Thyroid Profile in Liver Cirrhosis Patients-Correlation with Disease Severity and Recommendations for Clinical Practice: A Cross-sectional Observational Study.

INTRODUCTION: Liver diseases are increasingly recognized as significant public health concerns in India, prompting investigations into novel approaches for assessing disease severity and prognosis. Recognizing the potential utility of thyroid hormone levels in these assessments, we conducted an observational cross-sectional study at our tertiary care hospital. Our study included 89 patients aged 12 years and above, admitted to medicine wards with ultrasound-diagnosed liver cirrhosis, excluding pregnant women and those on thyroid-altering medications. OBSERVATIONS: Our findings revealed a male-to-female ratio of 4.23:1, with the majority of patients falling within the 40-60 age-group, averaging 46.93 years. Notably, 87.6% of patients exhibited thyroid abnormalities, primarily low free T3 (FT3) syndrome and subclinical hypothyroidism. Classifying patients according to Child-Pugh (CP) score, 2.2% were CP class A, 22.5% were CP class B, and the remaining 75.3% were CP class C. Across all CP classes, low FT3 syndrome was prevalent, particularly in CP class C. Correlations between thyroid hormone levels and liver disease severity, assessed via CP and model for end-stage liver disease (MELD) scoring systems, were observed. Specifically, FT3 levels demonstrated a negative correlation with liver disease severity (p = 0.001), while no significant correlations were found for free T4 (FT4) and thyroid-stimulating hormone (TSH) levels. Based on our findings, we recommend routine thyroid function testing for all liver cirrhosis patients, irrespective of disease severity, to facilitate early detection and intervention. However, our study had limitations, including a small sample size and a precision error of 10% due to resource constraints for thyroid function testing. Moreover, reliance solely on ultrasound for liver cirrhosis diagnosis may lead to missed diagnoses, highlighting the need for complementary noninvasive tests such as FibroScan and aspartate aminotransferase to platelet ratio index (APRI) scores. CONCLUSION: Our study underscores the importance of considering thyroid function in the management of liver cirrhosis patients and provides valuable insights for enhancing clinical practice in this context.

The Effects of Triiodothyronine on the Free Thyroxine Set Point Position in the Hypothalamus Pituitary Thyroid Axis.

In clinical endocrinology, it is often assumed that the results of thyroid hormone function tests (TFTs) before total thyroidectomy are considered euthyroid when the circulating concentrations of thyrotropin [TSH] and free thyroxine [FT4] are within the normal reference ranges. Postoperative thyroid replacement therapy with levothyroxine. The aim of L-T4 is to reproduce the preoperative euthyroid condition. Currently, intra-individual changes in the euthyroid set point before and after total thyroidectomy are only partly understood. After total thyroidectomy, a greater postoperative [FT4] than preoperative [FT4] for equivalent euthyroid [TSH] was found, with differences ranging from 3 to 8 pmol/L. This unexplained difference can be explained by the use of a mathematical model of the hypothalamus-pituitary-thyroid (HPT) axis set point theory. In this article, the postoperative HPT euthyroid set point was calculated using a dataset of total thyroidectomized patients with at least three distinguishable postoperative TFTs. The postoperative [TSH] set point was used as a homeostatic reference for the comparison of preoperative TFTs. The preoperative [FT4] value was equal to the postoperative [FT4] value in 50% of the patients, divided by a factor of ~ 1.25 (within +/- 10%). The factor of 1.25 stems from the lack of postoperative use of thyroidal triiodothyronine (T3). Furthermore, approximately 25% of the patients presented a greater preoperative [FT4] difference than postoperative [FT4]/1.25 combined with a normal [TSH] difference. Based on these observations, the effect of T3 on the value of the [FT4] set point was analyzed and explained from a control theory perspective.

Low free T3 level may predict the severity of acute pancreatitis.

OBJECTIVES: To demonstrate that deterioration in thyroid function tests can serve as an indicator of severity and prognosis in acute pancreatitis despite a healthy thyroid gland. METHODS: This study is a retrospective, single-center study. Patients diagnosed with acute pancreatitis between May 2020 and June 2021 were evaluated. Acute pancreatitis was diagnosed and classified according to the 2012 revised Atlanta criteria. Patients were categorized into Non-Thyroidal Illness Syndrome and euthyroid groups and compared in terms of biochemical parameters and scoring systems such as Ranson, Glasgow, Balthazar and BISAP scores. RESULTS: A total of 152 patients were included in the study. Eighty-three patients (54%) were euthyroid, with free triiodothyronine (T3), free thyroxine (T4), and Thyroid-stimulating hormone (TSH) levels within normal limits. Sixty-nine patients (46%) had Non-Thyroidal Illness Syndrome with low serum free T3 levels and low/normal TSH levels. As expected, free T3 was significantly lower in the Non-Thyroidal Illness Syndrome group than in the euthyroid group (1.5 ± 0.04 vs 2.6 ± 0.04, respectively, p < 0.0001). In the Non-Thyroidal Illness Syndrome group, Ranson score (3.35 ± 0.2 vs 2.11 ± 0.18 p < 0.0001), Glasgow (2.4 ± 0.2 vs 1.3 ± 0.1, p < 0.0001), Atlanta (p = 0.007), and Balthazar (2.1 ± 0.1 vs 1.4 ± 0.1, p = 0.001) scores were significantly higher than euthyroid group. CONCLUSION: Non-Thyroidal Illness Syndrome provides insight into the prognosis of acute pancreatitis. Free T3 values are a significant parameter that may indicate the prognosis of acute pancreatitis. We believe that free T3 could be incorporated into an ideal scoring system in a disease such as acute pancreatitis, where early determination of prognosis is known to significantly reduce mortality.

Defining Trimester-Specific Reference Intervals for Thyroid Hormones: Insights from a Bulgarian Monocenter Study.

Background and Objectives: Pregnancy introduces various interfering factors that, alongside individual variations, impact the assessment of thyroid function tests. This underscores the necessity of defining trimester-specific reference intervals for thyroid-stimulating hormone (TSH) levels. Differences in population characteristics, including ethnicity, socio-economic factors, iodine prophylaxis, and obesity, emphasize the need to establish trimester-specific TSH ranges for women of reproductive age in the respective region or center. The aim of the present study was to establish first- and second-trimester-specific reference intervals for TSH and free thyroxine (FT4) in a relevant pregnant population. Materials and Methods: A retrospective monocenter analysis utilized the electronic database of Ob/Gyn Hospital "Dr. Shterev", Sofia, Bulgaria. The analysis involved data from 497 pregnant and 250 non-pregnant women, all without evidence of thyroid dysfunction or a family history thereof, no indication of taking medication interfering with thyroid function, no evidence of levothyroxine treatment, and no history of sterility treatment. To establish the limits of the TSH reference range, the percentile method was applied using a bootstrapping procedure following the recommendations of the International Federation of Clinical Chemistry (IFCC). Results: Trimester-specific reference intervals for TSH and FT4 in our center were established as follows: first trimester-0.38-2.91 mU/L, FT4-12.18-19.48 pmol/L; second trimester-0.72-4.22 mIU/L and 9.64-17.39 pmol/L, respectively. We also established the normal reference range for the non-pregnant control group, which is similar to that applicable in our laboratory. Conclusions: Our results differ from the fixed limits recommended by the American Thyroid Association, European Thyroid Association, and Endocrine Society Guidelines. Following the relevant established intervals would significantly impact timely diagnosis and therapy requirements for a substantial proportion of pregnant women.

Agreement between routinely used immunoassays for thyroid function testing in non-pregnant and pregnant adults.

OBJECTIVE: Thyroid function tests are common biochemical analyses, and agreement between the routinely used immunoassays is important for diagnosis and monitoring of thyroid disease. Efforts are continuously made to align the biochemical assays, and we aimed to evaluate the agreement between immunoassays used in a clinical laboratory setting among non-pregnant and pregnant adults. DESIGN: Cross-sectional study. PARTICIPANTS: Serum samples were obtained from 192 blood donors (non-pregnant adults) and from 86 pregnant women in the North Denmark Region with no known thyroid disease. MEASUREMENTS: Each sample was used for measurement of thyroid-stimulating hormone (TSH) with the routinely used automatic immunoassays in the regional Departments of Clinical Biochemistry (Alinity, Abbott Laboratories, Cobas, Roche Diagnostics, and Atellica, Siemens Healthineers) and reported as the median with 95% confidence interval (95% CI). RESULTS: In nonpregnant adults, the level of TSH was higher with Cobas and Atellica than with Alinity as reflected by median (Alinity: 1.39 mIU/L (95% CI: 1.30-1.51 mIU/L); Cobas: 1.57 mIU/L (95% CI: 1.48-1.75 mIU/L); Atellica: 1.74 mIU/L (95% CI: 1.61-1.83 mIU/L)). Similarly, a trend was seen towards higher median TSH with Cobas than with Alinity among pregnant women (Alinity: 1.90 mIU/L (95% CI: 1.37-2.82 mIU/L); Cobas: 2.33 mIU/L (95% CI: 1.69-3.62 mIU/L)). CONCLUSION: Results of thyroid function tests obtained with different immunoassays were not interchangeable when evaluated among pregnant and non-pregnant adults. The distinct differences are relevant for clinical decision making and emphasize the necessity of clinical laboratory information when different assays are used for diagnosis and monitoring of patients with thyroid disease.

Salivary iodine concentration in pregnant women and its association with iodine status and thyroid function.

PURPOSE: There have been no reports on the application of salivary iodine concentration (SIC) in evaluating iodine nutrition in pregnant women. This study aimed to clarify the relationship between SIC and indicators of iodine nutritional status and thyroid function during pregnancy, to investigate whether salivary iodine can be applied to the evaluation of iodine nutritional status in pregnant women, and to provide a reference basis for establishing a normal range of salivary iodine values during pregnancy. METHODS: Pregnant women were enrolled in the Department of Obstetrics, the people's hospital of Yuncheng Country, Shandong Province, from July 2021 to December 2022, using random cluster sampling. Saliva, urine, and blood samples were collected from pregnant women to assess iodine nutritional status, and venous blood was collected to determine thyroid function. RESULTS: A total of 609 pregnant women were included in this study. The median spot urinary iodine concentration (SUIC) was 261 µg/L. The median SIC was 297 µg/L. SIC was positively correlated with SUIC (r = 0.46, P < 0.0001), 24-h UIC (r = 0.30, P < 0.0001), 24-h urinary iodine excretion (24-h UIE) (r = 0.41, P < 0.0001), and estimated iodine intake (EII) (r = 0.52, P < 0.0001). After adjusting for confounders, there was a weak correlation between SIC and serum total iodine and serum non-protein-bound iodine (P = 0.02, P = 0.04, respectively). Pregnant women with a SIC < 176 µg/L had a higher risk of insufficient iodine status (OR = 2.07, 95% CI 1.35-3.19) and thyroid dysfunction (OR = 2.71, 95% CI 1.18-6.21) compared to those with higher SIC. Those having SIC > 529 µg/L were more likely to have excessive iodine status (OR = 2.82, 95% CI 1.81-4.38) and thyroid dysfunction (OR = 3.04, 95% CI 1.36-6.78) than those with lower SIC values. CONCLUSION: SIC is associated with urinary iodine concentration and thyroid function in pregnant women. SIC < 176 µg/L was associated with an increased risk for iodine deficiency and hypothyroxinemia, while SIC > 529 µg/L was related to excess and thyrotoxicosis. SIC can be used as a reference indicator for evaluating the iodine nutrition status of pregnant women, but it needs further investigation and verification. TRIAL REGISTRATION: NCT04492657(Aug 9, 2022).

Should we depend on reference intervals from manufacturer package inserts? Comparing TSH and FT4 reference intervals from four manufacturers with results from modern indirect methods and the direct method.

OBJECTIVES: Correct interpretation of thyroid function tests relies on correct reference intervals (RIs) for thyroid-stimulating hormone (TSH) and free thyroxine (FT4). ISO15189 mandates periodic verification of RIs, but laboratories struggle with cost-effective approaches. We investigated whether indirect methods (utilizing historical laboratory data) could replace the direct approach (utilizing healthy reference individuals) and compared results with manufacturer-provided RIs for TSH and FT4. METHODS: We collected historical data (2008-2022) from 13 Dutch laboratories to re-establish RIs by employing indirect methods, TMC (for TSH) and refineR (for FT4). Laboratories used common automated platforms (Roche, Abbott, Beckman or Siemens). Indirect RIs (IRIs) were determined per laboratory per year and clustered per manufacturer (>1.000.000 data points per manufacturer). Direct RIs (DRIs) were established in 125 healthy individuals per platform. RESULTS: TSH IRIs remained robust over the years for all manufacturers. FT4 IRIs proved robust for three manufacturers (Roche, Beckman and Siemens), but the IRI upper reference limit (URL) of Abbott showed a decrease of 2 pmol/L from 2015. Comparison of the IRIs and DRIs for TSH and FT4 showed close agreement using adequate age-stratification. Manufacturer-provided RIs, notably Abbott, Roche and Beckman exhibited inappropriate URLs (overall difference of 0.5-1.0 µIU/mL) for TSH. For FT4, the URLs provided by Roche, Abbott and Siemens were overestimated by 1.5-3.5 pmol/L. CONCLUSIONS: These results underscore the importance of RI verification as manufacturer-provided RIs are often incorrect and RIs may not be robust. Indirect methods offer cost-effective alternatives for laboratory-specific or platform-specific verification of RIs.

A National Laboratory Perspective: The Impact of the Covid-19 Pandemic on the Management of Patients With Non-Communicable Disease in South Africa: Impact of COVID-19 on patients with noncommunicable diseases.

OBJECTIVE: The aim of this study was to determine the impact of the COVID-19 pandemic on test requests for the diagnosis and routine care of patients with various non-communicable diseases (NCD) across South Africa (SA). METHODS: A retrospective audit of laboratory test requests received from hospital outpatient departments and primary healthcare facilities across SA was performed. The following analytes were studied: glycated hemoglobin (HbA1c), lipids profiles, thyroid-stimulating hormone (TSH), and thyroxine (fT4), as well as triiodothyronine (fT3), serum protein electrophoresis (SPE), serum free light chains (SFLC), and prostate specific antigen (PSA); these tests were used as a proxy of NCD detection and follow-up. Requests received during the 3 waves of the pandemic were compared to requests received within the same period during 2017 - 2019. RESULTS: During the first wave, requests for all analytes were reduced, with the biggest reduction observed for SPE (- 37%); TSH (- 29%); fT4 (- 28%); and HbA1c (- 25%). Requests received from urban facilities showed a larger decrease compared to those from rural facilities. During the third wave there was an increase in requests for all analytes; the biggest increase observed was for fT3 (21%) and HbA1c (18%). CONCLUSIONS: The COVID-19 pandemic had a significant impact on the South African population receiving care in the public healthcare sector.

Establishment of reference intervals for fT3, fT4, and TSH levels in Japanese children and adolescents.

The present study aimed to establish new reference intervals (RIs) for serum free triiodothyronine (fT3), free thyroxine (fT4), and thyroid stimulating hormone (TSH) levels in Japanese children and adolescents aged 4 to 19 years. A total of 2,036 (1,611 girls, 425 boys) participants were included over a 17-year period; they all tested negative for antithyroid antibodies (TgAb, TPOAb) and were found to have no abnormalities on ultrasonography. RIs were determined by nonparametric methods. The results showed that serum fT3 was significantly higher in the 4-15-year-olds than in the 19-year-olds. The serum fT4 was significantly higher in the 4-10-year-olds than in the 19-year-olds. The serum TSH was significantly higher in the 4-12-year-olds than in the 19-year-olds. All of them gradually decreased with age to approximate the adult levels. The upper limit of TSH was lower in those aged 13 to 19 years than in adults. The differences were examined by sex. The serum fT3 was significantly higher in boys than in girls between the ages of 11 and 19 years. The serum fT4 was significantly higher in boys than in girls between the ages of 16 and 19 years. There did not seem to be any sex difference in those under 10 years of age. In conclusion, serum fT3, fT4, and TSH levels in children and adolescents differ from those in adults. It is important to evaluate thyroid function using the new RIs that are appropriate for chronological age.

Laboratorio de función tiroidea en pediatría. Ventajas y limitaciones de los métodos indirectos para la obtención de intervalos de referencia / Thyroid function laboratory in pediatrics. Advantages and limitations of indirect methods to obtain reference intervals

Obtener intervalos de referencia (IRs) confiables para pruebas de laboratorio en pediatría es particularmente complejo y costoso. Una alternativa a este problema es el uso de métodos indirectos, donde se usan grandes bases de datos preexistentes de pacientes. Nuestros objetivos fueron: calcular IR para TSH y hormonas tiroideas (Perfil tiroideo, PT) en población pediátrica que asiste al Hospital de Pediatría Juan P. Garrahan, por método indirecto y verificar la confiabilidad de los mismos para su aplicación. Se recolectaron datos de 19.842 pacientes entre enero de 2020 y diciembre de 2021. Se aplicaron filtros para eliminar los pacientes que pudieran tener afectado el PT. Los 4.861 pacientes incorporados al análisis fueron divididos en 3 grupos: G1: 0-12 meses (n: 551), G2:13 meses- 7 años (n: 1347) y G3: 8 -18 años (n: 2963). Los IR fueron calculados por 2 métodos: el de Hoffman adaptado y el de CLSI EP28A3, para cada grupo de edad. TSH, TT3 y T4L se analizaron con Architect i4000-Abbott y TT4 con Immulite 2000XPi-Siemens. Para la primera etapa de verificación se utilizaron 20 sueros de pacientes provenientes de análisis prequirúrgicos. Los outliers se detectaron aplicando el método de Tukey. Los datos fueron procesados según CLSI EP28A3c. Los IR obtenidos fueron similares a los previamente publicados obtenidos por método directo. Los resultados de la verificación fueron en su mayoría aceptados. Por lo tanto, los métodos indirectos son una buena alternativa de cálculo de IR en pediatría (AU)

Obtaining reliable reference ranges (RRs) for laboratory tests in pediatrics is particularly complex and costly. An alternative to this problem is to use of indirect methods, where large pre-existing patient databases are used. Our aims were to calculate RRs for TSH and thyroid hormones (thyroid profile, PT) in children seen at Hospital de Pediatría Juan P. Garrahan by indirect methods and to verify their reliability for their application. Data were collected from 19,842 patients seen between January 2020 and December 2021. Filters were applied to eliminate patients in whom the PT was potentially affected. The remaining 4,861 patients included in the analysis were divided into 3 groups: G1: 0-12 months (n: 551), G2: 13 months-7 years (n: 1347) and G3: 8-18 years (n: 2963). RRs were calculated by 2 methods: the adapted Hoffman method and the CLSI EP28A3 method, for each age group. TSH, TT3, and FT4 were analyzed with Architect i4000-Abbott and TT4 with Immulite 2000XPi-Siemens. For the first stage of verification, 20 patient sera from pre-surgical analysis were used. Outliers were detected by applying the Tukey method. The data were processed according to CLSI EP28A3c. The RRs obtained were similar to those previously published using the direct method. The verification results were mostly acceptable. Therefore, indirect methods are a good option for calculating RRs in children (AU)

Indirect Estimation of the Pediatric Reference Intervals for Thyroid Function Tests in Public Health Laboratory.

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

Trimester-specific reference intervals for thyroid function parameters in pregnant Caucasian women using Roche platforms: a prospective study.

BACKGROUND: Standard thyroid function parameters reference intervals (RI) are unsuitable during pregnancy, potentially resulting in incongruous treatments that may cause adverse effects on pregnancy outcomes. We aimed at defining trimester-specific TSH, FT4 and FT3 RI, using samples longitudinally collected from healthy Caucasian women. MATERIALS AND METHODS: Blood samples from 150 healthy Caucasian women, who had a physiological gestation and a healthy newborn at term, were collected in each trimester and at around six months post-partum. They showed mild iodine deficiency. After excluding women with overt TSH abnormalities (> 10 mU/L) and/or TPO antibodies, data from 139 pregnant women were analyzed by means of widely used Roche platforms, and TSH, FT4 and FT3 trimester-specific RI were calculated. Post-partum data were available for 55 subjects. RESULTS: Serum TSH RI were 0.34-3.81 mU/L in the first trimester, and changed slightly to 0.68-4.07 U/L and 0.63-4.00 mU/L in the second and third trimester, respectively. Conversely, both FT4 and FT3 concentrations progressively decreased during pregnancy, the median values in the third trimester being 14.8% and 13.2% lower, respectively, than in the first trimester. Thyroid function parameters in the first trimester were similar to those measured after the end of pregnancy. CONCLUSIONS: This study calculates trimester-specific RI for thyroid function parameters in pregnancy, and proposes the reference limits that should be adopted when using Roche platforms in Caucasian women.

An elevated parametric thyroid feedback quantile-based index is associated with atrial fibrillation.

Introduction: Atrial fibrillation is associated with hyperthyroidism. Within the euthyroid range, it is also associated with high thyroxine (fT4), but not with thyrotropin (TSH). We aim to describe differences in thyroid regulation, measured by the Parametric Thyroid Feedback Quantile-Based Index (PTFQI), between patients with atrial fibrillation and the general population. Materials and methods: Thyroid parameters (PTFQI, TSH, and fT4) of a sample of 84 euthyroid subjects with atrial fibrillation (cases) were compared to a reference sample of euthyroid healthcare patients (controls). We calculated age and sex adjusted ORs for atrial fibrillation across tertiles of these parameters. Also, within cases, we studied thyroid parameters association with clinical characteristics of the atrial fibrillation. Results: After adjusting for age and sex, fT4 and PTFQI were higher in subjects with atrial fibrillation when compared to the general sample (p<0.01 and p=0.01, respectively). Atrial fibrillation ORs of the third versus the first PTFQI tertile was 1.88(95%CI 1.07,3.42), and there was a gradient across tertiles (p trend=0.02). Among atrial fibrillation patients, we observed that higher PTFQI was associated with sleep apnea/hypopnea syndrome (OSAS) (p=0.03), higher fT4 was associated with the presence of an arrhythmogenic trigger (p=0.02) and with heart failure (p<0.01), and higher TSH was also associated with OSAS (p<0.01). Conclusions: Euthyroid subjects with atrial fibrillation have an elevation of the pituitary TSH-inhibition threshold, measured by PTFQI, with respect to the general population. Within atrial fibrillation patients, high PTFQI was associated with OSAS, and high fT4 with heart failure. These results hint of the existence of a relationship between thyroid regulation and atrial fibrillation.

Identifying elevated plasma free triiodothyronine levels: age-adapted reference intervals for pediatrics.

OBJECTIVES: Elevated free T3 (FT3) is an important feature for the early diagnosis of several diseases among which Grave's disease or Allan-Hernon-Dudley syndrome. However, there is a lack of age-adapted reference intervals for plasma thyroid hormones in children. We conducted a study to define reference values of peripheral FT3 in children using a commonly used automated immunoassay. METHODS: All thyroid function test (TFT) results from our lab collected during 9 months were extracted anonymously, and reference intervals establishment followed recommendations validated by International Federation of Clinical Chemistry (IFCC). RESULTS: We defined five reference intervals covering the whole pediatric period. Overall, 26.1% of peripheral FT3 measured in children with normal TSH are out of the adult reference range, and 22.2% are upper it leading to misinterpretation. In a 9-month old patient with severe neurodevelopmental disorders, a pathological elevated FT3 has been securely interpreted using the newly established interval. CONCLUSIONS: The study highlights the poor relevance of adult intervals in pediatric cares, as it confirms that plasmatic FT3 is higher during the whole pediatric period. This work reports useful age-adapted reference intervals for free T3 in pediatrics using a widely used electrochemiluminescent Immunoassay (ECLIA) kit.

Comparison of developmental outcomes in children with permanent and transient congenital hypothyroidism.

OBJECTIVES: Congenital hypothyroidism (CH) is still one of the most common causes of preventable cognitive impairment in children, and its early detection and treatment prevent irreversible neurodevelopmental delay. Depending on the underlying cause, cases with CH may be transient or permanent. This study aimed to compare the developmental evaluation results of transient and permanent CH patients and to reveal any differences. METHODS: A total of 118 patients with CH, who were followed up jointly in pediatric endocrinology and developmental pediatrics clinics, were included. The patients' progress was evaluated per the International Guide for Monitoring Child Development (GMCD). RESULTS: Of the cases, 52 (44.1%) were female, and 66 (55.9%) were male. While 20 (16.9%) cases were diagnosed with permanent CH, 98 (83.1%) were diagnosed with transient CH. According to the results of the developmental evaluation made with GMCD, the development of 101 (85.6%) children was compatible with their age, while 17 (14.4%) children had delays in at least one developmental area. All 17 patients had a delay in expressive language. Developmental delay was detected in 13 (13.3%) of those with transient CH and 4 (20%) with permanent CH. CONCLUSIONS: There is difficulty in expressive language in all cases of CH with developmental delay. No significant difference was found between the developmental evaluations of permanent and transient CH cases. The results revealed the importance of developmental follow-up, early diagnosis and interventions in those children. GMCD is thought to be an important guide to help monitoring the development of patients with CH.

Thyroid-Stimulating Hormone Levels within the Trimester-Specific Reference Intervals Are Correlated with Non-High-Density Lipoprotein Cholesterol and Remnant Cholesterol Concentrations in Pregnant Women.

OBJECTIVE: Thyroid-stimulating hormone (TSH) levels are associated with serum lipid concentrations in the general nonpregnant population. Here, we aimed to establish trimester-specific reference intervals and to explore the associations of their variations within the specific reference intervals during pregnancy. METHODS: Trimester-specific reference intervals were established according to the Clinical and Laboratory Standard Institute EP28-A3c guidelines using a direct sampling method based on a large prospective cohort. After making one-to-one matches, correlation analyses between TSH and lipid index levels, especially within the reference intervals, were conducted. RESULT: A total of 1648 pregnant women for TSH and 2045 subjects for lipids were recruited to establish the trimester-specific reference intervals. The upper reference limit (90% confidence interval) of TSH for pregnant women in the first trimester is 3.95 (3.66-4.29) mIU/L, which is very close to the default value (4.0 mIU/L) recommended by the American Thyroid Association in 2017. Apart from triglyceride and high-density lipoprotein cholesterol, TSH levels were positively associated with the serum concentrations of total cholesterol, low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol (non-HDL-C), and remnant cholesterol (RC) either in the entire range or within the specific reference intervals. Of note, the positive correlations between TSH and non-HDL-C and RC were, albeit similarly weak (r < 0.25), relatively more robust (P < .001). CONCLUSION: In this study, we showed positive correlations between TSH and lipid components within trimester-specific reference intervals, highlighting the need for the integrated management of pregnant women over age 35 and with nonoptimal lipid status in China.

Factores clínicos y ambientales asociados a la tiroiditis de Hashimoto / Clinical and environmental factors associated with Hashimoto's thyroiditis

Introducción: La tiroiditis de Hashimoto es una enfermedad tiroidea autoinmune poligénica y multifactorial resultante de una interacción compleja de factores genéticos y ambientales. Objetivo: Determinar la posible asociación de los factores clínicos y ambientales con los niveles de anticuerpos antitiroideos y las pruebas de función tiroidea en la tiroiditis de Hashimoto. Métodos: Estudio observacional, descriptivo y transversal con 120 personas con diagnóstico de tiroiditis de Hashimoto. Variables estudiadas: edad, sexo, color de la piel, estado nutricional, paridad, hábito de fumar, consumo de alcohol, preparados estrogénicos, antecedentes familiares de enfermedad autoinmune tiroidea y personales de otras enfermedades autoinmunes. Se realizaron determinaciones de anticuerpos AbTPO, TSH, T3 y T4. Resultados: Predominio del sexo femenino (92,5 por ciento), de pacientes de piel blanca (50,8 por ciento) y con sobrepeso corporal (40 por ciento). El 73 por ciento no consumían preparados estrogénicos. El 20 por ciento tenían antecedentes familiares de enfermedad tiroidea y personales de diabetes mellitus tipo 1 (7,5 por ciento). La media del anticuerpo en pacientes con antecedentes de infecciones virales fue superior a los que no tuvieron este antecedente (732,6 vs. 624,6). El resto de las variables no mostraron diferencias entre las medias del anticuerpo. Ninguno de los factores estudiados mostró asociación con el estado de la función tiroidea. (p>0,05). Conclusiones: No existió asociación entre los factores clínicos y ambientales en relación a los niveles de Ac TPO y el estado de la función tiroidea, con predominio del hipotiroidismo manifiesto al diagnóstico de la TH(AU)

Introduction: Hashimoto's thyroiditis is a polygenic and multifactorial autoimmune thyroid disease, resulting from a complex interaction of genetic and environmental factors. Objective: To determine the possible association of clinical and environmental factors with antithyroid antibody levels and thyroid function tests in HT. Methods: An observational, descriptive, cross-sectional study was carried out with 120 subjects diagnosed with Hashimoto's thyroiditis. We studied variables such as age, sex, skin color, nutritional status, parity, smoking, alcohol consumption, estrogen preparations, family history of autoimmune thyroid disease and personal history of other autoimmune diseases. Additionally, AbTPO, TSH, T3 and T4 antibody determinations were made. Results: Predominance of the female sex (92.5 percent), white skin (50.8 percent) and body overweight (40 percent). 73 percent did not consume estrogenic preparations. Twenty percent had family history of thyroid disease and personal history of type 1 diabetes mellitus (7.5 percent). The mean antibody in patients with history of viral infections was higher than those without this history (732.6 vs. 624.6). The rest of the variables did not show differences between the means of the antibody. None of the factors studied showed association with the state of thyroid function. (p > 0.05). Conclusions: There was no association between clinical and environmental factors in relation to Ac TPO levels and the state of thyroid function, with a predominance of overt hypothyroidism at diagnosis of HT(AU)

Thyroid function in the subacute phase of traumatic brain injury: a potential predictor of post-traumatic neurological and functional outcomes.

PURPOSE: That thyroid hormones exert pleiotropic effects and have a contributory role in triggering seizures in patients with traumatic brain injury (TBI) can be hypothesized. We aimed at investigating thyroid function tests as prognostic factors of the development of seizures and of functional outcome in TBI. METHODS: This retrospective study enrolled 243 adult patients with a diagnosis of mild-to-severe TBI, consecutively admitted to our rehabilitation unit for a 6-month neurorehabilitation program. Data on occurrence of seizures, brain imaging, injury characteristics, associated neurosurgical procedures, neurologic and functional assessments, and death during hospitalization were collected at baseline, during the workup and on discharge. Thyroid function tests (serum TSH, fT4, and fT3 levels) were performed upon admission to neurorehabilitation. RESULTS: Serum fT3 levels were positively associated with an increased risk of late post-traumatic seizures (LPTS) in post-TBI patients independent of age, sex and TBI severity (OR = 1.85, CI 95% 1.22-2.61, p < 0.01). Measured at admission, fT3 values higher than 2.76 pg/mL discriminated patients with late post-traumatic seizures from those without, with a sensitivity of 74.2% and a specificity of 60.9%. Independently from the presence of post-traumatic epilepsy and TBI severity, increasing TSH levels and decreasing fT3 levels were associated with worse neurological and functional outcome, as well as with higher risk of mortality within 6 months from the TBI event. CONCLUSIONS: Serum fT3 levels assessed in the subacute phase post-TBI are associated with neurological and functional outcome as well as with the risk of seizure occurrence. Further studies are needed to investigate the mechanisms underlying these associations.

Identification of a novel mutation in thyroxine-binding globulin (TBG) gene associated with TBG-deficiency and its effect on the thyroid function.

PURPOSE: This study presents a case of familial transmission of thyroxine-binding globulin (TBG) deficiency. The SERPINA7-gene which codes for TBG is located on the X-chromosome (Xq21-22). More than 45 mutations have been reported to cause TBG- deficiency from various countries, but none from India so far. Genetic analysis of SERPINA7 gene was carried out to determine the cause of low TBG levels in one family. METHODS: DNA samples of the propositus and the family members were subjected to Polymerase Chain Reaction (PCR) followed by direct sequencing. Allele-specific PCR and Next-gen sequencing (NGS) were employed to confirm the site of the mutation. Thyroid function tests were estimated by Radioimmunoassay (RIA) and Immunoradiometric assay (IRMA) kits. X-chromosomal inactivation status was analyzed in the female members harboring the mutation. RESULTS: A mutational screening in this family revealed a novel frame-shift mutation S353Q, 354fs3X in the exon 4 of the SERPINA7 gene which will be referred to as TBG-complete deficiency-India (TBG-CD-Ind). One out of four female family members harboring the mutation showed selective X-chromosomal inactivation. The affected family members were clinically euthyroid initially, showed changes in the thyroid function when tested after a long time span. However, the changes in the thyroid function in the affected family members had an autoimmune etiology. CONCLUSION: This study presents the first report of TBG-CD from India wherein a novel frameshift mutation referred to as TBG-CD-Ind (S353Q, 354fs3X) in the SERPINA7 gene was detected. No apparent association was identified between thyroid function and the TBG-mutation in the affected subjects. A detailed biochemical and genomic testing to determine the exact cause of discordant TFT in the patients would certainly aid in the unequivocal diagnosis of the thyroid function and for the precise individualized treatment.