T3 is one of the two major hormones released from the thyroid. It is also the more important one because it is more potent than T4. Therefore, T3 level is crucial to.Thyroid hormone influences a wide range of processes, including growth, development, maturation of the nervous system, reproduction, metabolism, and muscle function. Hyperthyroidism: Practice Essentials, Background, Pathophysiology. Genetic factors appear to influence the incidence of thyrotoxicosis. Autoimmune thyroid disease, including Hashimoto hypothyroidism and Graves disease, often occurs in multiple members of a family. Several genetic syndromes have been associated with hyperthyroidism, especially autoimmune thyroid disease. Mc. Cune- Albright syndrome is caused by mutations in the GNAS gene. This gene encodes the stimulatory G- protein alpha subunit, which is a key component of many signal transduction pathways. Levothyroxine is typically used to treat hypothyroidism, and is the treatment of choice for people with hypothyroidism, who often require lifelong. ![]()
Patients present with the classic triad of polyostotic fibrous dysplasia, irregular caf. The syndrome may also include facial asymmetry, Cushing syndrome, hyperthyroidism, and acromegaly. These disorders include the following: Familial gestational hyperthyroidism. One type of nonimmune hyperthyroidism. Congenital nongoiterous thyrotoxicosis. Toxic thyroid adenoma with somatic mutation. Type II autoimmune polyendocrine syndrome is associated with hyperthyroidism and hypothyroidism, as well as type 1 diabetes mellitus and adrenal insufficiency. Patients may also have immune deficiency, as manifested by chronic mucosal candidiasis. Graves disease is felt to be an HLA- related, organ- specific defect in suppressor T- cell function. Similarly, subacute painful or granulomatous thyroiditis occurs more frequently in patients with HLA- Bw. Like other immune diseases, these thyroid conditions occur more frequently in women than in men. With the availability of genome- wide association studies, more than a dozen genes and gene regions have been found to be associated with an increased risk for development of thyrotoxicosis, particularly Graves disease. One study, however, found an association between development of toxic multinodular goiter (Plummer disease) and a single- nucleotide polymorphism (SNP) in the TSHR gene. This SNP was seen in 9. Graves disease, and 3. Iodine intake. Iodine intake also appears to influence the occurrence of thyrotoxicosis. Clearly, patients in borderline iodine- deficient areas of the world develop nodular goiter, often with areas of thyroid autonomy. When members of this population move to areas of sufficient iodine intake, thyrotoxicosis occurs. Evidence exists that iodine can act as an immune stimulator, precipitating autoimmune thyroid disease and acting as a substrate for additional thyroid hormone synthesis. Graves disease. The most common cause of thyrotoxicosis is Graves disease (5. Graves disease is an organ- specific autoimmune disorder characterized by a variety of circulating antibodies, including common autoimmune antibodies, as well as anti- TPO and anti- TG antibodies. The most important autoantibody is TSI, which is directed toward epitopes of the TSH receptor and acts as a TSH- receptor agonist. Like TSH, TSI binds to the TSH receptor on the thyroid follicular cells to activate thyroid hormone synthesis and release and thyroid gland growth (hypertrophy). This results in the characteristic picture of Graves thyrotoxicosis, with a diffusely enlarged thyroid, very high radioactive iodine uptake, and excessive thyroid hormone levels compared with a healthy thyroid (see the images below). Thyroid hormone levels can be highly elevated in Graves disease. Clinical findings specific to Graves disease include thyroid ophthalmopathy (periorbital edema, chemosis . This autoimmune condition may be associated with other autoimmune diseases, such as pernicious anemia, myasthenia gravis, vitiligo, adrenal insufficiency, celiac disease, and type 1 diabetes mellitus. Subacute thyroiditis. The next most common cause of thyrotoxicosis is subacute thyroiditis (approximately 1. A typical nuclear scintigraphy scan shows no radioactive iodine uptake (RAIU) in the thyrotoxic phase of the disease (see the images below). Thyroid hormone levels can be highly elevated in this condition. Absence of iodine 1. I) radioactive iodine uptake in patient with thyrotoxicosis and subacute painless or lymphocytic thyroiditis. Laboratory studies at time of scan demonstrated the following: thyroid- stimulating hormone (TSH), less than 0. IU/m. L; total thyroxine (T4), 2. Absence of thyroid uptake, low T3- to- T4 ratio, and low ESR confirm diagnosis of subacute painless thyroiditis. Toxic multinodular goiter. Toxic multinodular goiter (Plummer disease) accounts for 1. It occurs more commonly in elderly individuals, especially those with a long- standing goiter. Thyroid hormone excess develops very slowly over time and often is only mildly elevated at the time of diagnosis. Symptoms of thyrotoxicosis are mild, often because only a slight elevation of thyroid hormone levels is present, and the signs and symptoms of thyrotoxicosis often are blunted (apathetic hyperthyroidism) in older patients. However, very high thyroid hormone levels may occur in this condition after high iodine intake (eg, with iodinated radiocontrast or amiodarone exposure). Toxic adenoma. Toxic adenoma is caused by a single hyperfunctioning follicular thyroid adenoma. This disorder accounts for approximately 3- 5% of thyrotoxicosis cases. The excess secretion of thyroid hormone occurs from a benign monoclonal tumor that usually is larger than 2. The excess thyroid hormone suppresses TSH levels. RAIU usually is normal, and the radioactive iodine scan shows only the hot nodule, with the remainder of the normal thyroid gland suppressed because the TSH level is low. Other causes of thyrotoxicosis. Several rare causes of thyrotoxicosis exist that deserve mention. Struma ovarii is ectopic thyroid tissue associated with dermoid tumors or ovarian teratomas that can secrete excessive amounts of thyroid hormone and produce thyrotoxicosis. The antiarrhythmic drug amiodarone, which is rich in iodine and bears some structural similarity to T4, may cause thyrotoxicosis (see Thyroid Dysfunction Induced by Amiodarone Therapy). Iodide- induced thyrotoxicosis also occurs in patients with areas of thyroid autonomy, such as a multinodular goiter or autonomous nodule. Iodide- induced thyrotoxicosis appears to result from loss of the normal adaptation of the thyroid to iodide excess. It is treated with cessation of the excess iodine intake and with administration of antithyroid medication. Usually, after depletion of the excess iodine, thyroid functions return to preexposure levels. Patients with a molar hydatidiform pregnancy or choriocarcinoma have extremely high levels of beta human chorionic gonadotropin (. At very high levels of . These lesions maintain the ability to make thyroid hormone, and in patients with bulky tumors, production may be high enough to cause thyrotoxicosis. Reference Range, Interpretation, Collection and Panels. Description. The chemical structure of triiodothyronine is C1. H1. 2 I3 NO4. The thyroid is the only tissue that can oxidize iodide to a higher valence state that is essential for iodide organification and thyroid hormone biosynthesis. This is mediated by an enzyme called peroxidase (thyroperoxidase) and occurs at the luminal surface of the follicular cells of the thyroid gland. Thyroperoxidase, a tetrameric protein with a molecular weight of 6. Da, requires hydrogen peroxide (H2 O2) as an oxidizing agent. The H2 O2 is produced by a nicotinamide adenine dinucleotide phosphate (NADPH). Antithyroid drugs such as the thiourea group inhibit iodide oxidation and therefore its subsequent incorporation into monoiodotyrosine (MIT) and diiodotyrosine (DIT). Once iodination occurs, the iodine does not readily leave the thyroid. Free tyrosine can be iodinated but is not incorporated into proteins since t. RNA does not recognize iodinated tyrosine. The coupling of two DIT molecules to form T4 or of one DIT and one MIT to form T3 occurs within the thyroglobulin molecule. A separate coupling enzyme has not been found, and, since this is an oxidative process, it is believed to be mediated by the same thyroperoxidase by stimulation of free radical formation from iodotyrosine. Thyroid hormones thus formed are stored in the thyroglobulin until it is degraded and the hormones are released into the circulation. An enzyme called deiodinase removes iodide from the inactive monoiodothyronine and diiodothyronine molecules in the thyroid, which restores most of the iodide used in the biosynthesis of T4 and T3. From the thyroid hormones released into the bloodstream, a peripheral deiodinase in target tissues such as the pituitary, kidney, and liver selectively removes iodide from the 5. In the end organ, T3 is present in the two following forms: Type 1, which is present within the liver and accounts for 8. T4. Type 2, which is present within the pituitary gland. Thus, like thyroglobulin, T4 may also be considered a prohormone, the difference being that T4 has some intrinsic activity, while T3 is actually used by the end organ, and almost all metabolic activity depends on the action of T3. The effect of T3 on target tissues is about 4 times more than T4. T3 is just 2. 0% of the total thyroid hormones produced by the thyroid gland, while T4 is 8. However, the concentration of T3 in the human blood plasma is about 1/4. T4. This is observed in fact because of the short half- life of T3, which is only 2. T4 is about 6. 5 days. The thyroid hormones T3 (and T4) are transported in the circulation bound mainly to the protein carrier thyroid- binding protein thyroxine- binding globulin (TBG). Other binding proteins such as thyroxine- binding prealbumins and albumins are also present. More than 9. 9% of the T3 in the circulation is bound to TBG and several other minor proteins, while the remaining T3 exists as free hormone. In other words, the amount of free triiodothyronine is about 1/1. It is a measurement of the fraction of the circulatory T3 that exists in the free state in the blood, unbound to protein. It is important in evaluating the effectiveness of thyroid replacement therapy, in ruling out T3 thyrotoxicosis, and in detecting protein- binding abnormalities. In the peripheral tissues, the hormones bind to thyroid receptors in almost all the major organ systems in the body that are concerned with metabolism (eg, heart, brain, liver, muscle, skin). Being lipophilic, T3 (and T4) passes through the phospholipid bilayers of target cells. At the cellular level, T3 increases the basal metabolic rate by the production of the Na+/K+ - ATPase and, thus, increases the body's oxygen and energy consumption. T3 stimulates the production of RNA polymerase I and II and, therefore, increases the rate of protein synthesis, as well as its breakdown. Thus, when T3 levels are increased, the rate of protein breakdown exceeds the rate of synthesis, and weight is lost. It increases the rate of glycogen breakdown and glucose synthesis, resulting in gluconeogenesis. It also stimulates the breakdown of cholesterol and increases the number of low- density lipoprotein (LDL) receptors, thereby increasing the rate of lipolysis. In the target organs (eg, heart), T3 increases the heart rate and force of contraction, thus increasing cardiac output by increasing . This results in increased systolic blood pressure and decreased diastolic blood pressure. T3 is essential for the development of the lungs and nervous system in the fetus and newborn and its growth through infancy and childhood. It is also important in the development of the musculoskeletal system. When the levels of thyroid hormones are deranged, the symptoms and signs of hyperthyroidism or hypothyroidism are apparent and may be reflected in the blood levels of these hormones, most specifically TSH, produced and secreted by the pituitary gland. In fact, TSH levels are generally measured as the first line of testing in determining thyroid status, whether normal (euthyroid), hyperfunctioning (hyperthyroid), or hypofunctioning (hypothyroid), because the production and release of thyroid hormones from the thyroid gland depends on the pituitary- hypothalamus axis, which functions on the principle of negative feedback. This means that, when normal amounts of thyroid hormones are present in the blood, TSH release is suppressed; it is elevated when hormone levels are low and depressed when hormone levels are high. TSH release is further controlled by thyrotropin- releasing hormone (TRH) secreted by the hypothalamus, again by negative feedback. Primary thyroid dysfunction (ie, hyperthyroidism or hypothyroidism) results from disease in the thyroid gland itself, caused by either deficiency or absence of processing enzymes or an autoimmune process attacking these enzymes or the cellular architecture of the gland. It also results from deficiency in the intake of thyroid hormones (eg, endemic goiter) or impaired uptake and processing of iodine due to drugs. Secondary hyperthyroidism or hypothyroidism results from disease and/or dysfunction of the pituitary or the hypothalamus, leading to abnormal stimulation of the thyroid gland. Goiter, or thyromegaly (ie, enlargement of the thyroid gland), may or may not occur with hyperthyroidism or hypothyroidism. The thyroid gland does not become smaller than normal. Hyperthyroidism may result from increased levels of both T3 and T4, T3 only (T3 toxicosis), or T4 only (T4 toxicosis). T3 toxicosis may be caused by a toxic nodule and is generally seen in elderly individuals. In these patients, a subnormal T4 level, if measured in isolation, may give a mistaken impression of hypothyroidism. T4 toxicosis may result from increased iodine intake; in T3 or T4 toxicosis, the peripheral conversion of T4 to T3 is not affected. The symptoms and signs of hyperthyroidism include insomnia, weight loss, increased sweating, fatigue, loose motions, oligomenorrhea, tremors, palpitations, intolerance to heat and/or light, anxiety, tachycardia, eye changes, infertility, and osteoporosis. All or some of these features may be present in the same patient. In elderly persons, these changes may be missed owing to the effects of aging; this is termed . The most common method for the estimation of T3 is enzyme- linked immunosorbent assay (ELISA). The detailed description of the contents of the kit, instructions as to its use, and interpretation of results are outlined in the kit and are not mentioned in detail here. The human T3 ELISA kit, which uses a monoclonal anti- T3 and T3- horseradish peroxidase (HRP) conjugate, can be used to measure very low concentrations of T3 in small serum volumes (5. The buffer and sample are incubated together with anti- T3 antibody. Afterward, the diluted T3- HRP conjugate is added to each well and incubated. After incubation is complete, the T3 ELISA kit. Then, the wells are incubated with a substrate for the enzyme, the reaction of which results in a complex with a blue color. In the final step, the reaction is stopped upon addition of a stopping solution, and the color of the solution then changes to yellow. The image below depicts an ELISA washer. The color intensity is measured in a microplate reader with spectrophotometry at 4. Because the T3 from the sample competes with the T3- HRP conjugate for the anti- T3 antibody. As the T3 from the sample occupies more sites, fewer sites are left to bind T3- HRP conjugate since the site number is limited. Standards of known T3 concentrations are processed simultaneously with the samples undergoing assay, and a standard curve that relates the color intensity (optical density) to T3 concentration is plotted. Indications. T3 levels are obtained in suspected cases of hyperthyroidism, either because the patient has typical symptoms or when the TSH levels are lower than normal. Mild or subclinical hyperthyroidism occurs when the TSH level is low but the T4 and T3 levels are normal. Obvious hyperthyroid signs and symptoms exist when the TSH is low and the T4 and T3 levels are high or at the higher end of normal. Normal or low T3 or T4 levels along with high TSH levels suggest mild or subclinical hypothyroidism and overt hypothyroidism, respectively, while normal to low T3 and T4 levels along with a low TSH level suggest nonthyroidal and pituitary or secondary hypothyroidism. A synthetic preparation of T3 may be used as replacement therapy in patients with low- T3 syndrome and concomitant cardiomyopathy. Drugs that cause elevated or false- positive values include amiodarone, aspirin, carbamazepine, fenoprofen, phenytoin, ranitidine, thyroxine, and levothyroxine. Drugs that cause reduced or false- negative values include corticosteroids, methimazole, propranolol, somatostatin, and radiographic agents. Side Effects, Interactions, Warning, Dosage & Uses. What are the possible side effects of liothyronine (Cytomel)? Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat. Less serious side effects may include temporary hair loss (especially in children). This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at.. Read All Potential Side Effects and See Pictures of Cytomel »What are the precautions when taking liothyronine sodium (Cytomel)? Before taking liothyronine, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details. Before using this medicine, consult your doctor or pharmacist if you have: decreased adrenal gland function, kidney disease (e. Levothyroxine - Wikipedia. This article is about levothyroxine as a pharmaceutical drug. For its role as a hormone, see Thyroid hormone. Levothyroxine. Clinical data. AHFS/Drugs. com. Monograph. Medline. Plusa. 68. Pregnancycategory. US: A (No risk in human studies)Routes ofadministrationby mouth, intravenous. ATC code. Legal status. Legal status. Pharmacokinetic data. Bioavailability~1. Metabolismmainly in liver, kidneys, brain and muscles. Biological half- lifeca. It may also be used to treat and prevent certain types of thyroid tumors. It is not indicated for weight loss. Levothyroxine is taken by mouth or given by injection into a vein. Maximum effect from a specific dose can take up to six weeks to occur. Use is not recommended in people who have had a recent heart attack. Use during pregnancy has been found to be safe. It is recommended that dosing be based on regular measurements of TSH and T4 levels in the blood. Much of the effect of levothyroxine is following its conversion to triiodothyronine (T3). Other predictors of the required dosage are sex, BMI, deiodinase activity (SPINA- GD) and etiology of hypothyroidism. Food and Drug Administration pregnancy categories, levothyroxoine has been assigned Pregnancy Category A. Long- term suppression of TSH values below normal values will frequently cause cardiac side- effects and contribute to decreases in bone mineral density (low TSH levels are also well known to contribute to osteoporosis). Acute overdose may cause fever, hypoglycemia, heart failure, coma, and unrecognized adrenal insufficiency. Acute massive overdose may be life- threatening; treatment should be symptomatic and supportive. Massive overdose can be associated with increased sympathetic activity and thus require treatment with beta- blockers. Examples include calcium and iron supplements taken within four hours of levothyroxine. Grapefruit juice may delay the absorption of levothyroxine, but based on a study of 1. Combination of levothyroxine with ketamine may cause hypertension and tachycardia. On the other hand, lithium can cause hyperthyroidism (but most often hypothyroidism) by affecting iodine metabolism of the thyroid itself and thus inhibits synthetic levothyroxine as well. The bioavailability of the drug is decreased by dietary fiber. There are also numerous generic versions. The related drug dextrothyroxine (D- thyroxine) was used in the past as a treatment for hypercholesterolemia (elevated cholesterol levels) but was withdrawn due to cardiac side effects. References. The American Society of Health- System Pharmacists. Retrieved 8 December 2. Pharmacology for Women's Health. Jones & Bartlett Publishers. World Health Organization. Retrieved 8 December 2. International Drug Price Indicator Guide. Retrieved 8 December 2. Tarascon Pocket Pharmacopoeia 2. Deluxe Lab- Coat Edition. Jones & Bartlett Learning. BMJ (Clinical research ed.). Retrieved 2. 0 April 2. American Academy of Family Physicians. Retrieved 2. 0 April 2. The Journal of Clinical Endocrinology and Metabolism. Annals of Internal Medicine. Retrieved 2. 0 April 2. Retrieved 2. 0 April 2. Retrieved 1. 8 July 2. Retrieved 2. 0 April 2. Scandinavian Journal of Surgery. Retrieved 3. 1 October 2. Neafsey; Laura Cox Dzurec (2. The Internet Journal of Advanced Nursing Practice. New York: Mary Ann Liebert. ISBN 9. 78- 3- 8. Clinical Practice and Epidemiology in Mental Health. ISBN 9. 78- 0- 4. IMS Institute for Healthcare Informatics. Retrieved 2. 0 April 2. Institute for Safe Medication Practices. Retrieved 2. 0 April 2.
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