Thyroiditis

THYROIDITIS

INTRODUCTION

Chronic autoimmune thyroiditis and Graves’ disease are two forms of autoimmune thyroid disease (AITD). It has been said that Hashimoto thyroiditis and Graves’ disease are the same autoimmune thyroid disease but at different ends of the spectrum. Transition between the two autoimmune thyroid

diseases may occur, which adds to the difficulty in differenti-ating between the two (1). The ultrasonographic appearance of both Graves’ disease and Hashimoto thyroiditis are similar as well, with both having a hypoechoic and heterogeneous echotexture. While Graves’ disease typically hows marked hypervascularity with power Doppler analysis, the vascularity of Hashimoto thyroiditis is ariable, ranging from avascular to hypervascular.Chronic autoimmune thyroiditis has two clinical forms: a goitrous form referred to as Hashimoto disease and an atrophic form called atrophic thyroiditis, which may represent the end stage of the former. The presence of serum thyroid autoantibodies, varying degrees of thyroid dysfunction and lymphocytic infiltration characterize both forms of chronic autoimmune thyroiditis (2). Both silent (or painless) thyroidi-tis and post-partum thyroiditis are transient disorders thought to be manifestations of chronic autoimmune thyroiditis (2).

The diagnosis of AITD is easy to make when patients are clinically symptomatic. However, AITD may be missed when thyroid autoantibodies are negative (4) or have not been ordered in the diagnostic work-up due to normal thyroid func-tion tests and normal palpation, making the diagnosis of AITD appear less likely (3). Ultrasonography, which has proven valu-able in clarifying number and size of thyroid nodules (5–8), can also be of value in the diagnosis of AITD due to radiographic findings often associated with AITD (9–17).

PATHOLOGY

The diagnosis of chronic autoimmune thyroiditis by cytology is not based just on the presence of chronic lymphocytic infiltra-tion. When lymphocytic infiltration alone is the only histologic finding, chronic autoimmune thyroiditis can be diagnosed with confidence only if the patient has high serum titers of antithy-roid autoantibodies. Pathology-proven chronic autoimmune thyroiditis requires diffuse lymphocytic infiltration with occa-sional germinal centers; small, colloid-deplete follicles; fibrosis; and Hürthle cells (2). Hurthle cells are enlarged-appearing thyroid cells containing oxyphilic cytoplasm (granular andpink) (26).

ULTRASONOGRAPHY

Since its introduction in clinical practice, ultrasonography has proven to be a useful tool in the management of patients with thyroid disease (3, 12, 16, 17). Besides identification of thyroid nodules (19), ultrasonography is able to character-ize the echostructure of thyroid tissue in patients with AITD (4, 20). In AITD, lymphocytic infiltration and disruption of tissue architecture cause a reduction in thyroid echogenicity (4). Hashimoto thyroiditis and Graves’ disease appear similar on gray-scale ultrasound, but power Doppler will demonstrate increased blood flow in Graves’ disease (“thyroid inferno”), with Hashimoto thyroiditis showing the full spectrum from absent to normal to increased blood flow. In granulomatous or deQuervain’s thyroiditis the hypoechogenicity may be localized to one lobe or even a portion of a lobe that is involved. The ultrasound appearance returns to normal when the subacute thyroiditis resolves. Several studies have indicated that reduction in thyroid echogenicity occurs at a relatively early stage in the AITD process, often before overt thyroid failure (3). Reduced thyroid echogenicity detected by thyroid ultrasonography is a strong predictor of AITD even when these disorders have not been suspected clinically (3). Subclinical thyroid dysfunction has gained importance due to greater knowledge of its negative effect on cholesterol, bone mineral density, heart rhythm and depression (18).Hypoechogenicity is a major characteristic finding on ultra-sound of patients having Hashimoto thyroiditis. In most of the studies, modifications in thyroid echogenicity were described subjectively as compared with the hyporeflective surrounding 

neck muscles (3, 12, 16, 21, 22, 23). Recently, the gray-scale histogram analysis has been proposed for a quantitative meas-urement of decrease in echogenicity of thyroid glands affected by autoimmune disease with respect to the normal glands (24, 25). However, other ultrasonographic findings in addition to hypoechogenicity occur in Hashimoto’s thyroiditis.

FIG. 5.1.  Extremely hypoechoic thyroid gland caused by lymphocytic infiltration of thyroid tissue. The echogenicity is similar to the surrounding musculature

FIG. 5.2.  This hypoechoic right lobe shows small dense areas of early fibrosis

These findings illustrate heterogeneity in the ultrasound appearance of the thyroid caused by destruction of the normal homogeneous “ground glass” architectural pattern of thyroid tissue, resulting in the formation of pseudonodules that may

FIG. 5.3.  “Bag of marbles.” The areas of fibrosis appear hyperechoic in comparison to the hypoechogenicity of the rest of the gland, and could be mistaken for hyperechoic nodules (pseudonodules)

FIG. 5.4.  This enlarged thyroid is typical of Hashimoto thyroiditis with a hypoechoic but heterogeneous pattern

be numerous and resemble a “bag of marbles.” These pseudo-nodules are not well outlined or defined. They may also come and go, meaning that they are there today but may disappear if ultrasonography is done even a week later. Pseudonodules are

FIG. 5.5.  This enlarged right lobe has lost the typical ground glass appearance of normal thyroid tissue. Infiltration by lymphocytes and other inflammatory cells causes the tissue to be less dense and appear more hypoechoic

FIG. 5.6.  Left lobe of patient with Hashimoto thyroiditis. Fibrosis has advanced in a sheet-like pattern with layers of connective tissue running through the hypoechoic thyroid parenchyma

thought to be “diffuse lakes of lymphocytes.” Another frequent finding is the presence of tiny cystic lesions, which may be described as a “swiss cheese” appearance of the gland. These diffuse cystic lesions are usually 2–3 mm in size. Yet another

FIG. 5.7.  “Swiss cheese.” Diffuse small cystic lesions scattered through-out normal appearing thyroid represent an early stage of Hashimoto thyroiditis

FIG. 5.8.  Pseudonodules and fibrosis lead to disruption of the architectural pattern of this enlarged thyroid, which causes the gland to appear very heterogeneous

characteristic feature of Hashimoto thyroiditis is echogenic strands, or septa. These strands have been described as thin echogenic septa traversing the thyroid tissue, sometimes giving the thyroid a lobulated appearance (3). They are thought to be due to fibrosis within the gland. Fibrosis can also develop in pseudonodules, changing them from hypoechoic to hyper-echoic.

FIG. 5.9.  Left lobe of a patient with chronic thyroiditis. Over a period of time areas of amorphous calcification and shadowing have developed

FIG. 5.10.  This patient with longstanding thyroiditis shows a small atrophic hypoechoic gland that blends in with the surrounding  muscles

FIG. 5.11.  This gland shows several pseudonodules (arrows) that might initially be mistaken as nodules. However these pseudonodules have no halo or sharp border, are not palpable and will change in appearance over time

FIG. 5.12.  This patient had a painful upper right lobe with elevated sedimentation rate typical of deQuervain’s thyroiditis. Note the line of demarcation (arrow) between the inflamed upper lobe and normal appearing lower lobe. After six weeks the entire gland appeared normal

Often the first indication of thyroiditis one finds on ultra-sound is the presence of enlarged lymph nodes. These may be unilateral or bilateral; they may be in the central compartment or the lateral compartments of the neck, and they may be single or multiple. Except for their size they typically resemble normal lymph nodes with a short/long ratio < 0.7. While they generally have a hilum with hilar blood flow on power Doppler, it is not unusual to see confluent, enlarged, atypical appearing lymph nodes in active Hashimoto thyroiditis. Nodes exhibiting highly suspicious features such as chaotic vascularity may warrant UGFNA.

FIG. 5.13.  These enlarged flattened lymph nodes under the sternoclei-domastoid muscle are commonly seen in early Hashimoto thyroiditis and are often a clue to early diagnosis.

FIG. 5.14.  This enlarged flattened paratrachael lymph node (calipers) in the central compartment is a common finding in Hashimoto thyroiditis

FIG. 5.15.  This patient with Hashimoto thyroiditis also had a true nodule (calipers) in the right lobe that required FNA 

FIG. 5.16.  This palpable nodule in the isthmus of a patient with Hashimoto thyroiditis proved to be a papillary carcinoma by FNA and surgical excision

  Care must be taken in performing ultrasound on a patient with Hashimoto thyroiditis, since there may be coincidental occurrence of malignancy. Although the incidence of papil-lary carcinoma does not appear to be increased in AITD, it does occur and may initially appear to be a pseudonodule.

FIG. 5.17.  Lymphoma of the thyroid occurs almost exclusively in patients having Hashimoto thyroiditis. The tumor is extremely hypoechoic with only a thin area of thyroid tissue seen (arrow). Diagnosis was made by FNA with flow cytometry, and an operation was avoided. When lymphoma is localized to the thyroid, it usually responds well to  chemotherapy and/or radiation

If a nodule is palpable or there is doubt about it being a true nodule, ultrasound-guided FNA is recommended. Lymphoma is known to be predisposed to Hashimoto thyroiditis. Virtually all patients with a lymphoma of the thyroid had preexisting AITD. The diagnosis can be confirmed by ultrasound-guided FNA with flow cytometry, and surgery can be avoided.

SUMMARY
Diffuse hypoechogenicity and heterogeneity are the two hallmarks of thyroid autoimmunity; however, the ultrasound appearance varies dramatically among patients depending upon the severity and duration of the disease. Negative  immunologic tests do not rule out the diagnosis of AITD, as illustrated by patients with histologically proven Hashimoto thyroiditis, who have a hypoechoic, heterogeneous echotexture on thyroid ultrasound despite negative immunologic tests. Reduced echo-genicity, lymph node enlargement, and the other ultrasono-graphic findings mentioned in this chapter can occur prior to overt thyroid dysfunction (3). These characteristic findings can be used to identify the risk of overt thyroid dysfunction many years before its development.

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