Reference values and the effect of clinical parameters on thyroid hormone levels during early pregnancy

Objective: Thyroid dysfunction is a common endocrine problem during pregnancy; correct diagnosis and appropriate treatments are essential to avoid adverse pregnancy outcomes. Besides, it is vital to identify and quantify the major risk factors for gestational thyroid dysfunction, including thyroid autoimmunity, human chorionic gonadotropin (HCG) concentration, body mass index (BMI) and parity. The study objective was to establish reference ranges during early pregnancy and to explore the relationship between risk factors and thyroid stimulating hormone (TSH), free thyroxine (FT4) and free triiodothyroxine (FT3).Design, patients and measurements: To establish the reference ranges of thyroid hormone during early pregnancy in China and to identify the risk factors for thyroid dysfunction, woman in the first trimester of pregnancy (4–12 weeks gestation) were recruited. After excluding thyroid peroxidase antibody (TPO-Ab) positive and/or thyroglobulin antibody (TG-Ab) positive women, previous thyroid disease, a lack of iodine intake, reference values were calculated by 2.5th to 97.5th percentiles.Results: After exclusion of TPO-Ab and/or TG-Ab positive women, reference values were as follows: TSH, 0.11–3.67 mIU/l; FT3, 3.19–5.91 pmol/l; FT4 10.95–16.79 pmol/l. Higher BMI was associated with lower FT4 concentrations (P=0.005). In multiple regression analysis, TSH was significantly and positively associated with TG (P=0.03). Maternal parity and maternal age may be risk factors for the abnormal thyroidal response to hCG concentrations.Conclusions: Our study defined first trimester-specific reference ranges for serum TSH, FT4, FT3 in a Chinese population, and demonstrated that BMI ≥23kg/m², maternal parity ≥3 and maternal age ≥30 years may increase the risk of thyroid dysfunction.     

Thyroid Autoimmunity and Recurrent Spontaneous Abortion in Iran: A Case-Control Study

ObjectiveTo determine the association of thyroglobulin antibodies (TG-Ab) and thyroid peroxidase antibodies (TPO-Ab) with recurrent spontaneous abortion in a euthy-roid, nonpregnant population of women in Iran.MethodsIn this case-control study conducted between November 2003 and September 2006 in Tehran, Iran, non pregnant women with a history of 3 or more consecutive pregnancy losses and age-matched, healthy parous women without a history of reproductive problems were assessed. Thyroid function tests were performed, which included assessment of thyroid-stimulating hormone, triiodothyro nine, thyroxine, and the presence of TG-Ab and TPO-Ab.ResultsA total of 641 patients and 269 controls were included. Mean age (± SD) was 30.6 ± 6.4 years (range, 16-51 years) in the patient group and 30.05 ± 6.6 years (range, 18-48 years) in the control group. Thyroid antibodies were present in 157 of 641 patients (24.5%) and in 34 of 269 controls (12.6%) (P < .001). The presence of thyroid antibodies was significantly associated with recurrent abortion independent of the impact of age with an odds ratio of 2.24 (95% confidence interval, 1.5-3.35).ConclusionsIn this population of women in Iran, TG-Ab and TPO-Ab were identified more frequently in women with recurrent abortions compared with controls, and thyroid autoimmunity was independently associated with a higher risk of recurrent abortion. (Endocr Pract. 2008;14:458-464)     

Association of First-Trimester Thyroid Function Test Values with Thyroperoxidase Antibody Status,Smoking, and Multivitamin Use

ObjectiveTo determine first-trimester thyroid function values and associations with thyroperoxidase antibody (TPO-Ab) status, smoking, emesis, and iodine-containing multivitamin use.MethodsWe collected information by interview, questionnaire, and blood draw at the initial obstetric visit in 668 pregnant women without known thyroid disease. We compared thyroid-stimulating hormone (TSH), total thyroxine (T₄), and free T₄ index (FT₄I) values by TPO-Ab status. Multiple regression was used to identify characteristics associated with thyroid function values.ResultsThe following median (range containing 95% of the data points) thyroid function test values were obtained in 585 TPO-Ab–negative women: TSH, 1.1 mIU/L (0.04-3.6); FT₄I, 2.1 (1.5-2.9); and T₄, 9.9 μg/dL (7.0-14.0). The following median (range containing 95% of the data points) thyroid function test values were obtained in 83 TPO-Ab–positive women: TSH, 1.8 mIU/L (0.3-6.4) (P < .001); FT₄I, 2.0 (1.4-2.7) (P = .06); and T₄, 9.3 μg/dL (6.8-13.0) (P = .03) (P values denote statistically significant differences between TPO-Ab–positive and negative participants). Among TPO-Ab–negative participants, TSH level was not associated with use of iodine-containing multivitamins, smoking, or race. TSH increased 0.03 mIU/L for every year of maternal age (P = .03) and decreased by 0.3 mIU/L for every increase in parity (P < .001). T₄ decreased 0.04 μg/dL for every year of maternal age (P = .04). Mean FT₄I was 2.05 in smokers and 2.20 in nonsmokers (P < .01). There were no relationships between T₄ or FT₄I and parity, race, or iodine-containing multivitamin use.ConclusionTPO-Ab status of pregnant women should be considered when constructing trimester-specific reference ranges because elevated serum TPO-Ab levels are associated with higher TSH and lower T₄ values. (Endocr Pract. 2008;14:33-39)     

Urinary iodine and thyroid function in a population of healthy pregnant women in the North of Spain

BackgroundIodine is an essential trace element for the synthesis of thyroid hormones, which are keys in maternal metabolism during pregnancy as well as in neurological development during fetal and postnatal life. This was a prospective study on iodine status and thyroid function in women during pregnancy in the Basque country to assess whether there was any relationship among maternal urinary iodine, maternal thyroid function and thyrotropin (TSH) in newborns, and to explore any difference in women experiencing miscarriages.MethodsWe analyzed TSH, free T₄ (FT₄), free T₃ (FT₃), thyroid peroxidase antibody (TPO-Ab) titers in serum and urinary iodine concentrations (UIC) in 2104 women in the first trimester of pregnancy and in 1322 of them in their second trimester. We obtained neonatal TSH levels in 1868 cases.ResultsIn the first (T1) and second trimesters (T2), the median UICs were 88.5 μg/L and 140 μg/L, respectively. No relationship was found between UIC and FT₄, or maternal and neonatal TSH. In T1 and T2, 9.7% and 7.5% of women were TPO-Ab positive, respectively. The total miscarriage rate was 10%. The percentage of miscarriages in healthy women was 8.9%, lower than in women with overt hypothyroidism (21.2%; p < 0.001) and than in women with subclinical hypothyroidism (15.6%; p < 0.025). The miscarriage rate was not higher in TPO-Ab-positive women.ConclusionsIn this study most women had iodine deficiency during pregnancy. Neonatal TSH is not correlated with maternal UIC during pregnancy. Pregnant women with hypothyroidism have a higher rate of miscarriages.     

High prevalence of TPO-Abs and subclinical hypothyroidism in iodine-sufficient pregnant women in Northern Algeria

BackgroundIodine is a trace element whose adequate intakes are essential during gestation to promote the correct growth and development of the fetus. Historically, endemic goiter and cretinism affected northern regions of Algeria, and iodized salt was introduced in 1990. However, there has been no national study of iodine nutrition in Algeria since 1994. The aim of this study was to assess the iodine status and thyroid function of women of reproductive age (WRA) and pregnant women (PW) in northern Algeria.MethodsHealthy WRA and PW were recruited from an urban area (Algiers) and healthy WRA from a rural area (Tizi-Ouzou). Spot urine and venous blood samples were collected to assess iodine status (urinary iodine concentration, UIC) and serum thyroid hormones (TSH, FT4), thyroglobulin (Tg), and anti-thyroid peroxidase antibodies (TPO-Ab) concentrations.ResultsThe median UIC in WRA was 256 μg/L (IQR: 166−354 μg/L; n = 151) in Algiers and 253 μg/L (167−341 μg/L; n = 150) in Tizi-Ouzou. The median UIC for the PW in Algiers was 233 μg/L (IQR: 157−326 μg/L; n = 173).Thirty-five percent of WRA and 30% of PW had an UIC > 300 μg/L. Median TSH, FT4 and Tg concentrations were within reference ranges in all groups of women. Among PW, 72.7%, 75.4% and 75.5% in the first, second and third trimester were TPO-Ab+. Among TPO-Ab + PW in the first, second and third trimesters, 18.7%, 13% and 10.3% had subclinical hypothyroidism.ConclusionIn northern Algeria, median UICs in PW indicate iodine sufficiency, and in WRA indicate more than adequate intakes. About 75% of PW are TPO-Ab + and the prevalence of subclinical hypothyroidism is high. Monitoring and surveillance of iodine fortification programs is vital to avoid both iodine deficiency and excess. There is an urgent need for a comprehensive national iodine status survey including school-age children and other vulnerable population groups in Algeria.     

Value of Baseline Serum Thyrotropin as a Predictor of Hypothyroidism in Patients With Diabetes Mellitus

ObjectiveTo determine whether serum thyrotropin measurement performed at diagnosis of diabetes mellitus or at initial patient contact predicts subsequent development of hypothyroidism.MethodsWe retrospectively reviewed the computerized records of patients attending annual visits between January 2008 and December 2008 at a hospital diabetes mellitus clinic. Serum free thyroxine and thyrotropin at current and baseline annual visits were documented. A Cox regression model was used to analyze the relationship between development of thyroid dysfunction and patient characteristics including age, sex, type of diabetes, and baseline serum thyrotropin concentration. KaplanMeier survival curves were generated for predictors of hypothyroidism.ResultsClinical records of 1101 patients were reviewed (595 men [54%] and 506 women [46%]). Mean age was 60.0 ± 17 years. Two hundred twenty-three patients (20.3%) had type 1 DM and 878 (79.7%) had type 2 diabetes. Thyroid dysfunction was present in 136 patients (12.4%) at baseline and developed in 71 patients (6.4%) at follow-up (median duration, 37 months). Overt and subclinical hypothyroidism developed in 28 (2.5%) and 38 (3.5%) patients, respectively. Incident hypothyroidism was associated with baseline thyrotropin concentration greater than 2.2 mIU/L (relative risk, 10.4; confidence interval, 5.6-19.6; P < .001) and female sex (relative risk, 1.8; confidence interval, 1.1-2.9; P = .007). The predictive influence of sex was abolished in patients with a thyrotropin value greater than 2.2 mIU/L. This TSH threshold yielded an optimal sensitivity and specificity of 83% and 72%, respectively, for predicting hypothyroidism.ConclusionsBaseline serum thyrotropin predicted hypothyroidism in patients with diabetes mellitus even at thyrotropin concentrations within the reference range. Selective annual thyroid screening in diabetic patients with baseline thyrotropin concentrations greater than 2.2 mIU/L may be more cost-effective than universal screening. (Endocr Pract. 2011;17:26-32)     

Association Between Thyroid Function and Objective and Subjective Sleep Quality in Older Men: The Osteoporotic Fractures in Men (MrOS) Study

ObjectiveTo determine the association between thyroid hormone levels and sleep quality in community-dwelling men.MethodsAmong 5,994 men aged ≥ 65 years in the Osteoporotic Fractures in Men (MrOS) study, 682 had baseline thyroid function data, normal free thyroxine (FT₄) (0.70 ≤ FT₄ ≤ 1.85 ng/dL), actigraphy measurements, and were not using thyroid-related medications. Three categories of thyroid function were defined: subclinical hyperthyroid (thyroid-stimulating hormone [TSH] < 0.55 mIU/L), euthyroid (TSH, 0.55 to 4.78 mIU/L), and subclinical hypothyroid (TSH > 4.78 mIU/L). Objective (total hours of nighttime sleep [TST], sleep efficiency [SE], wake after sleep onset [WASO], sleep latency [SL], number of long wake episodes [LWEP]) and subjective (TST, Pittsburgh Sleep Quality Index score, Epworth Sleepiness Scale score) sleep quality parameters were measured. The association between TSH and sleep quality was examined using linear regression (continuous sleep outcomes) and log-binomial regression (categorical sleep outcomes).ResultsAmong the 682 men examined, 15 had subclinical hyperthyroidism and 38 had subclinical hypothyroidism. There was no difference in sleep quality between subclinical hypothyroid and euthyroid men. Compared to euthyroid men, subclinical hyperthyroid men had lower mean actigraphy TST (adjusted mean difference [95% confidence interval (CI)], − 27.4 [− 63.7 to 8.9] minutes), lower mean SE (− 4.5% [− 10.3% to 1.3%]), and higher mean WASO (13.5 [− 8.0 to 35.0] minutes]), whereas 41% had increased risk of actigraphy-measured TST < 6 hours (relative risk [RR], 1.41; 95% CI, 0.83 to 2.39), and 83% had increased risk of SL ≥ 60 minutes (RR, 1.83; 95% CI, 0.65 to 5.14) (all P > .05).ConclusionNeither subclinical hypothyroidism nor hyperthyroidism is significantly associated with decreased sleep quality. (Endocr Pract. 2014;20:576-586)     

Effect of the inflammatory response on serum indices of iron status in late pregnancy

Background and aimsA systemic inflammatory response complicates the evaluation of iron status during pregnancy. We investigated the magnitude of this effect on indices of iron status in late pregnancy.MethodsWe retrospectively interrogated laboratory data and hospitalisation records from April 2016 to March 2017 and obtained results from pregnant women in which serum high-sensitivity C-reactive protein (hsCRP) or albumin had been examined together with indicators of iron status (serum ferritin [SF] and serum transferrin [ST], n = 11,571). We assessed the association of the inflammatory response, as evidenced by hsCRP and albumin, with iron status indicators by general linear regression analysis.ResultCompared to women with an hsCRP of ≤ 5 mg/L, the median SF level in those with an hsCRP of 6–10, 11–20, and > 20 mg/L significantly increased by 2.24 μg/L (95 % confidence interval [CI]: 1.22, 3.26), 4.04 μg/L (95 % CI: 2.05, 6.04), and 13.49 μg/L (95 % CI: 10.44, 16.53); while the ST level decreased by 0.10 g/L (95 % CI: 0.13, 0.06), 0.16 g/L (95 % CI: 0.23, 0.09), and 0.21 g/L (95 % CI: 0.32, 0.11), respectively (all P < 0.001). With regard to the association of inflammation with SF and ST, no significant interaction between albumin (< 35 and ≥ 35 g/L) and hsCRP was observed (SF: P for interaction = 0.426; ST: P for interaction = 0.872).ConclusionsMeasurement of hsCRP in late pregnancy is necessary to correct the levels of SF and ST. The impact of the inflammatory response on indices of iron status in late pregnancy could not be adjusted by albumin.     

Association of Thyroid Function During Pregnancy With the Risk of Pre-eclampsia and Gestational Diabetes Mellitus

ObjectiveTo estimate the association of maternal thyroid dysfunction with the risk of gestational hypertension and diabetes. Whether the association was affected by gestational age at diagnosis and thyroid autoimmunity was further explored.MethodsA cohort study of 41 647 participants was conducted. Thyroid function (ie, thyroid-stimulating hormone [TSH] and free thyroxine [FT4]) was measured by electrochemiluminescence immunoassay. Thyroid antibody positivity (eg, thyroperoxidase, thyroglobulin, and TSH receptor antibody) was indicated if the values of these antibodies exceeded the upper targets of the reference range. The relationship between maternal thyroid dysfunction and the risk of pre-eclampsia (PE) and gestational diabetes mellitus (GDM) was assessed by multivariate logistic regression.ResultsIsolated hypothyroxinemia (defined as 5th ≤ TSH ≤ 95th percentile, FT4 < 5th percentile) was associated with the risk of PE (odds ratio [OR], 1.32; 95% CI, 1.10-1.58). Overt hypothyroidism (TSH > 95th percentile; FT4 < 5th percentile) was related to the risk of severe PE (OR, 2.59; 95% CI, 1.05-6.37). Being positive for TSH receptor antibody was associated with a decreased risk of GDM (OR, 0.49; 95% CI, 0.35-0.70). A marginally significant association between overt hypothyroidism detected at the first trimester and the risk of GDM was found (OR, 1.60; 95% CI, 1.00-2.83). The association of thyroid dysfunction with the risk of PE and GDM was stronger among pregnant women who were negative for autoantibodies.ConclusionSome types of thyroid dysfunction during pregnancy were associated with the risk of PE and GDM. The associations varied by gestational age at diagnosis and by thyroid autoantibody status.     

Preconception Thyroid-Stimulating Hormone And Pregnancy Outcomes In Women With Hypothyroidism

ObjectivesMaternal hypothyroidism may adversely affect pregnancy outcomes. International practice guidelines recommend that women with hypothyroidism should attain a preconception and early gestation serum thyroid-stimulating hormone (TSH) level of <2.5 mU/L. Our objective was to ascertain what proportion of women realize this target in practice and whether a TSH level above this threshold has adverse fetal and maternal consequences.MethodsThis was an observational study of women with hypothyroidism referred to an endocrine antenatal clinic between 2008 and 2010 (n = 78; mean age, 30.4 years; range, 19 to 43 years). Thyroid profiles (free thyroxine [FT4] and TSH) before conception and through pregnancy were documented. Obstetrics outcomes were examined, including low birth weight, preterm births, preeclampsia, caesarean sections, and admissions to special care neonatal units.ResultsThyroid testing was undertaken in 80% of subjects before conception, and in 64, 94, and 96% of subjects in the first, second, and third trimesters of pregnancy, respectively. TSH >2.5 mU/L was seen in 49% of women before conception and in 68% of women in thefirst trimester. Six women were overtly hypothyroid before conception, attaining normal thyroid function at gestational ages ranging from 12 to 36 weeks. Neither the preconception nor the first postconception TSH level (>2.5 mU/L or ≤2.5 mU/L) was associated with gestational age at delivery, birth weight, or rates of caesarean section or preeclampsia.ConclusionThe majority of women with hypothyroidism do not achieve the recommended preconception and early gestation TSH targets. Preconception and early gestation TSH >2.5 mU/L was not associated with adverse fetal and maternal outcomes. Studies in larger cohorts will be required to confirm these findings, however. (Endocr Pract. 2013;19:656-662)     

Reporting Thyroid Function Tests in Pregnancy

While there is agreement that overt maternal hypothyroidism (serum thyroid stimulating hormone (TSH) >10 mIU/L) should be treated immediately, the evidence is mixed regarding the harm associated with subclinical hypothyroidism and the benefits of thyroxine replacement. The diagnosis of subclinical hypothyroidism rests on the recognition of an increased serum concentration of TSH which may be affected by many factors including gestational age, analytical method, the antibody status of the mother, ethnicity, iodine nutrition and even the time of day when the blood is collected. The 97.5^th percentile of TSH at the end of the first trimester is commonly used as the upper boundary of normal in early pregnancy with a default value of 2.5 mIU/L specified in a number of recent clinical guidelines. There have now been numerous papers showing that a more realistic figure is between 3.0 and 4.0 mIU/L depending on the analytical method that is used. There are suggestions that ethnicity may also have a significant effect on TSH and FT4 reference limits in pregnancy.     

Is there a link between blastomere contact surfaces of day 3 embryos and live birth rate?

Background

Limitations in our current knowledge of normative physiologic changes in thyroid function during the periconception window narrow our ability to establish an optimal approach to screening and diagnosis of thyroid disease in pregnant women. The objective of this study was to characterize changes in thyroid function during the transition from the pre-pregnant to pregnant state in normal fertile women.

Methods

Women (N = 60) ages 30-42 years without a history of thyroid disease, who were planning pregnancy, were observed prospectively before and during early pregnancy. Thyroid function (thyroid stimulating hormone, TSH and free thyroxine, FT4) was measured before conception and between 6 and 9 weeks gestation. Pre-pregnancy samples were analyzed for thyroid antibodies. Bivariate analyses and longitudinal curves (general estimating equation models) were used to analyze changes in thyroid function during the periconception window by antibody status.

Results

Pre-pregnancy TSH values were significantly higher than early pregnancy TSH (p < 0.001), but FT4 values did not differ (p = 0.53). TSH declined as gestational age increased (P < 0.01). Thyroid antibody positive women had a higher pre-pregnancy TSH compared to antibody negative women (p < 0.01). Periconceptional change in thyroid function was more variable among women with antibodies (p < 0.001). 50% of women with elevated pre-pregnancy TSH values (TSH > 3.0 mIU/L) had normal TSH values (TSH < 2.5 mIU/L) in pregnancy.

Conclusions

TSH values decline during the transition from pre-pregnancy to early pregnancy. The change in TSH appears to be less predictable in women with thyroid antibodies. Periconceptional changes in thyroid function should be considered in formulating prenatal thyroid screening guidelines.     

Impact of Thyroid Function on Serum Cystatin C and Estimated Glomerular Filtration Rate: A Cross-Sectional Study

ObjectiveTo determine the relationship between thyroid-stimulating hormone (TSH) and cystatin C (CysC) and estimated glomerular filtration rate calculated by Cys^C (e^GFRCysC).MethodsWe conducted a cross-sectional study including 8,126 male participants. Serum creatinine (Cr), CysC, eGFR calculated by Cr (eGFR_Cr), and eGFR_CysC were determined and compared in euthyroid and subclinical thyroid dysfunction patients. Relationships between TSH and Cr, cystatin C, eGFR_Cr, and eGFR_CysC were assessed by linear and quadratic trend analyses. Odds ratios (ORs) of chronic kidney disease (CKD; eGFR<60 mL/min/1.73m²) were calculated according to categories of thyroid function using TSH values of 2.01-3.00 mIU/L as a reference.ResultsSerum CysC level was significantly elevated, and eGFR_CysC was significantly reduced in both sub-clinical hypothyroidism and subclinical hyperthyroidism. TSH was negatively and linearly associated with Cr and eGFR_Cr (P<.001). Quadratic trends were found between TSH and cystatin C or eGFR_CysC (P<.001). Compared with individuals with TSH of 2.01-3.00 mIU/L, the prevalence of CKD_CysC was significantly higher in subjects with TSH<0.40 mIU/L, 3.01-4.00 mIU/L, and 4.01-7.00 mIU/L, while the prevalence of CKD_Cr was only significantly higher in subjects with TSH>7.0 mIU/L.ConclusionDespite only studying male subjects and using eGFR rather than standard GFR, we conclude that thyroid function differentially affects serum CysC and Cr concentrations. Subclinical hypothyroidism and subclinical hyperthyroidism are both associated with elevated CysC, reduced eGFR_CysC, and higher prevalence of CKD_CysC. Assessment of renal function with CysC should be avoided in patients with thyroid dysfunction. (Endocr Pract. 2013;19:397-403)     

Prevalence of Elevated Thyroid-Stimulating Hormone Levels in Obese Children and Adolescents

ObjectiveTo determine the prevalence of elevated thyroid-stimulating hormone (TSH) levels in obese children and adolescents referred to pediatric endocrinology clinics.MethodsWe undertook a retrospective review of medical records of 191 obese and 125 nonobese children (younger than 18 years old). Data about age, sex, body mass index, TSH, thyroid functions, thyroid antibodies, thyroid size, and medications were collected.ResultsSix obese patients had Hashimoto disease and TSH values from 0.73 to 12.73 mIU/L; they were excluded from the study analyses. Of the remaining 185 obese subjects, 20 (10.8%) had TSH levels > 4 mIU/L, but no control subject measurement exceeded this TSH value. The highest TSH concentration in an obese study subject was 7.51 mIU/L. When obese children with TSH levels > 4 mIU/L were classified in a third group, the mean TSH in the rest of the obese children was comparable with that in the control group (1.98 ± 0.84 [SD] and 1.95 ± 0.80 mIU/L, respectively; post hoc analysis of variance, P = .945). Obese subjects with increased TSH values had a mean body mass index similar to that for obese subjects with normal TSH levels (34.98 ± 6.12 [SD] and 34.29 ± 7.84 kg/m², respectively).ConclusionMild elevation of TSH values in the absence of autoimmune thyroid disease is not uncommon in some obese children and adolescents. This is the second study in the United States to report this observation. Our study did not identify any special characteristics of obese subjects with TSH elevation in comparison with obese children with normal TSH levels and the control group. Current medical knowledge does not support routine screening for thyroid dysfunction in obese children. (Endocr Pract. 2010;16:187-190)     

Increased maternal leptin levels may be an indicator of subclinical hypothyroidism in a newborn

BackgroundSeveral factors may influence newborn thyroid-stimulating hormone (TSH) concentrations and cause subclinical hypothyroidism in a newborn. A sufficient level of leptin signalling is needed for the normal production of TSH and thyroid hormones by the thyroid gland. Our study aimed to investigate the correlation between maternal serum leptin concentration during the third trimester of pregnancy and newborn screening-TSH levels.MethodsThis prospective cross-sectional study was conducted in obstetrics and gynaecology clinics of a state hospital between June and August 2013. Maternal venous blood samples were collected from 270 healthy pregnant women in the third trimester just before delivery. Measurements of maternal fT3, fT4, TSH, anti-thyroid peroxidase (TPO), and anti-thyroglobulin (anti-Tg) antibodies from serum samples were performed by chemiluminescence immunoassay. Maternal serum leptin levels were determined by ELISA. Dried capillary blood spots were used to measure newborn TSH levels.ResultsSubjects were divided into two groups according to the neonatal TSH levels using a cut-point of 5.5 mIU/L. Median maternal serum leptin levels were significantly higher in newborns whose TSH levels were higher than >5.5 mIU/L [13.2 μg/L (1.3 - 46.5) vs 19.7 μg/L (2.4 - 48.5), p<0.05]. Serum leptin levels showed a negative correlation with maternal fT4 (r=0.32, p<0.05), fT3 (r=0.23, p<0.05), and a positive correlation with BMI (r=0.30, p<0.05).ConclusionsOur results suggest that high leptin levels in the third trimester of pregnancy influence maternal thyroid functions and might cause an increase in newborn TSH levels. Detection of high maternal serum leptin levels may be a reason for subclinical hypothyroidism.     

Indirect estimation of reference intervals for thyroid parameters using advia centaur XP analyzer

BackgroundThe aim of this study was to determine the reference intervals (RIs) for thyroid stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3) and FT3/FT4 ratio using indirect methods.MethodsWe analyzed 1256 results TSH, FT4 and FT3 collected from a laboratory information system between 2017 and 2021. All measurements were performed on a Siemens ADVIA Centaur XP analyzer using the chemiluminescent immunoassay. We calculated the values of the 2.5th and 97.5th percentiles as recommended by the IFCC (CLSI C28-A3).ResultsThe RIs derived for TSH, FT4, FT3 and FT3/FT4 ratio were 0.34-4.10 mIU/L, 11.3-20.6 pmol/L, 3.5-6.32 pmol/L and 0.21-0.47, respectively. We found a significant difference between calculated RIs for the TSH and FT4 and those recommended by the manufacturer. Also, FT3 values were significantly higher in the group younger than 30 years relative to the fourth decade (5.26 vs. 5.02, p=0.005), the fifth decade (5.26 vs. 4.94, p=0.001), the sixth decade (5.26 vs. 4.87, p<0.001), the seventh decade (5.26 vs. 4.79, p<0.001) and the group older than 70 years old (5.26 vs. 4.55, p<0.001). Likewise, we found for TSH values and FT3/FT4 ratio a significant difference (p <0.001) between different age groups.ConclusionsThe establishing RIs for the population of the Republic of Srpska were significantly differed from the recommended RIs by the manufacturer for TSH and FT4. Our results encourage other laboratories to develop their own RIs for thyroid parameters by applying CLSI recommendations.     

桥本氏病合并甲状腺乳头状癌患者血清甲状腺相关激素水平的变化及意义

目的:探究桥本氏病(HT)合并甲状腺乳头状癌(PTC)患者血清甲状腺相关激素水平的变化及意义。方法:对我院148例HT患者的临床资料进行回顾性分析,根据其是否合并PTC分为HT合并PTC组(n=68)和单纯HT组(n=80)。比较两组患者性别、年龄及血清促甲状腺激素(TSH)、甲状腺功能指标[游离三碘甲腺原氨酸(FT3)、游离甲状腺素(FT4)]、抗甲状腺抗体[甲状腺球蛋白抗体(TGAb)、甲状腺过氧物酶抗体(TPOAb)]水平等临床资料差异,分析血清TSH水平变化及意义。结果:HT合并PTC组患者男性比例、年龄、病程及血清TSH水平均大于单纯HT组,血清TGAb、TPOAb水平则均小于单纯HT组(P0.05);血清FT3、FT4水平比较差异无统计学意义(P0.05)。HT合并PTC患者组血清TSH4.2 m IU/L患者占比高于血清TSH正常组(P0.05)。血清TSH4.2 m IU/L患者中HT合并PTC患者的占比大于血清TSH水平正常的患者(P0.05)。HT合并PTC患者中,血清TSH水平4.2 m IU/L患者中央区淋巴结转移发生率高于血清TSH水平正常患者(P0.05);血清TSH4.2 m IU/L与血清TSH正常患者多灶癌发生率比较差异无统计学意义(P0.05)。结论:HT患者血清TSH水平升高可能促进其甲状腺组织癌变,HT合并PTC患者血清TSH水平升高可能促进其中央区淋巴结转移。     

Valores de referencia y estudio de la variabilidad de hormonas tiroideas en gestantes de El Bierzo

Background and objectivesEl Bierzo area is characterized by low urinary iodine levels in the pregnant population. Guidelines recommend that local reference values are established for the diagnosis of thyroid dysfunction in pregnancy. Our objectives were to establish reference values for thyroid-stimulating hormone (TSH), free thyroxine (FT4) and free triiodothyronine (FT3) in women in the first trimester of pregnancy and to explore the factors influencing variability in these hormones.Patients and methodsA retrospective study of 412 women in the first trimester of pregnancy who were measured serum levels of TSH, FT4, and FT3; 163 women with conditions with a potential influence on thyroid function were excluded. Thirty smoking pregnant women were also excluded from the study of reference values. Factors examined in the variability study included age, body mass index (BMI), and smoking. A multifactorial analysis of covariance was performed.ResultsReference values in first-trimester pregnant women were: TSH: 0.497-3.595 mIU/L; FT4: 0.90–1.42 ng/dL; FT3: 2.49–3.56 pg/mL. TSH levels depended on mother age and on interaction between age and smoking. FT3 levels depended on the mother's BMI and smoking, and there was also an interaction between both factors.ConclusionThe reference values found may be used to assess thyroid dysfunction in pregnant women from El Bierzo. TSH and FT3 levels are influenced by age and BMI of the mother and by smoking, in addition to the interaction of these factors.     

Management of Hypothyroidism and Hypothyroxinemia During Pregnancy

ObjectiveTo review the diagnosis and management of hypothyroidism during pregnancy, in the preconception period, and in the postpartum period.MethodsA literature review of English-language papers published between 1982 and 2022, focusing on the most recent literature.ResultsDuring pregnancy, thyroid function laboratory tests need to be interpreted with regard to gestational age. Overt hypothyroidism, regardless of the thyroid-stimulating hormone (TSH) level, should always be promptly treated when it is diagnosed before conception or during pregnancy or lactation. Most women with pre-existing treated hypothyroidism require an increase in levothyroxine (LT4) dosing to maintain euthyroidism during gestation. LT4-treated pregnant patients need close monitoring of their serum TSH levels to avoid overtreatment or undertreatment. There is no consensus about whether to initiate LT4 in women with mild forms of gestational thyroid hypofunction. However, in light of current evidence, it is reasonable to treat women with subclinical hypothyroidism with LT4, particularly if the TSH level is >10 mIU/L or thyroperoxidase antibodies are present. Women who are not treated need to be followed up to ensure that treatment is initiated promptly if thyroid failure progresses. Additional studies are needed to better understand the effects of the initiation of LT4 in early gestation in women with subclinical hypothyroidism and hypothyroxinemia and determine optimal strategies for thyroid function screening in the preconception period and during pregnancy.ConclusionThe diagnosis and management of hypothyroidism in the peripregnancy period present specific challenges. While making management decisions, it is essential to weigh the risks and benefits of treatments for not just the mother but also the fetus.