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Differential Diagnosis
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True thyrotoxicosis must be distinguished from those conditions elevating serum T4 and T3 or suppressing serum TSH without affecting clinical status Some states of hypermetabolism without thyrotoxicosis notably severe anemia, leukemia, polycythemia, and cancer rarely cause confusion Pheochromocytoma is often associated with hypermetabolism, tachycardia, weight loss, and profuse sweating Acromegaly may also produce tachycardia, sweating, and thyroid enlargement Appropriate laboratory tests will easily distinguish these entities Cardiac disease (eg, atrial fibrillation, angina) refractory to treatment suggests the possibility of underlying ( apathetic ) hyperthyroidism Other causes of ophthalmoplegia (eg, myasthenia gravis) and exophthalmos (eg, orbital tumor, pseudotumor) must be considered Thyrotoxicosis must also be considered in the differential diagnosis of muscle weakness and osteoporosis Diabetes mellitus and Addison s disease may coexist with thyrotoxicosis
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Hypercalcemia, osteoporosis, and nephrocalcinosis may occur Decreased libido, impotence, decreased sperm count, and gynecomastia may be noted in men with hyperthyroidism Patients who have subclinical hyperthyroidism (suppressed TSH but normal FT4 and clinically euthyroid) generally do well without treatment In most such patients, serum TSH reverts to normal within 2 years No accelerated bone loss has been noted In one series, clinical hyperthyroidism developed in one of seven patients with subclinical hyperthyroidism after about 2 years
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A Graves Disease
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The treatment of Graves disease involves a choice of methods rather than a method of choice 1 Propranolol Propranolol is generally used for symptomatic relief until the hyperthyroidism is resolved It effectively relieves the tachycardia, tremor, diaphoresis, and anxiety that occur with hyperthyroidism due to any cause It is the initial treatment of choice for thyroid storm The periodic paralysis seen in association with thyrotoxicosis is also effectively treated with -blockade It has no effect on thyroid hormone secretion Treatment is usually begun with propranolol 20 mg orally, which is increased progressively until an adequate response is
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Patients with an established diagnosis of thyrotoxicosis usually undergo thyroid RAI uptake and scan A high RAI uptake is seen in Graves disease and toxic nodular goiter but can be
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with those taking propylthiouracil) have a lower risk of developing fulminant hepatic necrosis; methimazole therapy is also less likely to cause 131I treatment failure Rare complications peculiar to methimazole include serum sickness, cholestatic jaundice, loss of taste, alopecia, nephrotic syndrome, and hypoglycemia Methimazole is given orally in initial doses of 30 60 mg once daily; it may also be administered twice daily to reduce the likelihood of gastrointestinal upset The dosage is reduced as manifestations of hyperthyroidism resolve and as the FT4 level falls toward normal Methimazole is discontinued 4 days prior to 131I therapy for Graves disease and resumed at a lower dose 3 days after 131I therapy to avoid recurrence of hyperthyroidism About 4 weeks after 131I therapy, methimazole may be discontinued if the patient is euthyroid b Propylthiouracil Propylthiouracil is the drug of choice during breast-feeding or pregnancy, possibly causing fewer problems in the newborn Rare complications peculiar to propylthiouracil include arthritis, lupus erythematosus, aplastic anemia, thrombocytopenia, and hypoprothrombinemia Acute hepatitis occurs rarely and is treated with prednisone but may progress to liver failure Propylthiouracil is given orally in initial doses of 300 600 mg daily in four divided doses The dosage and frequency of administration are reduced as symptoms of hyperthyroidism resolve and the FT4 level approaches normal During pregnancy, the dose of propylthiouracil is kept below 200 mg/d to avoid goitrous hypothyroidism in the infant 3 Iodinated contrast agents These agents provide effective temporary treatment for thyrotoxicosis of any cause Iopanoic acid (Telepaque) or ipodate sodium (Bilivist, Oragrafin) is given orally in a dosage of 500 mg twice daily for 3 days, then 500 mg once daily These agents inhibit peripheral 5 -monodeiodination of T4, thereby blocking its conversion to active T3 Within 24 hours, serum T3 levels fall an average of 62% For patients with Graves disease, methimazole is begun first to block iodine organification; the next day, ipodate sodium or iopanoic acid may be added The iodinated contrast agents are particularly useful for patients who are very symptomatically thyrotoxic (see Thyroid Storm, below) They offer a therapeutic option for patients with T4 overdosage, subacute thyroiditis, and amiodarone-induced thyrotoxicosis and for those intolerant to thioureas and for newborns with thyrotoxicosis (due to maternal Graves disease) Treatment periods of 8 months or more are possible, but efficacy tends to wane with time In Graves disease, thyroid RAI uptake may be suppressed during treatment but typically returns to pretreatment uptake by 7 days after discontinuation of the drug, allowing 131I treatment 4 Radioactive iodine (131I) The administration of RAI is an excellent method of destroying overactive thyroid tissue (either diffuse or toxic nodular goiter) The RAI damages the cells that concentrate it There are ample data to conclude that patients who are treated with RAI in adulthood do not have an increased risk of subsequent thyroid cancer, leukemia, or other malignancies Similarly, individuals who were treated with RAI as teenagers have not shown any increased risk of malignancy in a 36-year retrospective study Children born to
achieved, usually 20 40 mg four times daily Doses as high as 80 mg four times daily are occasionally required A long-acting (LA) propranolol formulation provides more consistent relief; doses are 60, 80, 120, and 160 mg Propranolol LA is initially given every 12 hours for patients with severe hyperthyroidism, due to accelerated metabolism of the propranolol; it may be given once daily as hyperthyroidism improves 2 Thiourea drugs Methimazole or propylthiouracil is generally used for young adults or patients with mild thyrotoxicosis, small goiters, or fear of isotopes Carbimazole is another thiourea, available outside the United States, that is converted to methimazole in vivo Elderly patients usually respond particularly well Thiourea drugs may be administered long-term These drugs are also useful for preparing hyperthyroid patients for surgery and elderly patients for RAI treatment The drugs do not permanently damage the thyroid and are associated with a lower chance of posttreatment hypothyroidism (compared with RAI or surgery) When thiourea therapy is discontinued, there is a high recurrence rate for hyperthyroidism (about 50%) A better likelihood of long-term remission is seen in patients with small goiters or mild hyperthyroidism and those requiring small doses of thiourea Patients whose thyroperoxidase and thyroglobulin antibodies remain high after 2 years of therapy have been reported to have only a 10% rate of relapse Thiourea therapy may be continued long-term for patients who are tolerating it well Agranulocytosis occurs in about 03% of patients taking methimazole and about 04% of patients taking propylthiouracil Agranulocytosis usually occurs in the first 60 days of therapy, and it develops in a few patients after 5 months of therapy There is a genetic tendency to develop agranulocytosis with thiourea therapy; if a close relative has had this adverse reaction, other therapies should be considered for the patient Patients are warned that if a sore throat or febrile illness develops, they should stop the drug while a WBC is rechecked The agranulocytosis is generally reversible; recovery is not improved by filgrastim (granulocyte colony-stimulating factor [G-CSF]) Periodic surveillance of the WBC during treatment has been advocated, but the onset of agranulocytosis is generally abrupt Other side effects common to thiourea drugs include pruritus, allergic dermatitis, nausea, and dyspepsia Antihistamines may control mild pruritus without discontinuation of the drug Since the two thiourea drugs are similar, patients who have had a major allergic reaction from one should not be given the other Primary hypothyroidism may occur The patient may become clinically hypothyroid for 2 weeks or more before TSH levels rise, having been suppressed by the preceding hyperthyroidism Therefore, the patient s changing thyroid status is best monitored clinically and with serum levels of FT4 Rapid growth of the goiter usually occurs if prolonged hypothyroidism is allowed to develop; the goiter may sometimes become massive but usually regresses rapidly with thyroid hormone replacement a Methimazole Methimazole has the advantage of requiring less frequent dosing and fewer pills than propylthiouracil Patients treated with methimazole (compared
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