title: Beyond the Gland: Thyroid Disorders Unraveled as a Distinctive Challenge in Health and Disease Management
title: Thyroid hormones
titleType: Subtitle
title: Thyroid carcinoma
titleType: Subtitle
Creators: name: Khaliq, Hafiz Muhammad Haseeb
name: Arshad, Adnan
Publisher: name: Zenodo
Year: 2023

description: Thyroid disorder is a medical condition in which thyroid gland does not make the right amount of hormones. A subject might be at a higher risk of developing a thyroid condition if suffering from some medical conditions (anemia, Type 1 diabetes, primary adrenal insufficiency, lupus, rheumatoid arthritis, Sjögren’s syndrome and Turner syndrome), the co-occurrence of Hashimoto's thyroiditis and Garves’’ disease within one family suggests a common genetic basis for these diseases. The positive correlation between TPO antibody titres and TSH levels in euthyroid subjects suggests that TPO antibodies are indeed a marker of future thyroid failure [1]. Hyperthyroidism: The most common cause of hyperthyroidism, is an autoimmune disorder known as Garves’' disease. Pituitary gland problems along with certain medications (e.g., iodine pills) lead to hyperthyroidism. Hypothyroidism: Hypothyroidism, causing our body's metabolism becoming slow is most commonly caused by Hashimoto's thyroiditis. Other factors included Hypothyroidism (especially Hashimoto's thyroiditis).Family history of thyroid disease and noticing possible thyroid disease symptoms, should be informed to a doctor. Pathophysiology: Hyperthyroidism is a hypermetabolic state caused by elevated circulating levels of free T3 and T4.  Thyrotoxicosis often is referred to as hyperthyroidism.  In certain conditions, however excessive release of preformed thyroid hormone (e.g., in thyroiditis) or comes from an extrathyroidal source. The clinical manifestations of thyrotoxicosis are by overactivity of the sympathetic nervous system. Cardiac palpitations and tachycardia are common due to increased cardiac contractility. There is net increase in the basal metabolic rate. Neuromuscular: Patients frequently experience nervousness, tremor, and irritability due to the sympathetic overactivity [2]. Thyroid myopathy nearly 50% develop proximal muscle weakness. Ocular changes often call attention to hyperthyroidism. A wide, staring gaze and lid lag are present because of sympathetic overstimulation of the superior tarsal muscle (Müller’s muscle), which functions alongside the levator palpebrae superioris muscle to raise the upper eyelid. Thyroid storm designates the abrupt onset of severe hyperthyroidism. It occurs most often in patients with Grave’s disease and probably results from an acute elevation in catecholamine levels, as might be encountered during infection, surgery, cessation of anti-thyroid medication, or any form of stress. Thyroid storm is a medical emergency, as a significant number of untreated patients die of cardiac arrhythmias. Apathetic hyperthyroidism refers to thyrotoxicosis occurring in older adults, in whom the  typical features of thyroid hormone excess often are blunted. The underlying thyroid disease is usually detected during laboratory workup for unexplained weight loss or worsening cardiovascular disease [3].

 
description: Garves’’ disease: In Garves’’ disease, one of the most important causes of hyperthyroidism, accumulation of loose connective tissue behind the orbits also adds to the protuberant appearance of the eyes. A “violent and long continued palpitations in females” associated with enlargement of the thyroid gland. It is characterized by a triad of manifestations: Thyrotoxicosis, caused by a diffusely enlarged, hyperfunctional thyroid, An infiltrative ophthalmopathy with resultant exophthalmos, A localized, infiltrative dermopathy (sometimes designated pretibial myxedema), A genetic susceptibility to Garves’ disease is associated with the presence of certain human leukocyte antigen (HLA) haplotypes, specifically HLA-DR3, and polymorphisms in genes whose products regulate T-cell responses. Pathogenesis manifestations of Garves’ disease are caused by autoantibodies against the TSH receptor that bind to, and stimulate, thyroid follicular cells independent of endogenous trophic hormones. Multiple autoantibodies are produced in Garves’ disease, including the following: Thyroid-stimulating immunoglobulin (TSI). This IgG antibody binds to the TSH receptor and mimics the action of TSH, stimulating adenyl cyclase, with thr resultant increased release of thyroid hormones. Thyroid growth-stimulating immunoglobulins. Also directed against the TSH receptor, these antibodies have been implicated in the proliferation of thyroid follicular epithelium [4]. TSH-binding inhibitor immunoglobulins. These anti-TSH receptor antibodies prevent TSH from binding to its receptor on thyroid epithelial cells and in so doing may inhibit thyroid cell function. In Garves’ ophthalmopathy, the volume of the retroorbital connective tissues and extraocular muscles is increased due to marked infiltration of the retroorbital space by mononuclear cells, predominantly T cells, inflammatory edema and swelling of extraocular muscles , accumulation of extracellular matrix components, specifically hydrophilic glycosaminoglycans such as hyaluronic acid and chondroitin sulfate, Increased numbers of adipocytes (fatty infiltration). Occasionally, Hashimoto thyroiditis and Garves’’ disease may coexist within an affected kindred. Not surprisingly, there is also an element of histologic overlap between the autoimmune thyroid disorders (most characteristically, prominent intrathyroidal lymphoid cell infiltrates with germinal center formation). In both disorders, the frequency of other autoimmune diseases, such as systemic lupus erythematosus, pernicious anemia, type 1 diabetes, and Addison disease, is increased as well is GIT malignancies [5,10]. Hypothyroidism: Hypothyroidism may be divided into primary and secondary categories, depending on whether it arises from an intrinsic abnormality in the thyroid or from  hypothalamic or pituitary disease. Primary hypothyroidism can be secondary to congenital, autoimmune, or iatrogenic causes. Genetic defects: Genetic defects that perturb thyroid development (thyroid dysgenesis) or the synthesis of thyroid hormone (dyshormonogenetic goiter) are rare overall but the most common cause of congenital hypothyroidism. Iatrogenic hypothyroidism can be caused by either surgical or radiation-induced ablation of thyroid parenchyma. Enzyme defects that interfere with thyroid hormone synthesis are a cause of sporadic cretinism include impaired development of the skeletal system and central nervous system, severe mental retardation, short stature, coarse facial features, a protruding tongue, and umbilical hernia. Hypothyroidism in older children and adults results in a condition known as Myxedema [6]. Thyroid hormones regulate the transcription of several sarcolemmal genes, such as calcium ATPases, whose encoded products are critical in maintaining efficient cardiac output. In addition, hypothyroidism promotes an atherogenic lipid profile—an increase in total cholesterol and low-density lipoprotein (LDL) levels—that may contribute to the adverse cardiovascular mortality rates in this disease. Histologically, there is an accumulation of matrix substances, such as hyaluronic acid, in skin, subcutaneous tissue, and viscera. This results in non-pitting edema, broadening and coarsening of facial features, enlargement of the tongue and deepening of the voice [7].  
description: Autoimmune Thyroid Disease (AITD): Chronic lymphocytic (Hashimoto) thyroiditis is the most common cause of hypothyroidism in regions where dietary iodine levels are sufficient. Hashimoto thyroiditis is an autoimmune disease characterized by progressive destruction of thyroid parenchyma, Hürthle cell change, and mononuclear (lymphoplasmacytic) infiltrates, with or without extensive fibrosis. Multiple autoimmune mechanisms account for thyroid injury in Hashimoto disease, including cytotoxicity mediated by CD8+ T cells, cytokines (IFN-γ), an d anti-thyroid antibodies. Subacute granulomatous (de Quervain) thyroiditis is a self-limited disease, probably secondary to a viral infection, and is characterized by pain and the presence of a granulomatous inflammation in the thyroid. Subacute lymphocytic thyroiditis is a self-limited disease that often occurs after a pregnancy (postpartum thyroiditis), typically is painless, and is characterized by lymphocytic inflammation in the thyroid [8]. Pathogenesis of Hashimoto thyroiditis is the breakdown of immune tolerance to thyroid autoantigens results in progressive autoimmune destruction of thyrocytes by infiltrating cytotoxic T cells, locally released cytokines, or antibody-dependent cytotoxicity.Cytokine-mediated cell death. T-cell activation leads to the production of inflammatory cytokines such as interferon-γ in the thyroid gland, with resultant recruitment and activation of macrophages and damage to follicles. Binding of anti-thyroid antibodies (anti-thyroglobulin, and anti-thyroid peroxidase antibodies), followed by antibody-dependent cell–mediated cytotoxicity [8,9]. Goiter: Impairment of thyroid hormone synthesis leads to a compensatory rise in the serum TSH, which drives the hypertrophy and hyperplasia of thyroid follicular cells and, ultimately, enlargement of the thyroid gland. These compensatory changes overcome the hormone deficiency and maintain a euthyroid metabolic state in the vast majority of affected individuals. However, if the underlying disorder is severe (e.g., a congenital biosynthetic defect), the compensatory responses may be inadequate, resulting in goitrous hypothyroidism. Endemic goiter occurs in geographic areas where the diet contains little iodine. Such conditions are particularly common in mountainous areas of the world, including the Himalayas and the Andes. With increased availability of dietary iodine supplementation, endemic goiter have declined significantly. Sporadic goiter occurs less frequently than endemic goiter. The condition is more common in females than in males, with a peak incidence in puberty or young adulthood, when there is an increased physiologic demand for T4. Excessive ingestion of substances that interfere with thyroid hormone synthesis, such as calcium or vegetables belonging to the Cruciferae family (e.g., cabbage, Brussels sprouts, turnips), inherited enzymatic defects (dyshormonogenetic goiter) [10]. Thyroid Neoplasms range from circumscribed, benign adenomas to highly aggressive, anaplastic carcinomas. Nodules in very young (70 years) individuals are more likely to be neoplastic. Nodules in males are more likely to be neoplastic than are those in females. Nodules that take up radioactive iodine in imaging studies (hot nodules) are more likely to be benign. Such associations, however, are of little significance in the evaluation of a given patient, in whom the timely recognition of a malignancy may be lifesaving [1,7].  Adenomas of the thyroid are benign neoplasms derived from follicular epithelium. Follicular adenomas usually are solitary. Pathogenesis Driver mutations in the TSH receptor signaling pathway play a vital role in the pathogenesis of toxic adenomas. Activating (gain-of-function) somatic mutations in one of two components of signaling system—most often the gene encoding the TSH receptor itself (TSHR) and, less commonly, the α-subunit of Gs (GNAS)—allow follicular cells to secrete thyroid hormone independent of TSH stimulation (thyroid autonomy). In Residual Garves’’ Disease: The follicles are lined by tall columnar epithelial cells that are actively resorbing the colloid in the centers of the follicles, resulting in a “scalloped” appearance of the colloid, scattered lymphocytes. Adenomas are well-differentiated follicles resembling those of normal thyroid parenchyma, completely enveloped by thin fibrous capsule, architecturally different from surrounding gland; surrounding thyroid tissue shows signs of compression. Closely packed follicles, trabeculae or solid sheets [1]. Recent advancements in Management of Disease: One of the most definitive ways, thyroid blood tests are used to diagnose thyroid disorders associated with hyper- or hypothyroidism. The specific blood tests that will be done to test your thyroid can include hormones levels (TSH, T4, T3, FT4 and FT3), antibodies (Thyroid antibodies, TPO antibodies, thyroglobulin antibodies, and thyroid receptor antibodies), and Calcitonin and Thyroglobulin levels. Imaging test called a thyroid scan to look at your thyroid to check for an increased size, shape or growths (nodules) [1,7]. Another imaging test called an ultrasound. This is a diagnostic technique that transmits high-frequency sound waves, inaudible to the human ear, through body tissues. Unlike X-rays, ultrasounds do not use radiation. Physical exam is a very simple and painless test where your provider feels your neck for any growths or enlargement of the thyroid. Thyroid disease management is follow up procedure, the goal is to return thyroid hormones levels to normal. This can be done in a variety of ways and each specific treatment will depend on the cause of your thyroid condition. If you have high levels of thyroid hormones (hyperthyroidism), disease management with treatment can include Anti-thyroid drugs (methimazole and propylthioracil), these are medications that stop your thyroid from making hormones Radioactive iodine: This treatment damages the cells of your thyroid, preventing it from making high levels of thyroid hormones[11]. Beta blockers: These medications don’t change the amount of hormones in your body, but they help manage   your symptoms. Surgery:  A surgeon may surgically remove your thyroid (thyroidectomy). This will stop it from creating hormones. However, you will need to take thyroid replacement hormones for the rest of your life. If you have low levels of thyroid hormones (hypothyroidism), the main treatment option is Thyroid replacement medication: This drug is a synthetic (man-made) way to add thyroid hormones back into your body. One drug that’s commonly used is called levothyroxine. By using a medication, you can manage thyroid disease and thyroid tumorigenesis [12].
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