Assessment of human thyroid function using radioimmunoassay and enzyme-linked-immuno-sorbent-assay

Abstract Two hundred million people worldwide experience some form of thyroid disorder, with women being especially at risk. However, why human thyroid function varies between populations, individuals and across the lifespan has attracted little research to date. This limits our ability to evaluate the conditions under which patterns of variation in thyroid function are best understood as ‘normal’ or ‘pathological’. In this review, we aim to spark interest in research aimed at understanding the causes of variation in thyroid phenotypes. We start by assessing the biomedical literature on thyroid imbalance to discuss the validity of existing reference intervals for diagnosis and treatment across individuals and populations. We then propose an evolutionary ecological framework for understanding the phylogenetic, genetic, ecological, developmental and physiological causes of normal variation in thyroid function. We build on this approach to suggest testable predictions for how environmental challenges interact with individual circumstances to influence the onset of thyroid disorders. We propose that dietary changes, ecological disruptions of co-evolutionary processes during pregnancy and with pathogens, emerging infections and exacerbated stress responses can contribute to explaining the onset of thyroid diseases. For patients to receive the best personalised care, research into the causes of thyroid variation at multiple levels is needed.

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Interleukin-6 (IL-6) inhibits thyroid function in the presence of soluble IL-6 receptor in cultured human thyroid follicles.

Endocrinology ◽

10.1210/endo.137.11.8895357 ◽

1996 ◽

Vol 137 (11) ◽

pp. 4857-4863 ◽

Cited By ~ 11

Author(s):

K Yamazaki ◽

E Yamada ◽

Y Kanaji ◽

K Shizume ◽

D S Wang ◽

...

Keyword(s):

Thyroid Function ◽

Interleukin 6 ◽

Human Thyroid

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STUDIES ON THE EFFECT OF THYROTROPIN ON HUMAN THYROID FUNCTION*

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jcem-19-1-28 ◽

1959 ◽

Vol 19 (1) ◽

pp. 28-34 ◽

Cited By ~ 17

Author(s):

JERZY EINHORN ◽

LARS-GUNNAR LARSSON

Keyword(s):

Thyroid Function ◽

Human Thyroid

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Asialoagalacto-human chorionic gonadotropin, a carbohydrate-modified variant of human chorionic gonadotropin, antagonizes the stimulatory actions of bovine thyroid-stimulating hormone on thyroid function and HLA-DR expression in human thyroid in vitro and in vivo.

Journal of Clinical Investigation ◽

10.1172/jci115519 ◽

1991 ◽

Vol 88 (6) ◽

pp. 1947-1954 ◽

Cited By ~ 11

Author(s):

R Hoermann ◽

P M Schumm-Draeger ◽

K Rehbach ◽

K Mann

Keyword(s):

Thyroid Function ◽

Chorionic Gonadotropin ◽

Human Chorionic Gonadotropin ◽

Thyroid Stimulating Hormone ◽

Human Thyroid ◽

Hla Dr ◽

Bovine Thyroid ◽

Stimulating Hormone

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THYROID FUNCTION OF RATS WITH EXPERIMENTAL AIT AT AN EARLY PERIOD AFTER THE INJECTION OF BIOPREPARATIONS OF CORD BLOOD

PROBLEMS OF ENDOCRINE PATHOLOGY ◽

10.21856/j-pep.2021.4.14 ◽

2021 ◽

Vol 78 (4) ◽

pp. 104-109

Author(s):

Yuliia Kurylko ◽

Nataliya Malova ◽

Larisa Sirotenko

Keyword(s):

Cord Blood ◽

Thyroid Function ◽

Autoimmune Thyroiditis ◽

Early Period ◽

Male Rats ◽

Human Thyroid ◽

Enzyme Linked Immunosorbent Assay ◽

Actual Problem ◽

Autoimmune Thyroid ◽

Biological Preparation

The development of new methods for the treatment of autoimmune thyroid disease is an actual problem of endocrinology. The aim of research was studying of the cell-free effect biological product of cord blood with immunomodulatory properties "Cryocell-Cryocord " on rats’ thyroid function with AIT simulated at an early period of the study. Simulation of autoimmune thyroiditis was carried out by immunization with a suboperatively isolated human thyroid antigen in combination completing Freund's adjuvant on 30 adult male rats weighing 130 - 150 g. Correction was carried out by parenteral ingection of the "Cryocell-Cryocord". Hormonal research (determination of the content of thyroid hormones and antibodies to thyroglobulin (TG-AT) were effected by using standard test kits for enzyme-linked immunosorbent assay at early stages after exposure (7 days, 1 month). Statistical maintained of the results was carried out using the methods of variation statistics. It was used normal distribution to unpaired Student's test to compare indicators. The difference was considered significant at p<0.05. It has been shown the biological preparation of cord blood "Cryocell - Cryocord" has a positive effect with induced autoimmune thyroiditis. It has been noted the normalizing result of the effected correction on the thyroid function of animals in the early period of the studying. It has been proved after the introduction of the biological preparation "Cryocell - Cryocord" in animals with experimental autoimmune thyroiditis observed the inhibition of the manifestations of autoimmune aggression and the normalization of the functional activity of the thyroid gland. These investigations can be the foundation for the development of a new approach to the treatment of patients.

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Characterization of the human thyroid epigenome

Journal of Endocrinology ◽

10.1530/joe-17-0145 ◽

2017 ◽

Vol 235 (2) ◽

pp. 153-165 ◽

Cited By ~ 5

Author(s):

Celia Siu ◽

Sam Wiseman ◽

Sitanshu Gakkhar ◽

Alireza Heravi-Moussavi ◽

Misha Bilenky ◽

...

Keyword(s):

Thyroid Function ◽

Contextual Information ◽

Human Growth ◽

Normal Function ◽

Human Thyroid ◽

Chromatin States ◽

Normal Human ◽

Human Growth And Development ◽

Gland Function

The thyroid gland, necessary for normal human growth and development, functions as an essential regulator of metabolism by the production and secretion of appropriate levels of thyroid hormone. However, assessment of abnormal thyroid function may be challenging suggesting a more fundamental understanding of normal function is needed. One way to characterize normal gland function is to study the epigenome and resulting transcriptome within its constituent cells. This study generates the first published reference epigenomes for human thyroid from four individuals using ChIP-seq and RNA-seq. We profiled six histone modifications (H3K4me1, H3K4me3, H3K27ac, H3K36me3, H3K9me3, H3K27me3), identified chromatin states using a hidden Markov model, produced a novel quantitative metric for model selection and established epigenomic maps of 19 chromatin states. We found that epigenetic features characterizing promoters and transcription elongation tend to be more consistent than regions characterizing enhancers or Polycomb-repressed regions and that epigenetically active genes consistent across all epigenomes tend to have higher expression than those not marked as epigenetically active in all epigenomes. We also identified a set of 18 genes epigenetically active and consistently expressed in the thyroid that are likely highly relevant to thyroid function. Altogether, these epigenomes represent a powerful resource to develop a deeper understanding of the underlying molecular biology of thyroid function and provide contextual information of thyroid and human epigenomic data for comparison and integration into future studies.

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Environmental chemicals and thyroid function

Acta Endocrinologica ◽

10.1530/eje.1.02128 ◽

2006 ◽

Vol 154 (5) ◽

pp. 599-611 ◽

Cited By ~ 329

Author(s):

Malene Boas ◽

Ulla Feldt-Rasmussen ◽

Niels E Skakkebæk ◽

Katharina M Main

Keyword(s):

Thyroid Function ◽

Flame Retardants ◽

Reproductive Organs ◽

Environmental Chemicals ◽

Human Thyroid ◽

Thyroid Peroxidase ◽

Sodium Iodide Symporter ◽

Pituitary Thyroid Axis ◽

Thyroid Disruption ◽

Peroxidase Enzyme

There is growing evidence that environmental chemicals can disrupt endocrine systems. Most evidence originates from studies on reproductive organs. However, there is also suspicion that thyroid homeostasis may be disrupted. Several groups of chemicals have potential for thyroid disruption. There is substantial evidence that polychlorinated biphenyls, dioxins and furans cause hypothyroidism in exposed animals and that environmentally occurring doses affect human thyroid homeostasis. Similarly, flame retardants reduce peripheral thyroid hormone (TH) levels in rodents, but human studies are scarce. Studies also indicate thyroid-disruptive properties of phthalates, but the effect of certain phthalates seems to be stimulative on TH production, contrary to most other groups of chemicals. Thyroid disruption may be caused by a variety of mechanisms, as different chemicals interfere with the hypothalamic–pituitary–thyroid axis at different levels. Mechanisms of action may involve the sodium–iodide symporter, thyroid peroxidase enzyme, receptors for THs or TSH, transport proteins or cellular uptake mechanisms. The peripheral metabolism of the THs can be affected through effects on iodothyronine deiodinases or hepatic enzymes. Even small changes in thyroid homeostasis may adversely affect human health, and especially fetal neurological development may be vulnerable. It is therefore urgent to clarify whether the animal data showing effects of chemicals on thyroid function can be extended to humans.

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SCREENED: A Multistage Model of Thyroid Gland Function for Screening Endocrine-Disrupting Chemicals in a Biologically Sex-Specific Manner

International Journal of Molecular Sciences ◽

10.3390/ijms21103648 ◽

2020 ◽

Vol 21 (10) ◽

pp. 3648

Author(s):

Lorenzo Moroni ◽

Fulvio Barbaro ◽

Florian Caiment ◽

Orla Coleman ◽

Sabine Costagliola ◽

...

Keyword(s):

Stem Cell ◽

Thyroid Gland ◽

Thyroid Function ◽

In Vitro Assays ◽

Human Thyroid ◽

Adverse Outcome Pathway ◽

Thyroid Cells ◽

Cellular Assays ◽

Specific Manner

Endocrine disruptors (EDs) are chemicals that contribute to health problems by interfering with the physiological production and target effects of hormones, with proven impacts on a number of endocrine systems including the thyroid gland. Exposure to EDs has also been associated with impairment of the reproductive system and incidence in occurrence of obesity, type 2 diabetes, and cardiovascular diseases during ageing. SCREENED aims at developing in vitro assays based on rodent and human thyroid cells organized in three different three-dimensional (3D) constructs. Due to different levels of anatomical complexity, each of these constructs has the potential to increasingly mimic the structure and function of the native thyroid gland, ultimately achieving relevant features of its 3D organization including: (1) a 3D organoid based on stem cell-derived thyrocytes, (2) a 3D organoid based on a decellularized thyroid lobe stromal matrix repopulated with stem cell-derived thyrocytes, and (3) a bioprinted organoid based on stem cell-derived thyrocytes able to mimic the spatial and geometrical features of a native thyroid gland. These 3D constructs will be hosted in a modular microbioreactor equipped with innovative sensing technology and enabling precise control of cell culture conditions. New superparamagnetic biocompatible and biomimetic particles will be used to produce “magnetic cells” to support precise spatiotemporal homing of the cells in the 3D decellularized and bioprinted constructs. Finally, these 3D constructs will be used to screen the effect of EDs on the thyroid function in a unique biological sex-specific manner. Their performance will be assessed individually, in comparison with each other, and against in vivo studies. The resulting 3D assays are expected to yield responses to low doses of different EDs, with sensitivity and specificity higher than that of classical 2D in vitro assays and animal models. Supporting the “Adverse Outcome Pathway” concept, proteogenomic analysis and biological computational modelling of the underlying mode of action of the tested EDs will be pursued to gain a mechanistic understanding of the chain of events from exposure to adverse toxic effects on thyroid function. For future uptake, SCREENED will engage discussion with relevant stakeholder groups, including regulatory bodies and industry, to ensure that the assays will fit with purposes of ED safety assessment. In this project review, we will briefly discuss the current state of the art in cellular assays of EDs and how our project aims at further advancing the field of cellular assays for EDs interfering with the thyroid gland.

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