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Thyroiditis

The broad category of thyroiditis includes the following inflammatory diseases of the thyroid gland:
(1) acute suppurative thyroiditis, which is due to bacterial infection;
(2) subacute thyroiditis, which results from a viral infection of the gland; and
(3) chronic thyroiditis, which is usually autoimmune in nature. In childhood, chronic thyroiditis is the most
common of these 3 types. The second form of thyroiditis, Riedel struma, is rare in children. Secondary
thyroiditis may be due to the administration of amiodarone to treat cardiac arrhythmias or the
administration of interferon-alpha to treat viral diseases.

Pathophysiology
Acute suppurative thyroiditis is rare in childhood because the thyroid is remarkably resistant to hematogenously spread
infection. Most cases of acute thyroiditis involve the left lobe of the thyroid and are associated with a developmental
abnormality of thyroid migration and the persistence of a pyriform sinus from the pharynx to the thyroid capsule.
The usual organisms responsible include Staphylococcus aureus,Streptococcus hemolyticus, and pneumococcus. Other
aerobic or anaerobic bacteria may also be involved.
Subacute thyroiditis is generally thought to be due to viral processes and usually follows a prodromal viral illness.
Various viral illnesses may precede the disease, including mumps, measles, influenza, infectious mononucleosis,
adenoviral or Coxsackievirus infections, myocarditis, or the common cold.
Because chronic thyroiditis in children is usually due to an autoimmune process, it is HLA-associated, similar to other
autoimmune endocrine diseases.

Sex
The pediatric male-to-female ratio for autoimmune thyroiditis ranges from 1:2 to 1:6. This is low when compared with the
90% female predominance in adults

Acute thyroiditis

A history of acute illness, including fever, chills, neck pain, sore throat, hoarseness, and dysphagia, is
common.
Neck pain is frequently unilateral and radiates to the mandible, ears, or occiput. Neck flexion reduces the
severity of the pain. The pain worsens with neck hyperextension.

Subacute thyroiditis

Neck tenderness and swelling may occur.


Occasionally, the initial symptoms are those of hyperthyroidism.
Systemic symptoms such as weakness, fatigue, malaise, and fever are usually low grade.

Physical
Acute thyroiditis

The patient may have a fever of 38-40C.


Acute illness may be evident.
Neck tenderness is present, and the swollen thyroid gland is tender. The swelling and
tenderness may be unilateral. Erythemas develop over the gland, and regional lymphadenopathy may
develop as the disease progresses. Abscess formation may occur.

Subacute thyroiditis

The patient may have signs of systemic illness, such as low-grade fever and weakness.
Signs of hyperthyroidism, including increased pulse rate, widened pulse pressure, fidgeting, tremor,
nervousness, tongue fasciculations, brisk reflexes (possibly with clonus), weight loss, and warm moist skin,
may be present.

The thyroid gland may be enlarged and tender, with tenderness exacerbated by neck extension.

Chronic autoimmune thyroiditis

Initially, an enlarged, lumpy, bumpy, and nontender thyroid is often present. The gland may not
be enlarged, particularly in children who have profound hypothyroidism. Signs of hypothyroidism include
slow growth rate, weight gain, slow pulse, cold dry skin, coarse hair and facial features, edema, and delayed
relaxation of the deep tendon reflexes.
Signs of hyperthyroidism are occasionally present early in the disease.

Laboratory Studies
Acute thyroiditis

Laboratory abnormalities in acute thyroiditis reflect the acute systemic illness.


Findings include leukocytosis with a left shift and an increased sedimentation rate.
Thyroid function test results are within the reference range.

Subacute thyroiditis

The primary laboratory abnormalities are consistent with abnormal thyroid function. Initially, the thyroidstimulating hormone (TSH) level is suppressed, and the free thyroxine (T4) level is increased. As the disorder
progresses, transient or sometimes permanent hypothyroidism may develop.
The WBC count is usually within the reference range but may be mildly elevated. High-sensitivity Creactive protein levels are usually elevated in subacute thyroiditis.

Chronic thyroiditis

Laboratory abnormalities reflect thyroid function abnormality and evidence of autoimmunity.


TSH levels are increased in children with subclinical and overt hypothyroidism. Free T4 levels
are within the reference range in the former and low in the latter. In children with hyperthyroidism, TSH
levels are suppressed. Many children have normal thyroid function and normal TSH levels.
Antithyroid peroxidase (antithyrocellular, antimicrosomal) antibody levels elevated above the
reference range are the most sensitive indicator of thyroid autoimmunity. Many children also have
antithyroglobulin antibodies, although this is less sensitive and less specific.

Imaging Studies
Radioactive iodine thyroid scanning

Radioactive iodine thyroid scanning is not necessary for acute suppurative thyroiditis because the
results are normal and do not aid in diagnosis. A scan may be helpful after diagnosis to identify a persistent
thyroglossal duct as a route for infection.
This test is also unnecessary for chronic thyroiditis because the results can be misleading and may
show increased uptake consistent with Graves disease, a multinodular goiter, or a hypofunctioning or
hyperfunctioning nodule.
Radioactive iodine thyroid scanning is helpful in patients with hyperthyroidism who are thought to have
subacute thyroiditis because the extremely low uptake is consistent with the thyrocellular destruction in
progress.

Thyroid ultrasonography

Thyroid ultrasonography is useful in revealing abscess formation in patients with acute


thyroiditis.
The degree of hypoechogenicity on ultrasonography is related to the degree of thyroid dysfunction but
its clinical use in chronic thyroiditis is questionable and does not alter management in children with chronic
thyroiditis.[6]
The overall of specificity of thyroid ultrasonography to identify specific concerns is questionable. A
study in Germany found thyroid ultrasonography abnormalities in 40% of a random adult population, including
nodules in 35.6%.[7]

Procedures
Fine-needle thyroid aspiration

This procedure is advocated by some to document the presence of thyroid lymphocytic


infiltration in autoimmune thyroiditis. Histologic results are predictive of thyroid function; however, the
results can be misinterpreted and can lead to unnecessary thyroid surgery.
Reserve this test for patients in whom underlying malignancy is suggested by a discrete
thyroid nodule.
In patients with acute thyroiditis, needle aspiration can be used to obtain material for culture, enabling
appropriate antibiotic therapy.

Subacute Thyroiditis
Subacute thyroiditis is a self-limited thyroid condition associated with a triphasic clinical course of
hyperthyroidism, hypothyroidism, and return to normal thyroid function.
Recognizing this condition is important; because it is self-limiting, no specific treatment, 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 thyroiditis - Also known as subacute painful or de Quervain thyroiditis Subacute
lymphocytic thyroiditis - Also known as subacute painless thyroiditis
Subacute postpartum thyroiditis

Disease course
Although the etiology appears to be different for the 3 subtypes, the clinical courses are the same. High thyroid
hormone levels result from the destruction of the thyroid follicle and the release of preformed thyroid hormone into
the circulation, with thyrotoxicosis consequently developing. This phase lasts 4-10 weeks.

The disease undergoes remission in 2-4 months. At this time, the thyroid is depleted of colloid and is
now incapable of producing thyroid hormone, resulting in hypothyroidism. The hypothyroid phase may
last up to 2 months. Often, the hypothyroidism is mild, and no thyroid hormone therapy is required
unless the patient has signs or symptoms of hypothyroidism. As the follicles regenerate, the euthyroid
state is restored.

Subacute granulomatous thyroiditis


Subacute granulomatous thyroiditis is the most common cause of a painful thyroid gland. It is a transient
inflammation of the thyroid, the clinical course of which is highly variable. Most patients have pain in the region of
the thyroid, which is usually diffusely tender, and some have systemic symptoms. Hyperthyroidism often occurs
initially, sometimes followed by transient hypothyroidism. Complete recovery in weeks to months is characteristic.

Pathophysiology
Destruction of follicular epithelium and loss of follicular integrity are the primary events in the pathophysiology of subacute
granulomatous thyroiditis. Thyroglobulin (TG), thyroid hormones, and other iodinated compounds are released into the
blood, often in quantities sufficient to elevate the serum thyroxine (T4) and triiodothyronine (T3) concentrations and suppress
thyroid-stimulating hormone (TSH) secretion. This state lasts until the stores of TG are exhausted or until healing occurs.
Thyroidal iodine uptake and new hormone synthesis temporarily ceases because of the low level of TSH.
As inflammation subsides, the thyroid follicles regenerate and thyroid hormone synthesis and secretion resume. In some
patients, several months are required for thyroid hormone synthesis to return to a normal rate; during that period, clinical
hypothyroidism may be evident.

Thyrotoxicosis
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 the following:

Weight loss despite increased appetite


Lid lag and stare
Sinus tachycardia
Atrial fibrillation or high-output failure (in elderly persons)
Fine tremor
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.

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

Subacute granulomatous thyroiditis


The most accepted etiology for this condition is a viral illness. [1] 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. The occurrence of subacute granulomatous thyroiditis
in the course of novel H1N1 influenza infection has been reported from Greece

Subacute lymphocytic thyroiditis


This condition most likely is autoimmune in nature. Patients develop an autoimmune goiter and permanent hypothyroidism
more often than they do with subacute granulomatous thyroiditis. An HLA association may be present, suggesting a genetic
predisposition to subacute lymphocytic thyroiditis.
Certain drug exposures relating to excess iodine and cytokines may cause this form of silent thyroiditis. These drugs include
amiodarone (iodine-rich), interferon alfa, interleukin 2, and lithium. Cases of thyroiditis resulting from these drugs are
typically treated in a similar way.
Amiodarone

Subacute postpartum thyroiditis


This condition is likely autoimmune in nature.[5] Patients develop an autoimmune goiter and permanent hypothyroidism more
often than they do with subacute granulomatous thyroiditis. In iodine-sufficient countries, such as the United States,
postpartum thyroiditis occurs in approximately 5-8% of pregnant women. In Japan where the diet is rich in iodine, 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.

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.

History
Subacute granulomatous thyroiditis
Some patients experience a flulike prodromal episode 1-3 weeks prior to the onset of clinical disease. The natural
course of the disease can be divided into the following 4 phases, which usually unfold over a period of 3-6 months:

Acute phase - Lasts 3-6 weeks and presents primarily with pain; symptoms of hyperthyroidism also may
be present
Transient asymptomatic and euthyroid phase - Lasts 1-3 weeks
Hypothyroid phase - Lasts from weeks to months; it may become permanent in 5-15% of patients
Recovery phase - Characterized by normalization of thyroid structure and function
The diagnosis is made based on clinical findings. Prodromal flulike symptoms (fevers, myalgia, malaise) or known
infectious disease, such as pharyngitis, measles, mumps, Q fever, or typhoid fever, may occur. In young patients, de
Quervain thyroiditis may develop following an episode of Henoch-Schnlein purpura. However, a history of prodromal
symptoms often cannot be obtained.
Local symptoms
Local symptoms can include the following:

Dysphagia
Hoarseness (uncommon)
Pain over the thyroid area that is gradual or of sudden onset
Pain is the presenting symptom in over 90% of cases. It usually involves both lobes of the thyroid; in 30% of cases, it
starts on one side and then migrates contralaterally within a few days. While the pain may be limited to the region of the
thyroid, it may also involve the upper neck, throat, jaw, or ears. Some patients may first consult an otolaryngologist.
The pain may be so severe that the patient cannot tolerate palpation of the neck. The pain is most commonly bilateral.
Occasionally, it may be unilateral, beginning in one lobe and spreading to the opposite side (creeping thyroiditis). Coughing,
swallowing, or even tightening a necktie aggravates pain.
Constitutional symptoms

Constitutional symptoms (often absent) can include the following:

Fever
Malaise
Anorexia
Fatigue
Muscle aches
Symptoms of hyperthyroidism
Hyperthyroidism is usually is mild, becoming severe only in rare cases. The symptoms are transient, typically lasting 3-6
weeks. Symptoms of hyperthyroidism occurring in the acute phase of subacute granulomatous thyroiditis include the
following:

Tachycardia
Tremulousness
Heat intolerance
Sweating
Nervousness
Warm skin
Frequent bowel movements
Symptoms of hypothyroidism
Symptoms of hypothyroidism occur in the late phase of the disease in up to 50% of cases. The hypothyroidism is most often
mild or moderate. It is also transient, lasting weeks to months in 90-95% of cases. Symptoms of hypothyroidism occurring
during the second phase of subacute granulomatous thyroiditis include the following:

Fatigue
Dry skin
Lethargy
Eyelid swelling
Cold intolerance
Constipation
Atypical symptoms
Atypical presentations of subacute granulomatous thyroiditisthat is, extremely rare symptoms that have been documented
as case reportscan include the following:

Thyroid storm [11]


Fever of unknown origin
Painless subacute granulomatous thyroiditis
Occult de Quervain disease mimicking giant cell arteritis
Prominent prostration and confusion lasting several weeks
Solitary painless nodule

Subacute lymphocytic thyroiditis


This form of subacute thyroiditis 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 subacute lymphocytic thyroiditis.

Subacute postpartum thyroiditis


This condition 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. Patients may report lack of sleep, nervousness,
fatigue, and easy weight loss.[12, 7]
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 Examination
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.
Thyroid tenderness is usually symmetrical. In 30% of cases, however, it starts on one side and then migrates contralaterally
within a few days. While the pain may be limited to the region of the thyroid, it may also involve the upper neck, throat, jaw,
or ears. In many patients, the pain is so severe that he or she cannot tolerate palpation of the neck. The pain may be intense
enough to prevent the swallowing of saliva, liquids, and food.
Thyroid enlargement, however, is usually symmetrical and mild, occasionally with areas of localized firmness. Erythema and
hyperesthesia of the overlying skin may be present at the onset of severe cases. Cervical lymphadenopathy is uncommon.
Lid retraction is rare, and exophthalmos does not occur.
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.
Symptoms of hyperthyroidism occurring in the acute phase of subacute granulomatous thyroiditis include the following:

Tachycardia
Tremulousness
Heat intolerance
Sweating
Nervousness
Warm skin
A rapid relaxation phase of tendon reflexes

Subacute 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.
Sometimes, distinguishing between the usual postpartum changes in physiology and additional thyroid pathology is difficult

Hashimoto Thyroiditis

Practice Essentials
Hashimoto thyroiditis is part of the spectrum of autoimmune thyroid diseases (AITDs) and is characterized by the
destruction of thyroid cells by various cell- and antibody-mediated immune processes. This condition is the most
common cause of hypothyroidism in the United States in individuals older than 6 years.

Signs and symptoms


Hypothyroidism typically has an insidious onset with subtle signs and symptoms that may progress to more
advanced or even florid signs and symptoms over months to years. The presentation of patients with hypothyroidism
may also be subclinical, diagnosed based on routine screening of thyroid function. Such patients may have nonspecific
symptoms that are difficult to attribute to thyroid dysfunction. They frequently do not improve with thyroid hormone
supplementation..
Early nonspecific symptoms may include the following:

Fatigue
Constipation
Dry skin
Weight gain
More advanced/florid symptoms may include the following:

Cold intolerance
Voice hoarseness and pressure symptoms in the neck from thyroid enlargement
Slowed movement and loss of energy
Decreased sweating
Mild nerve deafness
Peripheral neuropathy
Galactorrhea
Depression, dementia, and other psychiatric disturbances
Memory loss
Joint pains and muscle cramps
Hair loss
Menstrual irregularities
Sleep apnea and daytime somnolence

Diagnosis
Physical findings are variable and depend on the extent of the hypothyroidism and other factors, such as age. Examination
findings may include the following:

Puffy face and periorbital edema typical of hypothyroid facies


Cold, dry skin, which may be rough and scaly
Peripheral edema of hands and feet, typically nonpitting
Thickened and brittle nails (may appear ridged)
Bradycardia
Elevated blood pressure (typically diastolic hypertension)
Diminished deep tendon reflexes and the classic prolonged relaxation phase
Macroglossia
Slow speech
Ataxia
Testing
Laboratory studies and potential results for patients with suspected Hashimoto thyroiditis include the following:

Serum TSH levels: Sensitive test of thyroid function; levels are invariably raised in hypothyroidism due to
Hashimoto thyroiditis and in primary hypothyroidism from any cause
Free T4 levels: Needed to correctly interpret the TSH in some clinical settings; low total T4 or free T4 level in the
presence of an elevated TSH level further confirms diagnosis of primary hypothyroidism
T3 levels: Low T3 level and high reverse T3 level may aid in the diagnosis of nonthyroidal illness
Thyroid autoantibodies: Presence of typically anti-TPO (anti-thyroid peroxidase) and anti-Tg (anti-thyroglobulin)
antibodies delineates the cause of hypothyroidism as Hashimoto thyroiditis or its variant; however, 10-15% of patients with
Hashimoto thyroiditis may be antibody negative
The following tests are not necessary for the diagnosis of primary hypothyroidism but may be used to evaluate complications
of hypothyroidism in some patients, as indicated:

Complete blood count: Anemia in 30-40% of patients with hypothyroidism


Total and fractionated lipid profile: Possibly elevated total cholesterol, LDL, and triglyceride levels in
hypothyroidism
Basic metabolic panel: Decreased glomerular filtration rate, renal plasma flow, and renal free water clearance in
hypothyroidism; may result in hyponatremia
Creatine kinase levels: Frequently elevated in severe hypothyroidism
Prolactin levels: May be elevated in primary hypothyroidism
Imaging tests
Features of Hashimoto thyroiditis are usually identifiable on an ultrasonogram; however, a thyroid ultrasonogram is usually
not necessary for diagnosing the condition. This imaging modality is useful for assessing thyroid size, echotexture,
and, most importantly, whether thyroid nodules are present.
Chest radiography and echocardiography are not usually performed and are not necessary in routine diagnosis or evaluation
of hypothyroid patients.
Procedures
Hashimoto thyroiditis is a histologic diagnosis. Therefore, perform fine-needle aspiration of any dominant or
suspicious thyroid nodules to exclude malignancy or the presence of a thyroid lymphoma in fast-growing thyroid
goiters.[1]
See Workup for more detail.

Management
Pharmacotherapy
The treatment of choice for Hashimoto thyroiditis (or hypothyroidism from any cause) is thyroid hormone
replacement. The drug of choice is individually tailored and titrated levothyroxine sodium administered orally,
usually for life.
Surgery
Indications for surgery include the following:

A large goiter with obstructive symptoms, such as dysphagia, voice hoarseness, and stridor, caused by
extrinsic obstruction of airflow
Presence of a malignant nodule, as demonstrated by cytologic examination
Presence of a lymphoma diagnosed on fine-needle aspiration
Cosmetic reasons (eg, large, unsightly goiters)
See Treatment and Medication for more detail.

Background
Hashimoto thyroiditis (or Hashimotos thyroiditis) is characterized by the destruction of thyroid cells by various cell- and
antibody-mediated immune processes. It is the most common cause of hypothyroidism in the United States after age 6
years. Hashimoto thyroiditis is part of the spectrum of autoimmune thyroid diseases(AITDs). (See Etiology, Presentation,
and Workup.)
By strict criteria, Hashimoto thyroiditis is a histologic diagnosis first described by Hakaru Hashimoto, a Japanese surgeon
working in Berlin, Germany. His report, published in 1912, was based on the examination of 4 postoperative cases. He is
also credited with introducing the term struma lymphomatosa in reference to the syndrome.
Other variants of AITD include the following conditions:

Atrophic thyroiditis
Juvenile thyroiditis [2]
Postpartum thyroiditis
Silent thyroiditis
Focal thyroiditis

Etiology
The initiating process in Hashimoto thyroiditis is not well understood. [3, 4, 5, 6] The thyroid gland is typically goitrous but may be
atrophic or normal in size. Antibodies binding to and blocking the thyroid-stimulating hormone (TSH) receptor, thyrotropin
receptor blocking antibodies (TBII) have also been described and may contribute to impairment in thyroid function. The
result is inadequate thyroid hormone production and secretion, although initially, preformed thyroxine (T4) and
triiodothyronine (T3) may "leak" into the circulation from damaged cells.
Patients with Hashimoto thyroiditis have antibodies to various thyroid antigens, the most frequently detected of which include
anti-thyroid peroxidase (anti-TPO), antithyroglobulin (anti-Tg), and to a lesser extent, TSH receptor-blocking antibodies
(TBII). Nevertheless, a small percentage of patients with Hashimoto thyroiditis (approximately 10-15%) may be serum
antibody negative.
Other antithyroid antibodies found in AITD (including Hashimoto thyroiditis) include thyroid-stimulating antibody and cytotoxic
antibody.
Hashimoto thyroiditis has a markedly higher clustering of other autoimmunity diseases, including pernicious anemia, adrenal
insufficiency, cedliac disease and type 1 diabetes mellitus.[7, 8]
In a study of 830 patients with Hashimoto thyroiditis, Tagami et al reported slight, but significant, increases in TSH serum
levels and decreases in free T4 serum levels, with increasing patient age. In addition, TSH levels were positively correlated
with levels of total cholesterol, triglycerides, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and non-HDL, as
well as with the ratio of LDL to HDL. Free T4 levels, on the other hand, were negatively correlated with these lipid
parameters.[9]

Epidemiology
Occurrence in the United States
Hashimoto thyroiditis is the most common cause of hypothyroidism in the United States after age 6 years, with the incidence
estimated to be 1.3% in a series of 5000 children aged 11-18 years. In adults, the incidence is estimated to be 3.5 per 1000
per year in women and 0.8 per 1000 per year in men. Incidence may be as high as 6% in the Appalachian region.
In the Colorado Thyroid Disease Prevalence Study, involving 25,862 adults, the prevalence of elevated TSH in symptomatic
and asymptomatic adults was 9.5%, with a greater percentage of those involved being women. The prevalence of
hypothyroidism and of thyroid disease in general increases with age.

International occurrence
Worldwide, the most common cause of hypothyroidism is iodine deficiency. However, Hashimoto thyroiditis remains the
most common cause of spontaneous hypothyroidism in areas of adequate iodine intake. The annual incidence of Hashimoto
thyroiditis worldwide is estimated to be 0.3-1.5 cases per 1000 persons. [10, 11]

Sex- and age-related demographics


The incidence of Hashimoto thyroiditis is estimated to be 10-15 times higher in females. The most commonly
affected age range in Hashimoto thyroiditis is 30-50 years, with the peak incidence in men occurring 10-15 years
later. The overall incidence of hypothyroidism increases with age in men and women.

Prognosis
With early diagnosis, timely institution of levothyroxine replacement therapy, informed patient follow-up care, and
attention to other attendant complications, the prognosis in Hashimoto thyroiditis is excellent, with patients leading
a normal life. Untreated myxedema coma has a poor prognosis and a high mortality rate.
Morbidity related to Hashimoto thyroiditis typically results from failure to make the diagnosis of hypothyroidism or to institute
l-thyroxine replacement therapy in adequate doses, or from failure on the part of the patient to take the replacement
medication.
The increased prevalence of lipid disorders in association with untreated hypothyroidism has the potential to increase
morbidity from coronary artery disease.
The risk for papillary thyroid carcinoma is increased in patients with Hashimoto thyroiditis. [12] These cancers are not clearly
more aggressive than other papillary thyroid carcinomas.

Therapeutic complications
Complications of overreplacement with levothyroxine sodium Include the following:

Accelerated bone loss


Reduction in bone mineral density
Osteoporosis
Increased heart rate
Increased cardiac wall thickness
Increased contractility
The last three problems above increase the risk of cardiac arrhythmias (especially atrial fibrillation), particularly in the elderly
population.

Patient Education
Patients should know that thyroid replacement therapy in Hashimoto thyroiditis is, except in very rare cases, lifelong.
Patients must be informed about the importance of compliance with their replacement therapy and must be instructed to
report any symptoms suggestive of hyperthyroidism caused by overreplacement.
Patients must be instructed to separateby at least 4 hoursingestion of levothyroxine from ingestion of cholestyramine,
ferrous sulfate, sucralfate, calcium carbonate, aluminum hydroxide (and other antacids), and iron-containing multivitamins,
all of which impair the absorption of levothyroxine.
For patient education information, see the Thyroid and Metabolism Center, as well as Thyroid Problems.

Riedel Thyroiditis

Background
Riedel thyroiditis, or Riedel's thyroiditis (RT), is a rare, chronic inflammatory disease of the thyroid gland
characterized by a dense fibrosis that replaces normal thyroid parenchyma. The fibrotic process invades adjacent
structures of the neck and extends beyond the thyroid capsule.
Involvement in RT may be unilateral or bilobar. Thyroid function depends on the extent to which the normal thyroid
gland has been replaced by fibrotic tissue. Most patients are euthyroid, but hypothyroidism is noted in
approximately 30% of cases. Rarely, hyperthyroidism can occur, but this is probably secondary to a coexisting condition.
(See Prognosis, Presentation, and Workup.)
Some experts have traditionally believed that RT is not primarily a thyroid disease but rather that it is a
manifestation of the systemic disorder multifocal fibrosclerosis. Approximately one third of RT cases are associated
with clinical findings of multifocal fibrosclerosis at the time of diagnosis. (See Etiology.)
In 1883, Professor Bernhard Riedel first recognized the disease. He published a description of 2 cases in 1896 and of a third
case in 1897.[1] Riedel used the term eisenharte struma to describe the stone-hard consistency of the thyroid gland and its
fixation to adjacent structures. He noted the presence of chronic inflammation with fibrosis and the absence of malignancy
on microscopic examination. Simple wedge resection of the thyroid isthmus was used to alleviate tracheal obstruction and is
still the preferred surgical therapy for RT.

Complications
Because of the encroachment beyond the thyroid capsule, nonthyroid problems can be associated with RT.
Complications of Riedel thyroiditis can include the following:

Airway obstruction
Dysphonia
Hoarseness - Due to recurrent laryngeal involvement
Hypothyroidism
Hypoparathyroidism
Dysphagia
Stridor - Due to tracheal compression

Etiology
The etiology of Riedel thyroiditis (RT) is unknown, but it may be related to a relatively new group of rare disorders,
IgG4-related systemic disease (IgG4-RSD). One theory of pathogenesis postulates that RT results from an
autoimmune process. A second theory holds RT to be a primary fibrotic disorder. However, IgG4-RSD may unify these 2
seemingly disparate etiologies.

Autoimmune theory
The following evidence supports an autoimmune pathogenesis for RT:

The presence of antithyroid antibodies in a significant percentage of patients with RT (67% of 178 cases reviewed
in one study) [2]
The pathologic features of cellular infiltration, including lymphocytes, plasma cells, and histiocytes
The frequent presence of focal vasculitis on pathologic examination
The favorable response of a subset of patients with RT to treatment with systemic corticosteroids

However, the presence of normal lymphocyte subpopulations and normal serum complement levels weighs against an
autoimmune mechanism. Elevated levels of antithyroid antibodies may merely reflect the immune system's exposure to
sequestered antigens released by the destruction of thyroid parenchyma from a primary fibrotic disorder.

Primary fibrotic disorder theory


The theory that RT is a primary fibrotic disorder is supported by its association with multifocal fibrosclerosis. This uncommon
idiopathic syndrome is characterized by fibrosis involving multiple organ systems. The extracervical manifestations of
multifocal fibrosclerosis can include retroperitoneal fibrosis, mediastinal fibrosis, orbital pseudotumor, pulmonary fibrosis,
sclerosing cholangitis, lacrimal gland fibrosis, and fibrous parotitis. RT may be but 1 manifestation of this multifocal disease.
The histopathologic changes of RT closely resemble those observed in multifocal fibrosclerosis. Additionally, one third of
published RT cases have demonstrated at least 1 manifestation of extracervical fibrosclerosis. The ability of systemic
corticosteroids and tamoxifen to inhibit fibrogenesis accounts for the favorable effect of such treatment in both conditions. [3]

IgG4-RSD disorder
IgG4-RSD is a relatively new group of disorders that share similar presentations. These disorders have in common a
preponderance of excess IgG4. The disorders are characterized by lymphoplasmacytic infiltrates containing IgG4-positive
plasma cells.[4] These infiltrates ultimately lead to fibrosis and elevated serum levels of IgG4. [5, 6]

Epidemiology
United States
Riedel thyroiditis (RT) is a very rare condition. At the Mayo Clinic, 37 cases of RT were diagnosed in a series of 57,000
thyroidectomies performed between 1920 and 1984, for an incidence of 0.06%. The overall incidence among outpatients
was 1.6 cases per 100,000 population. Based on large databases in referral centers, it appears that over the previous
decades, the incidence of RT has been decreasing.

Race-, sex-, and age-related demographics


Although predominantly reported in whites, RT has been described in all races. RT is most often seen in women; in a
review of 178 patients with RT, 83% were female. In the same study, the mean age at diagnosis of RT was 47.8 years
(range, 23-77 y).[2]

Prognosis
Riedel thyroiditis (RT) is generally a self-limited disease with a favorable prognosis. Death due to airway compromise
is very rare in treated patients. Occasionally, spontaneous remission has been reported. Patients can also relapse.
In RT, morbidity is most frequently related to local compressive symptoms, such as dysphagia, dyspnea, hoarseness, and
cough. Hypothyroidism is present in 30% of cases. Fibrotic invasion of adjacent anatomic structures may infrequently result
in symptoms related to recurrent laryngeal nerve paralysis or hypoparathyroidism.
One third of patients with RT ultimately develop at least 1 extracervical manifestation of multifocal fibrosclerosis (such as
retroperitoneal fibrosis, mediastinal fibrosis, or sclerosing cholangitis). [7] In such patients, the prognosis essentially becomes
that of extracervical fibrosclerosis. Therefore, when RT is diagnosed, it is essential to perform abdominal and chest imaging
studies to exclude concomitant, extracervical entities from multifocal fibrosclerosis. Fibrosclerosis of the surrounding tissue
by RT can lead to serious morbidity and death.
A retrospective institutional review of a rare form of invasive thyroiditis from the Mayo Clinic discussed the common
presenting symptoms and extrathyroidal involvement of the systemic fibrosclerosis. Treatments used in the 21 reported
patients included partial thyroidectomy, tamoxifen, and corticosteroid therapy. Other, less well validated studies include
mycophenolate mofetil[8] and rituximab.[9] Of note, no cause-specific mortality was noted, and the fibrotic process stabilized or
partially resolved in all patients.[3]

History and Physical Examination


Riedel thyroiditis (RT) is characterized by the replacement of normal thyroid parenchyma with dense fibrotic tissue
and by the extension of this fibrosis to adjacent structures of the neck. Most patients are euthyroid, but
hypothyroidism is noted in approximately 30% of cases. Rarely, hyperthyroidism can occur, but this is probably
secondary to a coexisting condition.
Clinical features of RT closely resemble those of anaplastic carcinoma of the thyroid. Patients note a nonpainful,
rapidly growing thyroid mass.
Patients typically present with a hard, fixed, painless goiter. The character of the thyroid gland is often described as
stony or woody. The onset of the goiter may be sudden, but it is usually gradual.
Local compressive symptoms are frequent and can include the following:

Neck tightness or pressure


Dyspnea
Dysphagia
Hoarseness
Choking
Cough
Such symptoms are the result of the increasing thyroid mass or are due to the extension of the fibrotic process to
adjacent neck structures (eg, strap muscles, trachea, esophagus, recurrent laryngeal nerve).
Hypoparathyroidism is rare and presumably reflects fibrotic involvement of the parathyroid glands. Recurrent laryngeal
nerve paralysis is also uncommon, but it can be observed in extensive disease. [10]
Approximately one third of patients with RT have an associated extracervical manifestation of multifocal fibrosclerosis.
These manifestations can include the following[7] :

Retroperitoneal fibrosis
Mediastinal fibrosis
Orbital pseudotumor
Pulmonary fibrosis
Sclerosing cholangitis
Lacrimal gland fibrosis
Fibrosing parotitis