TSH Reference Range Research Articles

Different Thyroidal Responses to Human Chorionic Gonadotropin Under Different Thyroid Peroxidase Antibody and/or Thyroglobulin Antibody Positivity Conditions During the First Half of Pregnancy.

Thyroid peroxidase antibody (TPOAb) positivity can attenuate gestational thyroid responses to human chorionic gonadotropin (hCG) during pregnancy, whereas the effects of thyroglobulin antibodies (TgAb) remain unknown. The aim of our study was to explore the thyroid response to hCG in women with thyrotropin (TSH) levels within the method-specific reference range under different conditions of thyroid autoimmunity. The study screened 822 women at 7-20 weeks of gestation using the pregnancy-specific reference range for TSH. Serum TSH, free thyroxine (fT4), TPOAb, TgAb, and β-hCG levels were measured using electrochemiluminescence immunoassays. The enrolled pregnant women were subdivided into four subgroups based on TPOAb/TgAb positivity: co-positive for TPOAb and TgAb (group 1), isolated TPOAb positive (group 2), isolated TgAb positive (group 3), and co-negative for TPOAb and TgAb (group 4). TSH was negatively associated with hCG in all four groups (p < 0.05). fT4 was positively associated with hCG in groups 3 and 4 (p < 0.01) but not in groups 1 (p = 0.096) and 2 (p = 0.758). Group 2 was further stratified into tertiles according to TPOAb concentrations. No negative TSH/hCG association was observed in the middle- and upper-tertile groups when TPOAb were ≥53 IU/mL (p > 0.05). There was no positive fT4/hCG association in any of the three subgroups (p > 0.05). Similarly, group 3 was further stratified into tertiles according to TgAb levels. TSH was negatively associated with hCG in the lower and middle tertiles (p < 0.01), but the association was not found in the upper tertile when TgAb was ≥356 IU/mL (p = 0.191). fT4 was positively associated with hCG in the lower tertile (p = 0.027) but not in subgroups when TgAb was ≥219 IU/mL (p > 0.05). When TSH was within the pregnancy-specific reference range, high concentrations of TPOAb and TgAb attenuated the fT4 stimulation and suppression of TSH by hCG. The results imply that TgAb, in addition to TPOAb, could also interfere with thyroidal responses to hCG during the first half of pregnancy.

Thyroid abnormalities among Down syndrome children from Kerala, India

Down syndrome (DS), caused by trisomy of human chromosome 21, is one of the most common chromosomal abnormalities in live born infants with a prevalence rate of 1 in 700 live births. Individuals with DS usually have comorbid conditions such as thyroid dysfunction, growth retardation, diabetes mellitus and obesity. The most frequent among these are the thyroid abnormalities which range from subclinical to overt hypothyroidism, and rarely hyperthyroidism.1-3 Individuals with DS are more susceptible to thyroid disorders compared to the general population. Primary hypothyroidism, referred to as elevated TSH, is the most common thyroid abnormality in DS; secondary hypothyroidism indicated by normal/reduced TSH is extremely rare. The prevalence of hypothyroidism varies between 3-54% in adults with DS.4 The aim of this study was to examine the incidence of thyroid abnormalities among children with DS registered in a tertiary referral center for neurodevelopmental disorders and non-communicable neurological disorders in Kerala, a south Indian state. 100 children with DS in the age range of 4 months-15 years, registered at Institute for Communicative and Cognitive Neurosciences (ICCONS), Shoranur, Kerala during the period of 2012-2016, were recruited for the study. The mean age of the participants (57 males, 43 females) was 5.4±3.8 years. The diagnosis of DS was confirmed by karyotyping. All the participants were drug-naive at the time of blood collection. 500 µl of serum samples was used for thyroid function test (TFT) which measured the levels of TSH, triiodothyronine (T3) and thyroxine (T4) by chemiluminescence immunoassay (CLIA). The reference range for TSH, T3 and T4 were as follows, TSH: 0.4-4mIU/ml, T3: 70-170ng/dl, T4: 4.5-12.5mg/dl.

Reference TSH levels in Spanish pregnant women. Is it possible to unify criteria?

IntroductionSpecific TSH and free thyroxine ranges are needed to adequately assess maternal thyroid function during pregnancy. AimThe aim of this review is to review studies reporting data on references TSH and free thyroxine levels in Spanish women during the first trimester of pregnancy. Material and methodsLiterature search and selection of studies providing reference TSH ranges in the first trimester of pregnancy. ResultsThe TSH cut-off point to define hypothyroidism (P97.5) was different depending on the immunoassay used. Gestational age, thyroid autoimmunity, and maternal iodide nutritional status can determine the variability seen in the results. ConclusionsDifferences found in the studies do not allow for establishing a unified TSH reference range. However, results suggest that the TSH upper reference limit is close to 4μU/mL. Reference TSH ranges specific for each population and immunoassay during pregnancy should be defined.

Subclinical Hypothyroidism: is it Really Subclinical with Aging?

No recent study has focused on clinical features of subclinical hypothyroidism (SCH), especially in older patients. TSH measurement has remarkably evolved these last 20 years and thus reconsideration is needed. In our prospective multicenter study (2012-2014) including 807 subjects aged <60 years (<60y) and 531 subjects ≥60 years (≥60y), we have monitored 11 hypothyroidism-related clinical signs (hCS) together with TSH, FT4, FT3 and anti-thyroperoxidase antibodies values. hCS expression has been compared in patients with SCH vs euthyroidism in each age group. The number of hCS above 60y of age were found to be more elevated in the euthyroid population (1.9 vs 1.6, p<0.01) than in the SCH population (2.3 vs 2.6, p=0.41) while increase in hCS is limited to SCH subjects in the <60y group (p<0.01). The percentage of subjects with at least 3 signs increased with SCH in the <60y group (42.6% vs 25.0%, p<0.01) but not ≥60y (34.4% vs 33.9%, p=0.96). In older individuals, only three hCS could be related to both SCH and a decreased T3/T4-ratio (0.26 vs 0.27, p<0.01), suggesting either a reduced activity of TSH, or an adaptive response with aging. While hCS are clearly associated with SCH in patients <60y, they are not so informative in older subjects. TSH measurements carried out on the basis of hCS need to be interpreted with caution in aged patients. A reassessment of the TSH reference range in older patients is clearly needed and should be associated to more appropriate monitoring of thyroid dysfunction

Valores de referencia de TSH en población gestante española. ¿Podemos unificar criterios?

IntroductionSpecific TSH and free thyroxine ranges are needed to adequately assess maternal thyroid function during pregnancy. AimThe aim of this review is to review studies reporting data on references TSH and free thyroxine levels in Spanish women during the first trimester of pregnancy. Material and methodsLiterature search and selection of studies providing reference TSH ranges in the first trimester of pregnancy. ResultsThe TSH cut-off point to define hypothyroidism (P97.5) was different depending on the immunoassay used. Gestational age, thyroid autoimmunity, and maternal iodide nutritional status can determine the variability seen in the results. ConclusionsDifferences found in the studies do not allow for establishing a unified TSH reference range. However, results suggest that the TSH upper reference limit is close to 4μU/mL. Reference TSH ranges specific for each population and immunoassay during pregnancy should be defined.

Recent recommendations from ATA guidelines to define the upper reference range for serum TSH in the first trimester match reference ranges for pregnant women in Rio de Janeiro.

American Thyroid Association (ATA)'s new guidelines recommend use of population-based trimester-specific reference range (RR) for thyrotropin (TSH) in pregnancy. The aim of this study was to determine first trimester TSH RR for a population of pregnant women in Rio de Janeiro State. Two hundred and seventy pregnant women without thyroid illness, defined by National Academy of Clinical Biochemistry, and normal iodine status were included in this sectional study. This reference group (RG) had normal median urinary iodine concentration (UIC = 219 μg/L) and negative anti-thyroperoxidase antibodies (TPOAb). Twin pregnancy, trophoblastic disease and use of drugs or supplements that influence thyroid function were excluded. In a second step, we defined a more selective reference group (SRG, n = 170) by excluding patients with thyroiditis pattern on thyroid ultrasound and positive anti-thyroglobulin antibodies. This group also had normal median UIC. At a final step, a more selective reference group (MSRG, n = 130) was defined by excluding any pregnant women with UIC < 150 μg/L. In the RG, median, 2.5th and 97.5th percentiles of TSH were 1.3, 0.1, and 4.4 mIU/L, respectively. The mean age was 270 ± 5.0 and the mean body mass index was 25.6 ± 5.2 kg/m2. In the SRG and MSRG, 2.5th and 975th percentiles were 0.06 and 4.0 (SRG) and 0.1 and 3.6 mIU/L (MSRG), respectively. In the population studied,TSH upper limit in the first trimester of pregnancy was above 2.5 mIU/L. The value of 3.6 mIU/L, found when iodine deficiency and thyroiditis (defined by antibodies and ultrasound characteristics) were excluded, matches recent ATA guidelines.

Where does subclinical hypothyroidism start? Implications for the definition of the upper reference limit for thyroid stimulating hormone

The upper limit of the TSH reference range is currently under discussion. In its recent guidelines, the National Academy of Clinical Biochemistry (NACB) recommended the use of approximately 2.5 mIU/L, rather than approximately 4 mIU/L, due to the fact that reference populations, on which the definition of the reference range is based, contain persons undergoing an initial phase of autoimmune thyroid disease. This will skew the upper reference limit of TSH. Ultrasonography, in addition to measurement of thyroid autoantibodies, should be used to exclude these persons. The present study investigates whether the NACB recommendation also applies for a region of mild iodine deficiency. According to NACB criteria, a reference population (713 persons) was defined out of a total study population of 1442. The TSH reference range was calculated in this reference group and in further subgroups by percentiles. The results were compared with the total study population and the NACB recommendation. All assays used were provided by BRAHMS Diagnostica AG, Hennigsdorf, Germany. As expected, all median TSH values, excluding the median of the group with a hypoechogenic thyroid were close to 1.2 mIU/L. The 97.5th percentile in the reference population was 3.35 mIU/L. However, there was no difference compared to the total study population. The upper reference limit for TSH based on a reference population according to NACB criteria came down to 3.35 mIU/L, but not to approximately 2.5 mIU/L. Interestingly, there is no difference compared to the total study population.

Marked increases in levothyroxine prescribing and laboratory testing following a reduction in the upper end of the TSH reference range

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Effect of Thyroid Function Variations Within the Laboratory Reference Range on Health Status, Mood, and Cognition in Levothyroxine-Treated Subjects.

There has been recent debate within the thyroid field regarding whether current upper limits of the thyrotropin (TSH) reference range should be lowered. This debate can be better informed by investigation of whether variations in thyroid function within the reference range have clinical effects. One important target organ for thyroid hormone is the brain, but little is known about variations in neurocognitive measures within the reference range for thyroid function. This was a cross-sectional study of 132 otherwise healthy hypothyroid subjects receiving chronic replacement therapy with levothyroxine (LT4) who had TSH levels across the full span of the laboratory reference range (0.34-5.6 mU/L). Subjects underwent detailed tests of health status, mood, and cognitive function, with an emphasis on memory and executive functions. Subjects with low-normal (≤2.5 mU/L) and high-normal (>2.5 mU/L) TSH levels did not differ on most tests of health status, mood, or cognitive function, and there were no correlations between TSH, free T4, or free T3 levels and most outcomes. There was, however, a suggestion that thyroid function affected performance on the Iowa Gambling Task, which mimics real life decision-making. Subjects with low-normal TSH levels made more advantageous decisions than those with high-normal TSH levels. Variations in thyroid function within the laboratory reference range do not appear to have clinically relevant effects on health status, mood, or memory in LT4 treated subjects. However, decision making, which encompasses many executive functions, may be affected. Unless further studies strengthen this finding, these data do not support narrowing the TSH reference range.

Trimester specific ranges for thyroid hormones in normal pregnancy

Maternal and fetal thyroid profiles differ throughout gestation. Due to many physiological changes during pregnancy, interpretation of thyroid function tests needs trimester specific reference intervals. American Thyroid Association strongly recommends to refer to population defined trimester-specific reference ranges with optimal iodine intake Though some studies have reported this reference range in South and a few in North, there has been no data from Central India yet. Aims and Objectives: To establish normative range of TSH in each trimester of pregnancy, To establish normative range of f T3 and f T4 in each trimester of pregnancy and to know the prevalence of subclinical hypothyroidism in normal pregnancies. Materials and Methods: in all 177 normal singleton pregnant women were screened and out of them 150 enrolled in the study(50 in each trimester). Their TSH, fT3, fT4 and urinary iodine was estimated. Observations and Results: The reference range of thyroid hormones for 1st trimester found in the present study are as follows: TSH: 0.24-4.17 (uIU/ml), fT3: 0.29-3 .1 (ng/100 ml), fT4: 01-2.2 (ng/100 ml). For 2 nd trimester: the reference range for TSH , fT3 and fT4 are 0.78-5.67 (uIU/ml) , 0.27-3.34(ng/100 ml) ,and 0.45-2.24 (ng/100 ml) respectively. For 3 rd trimester, the reference range for TSH , fT3 and fT4 are 0.47-5.78 (uIU/ml), 0.24-3.61(ng/100 ml) and 0.47-5.1 (ng/100 ml). Prevalence of subclinical hypothyroidism was found to be 4% in first and second trimesters and 8% in third trimester. No case was seen with clinical hypothyroidism. Conclusion: This study states the range of thyroid hormones in all 3 trimesters of pregnancy. The prevalence of subclinical hypothyroidism was found out to be 4% in first and second trimesters each and 8% in third trimester.

The limit of reference range of TSH: long-term discussion and possibilities of modern diagnostic.

The review considers problem of upper limit of reference interval of TSH that is discussed predominantly by endocrinologists out of laboratory community. The common values of 0.4-4.0 mE/l combine as a matter of fact two ranges: zone of practically full wellbeing (0.4-2.5 mE/l) and zone of latent pathology and/or high possibility of development of clinically significant hypothyroidism (2.5-4.0 mE/l). At one time, the proposal to diminish upper limit of reference interval provoked many discussions and on balance received no approval. However, no unanimity concerning this issue is still to be achieved. The article discusses data forcing medical specialists to be wary of values of TSH in the range of 2.5-4.0 mE/l. At the same time, the question is putted concerning suitability of using population reference intervals in the case of both of TSH and number of other indices of laboratory diagnostic.

Association Between Cardiovascular Risk Factors and Serum Thyrotropin Concentration Among Healthy Chinese Subjects and Subjects with Unsuspected Subclinical Hypothyroidism.

Even within the reference range, thyrotropin (TSH) levels were found to be positively associated with the risk of cardiovascular disease (CVD). However, the underlying mechanism of TSH remains ambiguous. This study investigated the association of TSH with cardiovascular risk factors among healthy Chinese subjects and subjects with unsuspected subclinical hypothyroidism (SCH). A total of 741 subjects were included in this cross-sectional study. The subjects were grouped into four, including tertile groups for the TSH reference range and an SCH group based on the TSH level. All the participants underwent physical examination and fasting blood analyses to determine the levels of TSH, free thyroxine, free triiodothyronine, plasma glucose, triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A1, apolipoprotein B (ApoB), lipoprotein(a), homocysteine (Hcy), and high sensitivity C-reactive protein (hs-CRP). The TSH subgroups exhibited a significant increasing trend in terms of LDL-C, ApoB, and Hcy levels (p = 0.01, p < 0.01, and p = 0.01, respectively), whereas the HDL-C levels exhibited a decreasing trend (p = 0.03). After adjusting for gender, age, and smoking status, the TSH levels were found to be positively correlated with body mass index, waist circumference, diastolic blood pressure (DBP), and TG, TC, LDL-C, ApoB, Hcy, and hs-CRP levels (p < 0.05 for all), but negatively correlated with the HDL-C levels (p < 0.01). Multiple linear regression analysis showed that the TSH levels were independently positively associated with the female gender (β = 0.21, p < 0.01), DBP (β = 0.14, β = 0.01), and Hcy levels (β = 0.10, p = 0.01), and negatively associated with the HDL-C (β = -0.11, p = 0.01) and FT4 levels (β = -0.15, p < 0.01). The TSH levels were independently associated with several cardiovascular risk factors in an apparently healthy Chinese population, and thus may increase the risk of CVD.

Thyroid screening in pregnancy - a compulsory preventive activity

ABSTRACT Obiectives: To assess the prevalence of thyroid dysfunction in a group of pregnant women, originating from Dobrogea region of southeastern Romania, considered to be an area without iodine deficiency, including the Black Sea area. Materials and methods: We enrolled 324 pregnant women in different trimesters of pregnancy. Each case was reviewed by a detailed madical history, clinical examination and by serum dosage of thyroid hormones: TSH, FT4, and the antithyroidperoxidase. They were evaluated by comparison with trimester -specific reference range for TSH recommended by American Thyroid Association, then the results were compared with those obtained using the manufacturers reference range. Abortion rate was also analysed. Results: The prevalence of thyroid dysfunction was different in all the 3 trimesters: subclinical hypothyroidism being the most frequently approx. 24% of all cases; 7% of pregnant women had overt hypothyroidism. Incidence of thyrotoxicosis in entire study cases was approx. 5.5%. The most frecvent thyroid autoimune disorders were Hashimoto thyroiditis: 42 % - I trimester, 26,6% in II trimester and about 12,5 % in III-trimester; Graves disease have an incidence of only 0,9 % (n=3).The difference between reference methods eluded a lower number of cases using manufactures reference range for TSH (P&lt; 0,001), but higher for recommended trimester - specific TSH value, confirming the undervalueted hypothesis. The risk of misclassifying the hypothyroidism is between 3 %-8 %. Conclusion: Necessity for thyroid hormone dosage periodic/trimesterly/ in pregnancy is a preventive measure. The reference values for hormonal dosage requires trimester-specific assessment. The possibility of hormonal disorders during pregnancy is common. The need for specific therapy at diagnosis depends on the nature of hormonal disorder. Further precautions are needed in pregnant women with known autoimmune thyroid disorder or newly diagnosed

Thyroid function parameters in normal pregnancies in an iodine sufficient population

BackgroundThe aim of this retrospective observational study was to describe thyroid function parameters (fT3, fT4 and TSH) in the course of normal pregnancies. MethodsData were obtained between 2006 and 2007 at the University Hospital in Innsbruck, Austria. The starting point was the identification of women who had had a normal birth as recorded in the birth registry of Tyrol. Thyroid function parameters were determined using methods implemented at the Department of Nuclear Medicine in Innsbruck. ResultsThe fT3 and fT4 values were normally distributed. Grouping the results by trimester revealed the following values: 4.93±0.59, 4.54±0.48, and 4.27±0.45pmol/l for fT3; and 15.23±2.43, 13.79±1.99, and 13.32±0.2.01pmol/l for fT4, respectively. The values corresponding to the 10th-percentile were 3.9pmol/l for fT3 and 11.3pmol/l for fT4, respectively. TSH values showed a typical left skewed distribution, thus the mean values were calculated after log transformation of the data. The corresponding mean trimestral values for TSH were 1.46±1.29, 1.68±1.23, and 1.70±2.22mIU/l, respectively. ConclusionIn an iodine sufficient population, thyroid function parameters in normal pregnancies do not differ from those in non-pregnant women. Our previously defined reference range for TSH of 0.3 to 3.5mIU/l is equally valid for normal pregnancies. General significanceThe question of cognition and IQ development of children has been proposed to be associated with thyroid function. The addition of data regarding normal thyroid function during pregnancy will contribute to this research.

Reference ranges for TSH and thyroid hormones

Though TSH remains the most commonly used endocrine test in clinical practice, the issue of an appropriate TSH, and to a lesser extent, free T4 and free T3 reference ranges is still under debate. First of all the distribution of TSH reference range is not normal, with median values (also depending on population iodine intake) usually between 1-1.5 mU/L [1-3]. On the other hand, upper TSH reference limit is (assay-dependent) usually around 4.2-4.5 mU/L. There is also an argument that significant number of patients (up to 30%) with TSH above 3.0 mU/L have an occult autoimmune thyroid disease [4]. On the other hand the upper normal TSH reference range in elderly subjects (i.e. 70 plus years) may extend up to around 6.0 mU/L, with relative small changes in free hormones. This phenomenon also applies to elderly patients, where autoimmune thyroid disease had been ruled out [1,2]. Furthermore, there is little evidence of any adverse effects of autoimmune thyroid disease in the elderly in the absence of an overt hypothyroidism. Indeed, Wang et al [5] surprisingly demonstrated decreased frailty in elderly subjects with raised titres of thyroid autoantibodies. It is also well known that in the setting of subclinical hypothyroidism, concentrations of free T4 start to decline below 10 pmol/L only with TSH above 6-7 mU/L in elderly subjects, though a decline in free T4 is more pronounced in the young (particularly in those aged 20-29 years), where free T4 starts to decline for TSH concentrations above 4.5 mU/l [6]. Another issue pertains to the risk of cardiovascular disease in subjects with subclinical hypothyroidism. There are data from post-menopausal women enrolled into the Women Health Initiative study, where an increase in the risk of myocardial infarction was demonstrated only for TSH concentrations above 7.0 mU/L [7]. A separate issue, extensively discussed elsewhere [8], pertains to alterations of TSH and free thyroid hormones during pregnancy. In particular there is decrease in TSH in the first trimester followed by a gradual return to pre-pregnancy values. In contrast, there is an increase in free T4 in the first trimester, while in the third trimester free T4 concentrations are usually at the lower end of the standard (i.e. pre-pregnancy) reference range, or even just below the lower reference limit. Hence, there is an urgent need (postulated in the Endocrine Society Guidelines [8]) to create separate reference ranges for TSH and free thyroid hormones during pregnancy, possible with reference to each trimester. There are also recent data from China [9], where the authors demonstrated that the above-mentioned first trimester-related alterations in TSH and free T4, become only really visible after about 5th-6th week of gestation. The authors of this study suggest that standard reference ranges for TSH and free T4 can be applied up to this point of gestation.

Feto-maternal Outcome Using New Screening Criteria of Serum TSH for Diagnosing Hypothyroidism in Pregnancy.

Evidence suggests that by using the classical non pregnant reference range for serum TSH (STSH), one might miss hypothyroidism in pregnancy. Therefore, upper normal cut off value of S TSH should be taken as <2.5 mIU/L in the first trimester and <3mIU/L in the second and third trimester. However, two Indian studies have reported higher trimester specific reference ranges in the Indian pregnant women. To assess the maternal and fetal outcomes using new screening criteria with upper S TSH cut off as >3mIU/L, for diagnosing hypothyroidism in pregnancy. This study was a cross sectional study, carried out in the Department of Obstetrics and Gynaecology of a tertiary care hospital, in collaboration with the Department of Endocrinology. Pregnant women with ≤ 20 weeks gestation, attending antenatal OPD from December 2010 to January 2012 were included in the study. On the basis of S TSH level, women were divided into Study Group with S TSH level between 3.1 to 6.2 mIU/L, (new range to be studied) and an equal number of age and parity matched Control Group with S TSH levels between 0.4 to 3 mIU/L. The maternal and fetal outcomes were compared between study and control groups. During the study period, a total of 66 women had S TSH between 3.1-6.2 mIU/L. Maternal and fetal outcomes in both the groups were comparable. There was no difference in the mode of delivery between study and control groups. The lower S TSH cut off recommended for diagnosing hypothyroidism in pregnancy may not be applicable to pregnant Indian women.

171-POS

Objectives Subclinical thyroid disorders are common in pregnant women, which are associated with adverse pregnancy outcomes. Physiological changes in pregnancy and the lack of pregnancy-specific reference ranges pose great challenge for the managements of subclinical thyroid disorders in pregnancy. We aimed to establish trimester-specific thyroid hormone reference intervals throughout pregnancy in southern Chinese population. Methods we measured the serum thyroid hormone (TSH, FT4, TPO-AB) using Abbott electrochemiluminescence immunoassay in 5589 pregnant women during 2012–2013. Patients with known thyroid disorders, autoimmune disease, recurrent miscarriage, hyperemesis gravidarum and pre-eclampsia were excluded. Trimester-specific reference ranges (2.5th, 97.5th centiles) were calculated. Results TSH median T1: 1.19 ± 0.99 mIU/L ( N = 3532), T2: 1.40 ± 1.02 mIU/L ( N = 1623), T3: 1.48 ± 1.30 mIU/L ( N = 434). FT4 median T1: 15.7 ± 3.12 pmol/L ( N = 3532), T2: 13.81 ± 2.99 pmol/L ( N = 1623), T3: 12.92 ± 2.98 pmol/L ( N = 434). TSH reference range T1: 0.01–3.55 mIU/L, T2: 0.01–4.13 mIU/L, T3: 0–4.67 mIU/L. FT4 reference range T1: 12–21.44pmol/L, T2: 10.01–19.36 pmol/L, T3: 9.29–20.31 pmol/L. TSH slightly increased throughout gestation. FT4 decreased throughout gestation. Conclusions We established pregnancy-specific thyroid function reference intervals of southern Chinese population, which is beneficial in clinical practice. Disclosures L. Liu: None. X. Zhang: None. J. Yang: None. X. Qian: None. Z. Zheng: None. X. Tang: None. H. Liu: None.

Reference range for thyrotropin. Post hoc assessment.

Setting the reference range for thyrotropin (TSH) remains a matter of ongoing controversy. We used an indirect method to determine the TSH reference range post hoc in a large sample. A total of 399 well characterised subjects showing no evidence of thyroid dysfunction were selected for definition of the TSH reference limits according to the method of Katayev et al.. To this end, the cumulative frequency was plotted against the individual logarithmic TSH values. Reference limits were calculated by extrapolating the middle linear part of the regression line to obtain the cut-offs for the 95% confidence interval. We also examined biological variation in a sample of 65 subjects with repeat measurements to establish reference change values (RCVs). Based on these, the reference interval obtained by the novel technique was in close agreement with the conventionally established limits, but differed significantly from earlier recommendations. Following unverified recommendations could result in a portion of patients with subclinical thyroid dysfunctions being missed, an important consideration in a setting with a high prevalence of thyroid autonomy. Indirect post hoc verification of reference intervals from a large retrospective sample is a modern approach that gives plausible results. The method seems particularly useful to assess the adequacy and performance of reference limits reported or established by others in a particular setting. The present data should encourage re-evaluation of reference systems on a broader scale.

Dynamic changes of thyroid function during gestation: A self-sequential longitudinal study

Objective To evaluate the trimester specific reference ranges and dynamic changes of thyroid functional indicators during gestation of healthy pregnant women.Methods According to the selection criteria,139 cases were selected as the normal pregnant population to establish a self-sequential longitudinal reference range.We collected samples eight times in every case throughout the gestation(including the 8th,12th,16th,20th,28th,36th week of prenatal,the 3rd and the 6th month postpartum) and detected the indicators of thyroid funciton.Meanwhile,301 healthy non-pregnant women of childbearing age were selected as the control group.Results The median of TSH was lowest in the first trimester,and then was increased in the second and third trimesters.The reference ranges of TSH were 0.20-4.01 mIU/L,0.43-3.97 mIU/L,and 0.57-3.96 mIU/L in the above trimesters.The free thyroxine (FT4) level from the 12th week of gestation to the 6th month of postpartum was gradually decreased and was lower than the non-pregnant level.The total thyroxine (TT4) was significantly increased at the 12th week of gestation and thereafter it was stable and returned to normal after childbirth.The free triiodothyronine(FT3) was gradually declined from the 12th week to the 28th week and returned to normal postpartum.Total triiodothyronine(TT3) was significantly increased at the 12th week and thereafter was stable,and returned to normal after childbirth.There was a significant negative correlation between TSH and FT4 in the first trimester(P＜0.01).There was no correlation between TSH and TT4 during the whole gestation.There were positive correlations between FT4 and TT4,FT3 and TT3 since the 12th week of gestation (P ＜ 0.01).Conclusions The gestational specific reference range of TSH based on the selfsequential longitudinal study was narrow,however,the upper limit was still higher than that recommended in foreign guidelines. Key words: Self-sequential ; Longitudinal ; Reference intervals; Thyroid function ; Pregnancy

New understanding of TSH reference range during the first trimester of pregnancy

Guidelines of the American Thyroid Association (ATA) proposed two diagnostic criteria for subclinical hypothyroidism during the first trimester of pregnancy:criterion 1 was based on the pregnancy-specific TSH reference range and criterion 2 on serum TSH＞2.5 mIU/L level with normal serum FT4.According to the results of the Subclinical hypothyroidism during early pregnancy study,author proposed that criterion 2 is not appropriate for Chinese pregnant women because the TSH concentration has become significantly higher in whole Chinese population.By using criterion 2,the prevalence may be as high as 27.8％,which may result in over-diagnosis and over treatment. Key words: Subclinical hypothyroidism; Pregnancy; Thyrotropin