Subacute Granulomatous (de Quervain) Thyroiditis

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1 ORIGINL RESERCH Subacute Granulomatous (de Quervain) Thyroiditis Grayscale and Color Doppler Sonographic Characteristics Mary C. Frates, MD, Ellen Marqusee, MD, Carol. enson, MD, Erik K. lexander, MD Received May 21, 2012, from the Department of Radiology (M.C.F., C...) and Thyroid Section, Division of Endocrinology, Hypertension, and Diabetes, Department of Medicine (E.M., E.K..), righam and Women s Hospital, Harvard Medical School, oston, Massachusetts US. Revision requested June 18, Revised manuscript accepted for publication July 24, ddress correspondence to Mary C. Frates, MD, Department of Radiology, righam and Women s Hospital, Harvard Medical School, 75 Francis St, oston, M US. mfrates@partners.org bbreviations ESR, erythrocyte sedimentation rate; TSH, thyrotropin Objectives To describe the sonographic characteristics of subacute granulomatous (De Quervain) thyroiditis. Methods We retrospectively identified all patients at our institution during the last 11 years who had thyroid sonography with findings suggestive of subacute granulomatous thyroiditis. We then reviewed clinical data and laboratory results to establish the clinical diagnosis. final diagnosis of subacute granulomatous thyroiditis was made on the basis of clinical symptoms, suppressed thyrotropin, an elevated erythrocyte sedimentation rate, and/or reduced or absent radionuclide uptake while hyperthyroid. Results Our study population consisted of 35 patients. Twenty-seven patients (79.4%) met clinical criteria for subacute thyroiditis. Symptoms included neck pain in 26 of 27 patients with subacute thyroiditis. The erythrocyte sedimentation rate ranged from 22 to 101 mm/h. In 21 cases (77.8%), sonography revealed focal, poorly defined, nonovoid areas of decreased echogenicity. Findings were bilateral in 16 patients and unilateral in 5. In the remaining 6, the gland or an entire lobe was diffusely heterogeneous. Color Doppler interrogation was performed in 20 patients. Flow was decreased to the sonographically abnormal areas in 19 (95%) and slightly increased in 1 patient. In all 9 patients who underwent radionuclide scanning, focal defects or large areas of decreased or absent uptake were found during the time of suppressed thyrotropin. Enlarged lymph nodes were noted in 16 patients (59.3%). Conclusions The positive predictive value of sonography for diagnosing subacute granulomatous thyroiditis is 79.4%. The most common sonographic appearance is poorly defined regions of decreased echogenicity with decreased vascularity in the affected areas. Key Words color Doppler sonography; sonography; thyroid; thyroiditis S ubacute granulomatous thyroiditis, or De Quervain thyroiditis, is an inflammation of the thyroid gland thought to be postviral in origin. It is an uncommon process that may go undetected if the sonographic findings are not recognized or if appropriate clinical information is not available to the sonologist. Patients typically present to their physician complaining of pain or tenderness in the neck and are frequently hyperthyroid, and then become hypothyroid with an elevated erythrocyte sedimentation rate (ESR). 1 3 While the diagnosis is usually clinical, the presence of neck pain often prompts imaging. Sonography is the first-line imaging study for abnormalities of the thyroid gland, and imagers should be aware of the appearance of subacute thyroiditis. The sonographic appearance of subacute thyroiditis may overlap with other types of 2013 by the merican Institute of Ultrasound in Medicine J Ultrasound Med 2013; 32:

2 thyroiditis and some types of thyroid cancer, but the clinical presentation should allow differentiation. Previous studies have reported poorly defined hypo - echoic thyroid lesions as characteristic for subacute granulomatous thyroiditis. 4 6 Several of these studies have relied on fine-needle aspiration to establish the diagnosis. 4,6 None have reported diffuse involvement of an entire lobe or gland. We report the sonographic grayscale and color Doppler findings of a series of patients with the clinical diagnosis of subacute thyroiditis first suggested from the sonographic findings. Materials and Methods From a computerized word search of sonography reports, we retrospectively identified all patients at our institution between December 1999 and March 2011 who had thyroid sonography in which the interpreting radiologist suggested the diagnosis of subacute granulomatous thyroiditis. We then reviewed the clinical data and laboratory results to establish or exclude the diagnosis of subacute thyroiditis in this group of patients. final diagnosis of subacute granulomatous thyroiditis was made on the basis of clinical symptoms (focal pain in the anterior neck), suppressed thyrotropin(tsh), elevated ESR, absent thyroid peroxidase antibodies, and/or reduced or absent radionuclide uptake while hyperthyroid. This study was approved by our Institutional Review oard, and was Health Insurance Portability and ccountability ct compliant. Sonograms were retrospectively reviewed by one of two radiologists, who were aware of the final diagnosis but blinded to clinical symptoms. The gland was assessed for the presence and location (diffuse or focal and single or multiple), shape (well defined or patchy, poorly defined), and echogenicity (hyperechoic, isoechoic, or hypoechoic) of any areas of heterogeneity in each gland, percentage of involvement of each lobe (0% 100%), size of the gland (normal, small, or large), presence of coexisting nodules, and presence of enlarged local lymph nodes (defined as >7 mm in transverse diameter). If performed, color Doppler flow in the affected area was characterized as normal, increased, or decreased compared to surrounding thyroid parenchyma. If the diagnosis of subacute thyroiditis was raised on more than one sonogram of the neck, the first examination was used for study purposes. Laboratory values that were assessed in the study patients were ESR and TSH measured within 5 weeks of diagnostic sonography and at follow-up. The medical records were reviewed for the presence of clinical symptoms, such as pain or tenderness, and to confirm the final diagnosis in each case (subacute thyroiditis or other). Results Our study population consisted of 33 female and 2 male patients, ranging in age from 26 to 81 years. One patient was excluded because sonograms could not be retrieved. The diagnosis of subacute thyroiditis was made on the basis of an elevated ESR and the presence of neck pain in 21 patients, on the basis of neck pain and the clinical impression in 5 patients, and by the presence of hyperthyroidism with complete absence of uptake on nuclear medicine imaging in 1 patient. Twenty-seven patients fulfilled our diagnostic criteria for subacute thyroiditis, for a positive predictive value of 79.4%. In the remaining 7, 4 had Graves disease; 2 were nontender with no ESR available and likely had Hashimoto or lymphocytic thyroiditis; and 1 had profound long-standing hypothyroidism with markedly elevated thyroid peroxidase levels, suggesting Hashimoto thyroiditis as well. In the 27 patients with clinically proven subacute thyroiditis, patient ages ranged from 30 to 69 years (average, 47.2 years). There were 25 female and 2 male patients. ll 26 patients in whom clinical information was available presented with pain or tenderness in the neck. The ESR was measured in 21 patients, 17 within 8 days of sonography and 4 within 30 days. In all 21 patients, the ESR was elevated, ranging from 22 to 101 mm/h (normal, 0 18 mm/h). Thyrotropin was suppressed in 24 of 26 patients in whom it was measured, ranging from 0.01 to 0.4 miu/l in 18 patients and undetectable in 6 patients. The TSH was low normal in the other 2 patients. Images and clips from the sonographic studies were reviewed in all 27 patients (Table 1). In 21 cases (77.8%), sonography revealed focal, poorly defined areas of decreased echogenicity (Figure 1). Findings were bilateral in 16 patients and unilateral in 5. In the remaining 6 patients (22.2%), the entire gland (4 of 6) or entire affected lobe (2 of 6) was diffusely heterogeneous. The affected portion of the gland was enlarged in 21 patients (77.8%). Estimates of the amount of gland involved ranged from 25% of a single lobe (1 patient) to 100% of the gland in 4 patients. Color Doppler interrogation was performed in 20 patients. Flow was decreased to the sonographically abnormal areas in 19 of 20 patients (95%) (Figure 2) and increased in 1 patient. In all 9 patients who underwent radionuclide scanning, focal defects or large areas of decreased or absent uptake were found. Enlarged lymph nodes were noted in 16 patients (59.3%), normal sized nodes in 8, and no images of nodes were available for review in 3 patients. In addition to the changes of thyroiditis, focal discrete nodules were found in the thyroid gland in 8 of the J Ultrasound Med 2013; 32:

3 affected patients. These nodules persisted after resolution of the thyroiditis in all patients. In 1 patient, fine-needle aspiration was performed in an area of subacute thyroiditis, which at the time was thought to be a nodule. This aspiration showed giant cells, inflammation, and atypical cells. When the patient returned for repeat aspiration of the area due to the cellular atypia, the abnormal region appeared sonographically normal, and the possibility of subacute thyroiditis was raised. One patient in our series underwent carotid arteriography at an outside institution as part of an extensive evaluation for neck pain radiating to the jaw before the diagnosis of subacute thyroiditis. Follow-up sonography was performed in 8 patients. In 3 patients, follow-up sonography done 1 to 8 weeks after diagnosis showed that the changes of subacute thyroiditis had migrated to the opposite side of the gland in 2 (Figure 3) and had worsened bilaterally in 1. The gland returned to normal in 5 (Figure 4), at 3 months (2 patients), 6 months (1 patient), and more than 1 year later (2 patients). Discussion Figure 1. Patchy subacute thyroiditis in a 57-year-old woman, with disease progression over 1 week., Sagittal image of the right lobe shows a focal, poorly defined hypoechoic area in the upper pole. The upper pole of the gland is enlarged., The borders of the hypoechoic area are poorly defined on the corresponding transverse image. C, Follow-up sagittal image 1 week later shows that the entire right lobe is now enlarged, and hypoechoic changes are more extensive. The diagnosis of subacute or De Quervain thyroiditis is uncommon, with an incidence of 12.1 per 100,000 per year, and is usually made on the basis of clinical symptoms of neck pain and fever together with corresponding laboratory abnormalities. 1 3 Prompt treatment to alleviate pain includes the use of nonsteroidal anti-inflammatory drugs Table 1. Sonographic Findings of Subacute Thyroiditis Finding n (%) Focal, poorly defined hypoechoic areas during acute illness 21 (77.8) ilateral 16 Unilateral 5 Diffusely heterogeneous gland/lobe during acute illness 6 (22.2) ilateral 4 Unilateral 2 ffected portion enlarged 21 (77.8) Color Doppler Decreased to affected portion 19 (95) Increased to affected portion 1 (5) Not performed 7 Lymph nodes Enlarged 16 (66.7) Normal size 8 (33.3) No images 3 Focal discrete nodule 8 (29.6) Follow-up sonography 8 Disease progression 3 (1 8 wk) Return to normal 5 (3 12 mo) C J Ultrasound Med 2013; 32:

4 or, in more severe cases, glucocorticoids. While most patients present with pain or tenderness of the neck, for some patients, the symptoms of hyperthyroidism prompt clinical evaluation. The differential diagnosis in patients presenting with neck pain includes hemorrhage into a thyroid nodule, Graves disease, suppurative or bacterial thyroiditis, and thyroid cancer. In some cases, sonography may assist in narrowing this differential. The sonographic characteristics of subacute thyroiditis are usually typical; however, this type of thyroiditis is uncommon and may be unexpected. Failure to consider the possibility of subacute thyroiditis led to the performance of carotid arteriography in 1 patient in our series and an unnecessary thyroid biopsy in another. The sonographic appearance of subacute thyroiditis found in our series is similar to previous reports. 4 6 Our series emphasizes the sonographic findings rather than clinical, laboratory, or cytologic correlation and shows that the typical appearance of subacute thyroiditis is a patchy, poorly defined hypoechoic process that can affect a portion of one or both lobes, an entire lobe, or the entire gland. Our series also reports the new finding of a completely heterogeneous gland or lobe entirely affected by subacute thyroiditis, found in nearly one-fourth of our patients. Color Doppler interrogation shows decreased flow to the affected areas of the thyroid, in contrast to the thyroid inferno or markedly increased flow on color imaging that may be seen with Graves disease. 7,8 When the entire lobe or gland is affected with subacute thyroiditis, it can mimic a large nodule replacing the lobe. In this instance, the lack of flow in subacute thyroiditis should help differentiate this entity from a nodule. Prior studies have reported that decreased flow is seen in the affected areas during the acute phase of the disease, and that this pattern is usually followed by increased flow during the recovery phase of the disease. 4,9 This process may explain the finding of increased flow to the affected area in the single patient in our series, who may have been imaged during the recovery phase. The heterogeneity of the thyroid affected by subacute thyroiditis can mimic the changes of lymphocytic or Hashimoto thyroiditis. 10 The sonographic changes of these two processes are very similar. The differences are clinical and biochemical. Patients with subacute thyroiditis present with pain or tenderness of the gland, while patients with Hashimoto thyroiditis typically have no clinical symptoms. With subacute thyroiditis, when detected acutely, laboratory changes include an elevated ESR (seen in 100% of the patients in our series in whom it was measured) and low TSH (found in 24 of 26 in our series). Subacute thyroiditis can occasionally mimic thyroid carcinoma or thyroid lymphoma due to its hypoechoic appearance at sonography and firmness on palpation. 10,11 However, the presence of pain or tenderness should allow differentiation of subacute thyroiditis from these other typically nontender entities. Nuclear medicine and sonography can both be used in the evaluation of patients with painless thyroiditis. However, sonography may be requested more commonly in patients presenting with anterior neck pain to search for explanations such as acute hemorrhage into a thyroid nodule or an abscess due to infection. The characteristic findings of subacute thyroiditis on sonography in combination with the presence of neck pain can provide a more sensitive and specific diagnosis in comparison to nuclear medicine studies. While nuclear medicine studies can provide supportive data for the diagnosis of subacute thyroiditis, as seen in several of Figure 2. Subacute thyroiditis in a 37-year-old patient with pain and swelling of the right neck., Poorly defined patchy hypoechoic areas are seen in the mid and lower poles of the right lobe., Corresponding color Doppler image reveals decreased to absent flow in the affected areas of the right lobe. 508 J Ultrasound Med 2013; 32:

5 our patients, other types of thyroiditis can have similar results depending on the phase of the thyroid illness. Sonography performed 3 months or more from the initial sonographic examination showed complete resolution of the changes of subacute thyroiditis in all 5 (100%) of the patients in whom it was performed. This result is similar to the resolution rate previously reported of 100% by some 6,12 but higher than the 57% reported in at least one other study. 13 When there is a question of both subacute thyroiditis and nodular thyroid disease, another sonographic examination when symptoms have resolved and laboratory values have returned to normal may be useful for documentation of underlying nodular disease, particularly if microcalcifications are noted in the background of the thyroiditis changes. 14 This study had several limitations. First, it was a retrospective case series. We have no way of knowing how many patients with subacute thyroiditis we might have excluded from our analysis because they had a normal sonogram. Second, there was a selection bias. Only cases in Figure 3. Progression of subacute thyroiditis in a 50-year-old woman, who returned for follow-up due to migration of symptoms from the right to left neck., Sagittal image of the right lobe, which is enlarged. The mid and lower poles are hypoechoic and heterogeneous., Corresponding color Doppler image of the right lobe shows decreased flow in the mid and lower poles. C, Sagittal image of the left lobe on the same date as and. There is an easily identifiable discrete nodule (black arrows) in the posterior mid lobe. The surrounding parenchyma has a normal sonographic appearance. D, Two-month follow-up of the right lobe shows that the gland has returned to normal in size. It is mildly heterogeneous but overall has an improved appearance. E, Sagittal image of the left lobe on the same date as D. The left lobe is now enlarged, diffusely hypoechoic, and heterogeneous. The preexisting nodule (white arrows) is nearly obscured by the thyroiditis. C D E J Ultrasound Med 2013; 32:

6 C D Figure 4. Subacute thyroiditis affecting the entire right lobe in a 39-year-old woman with neck pain, with return to normal at 6 months., Sagittal image of the right lobe shows that the hypoechoic and heterogeneous changes of subacute thyroiditis (white arrowheads) affected almost the entire lobe (black arrowheads)., Transverse image of the right lobe. The poorly defined hypoechoic pattern is more prominent in the lateral aspect of the gland. C, Color Doppler image shows minimal flow to the affected portion of the right lobe. More normal flow is present in the periphery of the lobe. D, Follow-up imaging at 6 months shows a normal right lobe with all changes resolved. which the radiologist identified the changes of subacute thyroiditis and used that terminology in the sonography report were included. In conclusion, our series documents the typical sonographic and color Doppler findings of subacute thyroiditis. The findings of poorly defined hypoechoic areas involving all or part of the thyroid associated with diminished blood flow at color Doppler interrogation should prompt the diagnostic consideration of subacute thyroiditis, particularly in patients who present with pain or tenderness of the anterior neck. The appearance of a diffusely heterogeneous gland with diminished blood flow should also raise concern for subacute thyroiditis in the appropriate patient population. Characteristic sonographic findings should be used in combination with laboratory assessment of ESR and TSH for accurate diagnosis of this uncommon painful condition, allowing prompt treatment and preventing delay in diagnosis of other entities. References 1. Pearce EN, Farwell P, raverman LE. Thyroiditis. N Engl J Med 2003; 348: Fatourechi V, niszewski JP, Fatourechi GZ, tkinson EJ, Jacobsen SJ. Clinical features and outcome of subacute thyroiditis in an incidence cohort: Olmsted County, Minnesota, study. J Clin Endocrinol Metab2003; 88: J Ultrasound Med 2013; 32:

7 3. Nishihara E, Ohye H, mino N, et al. Clinical characteristics of 852 patients with subacute thyroiditis before treatment. Intern Med 2008; 47: Park SY, Kim E-K, Kim MJ, et al. Ultrasonographic characteristics of subacute granulomatous thyroiditis. Korean J Radiol 2006; 7: Omori N, Omori K, Takano K. ssociation of the ultrasonography findings of subacute thyroiditis with thyroid pain and laboratory findings. Endocr J 2008; 55: rander. Ultrasound appearances in de Quervain s subacute thyroiditis with long-term follow-up. J Intern Med 1992; 232: Ralls PW, Mayekawa DS, Lee KP, et al. Color-flow Doppler sonography in Graves disease: thyroid inferno. JR m J Roentgenol1988; 150: Ota H, mino N, Morita S, et al. Quantitative measurement of thyroid blood flow for differentiation of painless thyroiditis from Graves disease. Clin Endocrinol (Oxf) 2007; 67: Hiromatsu Y, Ishibashi M, Miyake I, et al. Color Doppler ultrasonography in patients with subacute thyroiditis. Thyroid 1999; 9: Takashima S, Sone S, Horii, Honjho Y, Yoshida J. Subacute thyroiditis in Hashimoto s thyroiditis which mimicked primary thyroid lymphoma. J Clin Ultrasound 1997; 25: Zacharia TT, Perumpallichira JJ, Sindhwani V, Chavhan G. Gray-scale and color Doppler sonographic findings in a case of subacute granulomatous thyroiditis mimicking thyroid carcinoma. J Clin Ultrasound2002; 30: Tokuda Y, Kasagi K, Iida Y, et al. Sonography of subacute thyroiditis: changes in the findings during the course of the disease. J Clin Ultrasound 1990; 18: ennekbæk FN, Hegedüs L. The value of ultrasonography in the diagnosis and follow-up of subacute thyroiditis. Thyroid 1997; 7: Nishihara E, Hirokawa M, Ohye H, et al. Papillary carcinoma obscured by complication with subacute thyroiditis: sequential ultrasonographic and histopathological findings in five cases. Thyroid 2008; 18: J Ultrasound Med 2013; 32: