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Levothyroxine (thyroxine; T4) is the treatment of choice It is partially converted in the body to T3, the more active thyroid hormone Hypothyroid patients who are taking thyroxine replacement typically have serum T3 levels that are lower than normal, owing to their lack of thyroidal T3 secretion Oral administration of T3 causes abnormal peaks in serum T3 and the usefulness of T3 for hypothyroidism is controversial; a sustained-release T3 preparation is not commercially available In patients taking a certain daily dose of levothyroxine, significant increases in serum T4 levels are seen within 1 2 weeks, and near-peak levels are seen within 3 4 weeks It is best taken in the morning with water, avoiding concomitant intake of foods and drugs that may interfere with its absorption (see below) Brand preparations of levothyroxine in the United States appear to be bioequivalent to each other and certain generics Before therapy with thyroid hormone is commenced, the hypothyroid patient requires at least a clinical assessment for adrenal insufficiency, which would require concurrent treatment
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Patients without coronary insufficiency who are under age 60 years may receive starting doses of oral levothyroxine of 50 100 mcg/daily up to a maximum of 16 mcg/kg body weight daily Women who are pregnant with significant hypothyroidism may begin therapy with levothyroxine at doses of 100 150 mcg orally daily Patients with coronary disease or those who are over age 60 years are treated with smaller initial doses of levothyroxine, 25 50 mcg daily; higher initial doses may be used if such patients are severely hypothyroid The dose can be increased by 25 mcg every 1 3 weeks until the patient is euthyroid Patients with hypothyroidism and ischemic heart disease may begin thyroxine therapy following coronary artery angioplasty or bypass Patients with severe hypothyroidism require larger initial doses of levothyroxine, particularly since myxedema itself can interfere with the intestinal absorption of T4 Myxedema coma is a medical emergency with a high mortality rate Levothyroxine sodium 400 mcg is given intravenously as a loading dose, followed by 100 mcg intravenously daily The hypothermic patient is warmed only with blankets, since faster warming can precipitate cardiovascular collapse Patients with hypercapnia require intubation and assisted mechanical ventilation Infections must be detected and treated aggressively Patients in whom concomitant adrenal insufficiency is suspected are treated with hydrocortisone, 100 mg intravenously, followed by 25 50 mg every 8 hours
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receiving oral estrogens) may help make the difficult decision about whether to increase the levothyroxine dose If the serum T3 level is low or low normal, such a patient may benefit from a careful increase in T4 dosage; if a definite clinical benefit is achieved, the higher dose is continued However, long-term monitoring for atrial arrhythmias and for osteoporosis is recommended for such patients, though such complications are uncommon in those who are clinically euthyroid The malaise felt by some hypothyroid patients despite apparent optimal replacement therapy with T4 may be caused by a low concentration of T3 in certain tissues Studies adding T3 to T4 therapy have not typically shown objective improvement, but patients tend to lose weight and to subjectively prefer combined T4/T3 mixtures to T4 alone A Dutch double-blind study of 141 hypothyroid patients found that most patients subjectively preferred not T4 but a combined T4/T3 preparation in 5:1 or 10:1 ratios, such that TSH was often suppressed; satisfaction correlated with weight loss
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The increased T4 dosage requirements during pregnancy are believed to be due to several factors: (1) Rising estrogen levels during pregnancy increase thyroxine binding globulin (TBG) serum concentrations, reducing FT4 levels (2) Placental deiodinase promotes the turnover of T4 (3) Supplemental iron and prenatal multivitamins containing iron can bind to oral T4 and reduce its intestinal absorption Similarly, supplemental calcium can also reduce T4 absorption Therefore, it is important that patients take their T4 replacement at least 4 hours before or after such dietary supplements Postpartum, T4 replacement requirements ordinarily return to prepregnancy levels Elevated serum TSH levels usually indicate underreplacement with levothyroxine However, before increasing the T4 dosage, it is wise to (1) confirm that the patient is receiving the prescribed dosage of thyroxine replacement and (2) question the patient about compliance and the presence of angina It is also important to consider the following: A high TSH in a patient receiving standard replacement doses of T4 may indicate malabsorption of levothyroxine due to concurrent administration with binding substances, particularly iron preparations, raloxifene, sucralfate, aluminum hydroxide antacids, calcium supplements, and soy milk or soy protein supplements Bile acid-binding resins such as cholestyramine can bind T4 and impair its absorption even when administered 5 hours before the T4 Malabsorption of T4 can also occur in short bowel syndrome; therapy with medium chain triglyceride oil may improve absorption Impaired absorption of T4 can also be caused by diarrhea of any cause or malabsorption due to sprue, regional enteritis, liver disease, or pancreatic exocrine insufficiency Serum TSH may be elevated transiently in acute psychiatric illness and during recovery from nonthyroidal illness Autoimmune disease can cause false elevations of TSH by interfering with the assay A high TSH can also be caused by thyrotropin-secreting pituitary tumors TSH may be increased by phenothiazines and atypical antipsychotics Suppressed serum TSH levels < 01 mU/L (using a sensitive assay) may indicate overreplacement with levothyroxine; if such a patient has manifestations of hyperthyroidism, the dosage of levothyroxine is reduced However, some patients with suppressed serum TSH levels exhibit no symptoms of hyperthyroidism For such patients, it is important to determine whether hypopituitarism or severe nonthyroidal illness is present, which can result in low serum TSH levels without hyperthyroidism TSH can also be suppressed by certain medications, such as nonsteroidal anti-inflammatory drugs, opioids, nifedipine, verapamil, and urgent administration of corticosteroids Absent such conditions, a clinically euthyroid patient with a low serum TSH should be given a lower dosage of levothyroxine Patients who exhibit hypothyroid symptoms on the reduced dosage of levothyroxine may have their higher dosage resumed, unless they have coronary insufficiency Some hypothyroid patients treated with levothyroxine complain of hypothyroid-type symptoms, particularly fatigue, despite having normal or suppressed levels of TSH and normal levels of FT4 Such patients require careful assessment for other concurrent illnesses such as adrenal insufficiency, hypogonadism, anemia, or depression If such conditions are treated and hypothyroid-type symptoms persist despite normal or low TSH levels, a serum T3 level (FT3 in pregnancy and women
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