Free T4 Concentrations Research Articles

Everolimus assay* with automated pretreatment for the dimension chemistry systems

We examined the correlation between thyroid hormone (TH) concentrations and the serum fibroblast growth factor 21 (FGF21) concentration in septic patients and to assess the collaborative value of these factors in predicting 28-day mortality in septic patients.A total of 120 consecutive patients with sepsis were divided into two groups according to their survival or death within 28 days after initial diagnosis of sepsis.Patients in the non-survivor group had significantly higher serum FGF21 concentrations but lower total and free triiodothyronine (T3) and tetraiodothyronine (T4) concentrations than those in the survivor group. Thyroid hormone concentrations, including T3, free T3, T4 and free T4, were significantly negatively correlated with the ∆SOFA and APACHE II scores as well as the serum FGF21, IL-6, tumor necrosis factor-α, IL-10, procalcitonin, and C-reactive protein concentrations. Logistic regression analysis showed that the ∆SOFA score, serum FGF21 concentration, and free T3 concentration were significant predictors of 28-day mortality. The model with variables of ∆SOFA score and serum FGF21 and free T3 concentrations had the greatest area under the curve of 0.969.The addition of free T3 and serum FGF21 to ∆SOFA score provided a significantly improved ability to predict 28-day mortality in septic patients.

Low triiodothyronine syndrome and selenium deficiency - undervalued players in advanced heart failure? A single center pilot study

BackgroundThe function of deiodinases – selenoproteins converting thyroid hormones may be disturbed by oxidative stress accompanying heart failure. Selenium (Se) may be used by glutathione peroxidase, leading to a lack of deiodinase and triiodothyronine (T3). The aim of the study was the evaluation of the prevalence and clinical significance of low T3 syndrome in heart failure and the assessment of the association of low fT3 and Se deficiency.MethodsThe study group consisted of 59 consecutive patients hospitalized due to decompensated HFrEF NYHA III or IV. Exclusion criteria were: thyroid dysfunction, severe systemic disease, treatment with amiodarone, steroids or propranolol. Group A included 9 patients with low free T3 (fT3) concentration below 3.1 pmol/L. Group B consisted of the remaining 50 patients with normal fT3 levels.ResultsThe prevalence of low T3 syndrome was 15.3%. The prevalence of Se deficiency was 74.6%. We demonstrated correlations between fT3 and main clinical variables (i.e. NT-proBNP, LVEF, hsCRP), but we did not find correlation between fT3 and the Se level. Kaplan-Meier survival analysis showed lower survival probability in patients with low fT3 (p < 0.001).ConclusionsLow T3 syndrome is frequently found in patients with HFrEF and is associated with a poor outcome. We did not identify any significant correlation between Se and fT3 level.

Evaluation of cardiovascular risk by growth-differentiation factor-15 and tissue Doppler imaging in children with subclinical hypothyroidism.

Subclinical hypothyroidism, defined as increased TSH serum levels and normal serum free T4 concentrations, has been associated with an increased risk of heart disease in adults. But, data in children and adolescents are scanty and treatment of subclinical hypothyroidism is controversial. Growth differentiation factor-15 (GDF-15) is a promising biomarker of cardiac remodeling. This study aimed to evaluate the cardiovascular risk factors in children with subclinical hypothyroidism, measured with tissue Doppler echocardiography (TDE), and conventional echocardiography and GDF-15 level. The study comprised a total of 41 pediatric patients with subclinical hypothyroidism (SH) (mean age 9.6 ± 4.7 years) and 31 healthy children (mean age 11.2 ± 3.4 years) as the control group. Subclinical hypothyroidism was defined as a thyroid-stimulating hormone level higher than 4 mIU/l and a normal free-thyroxine level (0.6-1.8 ng/dl). Tissue Doppler echocardiography was performed to all individuals in the control group and patient group at the beginning of the study. Global systolic function as assessed by left ventricular ejection fraction was compared between groups. The serum GDF-15 level was measured. There were no significant differences in demographic parameters between the SH and control groups. The left ventricular internal diameter end systole, interventricular septal end diastole, left ventricular posterior wall end diastole, and tricuspid annular plane systolic excursion values were significantly different between the SH and control groups (p = 0.038, 0.028, 0.005, and 0.000, respectively). The mean mitral isovolumic relaxation time value of the SH group was 57.2 ± 9.3 ms, compared to 44.5 ± 5.6 ms for the control group (p = 0.000). The mean tricuspid isovolumic contraction time value of the SH group was 58.7 ± 9.4 ms, and that of the control group was 45.1 ± 5.3 ms (p = 0.000). The mean tricuspid isovolumic relaxation time value of the SH group was 58.03 ± 9.5 ms, and that of the control group was 45.1 ± 5.3 ms (p = 0.000). There were no significant differences in the other m-mode or pulse Doppler echocardiography values between two groups. The GDF-15 value of the SH group was 382.6 ± 268.2 pg/mL, and that of the control group was 473.6 ± 337.9 pg/mL; this difference was not significant. Patients with subclinical hypothyroidism versus healthy individuals had some changes in echocardiographic parameters that indicate involvement of diastolic function of the left ventricle. They were significantly different when compared SH group and the control group. This study demonstrated ventricle diastolic dysfunction in pediatric patients with hypothyroidism. The results of our study suggest that cardiac follow-up may be useful in patients with subclinical hypothyroidism and clinical trials are needed to explore therapeutic effects of T4 and T3 administration in this patients.

OR19-2 Big Data Strategy Used to Draw TSH Reference Values for Elderly Population

Introduction: Determination of reference ranges for thyroid function tests, such as TSH, are not a simple task. There are several biological and individual aspects to be considered, one of the most important is age, particularly for the extremes, children and the elderly population. Several studies demonstrated a progressive increase in age-related TSH in older adults. Therefore, the aim of this study is to establish specific reference values for Brazilian population over 60 years old using Big Data strategy. Methods: Data from 10.43 million TSH tests performed in the same method were retrospectively analyzed. All the samples are from the same clinical laboratory, with samples from several regions of Brazil. The samples were selected using the following filters: free T4 concentration within the reference values (RV), absence of anti-thyroid antibodies and of medication use. Groups were divided by age from 18 to 59 years old (under-60), and over 60 up to 107 years old (over-60). Statistical analyzes were performed using R software and EP Evaluator. Both R package ‘boot’ and EP Evaluator nonparametric (CLSI C28-A) were used to estimate the 97.5% confidence interval (IC). Results: After filtering the samples, 306,289 were selected. Mean TSH was similar in both sex. However, there were differences between the two age-groups, in under-60 group, the lower RV was 0.59 mUI/L (95% IC = 0.57, 0.59) and the upper RV was 6.00 mUI/L (95% IC = 5.94, 6.08). Interestingly, in over-60 group the lower RV was 0.36 mUI/L (95% IC = 0.34, 0.38) and the upper RV was 9.38 mUI/L (95% IC = 8.86, 9.44). Furthermore, this upper limit of reference range increases within the older group with TSH of 7.4 mUI/L from 60 to 69, 9.60 mUI/L from 70 to 79 and 12.30 mUI/L above 80 years old. Conclusion: Big data strategy could be a useful tool to reach agreeable population reference values. In particular, for TSH, the higher upper reference limits for adults over 60 years old would be important to avoid overdiagnosis and over-treatment of subclinical hypothyroidism in this population.

Para-occupational exposure to pesticides, PON1 polymorphisms and hypothyroxinemia during the first half of pregnancy in women living in a Mexican floricultural area

BackgroundAdequate maternal thyroxine (T4) concentrations during the first half of pregnancy are fundamental to the embryo’s or fetus’ neural development. Organophosphate pesticides (OP) can act as thyroid disruptors and genetic polymorphisms for paraoxonase 1 (PON1), an enzyme that detoxifies OP, could be involved in individual’s susceptibility to them. We assessed the association between para-occupational exposure to pesticides, including OP, during pregnancy and maternal hypothyroxinemia, as well as the potential genetic susceptibility conferred by PON1 polymorphisms.MethodsWe analyzed information from 381 healthy pregnant women (< 17 gestational weeks), who lived in a floricultural region of Mexico where pesticides, including OP, are routinely used. Women who were para-occupationally exposed to pesticides were those whose partner had an occupation involving contact with these products. Thyroid-Stimulating Hormone (TSH) and free T4 concentrations were determined using ELISA, and hypothyroxinemia was defined as free T4 concentrations <0.76 ng/dL. PON1192QR, PON155LM and PON1–108CT polymorphisms were determined through Polymerase Chain Reaction (PCR). The association between para-occupational exposure and genetic polymorphisms and hypothyroxinemia was estimated using logistic regression models.ResultsOne hundred and sixty two women (42.52%) were classified as para-occupationally exposed to pesticides. Hypothyroxinemia prevalence was 54%, and it was not significantly associated with pesticide para-occupational exposure (OR: 1.21 95% CI 0.75–1.94). Independently of para-occupational exposure, the likelihood of hypothyroxinemia was higher among women who were carriers of PON155MM than in those with PON155LL genotype (OR MM vs LL: 3.03; 95%CI 1.62, 5.70). PON1192 RR (OR RR vs QQ: 1.72; 95%CI 0.93, 3.17) and PON1–108TT (OR TT vs CC: 1.60; 95%CI 0.90, 2.70) genotypes were marginally associated with hypothyroxinemia. No significant interaction was observed between pesticides para-occupational exposure and PON1 polymorphisms.ConclusionsThese results suggest that PON1 polymorphisms could affect thyroid function during pregnancy in women living in areas where pesticides, including OP, are routinely used. Low exposure variability in this population, could be a possible explanation for the lack of association between para-occupational exposure and thyroid function.

The prognostic value of total T3 after acute cerebral infarction is age-dependent: a retrospective study on 768 patients

BackgroundSerum triiodothyronine (T3) concentration was reported to be associated with the prognosis after acute ischemic stroke. The aim of this study was to evaluate the effect of age on the prognostic value of thyroid-related hormones after an acute ischemic stroke.MethodsThis was a retrospective study involving the review of 1072 ischemic stroke patients who had been consecutively admitted to the hospital within 72 h of symptom onset. Total triiodothyronine (T3), total thyroxine (T4), free T3, free T4, and thyroid-stimulating hormone (TSH) were assessed to determine their values for predicting functional outcome at the first follow-up clinic visits, which usually occurred 2 to 4 weeks after discharge from the hospital.ResultsA total of 768 patients were finally included in the study and divided into two age groups: a younger group (age < 65 years) and an older group (age ≥ 65 years). On univariate analysis, four factors—lower total T3, free T3 concentrations, higher scores on the National Institute of Health Stroke Scale (NIHSS) and the presence of atrial fibrillation—were associated with poor functional outcomes in both groups. In addition, older age, female gender, higher free T4, and lower TSH levels were also associated with poor function in the older group. On multiple logistic regression analysis, higher NIHSS scores (odds ratio [OR] =1.95; 95% confidence interval [CI], 1.66–2.30; P ≤ .001) and lower total T3 concentrations (OR = 0.06; 95% CI, 0.01–0.68; P = .024) remained independently associated with poor functional outcome in the older group. However, the independent association with poor function of lower total T3 was not confirmed in the younger group.ConclusionsThe prognostic value of low total T3 is age-associated and more meaningful in an older population.

Predictive value of combined serum FGF21 and free T3 for survival in septic patients

BackgroundWe examined the correlation between thyroid hormone (TH) concentrations and the serum fibroblast growth factor 21 (FGF21) concentration in septic patients and to assess the collaborative value of these factors in predicting 28-day mortality in septic patients. MethodsA total of 120 consecutive patients with sepsis were divided into two groups according to their survival or death within 28 days after initial diagnosis of sepsis. ResultsPatients in the non-survivor group had significantly higher serum FGF21 concentrations but lower total and free triiodothyronine (T3) and tetraiodothyronine (T4) concentrations than those in the survivor group. Thyroid hormone concentrations, including T3, free T3, T4 and free T4, were significantly negatively correlated with the ∆SOFA and APACHE II scores as well as the serum FGF21, IL-6, tumor necrosis factor-α, IL-10, procalcitonin, and C-reactive protein concentrations. Logistic regression analysis showed that the ∆SOFA score, serum FGF21 concentration, and free T3 concentration were significant predictors of 28-day mortality. The model with variables of ∆SOFA score and serum FGF21 and free T3 concentrations had the greatest area under the curve of 0.969. ConclusionThe addition of free T3 and serum FGF21 to ∆SOFA score provided a significantly improved ability to predict 28-day mortality in septic patients.

Depressive Symptoms After PCB Exposure: Hypotheses for Underlying Pathomechanisms via the Thyroid and Dopamine System.

Polychlorinated biphenyls’ (PCB) exposure has been reported to be associated with depressive symptoms, which is correlated to lower dopamine- (DA) and thyroxine-concentrations (T4). T4 is necessary for DA-synthesis and it binds to transthyretin (TTR) being transported into the brain. PCBs can displace T4 by binding to TTR itself, being transported into the brain and disturbing DA-synthesis, where depressive symptoms might occur. Consequently, the free T4-concentration (fT4) increases when PCBs bind to TTR. The interaction of PCBs with fT4 and its associations with the main DA metabolite, homovanillic acid (HVA), and depressive symptoms were investigated. In total, 116 participants (91.6% men) were investigated, who took part in three annual examinations (t1–t3) of the HELPcB health surveillance program. Blood was collected for measuring PCBs, hydroxy PCBs (OH-PCBs), and fT4 and urine for HVA. Depressive Symptoms were assessed with a standardized questionnaire. Interactions were tested cross-sectionally with multiple hierarchical regressions and longitudinally with mixed effect models. Related to HVA, an interaction was cross-sectionally found for lower-chlorinated PCBs (LPCBs) and dioxin-like PCBs (dlPCBs); longitudinally only for LPCBs. Related to depressive symptoms, the interaction was found for LPCBs, dlPCBs, and OH-PCBs; longitudinally again only for LPCBs. The results give first hints that a physiological process involving the thyroid and DA system is responsible for depressive symptoms after PCB exposure.

Comparison of Intra-Operative Vital Sign Changes during Total Thyroidectomy in Patients with Controlled and Uncontrolled Graves' Disease.

Thyroid storm (TS) is a life-threatening emergency endocrine condition. Thyroid hormones should be normalized before thyroidectomy is performed in patients with Graves’ disease. However, thyroid hormone levels are inevitably high in patients undergoing surgery. This study analyzed differences in vital sign changes during thyroidectomy between patients with controlled and uncontrolled Graves’ disease and assessed thyroid hormone cutoffs for TS. Preoperative levels of the thyroid hormones free T4 (FT4), T3, and thyroid stimulating hormone (TSH) were retrospectively analyzed in patients who underwent total thyroidectomy for Graves’ disease. Patients were divided into those with uncontrolled Graves’ (UG) disease, defined as preoperative TSH <0.3 µIU/mL and FT4 >1.7 ng/dL, those with controlled Graves’ (CG) disease, those with extremely uncontrolled Graves’ (EUG) disease, defined as TSH <0.3 µIU/mL and FT4 >3.4 ng/dL, and finally, those without EUG (non-EUG). The 29 patients with Graves’ disease included 12 with CG group and 17 with UG. FT4 and T3 concentrations were significantly higher in the UG group. There were no differences in vital sign and anesthetic agent. These 29 patients could also be divided into those with (n = 4) and without EUG (n = 25). The mean age was lower (21.5 vs. 40.9 years, p < 0.001) and the mean operation time was shorter (121.4 vs. 208.8 min, p = 0.003) in the EUG group. Requirements for anesthetic agents were greater in the EUG group. Mean FT4 concentration in the EUG group was 3.8 ng/dL, and there were no changes in vital signs during surgery. Vital sign change during thyroid surgery was not observed in patients with uncontrolled Graves’ disease up to the twice upper normal limit of T4 level.

Spontaneous primary hypothyroidism in 7 adult cats.

BackgroundNaturally occurring hypothyroidism in adult cats is rare, with only 4 cases reported.ObjectivesTo describe the historical, clinical, laboratory, and scintigraphic features of adult cats with spontaneous hypothyroidism.AnimalsSeven adult cats referred for suspected hypothyroidism.MethodsProspective case series. We collected data on cats’ signalment, clinical signs, results of physical examination, routine laboratory and thyroid hormone testing, and thyroid imaging (thyroid scintigraphy or ultrasound). We subsequently treated cats with levothyroxine and evaluated their response to treatment.ResultsCats ranged from 3.5 to 11 years, with no apparent breed predilection; 6/7 cats were male. Only 2/7 cats were initially tested because of signs of hypothyroidism (hair‐coat changes, lethargy, obesity); others were tested for routine thyroid monitoring or palpable thyroid nodules. Four were azotemic (serum creatinine, 2.2‐3.4 mg/dL). Six of the cats had low serum thyroxine (T4) and free T4 (fT4) concentrations, whereas all 7 cats had high thyroid‐stimulating hormone (TSH) concentrations. In 6/7 cats, thyroid scintigraphy revealed bilateral goiter with intense radionuclide uptake; imaging showed no visible thyroid tissue in the other. After levothyroxine treatment, serum concentrations of T4 and fT4 increased and TSH fell; high serum creatinine normalized in azotemic cats; and repeat imaging showed reduction in goiter size.Conclusions and Clinical ImportancePrimary hypothyroidism develops in adult cats, with a higher prevalence than previously thought. Most cats appear to develop a goitrous form of hypothyroidism associated with thyroid hyperplasia, whereas thyroid atrophy appears to be less common. With levothyroxine replacement, clinical and laboratory abnormalities improve or resolve.

Canine visceral leishmaniosis: the relationship of blood serum thyroid hormones, lipids, and lipoproteins with clinical status.

The objective of the present study was to investigate the role of thyroid hormones and lipid profile in development and outcome of canine visceral leishmaniosis (CVL). We therefore studied the relationships between blood serum thyroid hormones [total T4, free T4, total T3, and free T3], lipids, and lipoproteins [total cholesterol, triglyceride, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C)] and clinical status in dogs naturally infected with Leishmania infantum. Two groups of Leishmania-infected dogs [with no clinical signs (NCS; n = 15), and with clinical signs (CS; n = 16)] were assessed and compared with a group of healthy control dogs (n = 15). A significant decrease in serum total T4 (p < 0.05) concentration in the CS group was observed when compared to the NCS and control groups. The dogs in CS group revealed a significant decrease (p < 0.05) in free T4 concentration in comparison to the control group. The CS group presented a significant decrease in HDL-C (p < 0.01) concentrations, when compared to NCS and control groups. The observed findings in the present study suggested that thyroid hormone and lipoprotein alterations may have a role in susceptibility of dogs with Leishmania infection.

Prospective Echocardiographic Evaluation of the Right Ventricle and Pulmonary Arterial Pressure in Hyperthyroid Patients

Pulmonary arterial hypertension (PAH) occurs in 35% to 65% of hyperthyroid patients. Despite this high frequency, only a few authors have examined the effects of hyperthyroidism treatment on PAH and the right ventricle. We evaluated the effects of hyperthyroidism and its reversal on cardiovascular structure and function using Doppler echocardiography. We prospectively evaluated 32 patients (42.5±11.9years old) with thyrotoxicosis. Exclusion criteria included previous cardiovascular disease. An echocardiogram was performed at the time of hyperthyroidism diagnosis and after normalisation of free thyroxine (T4) levels. Patients were divided into two groups according to the presence or absence of PAH at the diagnosis, or at two moments, before and after T4 normalisation. Graves' disease was the most frequent aetiology (75%) of hyperthyroidism. Pulmonary arterial hypertension was observed in 43.8% of patients. Free T4 concentration was higher in PAH than non-PAH patients. Free T4 normalised after 5 (2.0-10.5; median and percentiles) months of treatment. Cardiac chamber sizes and cardiac output were higher in PAH. Right ventricular (RV) systolic function was impaired in PAH. Cardiac output and free T4 (r=0.42; p<0.05) correlated with pulmonary artery systolic pressure (PASP). Cardiac chamber size, cardiac output, left ventricular ejection fraction, and PASP (34.0±8.6 to 21.7±4.5mmHg) reduced after treatment. Right ventricular myocardial performance index and fractional area change improved after T4 normalisation. Pulmonary arterial hypertension is highly prevalent in hyperthyroid patients and is combined with increased cardiac chambers size and cardiac output, and impaired RV function. Cardiovascular changes are reversible after T4 normalisation in patients without cardiovascular disease.

Hypothyroidism in Clinical Practice

Hypothyroidism in Clinical Practice

Mild Hypothyroidism in Childhood: Who, When, and How Should Be Treated?

Mild hypothyroidism, also known as subclinical hypothyroidism (SH), is biochemically defined as serum TSH levels above the upper limit of the reference range, in the presence of normal serum concentrations of total T4 and free T4 (FT4). In the neonatal period, mild hypothyroidism can be defined by the presence of a TSH value between 6 and 20 mIU/L and normal FT4 levels. After the neonatal period, SH can be defined mild if TSH ranges between 4.5 and 10 mIU/L. The management of mild hypothyroidism in childhood is challenging. The major concern is to establish whether this condition should always be considered an expression of mild thyroid dysfunction. Indeed, the effects of untreated mild hypothyroidism are still not completely defined. In the neonatal period, concern exists about neurocognitive outcome; in children, although there is no clear evidence of alterations in growth or neurocognitive development, subtle cardiovascular abnormalities have been documented. Therefore, there is still uncertainty about the need of treatment across all ages, and the management should be based on the age of the child, the etiology, and the degree of TSH elevation, as well as on other patient factors. This review updates current evidences on diagnosis and management of mild hypothyroidism in childhood.

The Association of Maternal Thyroid Autoimmunity During Pregnancy With Child IQ.

Thyroperoxidase antibody (TPOAb) positivity is a major risk factor for gestational thyroid dysfunction. During the first 18 to 20 weeks of pregnancy, high concentrations of human chorionic gonadotropin (hCG) stimulate the thyroid to ensure adequate thyroid hormone availability for the developing fetus. However, TPOAb-positive women have an impaired thyroidal response to hCG stimulation. To study the association of maternal TPOAb positivity during pregnancy with child IQ. This study was embedded in two prospective birth cohorts: Generation R (Rotterdam, the Netherlands) and Avon Longitudinal Study of Parents and Children (ALSPAC; United Kingdom). Mother-child pairs with available data on early pregnancy TPOAb (≤18 weeks of gestation) and offspring IQ were included (n = 3637 for Generation R and n = 2396 for ALSPAC). Child IQ at 5 to 10 years of age. In Generation R, TPOAb positivity was associated with a 2.0 ± 0.9-point lower mean child IQ (P = 0.03). Sensitivity analyses showed negative effect estimates already from TPOAb concentrations considerably lower than currently used manufacturer cutoffs. In ALSPAC, neither TPOAb positivity nor TPOAb concentrations below manufacturer cutoffs were associated with child IQ (TPOAb positivity: 0.7 ± 1.0; P = 0.45). Adjustment for maternal TSH or free T4 concentrations or urinary iodine/creatinine ratio did not change the results. TPOAb positivity during pregnancy was associated with lower child IQ in Generation R but not in ALSPAC. Further studies are needed to elucidate whether differences between the study populations, such as maternal iodine status, could be the underlying cause for these differences.

The Association of Thyroid Function With Bone Density During Childhood.

Although the skeleton is a well-known thyroid hormone target organ, very little data are available on the association of thyroid function with bone outcomes during childhood. To study the association of thyroid function with bone mass during childhood. Population-based prospective cohort including 4204 children with TSH and free T4 (FT4) measured at the age of 6 years. Bone density was assessed by a total body dual-energy X-ray absorptiometry scan at the median age of 6 years (95% range, 5.6 to 7.9) and at the age of 10 years (95% range, 9.0 to 10.9) in 4204 and 3404 participants, respectively. There was an inverse association of TSH with bone mineral density (BMD) at the age of 6 (β -0.028 ± 0.011, P = 0.009) and with follow-up measurements at the age of 10 (β -0.027 ± 0.011, P = 0.014), but not with bone mineral content (BMC) at the age of 6 (β -0.028 ± 0.015, P = 0.06) or for follow-up measurements of BMC at the age of 10 (β -0.011 ± 0.015, P = 0.47). There was an inverse association of FT4 with BMD (β -0.016 ± 0.006, P = 0.014) and BMC (β -0.023 ± 0.009, P = 0.009) cross-sectionally, and also at the age of 10 years (BMD: β -0.018 ± 0.007, P = 0.007; BMC: β -0.021 ± 0.009, P = 0.020). A higher FT4 concentration is associated with lower bone mass at the age of 6 and at the age of 10 years. These data provide insights into the effects of thyroid function on bone physiology during childhood.

Triiodothyronine replacement in critically ill adults with non-thyroidal illness syndrome

Non-thyroidal illness syndrome is commonly encountered in critically ill patients, many of whom are treated with thyroid hormones despite uncertainty regarding their safety and effectiveness. This retrospective observational study sought to evaluate the utilization, safety, and effectiveness of triiodothyronine (T3) supplementation in critically ill adults admitted to either of two non-cardiac surgery mixed-medical/surgical intensive care units (ICU). Consecutive adults admitted to an ICU and treated with enterally administered T3 were identified over a two-year period. Data pertaining to demographics, T3 utilization, safety, and clinical outcomes were collected. Data were extracted from the medical records of 70 consecutive patients. All had baseline serum free T3 concentrations below the lower limit of our laboratory's reference range and 22 (31%) patients also had low thyroxine (T4) concentrations. The most commonly prescribed replacement doses were 25 and 50 µg for a median of seven days and almost half of the patients also received concomitant T4 supplementation. Serum thyroid hormones were available in 48 of 70 patients (69%) at a median [interquartile range (IQR)] of 7 [6-38] days. Normalization of free T3 serum concentrations occurred in 30 of 48 patients (63%) at a median [IQR] of 8 [7-33] days. A dose-response relationship was identifiable. New adverse events (atrial fibrillation/flutter, hypertension, sinus tachycardia, myocardial infarction) during therapy were less frequent than at baseline. This study suggests that with T3 supplementation there was evidence of serum free T3 normalization without evidence of associated harms. A definitive trial is needed to evaluate clinical effectiveness.

Associations between serum polybrominated diphenyl ethers and thyroid hormones in a cross sectional study of a remote Alaska Native population

Polybrominated diphenyl ethers (PBDEs) are ubiquitous environmental pollutants. Arctic indigenous peoples are exposed to PBDEs through a traditional diet high in marine mammals. PBDEs disrupt thyroid homeostasis. The aim of this study was to assess the relationship between serum PBDEs and thyroid function in a remote population of St. Lawrence Island Yupik. Serum samples were collected from 85 individuals from St. Lawrence Island, Alaska and measured for concentrations of PBDEs, free and total thyroxine (T4), free and total triiodothyronine (T3), and thyroid stimulating hormone (TSH). The relationships between PBDEs and thyroid hormones were assessed using multiple linear regression fit with generalized estimating equations. Serum concentrations of several Penta-BDE congeners (BDE-28/33, 47, and 100) were positively associated with concentrations of TSH and free T3, while serum concentration of BDE-153 was negatively associated with total T3 concentrations. Both BDE-47 and 153 remained significantly associated with thyroid hormones when BDE-47, BDE-153, and BDE-209 were covariates in the same model. There were no significant relationships between serum concentrations of PBDEs and either free or total T4. Individual PBDEs are associated with thyroid hormones in serum from a remote population of Alaska Natives, and directions of effect differ by congener.

Gestational impaired glucose tolerance (GIGT)-induced suppression of fetal thyroid secretion: effect on fetal outcome

Introduction: Gestational impaired glucose tolerance (GIGT) is a milder form of gestational diabetes mellitus (GDM), which is often poorly managed. Although, GDM is known to be associated with increased incidence of thyroid dysfunction, no study has been done to study the effect of GIGT on thyroid status and its effect on fetal outcome. Here, we carried out a study to assess thyroid function and glycemic status in both maternal and cord blood of the subjects with GIGT, and to find their association with the fetal outcome.Materials and methods: Women who came to the hospital for safe confinement during 37–40th weeks of gestation were recruited in the study. Based on the 2 hours post prandial blood glucose levels with 75 grams OGTT, done at 24–28 weeks of gestation, all the subjects were stratified into two groups: (1) Cases or GIGT group – women with blood glucose levels between 120 and 140 mg/dl and (2) Controls – women with blood glucose levels of less than 120 mg/dl. Three milliliters of venous blood was collected from mothers and 3 ml of cord blood was collected during delivery. New-borns were assessed for birth weight, head circumference, abdominal circumference, thigh circumference, and crown-heel length. Glycated hemoglobin was carried out using immunoturbidimetry (DiaSys Diagnostic Systems GmbH, Holzheim, Germany) and fructosamine was estimated using dye binding method (Biosystems, Spain). Estimation of total T3 (TT3), free T3 (FT3), total T4 (TT4), free T4 (FT4), and TSH was done by chemiluminescence in Siemens Advia Centaur CP using competitive immunoassay.Results: Although within the normal reference range, GIGT mothers had higher concentration of free and total T4 than controls. Cord fructosamine levels were significantly higher in babies of GIGT mothers than controls, indicating the reflection of maternal hyperglycemia. There was a positive correlation between the maternal glycated hemoglobin and cord blood fructosamine in the GIGT group. Statistically significant lower levels of total T3 and T4 with high TSH levels were found in babies with GIGT mothers, indicating the suppressive effect of maternal hyperglycemia on fetal thyroid function. Birth weight, head circumference, and thigh circumference were significantly higher in babies born to mothers with GIGT, which may be a combined effect of maternal hyperglycemia and fetal thyroid suppression.Conclusions: Maternal hyperglycemia, even in milder form of GIGT may cause suppression of fetal thyroid function. Both these factors may predispose to change in fetal anthropometry, leading to a large baby. Therefore, it is recommended to evaluate maternal and cord thyroid function for timely management strategies.

Determination of free thyroid hormones in animal serum/plasma using ultrafiltration in combination with ultra-fast liquid chromatography-tandem mass spectrometry

Thyroid hormones (THs), which mainly consist of 3, 3′, 5-triiodo-l-thyronine (T3) and L-thyroxine (T4), play a critical role in regulating biological processes such as growth and metabolism in various animal species. Thus, accurate measurement of T3 and T4, especially physiologically active free (protein-unbound) forms, in serum/plasma is needed for the evaluation of TH homeostasis. However, such high-precision determination of free THs is lacking for non-human species. The present study aimed to develop a highly sensitive and reliable liquid chromatography-tandem mass spectrometry (LC–MS/MS) method for the determination of six free THs in serum/plasma, which is applicable to not only humans but also non-human species. Two different physical separation steps, ultrafiltration (UF) and equilibrium dialysis (ED), were examined to obtain the free TH fraction. Several experimental conditions were carefully optimized and validated for UF or ED using the commercially available bovine serum. As a result, UF at 1100 × g and 37 °C for 30 min with a 30 kDa ultrafiltration device (Centrifree YM-30, Millipore) yielded excellent precision (CV: <10%). The optimized ED step also yielded high precision (CV: <10%) and the measurement values were approximately equal to those of UF, but at least 16 h were required to reach equilibrium. Thus, UF combined with LC–MS/MS was finally chosen, in terms of the time needed for the measurement. Acceptable accuracy (recovery: 70%–110%) and intra- and inter-day precision (CV: <10% and <12%, respectively) were obtained, when triplicate analyses in three different days were conducted using the bovine serum. The developed analytical method was successfully applied to the determination of free THs in serum/plasma samples of humans, cats, and dogs. Furthermore, comparison with free T4 concentrations measured by a common immunoassay method evidently indicated that the ultrafiltration-LC–MS/MS method developed in this study can increase the specificity and accuracy of TH measurement.