Deficiência na Globulina de Ligação de Tiroxina: uma Revisão de Literatura

O hipotireoidismo congênito é classificado como a falta de hormônios tireoidianos após o nascimento, e que quando não tratado inicialmente,contribui para o atraso acentuado do desenvolvimento e retardo mental. A ingestão adequada de iodo é necessária para a produção de hormônios tireoidianos. Visto que sua deficiência pode levar ao hipotireoidismo congênito em neonato, uma condição caracterizada, geralmente, por deficiência intelectual e nanismo, podendo ainda afetar a audição. O presente estudo teve como objetivo realizar uma revisão de literatura acerca da Hipotebegenemia e seus agravos relacionados à saúde. Hipotebegenemia doença genética, ligada ao cromossomo X e que acomete, principalmente, meninos. Ocorre por uma deficiência na proteína transportadora dos hormônios tireodianos - TBG. Para isto, realizaram-se buscas bibliográficas em bases eletrônicas, tais como: Bireme, Lilacs, SciELO, Pubmed e Periódicos Capes. Conclui-se que o hipotireoidismo subclínico na infância parece ser reversível na maioria dos casos. Contudo, os riscos de progressão desta condição não devem ser afastados, uma vez que as manifestações clínicas irão depender de determinadas condições, tal como as formas autoimunes.Palavras chaves: Hipotireoidismo. Tireoglobulina Ligadora. Doença Genética.AbstractCongenital hypothyroidism is classified as the lack of thyroid hormones after birth, and when not treated initially, it contributes to markeddevelopmental delay and mental retardation. The ingestion of iodide it is necessary for the thyroid hormones production. Its deficiency can leadto congenital hypothyroidism in the neonate, a condition usually characterized by intellectual deficiency and dwarfism, and may even affect hearing. The objective of the present study was to carry out a review of the literature on Hypothembemia and its health related diseases. It is a Hipotebegenemia genetic disease, linked to the X chromosome and affects mainly boys. It occurs due to a deficiency in thyroid hormone carrier protein - TBG. For this, bibliographic searches were carried out in electronic databases, such as: Bireme, Lilacs, SciELO, Pubmed and Periodicals CAPES. It is concluded that subclinical hypothyroidism in childhood seems to be reversible in most cases. However, the risks of progress by category are not required, since that the clinical manifestations will depend on conditions, such as autoimmune forms.Keywords: Hypothyroidism. Binding Thyroglobulin. Genetic Disease.

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Causes and laboratory investigation of hypothyroidism

Oxford Textbook of Endocrinology and Diabetes ◽

10.1093/med/9780199235292.003.3243 ◽

2011 ◽

pp. 530-537 ◽

Cited By ~ 1

Author(s):

Ferruccio Santini ◽

Aldo Pinchera

Keyword(s):

Thyroid Hormone ◽

Thyroid Gland ◽

Thyroid Hormones ◽

Thyroid Hormone Receptor ◽

Hormone Secretion ◽

Thyroid Tissue ◽

Clinical Manifestations ◽

Primary Hypothyroidism ◽

Central Hypothyroidism ◽

Resistance To Thyroid Hormones

Hypothyroidism is the clinical state that develops as a result of the lack of action of thyroid hormones on target tissues (1). Hypothyroidism is usually due to impaired hormone secretion by the thyroid, resulting in reduced concentrations of serum thyroxine (T4) and triiodothyronine (T3). The term primary hypothyroidism is applied to define the thyroid failure deriving from inherited or acquired causes that act directly on the thyroid gland by reducing the amount of functioning thyroid tissue or by inhibiting thyroid hormone production. The term central hypothyroidism is used when pituitary or hypothalamic abnormalities result in an insufficient stimulation of an otherwise normal thyroid gland. Both primary and central hypothyroidism may be transient, depending on the nature and the extent of the causal agent. Hypothyroidism following a minor loss of thyroid tissue can be recovered by compensatory hyperplasia of the residual gland. Similarly, hypothyroidism subsides when an exogenous inhibitor of thyroid function is removed. Peripheral hypothyroidism may also arise as a consequence of tissue resistance to thyroid hormones due to a mutation in the thyroid hormone receptor. Resistance to thyroid hormones is a heterogeneous clinical entity with most patients appearing to be clinically euthyroid while some of them have symptoms of thyrotoxicosis and others display selected signs of hypothyroidism. The common feature is represented by pituitary resistance to thyroid hormones, leading to increased secretion of thyrotropin that in turn stimulates thyroid growth and function. The variability in clinical manifestations depends on the severity of the hormonal resistance, the relative degree of tissue hyposensitivity, and the coexistence of associated genetic defects (see Chapter 3.4.8).

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Clinical and genetic characteristics of X-linked mental retardation 102 type caused by novel mutations in the DDX3X gene (OMIM:300958)

Neuromuscular Diseases ◽

10.17650/2222-8721-2020-10-1-75-80 ◽

2020 ◽

Vol 10 (1) ◽

pp. 75-80

Author(s):

E. L. Dadali ◽

T. V. Markova ◽

O. A. Levchenko ◽

A. L. Chukhrova ◽

O. A. Shchagina

Keyword(s):

Mental Retardation ◽

Amino Acid ◽

Sanger Sequencing ◽

Genetic Correlations ◽

Clinical Manifestations ◽

Heterozygous State ◽

Intellectual Deficiency ◽

Novel Mutations ◽

Genetic Characteristics ◽

Female Patients

Introduction. X-linked mental retardation 102 type caused by novel mutations in the DDX3X gene is one of the most common monogenic variants of intellectual deficiency in women.Purpose of the study. Description of the clinical and genetic characteristics of Russian female patients with type 102 mental retardation due to newly identified mutations.Materials and methods. The diagnosis of mental retardation of type 102 was established on the basis of the features of clinical manifestations and the detection of the mutations in the DDX3X gene as a result of exome sequencing and subsequent confirmation of the identified variants of Sanger sequencing.Results. A description is given of the clinical and genetic characteristics of two female patients with type 102 X-linked mental retardation due newly to identified mutations p.1703C> G and c.113A> G (NM_001193416) in the DDX3X gene in the heterozygous state. New features of the phenotype are described. The mechanism of the appearance of clinical and genetic correlations is suggested, which can be used as a prognostic marker of the development of the disease.Conclusion. Clinical and genetic characteristics of two patients with mutations in the DDX3X gene that violate the amino acid sequence of different protein regions with different severity of clinical manifestations are described. The results obtained may testify in favor of the existence of a dependence of the severity of the phenotype on the localization and nature of mutations in the gene and determine the relevance of further research aimed at searching for clinical and genetic correlations.

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Clinical assessment and systemic manifestations of thyrotoxicosis

Oxford Textbook of Endocrinology and Diabetes ◽

10.1093/med/9780199235292.003.3162 ◽

2011 ◽

pp. 441-452

Author(s):

Claudio Marcocci ◽

Filomena Cetani ◽

Aldo Pinchera

Keyword(s):

Thyroid Hormone ◽

Thyroid Gland ◽

Thyroid Hormones ◽

Clinical Manifestations ◽

Clinical Syndrome ◽

Graves Disease ◽

Free Triiodothyronine ◽

Excessive Secretion ◽

Almost All ◽

Symptoms And Signs

The term thyrotoxicosis refers to the clinical syndrome that results when the serum concentrations of free thyroxine, free triiodothyronine, or both, are high. The term hyperthyroidism is used to mean sustained increases in thyroid hormone biosynthesis and secretion by the thyroid gland; Graves’ disease is the most common example of this. Occasionally, thyrotoxicosis may be due to other causes such as destructive thyroiditis, excessive ingestion of thyroid hormones, or excessive secretion of thyroid hormones from ectopic sites; in these cases there is no overproduction of hormone by thyrocytes and, strictly speaking, no hyperthyroidism. The various causes of thyrotoxicosis are listed in Chapter 3.3.5. The clinical features depend on the severity and the duration of the disease, the age of the patient, the presence or absence of extrathyroidal manifestations, and the specific disorder producing the thyrotoxicosis. Older patients have fewer symptoms and signs of sympathetic activation, such as tremor, hyperactivity, and anxiety, and more symptoms and signs of cardiovascular dysfunction, such as atrial fibrillation and dyspnoea. Rarely a patient with ‘apathetic’ hyperthyroidism will lack almost all of the usual clinical manifestations of thyrotoxicosis (1). Almost all organ systems in the body are affected by thyroid hormone excess, and the high levels of circulating thyroid hormones are responsible for most of the systemic effects observed in these patients (Table 3.3.1.1). However, some of the signs and symptoms prominent in Graves’ disease reflect extrathyroidal immunological processes rather than the excessive levels of thyroid hormones produced by the thyroid gland (Table 3.3.1.2).

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Response of total and 'free' thyroid hormones and diiodotyrosine to bovine TSH in subclinical hypothyroidism

Acta Endocrinologica ◽

10.1530/acta.0.1120509 ◽

1986 ◽

Vol 112 (4) ◽

pp. 509-516

Author(s):

G. Benker ◽

H. Rasche ◽

Th. Olbricht ◽

H. Meinhold ◽

J. Teuber ◽

...

Keyword(s):

Thyroid Hormone ◽

Thyroid Hormones ◽

Subclinical Hypothyroidism ◽

Thyroid Autoimmunity ◽

Addison’S Disease ◽

Primary Hypothyroidism ◽

Addison's Disease ◽

Thyroid Autoantibodies ◽

Schmidt’S Syndrome ◽

Normal Controls

Abstract. Thirty-three patients with Addison's disease were studied. Twenty-two had idiopathic Addison's disease; within this group, 14 patients had clinical or subclinical hypothyroidism, and 16 had increased titres of thyroid autoantibodies. Five patients had tuberculous, and eight had unclassifiable Addison's disease; only one patient in the latter group had evidence of thyroid autoimmunity. A stimulation test with 15 mU bTSH/kg was performed in three patients with Schmidt's syndrome (coexisting Addison's disease and manifest primary hypothyroidism), 15 patients with either subclinical hypothyroidism or increased titres of thyroid autoantibodies, 10 patients without thyroid involvement, and 10 normal controls. There was no detectable increase of 'free' and total thyroid hormones in Schmidt's syndrome. The mean increases after 3–4 h of T4, fT4, T3 and fT3 were 22, 35, 63 and 66%, respectively, in patients without thyroid involvement, and 13, 24, 46 and 45% in patients with subclinical hypothyroidism. 'Free' but not total thyroid hormones rose significantly (P <0.01) higher in patients without signs of thyroid involvement than in patients with subclinical hypothyroidism and/or thyroid autoantibodies. Thyroid hormone response to bTSH in Addison's disease with apparently healthy thyroid glands was not different from normal controls. Serum diiodotyrosine rose in all groups except in hypothyroidism; hypothyroid patients had, however, basal levels well within the normal range. Thus, thyroid hormone synthesis appears to be blocked at a point distal to diiodotyrosine formation in this particular situation. These results support the assumption that TSH elevation in idiopathic Addison's disease is due to coexisting thyroid autoimmunity and that it reflects incipient thyroid failure. This can be demonstrated by a diminished response of 'free' T4 and 'free' T3 to exogenous stimulation with bTSH.

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Update on resistance to thyroid hormone syndromeβ

Italian Journal of Pediatrics ◽

10.1186/s13052-020-00929-x ◽

2020 ◽

Vol 46 (1) ◽

Author(s):

Hongping Sun ◽

Lin Cao ◽

Rendong Zheng ◽

Shaofeng Xie ◽

Chao Liu

Keyword(s):

Thyroid Hormone ◽

Genetic Disease ◽

Autosomal Dominant ◽

Clinical Manifestations ◽

Serum Levels ◽

Thyroid Stimulating Hormone ◽

Target Tissue ◽

Free Triiodothyronine ◽

Resistance To Thyroid Hormone ◽

Inappropriate Secretion

Abstract Resistance to thyroid hormone syndrome (RTH) is an autosomal dominant or recessive genetic disease caused by mutation of either the thyroid hormone receptorβ (THR-β) gene or the thyroid hormone receptorα (THR-α) gene. RTH due to mutations of the THR-β gene (hereafter, RTH-β) is characterized by a decreased response of the target tissue to thyroid hormone, increased serum levels of free triiodothyronine (FT3) and/or free thyroxine (FT4), and inappropriate secretion of thyroid-stimulating hormone (TSH, normal or elevated). Clinical manifestations of RTH-β vary from hyperthyroidism to hypothyroidism or simple goiter, and RTH-β is often misdiagnosed clinically. The present review was prepared for the purpose of expanding knowledge of RTH-β in order to reduce the rate of misdiagnosis.

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The Role of Thyroid Diseases and their Medications in Cardiovascular Disorders: A Review of the Literature

Current Cardiology Reviews ◽

10.2174/1573403x15666191008111238 ◽

2020 ◽

Vol 16 (2) ◽

pp. 103-116

Author(s):

Negar Omidi ◽

Mohammadrafie Khorgami ◽

Farbod Z. Tajrishi ◽

Amirhosein Seyedhoseinpour ◽

Parichehr Pasbakhsh

Keyword(s):

Blood Pressure ◽

Thyroid Hormone ◽

Thyroid Hormones ◽

Cardiovascular System ◽

Thyroid Disease ◽

Cardiac Rhythm ◽

Thyroid Dysfunction ◽

Cardiovascular Disorders ◽

Review Of The Literature

The association between thyroid disease and cardiovascular manifestations is significant and undeniable. Previous studies have explained several aspects of the effects of thyroid hormone on the heart and cardiovascular system. Accordingly, both hyper and hypothyroidism can cause important alterations in cardiac rhythm, output and contractility as well as vascular resistance and blood pressure. Since treating the thyroid abnormality, especially in its initial stages, could lead to a significant improvement in most of its resultant cardiovascular disturbances, early suspicion and recognition of thyroid dysfunction, is necessary in patients with cardiovascular manifestations. In this in-depth review, we discuss the physiological roles as well as the effects of abnormal levels of thyroid hormones on the cardiovascular system. We also review the effects of the medications used for the treatment of hyper and hypothyroidism on cardiac function. In the end, we discuss the association between thyroid function and amiodarone, an effective and frequently-used antiarrhythmic drug, because of its well-known effects on the thyroid.

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Genetic Manipulation on Zebrafish duox Recapitulate the Clinical Manifestations of Congenital Hypothyroidism

Endocrinology ◽

10.1210/endocr/bqab101 ◽

2021 ◽

Author(s):

Feng Sun ◽

Ya Fang ◽

Man-Man Zhang ◽

Rui-Jia Zhang ◽

Feng-Yao Wu ◽

...

Keyword(s):

Thyroid Hormone ◽

Thyroid Hormones ◽

Congenital Hypothyroidism ◽

Growth Retardation ◽

Genetic Manipulation ◽

Clinical Manifestations ◽

Primary Sources ◽

H2o2 Production ◽

Endocrine Disorder ◽

Thyroid Dyshormonogenesis

Abstract Congenital hypothyroidism (CH) is a highly prevalent but treatable neonatal endocrine disorder. Thyroid dyshormonogenesis is the main cause of congenital hypothyroidism in Chinese CH patients and DUOX2 is the most frequent mutated gene involved in H2O2 production. In human, the primary sources for H2O2 production are DUOX1 and DUOX2, while in zebrafish, there is only a single orthologue for DUOX1 and DUOX2. In this study, duox mutant zebrafish were generated through knockdown duox by morpholino or knockout duox by CRISPR Cas9. The associated phenotypes were investigated and rescued by thyroxine (T4) treatment. Mutant zebrafish displayed hypothyroid phenotypes including growth retardation and goiter and infertility. Homozygous mutants in adults also displayed extra-thyroidal abnormal phenotypes including lacking barbels, pigmentation defects, erythema in the opercular region, ragged fins and delayed scales. All these abnormal phenotypes can be rescued by 10 nM T4 treatment. Strikingly, the fertility of zebrafish was dependent on thyroid hormone, T4 treatment should be continued and cannot be stopped over two weeks in hypothyroid zebrafish in order to achieve fertility. Thyroid hormones played a role in the developing and maturing of reproductive cells. Our work indicated that duox mutant zebrafish may provide a model for human congenital hypothyroidism.

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Clinical and molecular cytogenetic characterization of two cases of inverted duplication deletion 8p

Nauchno-prakticheskii zhurnal «Medicinskaia genetika» ◽

10.25557/2073-7998.2020.03.41-42 ◽

2020 ◽

pp. 41-42

Author(s):

Д.А. Юрченко ◽

М.Е. Миньженкова ◽

Е.Л. Дадали ◽

Н.В. Шилова

Keyword(s):

Mental Retardation ◽

Congenital Heart ◽

Heart Defects ◽

Clinical Manifestations ◽

Formation Mechanisms ◽

Agenesis Of Corpus Callosum ◽

Molecular Cytogenetic ◽

Inverted Duplication ◽

Cytogenetic Characterization

Синдром инвертированной дупликации короткого плеча хромосомы 8 со смежной терминальной делециенй (inv dup del(8p), ORPHA 96092) - редкая хромосомная аномалия (ХА) с частотой 1/10000-1/30000 живорожденных. В статье представлены клинические и молекулярно-цитогенетические характеристики двух неродственных пациентов с синдромом inv dup del(8p) и уточнены механизмы формирования хромосомного дисбаланса. Inverted duplication deletion 8p syndrome (inv dup del(8p), ORPHA 96092) is a rare chromosomal abnormality with a frequency of 1:10,000 - 30,000 newborns. Clinical manifestations of this syndrome include mental retardation, facial anomalies, hypoplasia/agenesis of corpus callosum, scoliosis and/or kyphosis, hypotonia, congenital heart defects. The article presents the clinical and molecular cytogenetic characteristics of two patients with inv dup del (8p) syndrome and clarifies the formation mechanisms.

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