AUTHOR AND EDITOR INFORMATION

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INTRODUCTION

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Background

Subacute thyroiditis is a self-limited thyroid condition associated with a triphasic clinical course of hyperthyroidism, hypothyroidism, and return to normal thyroid function. Subacute thyroiditis may be responsible for 15-20% of patients presenting with thyrotoxicosis and 10% of patients presenting with hypothyroidism. Recognizing this condition is important because it is self-limiting, and no specific therapy, such as antithyroid or thyroid hormone replacement therapy, is necessary in most patients.

In general, 3 forms of subacute thyroiditis are recognized. Although the etiology appears to be different for the 3 subtypes, the clinical courses are the same.

The high thyroid hormone levels are a result of destruction of the thyroid follicle and release of preformed thyroid hormone into the circulation. The high thyroid hormone levels are not a function of new thyroid hormone synthesis and secretion. Conditions of excess thyroid hormone synthesis and secretion (eg, Graves disease, toxic multinodular goiter, toxic adenoma) are discussed in Hyperthyroidism.

Eventually, thyroid hormone is depleted and the patient may become hypothyroid. Often the hypothyroidism is mild, and no thyroid hormone therapy is required unless the patient has signs or symptoms of hypothyroidism. The hypothyroid phase may last up to 2 months.

Ninety to 95% of patients return to normal thyroid function.

Pathophysiology

The hypermetabolic effect of thyrotoxicosis is the same regardless of cause. Thyrotoxicosis affects every organ system because thyroid hormones made in the thyroid travel via the circulation to reach every cell in the body. Thyroid hormone is necessary for normal growth and development, and it regulates cellular metabolism. Excess thyroid hormone causes an increase in metabolic rate that is associated with increased total body heat production, increased cardiovascular activity (eg, increased heart contractility, heart rate, vasodilation) to remove heat to the periphery and remove metabolic wastes, and perspiration to cool the body.

The major symptoms of thyrotoxicosis include palpitations, nervousness, sweating, hyperdefecation, and heat intolerance. Women often note a reduction in menstrual flow or oligomenorrhea. Common signs of thyrotoxicosis include weight loss despite increased appetite, lid lag and stare, sinus tachycardia, atrial fibrillation or high-output failure (in elderly persons), fine tremor, and muscle weakness. Synergism occurs between thyrotoxicosis and the adrenergic system, with increases in nervousness, stare, tremor, and tachycardia.

The manifestations of thyrotoxicosis vary among patients. Younger patients tend to exhibit more sympathetic activations (eg, anxiety, hyperactivity, tremor), while older patients have more cardiovascular symptoms (eg, dyspnea, atrial fibrillation) and unexplained weight loss. The clinical manifestation of thyrotoxicosis does not always correlate with the extent of the biochemical abnormality.

Subacute thyroiditis is a destructive thyroiditis resulting in the release of preformed thyroid hormone and not in the new synthesis of thyroid hormone. A characteristic finding in this thyrotoxic condition is a very low radioactive iodine uptake by the thyroid (see Images 1-2). The 3 types of subacute thyroiditis are subacute granulomatous, also referred to as painful thyroiditis; subacute painless thyroiditis, which is silent and also referred to as lymphocytic thyroiditis; and postpartum thyroiditis. The etiology of each of these conditions is different, but all of the conditions follow the same clinical course, including 6-8 weeks of thyrotoxicosis, 2-4 months of mild hypothyroidism, and, finally, a return to the euthyroid state in 90-95% or more of the patients. A patient may experience 1 or more of these phases. The course is illustrated in Image 2.

Thyroid biopsies in subacute painful or granulomatous thyroiditis show characteristic multinucleated giant cell granulomas and a mononuclear infiltration (see Image 3). Thyroid biopsy tissue from patients with postpartum and painless or lymphocytic thyroiditis shows a lymphocytic infiltration.

Frequency

United States

The thyrotoxicosis caused by these forms of subacute thyroiditis (ie, silent thyroiditis, painful or granulomatous thyroiditis, postpartum thyroiditis) is more frequently recognized as a cause of transient thyrotoxicosis. Estimates indicate that 20-25% of thyrotoxicosis is caused by these destruction-induced forms.

International

No difference in the worldwide prevalence of subacute thyroiditis is apparent.

Mortality/Morbidity

The thyrotoxicosis from subacute thyroiditis is brief, usually no longer than 6-8 weeks. Patients can be extremely thyrotoxic during this brief period and can appear extremely ill, but concerns regarding left ventricular hypertrophy and osteoporosis are not as great compared to conditions of permanent hyperthyroidism. However, sudden-onset thyrotoxicosis and severe thyrotoxicosis can be associated with atrial arrhythmia and CHF.

Race

The condition appears to affect all races and ethnic groups equally.

Sex

• Subacute painful or granulomatous thyroiditis has a female-to-male prevalence ratio of 5:1.
• Subacute lymphocytic or silent thyroiditis and postpartum thyroiditis are associated with autoimmune thyroiditis. Silent thyroiditis occurs twice as often in women than in men.
• Postpartum thyroiditis occurs 1-6 months after giving birth. If a woman has postpartum thyroiditis with one baby, all other pregnancies are likely to be associated with this condition.

Age

• Silent, painless, or lymphocytic thyroiditis can occur in any age group, while painful or granulomatous thyroiditis usually occurs in adults (ie, 20-60 y).
• Postpartum thyroiditis occurs in women of childbearing age.

CLINICAL

Section 3 of 11  

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History

Patient presentation depends on the etiology of the thyrotoxicosis. Subacute granulomatous thyroiditis is associated with an acute virallike illness with fevers and myalgias with a painful thyroid. A recent birth signals postpartum thyroiditis. Often, the thyrotoxicosis of silent thyroiditis, postpartum thyroiditis, or surreptitious use of thyroid hormone is symptomatic because of persistent tachycardia, nervousness, and weight loss. Symptoms of thyrotoxicosis that persist for longer than 2 months are probably not caused by subacute thyroiditis.

• Subacute painful, granulomatous, or de Quervain thyroiditis: These patients have the classic presentation of a viral illness. The onset is sudden, with high fever, myalgia, and neck pain.



• Subacute silent thyroiditis or lymphocytic thyroiditis: This form is associated with a painless, firm enlargement of the thyroid gland and high thyroid hormone levels. Only suspicion by the clinician and use of radioactive iodine uptake measurement can distinguish Graves hyperthyroidism from silent thyroiditis.



• Subacute postpartum thyroiditis: This form is associated with a painless, firm enlargement of the thyroid gland and high thyroid hormone levels. The identifying feature is its occurrence 1-6 months after childbirth. Autoimmune hyperthyroidism from Graves disease can also occur for the first time postpartum and must be distinguished from postpartum thyroiditis. Both conditions are associated with high antithyroid antibody titers.

Physical

All conditions described are associated with thyrotoxicosis and the signs and symptoms of hypermetabolism. None of the forms of subacute thyroiditis is associated with the thyroid eye disease observed primarily with Graves hyperthyroidism. The presence of bilateral proptosis and chemosis with high thyroid hormone levels and goiter is highly suggestive of Graves disease.

• Subacute painful or granulomatous thyroiditis: Patients often present with an acute virallike illness characterized by high spiking fever, malaise, myalgia, fatigue, and prostration. Neck pain from the thyroiditis can be extremely painful, preventing swallowing of saliva, liquids, and food. The pain starts in the lower neck and can radiate to the jaw or ear on that side. Thyroid hormone levels are often extremely elevated, resulting in marked signs and symptoms of thyrotoxicosis. Cases of lesser severity also exist, and the etiology may be confusing.
• Subacute silent, painless, or lymphocytic thyroiditis: Patients present with a nonpainful thyroid enlargement and elevated thyroid hormone levels. This condition must be distinguished from Graves thyrotoxicosis because antithyroid medication is not indicated in this temporary condition.
• Subacute postpartum thyroiditis: Patients present 1-6 months postpartum with painless thyroid enlargement and elevated thyroid hormone levels. Patients may report lack of sleep, nervousness, fatigue, and easy weight loss. Sometimes, distinguishing between the usual postpartum changes in physiology and additional thyroid pathology is difficult.

Causes

The causes of subacute thyroiditis, other than painful granulomatous thyroiditis, are not entirely clear.

• Subacute painful or granulomatous thyroiditis: The most accepted etiology is a viral illness. Viral particles have never been identified within the thyroid, but episodes often follow upper respiratory infections and are associated with falling postconvalescent viral titers of various viruses, including influenza, adenovirus, mumps, and coxsackievirus. This condition is not associated with autoimmune thyroiditis but is associated with HLA-B35. A genetic predisposition clearly exists; patients with HLA-Bw35 have a significantly increased risk of developing this condition. Whether the destructive thyroiditis is caused by direct viral infection of the gland or by the host's response to the viral infection is unclear. Painful or granulomatous thyroiditis is not an autoimmune disease of the thyroid.



• Subacute silent, lymphocytic, or painless thyroiditis: This condition most likely is autoimmune in nature. Patients develop an autoimmune goiter and permanent hypothyroidism more often than with the painful form of subacute thyroiditis.
  
  
  • An HLA antigen association may be present, suggesting a genetic predisposition to painless thyroiditis.
  
  
  
  • Certain drug exposures relating to excess iodine and cytokines may cause this form of silent thyroiditis. These drugs include amiodarone (iodine-rich), interleukin-alpha, interleukin 2, and lithium. Silent thyroiditis resulting from these different medications is typically treated similarly (see Medications).
    
    
    • Amiodarone has multiple established effects on thyroid function. One of the 2 types of amiodarone-induced thyrotoxicosis is a destructive silent thyroiditis. This form of thyroiditis is more common in men, likely due to the higher prevalence of amiodarone therapy among men. [single space]  This form of silent thyroiditis typically occurs after more than 2 years of amiodarone therapy.
    
    
    
    • Up to 5% of patients taking interleukin-alpha may experience a silent thyroiditis. This condition is detected biochemically more often than clinically after 3 months of therapy. Silent thyroiditis in patients taking interferon-alpha is associated with an increased antithyroid antibody concentration.
    
    
    
    • Although case reports exist that interleukin 2 is associated with silent thyroiditis, its causative role is less established when compared with interleukin-alpha.
    
    
    
    • Lithium is a well-known cause of either subclinical or clinical hypothyroidism, as well as goiter. Because of lithium’s ability to inhibit the release of thyroid hormone, it has been used as a treatment of thyrotoxicosis. However, reports exist of lithium-associated thyrotoxicosis due to a silent thyroiditis, with the classic picture of hyperthyroidism, absent neck tenderness, and low radioactive iodine uptake (see Medications). The silent thyroiditis can occur during lithium administration as well as up to 5 months following discontinuation of lithium therapy. Increased thyroid antibodies in lithium users and a direct toxic effect of lithium have been proposed as possible mechanisms.
       
• Subacute postpartum thyroiditis: This condition is likely autoimmune in nature. Patients develop an autoimmune goiter and permanent hypothyroidism more often than with the painful form of subacute thyroiditis. In iodine-sufficient countries, such as the United States, postpartum thyroiditis occurs in approximately 5-8% of pregnant women. In Japan, nearly 20% of pregnancies are associated with this condition. Patients with positive test results for thyroid autoantibodies either before their pregnancy or during the third trimester are at much higher risk of developing postpartum thyroiditis. Cigarette smoking is also associated with an increased incidence of postpartum thyroiditis. Once patients have an episode of subacute postpartum thyroiditis, they are likely to have additional episodes following each pregnancy.

DIFFERENTIALS

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Other Problems to be Considered

Infectious thyroiditis
Radiation-induced thyroiditis
Trauma- or palpation-induced thyroiditis
Riedel or fibroid thyroiditis
Graves thyrotoxicosis
Toxic thyroid adenoma
Toxic multinodular goiter

WORKUP

Section 5 of 11  

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Lab Studies

• Thyroid-stimulating hormone levels
  
  
  • The most reliable measure of thyroid function is a thyroid-stimulating hormone (TSH) level. TSH levels are usually suppressed to unmeasurable levels (<0.05 µIU/mL) in thyrotoxicosis.
  
  
  
  • The degree of thyrotoxicosis cannot be estimated with a TSH level and must be measured by the thyroid hormone levels in the plasma.
  
  
  
  • Thyroid hormone circulates as triiodothyronine (T3) and thyroxine (T4). T3 is 20-100 times more biologically active than T4. Five percent of patients with thyrotoxicosis only have elevations in T3; therefore, measuring an estimate of free T4 and free T3 is recommended.
  
  
  
  • Most laboratories use a calculation to estimate the free T4 levels (ie, total T4 X correction for thyroid hormone binding = free thyroxin index).
     
• Thyroid autoantibodies
  
  
  • The most specific autoantibody for autoimmune thyroiditis is antithyroperoxidase (anti-TPO) antibody. Positive antithyroglobulin antibodies are not associated with autoimmune thyroid disease.
  
  
  
  • Antithyroid antibody titers can be elevated temporarily in all causes of subacute thyroiditis. The highest elevation in subacute thyroiditis is associated with postpartum subacute thyroiditis.
  
  
  
  • The antithyroid titers are usually elevated significantly in the most common type of hyperthyroidism, Graves thyrotoxicosis.
     
• Painful or granulomatous subacute thyroiditis (see Image 2)
  
  
  • The thyroid hormone levels are very elevated. The 6- to 8-week destructive phase of thyroiditis causes the release of preformed hormone stores from the thyroid. This form of thyroid hormone is highly iodinated, such that the release of hormone has a lower ratio of total T3 to total T4 than does Graves disease. A ratio of T3 to T4 less than 15 usually increases suspicion of subacute thyroiditis.
  
  
  
  • Episodes are associated with high fever, severe myalgia, thyroid pain that often radiates to the ear, and very high levels of thyroid hormone.
  
  
  
  • The hallmarks of subacute granulomatous or painful thyroiditis are a very high erythrocyte sedimentation rate (ESR), often as high as 60-100, and a radioiodine uptake of less than 1% at 24 hours (see Images 1-2).
  
  
  
  • After the thyroid is depleted of thyroid hormone, patients' serum levels of T4 and T3 decrease into the hypothyroid range. The hypothyroidism is usually mild but persists for 2-4 months. Supplementation with thyroid hormone is necessary only if the patients become symptomatic from the hypothyroidism. Ninety to 95% of patients spontaneously return to normal thyroid function.
     
• Painless, silent, or lymphocytic subacute thyroiditis
  
  
  • The time course is identical to subacute granulomatous thyroiditis (see Image 2). Thyroid hormone levels are very elevated. The destructive phase of thyroiditis causes the release of preformed hormone stores in the thyroid. This form of thyroid hormone is highly iodinated, such that the release of hormone has a lower ratio of total T3 to total T4 than does Graves disease. A ratio of T3 to T4 less than 15 usually increases suspicion of subacute thyroiditis.
  
  
  
  • The hallmark of subacute lymphocytic or painless thyroiditis is a radioiodine uptake of less than 1% at 24 hours. The ESR is within the reference range and the thyroid is not painful, which distinguishes this condition from subacute granulomatous thyroiditis.
  
  
  
  • After the thyroid is depleted of thyroid hormone, patients' serum levels of T4 and T3 decrease into the hypothyroid range. The hypothyroidism is usually mild but persists for 2-4 months. Supplementation with thyroid hormone is necessary only if the patient becomes symptomatic.
     
• Postpartum subacute thyroiditis
  
  
  • The time course of thyroid dysfunction is the same as subacute granulomatous thyroiditis (see Image 2). The ESR is within the reference range, and the thyroid is not painful, which distinguishes this condition from subacute granulomatous thyroiditis.
  
  
  
  • Thyroid hormone levels can be moderately or extremely elevated, with a radioiodine uptake of less than 1% at 24 hours.
  
  
  
  • After the thyroid is depleted of thyroid hormone, patients' serum levels of T4 and T3 decrease into the hypothyroid range. The hypothyroidism is usually mild but persists for 2-4 months. Supplementation with thyroid hormone is necessary only if patients become symptomatic.
  
  
  
  • Antithyroid antibody levels can become very elevated transiently.

Imaging Studies

• Nuclear scintigraphy
• • Subacute thyroiditis results in a very low radioactive iodine uptake (¹²³I or ¹³¹I) or technetium Tc 99m trapping. No iodine uptake occurs because the release of preformed thyroid hormone from the thyroid gland suppresses TSH levels, which are needed to express the sodium-iodine (Na-I) symporter responsible for iodine uptake into the gland.
  
  
  
  • Subacute thyroiditis causes focal thyroid destruction and release of preformed thyroid hormone. The unaffected parts of the gland do not take up iodine because the high thyroid hormone levels suppress the TSH level.
     
• Doppler ultrasonography
• • Thyroid ultrasound alone is not helpful in distinguishing between abnormalities caused by subacute thyroiditis and other causes of high thyroid hormone levels, including Graves thyroiditis.
  
  
  
  • The use of Doppler to detect increased blood flow has been shown to allow reliable differentiation between Graves disease and subacute thyroiditis in most patients. Subacute thyroiditis is not associated with increase in blood flow or Doppler signals, while the hyperthyroidism of Graves thyrotoxicosis is associated with a markedly increased blood flow and high Doppler signals. Thus, Doppler results may help to distinguish between these 2 types of thyrotoxicosis.

Procedures

• Fine-needle aspiration (FNA) biopsy: Occasionally, patients with subacute thyroiditis may present with a solitary hard nodule. An FNA in subacute thyroiditis contains a mononuclear infiltrate composed of mostly lymphocytes and multinucleated giant cells (see Image 3).

Histologic Findings

As with all types of thyroid inflammation, the thyroid histology contains inflammatory cells, primarily lymphocytes. The destructive nature of this condition is reflected in the disruption and disarray of the normal follicular unit composed of a monolayered sheet of thyroid follicular cells surrounding the storage form of thyroid hormone, colloid. Specific to subacute granulomatous thyroiditis, a plethora of multinucleated giant cells is present in the inflammatory cell mix (see Image 3).

TREATMENT

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Medical Care

Patients are often dehydrated from the thyrotoxicosis; encourage all patients to drink 6-8 cups per day of noncaffeinated fluids.

Subacute thyroiditis - All forms

The treatment of subacute thyroiditis is generally supportive to reduce the symptoms of thyrotoxicosis and to control neck pain in the setting of painful subacute thyroiditis. Because no new hormone is being made, antithyroid medications are not effective in these conditions. Although the abnormal thyroid levels are temporary, emotional support is often necessary.

• Thyroid hormone levels in subacute thyroiditis: The release of preformed hormone cannot be stopped in the destructive phase. In patients with very high levels of thyroid hormone, ipodate may be administered to inhibit the conversion of T4 to the more active form of thyroid hormone, T3. Ipodate or iopanoic acid is better known as Gastrografin. A dose of 1000 mg in 2 divided doses daily usually provides a rapid reduction in T3 and thyrotoxic symptoms.



• Pain in subacute painful thyroiditis: The thyroid pain can be extreme. Nonsteroidal medications are administered. Avoid high-dose aspirin because, in some circumstances, aspirin can competitively displace thyroid hormone from its binding protein and increase the free, or bioactive, fraction of thyroid hormone, which can make patients feel more thyrotoxic. In extreme cases, stronger pain medications, including narcotic analgesics, are indicated for a brief period of 2-3 weeks. In the most extreme cases, high-dose steroids (eg, prednisone 40-60 mg qd) must be administered. The high-dose steroids rapidly and dramatically decrease the pain and thyroid swelling, but the natural course of thyrotoxicosis and pain (ie, 4-6 wk) is not altered, and the glucocorticoid treatment must be continued for this period.



• Peripheral manifestations of thyrotoxicosis: Patients often find great relief from tachycardia, palpitations, anxiety, and tremor with beta-blocker therapy. Propranolol is generally recommended because of its CNS effects. The patient usually titrates the dose depending on the symptoms. Exercise caution with the initial dose; patients may become hypotensive because they are often dehydrated from the decrease in oral intake of fluids and increased perspiration from the thyrotoxicosis.

Surgical Care

Surgical care is almost never recommended for subacute thyroiditis. Surgery is recommended rarely in patients who have frequent recurrences of thyrotoxicosis from silent thyroiditis or recurrent pain from subacute painful thyroiditis.

Consultations

Generally, all patients with thyrotoxicosis should be referred to an endocrinology specialist. Distinguishing between the causes of thyrotoxicosis is important because the therapies are very different.

Diet

Avoiding high-dose iodine supplements, such as those found in seaweed tablets, during and after an episode of subacute thyroiditis is important. Inflammation appears to prevent the thyroid from escaping the iodine-induced Wolff-Chaikoff suppression of thyroid hormone synthesis. These patients are likely to become hypothyroid when ingesting large amounts of iodine.

Activity

No limitation in activity is necessary, but patients may experience tachycardia with exercise. Good hydration and beta-blocker therapy should allow patients to exercise normally with thyrotoxicosis caused by subacute thyroiditis.

MEDICATION

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Medical treatment for subacute thyroiditis is supportive in general. Thyrotoxicosis can be extreme but temporary (eg, 6-8 wk). The subsequent hypothyroid phase is usually mild and lasts 2-4 months. Therapy is directed to reducing the signs and symptoms of the hyperthyroidism with beta-blockers or iodine agents. Pain is treated with nonsteroidal anti-inflammatory agents. Rarely, high-dose steroids and narcotic analgesic agents are used for extremely painful or recurrent life-threatening hyperthyroidism.

Drug Category: Nonsteroidal anti-inflammatory drugs

Anti-inflammatory agents are administered to patients with painful subacute thyroiditis. Patients should avoid high-dose aspirin because it can increase free thyroid hormone levels by displacing thyroid hormone from its protein binding sites. Narcotic analgesics can be administered if the pain is extreme and prevents oral hydration. Rarely, high-dose steroids (eg, prednisone 40-60 mg PO qd for 4-6 wk) may be used to decrease the pain, if necessary.

Drug Name	Naproxen (Aleve, Naprosyn, Naprelan)
Description	For relief of mild to moderate pain. Inhibits inflammatory reactions and pain by decreasing activity of cyclooxygenase, which results in a decrease of prostaglandin synthesis.
Adult Dose	250-500 mg PO bid
Pediatric Dose	10-20 mg/kg PO divided bid
Contraindications	Documented hypersensitivity; peptic ulcer disease; recent GI bleeding or perforation; renal insufficiency
Interactions	Coadministration with aspirin increases risk of inducing serious NSAID-related adverse effects; probenecid may increase concentrations and, possibly, toxicity of NSAIDs; may decrease effect of hydralazine, captopril, and beta-blockers; may decrease diuretic effects of furosemide and thiazides; monitor PT closely (instruct patients to watch for signs of bleeding); may increase risk of methotrexate toxicity; phenytoin levels may be increased when administered concurrently
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Category D in third trimester of pregnancy; acute renal insufficiency, interstitial nephritis, hyperkalemia, hyponatremia, and renal papillary necrosis may occur; patients with preexisting renal disease or compromised renal perfusion risk acute renal failure; leukopenia occurs rarely, is transient, and usually returns to normal during therapy; persistent leukopenia, granulocytopenia, or thrombocytopenia warrants further evaluation and may require discontinuation of the drug

Drug Name	Indomethacin (Indocin)
Description	Rapidly absorbed. Metabolism occurs in liver by demethylation, deacetylation, and glucuronide conjugation. Inhibits prostaglandin synthesis.
Adult Dose	25-50 mg PO tid
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; GI bleeding; renal insufficiency
Interactions	Coadministration with aspirin increases risk of inducing serious NSAID-related adverse effects; probenecid may increase concentrations and, possibly, toxicity of NSAIDs; may decrease effect of hydralazine, captopril, and beta-blockers; may decrease diuretic effects of furosemide and thiazides; monitor PT closely (instruct patients to watch for signs of bleeding); may increase risk of methotrexate toxicity; phenytoin levels may be increased when administered concurrently
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Category D in third trimester of pregnancy; acute renal insufficiency, hyperkalemia, hyponatremia, interstitial nephritis, and renal papillary necrosis may occur; increases risk of acute renal failure in patients with preexisting renal disease or compromised renal perfusion; reversible leukopenia may occur, discontinue if patient has persistent leukopenia, granulocytopenia, or thrombocytopenia

Drug Category: Iodinated contrast agents

High iodine levels inhibit the peripheral conversion of T4 to T3. The most effective agents are the iodinated contrast agents, but high levels of iodine provided by SSKI (saturated solution of potassium iodide, 2 drops in full glass of water PO tid) can be substituted.

Drug Name	Ipodate (Oragrafin)
Description	One of the most effective inhibitors of deiodinase, which converts T4 to the more biologically active T3. Reduction in conversion of T4 to T3 can greatly reduce T3 levels and thyrotoxic symptoms.
Adult Dose	2 g PO, then 0.5 g PO bid
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity
Interactions	Coadministration with lithium may result in hypothyroid effects
Pregnancy	D - Unsafe in pregnancy
Precautions	Risk of hypotension increases with increased dose; anuria may develop if agents are administered to patients with combined hepatic and renal disease or severe renal impairment; prolonged iodine storage in tissues may lead to rebound thyrotoxicosis with potential to cause ethionamide resistance

Drug Category: Thyroid hormones

Most patients with subacute thyroiditis experience a hypothyroid phase following thyrotoxicosis. Asymptomatic patients do not need to be treated if TSH is mildly elevated (<15 µIU/mL), but they should be tested q4wk to confirm that hypothyroidism is not worsening or becoming permanent. Thyroid hormone is generally administered (usually 50 mcg/d) to normalize TSH. After 6 months, when 90-95% of patients have returned to normal thyroid function, thyroid hormone is discontinued and TSH level is checked 4 wk after discontinuation of therapy. If the TSH level is within the reference range, no further treatment is necessary. If the TSH level is elevated, the patient has permanent hypothyroidism, and therapy should be continued indefinitely.

Drug Category: Beta-adrenergic blocking agents

Beta-blockers reduce many of the symptoms of thyrotoxicosis, including tachycardia, tremor, and anxiety. Propranolol is usually recommended because of CNS penetration, but some patients prefer the longer-acting beta-blockers.

Drug Name	Atenolol (Tenormin)
Description	Selectively blocks beta1-receptors with little or no effect on beta2 types.
Adult Dose	50-100 mg PO qd
Pediatric Dose	1-2 mg/kg/d PO
Contraindications	Documented hypersensitivity; CHF; pulmonary edema; cardiogenic shock; AV conduction abnormalities; heart block (without a pacemaker)
Interactions	Coadministration with aluminum salts, barbiturates, calcium salts, cholestyramine, NSAIDs, penicillins, and rifampin may decrease effects; haloperidol, hydralazine, loop diuretics, and MAOIs may increase toxicity of atenolol
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Beta-adrenergic blockade may reduce symptoms of acute hypoglycemia and may mask signs of hyperthyroidism; abrupt withdrawal may exacerbate symptoms of hyperthyroidism and cause thyroid storm; monitor patients closely and withdraw drug slowly; during an IV administration, carefully monitor BP, heart rate, and ECG

Drug Category: Corticosteroids

If thyroid pain is extreme, high-dose steroids rapidly reduce thyroid hormone levels and swelling. Generally, therapy must be continued for 4-6 wk before tapering.

FOLLOW-UP

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Further Outpatient Care

• All forms of subacute thyroiditis: Patients should be seen every 4 weeks for reassurance and to measure thyroid hormone levels. Occasionally, patients have relapses of the thyrotoxic phase and have persistent symptoms. Monitor for the subsequent hypothyroid phase and treat with L-thyroxine if patients are symptomatic from the hypothyroidism.
• Subacute painful or granulomatous thyroiditis: Patients usually recover completely from painful subacute thyroiditis. The episodes rarely reoccur. Generally, patients are not prone to other thyroid disease and do not need long-term follow-up.
• Subacute painless and subacute postpartum thyroiditis: These conditions are sometimes associated with chronic thyroiditis. Postpartum thyroiditis usually reoccurs after each pregnancy. Occasionally, subacute painless thyroiditis is recurrent. Patients should be observed routinely every 6-12 months for the development of goiter or hypothyroidism from chronic thyroiditis.

Deterrence/Prevention

• No medical intervention is known to prevent any form of subacute thyroiditis.
• Recurrent episodes in patients with recurrent subacute thyroiditis with severe symptoms can be prevented by thyroidectomy.

Complications

• Subacute painful or granulomatous thyroiditis: This condition generally resolves completely in more than 90-95% of patients. No special follow-up of the thyroid is needed.



• Subacute painless and subacute lymphocytic thyroiditis: Occasionally, patients have recurrent episodes of painless thyrotoxicosis. No treatment exists except subtotal thyroidectomy to prevent the recurrences. This condition generally resolves completely in more than 90-95% of patients. Patients with goiters or permanent thyroid dysfunction should be monitored with a thyroid examination and thyroid functions tests every 6 months.



• Subacute postpartum thyroiditis: Repeat episodes occur after each pregnancy. No known treatment exists that prevents the recurrences after each pregnancy. Patients may have a residual goiter and thyroid hypofunction after postpartum thyroiditis because this condition is associated with chronic autoimmune thyroiditis. Patients should be observed routinely for goiter enlargement and thyroid hypofunction every 6-12 months.

Prognosis

• The prognosis is excellent in 90-95% of patients who experience subacute thyroiditis. Approximately 5-10% of patients have permanent thyroid dysfunction, usually hypothyroidism, after an episode of subacute thyroiditis. Permanent goiter and thyroid dysfunction occur most frequently after postpartum thyroiditis.

Patient Education

• Patients with postpartum subacute thyroiditis should be counseled that repeat episodes are likely to occur following every pregnancy.
• For excellent patient education resources, visit eMedicine's Endocrine System Center. Also, see eMedicine's patient education article Thyroid Problems.

MISCELLANEOUS

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Medical/Legal Pitfalls

• Determining that elevated thyroid hormones levels are from the causes listed in this article and not from excess synthesis of thyroid hormone is important. Generally, the conditions described here are temporary (eg, subacute thyroiditis) and, therefore, do not require definitive therapy such as thyroid surgery, radioactive iodine, or antithyroid therapy. Radioactive iodine and antithyroid therapy is never appropriate for these forms of subacute thyroiditis.

MULTIMEDIA

Section 10 of 11  

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• Multimedia
• References

Media file 1:  Absence of iodine I 123 radioactive iodine uptake in a patient with thyrotoxicosis and subacute painless or lymphocytic thyroiditis. Laboratory studies at the time of the scan demonstrated the following: thyroid-stimulating hormone (TSH) less than 0.06 mIU/mL, total thyroxine (T4) 21.2 mcg/dL (reference range, 4.5-11), total triiodothyronine (T3) 213 ng/dL (reference range, 90-180), T3-to-T4 ratio 10, and erythrocyte sedimentation rate (ESR) 10 mm/h. The absence of thyroid uptake, the low T3-to-T4 ratio, and the low ESR confirm the diagnosis of subacute painless thyroiditis.
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Media type:  X-RAY

Media file 2:  Example of laboratory values during subacute granulomatous thyroiditis. The entire episode may evolve through all 3 phases in as long as 6 months.
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Media type:  Image

Media file 3:  Three multinuclear giant cell granulomas observed in a fine-needle aspiration biopsy of the thyroid from a patient with thyrotoxicosis from subacute painful or granulomatous thyroiditis.
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Media type:  Photo

REFERENCES

Section 11 of 11

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

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• Roti E, Minelli R, Giuberti T, et al. Multiple changes in thyroid function in patients with chronic active HCV hepatitis treated with recombinant interferon-alpha. Am J Med. Nov 1996;101(5):482-7. [Medline].

Article Last Updated: Jul 27, 2006