Endogenous and exogenous interferences in thyroid function immunoassays

Laboratory diagnosis of endocrine diseases has undergone many important changes over the past decades, despite the progress of thyroid function immunoassays technologies interferences cannot be completely excluded. These interferences can affect measurement of analyte which leads to misinterpretation and subsequent wrong clinical decisions, the probability of which is about 1%. However, the scale of the problem may be greater due to the lack of awareness to the problem among doctors and the lack of laboratory screening for interfering factors. These factors can be both endogenous and exogenous, bind both to antibodies to the analyte and to the reagent in the test system. The specificity of the immunoassay depends not only on the binding properties of antibodies, the activity of reagent, but also on the composition of the test system and the format of the methodology (non-competitive two-site or “sandwich” and competitive assays). This review provides a description of the main interferences that can affect the measurement of thyroid hormones, in particular thyroid stimulating hormone, free thyroxine and triiodothyronine, calcitonin, and demonstrates clinical cases reported in the literature over the past few years.

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Establishment of Early Pregnancy Related Thyroid Hormone Models and Reference Intervals for Pregnant Women in China Based on Real World Data

Hormone and Metabolic Research ◽

10.1055/a-1402-0290 ◽

2021 ◽

Vol 53 (04) ◽

pp. 272-279

Author(s):

Chaochao Ma ◽

Xiaoqi Li ◽

Lixin Liu ◽

Xinqi Cheng ◽

Fang Xue ◽

...

Keyword(s):

Thyroid Hormone ◽

Thyroid Hormones ◽

Pregnant Women ◽

Early Pregnancy ◽

Gestational Age ◽

Dynamic Change ◽

Reference Intervals ◽

Thyroid Stimulating Hormone ◽

Free Thyroxine ◽

Stimulating Hormone

AbstractThyroid hormone reference intervals are crucial for diagnosing and monitoring thyroid dysfunction during early pregnancy, and the dynamic change trend of thyroid hormones during pregnancy can assist clinicians to assess the thyroid function of pregnant women. This study aims to establish early pregnancy related thyroid hormones models and reference intervals for pregnant women. We established two derived databases: derived database* and derived database#. Reference individuals in database* were used to establish gestational age-specific reference intervals for thyroid hormones and early pregnancy related thyroid hormones models for pregnant women. Individuals in database# were apparently healthy non-pregnant women. The thyroid hormones levels of individuals in database# were compared with that of individuals in database* using nonparametric methods and the comparative confidence interval method. The differences in thyroid stimulating hormone and free thyroxine between early pregnant and non-pregnant women were statistically significant (p<0.0001). The reference intervals of thyroid stimulating hormone, free thyroxine and free triiodothyronine for early pregnant women were 0.052–3.393 μIU/ml, 1.01–1.54 ng/dl, and 2.51–3.66 pg/ml, respectively. Results concerning thyroid stimulating hormone and free thyroxine reference intervals of early pregnancy are comparable with those from other studies using the same detection platform. Early pregnancy related thyroid hormones models showed various change patterns with gestational age for thyroid hormones. Early pregnancy related thyroid hormones models and reference intervals for pregnant women were established, so as to provide accurate and reliable reference basis for the diagnosing and monitoring of maternal thyroid disfunction in early pregnancy.

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Reference Intervals of Thyroid Hormones and Correlation of BMI with Thyroid Function in Healthy Zhuang Ethnic Pregnant Women

BioMed Research International ◽

10.1155/2018/2032413 ◽

2018 ◽

Vol 2018 ◽

pp. 1-8 ◽

Cited By ~ 1

Author(s):

Yonghong Sheng ◽

Dongping Huang ◽

Shun Liu ◽

Xuefeng Guo ◽

Jiehua Chen ◽

...

Keyword(s):

Thyroid Hormones ◽

Pregnant Women ◽

Thyroid Function ◽

Reference Intervals ◽

Thyroid Stimulating Hormone ◽

Specific Reference ◽

American Thyroid Association ◽

Reference Ranges ◽

Free Triiodothyronine ◽

Cross Sectional

Ethnic differences in the level of thyroid hormones exist among individuals. The American Thyroid Association (ATA) recommends that an institution or region should establish a specific thyroid hormone reference value for each stage of pregnancy. To date, a limited number of studies have reported the level of thyroid hormones in Chinese minorities, and the exact relationship between BMI and thyroid function in pregnant women is ill. This study was performed to establish trimester-specific reference ranges of thyroid hormones in Zhuang ethnic pregnant women and explore the role of body mass index (BMI) on thyroid function. A total of 3324 Zhuang ethnic health pregnant women were recruited in this Zhuang population-based retrospective cross-sectional study. The values of thyroid stimulating hormone (TSH), free thyroxine (FT4), and free triiodothyronine (FT3) were determined by automatic chemiluminescence immunoassay analyzer. Multivariate linear regression and binary logistic regression were constructed to evaluate the influence of BMI on the thyroid function. The established reference intervals for the serum thyroid hormones in three trimesters were as follows: TSH, 0.02–3.28, 0.03–3.22, and 0.08-3.71 mIU/L; FT4, 10.57–19.76, 10.05–19.23, and 8.96–17.75 pmol/L; FT3, 3.51–5.64, 3.42–5.42, and 2.93–5.03 pmol/L. These values were markedly lower than those provided by the manufacturers for nonpregnant adults which can potentially result in 6.10% to 19.73% misclassification in Zhuang pregnant women. Moreover, BMI was positively correlated with isolated hypothyroxinemia (OR=1.081, 95% CI=1.007–1.161), while the correlation between the BMI and subclinical hypothyroidism was not statistically significant (OR=0.991, 95% CI=0.917–1.072). This is the first study focusing on the reference ranges of thyroid hormones in Guangxi Zhuang ethnic pregnant women, which will improve the care of them in the diagnosis and treatment. We also found that high BMI was positively associated with the risk of isolated hypothyroxinemia.

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Iodide Metabolism and Effects

Diagnosing and Managing Hashimoto’s Disease - Advances in Medical Diagnosis, Treatment, and Care ◽

10.4018/978-1-5225-9655-4.ch004 ◽

2020 ◽

pp. 25-33

Keyword(s):

Thyroid Hormone ◽

Thyroid Gland ◽

Thyroid Hormones ◽

Dietary Supplement ◽

Thyroid Function ◽

Thyroid Stimulating Hormone ◽

Hormone Synthesis ◽

Serum Tsh ◽

Tsh Stimulation ◽

Sensitive Marker

Iodine (I2) is essential in the synthesis of thyroid hormones T4 and T3 and functioning of the thyroid gland. Both T3 and T4 are metabolically active, but T3 is four times more potent than T4. Our body contains 20-30 mg of I2, which is mainly stored in the thyroid gland. Iodine is naturally present in some foods, added to others, and available as a dietary supplement. Serum thyroid stimulating hormone (TSH) level is a sensitive marker of thyroid function. Serum TSH is increased in hypothyroidism as in Hashimoto's thyroiditis. In addition to regulation of thyroid function, TSH promotes thyroid growth. If thyroid hormone synthesis is chronically impaired, TSH stimulation eventually may lead to the development of a goiter. This chapter explores the iodide metabolism and effects of Hashimoto's disease.

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Subclinical hypothyroidism

Oxford Textbook of Endocrinology and Diabetes ◽

10.1093/med/9780199235292.003.3252 ◽

2011 ◽

pp. 543-547

Author(s):

Jayne A. Franklyn

Keyword(s):

Thyroid Function ◽

Subclinical Hypothyroidism ◽

Expert Panel ◽

Elevated Serum ◽

Thyroid Stimulating Hormone ◽

Free Thyroxine ◽

Thyroid Function Tests ◽

Free Triiodothyronine ◽

Function Tests ◽

Serum Tsh

Subclinical hypothyroidism is defined biochemically as the association of a raised serum thyroid-stimulating hormone (TSH) concentration with normal circulating concentrations of free thyroxine (T4) and free triiodothyronine (T3). The term subclinical hypothyroidism implies that patients should be asymptomatic, although symptoms are difficult to assess, especially in patients in whom thyroid function tests have been checked because of nonspecific complaints such as tiredness. An expert panel has recently classified individuals with subclinical hypothyroidism into two groups (1): (1) those with mildly elevated serum TSH (typically TSH in the range 4.5–10.0 mU/l) and (2) those with more marked TSH elevation (serum TSH >10.0 mU/l).

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Correlations of Free Thyroid Hormones Measured by Tandem Mass Spectrometry and Immunoassay with Thyroid-Stimulating Hormone across 4 Patient Populations

Clinical Chemistry ◽

10.1373/clinchem.2008.118752 ◽

2009 ◽

Vol 55 (7) ◽

pp. 1380-1388 ◽

Cited By ~ 62

Author(s):

Jacqueline Jonklaas ◽

Natasa Kahric-Janicic ◽

Offie P Soldin ◽

Steven J Soldin

Keyword(s):

Mass Spectrometry ◽

Thyroid Hormone ◽

Tandem Mass Spectrometry ◽

Thyroid Hormones ◽

Thyroid Stimulating Hormone ◽

Free Thyroxine ◽

Tandem Mass ◽

Free Triiodothyronine ◽

Free Thyroid Hormones ◽

Free Thyroid Hormone

Abstract Background: Accurate measurement of free thyroid hormones is important for managing thyroid disorders. Ultrafiltration liquid chromatography tandem mass spectrometry (LC-MS/MS) can reliably measure the concentrations of small molecules, including thyroid hormones. Our study was designed to compare free thyroid hormone measurements performed with immunoassay and LC-MS/MS. Methods: We studied the performance of LC-MS/MS in 4 different populations comprising pediatric patients, euthyroid adults, and healthy nonpregnant and pregnant women. The samples obtained from each population numbered 38, 200, 28, and 128, respectively. Free thyroxine, free triiodothyronine, and thyroid-stimulating hormone (TSH) concentrations were documented. Results: LC-MS/MS measurement of free thyroid hormones provided better correlation with log-transformed serum TSH in each population and also the populations combined. The correlations between free thyroxine measured by LC-MS/MS and log TSH in the pediatric outpatients and healthy adults were −0.90 and −0.77, respectively. The correlations for immunoassay were −0.82 and −0.48. The correlations between free triiodothyronine measured by LC-MS/MS and TSH for both pediatric and healthy adult populations were −0.72 and −0.68, respectively. Conclusions: Free thyroid hormone concentrations measured by LC-MS/MS correlate to a greater degree with log TSH values compared to concentrations measured by immunoassay. This correlation was maintained across the patient populations we studied and may reflect the accuracy and specificity of LC-MS/MS. The superior ability of LC-MS/MS to enable documentation of the well-known thyroid hormone–TSH relationship supports the use of this measurement technique in a variety of clinical situations.

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Combined effects of cadmium and decabrominated diphenyl ether on thyroid hormones in rats

Archives of Industrial Hygiene and Toxicology ◽

10.2478/10004-1254-63-2012-2179 ◽

2012 ◽

Vol 63 (3) ◽

pp. 255-262 ◽

Cited By ~ 14

Author(s):

Marijana Ćurčić ◽

Saša Janković ◽

Vesna Jaćević ◽

Sanja Stanković ◽

Slavica Vučinić ◽

...

Keyword(s):

Thyroid Hormone ◽

Thyroid Hormones ◽

Thyroid Function ◽

Wistar Rats ◽

Diphenyl Ether ◽

Thyroid Stimulating Hormone ◽

Combined Effects ◽

Single Substance ◽

Hormone Homeostasis ◽

Stimulating Hormone

The aim of this study was to see how a mixture of cadmium (Cd) and decabrominated diphenyl ether (BDE209) affect thyroid function, namely thyroid-stimulating hormone (TSH), thyroxin (T4), free thyroxin (FT4), triiodothyronin (T3), and free triiodothyronin (FT3) in Wistar rats (eight per group) receiving either a single substance or their combination by gavage for 28 days. Three groups were receiving Cd alone in the doses of 2.5 mg kg-1, 7.5 mg kg-1, or 15 mg kg-1 b. w. a day, three groups were receiving BDE209 in the doses of 1000 mg kg-1, 2000 mg kg-1, or 4000 mg kg-1 b. w. a day, while nine groups were receiving different mixtures of Cd and BDE209 in these doses (3x3 design). The results have indicated that the Cd+BDE209 mixtures more potently disrupt thyroid hormone homeostasis than would be expected from these chemicals alone.

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Understanding the Pathogenesis of Gestational Hypothyroidism

Frontiers in Endocrinology ◽

10.3389/fendo.2021.653407 ◽

2021 ◽

Vol 12 ◽

Author(s):

Oshini Mallawa Kankanamalage ◽

Qiongjie Zhou ◽

Xiaotian Li

Keyword(s):

Thyroid Function ◽

Fetal Loss ◽

Thyroid Stimulating Hormone ◽

Free Thyroxine ◽

Premature Delivery ◽

Overt Hypothyroidism ◽

Thyroglobulin Level ◽

Vulnerable Individual ◽

Levothyroxine Treatment ◽

Free Thyroxine Level

Pregnancy is a complex state with many endocrinological challenges to a woman’s physiology. Gestational Hypothyroidism (GHT) is an emerging condition where insufficiency of the thyroid gland has developed during pregnancy in a previously euthyroid woman. It is different to overt hypothyroidism, where marked elevation of thyroid-stimulating hormone with corresponding reduction in free thyroxine levels, is well known to cause detrimental effects to both the mother and the baby. During the past couple of decades, it has been shown that GHT is associated with multiple adverse maternal and fetal outcomes such as miscarriage, pre-eclampsia, placental abruption, fetal loss, premature delivery, neurocognitive and neurobehavioral development. However, three randomized controlled trials and a prospective cohort study performed within the last decade, show that there is no neurodevelopmental improvement in the offspring of mothers who received levothyroxine treatment for GHT. Thus, the benefit of initiating treatment for GHT is highly debated within the clinical community as there may also be risks associated with over-treatment. In addition, regulatory mechanisms that could possibly lead to GHT during pregnancy are not well elucidated. This review aims to unravel pregnancy induced physiological challenges that could provide basis for the development of GHT. During pregnancy, there is increased renal clearance of iodine leading to low iodine state. Also, an elevated estrogen level leading to an increase in circulating thyroglobulin level and a decrease in free thyroxine level. Moreover, placenta secretes compounds such as human chorionic gonadotropin (hCG), placental growth factor (PIGF) and soluble FMS-like tyrosine kinase-1 (s-Flt1) that could affect the thyroid function. In turn, the passage of thyroid hormones and iodine to the fetus is highly regulated within the placental barrier. Together, these mechanisms are hypothesized to contribute to the development of intolerance of thyroid function leading to GHT in a vulnerable individual.

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Clinical-laboratory and instrument indices of the thyroid gland state after surgical treatment of tumors of the chiasmatic-cellar region

Bulletin of Siberian Medicine ◽

10.20538/1682-0363-2010-4-59-62 ◽

2010 ◽

Vol 9 (4) ◽

pp. 59-62

Author(s):

Ya. A. Kan ◽

M. G. Zhestikova ◽

S. M. Bryzgalina ◽

N. P. Shakhvorost

Keyword(s):

Surgical Treatment ◽

Thyroid Gland ◽

Thyroid Hormones ◽

Operative Treatment ◽

Autoimmune Thyroiditis ◽

Clinical Laboratory ◽

Thyroid Stimulating Hormone ◽

Free Thyroxine ◽

Secondary Hypothyroidism ◽

Cellular Area

Hypopituitarism is often developed in the result of operative treatment of tumours in chiasmal-cellular area. One of frequent indications of hypophysis’ deficit is decreasing of product of thyroid-stimulating hormone (TSH) that leads to deficit of thyroid hormones. Most patients, who had been operated in terms of tumours of chiasmal-cellular area, have normal volume and structure of thyroid gland in the background of decreased level of free thyroxine and absence of increasing of level of TSH on the principle of feedback, it indicates to the secondary character of destruction of thyroid gland. Patients operated in terms of craniopharyngioma and somatoprolactinoma more often have secondary hypothyroidism. A high per cent of fibrotic changes of tissue of thyroid gland in patients operated in terms of prolactinoma is explain by autoimmune thyroiditis in anamnesis.

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Impact of vitamin C on concentrations of thyroid stimulating hormone and thyroid hormones in lambs under short-term acute heat stress

Veterinary Science Development ◽

10.4081/vsd.2015.5965 ◽

2015 ◽

Vol 5 (1) ◽

Cited By ~ 3

Author(s):

Arash Omidi ◽

Masoumeh Kheirie ◽

Hadi Sarir

Keyword(s):

Heat Stress ◽

Vitamin C ◽

Thyroid Hormones ◽

Antioxidant Properties ◽

Thyroid Stimulating Hormone ◽

Free Thyroxine ◽

Control Group ◽

Short Term ◽

Acute Heat Stress ◽

Humidity Index

The present study evaluated the effect of vitamin C on alteration in thyroid hormones induced by short-term acute heat stress. Eight male lambs were divided into two groups of 4 animals each. Both groups were placed in an environment with hyper-acute heat stress based on the temperature – humidity index (THI). Groups I and II were injected intramuscularly normal saline and vitamin C (20 mg/kg), respectively, for the first five consecutive days of the experiment. All lambs were fed ad libitum. Blood samples were collected from both groups on days one, two, four, six and eight. Thyroxine and free thyroxine numerically increased (91.03 vs. 70.78 nmol L-1, P=0.080 and 29.8 vs. 24.8 pmol L-1, P=0.080; respectively) in heat stressed lambs supplemented with vitamin C compared to control group. Respiration rates and heart rates were elevated until day five of the experiment and then decreased. Mechanism for increasing the levels of thyroxine and free thyroxine by vitamin C is not well known. However, it may occur in part because of vitamin C antioxidant properties. The present study revealed that vitamin C might ameliorate the adverse effect of heat stress in lambs.

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Thyroid status in patients undergoing maintenance haemodialysis: a South Indian cohort study

International Journal of Advances in Medicine ◽

10.18203/2349-3933.ijam20194187 ◽

2019 ◽

Vol 6 (5) ◽

pp. 1531

Author(s):

Bhaskaran S. ◽

Sakthidasan S. ◽

Lalitha Shanmugam ◽

Suthakaran C.

Keyword(s):

Thyroid Hormones ◽

Thyroid Function ◽

Thyroid Stimulating Hormone ◽

Thyroid Status ◽

Tertiary Referral Hospital ◽

Free T4 ◽

Cross Sectional ◽

Maintenance Haemodialysis ◽

South Indian ◽

The Status

Background: Hypothyroidism is common throughout the world and the prevalence of hypothyroidism is high in India. Ailment of thyroid function has been documented to occur at a higher rate in patients with chronic kidney disease (CKD), including those undergoing dialysis than in general population.Methods: A prospective cross-sectional observational clinical study in real time was carried out to assess the thyroid status in eighty-nine adult patients undergoing a 4 h three times weekly haemodialysis schedule in a rural tertiary referral hospital in South India. The status of the thyroid was monitored via Free T3 Free T4 and Thyroid Stimulating Hormone levels.Results: Subclinical hypothyroidism was common in patients undergoing haemodialysis. Although there was a negative correlation between the levels of thyroid hormones and other variables, it was clinically insignificant.Conclusions: The present study showed that abnormalities in thyroid function are high in patients undergoing haemodialysis and that there were no clinically significant correlation between the levels of thyroid hormones and clinical or biochemical characteristics.

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