMI, smoking status, parity, and gestational age at blood sampling as explanatory variables, yielded areas under the curve ranging from 0.58 to 0.63 for the primary outcomes. TPOAbs/TgAbs positivity was associated with overt hypothyroidism (approximate risk for antibody negativity 0.1%, isolated TgAb positivity 2.4%, isolated TPOAb positivity 3.8%, combined antibody positivity 7.0%; p < 0.001), subclinical hypothyroidism (risk for antibody negativity 2.2%, isolated TgAb positivity 8.1%, isolated TPOAb positivity 14.2%, combined antibody positivity 20.0%; p < 0.001) and a treatment indication (risk for antibody negativity 0.2%, isolated TgAb positivity 2.2%, isolated TPOAb positivity 3.0%, and combined antibody positivity 5.1%; p < 0.001). Twin pregnancy was associated with a higher risk of overt hyperthyroidism (5.6% vs. 0.7%; p < 0.001). Conclusions: The risk factors assessed in this study had poor predictive ability for detecting thyroid function test abnormalities, questioning their clinical usability for targeted screening. As expected, TPOAb positivity (used as a benchmark) was a relevant risk factor for (subclinical) hypothyroidism. These results provide insights into different risk factors for gestational thyroid dysfunction. [ABSTRACT FROM AUTHOR]

Objective Accurate estimation of serum thyrotropin (TSH) is crucial in the diagnosis of subclinical hypothyroidism (SCH) in pregnancy. We aimed to investigate whether there are significant differences between fasting and nonfasting thyroid function tests (TFTs) among pregnant mothers. Methods We studied 100 pregnant mothers with previously unknown thyroid dysfunction. An equal number of participants were included in each trimester. All pregnant mothers underwent fasting and 2-hour postprandial TFTs (TSH, free T4). Results Postprandial TSH (mean 1.01 mIU/L, SD 0.80) was significantly lower than the fasting TSH (mean 1.47 mIU/L, SD 1.18) in pregnancy (P <.01). Postprandial free T4 (mean 10.30 pmol/L, SD 2.01) was also lowered compared with fasting free T4 (mean 10.70 pmol/L, SD 1.99) in pregnancy (P <.01). The prevalence of SCH in pregnancy estimated using fasting TSH was 9.4% (SD 3%). In contrast, the prevalence was only 3.5% (SD 2%) when postprandial TSH was used. Conclusion Compared with the fasting state, postprandial TSH demonstrates a statistically significant reduction that greatly influences the diagnosis of SCH in pregnant mothers. Therefore, we conclude that the timing of sampling for TFTs should be standardized, especially in the pregnant population. [ABSTRACT FROM AUTHOR]

Objective To investigate the characteristics of thyroid function and its influencing factors in preterm infants born to mothers with preeclampsia. Methods A total of 222 preterm infants, who were admitted to the neonatal intensive care unit of our hospital from January to December 2019, were enrolled, and according to the presence or absence of preeclampsia in the mother, they were divided into experimental group with 120 infants and control group with 102 infants. Basic clinical data were collected from the preterm infants and their mothers, as well as the results of thyroid function test using peripheral venous blood of preterm infants at 10-14 d after birth. The Student’s t-test, a one-way analysis of variance, and the multiple stepwise regression analysis were used to investigate the influencing factors for thyroid function in preterm infants. Results There was no significant difference in maternal thyroid function between the two groups (P>0.05). The experimental group had a significantly higher se-rum level of thyroid stimulating hormone (TSH) than the control group (t=-2.76,P

Background: There are inconsistent results about the effect of gastric bypass surgery on thyroid function tests in morbidly obese subjects. The aim of this study was to investigate the changes in thyroid function tests and insulin resistance status in euthyroid morbidly obese subjects before and three months after gastric bypass surgery (GBS). Methods: Twenty-nine subjects with morbid obesity (BMI≥40) were enrolled in this before-after study. Patients with known thyroid disorders or a history of thyroid ablative therapy, users of drugs that affect thyroid function, or fasting blood sugar and insulin were excluded. TSH, Free T4, total T3, fasting blood sugar and insulin level, and BMI were measured before and 3 months after GBS. Statistical analysis was performed with appropriate tests and p

Background: To evaluate the effects of probe positioning on radioactive iodine uptake (RAIU) measurements and 131I quantification in Graves disease (GD) patients. Materials and Methods: We performed a cross-sectional study in GD patients between May 9 and June 27, 2013. 24 hr-RAIU was measured. Measurement A was the reference measurement and was obtained with the probe parallel to the bottom of the thyroid cartilage. Measurements B, C, D, and E were obtained by moving the probe 2.5 cm to the left, 5 cm to the left, 2.5 cm vertically upward, and 5 cm vertically upward, respectively. The 131I doses were calculated. Non-reference measurements were compared with measurement A using the paired t-test or Wilcoxon signed-rank test. Results: A total of 63 GD patients (17 men, 40.3±13.6 years old) were enrolled. Among them, 57 patients had 24 hr-RAIU measurement and 37 patients chose the 131I treatment. Significant changes were observed in 24 hr-RAIU and 131I dose between measurement A (24 hr-RAIU 60.40±12.67% and median 131I dose 8.17 mCi) and measurement E (24 hr-RAIU 48.67±11.74% and median 131I dose 9.50 mCi) (P<0.05). In one patient, the 24 hr-RAIU was 20.3% lower in measurement E compared with that in measurement A, resulting in a 30 mCi increase in the calculated 131I dose. Conclusions: The vertically upward movement by a distance of a radius of the collimator could affect the 24 hr-RAIU measurement and thus cause inaccurate calculation of the 131I dose. [ABSTRACT FROM AUTHOR]

Measurement of free thyroid hormones (THs) and thyrotropin (TSH) using automated immunoassays is central to the diagnosis of thyroid dysfunction. Using illustrative cases, we describe a diagnostic approach to discordant thyroid function tests, focusing on entities causing elevated free thyroxine and/or free triiodothyronine measurements with nonsuppressed TSH levels. Different types of analytical interference (eg, abnormal thyroid hormone binding proteins, antibodies to iodothyronines or TSH, heterophile antibodies, biotin) or disorders (eg, resistance to thyroid hormone β or α, monocarboxylate transporter 8 or selenoprotein deficiency, TSH-secreting pituitary tumor) that can cause this biochemical pattern will be considered. We show that a structured approach, combining clinical assessment with additional laboratory investigations to exclude assay artifact, followed by genetic testing or specialized imaging, can establish a correct diagnosis, potentially preventing unnecessary investigation or inappropriate therapy. [ABSTRACT FROM AUTHOR]

Background: There are inconsistent results about the effect of gastric bypass surgery on thyroid function tests in morbidly obese subjects. The aim of this study was to investigate the changes in thyroid function tests and insulin resistance status in euthyroid morbidly obese subjects before and three months after gastric bypass surgery (GBS). Methods: Twenty-nine subjects with morbid obesity (BMI=40) were enrolled in this before-after study. Patients with known thyroid disorders or a history of thyroid ablative therapy, users of drugs that affect thyroid function, or fasting blood sugar and insulin were excluded. TSH, Free T4, total T3, fasting blood sugar and insulin level, and BMI were measured before and 3 months after GBS. Statistical analysis was performed with appropriate tests and p<0.05 was considered significant. Results: Body mass index (BMI), insulin sensitivity index (HOMA-IR), and total T3 significantly decreased after bypass surgery (all with p<0.001) but no significant changes were seen in TSH (P=0.203) and FreeT4 (P=0.33). There was a significant negative correlation between changes in HOMA-IR and changes in FreeT4 (P=0.038, r= -0.38). There was no statistically significant correlation between the percentage of excess BMI loss (%EBMIL) and changes in T3 (P=0.66), Free T4 (P=0.92), TSH (P= 0.27), and HOMA-IR (P=0.17). Conclusion: Although significant changes can occur in BMI, insulin sensitivity index, fasting blood sugar, and T3 in short-time follow-up after bariatric surgery, significant TSH and FreeT4 changes may need longer follow-ups. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background & Objective: Occurrence of maternal or fetal complications during pregnancy may be related to development of postpartum thyroid dysfunction based on the underlying thyroid autoimmune status. The purpose of this study was to investigate the incidence of thyroid dysfunction after delivery in euthyroid mothers who have experienced adverse pregnancy outcomes. Materials & Methods: Among 387 euthyroid pregnant women, 118 experienced adverse pregnancy outcomes out of which only 96 subjects completed the study. The level of thyroperoxidase antibody in the first week after delivery and thyroid function tests including Total T4, T3RU and TSH three months after delivery were measured by electrochemiluminescence immunoassay method. SPSS version 22 was used to analyze the data and the significance level was defined as p<0.05. Results: Thyroperoxidase antibody was positive in 14 participants (14.6%). Overall maternal and fetal complications in the group with positive thyroperoxidase antibody were more than the group without this antibody (p<0.001). Total T4 level was significantly (p=0.02) higher in the group with negative thyroperoxidase antibody (8.03±1.91) comparing with the positive antibody group (6.72±1.96). Overt hypothyroidism was the only thyroid dysfunction that had a significant relationship with thyroid autoimmune status three months after delivery (p=0.02). Conclusion: This study indicates the possible occurrence of thyroid dysfunction after delivery in euthyroid mothers who have experienced maternal or fetal pregnancy complications. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

NPs play a pivotal role in caring for pregnant people. This article provides an overview of gestational and postpartum thyroid disorders, including their assessment, management, and indications for referral. The goal of this article is to help providers better assess and manage thyroid disorders during pregnancy and improve patient outcomes. [ABSTRACT FROM AUTHOR]

Background: Thyroid carcinoma closely resembles its benign counterpart in physical characteristics, measurable physiological parameters such as serum T3/T4 levels and ultrasound features. Therefore, the surgical excision of the nodule and its histological examination is important to differentiate between the more frequent benign and much less frequent malignant nodules. The highest incidence of thyroid lesions was seen between the 3rd and 4th decades of life with female preponderance. Colloid goiter was overall the most common lesion seen. Papillary carcinoma was the most common malignant lesion. Familiarity with the diverse morphology of neoplastic lesions of thyroid helps in providing quality care for patients as they have prognostic significance. Consequently, the diagnosis and management of thyroid lesions is dependent on both the clinician and pathologist for better patient care. Therefore, detailed histopathological analysis of thyroid lesions contributes significantly to the diagnosis, management and prognosis of the patient as small lesions in thyroid may present with dual pathology which can be picked up on detailed grossing and microscopic examination for accurate diagnosis and management. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective: To evaluate the association of TSH, free T3 (FT3), free T4 (FT4), and conversion (FT3:FT4) ratio values with incident hypertension. Materials and methods: The study included data from participants of the ELSA-Brasil study without baseline hypertension. Serum TSH, FT4 and FT3 levels, and FT3:FT4 ratio values were assessed at baseline, and incident hypertension (defined by blood pressure levels ≥ 140/90 mmHg) was estimated over a median of 8.2 years of follow-up. The risk of incident hypertension was evaluated considering a 1-unit increase in TSH, FT4, FT3, and conversion ratio values and after dividing these variables into quintiles for further analysis using Poisson regression with robust variance. The results are presented as relative risks (RR) and 95% confidence intervals (CIs) before and after adjustment for multiple variables. Results: The primary analysis incorporated data from 5,915 euthyroid individuals, and the secondary analysis combined data from all euthyroid individuals, 587 individuals with subclinical hypothyroidism, and 31 individuals with subclinical hyperthyroidism. The rate of incident hypertension was 28% (95% CI: 27%-29.3%). The FT4 levels in the first quintile (0.18-1.06 ng/dL) were significantly associated with incident hypertension (RR: 1.03, 95% CI: 1.01-1.06) at follow-up. The association between FT4 levels in the first quintile and incident hypertension was also observed in the analysis of combined data from euthyroid individuals and participants with subclinical thyroid dysfunction (RR: 1.04, 95% CI: 1.01-1.07). The associations were predominantly observed with systolic blood pressure levels in euthyroid individuals. However, in the combined analysis incorporating euthyroid participants and individuals with subclinical thyroid dysfunction, the associations were more pronounced with diastolic blood pressure levels. Conclusion: Low FT4 levels may be a mild risk factor for incident hypertension in euthyroid individuals and persons with subclinical thyroid dysfunction.

Background This study investigates the association between thyroid function and frailty in the old patients using representative data. Methods The study was conducted using data from the Korea National Health and Nutrition Examination Survey conducted from 2013 to 2015. The study population included 2,416 participants aged 50 years and older with available thyroid function test data. Frailty assessment was performed using the Fried frailty phenotype. The prevalence of frailty was analyzed across different thyroid diseases and thyroid function parameters. Results The significant association between thyroid dysfunction and frailty was observed in overt hyperthyroidism and subclinical hyperthyroidism. After adjusting for various factors, the association between thyroid dysfunction and frailty remained significant. On the other hand, overt hypothyroidism did not show a significant association with frailty in the adjusted analysis. For individuals with overt hyperthyroidism and subclinical hyperthyroidism, higher levels of free thyroxine (FT4) were significantly associated with an increased risk of frailty (aOR >999; 95% CI, >999 to 999). Among individuals with overt hypothyroidism, lower level of FT4 levels and high thyrotropin (TSH) levels showed a significant association with frailty risk (FT4: aOR,

Introduction: Type 2 deiodinase (DIO2) enzyme plays a vital role in peripheral T4 to T3 conversion and in the negative feedback regulation of pituitary thyroid-stimulating hormone (TSH) secretion. Thr92Ala polymorphism (rs225014) is a common single-nucleotide polymorphism (SNP) that lowers DIO2 activity and is associated with diverse physiological disorders. Differentiated thyroid cancer (DTC) patients are given L-T4 therapy after total thyroidectomy and 131I treatment to suppress TSH levels. Aim: The aim of the study was to determine the frequency of rs225014 in DTC patients and to investigate its effect on the thyroid function tests (TFTs) and L‑T4 dose required to suppress TSH levels. Materials and Methods: The study included a DTC patient group and a control group. TFTs were estimated by RIA/IRMA kits. Genomic DNA of all the subjects was screened for rs225014 SNP by polymerase chain reaction. Results: The frequency of Thr/Thr (wild type), Thr/Ala (heterozygous mutant), and Ala/Ala (homozygous mutant) genotypes in the DTC patients’ group was 0.21, 0.52, and 0.27, respectively. T3 levels and T3/T4 ratio were significantly low in the Ala/Ala genotype in the DTC group indicating impaired DIO2 activity. L-T4 dose requirement to suppress TSH levels in the DTC patients harboring rs225014 SNP was not statistically different from the wild-type genotype. Conclusion: The SNP rs225014 was observed to be associated with T3 and T3/T4 ratio but not with the L-T4 dose in DTC harboring SNP suggesting the presence of a compensatory pathway to overcome DIO2 impairment. However, it is essential to study the genetic makeup of DTC patients showing reduced response to TSH suppression to enable quicker decision‑making in the implementation of personalized L‑T4 dose to prevent any adverse effects. [ABSTRACT FROM AUTHOR]

The United States (US) Food and Drug Administration (FDA) has issued multiple statements and guidelines since 2015 on the topic of thyroid function testing in babies and children through 3 years old after receiving iodinated contrast media for medical imaging exams. In April 2023, the FDA adjusted this recommendation to target babies and young children younger than 4 years of age who have a history of prematurity, very low birth weight, or underlying conditions which affect thyroid gland function, largely in response to solid arguments from expert statements from the American College of Radiology (ACR) which is endorsed by the Society for Pediatric Radiology (SPR), Pediatric Endocrinology Society (PES), and the Society for Cardiovascular Angiography & Intervention (SCAI). Herein we describe our approach and development of a clinical care guideline along with the steps necessary for implementation of the plan including alterations in ordering exams requiring iodinated contrast media, automatic triggering of lab orders, reporting, and follow-up, to address the 2022 FDA guidance statement to monitor thyroid function in children after receiving iodinated contrast media. The newly implemented clinical care guideline at Ann and Robert H. Lurie Children's Hospital of Chicago remains applicable following the 2023 updated recommendation from the FDA. We will track patients less than 3 months of age who undergo thyroid function testing following computed tomography (CT), interventional radiology, and cardiac catheterization exams for which an iodinated contrast media is administered as a clinical care quality initiative. [ABSTRACT FROM AUTHOR]

Objective: Upper gastrointestinal complaints are common in patients with euthyroid goiter and subclinical hypothyroidism for whom follow-ups are performed without treatment. This study evaluated gastroparesis using radionuclide imaging in patients with dyspepsia. Methods: A total of 56 adult patients were included in this retrospective study. The average age of the patients was calculated as 70.88±2.33 years. Euthyroid goiter was observed in 29 patients and subclinical hypothyroidism in 27 patients. A liquid gastric emptying scintigraphy test was performed on all patients, and thyroid function tests, thyroid ultrasonography, and body mass index evaluations were performed. Regions of interest, including the antrum and fundus, were drawn from anterior images. A time activity curve was obtained. Results: The gastric emptying half-time was calculated using liquid gastric emptying scintigraphy. This value was found to be significantly higher in patients with subclinical hypothyroidism than in those with euthyroid goiter (p=0.033). Gastric emptying was prolonged in 17 subclinical hypothyroidism patients (63%) and 10 (34.5%) patients diagnosed with euthyroid goiter. Conclusion: Liquid gastric emptying scintigraphy may be preferred in elderly patients with suspected gastroparesis because of its easy application and short duration. Detecting the prolongation of gastric emptying time due to the presence of gastroparesis in subclinical hypothyroidism and euthyroid goiter cases followed up without treatment may guide the prescription of treatment. [ABSTRACT FROM AUTHOR]

Thyroid disorders have witnessed a surge in prevalence over the last two decades, ranking as the most prevalent endocrine disorders after metabolic syndrome. These encompass hyperthyroidism, hypothyroidism, thyroiditis, and the presence of potentially benign or malignant thyroid nodules. Thyroid hormone, crucial for normal development, growth, and metabolic regulation, undergoes activation from thyroxine to triiodothyronine, influencing a myriad of genes. The cellular signaling pathway is intricately regulated, involving thyroid hormone transporters, receptor isoforms, and interactions with corepressors and coactivators. Non-genomic actions of thyroid hormone have also come to light. The hypothalamic-pituitary-thyroid axis primarily governs thyroid function and hormone levels, complemented by other feedback loops. Thyroid function tests (TFTs) encompass thyrotropin (TSH), free thyroxine (FT4), and free triiodothyronine (FT3) levels. Evolving evidence suggests that optimal thyroid hormone levels may vary within the normal range, influencing clinical outcomes. There is no universally established optimum, but mid-range levels may best signify euthyroidism. In hypothyroidism, elevated TSH levels and low FT4 and FT3 levels are indicative, while hyperthyroidism manifests with low TSH levels and elevated FT4 and/or FT3 levels. Recent research proposes a paradigm shift towards evaluating and treating hypothyroidism based on thyroxinemia rather than relying solely on TSH levels. Furthermore, metabolic syndrome, characterized by interconnected metabolic abnormalities, exhibits a heightened risk in individuals with thyroid dysfunction, particularly hypothyroidism. Insulin resistance, attributed to thyroid dysfunction, potentially underlies metabolic syndrome. Understanding these intricacies paves the way for more effective clinical management. [ABSTRACT FROM AUTHOR]

Context: The lack of syndrome-specific reference ranges for thyroid function tests (TFT) among pediatric patients with Down syndrome (DS) results in an overestimation of the occurrence of hypothyroidism in this population. Objective: To (a) outline the age-dependent distribution of TFT among pediatric patients with DS; (b) describe the intraindividual variability of TFT over time; and (c) assess the role of elevated thyrotropin (TSH) in predicting the future onset of overt hypothyroidism. Methods: In this retrospective, monocentric, observational analysis, we included 548 patients with DS (0-18 years) longitudinally assessed between 1992 and 2022. Exclusion criteria were abnormal thyroid anatomy, treatments affecting TFT, and positive thyroid autoantibodies. Results: We determined the age-dependent distribution of TSH, FT3, and FT4 and outlined the relative nomograms for children with DS. Compared with non-syndromic patients, median TSH levels were statistically greater at any age (P < .001). Median FT3 and FT4 levels were statistically lower than controls (P < .001) only in specific age classes (0-11 for FT3, 11-18 years for FT4). TSH levels showed a remarkable fluctuation over time, with a poor (23%-53%) agreement between the TSH centile classes at 2 sequential assessments. Finally, the 75th centile was the threshold above which TSH values predicted future evolution into overt hypothyroidism with the best statistical accuracy, with a satisfactory negative predictive value (0.91), but poor positive predictive value (0.15). Conclusion: By longitudinally assessing TFT in a wide pediatric DS population, we outlined the syndrome-specific reference nomograms for TSH, FT3, and FT4 and demonstrated a persistent upward shift of TSH compared to non-syndromic children. [ABSTRACT FROM AUTHOR]

Introduction:Hospitalized coronavirus disease-2019 (COVID-19) individuals were studied in terms of their thyroid functioning with respect to their disease severity and mortality rate.Methods:The thyroid function tests of 781 in patients with severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) pneumonia outside the intensive care units were examined as part of this retrospective investigation, which was conducted in a single center. Data from the patients were categorized as deceased or discharged. Based on their diagnostic categories, the patients were grouped according to their thyroid stimulating hormone (TSH), free thyroxine (fT4), and free triiodothyronine (fT3) values. TSH, fT4, and fT3 levels were assessed within 24 h after admission.Results:Of the 781 patients who had COVID-19 of, 726 were discharged and 55 died. When compared to the discharged group, deceased patients exhibited lower than normal TSH and fT3 levels (p

ObjectiveTo investigate the correlations between thyroid function, renal function, and depression.MethodsClinical data of 67 patients with Major depressive disorder (MDD) and 36 healthy control subjects between 2018 and 2021 were collected to compare thyroid and renal function. Thyroid and renal functions of depressed patients were then correlated with the Hamilton Depression Rating Scale (HAMD) and the Hamilton Anxiety Rating Scale (HAMA).Spearman correlation analysis was used to find the correlation between renal function, thyroid function, and depression. A logistic regression was performed to find significant predictors of depression.ResultsTriiodothyronine protamine (T3), thyroxine (T4), free triiodothyronine protamine (FT3), uric acid, sodium, and anion gap were lower in the MDD group than in the control group (p

Introduction- Chronic thyroiditis embraces a heterogenous group of thyroiditis. Hashimoto’s thyroiditis forms the largest and clinically most significant cause of chronic thyroiditis. FNAC of thyroid provides a safe and accurate method of diagnosis of this condition. As there is paucity of literature on Hashimoto’s thyroiditis and the input of patients presenting with features of Hashimoto’s thyroiditis is on the rise, this study is under taken to correlate the cytomorphological features of Hashimoto’s thyroiditis with clinical, biochemical and with antithyroid antibodies where ever feasible. Objectives 1. Analysis of cytomorphological features on FNAC in Hashimito’s thyroiditis. 2. To determine the correlation between various cytomorphological features and biochemical & serological parameters in cases diagnosed as HT. 3. To correlate cytological diagnosis with histopathology wherever possible. Materials and Methods This prospective study was conducted on 100 patients attending the cytopathology department of Adichunchanagiri Institute Of Medical Sciences, B.G. Nagara. Cytologically proven, cases of Hashimoto’s thyroiditis over a period of two years, from November 2017 to May 2019 formed the study material. The various parameters like patients clinical presentation, antithyroid antibodies & hormonal profiles, were studied. Fine needle aspiration of thyroid gland and grading of thyroiditis was done on smears. The grades were correlated with above parameters and the correlation indices were evaluated statistically. RESULTS: Most of the patients were females (97%) who presented with a diffuse goiter (91.%). Hypothyroid features were present in 62.7% of cases. Anti TPO antibody showed positivity in.93.4% of patients. Cytomorphologic spectrum of Hashimoto’s thyroiditis was analysed and graded. Most of them had grade II disease by cytology. No correlation was observed between grades of cytomorphology and biochemical & serologic parameters. Conclusion Despite the availability of several tests for diagnosis of Hashimoto’s thyroiditis, ‘FNAC’ remains the gold standard. [ABSTRACT FROM AUTHOR]

Objective: The variability of thyroid function tests (TFTs) during antithyroid drug (ATD) therapy and its association with adverse health outcomes have not been previously studied. The aim of this study was to evaluate the association of TFT variability and cardiovascular morbidity during ATD therapy. Design: Retrospective cohort study. Patients and Measurements: Hyperthyroid patients (n = 394) treated with ATD therapy at Tampere University Hospital between March 2016 and December 2018 were followed up for a median time of 1.5 years (interquartile range 0.8–2.0). The coefficients of variation (CVs) of the follow‐up thyroid‐stimulating hormone (TSH), free thyroxine (fT4) and free triiodothyronine (fT3) measurements were determined. The associations of TFT variability and baseline clinical factors with cardiovascular disease (CVD) ‐associated hospital visits were assessed with logistic regression analyses. Results: In the multivariable analyses, age (odds ratio [OR]: 1.06, 95% confidence interval [CI]: 1.03–1.09), male gender (OR: 2.33, 95% CI: 1.03–5.28) and fT4‐CV (OR: 1.02, 95% CI: 1.01–1.04) were independent risk factors for cardiovascular morbidity, whereas baseline positive thyrotropin receptor antibodies (TRAbs) were associated with lower cardiovascular morbidity (OR: 0.29, 95% CI: 0.14–0.61). When the patients with baseline TRAb positivity were studied separately, fT4‐CV was associated with cardiovascular morbidity (OR: 1.03, 95% CI: 1.00–1.05). Conclusions: During ATD therapy, fT4 variability is associated with an increased cardiovascular morbidity. Although positive TRAbs are associated with a lower cardiovascular morbidity compared with hyperthyroidism with negative autoantibodies, the variability of fT4 is associated with cardiovascular morbidity also in patients with positive TRAbs. [ABSTRACT FROM AUTHOR]

Disorders of the thyroid gland are common within the global adult population. In the UK thyrotoxicosis has a prevalence of 2% in women and 0.2% in men. The prevalence increases to greater than 5% in those aged over 60. Similarly, hypothyroidism is found in 2% of the UK population and in a higher propotion of those over 60 at 5% (National Institute for Health and Care Excellence [NICE], 2019). Thyroid disease affects the normal structure and function of the thyroid gland with multisystemic effects and a range of disease severity. Certain thyroid disorders are amenable to surgical correction and are encountered with increasing frequency by the anaesthetist. A sound understanding of the pathophysiology of thyroid disease including associated systemic effects is essential in providing safe perioperative care to these patients. In this educational article we will consider thyroid anatomy, pathophysiology and perioperative anaesthetic management for patients presenting for thyroid surgery in the context of hyperthyroidism, hypothyroidism and thyroid malignany. [ABSTRACT FROM AUTHOR]

Objective: Although the role of thyroid hormones in functional and anatomical closure of patent ductus arteriosus (PDA) is well known, their effects on the medical or surgical closure of PDA in newborns remain unclear. This study aimed to assess the correlation between thyroid function tests and PDA closure through medical or surgical interventions in newborns. Methods: This retrospective study was conducted on 65 newborns diagnosed with hemodynamically significant PDA (hs-PDA), with a premature rate of 81.5% (n=53). The subjects were divided into two groups according to the nature of the ductal closure as medically responsive "MR-PDA" or surgically treated "ST-PDA". The groups were compared in terms of thyroid hormone levels and other clinical parameters. Results: Thirty-three (51%) of all 65 patients had PDA and responded to medical treatment. Gestational week, birth weight, and mode of delivery were similar between the medical and surgical treatment groups (p>0.05). Free thyroxine levels were significantly lower in the MR-PDA group than in the ST-PDA group (p=0.01). Conclusions: Because hs-PDA is associated with increased morbidity and mortality in the neonatal period, especially in premature infants, we hypothesize that thyroid hormone levels may play a role in the closure of hs-PDA. [ABSTRACT FROM AUTHOR]

Context: Somatostatin analogs are recommended for preoperative therapy in thyrotrophin secreting pituitary adenomas (TSHomas). Octreotide suppression test (OST) was designed to differentiate TSHomas with resistance to thyroid hormones, while its ability to test the sensitivity of SSA has not been fully studied. Objective: To test the sensitivity of SSA in TSHomas with OST. Patients: We collected 48 pathologically confirmed TSHoma patients with complete 72 h' data of OST into analysis. Intervention: Octreotide suppression test. Main Outcome: Sensitivity timepoint and cutoff of OST. Results: During the entire OST, the TSH descended maximally 89.07% (73.85%, 96.77%), while the FT3 and FT4 declined slowly [43.40% (37.80%, 54.44%) and 26.59% (19.01%, 33.13%), respectively]. The 24th hour was the timepoint wherein the stability occurs for TSH, and the 48th hour for FT3 and FT4 during OST. In the patients who received both short‐ and long‐acting somatostatin analogs (SSA), the 24‐h timepoint was the most predictive timepoint for the percentage of TSH decline (Spearman's rank correlation analysis, r =.571, p <.001), while the 72‐h timepoint was optimal for predicting the magnitude of TSH decline (Spearman's rank correlation analysis, r =.438, p =.005). In the 24th timepoint, a positive correlation was also observed between TSH suppression rate and the percentage decrease and absolute value decrease of FT3 and FT4. Furthermore, in patients treated with long‐acting SSA, the 72‐h timepoint was optimal for predicting both the percentage (Spearman's rank correlation analysis, r =.587, p =.01) and magnitude (Spearman's rank correlation analysis, r =.474, p =.047) of TSH decline. The 24th hour was the optimal timepoint with 44.54% (50% of median value of TSH in 72‐hOST) decrease of TSH being the observing cutoff. The adverse effect of OST was predominantly occurred in the gastrointestinal system and no severe event occurred during OST. Paradoxical response could occur in OST and it did not influence the effect of SSA as long as sensitivity was confirmed. A high level of hormonal control was achieved in the SSA‐sensitive patients. Conclusion: OST can be used as an efficient tool to guide the adequate use of SSA. [ABSTRACT FROM AUTHOR]

Introduction: Hospitalized coronavirus disease-2019 (COVID-19) individuals were studied in terms of their thyroid functioning with respect to their disease severity and mortality rate. Methods: The thyroid function tests of 781 in patients with severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) pneumonia outside the intensive care units were examined as part of this retrospective investigation, which was conducted in a single center. Data from the patients were categorized as deceased or discharged. Based on their diagnostic categories, the patients were grouped according to their thyroid stimulating hormone (TSH), free thyroxine (fT4), and free triiodothyronine (fT3) values. TSH, fT4, and fT3 levels were assessed within 24 h after admission. Results: Of the 781 patients who had COVID-19 of, 726 were discharged and 55 died. When compared to the discharged group, deceased patients exhibited lower than normal TSH and fT3 levels (p<0.001; for both). Notwithstanding, there was no significant difference between deceased and discharged patients regarding fT4 values. 115 (14.7%) patients had thyroid dysfunction (16 patients had elevated TSH, 99 had TSH levels below the reference value) and 154 (19.7%) patients had non-thyroidal illness (NTI). The individual effect of thyroid function tests on patient death was investigated using the log rank test, and fT3 levels were found to be significant for predicting mortality. Conclusion: Our findings imply that thyroid function tests, especially in severe patients, may have prognostic significance. Lower fT3 and TSH levels may be associated with systemic inflammation, which could be a prognostic value associated with the disease state and mortality rate. fT3 was shown to be an independent risk factor for death. As a result, approximately 15% of the patients were observed to have thyroid dysfunction and 19.7% were NTI, which were all linked to severe disease status. [ABSTRACT FROM AUTHOR]

Introduction: Various studies have assessed the link between the thyroid and kidney and concluded that dysfunction in one organ can disrupt the other. Thyroid dysfunction is more prevalent in individuals with end-stage renal disease (ESRD) compared to the general population. Hypothyroid ESRD patients have higher mortality than euthyroid patients. In this study, we evaluated the prevalence of hypothyroidism in dialysis-dependent ESRD patients and assessed the association of possible prognostic factors with mortality.Methods: Patients who were undergoing dialysis in centers affiliated with the Mashhad University of Medical Sciences were enrolled and followed for a year to obtain survival rates. Lab parameters including thyroid stimulating hormone (TSH), parathyroid hormone (PTH), and magnesium (Mg) were recorded at baseline, and the relationship between these values and mortality was assessed.Results: The prevalence of hypothyroidism was 23% and 32.5% in hemodialysis and peritoneal dialysis patients, respectively. Blood urea was meaningfully higher in hemodialysis patients, while hypocalcemia and hyponatremia were more common in peritoneal dialysis patients. Higher ages (P=0.006), lower baseline Mg (P=0.044) and PTH (P=0.01), and diabetes (P=0.037) were all linked to a higher risk of mortality.Conclusion: Hypothyroidism was notably prevalent in our study population. As hypothyroidism is associated with higher mortality, proper screening and intervention in this group are essential. We recommend the prescription of supplementary Mg in dialysis patients as baseline Mg and PTH levels are associated with better outcomes in this group. Diabetes was also associated with higher mortality. Maintaining glycated hemoglobin between 6%-8% is therefore suggested to increase the survival of diabetic patients.

Background: Multiple sclerosis is a chronic disease believed to be the result of autoimmune disorders of the central nervous system, characterised by inflammation, demyelination, and axonal transection, affecting primarily young adults. Disease modifying therapies have become widely used, and the rapid development of these drugs highlighted the need to update our knowledge on their short- and long-term safety profile. Objective: The study aim is to evaluate the impact of disease-modifying treatments on thyroid functions and thyroid autoantibodies with subsequent effects on the outcome of the disease. Materials and Methods: A retro prospective study enrolled 45 patients who were registered and diagnosed in the Multiple Sclerosis Clinic according to the revised McDonald criteria (2017). Blood samples for thyroid functions and thyroid autoantibody tests were taken before, 3 months and after 6 months from the start of disease modifying therapy. The Expanded Disability Status Scale was used to assess the severity of the disease before and after 6 months of receiving treatment. Results: 45 patients with the mean age of 33.3 years, a standard deviation (SD) of ± 9.5 years were enrolled in this study. (64.4%) patients’ age was between 20 - 39 years. The mean free T3 decreased significantly, while the mean anti-TPO and anti-TG increased after three months compared to its baseline level. After six months of treatment, the mean free T4 decreased significantly, while the mean TSH increased compared to its baseline level. There were no statistically significant correlations between the baseline (EDSS) score and after 6 months of therapy. Conclusion Thyroid hormone dysfunction and thyroid autoimmune antibody levels that changed in response to interferon beta therapy in patients with multiple sclerosis may be temporary and not associated with poor outcomes.

Introduction: Diabetes mellitus is the most common endocrine disorder. It is a state of persistent hyperglycemia secondary to defects in insulin secretion, insulin action, or both. The development of Diabetes involves several pathogenic processes ranging from autoimmune destruction of the β cells of the pancreas resulting in absolute insulin deficiency, to other abnormalities that result in insulin resistance. Thyroid hormones and Insulin have both agonist and antagonist action in glucose homeostasis. The most common endocrine disorder after diabetes mellitus is thyroid disorder. Hence, it is common to be affected by both thyroid disease and diabetes. This study also helps in recognition of the interdependent relationship between thyroid disease and diabetes and guides clinicians on the optimal management of both these conditions. Materials And Methods: 100 Type 2 Diabetic patients were analyzed in this study. A structured questionnaire designed for the study was used to collect the demographic details and the history related to their illnesses. A complete physical and systemic examination was conducted on all patients, and the findings were recorded. The following investigations were carried out on the study subjects like fasting and postprandial blood sugars, HbA1C levels, thyroid profile which includes t3, t4, TSH levels as needed. Results: The mean age (years) of the study group was 54.57. Males were outnumbered by females in the study. Thyroid dysfunction was present in 23% patients. Of this 16.0% of the patients had subclinical hypothyroidism,6.0%of the patients had Hypothyroidism,1.0%of the patients had Hyperthyroidism. None of them had subclinical hyperthyroidism. Of these 91 patients, 48.3% had subclinical hypothyroidism, 24.2% had subclinical hyperthyroidism and 23.1% had hypothyroidism, females had more prevalence of thyroid disorders compared to males Conclusion: After having reviewed the results and significant findings of the above study, it can be concluded that Thyroid dysfunctions are prevalent in the diabetic population, and this further emphasises the need to screen for thyroid dysfunctions routinely to improve the quality of life and reduce morbidity. [ABSTRACT FROM AUTHOR]

In patients with elevated thyroid-stimulating hormone levels but clinically euthyroid, non-thyroid causes of thyroid-stimulating hormone elevation should be considered. A careful approach is required when making a treatment decision for these patients because there are many different conditions, including macro -thyr oid-s timul ating hormone, that can increase thyroid-stimulating hormone levels. We present 2 patients, a 38-year-old man and an 87-year-old woman. Both of them applied to the endocrinology outpatient clinic because of their high thyroid-stimulating hormone levels. Both patients were using levothyroxine treatment at the time of admission. While thyroidstimulating hormone levels were high in both patients under levothyroxine treatment, free thyroxine and free tri-iodothyronine levels were within the normal range. Both were clinically euthyroid. When levothyroxine doses were increased in both patients due to high thyroid-stimulating hormone levels, symptoms of thyrotoxicosis developed and free thyroxine levels increased, but thyroid-stimulating hormone levels were still high. No pathological physical examination findings were detected. No discrepancy was found in the detailed query in terms of treatment compliance. There was no drug use or acute stress situations. Thyroid hormone resistance and heterophile antibody interference were excluded. The thyroid-stimulating hormone level was measured again with polyethylene glycol precipitation method in terms of immunoglobulin and thyroid-stimulating hormone complex macromolecule (macr o-thy roid-stimu latin g hormone). Polyethylene glycol -precipitated thyroid-stimulating hormone levels were found to be 0.16 and 0.128 µIU/mL (0.27-4.2), respectively. Macro -thyr oid-s timul ating hormone is a macromolecule formed as a result of the complex binding of thyroidstimulating hormone with immunoglobulins. Macro -thyr oid-s timul ating hormone is considered biologically inactive. These patients are clinically euthyroid. False-elevated thyroid-stimulating hormone may be detected in patients harboring macro -thyr oid-s timul ating hormone. Misdiagnosing these patients may result in unnecessary treatment. [ABSTRACT FROM AUTHOR]

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Current American Academy of Pediatrics (AAP) Guidelines recommend monitoring thyroid function in infants with Down syndrome (DS) at birth, 6 and 12 months, and annually thereafter. This study aimed to determine whether these guidelines are optimal for early diagnosis and treatment of (subclinical) hypothyroidism. Enrolled infants with DS less than age 7 months, born at ≥ 30 weeks gestation to monitor thyroid function test (TFT). A filter paper (FP) blood sample was analyzed for TSH and total T4 at ages 2 and 4 weeks and monthly thereafter until 12 months. Subjects with abnormal FP sample and confirmatory serum TFT for hypothyroidism promptly started treatment. Subjects with thyroid dysfunction identified had thyroid antibodies measured at diagnosis and 12 months. Descriptive statistics determined average time to diagnosis of abnormal TFT. Sixteen (30%) of 54 subjects were diagnosed with a thyroid disorder, the majority with subclinical hypothyroidism (SH) and 1 with hyperthyroidism. Diagnosis occurred in 6 (11%), 9 (17%), and 12 (22.2%) infants in the first 30, 60, and 90 days of life (DOL), respectively. Eight infants had an abnormal NBS and half were diagnosed with a thyroid disorder by DOL 8 and the remainder prior to 4 months. Among subjects with a normal NBS, four were diagnosed at a mean of 104 days and three at a mean of 101 days prior to the 6-month and 12-month routine screens, respectively. Conclusion: Based on current AAP guidelines, thyroid disorder diagnosis would have been delayed in nearly 20% of the subjects. An additional TFT screen at 1 and 3 months can lead to earlier diagnosis and treatment. What is Known: • Current American Academy of Pediatrics (AAP) Guidelines recommend thyroid function tests (TFT) in infants with Down syndrome (DS) at birth and 6 and 12 months. • Peer- reviewed retrospective studies report an increased incidence of hypothyroidism in infants with DS undetected by the newborn screen (NBS) and prior to 6 months. What is New: • This prospective study monitored TFT in infants with DS at age 2 weeks and monthly throughout the first year of life. • The findings in this study support additional TFT screens at 1 and 3 months in infants with DS. [ABSTRACT FROM AUTHOR]

Congenital hypothyroidism is one of the most common causes of preventable intellectual disability in the UK and worldwide. Early diagnosis is critical to allow for early intervention. At present, 1 in 2000 to 1 in 3000 babies born in the UK have congenital hypothyroidism. Of these, most will not display any clinical manifestations or symptoms in the first few weeks of life. In short, babies will develop intellectual disability if they go undiagnosed. It is therefore no surprise that the day 5 blood spot is essential for good outcomes and harm reduction. Diagnosis of thyroid disorder is based on measuring the thyroid hormones and thyroid stimulating hormone levels. The most common cause of congenital hypothyroidism is an abnormality in thyroid gland development (dysgenesis) but it may also be the result of a defect in thyroid hormonogenesis or may be temporary as a result of maternal medications passing through the placenta, maternal blocking antibodies or iodine excess or deficiency. Rarely, it is the result of pituitary or hypothalamic abnormality when it is called central or secondary/tertiary hypothyroidism. This short article offers practical advice on how to diagnose and treat congenital hypothyroidism and how to interpret the results of available biochemical tests. [ABSTRACT FROM AUTHOR]

Context: Reports of thyroid dysfunction following COVID-19 vaccination included cases of relapse of Graves’ disease and worsening of preexisting Graves’ disease. Little is known about the thyroid-specific outcomes among patients treated for hyperthyroidism who have received COVID-19 vaccination. Objective: Among patients treated for hyperthyroidism, we evaluated factors associated with not receiving the COVID-19 vaccination and whether COVID-19 vaccination was associated with thyroid function instability. Methods: We included consecutive patients treated for hyperthyroidism attending the thyroid clinic at a teaching hospital between January and September 2021. They were categorized into vaccinated and unvaccinated groups. The index date was the date of first-dose vaccination for the vaccinated group, and the first date of attendance in the inclusion period for the unvaccinated group. They were followed up until March 2022 or occurrence of thyroid function instability (worsening of thyroid function/increase in antithyroid drug dosage), whichever was earlier. Results: A total of 910 patients were included (mean age 51.6 years; 82.1% female). Of these, 86.2% had Graves disease and 67.3% were vaccinated (67.3% BNT162b2; 30.6% CoronaVac; 2.1% heterologous). Abnormal thyroid function and cardiovascular comorbidities were independently associated with unvaccinated status. Upon median follow-up of 5.3 months, thyroid function instability occurred in 15.9% of patients. COVID-19 vaccination did not increase risks of thyroid function instability (hazard ratio 0.78, 95% CI 0.56-1.09, P=.151); this was consistent in Graves disease, both types of vaccines, and regardless of whether baseline thyroid function was normal. Twenty-seven patients overtly thyrotoxic at the time of vaccination received COVID-19 vaccines without triggering a thyroid storm or difficulty in subsequent thyroid function control. Conclusion: Among patients treated for hyperthyroidism, abnormal thyroid function was a factor predicting unvaccinated status. Our results should encourage patients treated for hyperthyroidism to receive COVID-19 vaccination to protect themselves from adverse outcomes and potential long-term sequelae of COVID-19. [ABSTRACT FROM AUTHOR]

Purpose: We evaluated the evolution of thyroid function and autoimmunity among COVID-19 survivors over 6 months in relation to interferon beta-1b treatment and long COVID. Methods: We included COVID-19 survivors managed in a major COVID-19 centre between July 2020 and May 2021 who were reassessed three and/or six months after acute COVID-19. Thyroid function tests (TFTs) and anti-thyroid antibody titres were measured at acute COVID-19, 3-month and 6-month. Results: 250 COVID-19 survivors were included (mean age 52.7 years, 50.4% men). Persistent thyroid function abnormalities were more likely in those with abnormal TFTs in acute COVID-19 (P < 0.001). Among 51 patients with abnormal TFTs in acute COVID-19, 82.4% resolved upon follow-up. Of 199 patients with normal TFTs in acute COVID-19, only 4.5% had incident abnormal TFTs, more likely in interferon-treated patients (P = 0.044) and none clinically overt. Among 129 patients with complete 6-month follow-up for anti-thyroid antibody titres, there was no significant change overall, except for modest increase in anti-thyroid antibody titres among the 84 interferon-treated patients (P < 0.05 at both 3 months and 6 months). Long COVID occurred in 19.5% and 10.4% at 3 and 6 months respectively, where TFTs and anti-thyroid antibody titres were not predictive of its occurrence. Conclusion: Over 6 months, most abnormal TFTs in acute COVID-19 resolved, with no significant incident thyroid dysfunction. SARS-CoV-2 infection did not lead to change in thyroid autoimmunity, while interferon treatment was associated with modest increase in anti-thyroid antibody titres. Thyroid function and anti-thyroid antibodies did not play a significant role in long COVID. [ABSTRACT FROM AUTHOR]

Background: Reference intervals (RI) are an essential section of the information that medical laboratories present to clinicians to facilitate the management process of the patient. Thyroid-stimulating hormone (TSH), free thyroxine (fT4), and free triiodothyronine (fT3) are the most valuable and cost-effective parameters of thyroid functions. According to the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC), Clinical and Laboratory Standards Institute (CLSI), and American Thyroid Association (ATA), every laboratory should determine own RI on own population and method. In this study we aim to evaluate the pediatric reference intervals in a public health laboratory. Methods: The results of TSH, fT4, and fT3 from pediatric patients (aged: 0 - 18 years) were included in our study. These results were stored in our laboratory information system. TSH, fT4, and fT3 are measured in Abbott Architect i2000 (Abbott Diagnostics, Abbott Park, IL, USA) chemiluminescent microparticle immunoassay analyzer. RI study was conducted according to CLSI EP28-A3 guidelines. Results were evaluated with MedCalc ver. 19.2.1 (MedCalc Software Ltd., Ostend, Belgium), and Minitab 19.2 (Minitab Statistical Software, AppOnFly Inc., San Fransisco, CA, USA). Results: The final study included 483 samples. Study sample consisted of 288 girls and 195 boys. Our reference intervals for TSH, fT4 and fT3 were found as 0.74 - 4.11 mIU/L, 0.80 - 1.42 ng/dL, and 2.40 - 4.38 pg/mL, respectively. Reference intervals were compatible with expected values in the insert sheets, except for fT3. Conclusions: Laboratories should implement their reference intervals based on CLSI C28-A3 guidelines. [ABSTRACT FROM AUTHOR]

In subclinical hypothyroidism, the presence of depressive symptoms is often a reason for starting levothyroxine treatment. However, data are conflicting on the association between subclinical thyroid dysfunction and depressive symptoms. We aimed to examine the association between subclinical thyroid dysfunction and depressive symptoms in all prospective cohorts with relevant data available. We performed a systematic review of the literature from Medline, Embase, Cumulative Index to Nursing and Allied Health Literature, and the Cochrane Library from inception to 10th May 2019. We included prospective cohorts with data on thyroid status at baseline and depressive symptoms during follow-up. The primary outcome was depressive symptoms measured at first available follow-up, expressed on the Beck's Depression Inventory (BDI) scale (range 0-63, higher values indicate more depressive symptoms, minimal clinically important difference: 5 points). We performed a two-stage individual participant data (IPD) analysis comparing participants with subclinical hypo- or hyperthyroidism versus euthyroidism, adjusting for depressive symptoms at baseline, age, sex, education, and income (PROSPERO CRD42018091627). Six cohorts met the inclusion criteria, with IPD on 23,038 participants. Their mean age was 60 years, 65% were female, 21,025 were euthyroid, 1342 had subclinical hypothyroidism and 671 subclinical hyperthyroidism. At first available follow-up [mean 8.2 (± 4.3) years], BDI scores did not differ between participants with subclinical hypothyroidism (mean difference = 0.29, 95% confidence interval =  - 0.17 to 0.76, I2 = 15.6) or subclinical hyperthyroidism (- 0.10, 95% confidence interval =  - 0.67 to 0.48, I2 = 3.2) compared to euthyroidism. This systematic review and IPD analysis of six prospective cohort studies found no clinically relevant association between subclinical thyroid dysfunction at baseline and depressive symptoms during follow-up. The results were robust in all sensitivity and subgroup analyses. Our results are in contrast with the traditional notion that subclinical thyroid dysfunction, and subclinical hypothyroidism in particular, is associated with depressive symptoms. Consequently, our results do not support the practice of prescribing levothyroxine in patients with subclinical hypothyroidism to reduce the risk of developing depressive symptoms.

Background: Hypothyroidism is a common endocrine disorder in the general population. Most of the cardiovascular and neurological manifestations of hypothyroidism are due to autonomic dysfunction. The American Academy of Neurology has recommended simple bedside autonomic function tests for the diagnosis and follow-up of autonomic functions. Recognition of autonomic dysfunction and treatment of hypothyroidism may improve cardiovascular outcomes. This study aims to assess autonomic dysfunction in hypothyroidism and correlate it with serum thyroid-stimulating hormone (TSH) levels. Materials and Methods: This cross-sectional study was conducted on 60 patients diagnosed with hypothyroidism for 12 months at a tertiary care center in Southern India. Patients with a Zulewski clinical score over 5 and fulfilling the selection criteria were included in the study after obtaining written informed consent. Details of history, treatment, examination, and thyroid function tests data were collected and bedside tests for autonomic functions were performed. Results: Ninety percent of individuals were female, and the average age of the included study population was 40.38 ± 11.78 years. Based on TSH and FT4 values, the patients were subgrouped into currently euthyroid and overt hypothyroid individuals. The majority of the individuals (81.67%) included in the study had autonomic dysfunction. Based on the autonomic dysfunction score, there was a significantly higher proportion of overt hypothyroid individuals (n = 18) with severe autonomic dysfunction compared to euthyroid individuals (n = 4). About 75% of the study individuals had sympathetic dysfunction and 66.7% of individuals had parasympathetic dysfunction. There was no statistically significant association between autonomic dysfunction and the duration of hypothyroidism. Conclusion: Autonomic dysfunction in hypothyroidism is common; sympathetic dysfunction was observed more as compared to parasympathetic dysfunction.

Introduction: Thyroid function tests (TFT) are extensively used in daily clinical practice. Here, we described a case of incongruent TFT both in a pregnant woman and in her newborn. Case presentation: A 32-year-old woman, diagnosed with autoimmune thyroiditis during her first pregnancy, was monitored during her second gest ation. At week 5 + 2 days, thyroid-stimulating hormone (TSH) and free thyroxine (FT4) values (Dimension VISTA 1500, Siemens Healthineers) were within normal limits. At week 19 + 5 days, TSH remained normal while FT4 increased approximately by three-fold. FT4 inconsistency was with both TSH and the clinical status since she continued to be clinically euthyroid. On the same serum sample, thyroid autoantibodies were negative. At week 25 + 4 days, the patient complained of palpitations and dyspnea, with tachycardia. Even though TSH was normal, high levels of both FT4 and free triiodothyronine (FT3) were interpreted as evidence of thyroid overactivity and methimazole was started. TFT of the pregnant woman continued to be monitored throughout gestation. Postpartum FT4 and FT3 gradually returned to normal. TFT, performed on the daughter’s serum, 3 days after birth, showed the same inconsistency as her mother but without clinical signs of congenital hyperthyroidism. Based on the clinical and laboratory setting, the presence of circulating autoantibodies against T3 and T4 (THAb) was suspected and demonstrated by radioimmunoprecipitation. Conclusion: Analytical interferences should be supposed when TFT do not fit with the clinical picture and despite their infrequency, THAb must also be considered. To our knowledge, this is the first case describing the passage of THAb to the newborn.

BackgroundAdvanced chronic kidney disease (CKD) patients, including those receiving dialysis, have a high prevalence of thyroid dysfunction. Although hypothyroidism is associated with higher death risk in end-stage renal disease (ESRD) patients, no studies have examined whether thyroid status in the pre-ESRD period impacts mortality after dialysis initiation.MethodsAmong US veterans with CKD identified from the national Veterans Affairs database that transitioned to dialysis over the period from October 2007 to September 2011, we examined the association of pre-ESRD serum thyrotropin (TSH) levels averaged over the 1-year pre-dialysis ('prelude') period with all-cause mortality in the first year following dialysis initiation.ResultsAmong 15 335 patients in the 1-year prelude cohort, TSH levels >5.0 mIU/L were associated with higher mortality in expanded case-mix Cox models (reference: TSH 0.5-5.0 mIU/L): adjusted hazard ratio (aHR) [95% confidence interval (CI) 1.20 (1.07-1.33). Similar findings were observed for TSH >5.0 mIU/L and mortality in the 2- and 5-year cohorts: aHRs (95% CI) 1.11 (1.02-1.21) and 1.15 (1.07-1.24), respectively. Analyses of finer gradations of TSH in the 1-year prelude cohort demonstrated that incrementally higher levels >5.0 mIU/L were associated with increasingly higher mortality in expanded case-mix models (reference: TSH 0.5-3.0 mIU/L): aHRs (95% CI) 1.18 (1.04-1.33) and 1.28 (1.03-1.59) for TSH levels >5.0-10.0 mIU/L and >10.0 mIU/L, respectively. In the 2- and 5-year cohorts, mortality associations persisted most strongly for those with TSH >10.0 mIU/L, particularly after laboratory covariate adjustment.ConclusionsAmong new ESRD patients, there is a dose-dependent relationship between higher pre-ESRD TSH levels >5.0 mIU/L and post-ESRD mortality. Further studies are needed to determine the impact of TSH reduction with thyroid hormone supplementation in this population.