Subclinical Hypothyroidism and Thyroid Autoimmunity in Pregnancy: To Treat or Not to Treat.

Subclinical hypothyroidism and thyroid autoimmunity in pregnancy are common conditions. They are both associated with adverse maternal and offspring outcomes. Women with thyroid autoimmunity should be monitored with regular thyroid function tests preconception and during gestation to identify women who develop hypothyroidism. The effectiveness of thyroid hormone treatment in reducing adverse outcomes in pregnancy has been studied in a number of randomized controlled trials. Current evidence shows obstetrical benefits of levothyroxine treatment in pregnant women with a thyroid-stimulating hormone level greater than 4 mU/L.

Thyroid Disorders.

This article includes a review of information primary care physicians need to know direct their evaluation and treatment of thyroid disorders that include sick euthyroid, hyperthyroidism, hypothyroidism, and subclinical thyroid disorders.

Thyroid dysfunction in the wake of Omicron: understanding its role in COVID-19 severity and mortality.

Purpose: SARS-CoV-2 can invade the thyroid gland. This study was to delineate the risk of thyroid dysfunction amidst the prevalence of the Omicron variant, and to investigate the correlation between thyroid function and Coronavirus disease 2019 (COVID-19) outcomes. The study also aimed to ascertain whether thyroid dysfunction persisted during COVID-19 recovery phase. Methods: This was a retrospective cohort study. COVID-19 patients from the Renmin Hospital of Wuhan University, China during the epidemic of Omicron variants were included, and their thyroid function were analyzed in groups. Results: A history of thyroid disease was not associated with COVID-19 outcomes. COVID-19 can lead to a bimodal distribution of thyroid dysfunction. The severity of COVID-19 was inversely proportional to the levels of thyroid- stimulating hormone (TSH), free triiodothyronine (FT3) and free thyroxine (FT4), leading to a higher prevalence of thyroid dysfunction. Severe COVID-19 was a risk factor for euthyroid sick syndrome (ESS) (OR=22.5, 95% CI, 12.1 - 45.6). Neutrophil to lymphocyte ratio mediated the association between severe COVID-19 and ESS (mediation effect ratio = 41.3%, p < 0.001). ESS and decreased indicators of thyroid function were associated with COVID-19 mortality, while high levels of FT3 and FT4 exhibited a protective effect against death. This effect was more significant in women (p < 0.05). During the recovery period, hyperthyroidism was quite uncommon, while a small percentage of individuals (7.7%) continued to exhibit hypothyroidism. Conclusion: COVID-19 severity was linked to thyroid dysfunction. Severe COVID-19 increased the risk of ESS, which was associated with COVID-19 mortality. Post-recovery, hyperthyroidism was rare, but some individuals continued to have hypothyroidism.

[Related factors of euthyroid sick syndrome in patients with sepsis].

OBJECTIVE: To evaluate the prevalence of euthyroid sick syndrome (ESS) in sepsis patients and to explore its influencing factors. METHODS: In the study, 365 patients diagnosed with sepsis in the emergency critical care department of Shanghai First People's Hospital from January 2017 to January 2023 were retrospectively enrolled. The patients were divided into ESS and non-ESS groups based on whether the patients were complicated with ESS.Baseline variables and relevant clinical data of the enrolled patients were collected. The prevalence of ESS in sepsis patients and its influencing factors were evaluated by multivariate Logistic regression analysis, and the 30-day survival rates were compared between the two groups. The optimal cutoff value for free triiodothyronine (FT3) was explored to predict death in the patients with sepsis. RESULTS: There were 103 sepsis patients with ESS, accounting for 28.2% of the total cases. The severity of sepsis in ESS group was significantly higher than that in non-ESS group (P < 0.05). The acute physiology and chronic health evaluationⅡ(APACHEⅡ)score and sequential organ failure assessment (SOFA) score of ESS group were significantly higher than those of non-ESS group (P < 0.05). C-reactive protein (CRP), procalcitonin (PCT), serum amyloid A (SAA) and interleukin-6 (IL-6) in ESS group were higher than those in non-ESS group. total cholesterol(TC)and high-density liptein cholesterol(HDL-C)in ESS group were lower than those in non-ESS group, and the differences were statistically significant (P < 0.05).Multivariate Logistic regression analysis showed that PCT, IL-6, CRP, SAA and activated partial thromboplatin time (APTT) were independent risk factors for ESS in the sepsis patients (OR values were 1.105, 1.006, 1.005, 1.009 and 1.033, respectively; 95% CI were 1.044-1.170, 1.001-1.012, 1.001-1.009, 1.005-1.014, 1.004-1.062, respectively, P < 0.05).The 30-day survival rate in ESS group was significantly lower than that in non-ESS group, the Long-rank chi-square test value was 16.611, and the difference was statistically significant (P < 0.05).The receiver operation characteristic area under the curve (AUCROC)of FT3 predicted death in the patients with sepsis was 0.924 (95% CI 0.894-0.954). The serum FT3 cutoff point was 3.705 pmol/L, the specificity was 0.868, and the sensitivity was 0.950. CONCLUSION: In this study, the incidence of ESS in sepsis patients was determined to be 28.2% with poor prognosis. The results showed that PCT, IL-6, CRP, SAA and APTT were independent risk factors for ESS in sepsis patients, while HDL-C was a protective factor (P < 0.05). FT3 is a novel potential biomarker for predicting death in patients with sepsis.

Evaluation of the First Three Years of Treatment of Children with Congenital Hypothyroidism Identified through the Alberta Newborn Screening Program.

The effectiveness of newborn screening (NBS) for congenital hypothyroidism (CH) relies on timely screening, confirmation of diagnosis, and initiation and ongoing monitoring of treatment. The objective of this study was to ascertain the extent to which infants with CH have received timely and appropriate management within the first 3 years of life, following diagnosis through NBS in Alberta, Canada. Deidentified laboratory data were extracted between 1 April 2014 and 31 March 2019 from Alberta Health administrative databases for infants born in this time frame. Time to lab collection was anchored from date of birth. Timeliness was assessed as the frequency of monitoring of Thyroid Stimulating Hormone (TSH) and appropriateness as the frequency of children maintaining biochemical euthyroidism. Among 160 term infants, 95% had confirmation of diagnosis by 16 days of age. The cohort had a median of 2 (range 0-5) TSH measurements performed in the time interval from 0 to 1 month, 4 (0-12) from 1 to 6 months, 2 (0-10) from 6 to 12 months, and 7 (0-21) from 12 to 36 months. Approximately half were still biochemically hypothyroid (TSH > 7 mU/L) at 1 month of age. After becoming euthyroid, at least some period of hypo- (60%) or hyperthyroidism (TSH < 0.2 mU/L) (39%) was experienced. More work needs to be performed to discern factors contributing to prolonged periods of hypothyroidism or infrequent lab monitoring.

Gastric bypass surgery in morbid obesity: Influence on thyroid function tests and insulin resistance status.

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.

Is Low-free Triiodothyronine (fT3) Associated with Increased Morbidity in Patients Admitted to Coronary Care Units?

BACKGROUND: The effects of thyroid hormone on patients hospitalized in coronary intensive care units are still controversial. Objective: We retrospectively examined thyroid hormone levels and their impact on cardiovascular morbidity in patients admitted to coronary intensive care units. METHODS: A total of 208 (Female/Male; 46.6%/53.4%) patients without any history of thyroid disease were enrolled and screened. Patients with specific heart disease and existing thyroid hormone parameters were included in the study. Low triiodothyronine syndrome is characterized by reduced serum total or free T3 (fT3) concentrations in normal free T4 (fT4) and TSH levels. RESULTS: The common diagnosis of the patients in the coronary care unit is acute coronary syndrome (n=59, 28.2 %) and heart failure (n=46, 23.3%). Patients were divided into two groups according to left ventricular ejection fraction percentages (LVEF ≤39% vs LVEF ≥40%). Plasma fT3 levels were significantly correlated with low LVEF (≤39%) (p =0.002). fT3 (r=-0.183, p =0.013) and hospitalization etiology (r=-0.161, p =0.023) were also the most critical parameters affecting the length of hospitalization. CONCLUSION: Low fT3 was associated with reduced ejection fraction and prolonged hospitalization, which may lead to potential morbidities in HF patients and may be useful in risk stratification and treatment strategies.

Total thyroxine, triiodothyronine, and thyrotropin concentrations during acute nonthyroidal illness and recovery in dogs.

BACKGROUND: Acute illness can result in changes in serum total thyroxine (tT4), total triiodothyronine (tT3), and thyrotropin (TSH) concentrations in euthyroid dogs defined as nonthyroidal illness syndrome, but longitudinal evaluation of these hormones during the recovery phase is lacking. OBJECTIVES: To longitudinally evaluate serum tT4, tT3, and TSH concentrations during the acute phase and recovery from acute illness in dogs. ANIMALS: Nineteen euthyroid client-owned dogs hospitalized for acute illness at a veterinary teaching hospital. METHODS: Prospective longitudinal study. Serum tT4, tT3, and TSH concentrations were measured at the admission (T0), at last day of hospitalization (T1), and during the recovery phase at 3, 7, 14, and 21 days after the discharge (T2, T3, T4, and T5), respectively. RESULTS: tT4 and tT3 were below the reference interval (RI) at T0 in 3 (16%) and 18 (95%) dogs, respectively; tT4 normalized in all dogs early in the recovery phase, while low tT3 persisted at the end of the study in 16 (83%) dogs. Median TSH concentrations were increased at T5 compared with T1 (0.19 ng/mL [range 0.03-0.65] vs 0.11 ng/mL [range (0.05-0.26)], mean difference = 0.09 ng/mL; P = .03). Five (26%) dogs had TSH above the RI at least at 1 time point during the recovery phase. None of the dogs had concurrent low tT4 and high TSH during the study. CONCLUSIONS AND CLINICAL RELEVANCE: In euthyroid dogs acute illness can interfere with evaluation of thyroid function up to 21 days during the recovery phase. Thyroid testing should be avoided or postponed in these dogs.

A Cross-Sectional Study of Acute Coronary Syndrome and Thyroid Profile: Dissecting the Relationship to Improve Patient Care.

INTRODUCTION: Thyroid-releasing hormones are pivotal in regulating cardiovascular (CVS) function and maintaining its hemodynamics and homeostasis. Even a minor alteration in thyroid function has an enormous implication on CVS morbidity and mortality. Moreover, hypothyroidism was found to be a potential menace for coronary artery disease (CAD). The objective of this study was to determine the role of thyroid-releasing hormones in patients suffering from acute coronary syndrome (ACS). METHODOLOGY: Among a cohort of 100 patients suffering with ACS, a complete history and clinical information followed by physical examination and electrocardiography were recorded. Blood samples were also collected to record the blood sugar levels i.e., fasting blood sugar (FBS), postprandial blood sugar (PPBS), and thyroid profile, including free thyroid stimulating hormone (TSH), free thyroxine (fT4), free triiodothyronine (fT3), and reverse triiodothyronine (rT3). The data was analyzed using SPSS version 26 software (IBM Corp., Armonk, NY, USA). RESULT: The study identified alterations in the thyroid hormone levels in 27% of patients suffering from ACS. The prevalence of euthyroid sick syndrome was found to be 59.3%, while subclinical hypothyroidism and subclinical hyperthyroidism were reported among 18.5% and 14.8% of patients respectively. There was no significant difference found between males and females. The study illustrated a greater occurrence of aberrant thyroid hormone profiles among those aged 40-60 years. The ST-elevated myocardial infarction (STEMI) group had a statistically significant higher prevalence of an aberrant thyroid hormone profile compared to the non-ST-elevated myocardial infarction (NSTEMI) and unstable angina (UA) groups (p=0.02). A total of nine patients died with ACS and all of those had statistically significant low fT3 and TSH values while higher rT3 values (p<0.05). CONCLUSION: An atypical thyroid status has been found to elevate the likelihood of developing CAD and experiencing CVS mortality. This condition can impact ventricular function and serum cholesterol levels as well as heart rate and rhythm. Therefore, understanding this relationship could potentially lead to improved treatment strategies for individuals with ACS which will further prevent major CVS complications.

Ultrasound-Histopathological Presentation of Thyroid and Ovary Lesions in Adolescent Patients with DICER1 Syndrome: Case Reports and Literature Overview.

BACKGROUND: DICER1, a cancer predisposition syndrome (CPS), seems to escape timely diagnosis in pediatric patients. Case report 1: A 16-year-old female patient was referred to the endocrinology ward due to a large goiter. Her medical history indicated normal sexual maturation, with menarche occurring at 13.5 years. Over the past 2.5 years, she had developed pronounced androgenic symptoms, including a deepened male voice; facial, back, and neckline acne; hirsutism; and menstrual irregularities leading to secondary amenorrhea. A thyroid ultrasound identified a multinodular goiter (MNG) with cystic-solid lesions containing calcifications. An abdominal ultrasound identified a 5.7 × 6.9 cm solid mass in the right adnexal region, displacing the uterus to the left. Histopathological examination confirmed a Sertoli-Leydig cell tumor. The patient was subjected to a total thyroidectomy. Histopathology revealed benign follicular cell-derived neoplasms. Thyroid follicular nodular disease (TFND) was diagnosed bilaterally. DNA analysis using NGS, confirmed via the Sanger method, revealed a pathogenic heterozygotic variant c.2953C>T [p.Gln985*] in exon 18 of the DICER1 gene. Case report 2: A 12-year-old male patient was admitted to the pediatric surgery unit due to a 33 mL goiter. A month prior to his admission, the patient discovered a palpable nodule in his neck, accompanied by hoarseness. An ultrasound revealed MNG. Molecular analysis revealed a pathogenic heterozygotic variant c.2782C>T [p.Gln928*] in exon 17 of the DICER1 gene. Subsequently, a total thyroidectomy was performed, and histopathological examination revealed TFND bilaterally. CONCLUSIONS: Recent advances in genetic evaluation and in histological approaches indicate that MNG/TFND, although rare in the pediatric population, when accompanied by characteristic ultrasound and histopathological features, and by additional features such as androgenization, may warrant assessment also of the DICER1 gene within CPS molecular panel screening.

Impaired Sensitivity to Thyroid Hormone and Risk of Carotid Plaque Development in a Chinese Health Check-Up Population: A Large Sample Cross-Sectional Study.

Objective: Previous research on the correlation between thyroid function and carotid plaque has revealed conflicting results, possibly attributable to the sensitivity of thyroid hormone indices. In this study, we aimed to analyze the association between thyroid hormone sensitivity indices and the risk of carotid plaque development in a Chinese health check-up population. Methods: A total of 19,388 health check-up subjects were included in this study (mean age: 50.78±10.17 years). Central sensitivity to thyroid hormone was evaluated using the thyroid feedback quantile-based index (TFQI), the Chinese-referenced parametric TFQI (PTFQI), the TSH index (TSHI), and the thyrotropin thyroxine resistance index (TT4RI), while peripheral sensitivity to thyroid hormone was assessed by free triiodothyronine/free thyroxine (FT3/FT4) ratio. Multivariable logistic regression analyses were performed to detect the association between thyroid hormone sensitivity indices and carotid plaque risk, and subgroup analysis was also conducted to explore this association stratified by sex, age, obesity, and the status of smoking, drinking, diabetes, hypertension and dyslipidemia. Results: Among the 19,388 participants, 3753 (19.4%) had carotid plaque. In multivariable adjustment models, the risk of carotid plaque was positively associated with TSHI (odds ratio [OR]: 1.23; 95% confidence interval [CI]: 1.18~1.28), TT4RI (OR: 1.28; 95% CI: 1.23~1.33), TFQI (OR: 1.06; 95% CI: 1.02~1.10), and PTFQI (OR: 1.11; 95% CI: 1.07~1.16), respectively. Conversely, the risk of carotid plaque was negatively correlated with FT3/FT4 (OR: 0.94; 95% CI: 0.90~0.98). In stratified analyses, all thyroid hormone sensitivity indices significantly increased the risk of carotid plaque especially in females, subjects<65 years, non-obese individuals, and those without current smoking, drinking, diabetes, hypertension and dyslipidemia. Conclusion: In Chinese health check-up populations, a considerable connection between reduced sensitivity to thyroid hormones and carotid plaque has been observed, especially in females, those younger than 65 years, non-obese individuals, and those without any current smoking, drinking, diabetes, hypertension, or dyslipidemia.

Ocular surface and meibomian gland evaluation in euthyroid Graves' ophthalmopathy.

PURPOSE: Euthyroid Graves' ophthalmology (EGO) refers to the subgroup of thyroid eye disease patients with distinct clinical presentations. This study evaluated the ocular surface and meibomian gland changes in EGO patients. METHODS: A cross-sectional study was conducted at The Chinese University of Hong Kong including 34 EGO patients and 34 age-and sex- matched healthy controls. Outcome measures include anterior segment examination, keratographic and meibographic imaging. RESULTS: Between 34 EGO patients and 34 age and sex-matched healthy controls, EGO was associated with a higher ocular surface disease index (P < 0.01), higher severity of meibomian gland dropout (upper: P < 0.001, lower: P < 0.00001) and higher percentage of partial blinking (P = 0.0036). The worse affected eyes of the EGO patients were associated with corneal staining (P = 0.0019), eyelid telangiectasia (P = 0.0009), eyelid thickening (P = 0.0013), eyelid irregularity (P = 0.0054), meibomian gland plugging (P < 0.00001), expressibility (P < 0.00001), and meibum quality (P < 0.00001). When the two eyes of the same EGO patient were compared, the degree of meibomian gland dropout was higher among the worse affected eyes (upper: P < 0.00001, and lower: P < 0.00001). Tear meniscus height, lipid layer thickness, and noninvasive break-up time were comparable between the two eyes of EGO patients and also between EGO patients and healthy controls. TMH was positively correlated with the degree of exophthalmos (r = 0.383, P < 0.05). CONCLUSION: EGO patients have more ocular surface complications and meibomian gland dropouts than healthy controls. Almost 60% of them had dry eye symptoms, but aqueous deficiency was not apparent. Further studies are warranted to clarify the mechanism of dry eye in EGO. (249 words).

Serum FT3/FT4, but not TSH is associated with handgrip strength in euthyroid U.S. population: evidence from NHANES.

Objective: Although several studies have examined the relationship between thyroid function and muscle strength, their population primarily derived from Asian areas, and their results were controversial. Thus, this study aimed to explore the association between thyroid function and handgrip strength (HGS) in the U.S. population. Methods: A total of 1,067 participants from NHANES were categorized into three different age groups including young (<45 years), middle (45~64 years), and old (≥65 years) age groups. Thyroid function was measured by the competitive binding immune-enzymatic assays, while HGS was examined by a trained evaluator using a dynamometer. The weighted multiple linear regression models were used to examine the association between thyroid function and handgrip strength. The restricted cubic splines were employed to explore the non-linear relationship between these two variables. All statistical analyses were performed using the SPSS version 20.0 and R software. Results: After adjustment for potential covariates, FT3/FT4, but not TSH was positively associated with HGS in middle age group (ß=0.091, t=2.428, P=0.016). The subgroup analysis by sex revealed that the positive association between FT3/FT4 and HGS was observed in the middle age group for both male and female participants (ß=0.163, t=2.121, P=0.035; ß=0.157, t=2.180, P=0.031). The RCS analysis showed a statistically significant non-linear association between FT3/FT4 and HGS in overall population (P for non-linear=0.026). After adjustment for covariates, men with low HGS had a significant lower FT3/FT4 than those without low HGS in old age group (P=0.013). There was a significant increase in TSH level for female participants with low HGS in old age group compared to those with normal HGS (P=0.048). Conclusions: This study demonstrated FT3/FT4, but not TSH, was positively associated with HGS in middle age group, and the different association was observed in men in middle age group when participants were stratified by sex. Future longitudinal cohort study should be conducted to reveal the causal relationship between thyroid function and muscle strength.

Effects of Levothyroxine Treatment on Fertility and Pregnancy Outcomes in Subclinical Hypothyroidism: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: Subclinical hypothyroidism, defined by elevated thyrotropin (TSH) and normal free thyroxine levels, is associated with adverse pregnancy outcomes, including preterm birth, pre-eclampsia, and small for gestational age. Despite the uncertainty regarding the effectiveness of levothyroxine (LT4) treatment on pregnancy outcomes in subclinical hypothyroidism, LT4 is widely administered with a pre-treatment threshold TSH level of 2.5 mU/L. The aim of this study is to investigate the efficacy of periconceptional LT4 treatment for subclinical hypothyroidism, including TSH levels >2.5 mU/L, and identify the characteristics of subclinical hypothyroidism that can benefit from LT4 treatment. Methods: We conducted a systematic review and meta-analysis of randomized controlled trials from inception to February 2023. We analyzed the pooled effects of LT4 on subclinical hypothyroidism before and during pregnancy. The main outcomes before pregnancy were live birth, pregnancy, and miscarriage. The main outcomes during pregnancy were live birth, miscarriage, and preterm birth. We conducted subgroup analyses to compare the effects of LT4 on subclinical hypothyroidism with TSH levels of 2.5-4.0 and >4.0 mU/L. Results: Of the 888 studies identified, 27 full-text articles were screened for eligibility. Five studies on pre-conception treatment with 768 participants and eight studies on treatment during early pregnancy with 2622 participants were analyzed. One of the two studies on pre-conception treatment in subclinical hypothyroidism with TSH >4.0 mU/L had high risk of bias and the other was composed of 64 participants. Pre-conception LT4 treatment had no significant effect in improving rates of live births and pregnancies, or reducing miscarriages (risk ratio [RR], 95% confidence interval): 1.41 (0.84-2.36), 1.73 (0.88-3.39), and 0.46 (0.11-2.00), respectively. LT4 treatment during pregnancy was not significantly associated with higher rates of live births (RR 1.03, 0.98-1.09) nor decreased miscarriage rates (RR 1.01, 0.66-1.53). The effect of LT4 treatment on preterm birth during pregnancy was significantly different depending on the TSH values (p = 0.04); a positive effect was shown in the subclinical hypothyroidism subgroup with TSH >4.0 mU/L (RR 0.47, 0.20-1.10), while no significant effect was observed in the subgroup with TSH 2.5-4.0 mU/L (RR 1.35, 0.79-2.31). Conclusions: Pre-conceptional LT4 treatment for subclinical hypothyroidism does not improve fertility or decrease the incidence of miscarriages. However, further well-designed studies are needed for pre-conceptional treatment, especially in TSH >4.0 mU/L. LT4 treatment during pregnancy had a positive effect on preterm birth; nevertheless, this was only applicable to subclinical hypothyroidism with TSH >4.0 mU/L.

Impaired Sensitivity to Thyroid Hormones is Associated with the Risk of Diabetic Nephropathy in Euthyroid Patients with Type 1 Diabetes Mellitus.

Purpose: This study aims to investigate the relationship between thyroid and type 1 diabetic nephropathy (T1DN) in euthyroid populations, focusing on thyroid hormone sensitivity. Methods: A cross-sectional study was conducted between January 2016 and December 2021, including 357 euthyroid patients with type 1 diabetes mellitus (T1DM). Parameters representing thyroid hormone sensitivity were assessed, including the thyroid feedback quantile-based index (TFQI), parameter thyroid feedback quantile index (PTFQI), thyroid stimulating hormone index (TSHI), thyrotropin thyroxine resistance index (TT4RI), and free triiodothyronine/free thyroxine (FT3/FT4). Logistic regression and restricted cubic spline regression were performed to detect the association between thyroid hormone sensitivity and the risk of T1DN. Results: The study found a negative correlation between the risk of T1DN and FT3/FT4 in euthyroid T1DM patients (OR 0.71, 95% CI 0.51-0.97, P <0.01). PTFQI (P<0.05), TSHI (P<0.05), and TT4RI (P<0.01) showed an M-shaped nonlinear relationship with the risk of T1DN. Elevated risk of T1DN was associated with PTFQI, TSHI, and TT4RI values outside the range of zero, 2.3-3.88, and 27.56-32.19, respectively. Conclusion: This study confirms the relationship between impaired thyroid hormone sensitivity and the risk of T1DN in euthyroid patients. It emphasizes the importance of evaluating thyroid hormone sensitivity in T1DM patients, even when their thyroid function appears normal, to promptly prevent the occurrence of T1DN.

A Review of Thyroid Dysfunction Due to COVID-19.

Coronavirus disease 2019 (COVID-19) affects thyroid function. These changes are due to the direct impact of the virus on thyroid cells via angiotensin-converting-enzyme 2 (ACE2) receptors, inflammatory reaction, apoptosis in thyroid follicular cells, suppression of hypothalamus-pituitarythyroid axis, an increase in activity of adrenocortical axis, and excess cortisol release due to cytokine storm of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Euthyroid sick syndrome (ESS), thyroiditis, clinical and subclinical hypothyroidism, central hypothyroidism, exacerbation of underlying autoimmune thyroid disease, and clinical and subclinical hyperthyroidism can be associated with coronavirus. Adjuvants in coronavirus vaccines induce autoimmune/inflammatory syndrome known as vaccine adjuvants (ASIA) syndrome. Thyroiditis and Graves' disease have been reported to be associated with ASIA syndrome after some coronavirus vaccinations. Some coronavirus medications, such as hydroxychloroquine, monoclonal antibodies, lopinavir/ritonavir, remdesivir, naproxen, anticoagulants, and glucocorticoids can also affect thyroid tests, and correct diagnosis of thyroid disorders will be more difficult. Changes in thyroid tests may be one of the most important manifestations of COVID-19. These changes can be confusing for clinicians and can lead to inappropriate diagnoses and decisions. Prospective studies should be conducted in the future to increase epidemiological and clinical data and optimize the management of thyroid dysfunctions in patients with COVID-19.

Contrast-enhanced ultrasonography of the thyroid gland in healthy dogs, hypothyroid dogs and dogs with non-thyroidal illness.

Diagnosis of canine hypothyroidism remains challenging, as non-thyroidal illness (NTI)-syndrome and medical treatment can influence thyroid hormone concentrations. Conventional ultrasound may give additional hints, however high interobserver variability has been described. Contrast-enhanced ultrasound (CEUS) allows detection of changes in tissue perfusion. The purpose of the present study was to assess the possible diagnostic value of CEUS regarding diagnosis of hypothyroidism. CEUS of the thyroid gland was performed in 52 healthy dogs, 16 hypothyroid dogs, and 20 NTI patients. The following perfusion parameters were calculated: Thyroid/carotid artery (TG/CA) ratios for peak enhancement (PE) and area under the curve (AUC), time to peak (TTP) and wash-in and wash-out rates (WiR, WoR) of the thyroid gland. Impact of sedation on perfusion parameters was investigated in 8 calm healthy dogs which were examined before and after sedation using midazolam and butorphanol. Significantly higher median TG/CA ratios for PE were detected for the left and right thyroid lobe in dogs with hypothyroidism (0.97/0.96) compared to healthy dogs (0.85/0.85) and dogs with NTI (0.84/0.84). AUCs were also significantly increased in hypothyroid dogs when compared to other groups. Dogs with NTI showed significantly lower WiR and WoR compared to other groups. Values for TTP were not significantly different between groups. Sedation had only impact on results of TTP which was significantly prolonged in sedated dogs. In conclusion, CEUS of the thyroid gland can provide an additional tool for diagnosis of hypothyroidism in dogs and support its differentiation from NTI. Sedation has limited impact on CEUS results.

Real Practice Assessment of Persistent Symptoms After Initiation of Levothyroxine.

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

Impaired Sensitivity to Thyroid Hormones Is Associated With Decreased Vitamin D Levels in the Euthyroid Population.

CONTEXT: The relationship between vitamin D and thyroid profiles lacks consensus despite extensive investigations. Whether vitamin D levels correlate with thyroid hormone sensitivity remains largely unexplored. OBJECTIVE: To explore the relationship between vitamin D levels and thyroid hormone sensitivity among euthyroid individuals. METHODS: This study involved 6452 euthyroid participants. Clinical parameters, including TSH, free thyroxine, 25-hydroxyvitamin D [25(OH)D], and other relevant indicators were extracted from the National Health and Nutrition Examination Survey 2007-2012. To quantify thyroid hormone sensitivity, we calculated the Thyroid Feedback Quantile-based Index (TFQI), the TSH index (TSHI), and the thyrotropin thyroxine resistance index (TT4RI). RESULTS: Subjects with impaired thyroid hormone sensitivity have decreased 25(OH)D levels (TFQI, TT4RI: P < 0.05; TSHI: P = .05574) following adjustment of confounding variables. Age-specific analysis found negative correlations between thyroid hormone sensitivity indices and 25(OH)D within the 20 to 60 years subgroup, turning positive in the 60 to 80 years subgroup. In females, thyroid hormone sensitivity indices and vitamin D levels were negatively linked, while in males, vitamin D's relationships with TFQI, TT4RI, and TSHI shifted from negative to positive when 25(OH)D levels exceeded 63.5 nmol/L, 56.7 nmol/L, and 56.7 nmol/L, respectively. Stratification by race revealed U-shaped curvilinear patterns resembling those found in the males. In body mass index (BMI) subanalysis, vitamin D had differing associations with thyroid hormone sensitivity indices: negative in the <25 kg/m2 and ≥30 kg/m2 subgroups and U-shaped in the 25-30 kg/m2 subgroup. CONCLUSION: Impaired thyroid hormone sensitivity correlates with decreased vitamin D levels among euthyroid subjects, with associations varying by age, sex, race, and BMI.

Triiodothyronine hormone supplementation therapy in septic shock patients with euthyroid sick syndrome: two pilot, placebo-controlled, randomized trials.

BACKGROUND: To assess 28-day survival in two pilot groups of septic shock patients with euthyroid sick syndrome (ESS) supplemented with triiodothyronine (T3). METHODS: A total of 95 septic shock patients with ESS were divided according to values of the thyroid hormones into low T3 and low T3T4 groups. Among 48 patients with low T3, 24 (50%) were randomized to T3 for 4 days and 24 (50%) to placebo. Among 47 patients with low T3T4, 24 (51%) were randomized to T3 for 4 days and 23 (49%) to placebo. The analysis included 28-day survival as the primary outcome and laboratory with hemodynamics as the secondary outcomes. Laboratory data were analyzed on the day of admission (T0), on the first (T1), third (T2) and seventh day (T3) with hemodynamics analyzed for the first four days. RESULTS: In the low T3 population, 18 (75%) patients receiving T3 died at day 28 compared with 8 (33.3%) patients receiving placebo (p = 0.004). In the low T3T4 population, 6 (25%) patients receiving T3 died in ICU compared with 12 (52.1%) patients receiving placebo (p = 0.039). Oral T3 treatment increased mean arterial pressure values at day 1, day 3 and day 7 in the low T3T4 population, (p = 0.015, =0.005 and =0.042 respectively), and had no significant effect on these values in the low T3 population. CONCLUSION: T3 supplementation was associated with a low 28-day mortality rate in patients with low T3T4 but with increased mortality in patients with low T3 ESS. These results suggest caution before initiating thyroid supplementation in septic patients. REGISTRATION: ClinTrials.gov (NCT05270798).