Uso adecuado de las pruebas de laboratorio para la evaluación de la función tiroidea en pediatría / Appropriate use of laboratory tests for evaluation of thyroid function in pediatrics

Las pruebas de función tiroidea (PFT) son esenciales para el diagnóstico preciso y el seguimiento eficaz de la disfunción tiroidea. Existe un incremento progresivo y estable de los pedidos de PFT, incluso se han incorporado las mismas a los exámenes de salud anuales en niños sanos. Representan más del 60% de las pruebas realizadas en el laboratorio de endocrinología, tanto en adultos como en los laboratorios especializados en pediatría. Para hacer un uso eficiente de las PFT, antes de solicitarlas debemos preguntarnos… ¿Para quién? ¿Cuándo solicitarlas? ¿Qué pruebas solicitar? ¿Cómo solicitarlas? y ¿Cómo interpretar correctamente los resultados? Un resultado anormal en las PFT no siempre implica patología tiroidea asociada. Las PFT tienen importante variabilidad intra e interindividual lo que hace más compleja su correcta interpretación. La pesquisa de enfermedad tiroidea neonatal es un importante aporte a la prevención de la deficiencia mental en la infancia, su aplicación obligatoria posibilita un diagnóstico temprano, para asegurar su éxito debe considerarse en el marco de un programa integral de detección con estrategias de confirmación, tratamiento temprano y seguimiento a corto, mediano y largo plazo. No debe hacerse un uso indiscriminado de la prueba de estímulo con TRH en el diagnóstico de la patología tiroidea. En pediatría la estrategia de tamiz de enfermedad tiroidea es conveniente realizarla mediante la medición de por lo menos TSH y T4 libre e incluir la determinación de ATPO en grupos de riesgo, a diferencia de la determinación aislada de TSH como es recomendado en adultos. (AU)

Thyroid function tests (TFTs) are essential for accurate diagnosis and effective monitoring of thyroid dysfunction. There is a progressive and steady increase in requests for TFTs, and they have even been incorporated into annual health examinations in healthy children. They represent more than 60% of the tests performed in the endocrinology laboratory, both in adults and in specialized pediatric laboratories. To efficiently use TFTs, before requesting them we should ask ourselves... For whom? When to request them? Which tests to request? How to request them? and How to correctly interpret the results? An abnormal TFT result does not always imply thyroid disease. TFTs have significant intra- and inter-individual variability, which makes their correct interpretation more complex. Screening for newborn thyroid disease is an important contribution to the prevention of intellectual disability in childhood and its mandatory use enables early diagnosis; however, to ensure the test to be successful, it should be considered within the framework of a comprehensive screening program with strategies for confirmation, early treatment, and short-, medium-, and long-term follow-up. The TRH stimulation test in the diagnosis of thyroid disease should not be used indiscriminately. In children, the screening strategy for thyroid disease should be performed by measuring at least TSH and free T4 and include the measurement of TPO-ab in risk groups, as opposed to the isolated measurement of TSH as recommended in adults. (AU)

Correlation of serum 25-hydroxyvitamin D level with Thyrotropin receptor antibody and bone metabolism markers in patients with Graves' disease / 中华临床营养杂志

Objective:To investigate the serum 25-hydroxyvitamin D [25(OH)D] level in patients with Graves' disease (GD) and its correlation with thyrotropin receptor antibody (TRAb) and bone metabolism markers.Methods:A total of 124 patients with newly diagnosed or relapsed GD were selected and divided into three groups according to serum 25(OH)D level, namely vitamin D deficiency group with 25(OH)D <12 μg/L, vitamin D insufficiency group with 25(OH)D of 12 to 20 μg/L, and vitamin D sufficiency group with 25(OH)D ≥ 20 μg/L. The levels of serum 25(OH)D, TRAb, type I procollagen N-terminal pro-peptide (PINP), type I collagen cross-linked C-terminal peptide (S-CTX), parathyroid hormone (PTH), total triiodothyronine (TT 3), total thyroxine (TT 4) and thyroid-stimulating hormone (TSH) were measured in all patients, and the differences of these biochemical indices were compared across groups. Oneway analysis of variance or Kruskal-Wallis test was used for comparison between groups, and Pearson or Spearman correlation analysis was applied for correlation test. Results:The levels of serum TT 3, TT 4, PINP, and S-CTX significantly increased ( P < 0.01) and the level of phosphorus (P) decreased ( P < 0.01) with the decreased vitamin D levels. The levels of PTH and calcium (Ca) were significantly lower in the vitamin D sufficiency group compared with the vitamin D insufficiency group and vitamin D deficiency group ( P < 0.01). Correlation analysis showed that serum 25(OH)D level was negatively correlated with the levels of TT 3, TT 4, PINP, S-CTX, PTH and Ca ( P < 0.01), and positively correlated with the levels of P and TSH ( P < 0.01). Conclusions:Decreased serum 25(OH)D level is closely related with increased bone turnover, PTH, and thyroid hormone levels in patients with GD, but not related with TRAb. Thyroid hormone levels have a certain predictive value regarding vitamin D deficiency in GD patients. It is necessary to monitor the vitamin D levels in patients with GD and provide vitamin D supplementation to reduce the incidence of osteoporosis, improve the effectiveness of antithyroid treatment and reduce the recurrence of GD.

Relationship between thyroid hormone level and obesity related indices in patients with type 2 diabetes mellitus / 中国基层医药

Objective:To investigate the relationship between serum thyroid hormone levels in the normal range and body weight, blood glucose, blood lipids, and other obesity-related indexes in patients with type 2 diabetes mellitus.Methods:Seventy obese patients with type 2 diabetes mellitus and ninety-two patients with type 2 diabetes mellitus with normal weight who were treated in the Nangang Branch of Heilongjiang Provincial Hospital from May 2020 to May 2021 were included in this study. Thyroid-stimulating hormone level was in the normal range (0.35-4.94 mU/L) in all participants. Serum levels of free triiodothyronine, free thyroxine, thyroid-stimulating hormone, thyroid peroxidase antibody, thyroglobulin antibody, triglyceride, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, fasting blood glucose, glycosylated hemoglobin, fasting C peptide, fasting insulin, systolic blood pressure, diastolic blood pressure, and serum uric acid were measured in all participants.Results:Free triiodothyronine level was positively correlated with fasting blood glucose and glycosylated hemoglobin levels ( r = 0.19, P = 0.021; r = 0.21, P = 0.017). Free thyroxine level was positively correlated with serum glycosylated hemoglobin level ( r = 0.25, P = 0.009) and negatively correlated with total cholesterol ( r = -0.17, P = 0.029). Thyroid-stimulating hormone level was positively correlated with body mass index as well as total cholesterol and low-density lipoprotein cholesterol levels ( r = 0.33, P < 0.001; r = 0.33, P < 0.001; r = 0.32, P < 0.001). Conclusion:Thyroid hormones in the normal range play an important role in the regulation of body weight, blood glucose, and blood lipids in patients with type 2 diabetes mellitus. Blood glucose level increases markedly in patients with relatively high free triiodothyronine and free thyroxine levels. The risks of obesity and dyslipidemia increase in patients with relatively high serum thyroid-stimulating hormone levels

Reference ranges and influencing factors of thyroid function in preterm infants at 14 d after birth / 中华围产医学杂志

Objective:To investigate the reference ranges for thyroid function and its influencing factors in preterm infants at 14 d after birth.Methods:This retrospective study involved 514 preterm infants who met the inclusion criteria in Affiliated Hospital of Inner Mongolia Medical University from January 1, 2019 to December 31, 2021. They were divided into three group according to their gestational age [early premature group (26-31 +6 weeks, n=153), middle premature group (32-33 +6 weeks, n=129) and late premature group (34-36 +6 weeks, n=232)] or birth weight (BW) [<1 500 g group ( n=129), 1 500-2 000 g group ( n=120) and ≥2 000 g group ( n=265)]. Venous blood samples were collected from the infants at 14 d after birth and their thyroid function was determined by chemiluminescence immunoassay. The reference values of free triiodothyronine (FT 3), free thyroxine (FT 4) and thyroid stimulating hormone (TSH) were calculated based on the values of 95% confidence intervals ( CI) and expressed as percentiles in the range from P2.5 to P97.5. Mann-Whitney U test or Kruskal-Wallis H test was used to compare those thyroid hormone levels between groups. Spearman correlation analysis was used to study the correlation of gestational age or birth weight with FT 3, FT 4 and TSH levels. The factors influencing the levels of thyroid hormones were analyzed by multiple linear regression. Results:The reference ranges for FT 3, FT 4 and TSH were 1.53-3.72 pg/ml, 0.81-1.91 ng/dl and 1.32-7.80 μIU/ml in the early premature infants, 1.74-4.16 pg/ml, 0.90-2.82 ng/dl and 0.63-7.64 μIU/ml in middle prematures and 2.07-4.88 pg/ml, 1.09-2.27 ng/dl and 1.14-7.06 μIU/ml in late prematures. The reference ranges for the above three indexes were 1.53-4.06 pg/ml, 0.81-1.83 ng/dl and 1.14-7.84 μIU/ml in premature infants with BW<1 500 g, 1.67-3.98 pg/ml, 0.88-2.97 ng/dl and 0.94-7.64 μIU/ml in those whose BW between 1 500 g and 2 000 g and 1.91-4.75 pg/ml, 1.09-2.31 ng/dl and 1.14-6.32 μIU/ml in those whose BW≥2 000 g. Multiple linear regression showed that the level of FT 3 was positively correlated with gestational age ( β=0.119, P<0.05) and birth weight ( β=1.950×10 －4, P<0.05); that of FT 4 was positively correlated with gestational age only ( β=0.031, P<0.05); and TSH level was negatively correlated with birth weight ( β=－4.250×10 －4, P<0.05). Conclusions:Gestational age and birth weight are the factors influencing thyroid function in preterm infants at 14 d after birth. Evaluation of thyroid function with FT 4 and TSH should based on the references ranges of different gestational age and birth weight .

Palmitic acid inhibits the synthesis and secretion of thyroglobulin of rat thyroid follicular epithelial cell by downregulating thyrotropin receptor / 中华内分泌代谢杂志

Objective:Exploring the role of thyrotropin receptor(TSHR) in lipotoxicity-induced thyroid function damage.Methods:Rat thyroid follicular epithelial cells(RTC) were stimulated with different doses of palmitic acid(PA), and the lipid content of the cells was observed through Oil Red O staining. The expression levels of TSH receptor(TSHR), Ttf1, and SSBP1 mRNA and protein in each group were detected using RT-PCR and Western blot. The TSHR protein level in the cell culture supernatant was measured using ELISA. Membrane TSHR was assessed through immunofluorescence and compared with the control group. We used PA to stimulate the TSHR over-expression(TSHR OE) and normal RTC, as PA+ TSHR OE group and PA group respectively, then testing Tg mRNA and protein, cAMP and Tg in cell supernatants levels, then comparing with the control.Results:RTC were stained into peau d′orange in PA groups. Compared with the control group, we found TTf1, SSBP1 and TSHR mRNA as well as protein levels in PA groups were decreased(all P<0.05), TSHR of the cell membrane and supernatants were reduced(all P<0.05), characterizing dose-dependent changes partly. Moreover, we found in PA group Tg mRNA level was downregulated( P<0.05), Tg protein levels were reduced in the supernatants and cells( P<0.05), cAMP level was decreased in cells( P<0.05); in TSHR OE group, Tg mRNA level was upregulated( P<0.05), Tg protein levels in cells and supernatants were increased(all P<0.05), cAMP level was similar. Compared with the PA group, we found in PA+ TSHR OE group Tg mRNA level was upregulated( P<0.05), Tg protein levels were increased in the supernatants and cells(all P<0.05), cAMP level was elevated in cells( P<0.05). Conclusion:PA induces lipid deposition in RTC, decreased synthesis and secretion of Tg. This effect is likely achieved through the downregulation of the TSHR/cAMP signaling pathway.

Effects of arsenic exposure on E2 and TRH and their receptor mRNA expressions in rats / 环境与职业医学

Background Arsenic can enter the hypothalamus to induce estrogen effect and interfere with the function of the neuroendocrine system. The thyroid endocrine system (hypothalamic-pituitary-thyroid axis) is one of the main endocrine systems, and the mechanism of arsenic-induced thyroid endocrine toxicity is still unclear. Objective To investigate the effects of different arsenic exposure levels on estradiol (E2), hypothalamic thyrotropin-releasing hormone (TRH), and their receptor (ERα, ERβ, and TRHR) mRNAs in rats and the possible hypothalamic toxic pathway and mechanism. Methods Seventy Wister rats were randomly divided a control group (sterile water); low-, medium-, and high-dose arsenic exposure groups [0.8, 4.0, and 20.0 mg·kg−1 sodium arsenite (NaAsO2)]; estrogen receptor inhibitor (ICI182780) intervention + low-, medium-, and high-dose arsenic exposure groups; with 10 animals in each group, half male and half female. Rats in the arsenic exposure groups were exposed to NaAsO2 by drinking water for 19 weeks, and rats in the intervention groups were injected with 0.5 mg·kg−1 ICI182780 via tail vein at week 9, 3 times a week. The levels of E2 and TRH in serum of rats were detected by ELISA. The expression levels of estrogen receptor α (ERα), estrogen receptor β (ERβ), and TRH receptor (TRHR) mRNAs in hypothalamus of rats were detected by real-time PCR (RT-PCR). Results (1) E2 and its receptor mRNA: Compared with the control group, the serum E2 level of female rats was increased in the low-dose and the medium-dose arsenic exposure groups (P<0.05), and the serum E2 level of male rats was increased in the low-dose, the medium-dose, and the high-dose arsenic exposure groups (P<0.05), and the change of female E2 was greater than that of male rats. Compared with the control group, the relative expression levels of ERα mRNA and ERβ mRNA in female rats were increased in the low-dose, the medium-dose, and the high-dose arsenic exposure groups (P<0.05), so were the relative expression levels of ERα mRNA in male rats (P<0.05). (2) TRH and its receptor mRNA: Compared with the control group, the serum TRH level of female rats was increased in the high-dose arsenic group (P<0.05), the relative expression level of TRHR mRNA was increased in the low-dose, the medium-dose, and the high-dose arsenic exposure groups (P<0.05). Results (1) and results (2) suggested that females were more likely than males to have abnormal changes in E2, TRH, and related receptor genes after arsenic exposure. (3) Compared with female rats in the medium-high dose arsenic exposure group, the expressions of TRH and TRHR induced by arsenic exposure were inhibited after the intervention of ICI182780 (P<0.05), suggesting that arsenic in the hypothalamus may have toxic effects on TRH and TRHR by inducing estrogen-like effects. Conclusion Arsenic exposure can induce estrogen-like effects in the hypothalamus, interfere with thyroid function, and show dose-dependent and sex differences. E2 and TRH and their receptors may be the toxic pathway of arsenic-related estrogen-like effect.

Predictive factors for the diagnosis of permanent congenital hypothyroidism and its temporal changes in Sergipe, Brazil - A real-life retrospective study

ABSTRACT Objectives: Congenital hypothyroidism (CH) can be permanent (PCH) or transient (TCH). While the importance of thyroxine in myelination of the brain is undisputed, the benefits to neurodevelopmental outcomes of TCH treatment are controversial. Our objectives were to determine predictive factors for PCH and verify its prevalence changes over time. Subjects and methods: A total of 165 children were evaluated at 3 years of age to verify the diagnosis of PCH. 130 were submitted to a two-step cluster analysis, with the aim of grouping them into homogeneous clusters. The mean incidence of PCH and TCH was calculated from 2004 to 2010 and 2011 to 2015. Results: Sixty-six children were diagnosed with PCH, and 99 were diagnosed with TCH. Eighty-one percent of PCH children and all TCH children with thyroid imaging had glands in situ. Eighty children (61.5%) were in Cluster 1, 8 children (6.2%) were in Cluster 2 and 42 children (32.3%) were in Cluster 3. No children had PCH in Cluster 1, while 87.5% of children in Cluster 2 and all children in Cluster 3 had PCH. The most important predictor for PCH was the initial serum TSH, which was marginally higher in importance than the blood spot TSH, followed by the initial serum free T4. The mean incidence of PCH (odds ratio: 1.95, 95% CI 1.36 to 2.95, p < 0.0001) and TCH (odds ratio 1.33, 95%, CI 1.02 to 1.77, p = 0,038) increased over time. Conclusions: The most important PCH predictors are the initial serum TSH and the blood spot TSH. The mean incidence of both PCH and TCH in our series increased.

Valores de referencia para la tirotropina y hormonas tiroideas en embarazadas cubanas

Introducción: Los parámetros de función tiroidea en las embarazadas se modifican durante el embarazo y son específicos para cada población. Objetivo: Establecer los valores de referencia para la tirotropina y las hormonas tiroideas en una población de embarazadas cubanas. Métodos: Estudio transversal, en el municipio Plaza de la Revolución de La Habana, Cuba, a 362 gestantes sin antecedentes personales o familiares de enfermedad tiroidea, con anticuerpos anti-tiroideos negativos y ausencia de lesiones en el ultrasonido tiroideo. Se analizaron edad materna, edad gestacional, raza, hábito de fumar, paridad, uso de suplementos yodados, índice de masa corporal, tirotropina, tiroxina total y libre, triyodotironina total y libre. Se establecieron los intervalos de referencia para cada parámetro mediante los percentiles 2,5 y 97,5 como límites inferior y superior, respectivamente. Resultados: Los valores de referencia en el primer, segundo y tercer trimestres fueron para la tirotropina 0,1-3,3 mUI/L, 0,6-3,4 mUI/L y 0,3-3,9 mUI/L; para la TT4 90,1-204,1 nmol/L, 92,2-189,2 nmol/L y 79,8-170,4 nmol/L; para la FT4 7,3-16,7 pmol/L, 6,3-17,3 pmol y 5,6-12,7 pmol/L; para la TT3 1,8-3,9 nmol/L, 1,8-3,9 nmol/L y 1,7-4,0 nmol/L y para la FT3 1,0-7,4 pmol/L, 0,7-6,3 pmol/L y 0,7-5,4 pmol/L, respectivamente. Conclusiones: Se determinaron por primera vez los valores de referencia para la tirotropina y las hormonas tiroideas en una población de embarazadas cubanas; estos difieren de los establecidos por los kits diagnósticos y de los recomendados por las guías internacionales previas.

Introduction: Thyroid function parameters in pregnant women are modified during pregnancy and are specific for each population. Objective: To establish reference values for thyrotropin and thyroid hormones in a population of Cuban pregnant women. Methods: Cross-sectional study, in the Plaza de la Revolución municipality, of 362 pregnant women without personal or family history of thyroid disease, with negative anti-thyroid antibodies and absence of lesions in the thyroid ultrasound. Maternal age, gestational age, race, smoking, number of pregnancies, use of iodine supplements, body mass index, thyrotropin, total (TT4) and free (FT4) thyroxine, total (TT3) and free (FT3) triiodothyronine were analyzed. Reference intervals were established for each parameter using the 2.5 and 97.5 percentiles as lower and upper limits, respectively. Results: The reference values in the first, second and third trimesters were for thyrotropin 0.1-3.3 mIUI/L, 0.6-3.4 mIU/L and 0.3-3.9 mIU/L; for TT4 90.1-204.1 nmol/L, 92.2-189.2 nmol/L and 79.8-170.4 nmol/L; for FT4 7.3-16.7 pmol/L, 6.3-17.3 pmol and 5.6-12.7 pmol/L; for TT3 1.8-3.9 nmol/L, 1.8-3.9 nmol/L and 1.7-4.0 nmol/L and for FT3 1.0-7.4 pmol/L, 0.7-6.3 pmol/L and 0.7-5.4 pmol/L, respectively. Conclusions: Reference values for thyrotropin and thyroid hormones were determined for the first time in a population of Cuban pregnant women. These values differ from those established by the manufacturer of the diagnostic kits and from those recommended by previous international guidelines.

Syndrome of resistance to thyroid hormone and thyrotropin-secreting pituitary adenoma: Case series study / 中华内分泌代谢杂志

Objective:To outline clinical features in syndrome of resistance to thyroid hormone(RTH) and thyrotropin-secreting pituitary adenoma(TSH adenoma) based on a case series, and to assess the value of octreotide suppression test and high-dose dexamethasone suppression test(HDDST) in differentiating the two diseases.Methods:A total of 22 cases with RTH and TSH adenoma clinically diagnosed in Xiangya Hospital of Central South University from October 2010 to December 2021 were retrieved. The clinical characteristics of the two diseases and results to different tests were analyzed and summarized.Results:(1) The tumors in TSH adenoma patients were larger than those with RTH complicated with pituitary mass, which presented chiasmatic compression on images( P<0.05). (2) In octreotide suppression test, thyrotropin(TSH) inhibition rate in RTH patients was lower than that in TSH adenoma patients( P<0.05). In HDDST, TSH inhibition rate was higher in patients with RTH than in patients with TSH adenoma( P<0.05). (3) The TSH inhibition rate was calculated by receiver operating characteristic(ROC) curve. The sensitivity and specificity of octreotide suppression test were 91.9% and 55.6%, respectively, and the threshold value of TSH inhibition rate was 64.24%. The sensitivity and specificity of HDDST were 54.4% and 89.0%, respectively, and the threshold value of TSH inhibition rate was 65.73%.The combined sensitivity and specificity of the two tests were 77.8% and 90.9%, indicating better diagnostic value( P<0.05). Conclusions:The combination of octreotide suppression test and HDDST is of clinical value in differentiating RTH from TSH adenoma. TSH adenoma is more aggressive than that of pituitary adenoma with RTH.

Investigate the thyroid function of radiation workers and analysis of influence factors / 中华劳动卫生职业病杂志

Objective: To analyze the thyroid condition and influencing factors of radiation workers, and to provide scientific basis for radiation protection management. Methods: In April 2020, 4308 radiation workers from October 1, 2017 to September 30, 2019 were collected for occupational health examination in Hangzhou Occupational Disease Prevention and Treatment Hospital, the data included basic information, Thyroid hormone level and thyroid color doppler ultrasound results. The thyroid status of radiation workers in different subgroups was compared. The influencing factors of Thyroid nodule were analyzed by multiple logistic regression. Results: 616 radiation workers had abnormal thyroid gland (14.3%, 616/4308) . The main manifestations of thyroid gland abnormality were abnormal Thyroid nodule (5.1%, 220/4308) and abnormal TSH level (7.1%, 308/4308) . Compared with the male radiation workers, the abnormal rate of Thyroid nodule, T3 and Tsh in female radiation workers was higher (P<0.05) , and the abnormal rate of Thyroid nodule, T3 and T4 increased with the increase of working age (P<0.05) . Radiation Workers in non-rated medical institutions and private medical institutions had the highest detection rate of Thyroid nodule (P<0.05) , and there was no significant difference in thyroid abnormalities among Workers (P<0.05) . By multiple logistic regression analysis, Sex (female) , age and institution type (private) were all independent risk factors for Thyroid nodule (95% CI: 1.548~2.763、1.002~1.030, P<0.05) . Conclusion: Ionizing radiation can cause thyroid damage in radiation workers, so we should pay more attention to the radiation protection management of female, high age, private and district medical organizations, so as to protect the health of radiation workers.

Thyrotropin receptor antibody and bone turnover markers in the patients with newly-diagnosed Graves′ disease / 中华内分泌代谢杂志

Objective:To investigate the correlation between the level of thyrotropin receptor antibody(TRAb) and bone turnover markers(BTMs) in the patients with newly-diagnosed Graves′ disease(GD).Methods:The clinical data of GD patients who were newly-diagnosed in the First Affiliated Hospital of Zhengzhou University from October 2016 to June 2021 were collected, including free triiodothyronine(FT 3), free thyroxine(FT 4), thyroid stimulating hormone, thyroid related antibodies, N-terminal procollagen of type I collagen(PINP), N-terminal osteocalcin(N-MID), β-cross-linked C-telopeptide of type I(β-CTX), blood lipid and renal function, etc. Results:There were 618 GD patients with an average age of(43.7±13.2) years(male∶female=1∶1.99). The PINP and β-CTX level in male GD patients were significantly higher than those in female(all P<0.05). Spearman correlation analysis showed that PINP, N-MID and β-CTX were positively correlated with FT 3, FT 4, TRAb, serum calcium and serum phosphorus; and negatively correlated with body mass index and low density lipoprotein cholesterol(all P<0.05). Linear regression analysis showed that TRAb was positively correlated with lg-PINP, lg-N-MID and sqrt-β-CTX in the univariate model of total GD patients( β were 0.006, 0.005, and 0.006, respectively; all P<0.001); positive correlation remained after adjusting for thyroid function(all β=0.004, all P<0.001); and for multiple confounding factors(model 3 and 4, all P<0.05). Results of univariate and adjusted thyroid function models with GD in different genders were consistent with the total patients(all P<0.05). Conclusion:TRAb is a risk factor for accelerated bone turnover in GD patients which is independent of thyroid function.

Targeting TSHR and ICAM-1 for treatment of Graves′ disease in BALB/c mice / 中华核医学与分子影像杂志

Objective:To explore new methods of treating Graves′ disease (GD) by targeting thyroid stimulating hormone receptor (TSHR) and intercellular adhesion molecule-1 (ICAM-1).Methods:The small interfering RNA (siRNA) targeting TSHR and the ICAM-1 monoclonal antibody (mAb) were designed and synthesized. Thirty GD model mice were randomly divided into siRNA treatment group, ICAM-1 mAb treatment group, and untreated GD group (10 mice in each group), and 10 normal mice were taken as blank control. Serum thyroxine (T 4), thyroid stimulating hormone (TSH), TSH receptor-stimulating antibody (TSAb) and TSH-stimulation blocking antibody (TSBAb) were measured before and after treatment. At the end of the treatment, body mass and heart rate of mice in each group were measured, and thyroid uptake of 99Tc mO 4-, thyroid size and pathological changes were evaluated. Independent-sample t test, paired t test and one-way analysis of variance were used to analyze data. Results:After three treatments, the body mass of mice in siRNA group and ICAM-1 mAb group were significantly lower than that of normal mice ( F=3.50, P=0.025); the heart rates of the mice in two groups were significantly lower than that of untreated GD mice ( F=24.73, P<0.001). Heart rate of mice treated with siRNA decreased significantly, close to that of normal mice. After treatment, the serum T 4((27.58±1.94) vs (65.71±6.89) μg/L, (27.24±3.50) vs (70.84±8.46) μg/L), TSAb ((331.44±43.38) vs (457.33±45.85) mU/L, (275.16±45.80) vs (443.91±42.32) mU/L) and TSBAb ((13.94±1.11) vs (15.83±5.92) mU/L, (14.59±1.02) vs (17.05±6.16) mU/L) levels of mice in both siRNA group and ICAM-1 mAb group significantly decreased ( t values: 4.45-10.87, all P<0.05), while the serum TSH levels of mice in two groups significantly increased ((0.13±0.05) vs (0.04±0.05) mU/L, (1.46±0.34) vs (0.06±0.03) mU/L; t values: -2.22, -5.87, P values: 0.007, <0.001). The elevated TSH level and decreased TSAb level of mice treated with ICAM-1 mAb were significantly different from those treated with siRNA ( t values: 1.03, -1.63, P values: 0.002, 0.031). After treatment, the uptake of 99Tc mO 4- in part of the thyroid lobes of mice was decreased, and the enlargement degree of the corresponding lobes was reduced. The thyroid pathology of mice in the treated groups showed that the absorption vacuoles of thyroid follicles were reduced, and the phenomenon of thinner colloids was improved. No obvious damage was observed in the heart, liver and kidneys of the mice. Conclusions:Both the siRNA targeting TSHR and ICAM-1 mAb have therapeutic effects on GD model mice. The siRNA is better at controlling heart rate, and ICAM-1 mAb is better at increasing TSH and decreasing TSAb. Each of the above treatment methods is safe and effective, which can provide new ideas for GD targeted therapy.

Recombinant human thyroid-stimulating hormone for post-operative assessment in patients with low- to intermediate-risk differentiated thyroid cancer: results of phase Ⅰ study / 中华核医学与分子影像杂志

Objective:To evaluate the efficacy by using domestic recombinant human thyroid-stimulating hormone (rhTSH) in patients with differentiated thyroid cancer (DTC) before or after 131I therapy. Methods:From May 2019 to November 2020, a total of 24 patients with DTC (5 males, 19 females, median age 41 years) in Peking Union Medical College Hospital and Affiliated Tumor Hospital of Zhengzhou University were enrolled into the open-label, dose escalation phase Ⅰ study. All patients were divided into 4 domestic rhTSH dose groups: 0.9 mg×1 d (group A), 0.9 mg×2 d (group B), 1.8 mg×1 d (group C), 1.8 mg×2 d (group D) in succession, with 6 patients in each group. Each patient underwent rhTSH phase and thyroid hormone withdrawal (THW) phase. The end point included safety, tolerability, the quality of life (hypothyroidism symptom and sign score (Billewicz score), profile of mood states (POMS)), effectiveness (thyroid-stimulating hormone (TSH) and thyroglobulin (Tg) levels, diagnostic whole-body scan (Dx-WBS)) and pharmacokinetic characteristics (peak time, peak concentration) of rhTSH. Paired t test and Wilcoxon signed rank test were used for statistical analysis. Results:There were no dose-limiting toxicities, serious adverse events, or no grade ≥3 adverse events reported. The quality of life in rhTSH phase was significantly better than those in THW phase, including the lower Billewicz score (-53.00(-53.00, -53.00) vs -39.50(-47.00, -23.00); S=119.50, P<0.001) and the lower POMS score (91.92±12.06 vs 99.67±19.13; t=0.95, P=0.025). Serum TSH level was increased from 0.04(0.02, 0.11) mU/L (baseline) to 150.00(105.20, 173.31) mU/L 24 h after the last rhTSH administration, which was increased along with the elevation of rhTSH doses. In the THW phase, patients′ TSH levels were≥30 mU/L after 23 d (median) of THW, with the median of 73.51(57.22, 106.22) mU/L. Median Tg level of baseline was 0.10(0.10, 0.41) μg/L, which reached a peak of 0.85(0.12, 3.01) μg/L at 48 h after rhTSH administration. The peak Tg level in the THW phase was 0.88(0.15, 8.04) μg/L. The Dx-WBS consistency rate between rhTSH and THW phase was 95.8%(23/24). Conclusion:rhTSH is a safe and effective method to stimulate the serum Tg level and radioiodine uptake in patients undergoing post-operation or post- 131I assessment for DTC, as well as maintain a higher quality of life in comparison to THW phase.

Effect of Helicobacter pylori infection on standard dose of postoperative thyrotropin suppression therapy for differentiated thyroid cancer / 中华内分泌外科杂志

Objective:To study the effect of Helicobacter pylori (HP) infection on the standardized dose of postoperative thyrotropin suppression of differentiated thyroid carcinoma.Methods:A total of 82 patients diagnosed with differentiated thyroid carcinoma and receiving total thyroidectomy in Beijing Rehabilitation Hospital affiliated to Capital Medical University from Jan. 2019 to Jun. 2020 were enrolled in this study prospectively.19 patients with higher standardized dose of the thyrotropin suppression (>2.5 μg·kg -1·d -1) were selected as the experimental group, and 63 patients with the lower standardized dose of the thyrotropin suppression (≤2.5 μg·kg -1·d -1) were selected as the control group. The presence of HP infection was measured by C13 method, and the HP infection rate was compared between the two groups. The patients with HP infection in the experimental group received standard quadruple therapy to eradicate Helicobacter pylori. The standardized dose before and after treatment were observed and compared. Results:The HP infection rate in the experimental group (73.7%, 14/19) were significantly higher ( P<0.05) than those in the control group (31.7%, 20/63). In the experimental group, 14 patients with HP infection in the experimental group received standard quadruple therapy to eradicate HP. HP was successfully eradicated in 11 patients after the treatment (one patient quit the treatment before completion, the actual eradication rate was 84.6%) ; Eight weeks after the treatment, the dose adjustment of thyrotropin suppression reached steady-state in 13 patients completed the therapy. The average standardized dose was (2.15±0.25) μg·kg -1·d -1, significantly lower than that before treatment [ (2.89±0.21) μg·kg -1·d -1] ( P<0.05) . Conclusions:HP infection may be an important factor affecting the standardized dose of thyrotropin suppression in postoperative patients with thyroid cancer. For those patients with HP infection, eradication treatment of HP can significantly reduce the standardized dose and treatment-related complications.

Association between thyroid function in the first trimester in twin pregnancies and gestational diabetes mellitus / 中华围产医学杂志

Objective:To explore the associations between thyroid function in the first trimester in twin pregnancies and gestational diabetes mellitus (GDM) and the risk factors of twin pregnancies complicated by GDM.Methods:Retrospective analysis was performed on 745 twin pregnancies delivered after 28 weeks at the Third Affiliated Hospital of Sun Yat-sen University from January 2015 to December 2021, and they were divided into GDM group ( n=186) and the control (non-GDM) group ( n=559). Thyroid dysfunction was diagnosed based on the reference range of singleton and twin pregnancies recommended by the Guideline on diagnosis and management of thyroid diseases (2nd edition) in China and the literature, respectively. Independent sample t-test, Chi-square test, or Fisher exact test, and Mann-Whitney U test were used to compare the general clinical characteristics and thyroid function between the two groups. Spearman rank correlation analysis was performed to analyze the correlation between free thyroxine (FT 4), thyroid stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb), and fasting plasma glucose (FPG) in the first trimester as well as glucose levels in 75 g oral glucose tolerance test (OGTT). The associations between FT 4, TSH at different levels, and the detection rate of GDM, and the risk factors of GDM in twin pregnancies were analyzed using logistic regression. Results:(1) The prevalence of GDM in twin pregnancies was 25.0% (186/745). The positive rate of TPOAb was 13.6% (101/745). FPG in the first trimester was higher in the GDM group than that in the control [(4.7±0.5) vs (4.5±0.4) mmol/L, t=－5.08, P<0.001]. (2) No correlation between FT 4, TSH levels, the positive rate of TPOAb in the first trimester and FPG in the first trimester as well as OGTT results was found (all P>0.05). (3) There was no significant difference when using the thyroid function reference range for twin or singleton pregnancy in detecting hypothyroidism [0.5% (4/745) vs 0.4% (3/745)] and subclinical hypothyroidism [1.2% (9/745) vs 1.3% (10/745)] among the included subjects (both P>0.05), however, there were significant differences in the detection rates of hypothyroxinemia alone [25.0% (186/745) vs 12.9% (96/745)], hyperthyroidism [2.4% (18/745) vs 12.9% (96/745)] and subclinical hyperthyroidism [5.8% (43/745) vs 12.1% (90/745)]( χ2 were 35.43, 33.43 and 18.24, all P<0.001). There was no significant difference in the detection rate of thyroid disease between the GDM and control groups (all P>0.05). (4) FT 4 and TSH levels were grouped into quartiles ( Q1, Q2, Q3, and Q4), which showed that the detection rate of GDM was the highest [27.8% (52/187)] in women with FT 4 in Q1 and was the lowest [23.0% (43/187)] in those with FT 4 in Q2. However, the detection rate was the lowest in women with TSH in Q1 [24.1% (45/187)] and was the highest [27.4%(51/186)] in those with TSH in Q4. Taking Q1 of FT 4 and TSH as a reference, the logistic regression model showed that there were no statistically significant differences between FT 4, TSH at different levels, and GDM, even after adjusting for age, preconception-body mass index (pre-BMI), family history of diabetes, mode of conception, and chorionicity (all P>0.05). (5) Multivariate logistic regression analysis showed that maternal age ( OR=1.10, 95% CI: 1.05-1.15), pre-BMI ( OR=1.13, 95% CI: 1.07-1.21), family history of diabetes ( OR=2.73, 95% CI: 1.53-4.85), and FPG in the first trimester ( OR=2.14, 95% CI: 1.38-3.32) were independent risk factors for twin pregnancies complicated by GDM. Conclusions:Twin pregnant women with higher maternal age, pre-BMI, FPG in the first trimester and family history of diabetes were at higher risk of GDM. No significant correlation is found between maternal thyroid function in the first trimester and GDM in twin pregnancies.

A suggested screening method for hypothyroidism in very preterm and/or very low birth weight neonates / Método de triagem para hipotireoidismo sugerido em recém-nascidos muito prematuros ou de muito baixo peso

ABSTRACT Objective: To assess thyroid function in very preterm or very low birth weight (VLBW) neonates by measuring combination levels of thyroid-stimulating hormone TSH and free T4 (FT4) Methods: Inclusion criteria were defined as all very preterm (gestational age <32 weeks) or VLBW (birth weight ≤1500g) neonates with initial Thyroid Function Test (TFT) who were admitted to the Neonatal Intense Care Unit (NICU) of Taleghani Hospital, Tabriz, Iran, from March 2015 to March 2016. Exclusion criteria were the absence of initial TFT with any major congenital anomaly. The primary value of TSH was evaluated at 3-5 days, and mean levels of TSH with FT4 were measured at 2, 4, and 8-weeks. Results: Ninety-five neonates with a mean gestational age of 29.5 weeks were included, and the mean levels of thyrotropin and FT4 at postnatal week two were 4.4mIU/L and 1.4ng/dL, respectively. Two of the patients had serum TSH concentration >25mIU/L that was considered as permanent primary hypothyroidism. Among nine hypothyroxinemia cases, two had elevated TSH levels (10.8±0.4mIU/L at the end of 8 weeks) and normal FT4 concentration, and were considered transient hypothyroidism. Seven cases had normal TSH levels (1.6±1.0mIU/L at 2 weeks, 3.5±2.8mIU/L at 8 weeks) and low FT4 concentrations. Conclusions: Combined venous TSH and FT4 concentration at the end of the first postnatal month can be an efficient approach for detecting neonatal hypothyroidism.

RESUMO Objetivo: Avaliar a função da tireoide em recém-nascidos muito prematuros ou de muito baixo peso por meio dos níveis de combinação de TSH e T4 livre (FT4). Métodos: Os critérios de inclusão foram: todos os recém-nascidos muito prematuros (idade gestacional <32 semanas) ou de muito baixo peso (peso ao nascer ≤500g) com teste de função tireoidiana inicial e que foram admitidos na Unidade de Terapia Intensiva Neonatal do Hospital de Taleghani, Tabriz, Irã, de março de 2015 a março de 2016. Os critérios de exclusão foram: ausência de TFT inicial com qualquer anomalia congênita importante. Resultados: 95 neonatos com idade gestacional média de 29.5 semanas foram incluídos, e os níveis médios de tireotropina e FT4 na 2ª semana pós-natal foram 4.4mIU/L e 1.4ng/dL, respectivamente. Dois dos pacientes apresentavam concentração sérica de TSH >25mIU/L, considerada hipotireoidismo primário permanente. Entre nove casos de hipotiroxinemia, dois tinham níveis elevados de TSH (10.8±0.4mIU/L ao final de 8 semanas) e concentração normal de FT4 e foram considerados hipotireoidismo transitório. Sete casos tinham níveis normais de TSH (1,6±1,0mIU/L em 2 semanas, 3,5±2,8mIU/L em 8 semanas) e baixas concentrações de FT4. Conclusões: A concentração combinada de TSH e FT4 venoso no final do primeiro mês pós-natal pode ser uma abordagem eficiente para detectar hipotireoidismo neonatal.

A practical contemporary approach to decision-making on subclinical hypothyroidism

ABSTRACT Subclinical hypothyroidism (Shypo) is an increasingly frequent condition in common medical practice. Its diagnosis continues to pose a challenge since a series of non-thyroidal and temporary conditions can elevate serum TSH levels. In addition, the consequences of Shypo are still up for debate. Although detrimental cardiovascular effects have been consistently demonstrated in the young, they are less evident in older adults (65-79 years), and even more so in the oldest old (≥80 years). In the absence of evidence of any benefits of treating Shypo in patients' clinical manifestations and unfavorable outcomes, the most effective decision-making approach should include a thorough investigation of the patient's condition integrating all relevant clinical data, such as TSH levels, age, quality of life, comorbidities, cardiovascular risk, safety, and personal preferences. The decision-making process needs to take into account the risk of levothyroxine overtreatment and the resulting adverse consequences, such as reduction of bone mineral density, heart failure, and atrial fibrillation. Hence, current evidence suggests that individuals with TSH > 10 mU/L, who test positive for TPO Ab or are symptomatic may benefit from levothyroxine treatment. However, a more cautious and conservative approach is required in older (≥65 years of age), and oldest-old (≥80 years) patients, particularly those with frailty, in which the risk of treatment can outweigh potential benefits. The latter may benefit from a wait-and-see approach.

Thyroid hormone treatment of differentiated thyroid cancer: Reflection on current practices / 中华内分泌代谢杂志

Thyroid hormone therapy is the mainstay of differentiated thyroid cancer (DTC) management after surgery. By controlling thyrotropin within target levels, it hopes that patients could restore euthyroidism state and lower recurrence rates. However, thyroid hormone treatment has been facing challenges in termso of lenefit-risk assessment since the improved risk stratification system of persistent/recurrent disease was into use. Clinicians should weigh the potential benefits against downsides based on initial risk of disease and ongoing risk assessment of disease status. The optimal TSH level for patients with an intermediate- or high-risk for recurrence is to maintain the beneficial effects on tumor recurrence without increasing the risk of adverse events. Levothyroxine should be titrated to avoid excessive TSH suppression for low-risk patients. Only with holistic benefit-risk analysis of thyroid hormone therapy, can we further promote the quality of postoperative DTC management.

Relationship between thyrotropin levels and cardiovascular risk factors in elderly patients with type 2 diabetes mellitus / 中华老年医学杂志

Objective:To investigate the relationship between serum thyrotropin(TSH)levels and major cardiovascular risk factors in elderly type 2 diabetes(T2DM)patients with normal thyroid function.Methods:A total of 510 elderly T2DM patients with normal thyroid function were included in this study, including 265 males and 245 females.Blood samples of all patients were collected after an overnight fast.Thyroid function and blood levels of lipids, glucose, glycated hemoglobin(HbA1c)and other components were measured.Basic information of all patients was collected and body mass index(BMI), visceral adiposity index(VAI)and lipid accumulation product index(LAP)were calculated.Results:The levels of BMI, VAI, LAP, triglycerides(TG), total cholesterol(TC), low density lipoprotein(LDL-C), HbA1c, fasting blood glucose(FBG)and 2h-postprandial blood glucose(2 h PBG)were higher in the high TSH group than in the low TSH group(31.7±5.5 kg/m 2vs.27.6±2.1 kg/m 2, 7.20±1.18 vs.5.88±0.51, 61.88±6.36 vs.52.76±7.09, 6.49±2.64 mmol/L vs.5.84±2.41 mmol/L, 2.73±1.30 mmol/L vs.1.99±0.54 mmol/L, (2.86±0.93 mmol/L vs.2.55±0.81 mmol/L, 9.10±1.35% vs.7.80±1.76%, 9.64±2.03 mmol/L vs.7.55±1.72 mmol/L, 19.20±2.99 mmol/L vs.15.33±2.36 mmol/L, t=5.32, 8.06, 10.88, 8.13, 8.30, 5.90, 5.83, 6.51 and 6.82, all P<0.05). Multivariate Logistic regression analysis showed that cardiovascular risk factors including HbA1c( OR=1.21, 95% CI: 1.01-1.52, P=0.020), LDL-C( OR=1.88, 95% CI: 1.78-2.01, P=0.000), LAP( OR=3.01, 95% CI: 2.98-3.12, P=0.010), and BMI( OR=2.58, 95% CI: 2.45-2.68, P=0.000)were influencing factors for TSH. Conclusions:In elderly patients with T2DM, TSH levels within the normal range but close to the upper limit are closely related to cardiovascular risk factors such as increased visceral fat and high TG levels, and may increase the risk of cardiovascular disease.

Efficacy of methimazole combined with 1α-hydroxyvitamin D3 in patients with Graves disease of high-titer thyrotropin receptor antibodies / 中国医师杂志

Objective:To observe the efficacy of methimazole (MMI) combined with 1α-hydroxyvitamin D3 (alfacalcidol, ALF) in patients with Graves disease of high-titer thyrotropin receptor antibodies (TRAb) and to explore new clinical strategies to reduce serum TRAb in Graves disease.Methods:120 patients with Graves disease initially diagnosed in Quanzhou First Hospital Affiliated to Fujian Medical University and the People′s Hospital Affiliated to Quanzhou Medical College from June 2017 to June 2019 were prospectively selected as the research objects. All patients received conventional dose of MMI for anti hyperthyroidism treatment. The patients were randomly divided into three groups: group A [ n=40, treated with MMI combined with high-dose ALF (0.5 μg/d)], group B [ n=37, treated with MMI combined with low-dose ALF (0.25 μg/d)] and group C ( n=43, treated with MMI only). The treatment lasted for 24 weeks. The serum free triiodothyronine (FT 3), free thyroxine (FT 4), thyroid stimulating hormone (TSH) and TRAb in patients before and after above treatments were detected. The blood routine, liver function, alkaline phosphatase (ALP), 25(OH)D, serum calcium (CA) and serum phosphorus were detected regularly. Results:After drug treatment: ⑴ the thyroid function of the three groups returned to normal. The average daily dosage of MMI in group A was significantly lower than that in group B and C ( P<0.05), and that in group B was also lower than that in group C ( P<0.05), with significant difference. After 24 weeks of treatment, the daily dosage of MMI in group A and B was significantly lower than that in group C ( P<0.05). ⑵ There was no significant difference in thyroid function among the three groups. The concentration of serum TRAb in group A was significantly lower than that in group B and C ( P<0.05), and that in group B was also lower than that in group C ( P<0.05). ⑶ During the 24 week follow-up, there was no significant difference in serum 25(OH)D, ALP, Ca and P among the three groups ( P>0.05); no leukopenia in peripheral blood and no abnormal liver function were found in the three groups. Conclusions:MMI combined with ALF can effectively treat Graves′ disease, reduce the dosage of MMI drugs, decline the level of TRAb in the serum of Graves′ patients, and improve the prognosis of Graves′ disease.