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Book ; Online: TSH Receptor and Autoimmunity

Akamizu, Takashi / Hoon Chung, Jae / Giuliani, Cesidio / Latif, Rauf / Napolitano, Giorgio / Neumann, Susanne

2019

Keywords	Medicine ; Endocrinology ; thyroid ; TSH receptor ; TSH receptor autoantibodies ; Graves' disease ; Autoimmunity ; small molecules ; TSH ; Animal Models
Size	1 electronic resource (126 pages)
Publisher	Frontiers Media SA
Document type	Book ; Online
Note	English ; Open Access
HBZ-ID	HT021231230
ISBN	9782889458165 ; 2889458164
Database	ZB MED Catalogue: Medicine, Health, Nutrition, Environment, Agriculture

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Article: The Flavonoid Quercetin Induces AP-1 Activation in FRTL-5 Thyroid Cells.

Giuliani, Cesidio

Antioxidants (Basel, Switzerland)

2019 Volume 8, Issue 5

Abstract: Previous studies have shown that quercetin inhibits thyroid function both in vitro and in vivo. An attempt to evaluate the effect of quercetin at the promoter level of the thyroid-specific genes led to the observation that this compound induces the basal ...

Abstract	Previous studies have shown that quercetin inhibits thyroid function both in vitro and in vivo. An attempt to evaluate the effect of quercetin at the promoter level of the thyroid-specific genes led to the observation that this compound induces the basal activity of the reporter vector. Therefore, the action of quercetin has been evaluated on the basal activity of several reporter vectors: The PGL3 basic, promoter and control vectors from Promega, and a pSV-based chloramphenicol acetyltransferase (CAT) reporter vector. In the Fisher Rat Thyroid cell Line FRTL-5 thyroid cells transiently transfected, quercetin 10 μM increased the basal activity of all the reporter vectors evaluated, although the degree of the effect was significantly different among them. The analysis of the difference among the regulatory regions of these vectors identified the activator protein 1 (AP-1) binding site as one of the potential sites involved in the quercetin effect. Electromobility shift assay experiments showed that the treatment with quercetin induced the binding of a protein complex to an oligonucleotide containing the AP-1 consensus binding site. This is the first study showing an effect of quercetin on AP-1 activity in thyroid cells. Further studies are in progress to understand the role of AP-1 activation in the effects of quercetin on thyroid function.
Language	English
Publishing date	2019-04-29
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2704216-9
ISSN	2076-3921
ISSN	2076-3921
DOI	10.3390/antiox8050112
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Plant constituents and thyroid: A revision of the main phytochemicals that interfere with thyroid function.

Di Dalmazi, Giulia / Giuliani, Cesidio

Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association

2021 Volume 152, Page(s) 112158

Abstract: In the past few decades, there has been a lot of interest in plant constituents for their antioxidant, anti-inflammatory, anti-microbial and anti-proliferative properties. However, concerns have been raised on their potential toxic effects particularly ... ...

Abstract	In the past few decades, there has been a lot of interest in plant constituents for their antioxidant, anti-inflammatory, anti-microbial and anti-proliferative properties. However, concerns have been raised on their potential toxic effects particularly when consumed at high dose. The anti-thyroid effects of some plant constituents have been known for some time. Indeed, epidemiological observations have shown the causal association between staple food based on brassicaceae or soybeans and the development of goiter and/or hypothyroidism. Herein, we review the main plant constituents that interfere with normal thyroid function such as cyanogenic glucosides, polyphenols, phenolic acids, and alkaloids. In detail, we summarize the in vitro and in vivo studies present in the literature, focusing on the compounds that are more abundant in foods or that are available as dietary supplements. We highlight the mechanism of action of these compounds on thyroid cells by giving a particular emphasis to the experimental studies that can be significant for human health. Furthermore, we reveal that the anti-thyroid effects of these plant constituents are clinically evident only when they are consumed in very large amounts or when their ingestion is associated with other conditions that impair thyroid function.
MeSH term(s)	Alkaloids/toxicity ; Animals ; Brassicaceae/chemistry ; Glucosinolates/toxicity ; Goiter/etiology ; Humans ; Hydroxybenzoates/toxicity ; Hypothyroidism/etiology ; Phytochemicals/toxicity ; Polyphenols/toxicity ; Glycine max/chemistry ; Thyroid Gland/drug effects
Chemical Substances	Alkaloids ; Glucosinolates ; Hydroxybenzoates ; Phytochemicals ; Polyphenols ; phenolic acid (I3P9R8317T)
Language	English
Publishing date	2021-03-28
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	782617-5
ISSN	1873-6351 ; 0278-6915
ISSN (online)	1873-6351
ISSN	0278-6915
DOI	10.1016/j.fct.2021.112158
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Editorial: The Legacy of Dr. Leonard D. Kohn to Thyroid Pathophysiology.

Giuliani, Cesidio / Shimura, Hiroki / Chung, Jae Hoon / Napolitano, Giorgio

Frontiers in endocrinology

2022 Volume 13, Page(s) 906340

MeSH term(s)	Humans ; Thyroid Diseases ; Thyrotropin
Chemical Substances	Thyrotropin (9002-71-5)
Language	English
Publishing date	2022-06-08
Publishing country	Switzerland
Document type	Editorial
ZDB-ID	2592084-4
ISSN	1664-2392
ISSN	1664-2392
DOI	10.3389/fendo.2022.906340
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Article ; Online: Editorial

Cesidio Giuliani / Hiroki Shimura / Jae Hoon Chung / Giorgio Napolitano

Frontiers in Endocrinology, Vol

The Legacy of Dr. Leonard D. Kohn to Thyroid Pathophysiology

2022 Volume 13

Keywords	Leonard D Kohn ; thyroid cancer ; thyroid autoimmunity ; FRTL-5 cells ; thyroid biology ; Diseases of the endocrine glands. Clinical endocrinology ; RC648-665
Language	English
Publishing date	2022-06-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Phenylmethimazole is a candidate drug for the treatment of severe forms of coronavirus disease 2019 (COVID-19) as well as other virus-induced "cytokines storm".

Giuliani, Cesidio / Bucci, Ines / Napolitano, Giorgio

Medical hypotheses

2020 Volume 146, Page(s) 110473

Abstract: Severe forms of the Coronavirus disease 2019 (COVID-19) are characterized by an enhanced inflammatory syndrome called "cytokine storm" that produces an aberrant release of high amounts of cytokines, chemokines, and other proinflammatory mediators. The ... ...

Abstract	Severe forms of the Coronavirus disease 2019 (COVID-19) are characterized by an enhanced inflammatory syndrome called "cytokine storm" that produces an aberrant release of high amounts of cytokines, chemokines, and other proinflammatory mediators. The pathogenetic role of the "cytokine storm" has been confirmed by the efficacy of immunosuppressive drugs such as corticosteroids along with antiviral drugs in the treatment of the severe forms of this disease. Phenylmethimazole (C10) is a derivative of methimazole with anti-inflammatory properties. Studies performed both in vitro and in vivo have shown that C10 is able to block the production of multiple cytokines, chemokines, and other proinflammatory molecules involved in the pathogenesis of inflammation. Particularly, C10 is effective in reducing the increased secretion of cytokines in animal models of endotoxic shock. We hypothesize that these effects are not limited to the endotoxic shock, but can also be applied to any disease characterized by the presence of a "cytokine storm". Therefore, C10 may be a potential drug to be used alternatively or in association with the corticosteroids or other immunosuppressive agents in the severe forms of COVID-19 as well as other viral diseases that induce a "cytokine storm". Preclinical and clinical studies have to be performed to confirm this hypothesis.
MeSH term(s)	Animals ; Anti-Inflammatory Agents/pharmacology ; Antiviral Agents/pharmacology ; COVID-19/drug therapy ; COVID-19/immunology ; Cytokine Release Syndrome/drug therapy ; Cytokine Release Syndrome/immunology ; Cytokines/antagonists & inhibitors ; Disease Models, Animal ; Drug Evaluation, Preclinical ; Humans ; Methimazole/analogs & derivatives ; Methimazole/pharmacology ; Mice ; Pandemics ; SARS-CoV-2 ; Shock, Septic/drug therapy ; Shock, Septic/immunology ; Thiones/pharmacology ; Translational Medical Research
Chemical Substances	Anti-Inflammatory Agents ; Antiviral Agents ; Cytokines ; Thiones ; phenyl methimazole ; Methimazole (554Z48XN5E)
Language	English
Publishing date	2020-12-24
Publishing country	United States
Document type	Journal Article
ZDB-ID	193145-3
ISSN	1532-2777 ; 0306-9877
ISSN (online)	1532-2777
ISSN	0306-9877
DOI	10.1016/j.mehy.2020.110473
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Article: Non-Conventional Clinical Uses of TSH Receptor Antibodies: The Case of Chronic Autoimmune Thyroiditis.

Napolitano, Giorgio / Bucci, Ines / Di Dalmazi, Giulia / Giuliani, Cesidio

Frontiers in endocrinology

2021 Volume 12, Page(s) 769084

Abstract: Anti TSH receptor antibodies (TSHrAb) are a family of antibodies with different activity, some of them stimulating thyroid function (TSAb), others with blocking properties (TBAb), it is a common finding that antibodies with different function might ... ...

Abstract	Anti TSH receptor antibodies (TSHrAb) are a family of antibodies with different activity, some of them stimulating thyroid function (TSAb), others with blocking properties (TBAb), it is a common finding that antibodies with different function might coexist in the same patient and can modulate the function of the thyroid. However, most of the labs routinely detect all antibodies binding to the TSH receptor (TRAb, i.e. TSH-receptor antibodies detected by binding assay without definition of functional property). Classical use of TSHr-Ab assay is in Graves' disease where they are tested for diagnostic and prognostic issues; however, they can be used in specific settings of chronic autoimmune thyroiditis (CAT) as well. Aim of the present paper is to highlight these conditions where detection of TSHr-Ab can be of clinical relevance. Prevalence of TSHrAb is different in in the 2 main form of CAT, i.e. classical Hashimoto's thyroiditis and in atrophic thyroiditis, where TBAb play a major role. Simultaneous presence of both TSAb and TBAb in the serum of the same patient might have clinical implication and cause the shift from hyperthyroidism to hypothyroidism and vice versa. Evaluation of TRAb is recommended in case of patients with Thyroid Associated Orbitopathy not associated with hyperthyroidism. At present, however, the most relevant recommendation for the use of TRAb assay is in patients with CAT secondary to a known agent; in particular, after treatment with alemtuzumab for multiple sclerosis. In conclusion, the routine use of anti-TSH receptor antibodies (either TRAb or TSAb/TBAb) assay cannot be suggested at the present for diagnosis/follow up of patients affected by CAT; there are, however, several conditions where their detection can be clinically relevant.
MeSH term(s)	Autoantibodies/blood ; Humans ; Receptors, Thyrotropin/immunology ; Thyroid Gland/immunology ; Thyroiditis, Autoimmune/blood ; Thyroiditis, Autoimmune/immunology
Chemical Substances	Autoantibodies ; Receptors, Thyrotropin
Language	English
Publishing date	2021-11-05
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2592084-4
ISSN	1664-2392
ISSN	1664-2392
DOI	10.3389/fendo.2021.769084
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Article: Thyroid Autoimmunity in Female Infertility and Assisted Reproductive Technology Outcome.

Bucci, Ines / Giuliani, Cesidio / Di Dalmazi, Giulia / Formoso, Gloria / Napolitano, Giorgio

Frontiers in endocrinology

2022 Volume 13, Page(s) 768363

Abstract: The regulation of the female reproductive system is one of the most relevant actions of thyroid hormones. Adequate thyroid hormones production is essential for normal menstrual function and fertility as well as for the successful maintenance of pregnancy. ...

Abstract	The regulation of the female reproductive system is one of the most relevant actions of thyroid hormones. Adequate thyroid hormones production is essential for normal menstrual function and fertility as well as for the successful maintenance of pregnancy. The relationship between reproductive failure and thyroid disorders is particularly relevant and attracts attention worldwide. Thyroid autoimmunity (TAI), defined by the presence of circulating antithyroid antibodies targeting thyroid peroxidase (TPOAb) and thyroglobulin (TgAb), is prevalent among women of reproductive age and is the most frequent cause of thyroid dysfunction. Several studies addressed the association between TAI, thyroid function, and fertility as well as pregnancy outcome after spontaneous or assisted conception. Infertility, miscarriages, and fetal-maternal complications are described in overt autoimmune hypothyroidism. More debatable is the role of mild thyroid dysfunction, mainly subclinical hypothyroidism (SCH), and TAI in the absence of thyroid dysfunction in infertility and reproductive outcome. Assisted reproductive technology (ART) has become an integral element of care for infertility. Women with TAI undergoing ART are of particular interest since they carry a higher risk of developing hypothyroidism after the ovarian stimulation but whether TAI, in absence of thyroid dysfunction, adversely affects ART outcome is still controversial. Likewise, the role of levothyroxine (LT4) in improving fertility and the success of ART in euthyroid women with TAI is unclear. This review discusses the role of TAI, in the absence of thyroid dysfunction, in infertility and in ART outcome.
MeSH term(s)	Autoimmunity ; Female ; Humans ; Hypothyroidism/complications ; Infertility, Female/complications ; Infertility, Female/therapy ; Pregnancy ; Reproductive Techniques, Assisted/adverse effects ; Thyroid Diseases/complications ; Thyroxine
Chemical Substances	Thyroxine (Q51BO43MG4)
Language	English
Publishing date	2022-05-26
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2592084-4
ISSN	1664-2392
ISSN	1664-2392
DOI	10.3389/fendo.2022.768363
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Hormonal Regulation of the MHC Class I Gene in Thyroid Cells: Role of the Promoter "Tissue-Specific" Region.

Giuliani, Cesidio / Verrocchio, Sara / Verginelli, Fabio / Bucci, Ines / Grassadonia, Antonino / Napolitano, Giorgio

Frontiers in endocrinology

2021 Volume 12, Page(s) 749609

Abstract: In previous studies we have demonstrated that the expression of the Major Histocompatibility Complex (MHC) class I gene in thyrocytes is controlled by several hormones, growth factors, and drugs. These substances mainly act on two regions of the MHC ... ...

Abstract	In previous studies we have demonstrated that the expression of the Major Histocompatibility Complex (MHC) class I gene in thyrocytes is controlled by several hormones, growth factors, and drugs. These substances mainly act on two regions of the MHC class I promoter a "tissue-specific" region (-800 to -676 bp) and a "hormone/cytokines-sensitive" region (-500 to -68 bp). In a previous study, we have shown that the role of the "tissue-specific" region in the MHC class I gene expression is dominant compared to that of the "hormone/cytokines-sensitive" region. In the present report we further investigate the dominant role of the "tissue-specific" region evaluating the effect of thyroid stimulating hormone (TSH), methimazole (MMI), phenylmethimazole (C10), glucose and thymosin-α1. By performing experiments of electrophoretic mobility shift assays (EMSAs) we show that TSH, MMI and C10, which inhibit MHC class I expression, act on the "tissue-specific" region increasing the formation of a silencer complex. Glucose and thymosin-α1, which stimulate MHC class I expression, act decreasing the formation of this complex. We further show that the silencer complex is formed by two distinct members of the transcription factors families activator protein-1 (AP-1) and nuclear factor-kB (NF-kB), c-jun and p65, respectively. These observations are important in order to understand the regulation of MHC class I gene expression in thyroid cells and its involvement in the development of thyroid autoimmunity.
MeSH term(s)	Animals ; Antithyroid Agents/pharmacology ; Cell Line ; Electrophoretic Mobility Shift Assay ; Gene Expression Regulation/drug effects ; Genes, MHC Class I/drug effects ; Genes, MHC Class I/genetics ; Glucose/pharmacology ; Hormones/physiology ; Methimazole/analogs & derivatives ; Methimazole/pharmacology ; Rats ; Thiones/pharmacology ; Thymosin/pharmacology ; Thyroid Gland/cytology ; Thyroid Gland/drug effects ; Thyroid Gland/physiology ; Thyroiditis, Autoimmune/genetics ; Thyroiditis, Autoimmune/pathology ; Thyrotropin/pharmacology ; Transcription Factors/genetics
Chemical Substances	Antithyroid Agents ; Hormones ; Thiones ; Transcription Factors ; phenyl methimazole ; Methimazole (554Z48XN5E) ; Thymosin (61512-21-8) ; Thyrotropin (9002-71-5) ; Glucose (IY9XDZ35W2)
Language	English
Publishing date	2021-12-06
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2592084-4
ISSN	1664-2392
ISSN	1664-2392
DOI	10.3389/fendo.2021.749609
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Parathyroid Apoplexy Following Cinacalcet Treatment in Primary Hyperparathyroidism.

Di Dalmazi, Giulia / Giuliani, Cesidio / Napolitano, Giorgio

Frontiers in endocrinology

2018 Volume 9, Page(s) 777

Abstract: Cinacalcet, a calcimimetic drug, is considered a safe and valid option for the treatment of hypercalcemia in patients with primary hyperparathyroidism who are unable to undergo parathyroidectomy. Hypocalcemia and gastrointestinal adverse reactions are ... ...

Abstract	Cinacalcet, a calcimimetic drug, is considered a safe and valid option for the treatment of hypercalcemia in patients with primary hyperparathyroidism who are unable to undergo parathyroidectomy. Hypocalcemia and gastrointestinal adverse reactions are the main side effects reported in patients treated with cinacalcet. We present here the case of an 80-years-old patient with primary hyperparathyroidism treated with cinacalcet for 17 months who developed a severe and symptomatic episode of hypocalcemia requiring hospitalization 1 month after reaching a daily dose of 180 mg. Follow-up laboratory and imaging exams showed remission of primary hyperparathyroidism and disappearance of the parathyroid adenoma, suggesting a possible association between cinacalcet therapy and parathyroid infarction resulting in normalization of the elevated serum parathyroid hormone levels and severe hypocalcemia. No known cases of iatrogenic parathyroid apoplexy have thus far been described. We report here the first case of parathyroid apoplexy associated with the administration of cinacalcet in a patient with primary hyperparathyroidism. Parathyroid apoplexy features heterogeneous clinical manifestations ranging from relatively asymptomatic to potentially life-threatening cases. The occurrence of this complication should be carefully considered in patients with primary hyperparathyroidism in therapy with cinacalcet.
Language	English
Publishing date	2018-12-21
Publishing country	Switzerland
Document type	Case Reports
ZDB-ID	2592084-4
ISSN	1664-2392
ISSN	1664-2392
DOI	10.3389/fendo.2018.00777
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