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24 Cards in this Set
- Front
- Back
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Thyroid disease |
- most common endocrine diseases, very frequent, divided into 2 groups 1st: alteration of function of thyroid gland (hypo and hyper function) 2nd: alteration of thyroid parenchyma + formation of nodules |
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Anatomy of thyroid |
- located in anterior lower neck, composed of 2 lobes connected by the isthmus, weight= 25grams but can reach 100-200 grams |
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Embryology |
- derives from thyroglossal duct that’s located during fetal life in midline of tongue - ectopic thyroid diseases rare but may be found around the thyroiglossal duct, laterally in the neck or in distal places as the tongue and mediastinum - completes development 12 weeks of life - thyroid hormones are fundamental for development of CNS - conditions that cause enlargement of thyroid gland can compress the trachea= dysphagia and dysphonia |
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Vascularization of thyroid |
- very vascularized, supplied by superior thyroid artery (branch of external carotid) and inferior thyroid artery (branch of subclavian) - venous system supplied by internal jugulars and brachiosaurus-cephalon veins - Vascularization of the thyroid is higher than the renal parenchyma and is related to function particularly in conditions of hyper function - near and posterior of the thyroid: right and left recurrent laryngeal nerves (rln)= important for laryngeal function - posterior of the thyroid: 4 parathyroid glands devoted to secretion of PTH = crucial for regulating calcium metabolism |
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Internal structure of the thyroid |
- formed by irregularly shaped lobules divided by thin connective tissue - functional unit: follicle that is made of the central colloid core surrounded by a single layered epithelium composed by thyrocytes - colloid is produced by the follicular epithelial cells and consists of a iodinated glycoprotein iodothyroglobulin stored in the form of active thyroid hormones T3 and T4 - this is a unique case of the endocrine system in which we have a continuous storage of inactive hormones in the gland - in the thyroid we have other cells: C cells (parafollicular/clear cells) different from thyrocytes and derive from neuroendocrine system,secrete calcitonin important for medullary thyroid carcinoma (hyperactivity of C cells) |
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Physiology of the thyroid |
- main function of the gland is to secrete T3 and T4, this secretion occurs in 3 phases: 1st: iodine trapping 2nd: thyroglobulin synthesis 3rd: organification of iodide and iodothyronine synthesis |
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Iodine trapping |
- iodine is fundamental to produce T3 AND T4, 1mg is needed weekly, ingested orally, absorbed by GI tract 1/5 is transported with circulation to thyroid and used for synthesis of thyroid hormones, the rest is excreted by the kidney - uptake of iodine from the circulation is mediated by the action of sodium iodide symporter (NIS) - iodine is transported out of the thyroid cells across apical membrane into follicle by a chloride-iodide ion counter transporter molecule called pendrin |
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Dietary iodine |
- thyroid gland requires 60-75 mcg of iodine daily to produce normal amount of thyroid hormones - daily intake is around 150mcg in adults - iodine can be introduced through medication, diagnostic agents, dietary supplements and food additives - the most common cause of thyroid dysfunction is IODINE INSUFFICIENCY THYROID HORMONE ARE FUNDAMENTAL FOR CNS DEVELOPMENT IN FETAL LIFE SO IODINE INSUFFICIENCY DURING PREGNANCY CAN RESULT IN CRETINISM |
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THYROGLOBULIN synthesis |
- large glycoprotein, 70 as of tyrosine, major substrates that combine with iodine to form thyroid hormones - thyroglobulin is produced by thyrocytes |
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Iodine oxidation and organification |
- iodine has to undergo oxidation performed by peroxidase (tpo) to be combined with thyroglobulin - dysfunction of this enzyme can result in thyroid dysfunction After this process, we have the combination of iodine and tyrosine residues of thyroglobulin - binding of iodine with thyroglobulin molecule = organification of thyroglobulin - creating hormonally inactive iodotyrosine = monoiodotyrosine(MIT) and diiodotyrosine (DIT) |
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T3 and T4 formation |
- 2 molecules of DIT are joined together = formation of thyroxin T4, which is a major hormonal product of the coupling reaction - when 1 molecule of MIT couples with 1 molecule of DIT they form T3 |
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Storage of thyroid hormones |
- in the colloid: we have storage of inactive thyroid hormones that can supply the patient for 3 months of thyroid inactivity |
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T3 and T4 in circulation |
- T4 prevalent in circulation (93%) - biologically active hormone: T3 WHY? Because T3 is formed by diiodination of T4 in target cells: this is a mechanism to protect our body and avoid large access to the active thyroid hormone - 99% of T3 and T4 are bound to plasma proteins The most important plasma protein is thyroxine binding globulin. |
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Hypothalamus pituitary thyroid axes |
- thyroid hormones secretion is regulated by 2 feedbacks: 1st: positive feedback constituted of TRH by hypothalamus which stimulates the pituitary to secrete TSH. TSH stimulates the thyroid to produce T3 and T4 2nd: negative feedback of T3 and T4 on hypothalamus and hypophysis to avoid overstimulation of the thyroid |
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TRH (thyrotropin releasing hormone) |
- polypeptide hormone produced by hypothalamus - undetectable in circulation, stimulates secretion of TSH - inhibited by thyroid hormones, inflammation and glucocorticoids, hence in every condition of hyper inflammation/sepsis we can observe a depression of TRH and TSH. It is stimulated by the sympathetic nervous system activity and cold - TRH has an effect on pituitary by stimulating secretion of prolactin by lactotroph cells that in pathological conditions results in an increase of TRH and hyper production of prolactin In hypothyroidism, the lack of T3 and T4= absence of negative feedback on TRH so it results in an increase in prolactin |
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TSH |
- produced by anterior pituitary glycoprotein hormone formed by alpha and beta subunit secreted in pulsatilla fashion, inhibited by thyroid hormones, somatostatin analogs, inflammation, dopaminergic agonists and glucocorticoids - has several effects on thyroid: Increased proteolysis of thyroglobulin releasing thyroids into circulation Increased activity of iodide pump which increases iodide trapping Increased iodinating of tyrosine to form thyroid hormones and increase size and secretory activity of thyroid cells |
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T3 and T4 activity |
- mediate by intracellular binding to their specific receptors - thyroid hormone receptors are either attached to DNA genetic strands or close to them , the binding activates a large number of genes thyroid hormone actions: - Rate of utilization of foods for energy is accelerated - rate of protein synthesis is increased and catabolism is increased - mental processes are excited and activities of most endocrine glands are increased - thyroid hormones increase the number and activity of mitochondrion and active transport of ions through cells membranes - regulation of energy and body temperature - effects on glucose metabolism - lipolysis and lipogenesis - protein synthesis - effects on CNS - effects on CV system |
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Effects on cardiovascular system |
- in order to supply the increased energy our organs require increased blood supply, thyroid hormones increase the contractility of the cardiac muscle= positive ionotropic effect heart frequency = positive chronic topic effect Hypothyroidism= increased stimulation of heart= aryhtmias/ heart failures |
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Other thyroid functions |
- increased intestinal motility - increased synthesis of erythropoietin - increased renal perfusion and glomerular filtration - regulate skin and appendages tropism - stimulated endogenous hormonal production (GH) - facilitate reproductive functions |
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Thyroid diseases |
- functionality alterations: hyperfunctioning or hypofunctioning - nodular: benign or malignant Hyper function: - thyrotoxicosis caused by increased circulating levels of T3 AND T4 - hyperthyroidism caused by increasing circulating levels of T3 and 4 BUT CAUSED BY A SPECIFIC THYROID HYPERFUNCTION - Hypofunction: hypothyroidism characterized by lower circulating thyroid hormone level and final lowering in metabolic activity |
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Biochemical examinations |
- thyroid hyperfunction = high T4 and T3 and low TRH and TSH - thyroid hypofunction= low T4 and T3 and high TRH and TSH - overt hyper/hypothyroidism: reduced/suppressed TSH with increased T4 and T3 - sublinical hyper/hypothyroidism: reduced or suppressed TSH with normal T4 and T3 - overt hypothyroidism: high TSH and low T4 and/or T3 - subclinical hypothyroidism: high TSH and normal T3 and T4 |
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Imaging |
- ultrasound (best) - thyroid scintigraphy: evaluates uptake of iodine |
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Iodine deficiency |
- thyroid cannot produce enough iodine - increase of TSH = goiter - goiter is an enlarged thyroid gland preventing production of T3 AND T4, secreted large quantities of TSH, tropic action of TSH leading to cells secreting thyroglobulin colloid into follicles and the gland becomes larger |
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Iodine excess |
- in normal individuals it causes a mild transient hypothyroidism: WOLFF-CHAIKOFF EFFECT: protective down regulation of thyroid hormone production in presence of large amounts of iodine, more pronounced in hypothyroidism patients JOD-BASEDOW EFFECT: overproduction of thyroid hormone in presence of large amounts of iodine, typically occurs in hyperthyroid patients/patients with endemic goiter |
