Current 26: Endocrine Disorders--Hyperthyroidism (Thyrotoxicosis)

Alemtuzumab immunotherapy:

--Alemtuzumab is an anti-CD52 monoclonal antibody used to treat pt's with multiple sclerosis. --Graves disease with hyperthyroidism (usually mild) followed by hypothyroidism develops in about 22% of pt's treated.

Subacute thyroiditis:

--Also known as "de Quervain" or "granulomatous" thyroiditis. --Typically caused by various viral infections. --Women affected 4 times more frequently than men. --Pt's typically experience a viral URI and develop an extremely painful thyroid that is tender to touch and typically enlarged 3-4 times its normal size. There is often dysphagia and ppain that can radiate to the jaw or ear. --50% of pt's experience a symptomatic thyrotoxic phase that lasts 3-6 weeks. --WBC, ESR, and CRP levels are usually elevated. About 25% have antithyroid antibodies (usually in low titer), so some cases may be autoimmune. --An important differential diagnosis is bacterial suppurative thyroiditis. --Pt's are treated with NSAIDs and corticosteroids for pain. --About 10% remain hypothyroid after 1 year. Recurrence rate is 1-4%.

Iodine-induced hyperthyroidism:

--Also known as Jod-Basedow disease. --Recommended iodine intake for nonpregnant adults is 150 mcg/day. --Higher iodine intake can precipitate hyperthyroidism in pt's with nodular goiters, autonomous thyroid nodules, or asymptomatic Graves disease, and less commonly in pt's with no detectable underlying thyroid disorder. --Common sources of excess iodine: IV iodinated radiocontrast dye, certain foods (eg, kelp, nori), and medications (eg, amiodarone and potassium iodide). --IV iodinated radiocontrast dye can rarely induce a painful, destructive subacute thyroiditis, similar to type 2 amiodarone-induced thyrotoxicosis.

Silent thyroiditis:

--Also known as subacute lymphocytic thyroiditis or "Hashitoxicosis." --It can occur spontaneously or be triggered by certain medications. --Women are affected 4 times more frequently than men. --Pt's either have no palpable goiter or a small, nontender goiter. --About 50% have antithyroid antibodies and such pt's have sometimes had chemotherapeutic agents (such as tyrosine kinase inhibitors, denileukin diftitox, alemtuzumab, thalidomide, and lenalidomide). Graves ophthalmopathy has been caused by ipilimumab. --Other drugs can cause silent thyroditis, including lithium and amiodarone. --Those with spontaneous silent thyroiditis, about 10-20% remain hypothyroid after 1 year. --Recurrence rate of 5-10%; rate is higher in Japan.

Medication-Induced Hyperthyroidism--Amiodarone-induced thyrotoxicosis:

--Amiodarone is a widely used antiarrhythmic drug that is 37% iodine by weight. --In the short term, amiodarone increases the serum TSH, though usually not over 20 mU/L. Serum T4 and free T4 rise about 40% and may become frankly elevated in clinically euthyroid pt's. Serum T3 levels decline. Due to these short-term changes, it's best to not check thyroid function tests during the first 3 months of amiodarone therapy unless clinically indicated. --After about 3 months, TSH usually normalizes. --Since T4 levels can be misleadingly high, serum TSH level must be suppressed to diagnose amiodarone-induced thyrotoxicosis. T3 or free T3 is usually high or high-normal. --Can occur quite suddenly at any time during treatment and may even develop several months after it has been DC'd. --Manifestations can be missed, particularly since amiodarone tends to cause bradycardia. --Prudent to check thyroid function tests (TSH, free T4, and T3) prior to starting, rechecking at 3-6 months, then every 6 months; sooner if clinically indicated. --Separated into 2 categories: Type 1 and Type 2, about 27% are mixed type 1-2. --Type 1 amiodarone-induced thyrotoxicosis: caused by the active production of excessive thyroid hormone. Thyroid color-flow doppler typically shows an enlarged gland with increased vascularity. --Type 2 amiodarone-induced thyrotoxicosis: caused by thyroiditis with the passive release of stored thyroid hormone. Thyroid color-flow doppler shows a normal sized gland without increased vascularity.

Treatment of Complications--Graves Dermopathy:

--Application of topical corticosteroids (eg, fluocinolone) with nocturnal plastic occlusive dressings.

Toxic multinodular goiter and thyroid adenomas:

--Autonomous toxic adenomas of the thyroid may be multiple (toxic multinodular goiter) or single (Plummer disease).

Treatment of Hyperthyroidism during Pregnancy-planning, Pregnancy, and Lactation:

--Both men and women with Graves disease who are planning pregnancy should not have RAI treatments within about 3 months of conception. --Increased risk of fetal anomalies with methimazole in the first trimester. Women should be treated with propylthiouracil through the 1st semester and then switched to methimazole. Should be given in the lowest possible dose, permitting mild subclinical hyperthyroidism. --Both methimazole and propylthiouracil cross the placenta and can induce hypothyroidism, with fetal TSH hypersecretion and goiter.

Propylthiouracil:

--Drug of choice during breastfeeding because its not concentrated in the breast milk as much as methimazole. --Also favored during pregnancy, possibly causing fewer problems in the newborn. --Rare complications peculiar to propylthiouracil: arthritis, lupus, aplastic anemia, thrombocytopenia, and hypoprothrombinemia.

Methimazole:

--Generally preferred over propylthiouracil, except during the 1st trimester of pregnancy. --More convenient to use and is less likely to cause fulminant hepatic necrosis. --Rare complications peculiar to methimazole: serum sickness, cholestatic jaundice, alopecia, nephrotic syndrome, hypoglycemia, and loss of taste. --Use in pregnancy: has been associated with an increased risk of major fetal anomalies.

Prognosis:

--Graves disease may rarely subside spontaneously, particularly when it is mild or subclinical. --Graves disease that presents in early pregnancy has a 30% chance of spontaneous remission by the 3rd trimester. --Ocular, cardiac, and psychological complications can become serious and persistent even after treatment. --With adequate treatment and long-term follow-up, the results are usually good. --However, despite treatment for their hyperthyroidism, women experience an increased long-term risk of death from thyroid disease, cardiovascular disease, stroke, and fracture of the femur. --Posttreatment hypothyroidism is common. --Subclinical hyperthyroidism: most pt's do well without treatment. In most pt's, the TSH reverts to normal within 2 years. --Asymptomatic pt's with very low TSH are monitored closely but are not treated unless A. Fib or other manifestations of hyperthyroidism develop.

Complications:

--Hypercalcemia, osteoporosis, and nephrocalcinosis may occur. --Decreased libido, ED, diminished sperm motility, and gynecomastia may be noted in men. --Other: cardiac arrhythmias and heart failure, thyroid crisis, ophthalmopathy, dermopathy, and thyrotoxic hypokalemic periodic paralysis.

Factors that can cause high serum T4 or T3:

--Lab error --Collecting serum in vial with gel barrier for T3 --Acute psychiatric problems (30%) --Acute medical illness (eg, acute intermittent porphyria) --AIDS (increased thyroid-binding globulin) --Autoimmunity --Hepatitis: acute or chronic active --Primary biliary cirrhosis --Pregnancy (especially with morning sickness) --Hyperemesis gravidarum --Familial thyroid-binding abnormalities. --Familial generalized resistance to thyroid (Refetoff syndrome) --Drugs: amiodarone, amphetamines, clofibrate, estrogens (oral), heparin (dialysis method), heroin, thyroid hormone therapy (excessive or factitious), methadone, perphenazine, tamoxifen.

Factors that can cause low serum TSH:

--Lab error. --Autonomous thyroid or thyroid nodule. --Acute corticosteroid administration. --Elderly euthyroid. --Nonthyroidal illness (severe) --Pregnancy (especially with morning sickness) --hCG-secreting trophoblastic tumors. --Drugs: thyroid hormone, amphetamines, dopamine, dopamine agonists, calcium channel blockers (nifedipine, verapamil).

Treatment of Toxic Multinodular Goiter:

--May also be treated with propranolol ER and methimazole as in Graves disease. --Definitive treatment for large multinodular goiters is surgery.

Graves Disease: --Also known as Basedow disease in Europe.

--Most common cause of thyrotoxicosis. --Autoimmune disorder affecting the thyroid gland, characterized by an increase in synthesis and release of thyroid hormones. --More common in women than men (8:1), and it's onset is usually between 20-40. --May be accompanied by infiltrative ophthalmopathy (Graves exophthalmos) and, less commonly, by infiltrative dermopathy (pretibial myxedema). --Thymus gland is typically enlarged and serum antinuclear antibodies are usually elevated, reflecting the underlying autoimmunity. --Many pt's have family hx of Graves disease or Hashimoto thyroiditis. --Dietary iodine supplementation can trigger Graves disease. An increased incidence of Graves disease occurs in countries that have embarked on a national program to fortify commercial salt with potassium iodide; the increase in Graves disease lasts about 4 years. --Similarly, pt's being treated with potassium iodide or amiodarone (has iodine) have an increased risk of developing Graves disease. --Pt's with Graves disease have an increased risk of other systemic autoimmune disorders, including Sjogren syndrome, celiac disease, pernicious anemia, Addison disease, alopecia areata, vitiligo, autoimmune type 1 DM, hypoparathyroidism, myasthenia gravis, and cardiomyopathy.

Graves dermopathy (pretibial myxedema):

--Occurs in about 3% of pt's with Graves disease usually in the pretibial region. --More common in pt's with high levels of serum TSI and severe Graves ophthalmopathy. --Glycosaminoglycans accumulation and lymphoid infiltration occur in affected skin, which becomes erythematous with a thickened, rough texture. --Elephantiasis of the legs is a rare complication.

Treatment of Complications--Hyperthyroidism from postpartum thyroiditis:

--Propranolol ER is given during the hyperthyroid phase. --Levothyroxine during the hypothyroidism phase.

Tyrosine kinase inhibitors:

--Pt's receiving chemotherapy with tyrosine kinase inhibitors (eg, axitinib, sorafenib,sunitinib) frequently develop silent thyroiditis that releases stored thyroid hormone, resulting in hyperthyroidism. --Hyperthyroidism may be subclinical, thyrotoxic crisis has been reported. The hyperthyroidism is usually followed by spontaneous hypothyroidism.

Imaging:

--Radioactive iodine (RAI): should never be given to pregnant women. In others, it may be useful to determine the cause of hyperthyroidism. --Thyroid ultrasound (US): can be helpful in pt's with hyperthyroidism, particularly in pt's with palpable thyroid nodules.

Tetany:

--Rare presenting feature. --In hyperthyroidism, renal excretion of magnesium is increased and hypomagnesemia is common. --Severe magnesium depletion causes hypoparathyroidism that can result in hypocalcemia.

Treatment of Complications--Thyroid Crisis:

--Rarely seen today. --Extreme form of thyrotoxicosis. --Acute care.

Postpartum thyroiditis:

--Refers to Hashimoto thyroiditis that occurs in the first 12 months after delivery. --Usually occurs after term pregnancies, it can also occur after miscarriages. It is common, occuring in 5% of postpartum women, with an increased incidence in women pre-existing type 1 DM and other immune disorders. --22% of such women experience hyperthyroidism followed by hypothyroidism, whereas 30% of such women have isolated thyrotoxicosis and 48% have isolated hypothyroidism. --Thyrotoxic phase typically occurs 2-6 weeks postpartum and lasts 2-3 months. --Affected women are often asymptomatic or experience minor symptoms, such as palpitations, heat intolerance, and irritability. Pt's have either no palpable goiter or a small, non-tender goiter. --Over 80% have antithyroid antibodies. Most women progress to a hypothyroid phase that usually lasts a few months but that is frequently permanent. --Affected women experience a recurrence rate of about 70% with subsequent pregnancies.

Hyperthyroid during pregnancy:

--Relatively common. --Manifestations include many of the features of normal pregnancy: tachycardia, warm skin, heat intolerance, increased sweating, and a palpable thyroid. --Undiagnosed or undertreated hyperthyroidism in pregnancy carries an increased risk of miscarriage, preeclampsia-eclampsia, preterm delivery, abruptio placenta, maternal heart failure and thyrotoxic crisis (thyroid storm). --Thyrotoic crisis (thyroid storm) can be precipitated by trauma, infection, surgery, or delivery and confers a fetal/maternal mortality rate of about 25%. --Thyrotoxic newborns have an increased risk of growth retardation and prematurity.

Treatment of Amiodarone-Induced Thyrotoxicosis:

--Require Propranolol ER for symptomatic relief. --Difficult to categorize as type 1 or type 2.

Treatment of Complications--Graves orbitopathy:

--Risk of having a "flare" of orbitopathy following I treatment is higher for smokers. --Can also be aggravated by thiazolinediones (pioglitazone, rosiglitazone) and these oral diabetic agents should be avoided or withdrawn in pt's with Graves disease. --Pt's with MILD orbitopathy may be treated with selenium BID which may slow the progression of the disease. --Acute progressive orbitopathy should be given IV methylprednisolone.

Laboratory Findings:

--Serum free T3, T3, free T4, T4, thyroid resin uptake, and free T4 index are all usually increased. --Sometimes the free T4 level may be normal but with an elevated T3 (T3 toxicosis). --Serum TSH is suppressed in hyperthyroidism (except in very rare cases of pituitary inappropriate secretion of thyrotropin). --Subclinical hyperthyroidism: used to describe symptomatic individuals with a low serum TSH but normal serum levels of free T4 and T3. --Hyperthyroidism can cause other laboratory abnormalities, including hypercalcemia, increased alkaline phosphatase, anemia, and decreased granulocytes. Hypokalemia and hypophosphatemia occur in thyrotoxic periodic paralysis. --Graves disease: serum TSI is usually detectable (65%). Antithyroglobulin or antithyroperoxidase antibodies are usually elevated but nonspecific. Serum antinuclear antibodies are also usually elevated without any evidence of lupus or other rheumatologic disease. --Subacute thyroiditis: pt's often have an increased ESR. Serum antithyroid antibodies are usually not present and serum TSI (TSHrAb) levels are normal. --Hyperthyroidism during pregnancy: women have an elevated serum total T4 and free T4, while the TSH is suppressed. (However, about 18% of pregnant women have low serum TSH.)

Treatment of Hyperthyroidism from Thyroiditis:

--Subacute (de Quervain) and lymphocytic (Hashimoto) thyroiditis can cause transient hyperthyroidism from release of stored thyroid hormone from the inflamed thyroid. --Subsides spontaneously within weeks to months. --Thioureas are ineffective, since thyroid hormone is actually low. --Symptomatic relief: Propranolol ER BID and increase every 3 days until the HR is < 90. --Pt's need to be monitored carefully for the development of hypothyroidism and treated as needed. --Subacute thyroiditis: pain can usually be managed with NSAIDs, but opioid analgesics are sometimes required.

Treatment of Complications--Thyrotoxic Hypokalemia Periodic Paralysis:

--Sudden symmetric flaccid paralysis, along with hypokalemia and hypophosphatemia can occur with hyperthyroidism. --It is most common in Asian and Native Americans with hyperthyroidism and is 30 times more common in men than women.

Essentials of Diagnosis:

--Sweating, weight loss or gain, anxiety, palpitations, loose stools, heat intolerance, irritability, fatigue, weakness, menstrual irregularity. --Tachycardia; warm, moist skin; stare; tremor. --In Graves disease: goiter (often with bruit); opthalmopathy. --Suppressed TSH in primary hyperthyroidism; increased T4, free T4, T3, and free T3.

General considerations:

--The term "thyrotoxicosis" refers to the clinical manifestations associated with serum levels of T4 or T3 that are excessive for the individual (hyperthyroidism). --Serum TSH levels are suppressed in primary hyperthyroidism. --Certain drugs and conditions can affect lab tests and lead to the erroneous diagnosis of hyperthyroidism in euthyroid individuals. --The causes of hyperthyroidism are many and diverse.

Treatment--Graves disease:

--The treatment of Graves disease involves a choice of methods rather than a method of choice. --Propranolol: generally used for symptomatic relief until hyperthyroidism is resolved. Effectively relieves accompanying tachycardia, tremor, diaphoresis, and anxiety. Initial treatment of choice for thyroid storm. Has no effect on thyroid hormone secretion. --Thiourea drugs: methimazole or propylthiouracil is generally used for young adults or pt's with mild thyrotoxicosis, small goiters, or fear of isotopes. Elderly pt's usually respond particularly well. May be continued long-term for pt's who are tolerating it well. All pt's receiving thiourea therapy must be informed of the danger of agranulocytosis or pancytopenia and the need to stop the drug and seek immediate medical attention with the onset of any infection or unusual bleeding. --Iodinated contrast agents: effective temporary treatment for thyrotoxicosis of any cause. Iopanoic acid (Telepaque) or ipodate sodium (Bilivist, Oragrafin) is given orally. These agents block the conversion T4 to active T3. Particularly useful in pt's in thyroid storm. Offer a therapeutic option for pt's with T4 overdosage, subacute thyroiditis, and amiodarone-induced thyrotoxicosis. --Radioactive Iodine (RAI): excellent method for destroying overactive thyroid tissue. ***Should not be given to pregnant or lactating women or to mothers who lack childcare*** Lifelong follow up is necessary, with mandatory measurements of TSH, free T4, and calcium when indicated. --Thyroid surgery: thyroidectomy may be performed for pregnant women whose thyrotoxicosis is not controlled with low doses of thioureas, and for women who desire to become pregnant in the near future. Also an option for nodular goiters when there is suspicion for malignancy. Surgical procedure of choice for Graves disease is a total resection of one lobe and a subtotal resection of the other lobe, leaving about 4 g of thyroid tissue (Hartley-Dunhill operation).

Signs and symptoms:

--Thyrotoxicosis due to any cause produces nervousness, restlessness, heat intolerance, increased sweating, pruiritis, fatigue, weakness, muscle cramps, frequent bowel movements, or weight change (usually loss). May be palpitations or angina pectoris. Women frequently report menstrual irregularities. --Signs of thyrotoxicosis also include fine resting finger tremors, moist warm skin, fever, hyperreflexia, fine hair, and onycholysis. --Chronic thyrotoxicosis may cause osteoporosis. --Clubbing and swelling of the fingers (acropachy) develop in a small number of pt's. --In pt's with Grave's disease, physical exam usually reveals a diffusely enlarged thyroid, frequently asymmetric, often with a bruit. Some pt's have no palpable thyroid enlargement. --The thyroid gland in subacute thyroiditis is usually moderately enlarged and tender. Pt's with toxic multinodular goiter, they thyroid usually has palpable nodules.

Rare causes of hyperthyroidism:

--Thyrotoxicosis factitia: due to intentional or accidental ingestion of excessive amounts of exogenous thyroid hormone. Isolated epidemics of thyrotoxicosis have been caused by consumption of ground beef contaminated with bovine thyroid gland. --Struma ovarii: thyroid tissue contained in 3% of ovarian dermoid tumors and teratomas. Such ectopic thyroid tissue may develop thyroid nodules that produce excess thyroid hormone, causing hyperthyroidism. Also, in Graves disease, ectopic thyroid tissue in dermoid tumors can secrete excessive thyroid hormone, along with the normal thyroid. --Pituitary TSH hypersecretion: caused by a pituitary thyrotrophe tumor or hyperplasia can rarely cause hyperthyroidism. TSH is elevated or inappropriately normal in the presence of true thyrotoxicosis. Pituitary hyperplasia may be detected on MRI scan as pituitary enlargement without a discrete adenoma being visible. --Metastatic functioning thyroid carcinoma: can cause hyperthyroidism in pt's with a heavy tumor burden. Hyperthyroidism can be induced or aggravated by recombinant human thyroid-stimulating hormone (rhTSH) that is given prior to radio-iodine therapy or scanning.

Differential Diagnosis:

--True thyrotoxicosis must be distinguished from those conditions that elevate serum T4 and T3 or suppress serum TSH without affecting clinical status. --Serum TSH is commonly suppressed in early pregnancy and only about 10% of pregnant women with low TSH have clinical hyperthyroidism. --Some states of hypermetabolism without thyrotoxicosis (rarely cause confusion): severe anemia, leukemia, polycythemia, cancer, and pheochromocytoma. --Cardiac disease (eg, A. Fib, 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. --DM and Addison disease may coexist with thyrotoxicosis.

Graves eye manifestations:

--can occur with hyperthyroidism of any etiology, including upper eyelid retraction (Dalrymple sign), lid lag with downward gaze (von Graefe sign), and a staring appearance (Kocher sign).

Ophthalmopathy:

--clinically apparent in 20-40% of pt's with Graves disease and some cases of amiodarone-induced thyrotoxicosis. --It usually consists of conjunctival edema (chemosis), conjunctivitis, and mild exophthalmos (proptosis). --About 5-10% of pt's experience more severe exopthalmos, with the eye being pushed forward by increased retro-orbital fat and eye muscles that have been thickened by lymphocytic infiltration. Such pt's can experience diplopia from extraocular muscle entrapment. --There may be weakness of upward gaze (Stellwag sign). --The optic nerve may be compressed in severe cases, causing progressive loss of color vision, visual fields, and visual acuity. --Corneal drying may occur with inadequate lid closure. Eye changes may sometimes be asymmetric or unilateral. Severity of the disease is not closely correlated with the severity of the thyrotoxicosis. --Exopthalmometry should be performed on all pt's with Graves disease to document their degree of exophthalmos and detect progression of obitopathy. --The differential diagnosis for Graves opthalmopathy includes diplopia caused by an orbital lymphoma. Ocular myasthenia gravis is another autoimmune condition that occurs more commonly in Graves disease but is usually mild, often with unilateral eye movement. --Acetylcholinesterase receptor antibody (AChR Ab) levels are elevated in only 36% of pt's, and a thymoma is present in 9%.

Cardiopulmonary manifestations of thyrotoxicosis:

--commonly include a forceful heartbeat, premature atrial contractions, and sinus tachycardia. --Pt's often have exertional dyspnea. --A. fib or a. tach occurs in about 8% of pt's with thyrotoxicosis, more commonly in men, the elderly, and those with ischemic or valvular heart disease. The ventricular response from the a. fib may be difficult to control. --Thyrotoxicosis itself can cause a thyrotoxic cardiomyopathy, and the onset of a. fib can precipitate heart failure. --Even "subclinical hyperthyroidism" increases the risk for a. fib and overall mortality. --Hemodynamic abnormalities and pulmonary HTN are reversible with restoration of euthyroidism.

Thyroid acropachy:

--extreme and unusual manifestation of Graves disease. --Presents with digital clubbing, swelling of fingers and toes, and a periosteal reaction of extremity bones. --Ordinarily associated with ophthalmopathy and thyroid dermopathy. --Most pt's are smokers.

Pregnancy and hCG-secreting trophoblastic tumors:

--hCG can bind to the thyroid's TSH receptors, so very high levels of hCG, particularly during the first 4 months of pregnancy, may cause sufficient receptor activation to cause hyperthyroidism. --About 18% of pregnant women have a low serum TSH during pregnancy, but only about 10% have clinical hyperthyroidism that requires treatment. --Pregnant women are more likely to have hCG-induced thyrotoxicosis if they have high serum levels of asialo-hCG, a sub-fraction of hCG that has a greater affinity for TSH receptors. These women are also more likely to suffer from hyperemesis gravidarum. --This condition must be distinguished from true Graves disease in pregnancy, which usually predates conception and may be associated with high serum levels of TSI and antithyroid antibodies or with exophthalmos. --High levels of hCG can also cause thyrotoxicosis in some cases of pregnancies with gestational trophoblastic disease that has manifestations ranging from molar pregnancy to choriocarcinoma. Such molar pregnancies have produced thyrotoxic crisis. --Men have developed hyperthyroidism from high serum levels of hCG secreted by a testicular choriocarcinoma.

Hypokalemic periodic paralysis:

--occurs in about 15% of Asian and Native American men with thyrotoxicosis. --Usually presents abruptly with symmetric flaccid paralysis (and few thyrotoxic symptoms), often after IV dextrose, oral carbohydrates, or vigorous exercise. --Attacks last 7-72 hours.

Common side effects of thiourea drugs:

--pruritus, allergic dermatitis, nausea, and dyspepsia. --Since the 2 drugs are similar, pt's who have a major allergic reaction to one should not be given the other.

Subacute, postpartum, and silent thyroiditis:

--these cause thyroid inflammation with release of stored hormone. --They all produce a variable triphasic course: variable hyperthyroidism is followed by transient euthyroidism, and progresses to hypothyroidism. --Thyroid radioiodine uptake is low during the thyrotoxic phase. --All pt's are treated with propranolol during the thyrotoxic phase and levothyroxine during the hypothyroid phase. There may be some overlap during these conditions.

Treatment of Toxic Solitary Thyroid Nodules:

--usually benign but may rarely be malignant. --If non-surgical treatment is elected, nodule should be evaluated with a fine-needle aspiration (FNA) biopsy. --Hyperthyroidism caused by a single hyperfunctioning thyroid may be treated symptomatically with propranolol ER and methimazole or propylthiouracil

Treatment of Complications--Cardiac complications:

A. Sinus Tach: Treatment consists of treating the thyrotoxicosis. A beta-blocker such as propranolol is used in the interum unless there is associated cardiomyopathy. B. A. Fib: Hyperthyroidism must be treated immediately. Other drugs, including digoxin, beta-blockers, and anti-coagulants, may be required. C. Heart Failure: Thyrotoxicosis can cause HF due to extreme tachycardia, cardiomyopathy, or both. Very aggressive treatment is required in either case. Tachycardia from A. Fib is treated with digoxin. D. Apathetic Hyperthyroidism: may present with angina. Treatment is directed at reversing hyperthyroidism as well as providing standard antianginal therapy.