Academic literature on the topic 'Thyroid stimulating hormone receptor (TSHR)'

• The thyroid gland produces all of the T₄ and 20% of T₃. • Congenital hypothyroidism is caused by: ◦ anatomical defects: agenesis/dysgenesis, ectopic, sublingual ◦ inborn errors of thyroid hormone metabolism ◦ secondary (pituitary thyroid-stimulating hormone (TSH)) or tertiary (hypothalamic thyrotropin-releasing hormone) deficiency ◦ iodine deficiency (commonest cause worldwide of hypothyroidism, patients are usually euthyroid). • Genetic causes are rare. • In most countries worldwide, newborn TSH screening is performed at 0–5 days of age. Treatment with l-thyroxine is (usually) lifelong. • Neonatal thyrotoxicosis due to transplacental passage of thyroid-stimulating immunoglobulins (TSIs) from mothers with thyrotoxicosis/Graves’ disease and may require antithyroid drugs (ATDs). • Acquired autoimmune hypothyroidism in children and adolescents: ◦ is caused by lymphocytic infiltration of the thyroid gland (Hashimoto’s disease/thyroiditis) • raised thyroid peroxidase antibodies are diagnostic • treatment is with l-thyroxine. • Hyperthyroidism (Graves’ disease, Hashimoto’s stimulatory phase (Hashitoxicosis)): ◦ is caused by autoantibodies to the TSH receptor (TSI, or TRAbthyrotropin receptor antibody) ◦ the first-line drug of choice is the ATD carbimazole ◦ thyroidectomy or radioiodine treatment can be considered for drug-resistant cases or after relapse. • Thyroid cancer is rare in childhood and adolescence, usually presenting with a nodule, but can be part of the multiple endocrine neoplasia syndromes.

Graves’ disease is a form of specific autoimmune disorder in the thyroid organ characterized by thyroid-stimulating antibodies (TSAb). Pregnant women are the most susceptible to GD due to hormonal changes and tolerance of immune responses during pregnancy. The incidence of prematurity, low birth weight (LBW), and neonatal thyrotoxicosis risk are the most complications that can be acquired if treatment is late and inadequate. It has implications for increased fetomaternal morbidity and mortality. Apart from being a biomarker for definitive diagnosis, TSAb testing is also beneficial for assessing treatment response and predicting relapse of GD (relapse) after oral anti-thyroid treatment. GD patients with high TPOAb titers also tend to have a high relapse rate. However, the evaluation of both TSAb and TPOAb examinations during and after treatment is rarely done routinely due to the examination’s high cost. This works proposed developing TSHR and TPO antigen-based rapid diagnostic tests through the immunochromatography method to address the challenges of financing and limited laboratory facilities in the area. Besides, understanding the importance of examining thyroid antibodies (TSAb and TPOAb) and interpretation in clinical practice is still a matter of debate in clinical circles, so it requires in-depth information.

The origin of hyperthyroidism in Graves’ disease was displayed demonstrating the complexity of the processes. The role of stimulating TSH receptor antibodies is the one factor for the production of increased thyroidal T3 and T4. The T3 and T4 formation in colloid-embedded thyroglobulin and the activities of thyroidal deiodinases [type 1 (DIO1) and type 2 (DIO2)] play a crucial role in that. The findings of different authors were summarized with respect to highlighting the role of tissue-specific deiodinase activities. Apart from the results of experimental studies, the clinical results were brought to the front. The role of tissue-specific type 2 deiodinase activity was demonstrated according to thyroid function, the presence of autoantibodies against thyroid peroxidase (TPO), thyroglobulin (Tg) and TSH receptor. Autoantibodies against human eye muscle membrane and cytosol antigens had influencing effects on tissue-specific DIO2 activities, and the antieye muscle antibody immunoglobulin isotypes were associated with eye muscle enlargements. Antithyroid drug (ATD) therapy demonstrated relevant effects on tissue-specific DIO2 activities, which were manifested in the alterations of thyroid hormone levels. An asymptomatically appearance of autoantibodies against peptides corresponding to amino acid sequence of DIO2 was detected associating with thyroid hormone and anti-TPO, anti-Tg and TSH receptor antibody levels during the therapy.

Graves’ disease (GD) is the commonest cause of hyperthyroidism followed by toxic nodular goitre. Patients presenting as goitre with clinical features of hyperthyroidism are to be carefully evaluated with biochemically with thyroid stimulating hormone (TSH), free thyroxine (fT4) and radionuclide scan (Technitium-99/Iodine-123). Those with GD also have raised thyroid receptor stimulating antibody levels. Patients are simultaneously evaluated for eye disease and managed accordingly. Initial treatment is rendering patient euthyroid using anti thyroid drugs (ATD) and if remission does not occur either continue medical therapy or proceed for definitive therapy by radioactive iodine ablation (RAI) or surgery. In last decades there is ample literature preferring surgery as preferred definitive therapy. Surgery in thyroid disease has become safer with development of many intra-operative adjuncts but it should be performed by high volume thyroid surgeon. The procedure of choice is near total or total thyroidectomy as it avoids recurrences. Patients who are not eligible or willing for surgery can be managed with RAI.

Congenital hypothyroidism (CH) affects approximately 1 in 3,500 newborns. There is a female preponderance. In areas of iodine insufficiency, the incidence is higher, since iodine is a key element in the synthesis of thyroid hormone. Approximately 85% of CH cases are sporadic, whereas 15% are hereditary. Thyroid hormone is essential for normal pre- and postnatal brain development. The importance of in utero thyroid hormone status is demonstrated by the fact that maternal hypothyroidism during pregnancy is known to result in cognitive and motor deficits in the offspring (Forrest 2004; Zoeller and Rovet 2004). Congenital hypothyroidism is already expressed in fetal life; maternal T4, transferred via the placenta, is not sufficient for normal brain development (Forrest 2004; Haddow et al. 1999; Opazo et al. 2008; Pop and Vulsma 2005). Prior to newborn screening, CH that went undiagnosed and untreated for more than 3 months was associated with permanent and significant mental retardation, as well as behavioral problems. Outcome is now significantly better. Children with CH have normal intelligence, although subtle and specific cognitive and behavioral problems occur. Congenital hypothyroidism can be caused by primary hypothyroidism, due to a defect of the thyroid gland, or by central hypothyroidism secondary to defective hypothalamic or pituitary regulation of thyroid hormone. Several types of primary thyroid abnormalities may occur. Thyroid dysgenesis is the result of a missing, ectopic, or hypoplastic gland. Proteins that are crucial for normal thyroid gland development include the thyroid transcription factors PAX8, TTF1, TTF2, FOXE1 and the thyroid stimulating hormone (TSH) receptor gene. Thyroid dyshormonogenesis is generally due to an autosomal recessive genetic defect in any of many stages of thyroid hormone synthesis, secretion and transport (Moreno and Visser 2007). One in 50,000 children has autosomal dominant thyroid hormone resistance (RTH) due to a mutation in the gene encoding for the TRb thyroid receptors (Hauser et al. 1993; Weiss et al. 1993). Iodine deficiency can also cause CH (endemic cretinism) (DeLange et al. 2000). Gaudino and colleagues (2005) determined the etiology of CH in 49 non-athyroid cases.

The pituitary gland (hypophysis) is an endocrine organ located at the base of the skull in a bony recess, called the sella turcica, consisting primarily of an anterior (adenohypophysis) and posterior (neurohypophysis) lobe. Collectively, under the influence of the hypothalamus, these lobes control the hormone secretions responsible for growth, reproduction, behaviour/ emotion, metabolism, and homeostasis, via a complex interplay of feedback loops. Dysfunction through failed synthesis of hormones, ‘breaks’ in the feedback pathways, or receptor malfunction can have diverse effects on plasma hormone levels and, hence, end organ function. The hypothalamus is located within the base of the third ventricle in the diencephalon and is responsible for maintaining homeostasis, as well as influencing emo­tion and behaviour. It is linked to the pituitary gland, which sits outside the dura, via the pituitary stalk and the hypothalamic– hypophyseal portal system. The anterior pituitary lobe makes up about 80% of the pituitary gland and is linked indirectly to the hypothalamus. It receives hormones released from neurosecretory cells in the paraventricular region of the hypothalamus, via a dense network of capillaries that make up the hypothalamic– hypophyseal portal system. These hormones subsequently bind to specific receptors on the pituitary cells to regulate a number of physio­logical processes including stress, growth, metabolism, reproduction, and lactation. There are six hormones re­leased by the anterior pituitary— adrenocorticotropic hormone (ACTH), growth hormone (GH), thyroid-stimulating hormone (TSH), follicle- stimulating hor­mone (FSH)/ luteinizing hormone (LH), and prolactin (PRH) (see Table 4.1). The posterior pituitary lobe is controlled via axons and nerve terminals that extend down from the hypothalamus through the pituitary stalk and into the lobe, which sub­sequently releases neurohormones (oxytocin and vaso­pressin) into the blood stream (see Table 4.2). Vasopressin (also called antidiuretic hormone, ADH), is essential in maintaining fluid homeostasis to ensure adequate blood volume and salt concentration. Its release is modulated by osmoreceptors (rising osmolality) in the hypothal­amus and baroreceptors (falling BP) in the cardiovascular system, and acts directly on the distal nephron to ensure water is conserved. Dysregulation of ADH may lead to conditions such as diabetes insipidus (DI) or SIADH (syn­drome of inappropriate ADH).

Toxic adenoma and toxic multinodular goitre represent the clinically important presentations of thyroid autonomy. Thyroid autonomy is a condition where thyrocytes produce thyroid hormones independently of thyrotropin (TSH) and in the absence of TSH-receptor stimulating antibodies (TSAB). Toxic adenoma (TA) is a clinical term referring to a solitary autonomously functioning thyroid nodule. The autonomous properties of TA are best shown by radio-iodine or ^99mTc imaging. The classic appearance of TA is that of circumscribed increased uptake with suppression of uptake in the surrounding extranodular thyroid tissue (‘hot’ nodule, Fig. 3.3.11.1). Toxic multinodular goitre (TMNG) is a heterogeneous disorder characterized by the presence of autonomously functioning thyroid nodules in a goitre with or without additional nodules. These additional nodules can show normal or decreased uptake (cold nodules) on scintiscan. TMNG constitutes the most frequent form of thyroid autonomy.