Thyroid-stimulating Hormone Reference Research Articles

Towards Personalized TSH Reference Ranges: A Genetic and Population-Based Approach in Three Independent Cohorts.

Background: Serum thyroid-stimulating hormone (TSH) measurement is the diagnostic cornerstone for primary thyroid dysfunction. There is high inter-individual but limited intra-individual variation in TSH concentrations, largely due to genetic factors. The currently used wide population-based reference intervals may lead to inappropriate management decisions. Methods: A polygenic score (PGS) including 59 genetic variants was used to calculate genetically determined TSH reference ranges in a thyroid disease-free cohort (n = 6,834). Its effect on reclassification of diagnoses was investigated when compared to using population-based reference ranges. Next, results were validated in a second independent population-based thyroid disease-free cohort (n = 3,800). Potential clinical implications were assessed in a third independent population-based cohort including individuals without thyroid disease (n = 26,321) as well as individuals on levothyroxine (LT4) treatment (n = 1,132). Results: PGS was a much stronger predictor of individual TSH concentrations than FT4 (total variance in TSH concentrations explained 9.2-11.1% vs. 2.4-2.7%, respectively) or any other nongenetic factor (total variance in TSH concentrations explained 0.2-1.8%). Genetically determined TSH reference ranges differed significantly between PGS quartiles in all cohorts, while the differences in FT4 concentrations were absent or only minor. Up to 24.7-30.1% of individuals, previously classified as having subclinical hypo- and hyperthyroidism when using population-based TSH reference ranges, were reclassified as euthyroid when genetically determined TSH reference ranges were applied. Individuals in the higher PGS quartiles had a higher probability of being prescribed LT4 treatment compared to individuals from the lower PGS quartiles (3.3% in Q1 vs. 5.2% in Q4, Pfor trend =1.7 × 10-8). Conclusions: Individual genetic profiles have the potential to personalize TSH reference ranges, with large effects on reclassification of diagnosis and LT4 prescriptions. As the currently used PGS can only predict approximately 10% of inter-individual variation in TSH concentrations, it should be further improved when more genetic variants determining TSH concentrations are identified in future studies.

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

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

Cardiovascular and bone health outcomes in older people with subclinical hypothyroidism treated with levothyroxine: a systematic review and meta-analysis

BackgroundThyroid dysfunction is common in older people, with females at higher risk. Evidence suggests that thyroid-stimulating hormone (TSH) levels naturally increase with age. However, as uniform serum TSH reference ranges are applied across the adult lifespan, subclinical hypothyroidism (SCH) diagnosis is more likely in older people, with some individuals also being commenced treatment with levothyroxine (LT4). It is unclear whether LT4 treatment in older people with SCH is associated with adverse cardiovascular or bone health outcomes.MethodsA systematic review and meta-analysis were performed to synthesise previous studies evaluating cardiovascular and bone health outcomes in older people with SCH, comparing LT4 treatment with no treatment. PubMed, Embase, Cochrane Library, MEDLINE, and Web of Science databases were searched from inception until March 13, 2023, and studies that evaluated cardiovascular and bone health events in people with SCH over 50 years old were selected.ResultsSix articles that recruited 3853 participants were found, ranging from 185 to 1642 participants, with the proportion of females ranging from 45 to 80%. The paucity of data resulted in analysis for those aged over 65 years only. Additionally, a study with 12,212 participants aged 18 years and older was identified; however, only data relevant to patients aged 65 years and older were considered for inclusion in the systematic review. Of these 7 studies, 4 assessed cardiovascular outcomes, 1 assessed bone health outcomes, and 2 assessed both. A meta-analysis of cardiovascular outcomes revealed a pooled hazard ratio of 0.89 (95% CI 0.71–1.12), indicating no significant difference in cardiovascular risk between older individuals with SCH treated with LT4 compared to those without treatment. Due to overlapping sub-studies, meta-analysis for bone health outcomes was not possible.ConclusionsThis systematic review and meta-analysis found no significant association between LT4 use and cardiovascular and bone health outcomes in SCH participants over 65 years.Systematic review registrationPROSPERO CRD42022308006

Reference intervals for thyroid function from the fifth to seventh day of life in twin-pregnancy preterm neonates: an 8-year retrospective study.

The immature and developing hypothalamic-pituitary-thyroid axis leads to different levels of thyroid function in twin neonates, including free thyroxine (FT4), free triiodothyronine (FT3), and thyroid stimulating hormone (TSH) levels. No reference intervals for twins have been established until now. To compensate for this lack, we collected data and established this standard across different gestational ages (GAs) and sexes. A total of 273 pairs of neonates admitted to the NICU in Southeast China from 2015 to 2022 were included. Each pair was divided into Neonate A (relatively heavy birth weight (BW)) and Neonate B (relatively light BW). Their thyroid functions were analyzed to establish reference intervals and comparisons were made stratified by GA and sex. The FT3, FT4, and TSH reference intervals in twin neonates with a GA of 26-36 weeks were as follows: Neonate A and B: 3.59 ± 0.99 and 3.57 ± 1.00 pmol/L; Neonate A and B: 17.03 ± 5.16 and 16.77 ± 5.29 pmol/L; and Neonate A and B: 4.097 ± 3.688 and 4.674 ± 4.850 mlU/L, respectively. There were significant differences between serum FT3 and FT4 reference intervals and GA (p < 0.05). The serum FT3 and FT4 reference intervals for male neonates were lower than those for female neonates in the 29-32-week group (p < 0.05). This was the first study, to our knowledge, to establish reference intervals for thyroid function in twin neonates from the fifth to seventh day of life, which will be beneficial for the diagnosis and management of congenital hypothyroidism.

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

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

Deciphering the roles of triiodothyronine (T3) and thyroid-stimulating hormone (TSH) on cardiac electrical remodeling in clinical and experimental hypothyroidism.

Hypothyroidism is the most frequent endocrine pathology. Although clinical or overt hypothyroidism has been traditionally associated to low T3 / T4 and high thyrotropin (TSH) circulating levels, other forms exist such as subclinical hypothyroidism, characterized by normal blood T3 / T4 and high TSH. In its different forms is estimated to affect approximately 10% of the population, especially women, in a 5:1 ratio with respect to men. Among its consequences are alterations in cardiac electrical activity, especially in the repolarization phase, which is accompanied by an increased susceptibility to cardiac arrhythmias. Although these alterations have traditionally been attributed to thyroid hormone deficiency, recent studies, both clinical trials and experimental models, demonstrate a fundamental role of TSH in cardiac electrical remodeling. Thus, both metabolic thyroid hormones and TSH regulate cardiac ion channel expression in many and varied ways. This means that the different combinations of hormones that predominate in different types of hypothyroidism (overt, subclinic, primary, central) can generate different forms of cardiac electrical remodeling. These new findings are raising the relevant question of whether serum TSH reference ranges should be redefined.

A-338 TSH Reference Range in the First Trimester in a Iodine Sufficient Population of Pregnant Women Attended by the Public Health System in Curitiba South of Brazil

Abstract Background Thyroid diseases are common among women of reproductive age, and the serum concentration of thyroid-stimulating hormone (TSH) is the most used index to assess thyroid function during pregnancy. Changes in thyroid function during pregnancy can have a clinical impact on a woman's health and pregnancy outcome, as well as interfere with fetal health and child development. An adequate thyroid function is essential for normal intrauterine development. When comparing the levels of TSH between pregnant and non-pregnant women, TSH levels are lower in pregnancy, mainly in the first trimester, with gradual increase during pregnancy. Although some guidelines propose fixed TSH reference values in pregnancy according to the gestational trimester, the main recommendation is to carry out a study of their local population due to the significant variation in TSH reference range levels in different populations and different assays. Therefore, it is necessary to determine values of a reference interval for TSH for the local population of pregnant women. This study aims to determine the normal reference range of TSH in the first trimester of gestation in the public health system pregnant women from Curitiba. Methods This is an ongoing prospective cohort study, with the population sample from the pregnant women using the public health system, with age &amp;gt;18 years old in Curitiba, South of Brazil. 383 pregnant women were invited to participate. After evaluate the exclusion criteria (gestational age more than 13 weeks, twin pregnancy, thyroid disease, iodine ingestion, identification of the samples in the laboratory), 225 pregnant women had the TSH measured by chemiluminescent immunoassay on Atellica IM Analyzer (Siemens Healthineers), as well as the TPO-ab presence, FreeT4 and Total T4. The 2.5, 50 end 97,5 TSH percentiles were estimated for the normal pregnant population. Results The mean gestational age was 8,6 weeks (standard deviation 2.33). From 225 pregnant women, 22 (9.8%) had TPO-ab positive. The 2.5 and 97.5 percentiles of TSH were 0.12 and 5.28 μIU/mL after using de exclusion criteria. The populational iodine status was sufficient. In the TPO-ab positive population was found a higher level of TSH. The proportion of TPO-ab positive was significantly higher in the population with TSH &amp;gt;2.5 μIU/mL. Conclusions This preliminary data shows the TSH reference range with levels higher than other regions, reinforcing to do not use fixed values of TSH from other populations to evaluate the thyroid function in pregnancy. Comparing to the laboratory reference for non-pregnant adult (0.48 to 5.60 μIU/mL), the recommended reduction of 0.5 μIU/mL on upper limit and 0.4 μIU/mL on the lower limit found similar values to our findings.

Corrigendum: Abstract and Text Correction. Thyroid Stimulating Hormone Reference Range and Prevalence of Thyroid Dysfunction in the Korean Population: Korea National Health and Nutrition Examination Survey 2013 to 2015.

Corrigendum: Abstract and Text Correction. Thyroid Stimulating Hormone Reference Range and Prevalence of Thyroid Dysfunction in the Korean Population: Korea National Health and Nutrition Examination Survey 2013 to 2015.

Generation of de novo reference values for the thyroid hormones TT4, fT4 and TSH in healthy pet rabbits (Oryctolagus cuniculus) and healthy pet guinea pigs (Cavia porcellus) in conjunction with a TRH-stimulation test

In rabbits and guinea pigs, total thyroxine (TT4) and free thyroxine (fT4) reference values have been previously published. However, most studies have been performed on laboratory animals with small sample sizes. A reference value for thyroid-stimulating hormone (TSH) measurement has not yet been established for either species. With the increasing popularity of pet guinea pigs and rabbits in veterinary practice, established reference values are needed to make a diagnosis and promptly initiate appropriate treatment. Plasma samples from a healthy and defined animal population of 41 pet rabbits (n = 41 TT4, fT4, TSH) and 73 pet guinea pigs (n = 73 TT4 and fT4; n = 51 TSH) were evaluated using chemiluminescence assay (CLIA; for TT4, fT4) and enzyme-linked immunosorbent assay (ELISA; for TSH) to establish reference values. A thyrotropin teleasing hormone (TRH)-stimulation test (n = 4; for each species) was conducted to validate the TSH ELISA test kits. Range, mean, median, standard deviation, interquartile range, 95% reference interval, and 90% confidence intervals for lower and upper reference limits of TT4, fT4, and TSH in healthy pet guinea pigs and healthy pet rabbits were assessed. In addition, the influence of age, sex, and housing on TT4, fT4, and TSH levels was investigated. In this study, TSH reference values were established in pet rabbits and guinea pigs for the first time. Reference values for both TT4 and fT4 were also established de novo for both species. Only with evidence- and population-based reference values can thyroid diseases be precisely and correctly diagnosed to prevent inadequate treatment.

Impact of Thyroid Function on the Prevalence and Mortality of Metabolic Dysfunction-Associated Fatty Liver Disease.

Thyroid function variation within the thyroxine reference range has negative metabolic effects. Metabolic dysfunction-associated fatty liver disease (MAFLD) is a recently proposed definition. We aim to explore the effects of thyroid function status on prevalence and mortality of MAFLD. Data of 10 666 participants from the Third National Health and Nutrition Examination Survey (NHANES III) were used. MAFLD was diagnosed based on the new definition. Thyroid function variation within the thyroxine reference range was defined based on thyroid-stimulating hormone (TSH) levels: subclinical hyperthyroidism, <0.39 mIU/L; strict-normal thyroid function, 0.39-2.5 mIU/L; and low thyroid function, >2.5 mIU/L, which comprised low-normal thyroid function (2.5-4.5 mIU/L) and subclinical hypothyroidism (> 4.5 mIU/L). Logistic and Cox regression were used in multivariate analysis. Low thyroid function is independently associated with MAFLD (odds ratio: 1.27). Compared with strict-normal thyroid function, subclinical hypothyroidism was significantly associated with increased risk for all-cause and cardiovascular mortality in the total population (hazard ratio [HR] for all-cause: 1.23; cardiovascular: 1.65) and MAFLD population (HR for all-cause: 1.32; cardiovascular: 1.99); meanwhile, in the low-normal thyroid function group, an increasing trend in mortality risk was observed. Furthermore, low thyroid function also showed significant negative impact on mortality in the total and MAFLD population. Among thyroid function spectrum, mild subclinical hypothyroidism showed the highest HRs on mortality. Low thyroid function is independent risk factor of MAFLD and is associated with increased risk for all-cause and cardiovascular mortality in the MAFLD population. Reevaluation of TSH reference range should be considered.

Age-specific serum thyrotropin reference range for the diagnosis of subclinical hypothyroidism and its association with lipid profiles in the elderly population

The overdiagnosis of subclinical hypothyroidism (SCH) in the elderly has driven researchers to establish age-specific thyroid stimulating hormone (TSH) intervals to precisely evaluate the prevalence of SCH. Moreover, abnormal lipid profiles, an insidious manifestation of SCH, show various impacts on different age groups. This study aimed to establish an age-specific TSH reference range to clarify the spectrum of SCH in the elderly. The prevalence of dyslipidemia and the age-specific association between TSH and lipid profiles were analyzed to elucidate the relationship between SCH and dyslipidemia. This cross-sectional study enrolled 2460 participants aged ≥ 65 years via cluster sampling. All participants received physical, laboratory tests and thyroid ultrasound examination and completed the questionnaire. The chi-square test was used to analyze variations of dyslipidemia prevalence among different groups. The Cochran-Armitage trend test was applied for testing the linear trends of age-specific prevalence of dyslipidemia among different TSH intervals in each age group. After adjusting for confounding factors, the age-specific association between TSH and lipid profiles was identified using multi-variate linear regression analysis. The TSH reference ranges in the 65–70 age group, 71–80 age group and > 80 age group were 0.65–5.51 mIU/L, 0.85–5.89 mIU/L and 0.78–6.70 mIU/L, respectively. Using these age-specific reference ranges, the prevalence of SCH in the whole population was 3.74%, which was significantly lower than the prevalence based on the laboratory reference range (10.28%). In the 65–70 age group, only the prevalence of high total cholesterol (TC) increased significantly with the age-specific TSH intervals, and TSH was positively associated with TC and low-density lipoprotein cholesterol (LDL-C). In the 71–80 and > 80 age groups, the prevalence of high TC, high triglycerides (TGs), and high LDL-C increased significantly with elevated TSH reference ranges. The levels of TC, TGs, and LDL-C were also positively associated with TSH level in 71–80 age group. However, such an association disappeared in > 80 age group. An age-specific reference range for TSH can effectively prevent the overdiagnosis of SCH in the elderly. Aging could somewhat attenuate the impact of TSH on lipid profiles.

Regional Differences in Thyroid Function Parameters: A Comparison of European Cohort Studies

The aim of the project was to investigate regional differences in thyroid stimulating hormone (TSH), and free thyroxine (fT4) concentrations and iodine status in comparable German and European cohort studies. Sex- and age-stratified TSH, fT4, and urine iodine concentrations of thyroid-healthy participants (age group 45-75 years) of the HNR (Heinz Nixdorf Recall) Study in the Ruhr region of Germany, the southern German KORA (Cooperative Health Research in the Augsburg Region) and northeastern German SHIP (Study of Health in Pomerania) studies, as well as the Norwegian HUNT (Nord-Trøndelag Health) study (age group 40-79 years), the English EPIC (European Prospective Investigation of Cancer)-Norfolk study, and the Dutch Rotterdam study were compared. The TSH reference range for the HNR study population was calculated and compared to the KORA and SHIP studies. Regional differences showed a stronger influence on TSH and fT4 concentrations than sex and age of the subjects in the 45- to 75-year age group. The estimated difference in medians, as measured by the HNR study, was lowest in the SHIP study, -0.47 (95% CI: -0.53; -0.41) for men and -0.41 (-0.53; -0.41) for women. The Rotterdam study had the highest difference in medians for both men and women (men: 0.56 with 0.44; 0.68 and women: 0.62 with 0.46; 0.78). The lowest median TSH concentrations, across all age categories considered, were seen in the German cohorts. Comparison of thyroid function parameters and iodine in elderly subjects between six comparable cohort studies from Germany and Europe showed a significant influence of region, which exceeded the sex and age dependence of the parameters.

Adult and neonate TSH blood spot reference intervals.

Background: Neonatal congenital hypothyroidism screening is performed by measuring thyroid-stimulating hormone (TSH) in a dried blood spot (DBS) sample, whereas acquired hypothyroidism uses serum TSH. There is no established DBS TSH reference interval, but knowing this is useful, as some patients cannot tolerate venepuncture, so DBS collection is seen as an acceptable alternative. The aim of this study was to establish DBS TSH reference intervals in adults and neonates (day 5-8), and determine the relationship between serum and DBS TSH.Methods: Euthyroid adults, not on thyroid medication and with a normal haematocrit, were selected. If they had a paired lithium heparin sample, DBS were prepared by spotting 50µL of whole blood onto filter paper. Dried blood spot TSH was measured using the PerkinElmer Neonatal hTSH kit on the GSP instrument and serum using the Abbott Architect assay. The relationship between DBS and serum TSH was analysed using Passing-Bablok regression and the adult DBS TSH reference interval calculated using transformed data. The neonatal reference interval was calculated from screening results using the non-parametric method.Results: Overall, 109 adult samples were included in the study (61 female). The Passing-Bablok regression was: DBS TSH = 0.68 × serum TSH + 0.07, and reference interval was 0.49-3.07 mU/L. The neonatal DBS reference interval was 0.40-4.10 mU/L from 8351 results.Conclusion: This study derived adult and neonate TSH DBS reference intervals using the GSP analyser and established the relationship between serum and DBS TSH. Knowing this information will allow for improved interpretation of DBS TSH results.

Reference Intervals for Thyrotropin Hormone in the General Andean Population of Quito-Ecuador Using Electrochemiluminescence Assay.

Thyroid function is one of the most current procedures in the evaluation of endocrine function performed in daily practice; the reference intervals for thyrotropin (TSH) depend on the assay technology and the instruments in each laboratory. The main objective of this study is to determine the thyrotropin reference values in patients considered as euthyroid, living in the Andean region, at 2850 meters above sea level (Quito, Ecuador). A cross-sectional, analytical, epidemiological study was conducted using a sample of 595 healthy adult volunteer donors from the Military Hospital Blood Bank in Quito-Ecuador. Serum samples were analyzed for thyrotropin levels using electrochemiluminescence. The reference values were calculated using recommendations from the CLSI C28A3 guide. The mean age of the overall sample was 35.7 (7.2) years, 50.9% (n = 303) were women. TSH recovered in the total sample showed a median of 2.64 mIU/L (2.5th-97.5th percentiles: 0.91-8.35 mIU/L); after removing outliers the reference values for the studied population were 0.87 to 5.21 mIU/L, without differences by sex. General laboratory practice should improve harmonization of TSH assays. This is a must in daily clinical practice, since it would allow us to share real reference intervals in an established population and may be related to the presence or absence of thyroid pathology.

Preterm to term infant postmenstrual age reference intervals for thyroid-stimulating hormone and free thyroxine.

Infants born preterm are affected by a hypothalamic-pituitary-thyroid axis that is immature and still developing as they progress closer to corrected term gestation. Multiple risk factors place preterm infants at risk for a hypothyroid state. However, there is variability in thyroid-stimulating hormone cutoff values and limited data on free thyroxine reference intervals to guide clinicians. 1584 thyroid-stimulating hormone and 1576 free thyroxine laboratory samples that were originally collected to screen hospitalized infants for delayed-onset of hypothyroidism were retrospectively evaluated from a group of 1087 infants who ranged in postmenstrual age from 25 to 43 weeks gestation at the time of laboratory sample collection. Median thyroid hormone values and reference intervals were established using R and the mixtools package. Thyroid-stimulating hormone reference intervals remained similar across gestational ages from 0.340-9.681 µIU/mL in 25-27 6/7-week infants to 1.090-7.627 µIU/mL in 40-43-weeks infants. For the same age groups, free thyroxine reference intervals increased from 0.42-0.91 ng/dL to 0.87-1.32 ng/dL. The reference intervals identified suggest that infants <31 weeks gestation have a higher thyroid-stimulating hormone and lower free thyroxine level at baseline than previously anticipated. The increasing free thyroxine values in preterm to term infants indicate a maturing hypothalamic-pituitary-thyroid axis. Clinicians need thyroid hormone reference intervals that also vary by postmenstrual age to aid the evaluation of sick preterm infants who are at risk of a delayed hypothyroidism diagnosis that can be missed on the initial newborn screen. This study provides one of the largest samples of thyroid-stimulating hormone and free thyroxine data to establish reference intervals in preterm infants. Clinicians may utilize the identified postmenstrual age-based reference intervals to inform follow-up thyroid testing in preterm infants at several weeks postnatal age.

The role of serum thyroid stimulating hormone reference interval in the diagnosis of subclinical hypothyroidism and its influencing factors

亚临床甲状腺功能减退症（甲减）是最常见的甲状腺功能异常，血清促甲状腺激素（TSH）是诊断亚临床甲减的关键指标。TSH参考范围不统一是既往亚临床甲减患病率差异较大的主要原因。目前推荐采用美国国家临床生物化学学会（NACB）标准选择参考人群，用经对数转换后的2.5%~97.5%可信区间确定TSH参考范围。但是，我们还应充分考虑个体内和个体间因素对TSH参考范围的影响，在试剂盒参考范围的基础上，结合上述因素，分析患者血清TSH升高的原因，才能对亚临床甲减做出合理的诊断和干预。.

Age-specific thyrotropin references decrease over-diagnosis of hypothyroidism in elderly patients in iodine-excessive areas.

Acute or chronic exposure to excess iodine has detrimental effects on thyroid physiology; therefore, this study aimed to determine the prevalence of overt hypothyroidism (OH) and subclinical hypothyroidism (SCH) in an elderly population residing in geographical areas with chronic exposure to excess iodine intake and to analyse contributing risk factors. This cross-sectional study was conducted from 2016 to 2017 in areas of Jiangsu Province that have documented chronic exposure to high iodine intake. We enroled 2559 adult participants using a multistage, stratified sampling method. Urinary iodine concentration (UIC), serum thyroid-stimulating hormone (TSH) level and other relevant parameters were measured. Demographic information was recorded using a standardized questionnaire. The age-specific TSH references were determined by the National Academy of Clinical Biochemistry guidelines. Univariate and multivariate logistic regression analyses were performed to identify risk factors for hypothyroidism in the study population. The median UIC of participants was 307.3 µg/L (interquartile range: 200.7, 469.8 μg/L). The prevalence of OH in subjects ≥70 years using laboratory reference ranges was 2.37%; however, it decreased to 1.78% with the use of an age-specific reference range. Similarly, the prevalence of SCH also declined drastically from 29.59% to 2.96% with the application of an age-specific reference range. In both univariate and multivariate models, advanced age, female gender and high UIC were identified as risk factors for hypothyroidism. Usage of age-specific TSH reference ranges led to a significantly lower prevalence of OH and SCH in the study population, thus preventing unnecessary over-diagnosis and over-treatment.

Optimal Serum Thyroid-Stimulating Hormone Level for Patients With Papillary Thyroid Carcinoma After Lobectomy

Background: The optimal serum thyroid-stimulating hormone (TSH) level for post-lobectomy papillary thyroid carcinoma (PTC) patients is unclear. The objective of this study was to examine the association of TSH and recurrence in post-lobectomy patients. Methods: Patients who underwent lobectomy for PTC in a single tertiary hospital from January 2000 to December 2014 were enrolled. The mean TSH score of a patient was calculated based on each serum TSH value during follow-up. The TSH value of each follow-up visit was scored as 0-20 with an interval of 0.5 mU/L, and the mean TSH score (MTS) was calculated as the average of all available scores for a patient. The reference range of serum TSH was 0.5-4.0 mU/L (MTS 0-7). Univariate and multivariable analyses were performed with Cox proportional hazards models. Restricted cubic spline (RCS) functions were used to model relationships between MTS and recurrence-free survival (RFS). Results: A total of 2297 patients (median age, 42 years; 1750 (76.2%) female) were analyzed. MTS below (≤0.5), in the lower half (0.5-3), in the upper half (3-7) and above (>7) the reference range were observed in 415 (18.1%), 1376 (59.9%), 409 (17.8%), and 97 (4.2%) patients, respectively. According to the Cox model and RCS, no association was observed between MTS and RFS (adjusted P=0.5071, adjusted P for nonlinear=0.5182). The only RFS difference observed in the stratified univariate analysis was between patients with MTS in the lower half (n=793) and above the reference range (n=54) in the intermediate- to high-risk group (10-year RFS by Kaplan-Meier 82.1% vs 70.5%, log rank p=0.023). Conclusions: Mean serum TSH levels are not associated with recurrence. A normal TSH reference range is recommended for post-lobectomy PTC patients. Funding Information: The study was funded by the CAMS Innovation Fund for Medical Sciences (CIFMS) (Grant no.2016-I2m-1-002) and Beijing Hope Run Special Fund of Cancer Foundation of China (Grant no.LC2018A26) Declaration of Interests: The authors have no conflicts of interest to disclose. Ethics Approval Statement: The study was approved by the Ethics Committee of the Cancer Hospital, Chinese Academy of Medical Sciences. Informed consent was obtained at the time of surgery with surgical consent for general use of clinical information for future studies.

Trimester-Specific Thyrotropin Hormone Reference Levels in Mosul City, Iraq

Thyroid disorders during pregnancy is widespread and it is linked with adverse obstetric outcomes. Serum thyroid – stimulating hormone ( TSH ), also known as thyrotropin hormone is optimal indicator for monitoring and evaluating thyroid function. There are significant changes in thyroid physiology during gestation. Thus different TSH levels are recorded in pregnant women in different countries, Therefore. the aim of current study : To determine trimester (Tri) specific levels of TSH in the apparently healthy pregnant women in Mosul city. A cross – sectional study was conducted at Hospitals, Primary Health Centers and Outpatient clinics in Mosul city and collected from December 2020 to April 2021. Total enrolled pregnant women were 200 of age 18 – 32 years, 80 of them were excluded from study for meeting one or more of exclusion criteria . The remaining of 120 women were included in study, 40 women were assigned to each Tri. Thyrotropin and anti – thyroid peroxidase were measured for participants. The study results showed TSH levels increased over the Tri with very significantly higher TSH levels in the third in compared with first Tri. Accordingly the reference levels of TSH 0.33-2.79 mIU/L, 0.43-3.88 mIU/L, 0.57-3.39 mIU/L for the first, second and third Tri respectively. Our conclusion that the upper limit of TSH reference ranges for pregnant women in the first and second Tri was closer to that suggested by the American Thyroid Association( ATA) guidelines 2011 and some other countries.

Factors influencing the reference interval of thyroid-stimulating hormone in healthy adults: A systematic review and meta-analysis.

BackgroundMany studies have reported that the thyroid‐stimulating hormone (TSH) reference interval is susceptible to external factors, such as age, sex, race, region and iodine intake. However, no meta‐analysis has comprehensively explored the effect of these factors on the TSH reference interval.MethodsArticles published from January 1960 to January 2020 were searched in PubMed, Embase, Cochrane, Scopus, Medline English databases and CNKI, WanFang and CQVIP Chinese databases. In total, 19 studies were ultimately included. All data were analysed using Review Manager 5.3, STATA 16.0 software, GraphPad Prism 8.0 and Microsoft Excel 2010 to draw the TSH concentration curve.ResultsThe TSH reference interval was significantly influenced by sex and age. The mean of TSH concentration in females was 0.27 mIU/L higher than that in males. Reference interval of TSH is divided into 20–59 years old and >60 years old age groups in males, and 20–39 years old and >40 years old age groups in females. Regardless of sex, TSH concentrations all increase with age. In iodine‐deficient areas, TSH reference intervals were generally lower than those in iodine‐sufficient or iodine‐excessive areas. The TSH reference interval in Asia and North American countries was generally higher than that in most European countries. In the subgroup analyses of sample size, region and assay methods and manufacturers, the between‐group differences were significant.ConclusionThe TSH reference interval was significantly influenced by sex, age, iodine intake, sample size, region, and assay methods and manufacturers, but other factors should not be ignored. Therefore, it is necessary for each laboratory to validate an appropriate TSH reference interval based on local conditions.