The Independent Association of TSH and Free Triiodothyronine Levels With Lymphocyte Counts Among COVID-19 Patients

BackgroundBoth lymphopenia and thyroid dysfunction are commonly observed among COVID-19 patients. Whether thyroid function independently correlates with lymphocyte counts (LYM) remains to be elucidated.MethodsWe included consecutive adults without known thyroid disorder admitted to Queen Mary Hospital for COVID-19 from July 2020 to April 2021 who had thyroid-stimulating hormone (TSH), free thyroxine (fT4), free triiodothyronine (fT3) and LYM measured on admission.ResultsA total of 541 patients were included. Median LYM was 1.22 x 109/L, with 36.0% of the cohort lymphopenic. 83 patients (15.4%) had abnormal thyroid function tests (TFTs), mostly non-thyroidal illness syndrome (NTIS). Patients with lymphopenia had lower TSH, fT4 and fT3 levels than those without. Multivariable stepwise linear regression analysis revealed that both TSH (standardized beta 0.160, p<0.001) and fT3 (standardized beta 0.094, p=0.023), but not fT4, remained independently correlated with LYM, in addition to age, SARS-CoV-2 viral load, C-reactive protein levels, coagulation profile, sodium levels and more severe clinical presentations. Among the 40 patients who had reassessment of TFTs and LYM after discharge, at a median of 9 days from admission, there were significant increases in TSH (p=0.031), fT3 (p<0.001) and LYM (p<0.001). Furthermore, patients who had both lymphopenia and NTIS were more likely to deteriorate compared to those who only had either one alone, and those without lymphopenia or NTIS (p for trend <0.001).ConclusionTSH and fT3 levels showed independent positive correlations with LYM among COVID-19 patients, supporting the interaction between the hypothalamic-pituitary-thyroid axis and immune system in COVID-19.

Serum Antithyroglobulin Antibody Levels Are Associated with Diabetic Retinopathy among Euthyroid Type 2 Diabetes Patients: A Hospital-Based, Retrospective Study

Background. Previous studies have revealed that the variation of thyroid indicators may be associated with the risk of diabetic retinopathy (DR) among euthyroid type 2 diabetes (T2D) patients. But the specific conclusions are currently inconsistent. Methods. This is a hospital-based retrospective survey. We recruited 1,145 euthyroid T2D patients and checked the thyroid function and fundus photographs. The modified Airlie House classification system was used to categorize the stages of DR. The association between thyroid indicators and different stages of DR was analyzed. Results. We divided free triiodothyronine (FT3) into tertiles and found that the prevalence of mild nonproliferative DR (NPDR) was significantly higher in T2, compared with T1 (32.0% vs. 25.2%, p < 0.05 ). When FT3 was within the level of T2, FT3 could be an independent risk factor for mild NPDR (OR 1.426, 95% CI (1.031, 1.971), p < 0.05 ). In addition, the prevalence of severe NPDR and proliferative DR (PDR) was significantly higher in thyroglobulin antibody (TgAb) positive group (8.8% vs. 4.1%, p < 0.05 ) and vice versa (33.3% vs. 18.4%, p < 0.05 ). TgAb positivity was also an independent risk factor for severe NPDR and PDR (OR 2.212, 95% CI (1.244, 3.934), p < 0.05 ). Conclusions. We hardly observed a significant change in DR risk with the elevation or reduction of serum TSH or thyroid hormone within the reference interval. Although the slightly elevated FT3 may be associated to mild NPDR, the extensibility of this result remains to be seen. For T2D patients with euthyroid function, there may be a significant correlation between serum TgAb positivity and severe NPDR and PDR.

The Association Between COVID-19 and Thyroxine Levels: A Meta-Analysis

ObjectivesRecently, a number of reports have described the potential relationship between COVID-19 and thyroid hormones, but the results were conflicting. We performed a meta-analysis to evaluate the effect of the severity of COVID-19 on thyroid-related hormones and the effect of thyroid-related hormones on the outcome of COVID-19 in order to try to confirm the association between the serum levels of free triiodothyronine (FT3), free thyroxine (FT4) and thyroid stimulating hormone (TSH) and the severity or mortality of coronavirus-19 patients.MethodsThe methodology was already registered in the International Prospective Register of Systematic Reviews (PROSPERO) database, and the protocol number is CRD42021269246. Systematic searches were carried out on the Cochrane Library, Embase, PubMed and Web of Science databases on November 15, 2021. We set up the literature search strategy based on the following keywords: [(T3 OR FT3 OR triiodothyronine) or (T4 OR FT4 OR thyroxine) or (TSH or thyrotropin)] and (COVID-19 OR SARS-CoV-2), without time restrictions.ResultsTwenty studies satisfied the inclusion/exclusion criteria and were included in the meta-analysis. A total of 3609 patients were enrolled in the study. From the analysis of the included studies, the incidence of thyroid-related hormone abnormalities was higher in patients with severe COVID-19, and the serum levels of FT3 and TSH were lower than those of patients with nonsevere COVID-19. However, the difference in the FT4 levels was not significant. Similar characteristics were shown between survivors and nonsurvivors. In addition, the outcomes of the meta-analysis showed that patients with abnormal thyroid-related hormones had greater mortality.ConclusionsLow FT3 serum levels, low FT4 serum levels and low TSH serum levels may increase the mortality of COVID-19 patients during admission. On the other hand, the higher the severity level of COVID-19, the higher the probability of decreases in the FT3, FT4, TSH levels.

The Association of Thyroid Hormones with Coronary Atherosclerotic Severity in Euthyroid Patients

The aim of the work was to explore the correlation between thyroid hormones and coronary atherosclerotic severity. This cross-sectional study included 340 euthyroid patients who underwent diagnostic coronary artery angiography (CAG). Gensini Score (GS) was applied to assess the severity of coronary atherosclerosis. Thyroid hormones and routine biochemical parameters were measured. The associations between thyroid hormones and coronary atherosclerosis severity were analyzed. Thyroid hormones levels or parameters were taken as both continuous variables and tertiles into analysis, and the lowest tertile was usually used as the reference (OR=1) for medium and highest tertiles. Free triiodothyronine (FT3) level was associated with GS≥22 (Median GS) in Model I adjusted for age and sex [Continuous: OR=0.46, 95% CI (0.23, 0.92), p=0.029; Tertile 3: OR=0.54, 95% CI (0.30, 0.97), p=0.038], and Model II adjusted for all known risk factors of coronary artery disease (CAD) [Continuous: OR=0.44, 95% CI (0.20, 0.95), p=0.036; Tertile 3: OR=0.49, 95% CI (0.25, 0.96), p=0.039]. Subjects with highest tertile of FT3 to free thyroxine (FT4) ratio (FT3/FT4 ratio) appeared to have the remarkably decreased risk of CAD in both Non-adjusted Model [OR=0.49, 95% CI (0.24, 0.98), p=0.044] and Model I [OR=0.45, 95% CI (0.22, 0.93), p=0.031]. Higher FT3 level within normal range was independently and negatively associated with severity of coronary atherosclerosis. Besides, FT3/FT4 ratio was remarkably correlated with the prevalence of CAD in euthyroid population.

Subacute Thyroiditis Presenting as Idiopathic Intracranial Hypertension

Background. Several case reports have illustrated a rare neurological manifestation, idiopathic intracranial hypertension (IIH), in patients with thyrotoxicosis. However, none were diagnosed with thyroiditis. We report the case of a patient with subacute thyroiditis who presented with severe intractable headache due to IIH. Case Presentation. A 36-year-old woman visited Lampang Hospital in February 2021 complaining of neck pain and progressive severe intractable headache. Her vital signs and neurological examination were normal. Thyroid examination revealed a single 1 cm right thyroid nodule. A computed tomography (CT) scan of her brain illustrated diffuse brain edema. However, CT angiography and venography of the brain did not show abnormalities. The opening pressure of the cerebrospinal fluid was elevated (27 cmH2O). The free triiodothyronine level was 6.19 pg/mL, free thyroxine was 2.32 ng/dL, and thyroid-stimulating hormone was 0.0083 μIU/mL. Anti-Tg was positive at a low titer, but anti-TPO was negative. TRAb was also negative. Methimazole and acetazolamide were prescribed and monitored. The symptoms resolved completely within 2 weeks of onset. Thyroid hormones had returned to normal by 8 weeks. Conclusion. This is the first case report of subacute thyroiditis presenting with IIH.

Cord Blood Thyroid Hormones and Neurodevelopment in 2-Year-Old Boys and Girls

Objective: Thyroid hormones are essential for neurodevelopment in early life. However, the impact of mild alterations in neonatal thyroid hormones on infant neurodevelopment and its sex dimorphism is unclear. We aimed to assess whether mild variations in neonatal thyroid hormones of term-born newborns with maternal euthyroid are related to neurodevelopment in 2-year-old boys and girls.Methods: This study used data from 452 singleton term-born infants of mothers with normal thyroid function in Shanghai, China, and their follow-up measure at the age of 2 years. Cord serum concentrations of free thyroxine (FT4), free triiodothyronine (FT3), thyroid-stimulating hormone (TSH), and thyroid peroxidase antibody (TPOAb) were measured by chemiluminescent microparticle immunoassays and classified into three groups: the low (1st, Q1), middle (2nd−4th, Q2–Q4), and high (5th, Q5) quintiles. Neurodevelopment indices were assessed using the Ages and Stages Questionnaire, third edition (ASQ-3), at 24 months of age.Results: Compared to infants with thyroid hormones in the middle (Q2–Q4), boys with FT4 in the lowest quintile had 5.08 (95% CI: 1.37, 8.78) points lower scores in the communication domain, 3.25 (0.25,6.25) points lower scores in the fine motor domain, and 3.84 (0.04, 7.64) points lower scores in the personal-social domain, respectively. Boys with FT3 in the highest quintile had 4.46 (0.81, 8.11) points increase in the personal-social domain. These associations were not observed in girls. No associations were observed between cord blood serum TSH and ASQ-assessed neurodevelopment in the boys or the girls.Conclusions: Mild alterations in thyroid hormones of newborns were associated adversely with neurodevelopment in boys, suggesting the importance of optimal thyroid hormone status for neurodevelopment in early life.

Association of Reduced Free T3 to Free T4 Ratio with Lower Serum Creatinine in Japanese Hemodialysis Patients

Purpose: Low T3 syndrome is defined by a fall in free triiodothyronine (FT3) in spite of normal serum thyroid-stimulating hormone (TSH) and often normal free thyroxin (FT4). A low FT3/FT4 ratio, a relevant marker for low T3 syndrome, is known as a risk of mortality in hemodialysis (HD) patients, as well as low muscle mass in the general population. Because of the local activation of T4 to FT3 in muscle tissue, we examined the association of FT3/FT4 ratio with serum creatinine, a marker of muscle mass and strength in HD patients to investigate the significance of muscle tissue in the development of low T3 syndrome in HD patients. Methods: This was a cross-sectional study derived from our prospective cohort study, named DREAM, of Japanese HD patients. After the exclusion of patients with treated and untreated thyroid dysfunction, 332 patients were analyzed in the study. Results: The serum FT4 and TSH of HD patients (n = 332) were 0.9 ± 0.1 ng/dL. and 2.0 ± 0.9IU/mL, which were within the respective normal range, while serum FT3 was 2.2 ± 0.3 pg/mL. As many as 101 out of 332 (30.4%) HD patients exhibited a serum FT3 less than the normal lower limit of 2.2 pg/mL. The serum FT3/FT4 ratio correlated significantly positively with serum creatinine, and inversely with serum log CRP and total cholesterol, while it exhibited a tendency towards positive correlation with serum albumin. Multiple regression analysis, which included serum creatinine, albumin, and log CRP, simultaneously, in addition to sex, age, diabetic kidney disease or not, log HD duration, body mass index, systolic blood pressure, and Kt/V, as independent variables, revealed an independent and significant positive association of serum creatinine, but not serum albumin or CRP, with the serum FT3/FT4 ratio. Conclusions: The present study demonstrated an independent and positive correlation of serum creatinine with the serum FT3/FT4 ratio in HD patients. The lack of association of the serum FT3/FT4 ratio with serum albumin and CRP suggested the presence of a creatinine-specific mechanism to associate with serum FT3/FT4 ratio. Because of the local activation of T4 to T3 at muscle tissue, a lower muscle mass may be causatively associated with low T3 syndrome.

Association of Sub-Clinical Hypothyroidism with Abnormal Levels of Lipid in the Population of Nawabshah, Pakistan

Aims: Aim of this investigation was to access the association of dyslipidemia with subclinical hypothyroidism. Methodology: In this cross-sectional investigation, 1948 participants were recruited. Two groups were made; participants up to 18 years were in group A and Subjects over 18 years were incorporated in group 2. They were subdivided into control, subclinical hypothyroid 1, and subclinical hypothyroid 2. SPSS 21 was used for data analysis. Results: Data of 1619 individuals were analyzed. The mean age of Group A participants was 12.79 ± 2.779, and the mean age of Group B participants was 42.58 ± 18.012. The prevalence of subclinical hypothyroid was found at 13.5 %. Significant differences have been observed while comparing Group A and Group B (P <0.001). Free tetraiodothyronine and Free triiodothyronine also showed a significant difference in both groups. (P<0.05). No significant difference between mean Thyroid-stimulating hormone levels was observed (P>0.05). No significant association between Controls and High-density Lipid values was found between Controls and subclinical hypothyroid. Conclusion: We conclude that subclinical hypothyroidism leads to increased dyslipidemia. Lower Serum total cholesterol and low-density lipid levels were detected among children and participants under the age of 18 with Thyroid-stimulating hormone greater than 10 mIU/L. Thyroid-stimulating hormone less than 10.0 mIU/L had no lipid abnormalities in subclinical hypothyroid participants.

Prognostic Value of Thyroid Hormone Dysfunction and Age in Septicemic Post-Surgical Patients

Introduction: Critical illness and sepsis are difficult to treat with increasing age because of the poor adaptive physiological system as age progresses. The study tries to identify prognostic markers among thyroid hormones for post-surgical critically ill subjects, who have sepsis, to improve the outcome of patients with increasing age. Methods: Free triiodothyronine (FT3), free thyroxine (FT4) and thyroid stimulating hormone (TSH) were estimated by ARCHITECT immunoassay kits in 127 post-surgical critically ill patients with sepsis. Sequential Organ Failure Assessment (SOFA) score was recorded for each patient. Results: The FT3, FT4 and TSH levels decreased and SOFA score increased with increasing age. Thyroid markers were significantly inversely correlated with age (for FT4 r= -0.616, p<0.0001 and for TSH r= -0.453, p<0.0001), with the strongest correlation between FT3 and age (r=0.674, p<0.0001). A positive correlation was observed between SOFA score and age (r=0.577, p<0.0001). FT3 decreases, SOFA and age increase from improved prognosis to worst prognosis (p<0.0001). Conclusions: FT3 surfaced as a prominent prognostic marker that may be used in predicting the prognosis of post-surgical critically ill geriatric patients with sepsis.

Thyroid hormone levels in Tortoises (Testudo spp.) depending on Season and Sex

Thyroid hormones and the factors influencing them are rarely studied in tortoises. This study therefore aimed to calculate reference intervals (RI) for specific species, sexes, and seasons for thyroid hormones and iodine levels in blood of four adult Mediterranean tortoise species and to evaluate possible correlations between thyroid hormones, serum iodine, plasma protein and increased liver and kidney values. Thyroid hormones (total tetraiodothyronine [tT4], free tetraiodothyronine [fT4], total triiodothyronine [tT3], and free triiodothyronine [fT3]) were measured in plasma from adult, healthy Hermann´s (Testudo hermanni, n = 255), spur-thighed (Testudo graeca, n = 89), marginated (Testudo marginata, n = 72), and Russian tortoises (Testudo horsfieldii, n = 30). Species, sex and season specific variations were determined by Bayesian information criterion (BIC) and correlations between plasma thyroid hormones, protein, iodine and increased liver/kidney values were evaluated by Spearman’s rank correlation test. Total T4 did not reveal any species, sex, or seasonal differences (RI 0.102 to 0.455 µg/dL), while seasonal differences were found for fT4 (RI spring 0.624 to 9.012; summer 0.379 to 5.476; fall 0.376 to 5.426 pmol/L). The tT3 levels differed significantly depending on species, season, and the interaction of species x season. Seasonal differences were also found for fT3 and iodine. Several significant (p &lt; 0.05) correlations were detected between the tested analytes, especially positive correlations between tT4 and fT4. These results provide a tool for the evaluation of thyroid hormone levels in Mediterranean tortoises and indicate the influence of season on the thyroid in these animals.