foreign hypothyroidism hypo refers to having too little and thyroid refers to thyroid hormones so hypothyroidism refers to a condition where there's not enough thyroid hormones now as treatment for hypothyroidism we can use thyroid hormone analogues as a replacement to supply the body with normal levels of thyroid hormones there are two different thyroid hormones triidothyronine or T3 and thyroxine or T4 there are two tyrosine-based iodine-containing hormones that are secreted by the thyroid gland which is located anteriorly in the neck and consists of two lobes that look like two thumbs hooked together in the shape of a v now if we zoom into the thyroid gland we'll find thousands of follicles which are small Hollow spheres whose walls are lined with follicular cells or thyrocytes zooming in these follicular cells have an apical side that surrounds a central Lumen filled with a viscous fluid called the colloid the colloid contains the precursor hormone thyroglobulin the basol lateral side of follicular cells is in contact with blood vessels that supply these cells now synthesis of thyroid hormones inside the follicles involves a few important steps first the inorganic iodide ions present in a low concentration in the blood are actively taken up by the basol lateral side of the follicular cells along with two sodium ions via a sodium iodide supporter this step is known as iodide trap the iodide ion is then pumped into the colloid via the pendrin protein where it undergoes oxidation with the enzyme thyroid peroxidase or TPO which changes it into an organic iodine atom it's then attached to tyrosine amino acid residues which are found throughout thyroglobulin this step is known as iodination some tyrosine residues are bound by only one iodine whereas others are bound by two iodine atoms yielding mono iodo tyrosine or MIT and diiodo tyrosine or dit respectively these molecules are then coupled together by the same enzyme thyroid peroxidase or TPO this process is known as coupling coupling one MIT with one dit creates T3 while linking two dit molecules creates T4 in general T4 is created in Greater amounts than T3 T3 is the more active form with a half-life of one to two days while T4 is the less active form with a longer half-life of six to eight days now production and secretion of thyroid hormones is under the control of the hypothalamus pituitary axis the hypothalamus located at the base of the brain secretes thyrotropin-releasing hormone or simply trh which stimulates the anterior pituitary cells called thyrotroph cells to release the thyroid stimulating hormone or TSH into the bloodstream TSH then travels to the thyroid gland and binds to the TSH receptors located in the membrane of the follicular cells of the thyroid gland when TSH binds to the TSH receptor it goes on to promote every aspect of T3 and T4 production ranging from the iodide trapping to the release of thyroid hormones into the bloodstream once released from the thyroid gland most of the T3 and T4 travel via the blood by binding with the thyroxine-binding globulin or tbg to reach the target cells alternatively small amounts of T3 and T4 stay Unbound and therefore they are referred to as free thyroid hormones only free thyroid hormones are physiologically active because they are able to enter the cell now once inside the cell T4 is mostly converted into T3 by the enzyme 5-diodinase T3 binds to thyroid hormone receptors which are within the cell's nucleus and these receptors regulate gene expression which ultimately lead to various metabolic and physiologic effects in the body this increase in metabolism uses up sugars and fats for energy and produces more body heat thyroid hormones also help activate the sympathetic nervous system which is responsible for the fight-or-flight response this increases heart rate and cardiac output respiratory rate and mental alertness thyroid hormones also increase the gastrointestinal motility and they are necessary for normal neuronal development in growing fetuses and young children now there are three types of hypothyroidism primary secondary and tertiary in primary hypothyroidism the thyroid gland is the problem because it isn't making enough thyroid hormones iodine deficiency can be a cause of primary hypothyroidism because the follicular cells don't have the iodide ions they need to produce T3 and T4 in countries that do fortify food with iodide the most common cause of primary hypothyroidism is Hashimoto thyroiditis an autoimmune disorder where T cells and auto antibodies like anti-thyroid peroxidase and antithyroglobulin infiltrate the thyroid and cause follicular cell damage and inhibit normal thyroid function primary hypothyroidism can also happen after treatment for hyperthyroidism which usually involves surgically removing the thyroid gland or destroying it with radioiodine therapy now in secondary hypothyroidism also called Central hypothyroidism the issue is that the body doesn't produce enough TSH is a really important hormone which stimulates the thyroid gland to uptake iodide from the circulation and produce T3 and T4 when needed it typically happens because there's a tumor in the anterior pituitary which compresses the gland and prevents TSH production which leads to decreased level of T3 and T4 finally in tertiary hypothyroidism the hypothalamus doesn't produce enough thyrotropin releasing hormone or trh as a result these individuals have decreased levels of TSH and subsequently decreased production of T3 and T4 another form of hypothyroidism is congenital hypothyroidism which is defined as thyroid hormone deficiency present at birth it can occur due to an absent or underdeveloped thyroid gland which is known as thyroid discgenesis or due to an ineffective production of thyroid hormones also known as thyroid dis-harmonogenesis a person with low thyroid hormone levels typically has cold dry skin cold intolerance hair loss weight gain and constipation they might also suffer mental symptoms like lethargy and fatigue in infants and children hypothyroidism could delay physical and mental development now in some elderly individuals with low levels of thyroid hormones any stressful event like an infection or a heart attack can lead to an acute decrease in T3 and T4 this leads to a medical emergency known as myxedema coma a rare condition associated with clinical features such as sudden drop in body temperature low heart rate low blood pressure hypoventilation confusion and coma okay now in a person with hypothyroidism we want to increase the T3 and T4 to normal levels and if the hypothyroidism is due to iodine deficiency the treatment is to give foods rich in iodine like fish eggs meat and iodized salt on the other hand in individuals with primary secondary tertiary or congenital hypothyroidism the treatment of choice is to give synthetic thyroid hormone Replacements or thyroid replacement therapy now the synthetic hormone that's similar to T3 is called lyothyranine and the one that's similar to T4 is called levothyroxine both lyothyronine and levothyroxine are usually given pororal but can also be given via the intravenous route of the two synthetic thyroid hormones lyothyronine is shorter acting but much more potent meaning it's able to treat the symptoms of hypothyroidism at a lower dose since it's a T3 analog it could directly enter the target cell and take effect very rapidly this is why intravenous lyothyronine is the drug of choice in emergencies like myxedema coma its high potency also leads to more severe side effects which are the same as hyperthyroidism this includes heat intolerance anxiety diarrhea Tremors and tachycardia which may lead to cardiac arrhythmias that's why lyothyronine is contraindicated in individuals with heart conditions on the other hand levothyroxine is much less potent but longer acting just like natural T4 when it reaches the target cells it first needs to be converted to T3 by the enzyme 5diodinase due to this levothyroxine takes effect much slower than lyothyronine and individuals may require six to eight weeks of therapy to achieve a normal T3 and T4 level levothyroxine is the medication of choice in the long-term treatment of hypothyroidism but also in the treatment of hypothyroid individuals during pregnancy it's important to note that the dose of Levothyroxine should be increased once the pregnancy is detected because during pregnancy there are high levels of circulating estrogen which increases the concentration of thyroxine-binding globulins and more thyroxine-binding globulins means less free T4 don't forget that the thyroid hormones are also important for normal fetal development after delivery the levothyroxine dose should be reduced to the dose that was taken before the pregnancy in contrast to lyothyronine the hyperthyroidism side effects associated with levothyroxine are less severe but the elderly individuals with cardiovascular problems and individuals with long-standing hypothyroidism are at risk for developing cardiovascular side effects these individuals have an increased sensitivity to stimulatory effects of T4 on the heart thus they should start the treatment with lower Doses and gradually increase it to prevent cardiovascular side effects now moving on to Major interactions of Levothyroxine with other medications which can be subdivided into several groups the first group includes medications that decrease levothyroxine absorption such as iron calcium aluminum hydroxide proton pump inhibitors or ppis sucralfate and bile acid binding agents like cholesteramine since they are associated with decreased absorption individuals treated with these medications require higher doses of Levothyroxine to achieve therapeutic effects the next group covers medications that increase thyroid hormone metabolism such as Rifampin phenytoin and carbamazepine just like with the first group these individuals require higher doses of Levothyroxine next we have medications that increase the concentration of thyroxine-binding globulins in the blood such as estrogen reloxaphene tamoxifen heroin and methadone more thyroxine binding globulins in the blood means less free T4 therefore these individuals also require more levothyroxine to achieve therapeutic effects on the flip side the last group covers medications that decrease the concentration of thyroxine binding globulins in the blood such as androgens glucocorticoids anabolic steroids and slow release nicotinic acid in other words less thyroxine binding globulins in the blood means more free T4 so these individuals require lower doses of Levothyroxine finally it's important to note that Propranolol inhibits the enzyme 5-de-iodinase and reduces the conversion of T4 to T3 as a result Propranolol favors the less active form of thyroid hormones T4 therefore individuals on Propranolol also require higher doses of Levothyroxine another indication of synthetic thyroid hormones is TSH suppressive therapy let's put it this way some conditions such as thyroid cancer or thyroid nodules are TSH sensitive meaning they grow when there are high levels of thyroid stimulating hormone in the blood in TSH suppressive therapy synthetic thyroid hormones inhibit the secretion of thyrotropin-releasing hormone thereby reducing the secretion of thyroid stimulating hormone now more specifically lyothyronine can be used to prevent the growth of thyroid nodules while levothyroxine can be used to prevent the recurrence of thyroid cancer since thyroid hormones stimulate bone resorption and bone remodeling long-term treatment with thyroid hormones can cause osteoporosis but they can also worsen glycemic control in individuals with diabetes finally thyroid replacement therapy should not be used to treat obesity or cause weight loss now as far as the contraindications go thyroid replacement therapy is contraindicated in individuals with uncorrected adrenal insufficiency this is because thyroid hormones increase the hepatic metabolism of glucocorticoids which are hormones produced by the adrenal glands now in adrenal insufficiency adrenal glands are unable to increase glucocorticoid production and compensate for increased turnover ultimately this can precipitate adrenal crisis so it's important to note that individuals with hypothyroidism should treat adrenal insufficiency before hypothyroidism other preparations of thyroid hormones used to treat hypothyroidism include liatrix and desiccated thyroid layatrix is a synthetically made mixture of T4 and T3 in a four to one weight-based ratio on the other hand porcine-derived desiccated thyroid also known as thyroid extract contains a mix of natural T3 and T4 hormones derived from pigs however it's not as reliable as the synthetic hormones since the amount of T3 and T4 in each dose could vary which leads to unpredictability in its potency and duration both liatrix and desiccated thyroid are given orally alright as a quick recap when treating hypothyroidism iodine deficiency can be treated by giving foods rich in iodine if the cause is thyroid or pituitary damage synthetic or non-synthetic thyroid hormone replacement therapy could be used lyothyronine and levothyroxine are synthetic forms of T3 and T4 levothyroxine is the drug of choice for treating chronic hypothyroidism while lyothyronine is used for myxedema coma liatrix is a synthetically made mixture of T4 and T3 in a four to one weight-based ratio non-synthetic thyroid hormone replacement uses porcine-derived desiccated thyroid which is a mix of natural T3 and T4 derived from pigs but its effects are much less reliable when compared to synthetic thyroid hormones helping current and future clinicians Focus learn retain and Thrive learn more