eMedicine Specialties > Endocrinology > Thyroid

Subacute Thyroiditis

Stephanie L Lee, MD, PhD, Fellow, Association of Clinical Endocrinology; Director of Thyroid Nodule and Cancer Center, Associate Chief, Section of Endocrinology, Diabetes and Nutrition, Boston Medical Center; Associate Professor, Department of Medicine, Boston University School of Medicine
Sonia Ananthakrishnan, MD, Attending Physician, Department of Medicine, Section of Endocrinology, Diabetes and Nutrition, Boston University School of Medicine/Boston Medical Center

Updated: Apr 27, 2009

Introduction

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, the following 3 forms of subacute thyroiditis are recognized:

• Subacute granulomatous, subacute painful, or de Quervain thyroiditis (see image below and Image 1.)
• Lymphocytic thyroiditis (also known as subacute painless thyroiditis)
• Subacute postpartum thyroiditis

Three multinuclear, giant cell granulomas observed in a fine-needle aspiration biopsy of the thyroid; from a patient with thyrotoxicosis from lymphocytic or subacute granulomatous thyroiditis.

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 the eMedicine article 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 below and Images 2-3).

The 3 types of subacute thyroiditis are subacute granulomatous thyroiditis, also referred to as subacute painful thyroiditis; lymphocytic thyroiditis, which is silent and is also referred to as subacute painless thyroiditis; and postpartum thyroiditis. The etiology of each of these conditions is different, but all of them 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 3.

Absence of iodine-123 (¹²³I) radioactive iodine uptake in a patient with thyrotoxicosis and lymphocytic (subacute painless) 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 lymphocytic thyroiditis.

Example of laboratory values during subacute granulomatous thyroiditis. The entire episode may evolve through all 3 phases over a period of as long as 6 months.

Three multinuclear, giant cell granulomas observed in a fine-needle aspiration biopsy of the thyroid; from a patient with thyrotoxicosis from lymphocytic or subacute granulomatous thyroiditis.

Frequency

United States

The thyrotoxicosis caused by lymphocytic, subacute painful, or 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

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

Race

Subacute thyroiditis appears to affect all races and ethnic groups equally.

Sex

• Subacute granulomatous thyroiditis has a female-to-male prevalence ratio of 5:1.
• Lymphocytic thyroiditis and postpartum thyroiditis are associated with autoimmune thyroiditis. Lymphocytic thyroiditis occurs 2 times more often in women than it does 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

• Lymphocytic thyroiditis can occur in any age group, while granulomatous thyroiditis usually occurs in adults (ie, aged 20-60 y).
• Postpartum thyroiditis occurs in women of childbearing age.

Clinical

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 lymphocytic 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 granulomatous thyroiditis - These patients have the classic presentation of a viral illness. The onset is sudden, with high fever, myalgia, and neck pain.
• 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 lymphocytic 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 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.
• 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 those of subacute granulomatous thyroiditis, are not entirely clear.

• Subacute granulomatous thyroiditis - The most accepted etiology is a viral illness.² 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 (human leukocyte antigen)-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. Granulomatous thyroiditis is not an autoimmune disease of the thyroid.
• Lymphocytic thyroiditis - This condition most likely is autoimmune in nature. Patients develop an autoimmune goiter and permanent hypothyroidism more often than they do with the painful form of subacute thyroiditis.
  • An HLA 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), interferon-alpha, interleukin 2, and lithium. Lymphocytic thyroiditis resulting from these different medications is typically treated similarly (see Medication).
    • Amiodarone has multiple established effects on thyroid function. One of the 2 types of amiodarone-induced thyrotoxicosis is a destructive lymphocytic thyroiditis. This form of thyroiditis is more common in men, likely due to the higher prevalence of amiodarone therapy in men. This form of silent thyroiditis typically occurs after more than 2 years of amiodarone therapy.
    • Up to 5% of patients taking interferon-alpha may experience lymphocytic thyroiditis. This condition is detected biochemically more often than clinically after 3 months of therapy. Lymphocytic thyroiditis in patients taking interferon-alpha is associated with an increased antithyroid antibody concentration.
    • Although case reports exist that interleukin 2 is associated with lymphocytic thyroiditis, its causative role is less established than is that of interferon-alpha.
    • Lithium is a well-known cause of either subclinical or clinical hypothyroidism, as well as of goiter. Because of lithium’s ability to inhibit the release of thyroid hormone, it has been used as a treatment for thyrotoxicosis. However, reports exist of lithium-associated thyrotoxicosis due to a lymphocytic thyroiditis, with the classic picture of hyperthyroidism, absent neck tenderness, and low radioactive iodine uptake (see Medication). The lymphocytic 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.³ 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.

Differential Diagnoses

Riedel Thyroiditis

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

Laboratory Studies

• Thyroid-stimulating hormone (TSH) levels
  • The most reliable measure of thyroid function is a 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 have elevations only 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.
• Subacute granulomatous thyroiditis (see image below and Image 3)

Example of laboratory values during subacute granulomatous thyroiditis. The entire episode may evolve through all 3 phases over a period of as long as 6 months.

• 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 of 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 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 image below and Image 2).

Absence of iodine-123 (¹²³I) radioactive iodine uptake in a patient with thyrotoxicosis and lymphocytic (subacute painless) 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 lymphocytic 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 patients become symptomatic from the hypothyroidism. Ninety to 95% of patients spontaneously return to normal thyroid function.
• Lymphocytic thyroiditis
  • The time course is identical to subacute granulomatous thyroiditis (see Image 3). 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 of less than 15 usually increases suspicion of subacute thyroiditis.
  • The hallmark of lymphocytic 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 that for subacute granulomatous thyroiditis (see Image 3). 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 transiently become very elevated.

Imaging Studies

• Nuclear scintigraphy
  • Subacute thyroiditis results in a very low radioactive iodine uptake (¹²³ I or¹³¹ I) or technetium-99m (^99m Tc) 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 ultrasonography alone is not helpful in distinguishing between abnormalities resulting from subacute thyroiditis and other causes of high thyroid hormone levels, including Graves thyroiditis.⁴
  • The use of Doppler ultrasonography 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 below and Image 1).

Three multinuclear, giant cell granulomas observed in a fine-needle aspiration biopsy of the thyroid; from a patient with thyrotoxicosis from lymphocytic or subacute granulomatous thyroiditis.

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 1).

Treatment

Medical Care

Patients are often dehydrated from 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 subacute granulomatous 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 (iopanoic acid), better known as Gastrografin, may be administered to inhibit the conversion of T4 to the more active form of thyroid hormone, T3. A dose of 1000 mg in 2 divided doses daily usually provides a rapid reduction in T3 and in thyrotoxic symptoms.
• Pain in lymphocytic 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 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 lymphocytic thyroiditis or recurrent pain from subacute granulomatous 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 with subacute thyroiditis – caused thyrotoxicosis to exercise normally.

Medication

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 toward reducing the signs and symptoms of the hyperthyroidism with beta blockers or iodine agents. Pain is treated with nonsteroidal anti-inflammatory agents (NSAIDs). Rarely, high-dose steroids and narcotic analgesic agents are used for extremely painful or recurrent life-threatening hyperthyroidism.

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.

Ibuprofen (Advil, Motrin)

DOC for patients with mild to moderate pain. Inhibits inflammatory reactions and pain by decreasing prostaglandin synthesis.

Dosing

Adult

600-800 mg PO tid

Pediatric

4-10 mg/kg per dose PO tid/qid; not to exceed 50 mg/kg/d

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

Contraindications

Documented hypersensitivity; peptic ulcer disease; recent GI bleeding or perforation; renal insufficiency; high risk of bleeding

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Caution in CHF, hypertension, and decreased renal and hepatic function; caution in anticoagulation abnormalities or during anticoagulant therapy

Naproxen (Aleve, Naprosyn, Naprelan)

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.

Dosing

Adult

250-500 mg PO bid

Pediatric

10-20 mg/kg PO divided bid

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

Contraindications

Documented hypersensitivity; peptic ulcer disease; recent GI bleeding or perforation; renal insufficiency

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

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

Indomethacin (Indocin)

Rapidly absorbed. Metabolism occurs in liver by demethylation, deacetylation, and glucuronide conjugation. Inhibits prostaglandin synthesis.

Dosing

Adult

25-50 mg PO tid

Pediatric

Not established

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

Contraindications

Documented hypersensitivity; GI bleeding; renal insufficiency

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

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

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.

Iopanoic acid (Telepaque)

PO contrast agent for rapid and significant inhibition of peripheral conversion of T4 to T3. Inorganic iodide released also blocks release of thyroid hormones. Reduction in conversion of T4 to T3 can greatly reduce T3 levels and thyrotoxic symptoms over a few d.

Dosing

Adult

2 g PO, then 0.5 g PO bid

Pediatric

Not established

Interactions

Coadministration with lithium may result in hypothyroid effects

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Possibility of hypotension increases with increased dosage; 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

Ipodate (Oragrafin)

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.

Dosing

Adult

2 g PO, then 0.5 g PO bid

Pediatric

Not established

Interactions

Coadministration with lithium may result in hypothyroid effects

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

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

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 the 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.

Levothyroxine (Levoxyl, Synthroid)

In active form, influences growth and maturation of tissues. Involved in normal growth, metabolism, and development. L-thyroxine supplementation only during the hypothyroid phase of subacute thyroiditis. The goal of therapy is a TSH level within the reference range for 6 mo; then discontinue therapy. TSH should be checked 4 wk later, and, if TSH is elevated, L-thyroxine therapy must be reinstituted and continued indefinitely.

Dosing

Adult

50 mcg/d PO; after 6 wk, if TSH level is abnormal, adjust dose

Pediatric

1-2 mcg/kg/d PO; after 6 wk, if TSH level is abnormal, adjust dose

Interactions

Cholestyramine may decrease L-thyroxine absorption; concomitant administration with calcium or iron supplements may decrease L-thyroxine absorption; estrogens may decrease response to thyroid hormone therapy in patients with nonfunctioning thyroid glands; effect of anticoagulants is increased when administered with liothyronine; activity of some beta-blockers may decrease when hypothyroid patient is converted to a euthyroid state

Contraindications

Documented hypersensitivity; uncorrected adrenal insufficiency; coronary artery disease; atrial arrhythmia

Precautions

Pregnancy

A - Fetal risk not revealed in controlled studies in humans

Precautions

Caution in angina pectoris or cardiovascular disease; monitor thyroid status periodically

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.

Propranolol (Inderal)

DOC in treating cardiac arrhythmia resulting from hyperthyroidism. Controls cardiac and psychomotor manifestations within minutes.

Dosing

Adult

20-40 mg PO q4-8h

Pediatric

2-4 mg/kg PO divided q6-8h

Interactions

Coadministration with aluminum salts, barbiturates, NSAIDs, penicillins, calcium salts, cholestyramine, and rifampin may decrease propranolol effects; calcium channel blockers, cimetidine, loop diuretics, and MAOIs may increase toxicity of propranolol; toxicity of hydralazine, haloperidol, benzodiazepines, and phenothiazines may increase with propranolol

Contraindications

Documented hypersensitivity; uncompensated CHF; bradycardia; cardiogenic shock; AV conduction abnormalities

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Beta-adrenergic blockade may decrease signs of acute hypoglycemia and hyperthyroidism; abrupt withdrawal may exacerbate symptoms of hyperthyroidism, including thyroid storm; withdraw drug slowly and monitor closely

Atenolol (Tenormin)

Selectively blocks beta1-receptors with little or no effect on beta2 types.

Dosing

Adult

50-100 mg PO qd

Pediatric

1-2 mg/kg/d PO

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

Contraindications

Documented hypersensitivity; CHF; pulmonary edema; cardiogenic shock; AV conduction abnormalities; heart block (without a pacemaker)

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

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

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.

Prednisone (Deltasone, Orasone, Sterapred)

May decrease inflammation by reversing increased capillary permeability and suppressing PMN activity.

Dosing

Adult

40-60 mg PO qd for 4-6 wk; taper as symptoms resolve

Pediatric

Not established

Interactions

Coadministration with estrogens may decrease prednisone clearance; concurrent use with digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism of glucocorticoids (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics

Contraindications

Documented hypersensitivity; viral infection; peptic ulcer disease; hepatic dysfunction; connective tissue infections; fungal or tubercular skin infections; GI disease

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Abrupt discontinuation of glucocorticoids may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections may occur with glucocorticoid use

Follow-up

Further Outpatient Care

• All forms of subacute thyroiditis - Patients should be seen every 4 weeks for reassurance and for measurement of 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 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.
• Lymphocytic and subacute postpartum thyroiditis - These conditions are sometimes associated with chronic thyroiditis. Postpartum thyroiditis usually recurs 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 with thyroidectomy.

Complications

• Subacute granulomatous thyroiditis - This condition generally resolves completely in more than 90-95% of patients. No special follow-up of the thyroid is needed.
• Lymphocytic thyroiditis - Occasionally, patients have recurrent episodes of painless thyrotoxicosis.⁵ No treatment exists to prevent the recurrences except subtotal thyroidectomy. 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 function tests every 6 months.
• Subacute postpartum thyroiditis - Usually, repeat episodes occur after each pregnancy, and no known treatment exists to prevent these. 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 subacute postpartum 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

Medicolegal 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 treatment, or antithyroid therapy. Radioactive iodine treatment and antithyroid therapy are never appropriate for these forms of subacute thyroiditis.

Multimedia

Media file 1: Three multinuclear, giant cell granulomas observed in a fine-needle aspiration biopsy of the thyroid; from a patient with thyrotoxicosis from lymphocytic or subacute granulomatous thyroiditis.

Media file 2: Absence of iodine-123 (¹²³I) radioactive iodine uptake in a patient with thyrotoxicosis and lymphocytic (subacute painless) 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 lymphocytic thyroiditis.

Media file 3: Example of laboratory values during subacute granulomatous thyroiditis. The entire episode may evolve through all 3 phases over a period of as long as 6 months.

References

1. Nishihara E, Ohye H, Amino N, et al. Clinical characteristics of 852 patients with subacute thyroiditis before treatment. Intern Med. 2008;47(8):725-9. [Medline]. [Full Text].

2. Desailloud R, Hober D. Viruses and thyroiditis: an update. Virol J. Jan 12 2009;6:5. [Medline]. [Full Text].

3. Filippi U, Brizzolara R, Venuti D, et al. Prevalence of post-partum thyroiditis in Liguria (Italy): an observational study. J Endocrinol Invest. Dec 2008;31(12):1063-8. [Medline].

4. Omori N, Omori K, Takano K. Association of the ultrasonographic findings of subacute thyroiditis with thyroid pain and laboratory findings. Endocr J. Jul 2008;55(3):583-8. [Medline]. [Full Text].

5. Nishimaki M, Isozaki O, Yoshihara A, Okubo Y, Takano K. Clinical characteristics of frequently recurring painless thyroiditis: contributions of higher thyroid hormone levels, younger onset, male gender, presence of thyroid autoantibody and absence of goiter to repeated recurrence. Endocr J. Feb 18 2009;[Medline]. [Full Text].

6. Bartalena L, Brogioni S, Grasso L, Bogazzi F, Burelli A, Martino E. Treatment of amiodarone-induced thyrotoxicosis, a difficult challenge: results of a prospective study. J Clin Endocrinol Metab. Aug 1996;81(8):2930-3. [Medline]. [Full Text].

7. Bartalena L, Grasso L, Brogioni S, et al. Serum interleukin-6 in amiodarone-induced thyrotoxicosis. J Clin Endocrinol Metab. Feb 1994;78(2):423-7. [Medline]. [Full Text].

8. Basaria S, Cooper DS. Amiodarone and the thyroid. Am J Med. Jul 2005;118(7):706-14. [Medline].

9. Dang AH, Hershman JM. Lithium-associated thyroiditis. Endocr Pract. May-Jun 2002;8(3):232-6. [Medline].

10. Emerson CE, Farwell AP. Sporadic silent thyroiditis, postpartum thyroiditis, and subacute thyroiditis. In: Braverman LE, Utiger RD, eds. Werner and Ingbar's The Thyroid. 8^th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2000:579-89.

11. Hamburger JI. The various presentations of thyroiditis. Diagnostic considerations. Ann Intern Med. Feb 1986;104(2):219-24. [Medline].

12. Hay ID. Thyroiditis: a clinical update. Mayo Clin Proc. Dec 1985;60(12):836-43. [Medline].

13. Lambert M, Unger J, De Nayer P, et al. Amiodarone-induced thyrotoxicosis suggestive of thyroid damage. J Endocrinol Invest. Jun 1990;13(6):527-30. [Medline].

14. Miller KK, Daniels GH. Association between lithium use and thyrotoxicosis caused by silent thyroiditis. Clin Endocrinol (Oxf). Oct 2001;55(4):501-8. [Medline].

15. Nikolai TF, Brosseau J, Kettrick MA, et al. Lymphocytic thyroiditis with spontaneously resolving hyperthyroidism (silent thyroiditis). Arch Intern Med. Apr 1980;140(4):478-82. [Medline].

16. 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].

Keywords

subacute thyroiditis, thyroid, hypothyroidism, thyroid disease, hyperthyroidism, hypothyroid, thyroid symptoms, thyroiditis, hyperthyroid, thyroid hormone, symptoms of thyroid, symptoms of thyroid problems, thyroid disorder, thyroxine, thyroid disorders, thyroid tests, thyroid hormones, T3 thyroid, T4 thyroid, thyrotoxicosis, postpartum thyroiditis, triiodothyronine, lymphocytic thyroiditis, de Quervain's, silent thyroiditis, de Quervain thyroiditis, subacute painless thyroiditis, subacute lymphocytic thyroiditis, subacute postpartum thyroiditis, subacute granulomatous thyroiditis, subacute painful thyroiditis, de Quervain's thyroiditis

Contributor Information and Disclosures

Author

Stephanie L Lee, MD, PhD, Fellow, Association of Clinical Endocrinology; Director of Thyroid Nodule and Cancer Center, Associate Chief, Section of Endocrinology, Diabetes and Nutrition, Boston Medical Center; Associate Professor, Department of Medicine, Boston University School of Medicine
Stephanie L Lee, MD, PhD is a member of the following medical societies: American College of Endocrinology, American Thyroid Association, and Endocrine Society
Disclosure: Nothing to disclose.

Coauthor(s)

Sonia Ananthakrishnan, MD, Attending Physician, Department of Medicine, Section of Endocrinology, Diabetes and Nutrition, Boston University School of Medicine/Boston Medical Center
Disclosure: Nothing to disclose.

Medical Editor

Stanley Wallach, MD, Executive Director, American College of Nutrition; Clinical Professor, Department of Medicine, New York University School of Medicine
Stanley Wallach, MD is a member of the following medical societies: American Society for Bone and Mineral Research, American Society for Clinical Investigation, American Society for Clinical Nutrition, American Society for Nutritional Sciences, Association of American Physicians, and Endocrine Society
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Arthur B Chausmer, MD, PhD, FACP, FACE, FACN, CNS, Professor of Medicine (Endocrinology, Adj), Johns Hopkins School of Medicine; Affiliate Research Professor, Bioinformatics and Computational Biology Program, School of Computational Sciences, George Mason University; Principal, C/A Informatics, LLC
Arthur B Chausmer, MD, PhD, FACP, FACE, FACN, CNS is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Endocrinology, American College of Nutrition, American College of Physician Executives, American College of Physicians, American College of Physicians-American Society of Internal Medicine, American Medical Informatics Association, American Society for Bone and Mineral Research, American Society of Law Medicine and Ethics, Endocrine Society, and International Society for Clinical Densitometry
Disclosure: Nothing to disclose.

CME Editor

Mark Cooper, MBBS, PhD, FRACP, Head, Diabetes & Metabolism Division, Baker Heart Research Institute, Professor of Medicine, Monash University
Disclosure: Nothing to disclose.

Chief Editor

George T Griffing, MD, Professor of Medicine, St Louis University School of Medicine
George T Griffing, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Medical Practice Executives, American College of Physician Executives, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Heart Association, Central Society for Clinical Research, Endocrine Society, International Society for Clinical Densitometry, and Southern Society for Clinical Investigation
Disclosure: Nothing to disclose.

Clinical guidelines:
Management of thyroid dysfunction during pregnancy and postpartum: an Endocrine Society clinical practice guideline.

Clinical trials:
Generic vs. Name-Brand Levothyroxine
Maternal Hypothyroidism in Pregnancy

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