Establishment of a serum thyroid stimulating hormone (TSH) reference interval in healthy adults. The importance of environmental factors, including thyroid antibodies

Author(s):  
Esther Jensen ◽  
Per Hyltoft Petersen ◽  
Ole Blaabjerg ◽  
Pia Skov Hansen ◽  
Thomas H. Brix ◽  
...  

AbstractIt has previously been shown that thyroid antibodies affect thyroid stimulating hormone (TSH) concentrations in men and women and that TSH levels are predictive of future thyroid disease. We investigated the validity of the National Academy of Clinical Biochemistry (NACB) guidelines regarding the TSH reference interval by studying 1512 individuals. Two hundred and fifty had at least one thyroid antibody, 121 were taking medications other than estrogens and occasional analgesics, and 105 reported a family history of thyroid disease. Serum TSH, thyroid peroxidase antibodies (TPOab) and thyroglobulin antibodies (Tgab) were determined on AutoDELFIA and TSHRab by a radioreceptor assay (RRA) from Brahms Diagnostica.For individuals without thyroid antibodies and other risk factors, no effect of age and gender was seen for serum TSH. Neither medication nor the presence of Tgab alone had any influence on serum TSH. TPOab alone or in combination with Tgab were associated with an increased serum TSH level.The ‘cumulative percentage distributions’ of subgroups, as well as the combined population, was ln-Gaussian distributed. The central 95% of the population was within the 95% CI in rankit-plots. Consequently, a common reference interval for serum TSH of 0.58–4.07 mIU/l for all adults between 17 and 66 years of age was established. This reference interval is much higher than expected from the NACB-guidelines.

2009 ◽  
Vol 55 (11) ◽  
pp. 2019-2025 ◽  
Author(s):  
H Alec Ross ◽  
Martin den Heijer ◽  
Ad R M M Hermus ◽  
Fred C G J Sweep

Abstract Background: Examination of the 2-dimensional probability distribution of thyroid-stimulating hormone (TSH) and free thyroxine (FT4) shows that the widths of the TSH and FT4 reference intervals derived from this bivariate distribution are mutually interdependent, an aspect commonly ignored when interpreting thyroid testing results with separate reference intervals for TSH and FT4. We desired to establish and critically evaluate a composite reference interval for TSH and FT4 to allow bivariate classification of biochemical thyroid conditions. Methods: FT4 and TSH results of 871 healthy individuals [361 women and 510 men, 18–40 years old, without history of thyroid-related disease or medication, negative for anti–thyroid peroxidase (anti-TPO) antibody] were transformed to standard normal variables by logarithmic transformation with correction for skewness and subsequent normalization. We established a 95% reference interval of the distance of each FT4/TSH pair of values to the center of the 2-dimensional probability distribution. Results: The bivariate 95% reference interval is enclosed by a circular profile with radius 2.45 SD. By contrast, conventional reference intervals comprise a square with the boundaries of −1.96 and +1.96 SD for both FT4 and TSH that enclose only 90% of all data. Compared with the ±1.96 SD square, the bivariate reference interval classified 4% fewer of 3651 healthy individuals older than 40 years as subclinically hyperthyroid and 14% fewer of 712 anti-TPO–positive healthy individuals as subclinically hypothyroid. Conclusions: Conventional application of separate cutoff values for FT4 and TSH leads to overestimation of the incidence of subclinical thyroid disease. Application of a composite overall reference interval is recommended.


Author(s):  
Ville L. Langén ◽  
Teemu J. Niiranen ◽  
Juhani Mäki ◽  
Jouko Sundvall ◽  
Antti M. Jula

AbstractPrevious studies with mainly selected populations have proposed contradicting reference ranges for thyroid-stimulating hormone (TSH) and have disagreed on how screening, age and gender affect them. This study aimed to determine a TSH reference range on the Abbott Architect ci8200 integrated system in a large, nationwide, stratified random sample. To our knowledge this is the only study apart from the NHANES III that has addressed this issue in a similar nationwide setting. The effects of age, gender, thyroid peroxidase antibody (TPOAb)-positivity and medications on TSH reference range were also assessed.TSH was measured from 6247 participants randomly drawn from the population register to represent the Finnish adult population. TSH reference ranges were established of a thyroid-healthy population and its subpopulations with increasing and cumulative rigour of screening: screening for overt thyroid disease (thyroid-healthy population, n=5709); screening for TPOAb-positivity (risk factor-free subpopulation, n=4586); and screening for use of any medications (reference subpopulation, n=1849).The TSH reference ranges of the thyroid-healthy population, and the risk factor-free and reference subpopulations were 0.4–4.4, 0.4–3.7 and 0.4–3.4 mU/L (2.5th–97.5th percentiles), respectively. Although the differences in TSH between subgroups for age (p=0.002) and gender (p=0.005) reached statistical significance, the TSH distribution curves of the subgroups were practically superimposed.We propose 0.4–3.4 mU/L as a TSH reference range for adults for this platform, which is lower than those presently used in most laboratories. Our findings suggest that intensive screening for thyroid risk factors, especially for TPOAb-positivity, decreases the TSH upper reference limit.


1997 ◽  
Vol 92 (6) ◽  
pp. 529-541 ◽  
Author(s):  
Richard S. McIntosh ◽  
M. Suhail Asghar ◽  
Anthony P. Weetman

1. The analysis of the antibody response in autoimmune thyroid disease has followed several historical trends. It was the investigation of thyroid-reactive antibody that allowed the initial characterization of the three principle thyroid autoantigens, thyroglobulin, thyroid peroxidase and the thyroid stimulating hormone receptor. 2. Analysis can be grouped under two broad areas: analysis of the physiological and pathological effects of the antibody, and analysis of the structure of the antibodies themselves. This review will focus on the latter. 3. Within recent years there has been a great increase in knowledge of thyroid-reactive antibody structure, principally through the adoption of phage display combinatorial library methodologies. While this latter technique has established some general principles for antibodies to thyroglobin and especially thyroid peroxidase, there is still a substantial gap in our knowledge of the antibody response to the thyroid stimulating hormone receptor. 4. Thyroid peroxidase antibodies have a relatively restricted V-region usage, and there is a correlation between the V-regions used and the epitope on thyroid peroxidase bound. In particular the Vκ light chain, Vκl(O12), is associated with reactivity to one epitope. 5. The purpose of this review is to bring together the latest results concerning the molecular analysis of the antibody response in autoimmune thyroid disease, to highlight areas of ignorance and conflict, and to discuss the methods adopted to circumvent the problems associated with analysis of the antibody response.


2017 ◽  
Vol 25 (2) ◽  
pp. 270-278
Author(s):  
V. G. Likhvantseva ◽  
M. S. Afanasyev ◽  
E. A. Rudenko ◽  
С. С. Afanasyev ◽  
E. V. Korosteleva ◽  
...  

The influence of the carrier of thyroid autoantibodies (to thyroid-stimulating hormone receptor, to thyroglobulin, to thyroid peroxidase) on the clinical course of endocrine ophthalmopathy (EOP), developed on the background of diffuse toxic goiter (139 patients). We studied the role of carrier of monoantibodies and their combinations. It has been proven a direct link between the presence of the analyzed thyroid autoantibodies and the clinical course of EOP. It is shown that the presence of antibodies to thyroid peroxidase and anti-thyroglobulin antibodies is not a lesser important risk factor for the development of EOP in patients with diffuse toxic goiter than the presence of antibodies to the receptor for thyroid-stimulating hormone, and the multiple carriers is associated with more frequent development of active forms of EOP and higher amplitude of inflammation of the orbit. Thus, serological indices and spectrum of thyroid antibodies revealed the depth of systemic disorders of autoimmunity, associated with an increased risk of the development of local autoimmune inflammation in the orbit and can serve as prognostic risk markers of development of highly active and severe forms of EOP.


Author(s):  
Janeil M. Belle ◽  
Nektarios Vasilottos ◽  
Todd D. Nebesio ◽  
Benjamin C. James

AbstractBackground:Polycystic thyroid disease (PCTD) is a rare condition and has been described in adults in the setting of subclinical and clinical hypothyroidism. We present the first known case of a pediatric patient with diffuse macrocystic degeneration of the thyroid.Clinical presentation:A 6-year-old previously healthy patient was evaluated after presenting with a 16-month history of an enlarging polycystic thyroid and hyperthyroidism. Markers of autoimmune thyroid disease including thyroid stimulating immunoglobulin (TSI), thyroid stimulating hormone (TSH) receptor antibody, thyroid peroxidase antibody and thyroglobulin antibody were negative. No family history of benign or malignant thyroid or cystic disease was present. The patient underwent a total thyroidectomy without perioperative complication. She remains euthyroid with thyroid hormone replacement therapy.Summary:To our knowledge, this is the first report of PCTD in the pediatric population associated with hyperthyroidism without evidence of autoimmune disease. Somatic activating thyrotropin-receptor gene mutations are known to cause non-autoimmune hyperthyroidism in children, however it is unknown if similar mechanisms are responsible for pediatric PCTD.Conclusions:Polycystic thyroid degeneration can occur in children and may result in a hyperthyroid state.


Author(s):  
PK Prakash ◽  
H Bolusani ◽  
A Hameed ◽  
LDKE Premawardhana

Background: Subclinical hypothyroidism (SH) is a marker for overt hypothyroidism and vascular disease. Treatment guidelines are not universally followed. Thyroxine is recommended if serum thyroid-stimulating hormone (TSH) concentration is 10 mU/L or more, or if serum TSH is 5-9.9 mU/L (mild SH) with other risk factors, such as thyroid peroxidase antibodies (TPOAb). Methods: We examined the management of mild SH in a retrospective case note audit of 150 consecutive subjects. Twenty-seven subjects with a serum TSH concentration above 10 mU/L were excluded from analysis. Of the group with mild SH, 27 were also excluded because of previous thyroid disease or amiodarone therapy. Results: The prevalence of previous thyroid disease was similar in subjects with TSH 10 mU/L or more, compared to those with mild SH. Overall, both TPOAb and goitre status were determined in only 39% of subjects with mild SH, but in more by endocrinologists compared with general physicians (63% versus 22% for TPOAb; 47% versus 17% for goitre) ( P = 0.001). Endocrinologists treated a greater number of subjects with mild SH who were eligible for thyroxine therapy compared to nonendocrine colleagues (96% versus 67%) ( P = 0.024). Both groups treated subjects in whom TPOAb status was not determined (endocrinologists 21% versus general physicians 40%) ( P = 0.21). Conclusion: In subjects with mild SH, evaluation is incomplete, a large percentage who were TPOAb positive were on appropriate therapy, thyroxine was prescribed when TPOAb status was unknown and, on the whole, endocrinologists performed better than general physicians.


2020 ◽  
Vol 105 (8) ◽  
pp. 2667-2677 ◽  
Author(s):  
Rima K Dhillon-Smith ◽  
Aurelio Tobias ◽  
Paul P Smith ◽  
Lee J Middleton ◽  
Kirandeep K Sunner ◽  
...  

Abstract Objective To describe the prevalence of and factors associated with different thyroid dysfunction phenotypes in women who are asymptomatic preconception. Design Observational cohort study. Setting A total of 49 hospitals across the United Kingdom between 2011 and 2016. Participants Women aged 16 to 41years with history of miscarriage or subfertility trying for a pregnancy. Methods Prevalences and 95% confidence intervals (CIs) were estimated using the binomial exact method. Multivariate logistic regression analyses were conducted to identify risk factors for thyroid disease. Intervention None. Main Outcome Measure Rates of thyroid dysfunction. Results Thyroid function and thyroid peroxidase antibody (TPOAb) data were available for 19213 and 19237 women, respectively. The prevalence of abnormal thyroid function was 4.8% (95% CI, 4.5-5.1); euthyroidism was defined as levels of thyroid-stimulating hormone (TSH) of 0.44 to 4.50 mIU/L and free thyroxine (fT4) of 10 to 21 pmol/L. Overt hypothyroidism (TSH > 4.50 mIU/L, fT4 < 10 pmol/L) was present in 0.2% of women (95% CI, 0.1-0.3) and overt hyperthyroidism (TSH < 0.44 mIU/L, fT4 > 21 pmol/L) was present in 0.3% (95% CI, 0.2-0.3). The prevalence of subclinical hypothyroidism (SCH) using an upper TSH concentration of 4.50 mIU/L was 2.4% (95% CI, 2.1-2.6). Lowering the upper TSH to 2.50 mIU/L resulted in higher rates of SCH, 19.9% (95% CI, 19.3-20.5). Multiple regression analyses showed increased odds of SCH (TSH > 4.50 mIU/L) with body mass index (BMI) ≥ 35.0 kg/m2 (adjusted odds ratio [aOR] 1.71; 95% CI, 1.13-2.57; P = 0.01) and Asian ethnicity (aOR 1.76; 95% CI, 1.31-2.37; P < 0.001), and increased odds of SCH (TSH ≥ 2.50 mIU/L) with subfertility (aOR 1.16; 95% CI, 1.04-1.29; P = 0.008). TPOAb positivity was prevalent in 9.5% of women (95% CI, 9.1-9.9). Conclusions The prevalence of undiagnosed overt thyroid disease is low. SCH and TPOAb are common, particularly in women with higher BMI or of Asian ethnicity. A TSH cutoff of 2.50 mIU/L to define SCH results in a significant proportion of women potentially requiring levothyroxine treatment.


2013 ◽  
Vol 12 (2) ◽  
pp. 164-171
Author(s):  
Nishat Un Nahar ◽  
Zeba Un Naher ◽  
Md. Ashanul Habib ◽  
Forhadul Hoque Mollah

Introduction: Maternal thyroid dysfunction during pregnancy has been associated with a number of adverse outcomes, like preterm birth, placental abruption, foetal death and impaired neurological development in the child. Simultaneously the presence of antibody to thyroid peroxidase results miscarriage, preterm birth and maternal post partum thyroid disease. Post partum thyroiditis is closely associated with the presence of antibodies to thyroid peroxidase (TPO). Indeed if a pregnant woman is positive for TPO antibodies early in pregnancy, her chances of developing post partum thyroiditis is 30-52%. Objective: To find out the level of TPO-Ab and thyroid status in first trimester of pregnancy. Method: The cross sectional study was designed in Department of Biochemistry, BSMMU, Dhaka. Following inclusion and exclusion criteria 200 sample was selected by purposive and convenient sampling. The study parameters were- thyroid peroxidase antibody (TPO-Ab); serum thyroid stimulating hormone (TSH); serum free thyroxin (FT4). Results: 43 (21.5%) pregnant women of first trimester was found to be TPO-Ab positive, among these 43 subjects 16 (8.0%) had raised TSH i.e. >2.5 mIU/L and 27 had TSH level <2.5 mIU/L. Low serum FT4 was in 9 (4.5%) subjects. The study revealed that, there was a significant positive correlation between positive TPO-Ab (>12 IU/mL) and serum TSH level of study subjects and there was negative correlation between serum TSH (>2.5 mIU/L) and serum FT4 in study subjects. Conclusion: TPO-Ab positivity in first trimester of pregnancy and TPOAb positivity was associated with higher TSH and low FT4 level. Bangladesh Journal of Medical Science Vol. 12 No. 02 April’13 Page 164-170 DOI: http://dx.doi.org/10.3329/bjms.v12i2.14945


Author(s):  
Jing Zhang ◽  
Wei Li ◽  
Qiao-Bin Chen ◽  
Li-Yi Liu ◽  
Wei Zhang ◽  
...  

AbstractThyroid-stimulating hormone (TSH) and free thyroxine (FT4) reference intervals are essential for screening and diagnosing thyroid dysfunction during pregnancy. The aim of this study was to establish method- and trimester-specific TSH and FT4 reference intervals in pregnant Chinese women using the Beckman Coulter UniCel™ DxI 600.A cross-sectional dataset analysis was performed. A total of 3507 participants were recruited, and 2743 were eligible for analysis to set reference intervals. TSH, FT4, and thyroid peroxidase antibody (TPOAb) levels were analyzed with the Beckman Coulter UniCel™ DxI 600 AccessThe calculated reference intervals for the first, second, and third trimesters were TSH: 0.06–3.13, 0.07–4.13 and 0.15–5.02 mIU/L, respectively, and FT4: 8.72–15.22, 7.10–13.55 and 6.16–12.03 pmol/L, respectively.Our reference intervals for TSH and FT4 are distinct from the ranges reported in the DxI 600 instruction manual and previously reported data, confirming the importance of method-specific reference intervals.


2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A848-A848
Author(s):  
Rasha Alradadi ◽  
Erica A Eugster

Abstract Background: The most common cause of acquired primary hypothyroidism is autoimmune thyroiditis which is typically associated with positive anti-thyroid peroxidase and/or anti-thyroglobulin antibodies. However, some children present with primary hypothyroidism and negative antibodies. Whether there are differences between patients with acquired primary hypothyroidism who have positive vs negative anti-thyroid antibodies has not been systematically examined. Aim:To define the characteristics of patients with primary hypothyroidism and negative antibodies. Methods: A retrospective chart review of patients with hypothyroidism seen in the pediatric endocrine clinic at Riley Hospital for Children in Indianapolis, Indiana from August 2016 until December 2019 was performed. Variables examined included age at diagnosis, signs and symptoms at presentation, height, weight, BMI, TSH, FT4, T4, thyroid peroxidase and anti-thyroglobulin antibodies, family history of thyroid disease, physical exam at diagnosis, and associated diseases. Results: Of 173 patients aged 10.6 ± 3.9 years, 128 (74%) had positive antibodies and 44 (26%) had negative antibodies. Of those with positive antibodies, 80 % were female and 20% were male. Of those with negative antibodies, 53% were female and 47% were male. No differences were seen in the incidence of obesity or Down syndrome in patients with positive antibodies compared with those who had negative antibodies. A positive family history of thyroid disease was present in 45% of those with positive antibodies and in 22% of those with negative antibodies, P=0.006 Fifty-eight patients (45%) with positive antibodies reported excessive fatigue and 40 (31%) had a goiter. In contrast, 10 (22.7%) who had negative antibodies reported mild intermittent fatigue, P=0.006 and 7 (15.9 %) had a goiter, P=0.04 The average TSH in the antibody positive group was 129± 230 mcu/ml compared with 48 ± 131 mcu/ml in those with negative antibodies, p=0.04. A trend was also noted for a lower FT4 in those with positive antibodies (0.68±0.37 vs 0.85±0.27, p=0.050) No other differences in baseline characteristics were seen between patients with negative vs positive antibodies. Conclusion: Patients with positive anti-thyroid antibodies had more severe hypothyroidism and were more likely to report extreme fatigue than those with negative antibodies. It is unknown why some children with acquired primary hypothyroidism presumed due to autoimmune thyroid disease have negative antibodies. Long-term follow-up will be needed to determine whether the natural history of thyroid disease in children with primary hypothyroidism is associated with antibody status.


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