Higher FT4 Research Articles

Tachycardia in hyperthyroidism: Not so common.

The commonly held association of hyperthyroidism with sinus tachycardia and widened pulse pressure (PP) has not been reassessed in decades despite patients with hyperthyroidism in current practice not always present with these signs. The study objective was to assess prevalence and variability of sinus tachycardia and widened PP in present day among individuals with different degrees of hyperthyroidism. Data was collected retrospectively from 248 adult patients in an outpatient setting with biochemical evidence of hyperthyroidism, recorded heart rate (HR) and blood pressure (BP) who were not treated with medications that can influence these parameters. Mean age was 42.0 ± 14.2 years with 66.9% being female. Median free thyroxine (fT4) level was 3.49 (IQR 2.42-4.58) ng/dL and thyroid stimulating hormone (TSH) 0.02 (IQR 0.01-0.03) mIU/L. Tachycardia, defined as HR >100 bpm, was present in 28.2%. In the lowest and highest fT4 quartiles, tachycardia was present in 16.4% and 38.7% respectively. Using logistic regression, tachycardia was associated with higher fT4 and diastolic BP. More lenient outcome of tachycardia with HR >90 bpm was seen in 47.2%. Widened PP, defined as >50 mmHg, was observed in 64.1% of patients and correlated with higher fT4 and BP. Tachycardia is not a common feature of hyperthyroidism today. The relatively infrequent finding of tachycardia in this study compared to older studies may reflect differences in the way medicine is practiced today. The increased ordering of thyroid function tests most likely unmasked cases of mild or asymptomatic thyrotoxicosis. A widened PP was a more prevalent clinical finding in this study.

Association of per- and polyfluoroalkyl substances with thyroid homeostasis during pregnancy in the SELMA study.

To investigate the association of exposure to per- and polyfluoroalkyl substances (PFAS) during early pregnancy with markers of the maternal thyroid system. Serum concentrations of seven PFAS as well as thyroid stimulating hormone (TSH), free and total thyroxine (FT4 and TT4), free and total triiodothyronine (FT3 and TT3) were measured in pregnant women in early pregnancy in the Swedish Environmental Longitudinal, Mother and child, Asthma and allergy (SELMA) study. Outcomes were concentrations of TSH and thyroid hormones, FT4/FT3 or TT4/TT3 ratios, TSH/FT4 ratio as a marker of the negative feedback loop, TT4/FT4 or TT3/FT3 ratios as markers of the binding of thyroid hormones to binding proteins. The study population comprised 2,008 women with median (95% range) gestational age of 10 (6-14) weeks. There was no association between PFAS and TSH. Higher PFNA, PFDA, PFHpA and PFOA levels were associated with a higher FT4 (largest effect estimate for PFDA: β [95% CI]: 0.27 [0.10 to 0.45], P=0.002). Higher PFUnDA levels, but no other PFAS, were associated with a lower FT3 (β [95% CI]: -0.05 [-0.09 to -0.01], P=0.005). Higher PFUnDA levels were associated with lower TT4 (β [95% CI]: -1.58 [-3.07 to -0.09]) and there was an inverted U-shaped association of PFOS with TT4 (P=0.03). Higher PFDA, PFUnDA, PFHpA levels were associated with a lower TT3. Overall, higher PFAS concentrations were associated with a higher FT4/FT3 ratio and a higher TT4/TT3 ratio. There was no association of PFAS with the TSH/FT4 ratio. Higher concentrations of several PFAS were associated with lower TT4/FT4 and TT3/FT3 ratios. These findings translate results from experimental studies suggesting that exposure to PFAS may interfere with the thyroid system during pregnancy. Further experimental studies should take into account human evidence to better understand the potential underlying mechanisms of thyroid disruption by PFAS exposure.

Clinical Manifestation and Diagnosis of a Thyroid Adenoma in a 3-year-old Horse

Hyperthyroidism in horses is a rare disorder in young horses that causes diverse findings such as weight loss, tachypnea, aggression, change in appetite and cachexia. In this report, the clinical manifestation and methods that used in the diagnosis of thyroid adenoma are presented. It was learned that a 3-year-old male Thoroughbred horse became aggressive and had been losing weight despite an adequate diet and appetite. During the inspection, a palpable, painless and moving mass was detected caudal to the larynx, on the left side. For further diagnosis, hemogram, serum biochemistry, urine dipstick analysis and ultrasonographic examination were performed. In serum biochemistry, high HDL, LDH, triglyceride, AST, direct bilirubin, creatine kinase and fT3; low TSH, fT4 and ferritin levels were determined. Ultrasonographic examination revealed that the left thyroid tissue was 2.83 cm x 4.81 cm in size. In the microscopic examination of the aspirate, it was observed that follicles were rich in cytoplasm and surrounded by cuboidal epithelial cells of varying sizes. Dilatation was observed in some follicles, while others were small or even atrophic. As a result, high fT3 and low TSH levels were consistent with the fact that the gland was overactive, the circulating thyroid hormone level was high, and the pineal gland produced less TSH by the feedback mechanism, all of which indicated hyperthyroidism. In addition, it was concluded that thyroid adenoma can also be seen in young horses, may cause clinical symptoms, ultrasonographic examination, microscopic examination of the aspirate and comprehensive serum biochemistry analysis are sufficient for diagnosis.

Circulating free triiodothyronine concentration is positively associated with β-cell function in euthyroid patients with obesity and type 2 diabetes.

ObjectiveTo investigate the relationship between thyroid hormone concentrations and β-cell function in euthyroid patients with obesity and type 2 diabetes.MethodsWe performed a single-center cross-sectional study of 254 patients with type 2 diabetes mellitus aged ≥40 years. The participants were allocated to an obesity group or non-obesity group on the basis of their body mass index (BMI). Their β-cell function was assessed by measuring C-peptide concentration during a 75-g oral glucose tolerance test (OGTT); and their serum free triiodothyronine (FT3), free thyroxine (FT4) and thyroid-stimulating hormone concentrations were measured.ResultsThe serum FT3 concentration and the C-peptide concentrations at five time points of the OGTT were significantly higher in the obesity group than in the non-obesity group. FT3 was positively associated with the β-cell function of the obesity group, but not that of the non-obesity group, in multiple linear regression analysis, after adjustment for potential confounding factors. Serum FT3 concentration was also significantly associated with indices of obesity (BMI, waist circumference, body fat percentage, fat mass, fat mass/height 2 and visceral fat area).ConclusionsObesity-associated high serum FT3 concentrations might affect β-cell function in euthyroid patients with obesity and type 2 diabetes.

Study on thyroid functions in chronic liver disease

In the present study, thyroid functions have been evaluated with all the clinically available indices and confirms the abnormalities in many parameters of thyroid function test in chronic liver disease patients. However euthyroid state is maintained virtually in all patients, probably as a result of low normal Free T3 and high normal FT4. Furthermore, serum T3 concentration appear to directly correlate with the severity of liver dysfunction.

Thyroid Hormones and Health-Related Quality of Life in Normal Pressure Hydrocephalus Patients before and after the Ventriculoperitoneal Shunt Surgery: A Longitudinal Study.

Objective: The aim of this study was to explore the serum levels of thyroid-stimulating hormone (TSH), free thyroxine (FT4), and free triiodothyronine (FT3), and to correlate the hormone levels among iNPH patients with their self-reported quality of life before and three months after the surgery. Methods: Twenty-five patients (52% women), mean age 63.5 (SD 9.5) years, were operated on by inserting a VP shunt. Patients with FT3 level ≤3.34 pmol/L were diagnosed as having low T3 syndrome. Results: The changes in thyroid hormones resulted in a U-shaped curve throughout the follow-up period. The significant changes occurred the next day after the surgery, including a decrease in TSH, FT3, and an increase in FT4. Additionally, the decrease occurred in mean FT3 for six patients with preoperative low T3 syndrome. Three months after the surgery, thyroid hormones were restored to their baseline and/or normal values. All six patients with preoperative low T3 syndrome had significant improvement in all SF-36 subscales (except for the role emotional and physical). Patients with preoperative normal high FT3 and low FT4 had increased FT3/FT4 ratio which was associated with deterioration in all SF-36 subscales 3 months after the surgery. Conclusion: Routine assessment of the FT3/FT4 ratio might be a simple and effective tool for the risk stratification of iNPH patients before VP shunt surgery.

Association Between Thyroid Dysfunction and Incidence of Atrial Fibrillation in Patients With Hypertrophic Obstructive Cardiomyopathy.

ObjectiveTo explore the correlation between the incidence of atrial fibrillation (AF) and thyroid dysfunction in patients with hypertrophic obstructive cardiomyopathy (HOCM).MethodsThyroid function testing in 755 consecutive patients with HOCM were examined at the National Center for Cardiovascular Diseases (China) from October 2009 to December 2013. Patients were divided into four groups according to the TSH levels: TSH<0.55 mIU/L(n=37)、0.55~2.49 mIU/L (n=490)、2.50~9.9 mIU/L (n=211) and >10.00mIU/L(n=17).ResultsA total of 107 patients were diagnosed with AF (14%).(1) Compared to HOCM patients without AF,HOCM patients with AF have older age (P<0.001), higher NT-proBNP (P=0.002), higher Cr (P=0.005), larger left atrial diameter(P=0.001), lower FT3 (P=0.046), higher FT4 (P=0.004).(2) In the four groups according to the TSH levels: TSH<0.55 mIU/L, 0.55~2.49mIU/L, 2.50~9.9mIU/L and ≥10.00mIU/L, the incidence of AF was 27.02%(10/37),10.20%(50/490), 19.43%(41/211), and 35.29%(6/17), respectively. Both high and low TSH levels were associated with an increased incidence of AF. After adjusting for the common risk factor (age, NT-proBNP, and so on), stepwise multiple logistic regression analysis revealed that TSH levels were significantly related to AF incidence.Compared to patients with TSH 0.55~2.49 mlU/L, the adjusted odds ratio of AF for TSH<0.55, 2.50~9.99, ≥10.00 mIU/L were 1.481 (95% CI 0.485~4.518,P=0.490), 1.977 (95%CI 1.115~3.506, p=0.02), 4.301 (95%CI 1.059~17.476, P=0.041), respectively.ConclusionOur results suggested that thyroid dysfunction was associated with an increased risk of AF in patients with HOCM.

How to approach clinically discordant FT4 results when changing testing platforms: real-world evidence

PurposeMeasurement of thyroid-stimulating hormone (TSH) and free thyroxine (FT4) is important for assessing thyroid dysfunction. After changing assay manufacturer, high FT4 versus TSH levels were reported at Ente Ospedaliero Cantonale (EOC; Bellinzona, Switzerland).MethodsExploratory analysis used existing TSH and FT4 measurements taken at EOC during routine clinical practice (February 2018–April 2020) using Elecsys® TSH and Elecsys FT4 III immunoassays on cobas® 6000 and cobas 8000 analyzers (Roche Diagnostics). Reference intervals (RIs) were estimated using both direct and indirect (refineR algorithm) methods.ResultsIn samples with normal TSH levels, 90.9% of FT4 measurements were within the normal range provided by Roche (12–22 pmol/L). For FT4 measurements, confidence intervals (CIs) for the lower end of the RI obtained using direct and indirect methods were lower than estimated values in the method sheet; the estimated value of the upper end of the RI (UEoRI) in the method sheet was within the CI for the UEoRI using the direct method but not the indirect method. CIs for the direct and indirect methods overlapped at both ends of the RI. The most common cause of increased FT4 with normal TSH was identified in a subset of patients as use of thyroxine therapy (72.6%).ConclusionsIt is important to verify RIs for FT4 in the laboratory population when changing testing platforms; indirect methods may constitute a convenient tool for this. Applying specific RIs for selected subpopulations should be considered to avoid misinterpretations and inappropriate clinical actions.

Offspring conceived through ART have normal thyroid function in adolescence and as young adults.

STUDY QUESTIONAre there differences in thyroid function between adolescents and young adults conceived with and without ART?SUMMARY ANSWERThis study demonstrated no evidence of clinically relevant differences in thyroid function between adolescents and young adults conceived with and without ART.WHAT IS KNOWN ALREADYStudies to date have reported an increase in subclinical hypothyroidism in offspring conceived after ART. It has been suggested that the increase in maternal estrogen (E2) after fresh embryo transfers could affect thyroid function of the offspring. Suboptimal thyroid function at a young age can cause irreversible damage to the central nervous system, which makes early detection and correct treatment essential.STUDY DESIGN, SIZE, DURATIONThe Growing Up Healthy Study (GUHS) is a prospective cohort study, which aimed to recruit all adolescents born after conception with ART between 1991 and 2001 in the study area. The included participants (n = 303, aged 13–20 years) completed various health assessments. Depending on the age at enrolment, participants completed thyroid assessments at the 14- or 20-year follow-up. The outcomes of these replicated thyroid assessments were compared to those of participants conceived without ART from the Raine Study Generation 2 (Gen2). The Gen2 participants (n = 2868) were born between 1989 and 1992 and have been recognized to be representative of the local population.PARTICIPANTS/MATERIALS, SETTING, METHODSThyroid function assessments were compared between n = 134 GUHS and n = 1359 Gen2 adolescents at age 14 years and between n = 47 GUHS and n = 914 Gen2 young adults at age 20 years. The following mean thyroid hormone concentrations were compared between the cohorts: thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4) and thyroid peroxidase antibodies (TPOAb). The prevalence of the following thyroid hormone profiles, based on individual thyroid hormone concentrations, was compared: euthyroidism, subclinical and overt hypo- and hyperthyroidism and thyroid autoimmunity. Outcomes were compared between the cohorts, and univariately between fresh embryo transfers (ET) and frozen ET (FET) within the GUHS. The correlation between maternal peak E2 concentrations (pE2) and fT4 was assessed within the GUHS.MAIN RESULTS AND THE ROLE OF CHANCEAll mean thyroid function outcomes fell within the normal range. At both ages, we report no differences in TSH concentrations. At age 14 years, lower fT3 concentrations (4.80 versus 5.35 pmol/L, P < 0.001) and higher fT4 concentrations (12.76 versus 12.19 pmol/L, P < 0.001) were detected in the GUHS adolescents compared to Gen2 adolescents. At age 20 years, higher fT3 and fT4 concentrations were reported in GUHS adolescents (4.91 versus 4.63 pmol/L, P = 0.012; 13.43 versus 12.45 pmol/L, P < 0.001, respectively) compared to Gen2 participants. No differences in the prevalence of subclinical and overt hypo- and hyperthyroidism or thyroid autoimmunity were demonstrated between the cohorts at age 14 and 20 years. Thyroid function did not differ between ET and FET, and no correlation between pE2 and fT4 was reported.LIMITATIONS, REASONS FOR CAUTIONThe observational nature of the study limits the ability to prove causation. Furthermore, the comparison of ET and FET offspring at age 20 years may be lacking power. We were unable to differentiate between different types of ART (e.g. IVF versus ICSI) owing to the low number of ICSI cycles at the time of study. As ART laboratory and clinic data were collected contemporaneously with the time of treatment, no other data pertaining to the ART cycles were sought retrospectively; hence, some factors could not be accounted for.WIDER IMPLICATIONS OF THE FINDINGSThis study does not support previous findings of clinically relevant differences in thyroid function when comparing a cohort of adolescents conceived after ART to counterparts conceived without ART. The minor differences detected in fT3 and fT4 were considered not biologically relevant. Although these findings appear reassuring, they warrant reinvestigation in adulthood.STUDY FUNDING/COMPETING INTERESTSThis project was funded by an NHMRC Grant (Hart et al., ID 1042269). R.J.H. is the Medical Director of Fertility Specialists of Western Australia and a shareholder in Western IVF. He has received educational sponsorship from MSD, Merck-Serono and Ferring Pharmaceuticals. P.B. is the Scientific Director of Concept Fertility Centre, Subiaco, Western Australia. J.L.Y. is the Medical Director and a shareholder of PIVET Medical Centre, Perth, Western Australia.TRIAL REGISTRATION NUMBERN/A.

Body Composition and Serum Concentration of Thyroid Hormones in Euthyroid Men and Women from General Population.

Body composition, especially an increased amount of fat mass and decreased lean body mass, is connected with metabolic complications. Thyroid hormones can influence body composition pattern. To date, scarce data defining the relationships between thyroid hormones and parameters of body composition using dual-energy X-ray absorptiometry (DXA), especially in cohort studies, are available. Therefore, the aim of the present study was to investigate the relationships among serum concentrations of (thyroid-stimulating hormone (TSH), thyroid hormones, and distribution of fat tissue assessed using the DXA method in a euthyroid cohort from the Białystok PLUS study. We examined 582 euthyroid subjects who were divided into lean (body mass index (BMI) < 25 kg/m2) and overweight/obese (BMI ≥ 25 kg/m2) (84 lean men, 182 overweight/obese men, 160 lean women, and 156 overweight/obese women). Serum concentrations of TSH, free T3 (fT3), and free T4 (fT4) were assessed, and DXA was performed. We observed lower serum levels of fT4 (p = 0.03) and higher serum levels of fT3 (p = 0.04) in overweight/obese vs. lean men, whereas serum levels of TSH did not differ between these groups (p = 0.38). In lean men, we only observed a relationship between serum levels of TSH and visceral adipose tissue (VAT) (r = −0.24, p = 0.02). In overweight/obese men, we found that serum levels of fT3 were positively connected with total fat mass (r = 0.16, p = 0.02), android fat mass (r = 0.15, p = 0.03), and gynoid fat mass (r = 0.17, p = 0.01), but not with VAT (r = 0.03, p = 0.63). We did not observe differences in serum levels of TSH, fT3, and fT4 between lean and overweight/obese women. Additionally, we did not notice relationships between serum levels of thyroid hormones and fat in different regions estimated by DXA in lean and overweight/obese women (all p > 0.05). We concluded that the serum concentration of TSH is connected with VAT in lean men, whereas, in overweight/obese men, higher fT3 is connected with an increased fat amount. These associations are absent in women.

Thyroid dysfunction incidence and risk factors in Chinese chronic hepatitis B patients treated with pegylated interferon alpha: A long‐term follow‐up study

The long-term impact, incidence and risk factors of thyroid dysfunction in chronic hepatitis B (CHB) patients receiving pegylated interferon (IFN) alpha (PegIFN-alpha) therapy remain unclear. We aim to investigate the long-term safety of thyroid dysfunction in CHB patients receiving PegIFN-alpha. A retrospective observational study of 425 CHB patients with normal baseline thyroid function was carried out. Patients were followed up over 10years to assess thyroid function after receiving IFN. At the end of the IFN therapy, 67 patients (15.8%) had developed thyroid dysfunction, 31 patients (46.3%) had hyperthyroidism and 64.4% presented with subclinical thyroid dysfunction. In follow-up of thyroid dysfunction patients, 37 patients (74.0%) spontaneously regained normal thyroid function. Pretreatment thyroid-stimulating hormone (TSH) level, thyroid peroxidase antibody (TPOAb) positivity and free thyroxine (FT4) were independent risk factors associated with thyroid dysfunction incidence. High TSH level (OR=9.866, 95%CI, 3.245-29.998) was associated with a greater likelihood of hypothyroidism. High FT4levels (OR=0.464, 95%CI, 0.248-0.868) indicate a low likelihood of thyroid dysfunction. Thyroid dysfunction is a common but acceptable side effect of IFN therapy for CHB. Most thyroid dysfunction is reversible. Pretreatment TSH level and TPOAb positivity are risk factors for thyroid dysfunction development during IFN therapy. A high TSH level predicts an increased incidence of hypothyroidism. Moreover, FT4may be a protective factor for thyroid dysfunction.

Increased Central and Peripheral Thyroid Resistance Indices During the First Half of Gestation Were Associated With Lowered Risk of Gestational Diabetes—Analyses Based on Huizhou Birth Cohort in South China

ObjectivesThe study aimed to explore the relationship of thyroid function and resistance indices with subsequent risk of gestational diabetes (GDM).DesignThis was a longitudinal study embedded in the Huizhou Birth Cohort.MethodsA total of 2,927 women of singleton pregnancy were recruited from January to October of 2019. Thyroid central resistance indices were evaluated by Thyroid Feedback Quartile-Based index (TFQI), Thyrotrophy T4 Resistance Index (TT4RI), and TSH Index (TSHI) based on plasma-free thyroxine (FT4) and thyroid-stimulating hormone (TSH) levels during the first half of pregnancy. Thyroid peripheral sensitivity was assessed by free triiodothyronine (FT3) to FT4 ratio (FT3/FT4), a proxy of deiodinase activity. GDM was diagnosed between 24 and 28 weeks of gestation by a standardized 75 g oral glucose tolerance test. Multivariable linear and logistic regression was applied to examine the associations of thyroid markers with GDM risk.ResultsFT3 and FT3/FT4 were positively associated with both fasting and post-load glucose levels, while TSH, TSHI, TT4RI, and TFQI were negatively associated with 1 and 2 h post-load glucose levels. Compared with the lowest quartile, GDM risk in the highest quartile increased by 44% [odds ratio (OR) = 1.44; 95%CI, 1.08–1.92; ptrend = 0.027] for FT3 and 81% (OR = 1.81; 95%CI, 1.33–2.46; ptrend < 0.001) for FT3/FT4, while it lowered by 37% (OR = 0.63; 95%CI, 0.47–0.86; ptrend = 0.002] for TSHI, 28% for TT4RI (OR = 0.72; 95%CI, 0.54–0.97; ptrend = 0.06), and 37% for TFQI (OR = 0.63; 95%CI, 0.46–0.85; ptrend < 0.001).ConclusionsThis longitudinal study indicated that higher FT3 and FT3/FT4 and lower central thyroid resistance indices were associated with increased risk of GDM.

Abstract 8: Thyroid amyloidosis presenting as persistent painless thyroiditis

Case Report: A 34-year-old patient with ESRF, found to have hereditary-amyloidosis, was referred with low TSH: 0.112 (0.340-4.250 micIU/mL), low FT3: 1.77 (2.40-4.20 pg/mL) and normal FT4:1.49 (0.80-2.30 ng/dL) in May 2018. Clinically asymptomatic, euthyroid and no goitre; was diagnosed “Sick-Euthyroid-Syndrome”. He underwent renal transplant in August 2018; his subsequent treatment included Prednisolone 20mg daily and immunosuppressants. On follow-up, his TSH was 0.303 in Oct 2018. Over next year, he had persistently low TSH: 0.005-0.196, with normal FT3, but elevated FT4: 2.39-5.21. His clinical-features varied from being asymptomatic to developing mild thyrotoxicosis. ESR: normal, Thyroid-antibodies negative, USG showed diffuse thyroid and repeated Technetium-99 scans revealed ‘gross thyroiditis’. He was managed on beta-blockers and ongoing Prednisolone. His health deteriorated since late 2019, with multiple episodes of pancreatitis due to pancreatic-duct-stones and stricture. He returned back in 2021 with neck-swelling; non-tender large-goitre with multiple nodules. TFT: low TSH, high FT4 and normal FT3. USG revealed bulky thyroid with few nodules; FNAC suggested Amyloid. He underwent Total Thyroidectomy; Histopathology confirmed ‘Amyloidosis’. Conclusion: Our patient had chronic painless thyroiditis and his steroid-therapy for post-transplant-immunosuppression probably masked the thyrotoxic-features. USG-thyroid indicated gradual structural changes, and TFT suggested possible impaired peripheral conversion of T4 to T3.

Thyroid function, thyroid antibodies and early postnatal development in neonates of mothers with thyroid disorders

BackgroundThyroid dysfunction during pregnancy is relatively common and can cause obstetric complications and significantly influence fetal development. AimsWe aimed to evaluate postnatal clinical and laboratory characteristics in the first days of life in infants born to mothers with a thyroid disorder. Study design and subjectsWe conducted a retrospective single-center study with neonates born between January 2010 and May 2020. Early laboratory parameters and clinical findings in neonates of mothers with different maternal thyroid disorders were analysed. ResultsWe included 314 newborns of mothers with Hashimoto's thyroiditis, 171 with non-Hashimoto's hypothyroidism, 42 with Graves' disease, 12 with non-Graves' hyperthyroidism, and 190 neonates born to mothers without thyroid dysfunction. No demographic, clinical, and laboratory differences were observed between neonates from mothers with a thyroid disorder and healthy mothers. FT3 and fT4 correlated positively with gestational age (p < 0.001; p < 0.001) and negatively with maximum postnatal weight loss (p = 0.043; p < 0.001). High fT3 values were associated with lower maximum bilirubin levels (p = 0.020). ConclusionDespite an increased morbidity risk due to the transplacental exposure to maternal antibodies, most neonates born to mothers with thyroid disorders show normal postnatal development and thyroid function tests during the first days of life.

Identifying Non-Linear Association Between Maternal Free Thyroxine and Risk of Preterm Delivery by a Machine Learning Model.

ObjectivePreterm delivery (PTD) is the primary cause of mortality in infants. Mounting evidence indicates that thyroid dysfunction might be associated with an increased risk of PTD, but the dose-dependent association between the continuous spectrum maternal free thyroxine (FT4) and PTD is still not well-defined. This study aimed to further investigate this relationship using a machine learning-based model.MethodsA hospital-based cohort study was conducted from January 2014 to December 2018 in Shanghai, China. Pregnant women who delivered singleton live births and had first-trimester thyroid function data available were included. The generalized additive models with penalized cubic regression spline were applied to explore the non-linear association between maternal FT4 and risk of PTD and also subtypes of PTD. The time-to-event method and multivariable Cox proportional hazard model were further applied to analyze the association of abnormally high and low maternal FT4 concentrations with the timing of PTD.ResultsA total of 65,565 singleton pregnancies with completed medical records and no known thyroid disease before pregnancy were included for final analyses. There was a U-shaped dose-dependent relationship between maternal FT4 in the first trimester and PTD (p <0.001). Compared with the normal range of maternal FT4, increased risk of PTD was identified in both low maternal FT4 (<11.7 pmol/L; adjusted hazard ratio [HR] 1.34, 95% CI [1.13–1.59]) and high maternal FT4 (>19.7 pmol/L; HR 1.41, 95% CI [1.13–1.76]). The association between isolated hypothyroxinemia and PTD was mainly associated with spontaneous PTD (HR 1.33, 95% CI [1.11–1.59]) while overt hyperthyroidism may be attributable to iatrogenic PTD (HR 1.51, 95% CI [1.18–1.92]) when compared with euthyroid women. Additionally, mediation analysis identified that an estimated 11.80% of the association between overt hyperthyroidism and iatrogenic PTD risk was mediated via the occurrence of hypertensive disorders in pregnancy (p <0.001).ConclusionsWe revealed a U-shaped association between maternal FT4 and PTD for the first time, exceeding the clinical definition of maternal thyroid function test abnormalities. Our findings provide insights towards the need to establish optimal range of maternal FT4 concentrations for preventing adverse outcomes in pregnancy.

Higher Free Triiodothyronine Is Associated With Higher HDL Particle Concentration and Smaller HDL Particle Size.

ContextThyroid function status has effects on the development of atherosclerotic cardiovascular disease by affecting lipid metabolism, but associations of high-density lipoprotein (HDL) particle concentrations and subfractions with thyroid hormone levels within the reference range remain elusive.ObjectiveThe aim of the present study was to determine the associations of free triiodothyronine (FT3), free thyroxine (FT4) and thyroid-stimulating hormone (TSH) levels with HDL particle characteristics in euthyroid individuals.MethodsThis cross-sectional study on the associations of thyroid hormones with HDL particle concentrations, HDL subfractions, and HDL particle size included 5844 euthyroid individuals (FT3, FT4, and TSH levels within the reference range and no medication use affecting thyroid function), participating in the Prevention of REnal and Vascular ENd-stage Disease (PREVEND) study. HDL particles and subfractions were measured by nuclear magnetic resonance using an optimized version of the NMR LipoProfile Test (LP4).ResultsIn multivariable linear regression analyses, FT3 was positively associated with total HDL particle concentration (std.β = 0.14; P < 0.001) and with small (std.β = 0.13; P < 0.001) and medium-sized HDL particles (std.β = 0.05; P = 0.001). Conversely, FT3 was inversely associated with large HDL particles (std.β = −0.07; P < 0.001) and with HDL particle size (std.β = −0.08; P < 0.001). Such associations with FT4 or reciprocally with TSH were less pronounced or nonsignificant.ConclusionIn euthyroid individuals, higher FT3 is cross-sectionally associated with higher total HDL particle concentration and with lower HDL particle size. These associations may be relevant to better understand the role of HDL in thyroid function–associated atherosclerotic cardiovascular disease.

Free Triiodothyronine and Free Triiodothyronine to Free Thyroxine Ratio Predict All-Cause Mortality in Patients with Diabetic Foot Ulcers.

PurposeFree triiodothyronine (FT3) and FT3/free thyroxine (FT4) ratio have been associated with mortality in various diseases. However, no study to date has identified a link between FT3, FT3/FT4 ratio and all-cause mortality in patients with diabetic foot ulcers (DFUs). This study aimed to investigate this relationship.MethodsThis retrospective cohort study included 726 patients diagnosed with DFUs in a public hospital from January 2015 to October 2019. Patients were classified by the optimal cut-off values of the FT3 and FT3/FT4 ratio, respectively. The association of FT3 and FT3/FT4 ratio with all-cause mortality was evaluated in a multivariable cox regression model. Directed acyclic graphs were used to assess the minimally sufficient sets of confounding variables.ResultsLog rank tests indicated that patients with low FT3 and FT3/FT4 ratio had lower overall survival rates (all p < 0.001). The adjusted HRs for all-cause mortality were 0.48 (95% CI: 0.32–0.73, P = 0.001) when comparing high versus low FT3 and 0.47 (95% CI: 0.32–0.70, P < 0.001) when comparing high versus low FT3/FT4 ratio. Subgroup analyses showed that these associations existed only in elderly patients (≥65 years) and women, after adjustment. In men, only high FT3/FT4 ratio was associated with low all-cause mortality, after adjustment.ConclusionRoutine assessment of FT3 and FT3/FT4 ratio may be a simple and effective way to identify high-risk patients with DFUs, especially in elderly patients and women.

Sex-specific Effect of Maternal Thyroid Hormone Trajectories on Preschoolers' Behavioral Development: A Birth Cohort Study.

Maternal thyroid hormone trajectories are a better predictor of offspring's neurodevelopment than hormone levels in single trimester of pregnancy. Programming effect of uterine hormonal environment on offspring's health is usually sex-specific. To examine the sex-specific effect of thyroid hormone trajectories on preschoolers' behavioral development. Based on Ma' anshan Birth Cohort in China, pregnant women were recruited at their first antenatal checkup from May 2013 to September 2014. Ma' anshan Maternal and Child Health Hospital in China. 1860 mother-child pairs were included in the analysis. Children were followed up at age of 4. Maternal thyroid hormones [thyroid-stimulating hormone (TSH), free thyroxine (FT4)] and thyroid peroxidase antibody in the first, second, and third trimesters of pregnancy were retrospectively assayed. Preschoolers' behavioral development was assessed by Achenbach Child Behavior Checklist/1.5~5. Maternal TSH and FT4 levels were respectively fitted into high, moderate, and low trajectories. In boys, maternal high TSH trajectory was related to withdrawn [odds ratio (OR) = 2.01, 95% CI: 1.16, 3.50) and externalizing problems (OR = 2.69, 95% CI: 1.22, 5.92), and moderate TSH trajectory was associated with aggressive behavior (OR = 3.76, 95% CI: 1.16, 12.23). Maternal high FT4 trajectory was associated with anxious/depressed (OR = 2.22, 95% CI: 1.08, 4.56) and total problems (OR = 1.74, 95% CI: 1.13, 2.66), and low FT4 trajectory was associated with aggressive behavior (OR = 4.17, 95% CI: 1.22, 14.24). Maternal thyroid hormone trajectories impact preschool boys' behavioral development.

Analysis of thyroid function in Japanese patients with coronavirus disease 2019.

Thyroid dysfunction that is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is becoming increasingly recognized. However, only a few reports in Japan have addressed this issue to date. In this study, we sought to clarify whether infection with SARS-CoV-2 affected thyroid hormone levels and whether these hormones could be better predictors of prognosis in patients with coronavirus disease 2019 (COVID-19). Accordingly, we retrospectively examined 147 cases wherein thyroid hormones were measured at the time of admission among 848 Japanese patients with COVID-19 admitted to the Hyogo Prefectural Kakogawa Medical Center. All patients underwent thyroid function testing upon hospital admission. More than half (59.1%) of the patients were euthyroid. Twenty-four percent of patients had serum thyroid-stimulating hormone (TSH) levels lower than the reference range with normal serum free thyroxine (fT4) levels, and 3.4% of the patients had low TSH with high fT4 levels. Over 70% of the patients with moderate and severe COVID-19 had low serum free triiodothyronine (fT3) levels. Serum TSH and fT3 levels were inversely correlated with disease severity. The mortality rate in patients with low serum fT3 levels was significantly higher than that in those with normal serum fT3 levels.

Are Changes in Thyroid Hormones Associated with Mortality in Non-Thyroidal Illness Syndrome?

Introduction: Non-thyroidal illness syndrome (NTIS) can be defined as afunctional impairment of the hypothalamic-pituitary-thyroid axis accompanied by signs of non-thyroidal disease with changes in thyroid stimulating hormone (TSH), free T3 (fT3) and free T4 (fT4) levels. NTIS and thyroid hormone levels in this syndrome are thought to be related with mortality. This study was performed to evaluate the relationship between hormone levels and mortality in this syndrome.&#x0D; Methods: The 5-year mortality data of patients who were hospitalized in the first 6 months of 2014 and whose thyroid hormone levels could be checked twice within 5 years were evaluated. In our study conducted with 405 patients whose thyroid function tests was repeated, the follow-up period was 5 years. Biochemical parameters including thyroid function tests were sent from all patients. NTIS was defined as a condition in patients with low fT3 levels (&lt;2.5 pg/mL) and TSH levels within the normal range (0.38-5.33 mIU / L).&#x0D; Results: 128 patients died, and the number of surviving patients was 277 during the follow-up period. Positive acute phase reactants such as CRP, sedimentation, ferritin was high and albumin (negative acute phase reactant) and fT3 levels were low in patients who died. In addition, these changes in biochemical values were statistically significant. The mortality rate was increased in patients with low fT3 and high fT4 levels. In the follow-up period, changes in TSH levels were not significantly associated with mortality.&#x0D; Conclusion: Both the decrease in fT3 levels and the increase in fT4 levels can be used as predictors and independent risk factors for long-term mortality risk in chronically ill and hospitalized patients with NTIS.