AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

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

INTRODUCTION

Section 2 of 10  

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

Background

De Quervain thyroiditis was first reported in 1825, but de Quervain recorded its pathological description in 1904.

De Quervain (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.

Some authors use the term subacute thyroiditis for this disease. However, subacute thyroiditis is a generic term that may be used for all types of thyroiditis with a subacute course, including subacute granulomatous thyroiditis (de Quervain disease), subacute lymphocytic (painless) thyroiditis, and some forms of postpartum thyroiditis and drug-induced thyroiditis.

Pathophysiology

A viral infection or a postviral inflammatory response is presumed to cause de Quervain thyroiditis. Serial studies of viral antibody titers have implicated many viruses (including coxsackievirus, Ebstein-Barr, mumps, measles, adenovirus, echovirus, and influenza), but the changes could be attributed equally to nonspecific anamnestic responses. Viral inclusion bodies are not observed in thyroid tissue.

A strong association exists with human leukocyte antigen (HLA)-B35 in most ethnic groups. A proposed mechanism is that the disease results from a viral infection that provides an antigen, either viral or resulting from virus-induced host tissue damage, that uniquely binds to HLA-B35 molecules on macrophages. The antigen–HLA-B35 complex activates cytotoxic T lymphocytes that damage thyroid follicular cells because they have some structural similarity with the infection-related antigen. The transient presence of autoantibodies (eg, inhibitory immunoglobulins that bind to thyrotropin [TSH], antibodies that block thyroid stimulation, thyroid antimicrosomal antibodies, thyroglobulin [TGB] antibodies) has been noted in the acute phase of the disease, but their presence is attributed to a virally induced autoimmune response and is not implicated in the pathological process. In contrast with autoimmune thyroid disease, the immune response is not self-perpetuating; therefore, the process is limited.

Destruction of follicular epithelium and loss of follicular integrity are the primary events in the pathophysiology of de Quervain thyroiditis. TGB, 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 TSH secretion. This state lasts until the stores of TGB are exhausted or until healing occurs. New hormone synthesis temporarily ceases because of the low 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.

Frequency

United States

De Quervain thyroiditis occurs in less than 5% of all patients with thyroid pathology. It tends to have seasonal and geographical distribution and is most common during the summer and fall. It tends to follow viral epidemics.

A systematic review of all cases diagnosed between 1960 and 1997 in Olmsted County, Minnesota revealed an age- and sex-adjusted incidence of 4.9 cases per 1000,000 per year.¹

International

International frequency is approximately the same as US frequency.

Mortality/Morbidity

De Quervain thyroiditis is a benign self-limited disease. Morbidity is caused during the initial phase by pain, which usually prompts the patient to consult a physician. Mild and transient hyperthyroidism occurs, and, in as many as 50% of patients, hypothyroidism may occur later. Recurrence of thyroiditis up to 21 years following the initial episode has been reported.

Sex

As is the case for most thyroid diseases, de Quervain thyroiditis appears more frequently in females, with a female-to-male ratio of 3-5:1.

Age

De Quervain thyroiditis has a peak incidence in the fourth and fifth decades of life. It is rare in the first decade and relatively infrequent in people older than 50 years, although it has been reported in extreme age groups.² Occurrence during pregnancy has been reported as well.³

CLINICAL

Section 3 of 10  

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

History

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 that usually unfold over a period of 3-6 months:

1. The acute phase, lasting 3-6 weeks, presents primarily with pain. Symptoms of hyperthyroidism also may be present.
2. The transient asymptomatic and euthyroid phase lasts 1-3 weeks.
3. The hypothyroid phase lasts from weeks to months, and it may become permanent in 5-15% of patients.
4. The recovery phase is characterized by normalization of thyroid structure and function.

Characteristic Course of de Quervain Thyroiditis

The diagnosis is made based on clinical findings. Prodromal flulike symptoms 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-Schönlein purpura. However, a history of prodromal symptoms often cannot be obtained.

• Local symptoms
• • Pain over the thyroid area that is gradual or of sudden onset; that usually involves both lobes (in 30% of cases, it starts on one side and then migrates contralaterally within a few days); that radiates to the neck, ear, jaw, throat, or occiput; and is aggravated by swallowing and head movement; pain is the presenting symptom in over 90% of cases 
  • Dysphagia
  • Hoarseness (uncommon)
• Constitutional symptoms (often absent)
• • Fever
  • Malaise
  • Anorexia
  • Fatigue
  • Muscle aches
• Symptoms of hyperthyroidism (palpitations, tremulousness, heat intolerance, sweating, nervousness) occurring in the initial phase of the disease
• • Hyperthyroidism that usually is mild and rarely is severe
  • Transient symptoms, usually lasting 3-6 weeks
• Symptoms of hypothyroidism, occurring in the late phase of the disease in as many as half the cases
• • Mostly mild or moderate
  • Transient hypothyroidism in 90-95% of cases
  • Hypothyroidism lasts weeks to months
• Atypical presentations (extremely rare, documented as case reports)
• • Thyroid storm⁴
  • 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

Physical

• Thyroid tenderness is usually symmetrical, but, occasionally, it starts in one lobe and then involves the contralateral lobe. Often, the pain is so severe that the patient cannot tolerate palpation of the neck.
• Thyroid enlargement is usually symmetric 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.
• Hyperthyroidism
• • Hyperthyroidism is present in approximately half the patients.
  • Signs of hyperthyroidism consist of tremor, tachycardia, warm skin, and a rapid relaxation phase of tendon reflexes
  • Lid retraction is rare; exophthalmos does not occur.

Causes

See Pathophysiology.

A viral infection or a postviral inflammatory response in genetically predisposed individuals is presumed to cause de Quervain thyroiditis. Serial studies of viral antibody titers have implicated many viruses (including coxsackievirus, Ebstein-Barr, mumps, measles, adenovirus, echovirus, and influenza), but the changes could be attributed equally to nonspecific anamnestic responses. Recent studies failed to demonstrate significant changes in serum antiviral antibody titers, or to detect viral DNA in the thyroid specimens.

DIFFERENTIALS

Section 4 of 10  

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

Other Problems to be Considered

Acute hemorrhage into a thyroid cyst, nodule, or neoplasm
Acute suppurative (pyogenic) thyroiditis

WORKUP

Section 5 of 10  

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

Lab Studies

• Usually, the diagnosis is made on clinical grounds, and the only laboratory studies needed initially are those to determine whether hyperthyroidism is present, including TSH and free T4.
• If any doubt exists as to whether de Quervain thyroiditis is the correct diagnosis, 2 other tests may be helpful.
• • Serum thyroglobulin is almost always markedly elevated.
  • Erythrocyte sedimentation rate (ESR) is usually higher than 50 mm/h in the initial phase. A normal or slightly elevated ESR makes the diagnosis of de Quervain thyroiditis relatively unlikely. ESR falls as the inflammatory process resolves, but following the ESR provides no useful information beyond what clinical observation yields.
• After the initial inflammatory phase subsides, TSH should be monitored at intervals of 4-6 weeks for a few months to determine whether hypothyroidism occurs.
• Antibodies to TGB, thyroid peroxidase, and TSH receptor are usually absent in de Quervain thyroiditis and need not be sought unless the clinical differential diagnosis includes immune thyroid disease (Graves disease, chronic lymphocytic [Hashimoto] thyroiditis).
• In rare cases with systemic multiorgan involvement, elevation of serum alkaline phosphatase, gamma-glutamyl transpeptidase, aminotransferases, and pancreatic enzymes may occur. Glucose intolerance has been reported.

Imaging Studies

• Ultrasonography of the thyroid gland^{5, 6, 7, 8}
• • Ultrasonography provides no additional information and is rarely indicated for diagnostic purposes.
  • In the first 3 phases of the disease, the thyroid gland is enlarged, shows unclear contour, and is diffusely or focally hypoechogenic.
  • In the recovery phase, the thyroid structure and dimensions return to normal.
  • Fibrosis is observed in some patients as hyperechogenicity and may occur as a form of healing. Extensive fibrosis is a predictor of hypothyroid state.
  • Doppler ultrasonography shows a near absence of vascularization in the acute phase and slightly increased vascularization in the recovery phase. During the acute phase, the more affected areas in the thyroid gland show the greatest decrease in vascularization, with the echogenically healthy-appearing regions of the thyroid showing normal or slightly increased vascularization.⁹
  • Ultrasonographic abnormalities are not correlated with the intensity of the inflammatory syndrome and/or thyroid function status. Recurrence can be seen as a new thyroid enlargement and an extension of hypoechoic regions. Risk of recurrence is not correlated with the initial ultrasonographic aspect, and there are no significant differences between patients with and without recurrence concerning the initial thyroid volume or echogenicity.
  • One study noted that thyroid volume is much smaller during the acute phase of the disease, and end-stage mean thyroid volume is significantly lower in patients who develop persistent hypothyroidism compared to patients with final normal thyroid function.
• CT scanning of the neck
• • CT scanning of the neck is not indicated for the diagnosis of thyroiditis. Consider that the administration of iodinated contrast material before measuring radioiodine uptake may result in a falsely decreased iodine uptake. If CT scanning is planned, it should be performed after any radioiodine uptake studies are completed.
  • The normal thyroid gland has a high attenuation (80-100 HU) because the normal thyroid gland concentrates iodine almost 100 times more than does the serum. In subacute thyroiditis, a diffusely swollen thyroid gland is observed, with a low attenuation corresponding to 45 HU. There is also moderate enhancement of the thyroid gland on contrast-enhanced scanning, suggesting the diffuse inflammatory nature of the disease process.
• Magnetic resonance imaging: MRI is not indicated for the diagnosis or evaluation of subacute granulomatous thyroiditis. If one is performed during the acute phase, the thyroid gland shows irregular margins and a higher than normal T1-weighted signal intensity and a much higher than normal T2-weighted signal intensity.^{10, 11}

Other Tests

• Tests of research interest but seldom of clinical value include the following:
• • Sex hormone–binding globulin (SHBG) levels usually are within the reference range because of the short time of exposure to increased thyroid hormone levels. SHBG is usually elevated in chronic hyperthyroid conditions.
  • Acute phase reactants, including serum C-reactive protein (CRP), are elevated in the initial phase.
  • Test results for viral nucleic acid fragments by polymerase chain reaction in the thyroid tissue are negative.
  • Soluble interleukin-2 receptor concentrations, CD4⁺ cell count, cytotoxic T cell count, and gamma interferon–positive lymphocytes have been used to assess the role of the immune system in de Quervain thyroiditis. Increased levels of these markers support a viral etiology of the disease.
  • Intercellular adhesion molecules have been found to be increased in de Quervain thyroiditis and in other thyroid disorders (eg, Graves disease, Hashimoto thyroiditis), independent of the hypothyroid or hyperthyroid state, reflecting the degree of inflammatory activity in the thyroid gland.
  • Sialic acid level was studied as a marker of disease activity and was found to be a better indicator than ESR, TGB, or CRP levels for active disease or relapse.
  • Genetic studies show a high incidence of HLA-B35 antigen in patients with subacute granulomatous thyroiditis in selected populations.¹²
• Neither radioiodine uptake (RAIU) nor thyroid scanning is indicated unless pain is mild or absent, in which case Graves disease might be considered in the differential diagnosis.
• • RAIU is very low in the initial phase of subacute thyroiditis (<1-2% at 24 h) but usually is elevated in Graves disease.
  • Technetium-99m-pertechnetate scintigraphy typically demonstrates markedly reduced uptake in the thyroid gland during the acute stage, but this finding is not present in all patients.
  • Technetium-99m-tetrafosmin uptake correlates with the stage of disease, particularly with inflammation, and shows increased uptake in the damaged area during the acute phase. However, this procedure is rarely used in the United States.
  • Technetium-99m-sestamibi scanning may show diffuse increased uptake in the region of the thyroid gland, suggesting increased perfusion. The clearance rate of Technetium-99m-sestamibi during the early phase (ie, from 10 min to 1 h) is decreased in the acute stage of subacute granulomatous thyroiditis.¹³

Procedures

• Fine-needle aspiration of the thyroid^{14, 15, 16, 17}
• • Fine-needle aspiration (FNA) is rarely needed; most of the time, the diagnosis of de Quervain thyroiditis can be made solely on clinical grounds. Some authors advocate that FNA should be performed in all patients with a tender thyroid to avoid misdiagnosis and inappropriate management.
  • FNA is useful for diagnosis when atypical presentations of thyroid carcinoma and thyroid abscess are considered in the differential diagnoses.
  • It usually shows the specific histological features of de Quervain thyroiditis (see Histologic Findings).
  • FNA may provide unclear results in the acute stage when atypical follicular cells may appear in the aspirate, mimicking thyroid carcinoma.

Histologic Findings

Macroscopic

The thyroid gland is moderately enlarged and edematous in de Quervain thyroiditis. It may be unilaterally or bilaterally enlarged and has an intact capsule. Affected areas are firm and yellow-white and stand out from the more rubbery, normal, brown thyroid substance.

Microscopic

The changes are patchy and vary with the stage of the disease. The early phase is the active inflammatory phase and is characterized by areas of entirely disrupted follicles, which are replaced by neutrophils, forming microabscesses.

In a later phase, the classic changes of granulomatous thyroiditis develop. This is characterized by aggregations of lymphocytes, large histiocytes, and plasma cells among damaged thyroid follicles. Multinucleated giant cells enclose pools or fragments of colloid, from which stems the designation giant cell thyroiditis. Colloid is also found within the giant cells, following a process called colloidophagy. In the final stages, the areas of injury are replaced by a chronic inflammatory infiltrate and fibrosis. Different histologic stages sometimes are found in the same gland, suggesting waves of destruction over a period of time.

Under a scanning electron microscope, the cytomorphology of subacute granulomatous thyroiditis shows loss of a uniform honeycomb cellular arrangement, variation in size and decreased or shortened microvilli in follicular cells, and the appearance of round or ovoid giant cells.

The giant cells are closely associated with the granulomas, and are CD68⁺, thyroglobulin negative, and cytokeratin negative. The small lymphocytes in the granulomas are CD3⁺, CD8⁺, CD45RO⁺ cytotoxic T cells. In the nongranulomatous lesions, the follicles are infiltrated by CD8⁺ T lymphocytes, plasmacytoid monocytes, and histiocytes, resulting in disrupted basement membrane and rupture of the follicles. These findings suggest that cellular immune response may play an important role in the pathogenesis of subacute thyroiditis.

TREATMENT

Section 6 of 10  

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

Medical Care

Management is directed towards 2 problems—pain and thyroid dysfunction.

• Pain
• • Some patients with mild pain require no treatment. Nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen (800-1200 mg/d in divided doses) or naproxen (1-1.5 g/d in divided doses), or aspirin (2-4 g/d in divided doses) are used. Treatment can be tapered as allowed by the patient's pain. Analgesic therapy can usually be stopped after 2-6 weeks.
  • Steroids have no proven superiority to NSAIDs in de Quervain thyroiditis and should be avoided. If NSAIDs provide insufficient relief of pain within 3 days, then prednisone may be tried at 30-40 mg/d initially. The response to prednisone is usually prompt (within 2-3 d), and, if a prompt response does not occur, prednisone should be stopped. The dose of prednisone should be tapered slowly; symptoms often recur upon withdrawal.
  • If pain does not respond within 3 days, the diagnosis should be reconsidered.
• Management of thyroid dysfunction
• • In the initial phase of de Quervain thyroiditis, symptomatic hyperthyroidism can be treated with beta-blockade (propranolol 10-20 mg qid or atenolol 25-50 mg/d), although mild symptoms may not require treatment. Beta-blockade, if needed, can usually be withdrawn in 2-6 weeks. Antithyroid drugs are of no value because the excess T4 and T3 results from release of preexisting thyroid hormone by follicular damage rather than from active synthesis.
  • If hypothyroidism occurs during the late phase, it is usually mild and transient. If symptoms are present or TSH is elevated, the patient needs replacement therapy with levothyroxine. Depending on the level of TSH, the starting dose can be 25-100 mcg/d and is adjusted for normalization of TSH. Usually, the hypothyroid stage lasts 2-3 months, but some authors recommend treatment for as long as 6 months, followed by discontinuation and monitoring of TSH.
  • Rare cases with permanent hypothyroidism require lifelong replacement therapy.

Surgical Care

No surgical treatment is required in de Quervain thyroiditis.

Consultations

Consultation with an endocrinologist is recommended in atypical or complicated cases.

Diet

Diet modification has no role in the management of de Quervain thyroiditis.

Activity

Activity limitations are not useful in de Quervain thyroiditis.

MEDICATION

Section 7 of 10  

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

The goals of pharmacotherapy are to reduce disease-associated morbidity and prevent complications due to abnormal thyroid function. No treatment has been shown to impact the occurrence of permanent hypothyroidism.

Drug Category: Salicylates

Used for symptomatic treatment. Aid in the relief of mild to moderate pain by inhibiting inflammatory reactions and pain.

Drug Category: Nonsteroidal anti-inflammatory drugs

Although most NSAIDs are used primarily for their anti-inflammatory effects, they are effective analgesics and are useful for the relief of mild to moderate pain.

Drug Category: Glucocorticoids

Have anti-inflammatory properties and cause profound and varied metabolic effects. They modify the body's immune response to diverse stimuli.

Drug Category: Beta-adrenergic blocking agents

Used for symptomatic relief of hyperthyroidism. Propranolol is used as an example, but any noncardioselective beta-blocker can be used. Use only in moderate to severe cases of hyperthyroidism, and many times it is not needed.

Drug Category: Thyroid hormones

Required during the recovery phase if transient hypothyroidism occurs. Required indefinitely in the occasional patient who develops permanent hypothyroidism.

FOLLOW-UP

Section 8 of 10  

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

Further Inpatient Care

Inpatient care is only recommended in the rare cases in which severe symptomatic hyperthyroidism is present.

Further Outpatient Care

The authors recommend monitoring thyroid function every 2-4 months for 1 year or until thyroid function normalizes (whichever occurs later).¹⁸ Yearly monitoring of thyroid function should be performed thereafter for several years, since permanent hypothyroidism may occur several years following the initial diagnosis.

Complications

• Acute complications
• • Severe hyperthyroidism may be observed during the inflammatory phase (see History).
  • Multiple system organ failure may complicate the course of the disease in exceptionally rare cases.
  • Pancreatitis or splenomegaly has been associated with de Quervain thyroiditis in case reports only.
  • Vocal cord paralysis occurs occasionally in cases with severe thyroid gland inflammation.
  • Cerebral venous thrombosis was reported in some cases. In one case, the patient was a heterozygous carrier for the G20210A mutation of the prothrombin gene, which predisposed her to this complication.
• Long-term complications
• • Permanent hypothyroidism is the most frequent long-term complication of de Quervain thyroiditis. It is observed in less than 5-10% of the patients and requires thyroid replacement therapy.
  • Disease recurrence has been documented in occasional cases (up to 20% of cases in some series). Recurrence is more frequent in the first year but has been reported even 30 years after the initial diagnosis. The risk of recurrence cannot be correlated with initial thyroid function, inflammatory syndrome, or ultrasonographic aspect (ie, thyroid volume, echogenicity).

Prognosis

Prognosis is excellent. More than 90% of the patients with de Quervain thyroiditis recover completely, with or without treatment. Even in the 5-10% of patients who develop hypothyroidism, treatment with thyroid hormone is effective.

Patient Education

For excellent patient education resources, visit eMedicine's Endocrine System Center. Also, see eMedicine's patient education article Thyroid Problems.

MISCELLANEOUS

Section 9 of 10  

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

Medical/Legal Pitfalls

An incorrect diagnosis potentially may lead to unnecessary surgery and surgical complications.

REFERENCES

Section 10 of 10

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

1. Fatourechi V, Aniszewski JP, Fatourechi GZ, Atkinson EJ, Jacobsen SJ. Clinical features and outcome of subacute thyroiditis in an incidence cohort: Olmsted County, Minnesota, study. J Clin Endocrinol Metab. May 2003;88(5):2100-5. [Medline].
2. Ogawa E, Katsushima Y, Fujiwara I, Iinuma K. Subacute thyroiditis in children: patient report and review of the literature. J Pediatr Endocrinol Metab. Jul-Aug 2003;16(6):897-900. [Medline].
3. Hiraiwa T, Kubota S, Imagawa A, Sasaki I, Ito M, Miyauchi A. Two cases of subacute thyroiditis presenting in pregnancy. J Endocrinol Invest. Nov 2006;29(10):924-7. [Medline].
4. Sherman SI, Ladenson PW. Subacute thyroiditis causing thyroid storm. Thyroid. Mar 2007;17(3):283. [Medline].
5. Bennedbaek FN, Hegedus L. The value of ultrasonography in the diagnosis and follow-up of subacute thyroiditis. Thyroid. Feb 1997;7(1):45-50. [Medline].
6. Birchall IW, Chow CC, Metreweli C. Ultrasound appearances of de Quervain's thyroiditis. Clin Radiol. Jan 1990;41(1):57-9. [Medline].
7. Brander A. Ultrasound appearances in de Quervain's subacute thyroiditis with long-term follow-up. J Intern Med. Oct 1992;232(4):321-5. [Medline].
8. Park SY, Kim EK, Kim MJ, Kim BM, Oh KK, Hong SW. Ultrasonographic characteristics of subacute granulomatous thyroiditis. Korean J Radiol. Oct-Dec 2006;7(4):229-34. [Medline].
9. Kunz A, Blank W, Braun B. De Quervain's subacute thyroiditis -- colour Doppler sonography findings. Ultraschall Med. Apr 2005;26(2):102-6. [Medline].
10. Jhaveri K, Shroff MM, Fatterpekar GM, Som PM. CT and MR imaging findings associated with subacute thyroiditis. AJNR Am J Neuroradiol. Jan 2003;24(1):143-6. [Medline].
11. Tezuka M, Murata Y, Ishida R, Ohashi I, Hirata Y, Shibuya H. MR imaging of the thyroid: correlation between apparent diffusion coefficient and thyroid gland scintigraphy. J Magn Reson Imaging. Feb 2003;17(2):163-9. [Medline].
12. Zein EF, Karaa SE, Megarbane A. Familial occurrence of painful subacute thyroiditis associated with human leukocyte antigen-B35. Presse Med. May 2007;36(5 Pt 1):808-9. [Medline].
13. Hiromatsu Y, Ishibashi M, Miyake I, Nonaka K. Technetium-99m tetrofosmin imaging in patients with subacute thyroiditis. Eur J Nucl Med. Oct 1998;25(10):1448-52. [Medline].
14. Chang TC, Lai SM, Wen CY, Hsiao YL. Three-dimensional cytomorphology in fine needle aspiration biopsy of subacute thyroiditis. Acta Cytol. Mar-Apr 2004;48(2):155-60. [Medline].
15. Garcia Solano J, Gimenez Bascunana A, Sola Perez J, Campos Fernandez J, Martinez Parra D, Sanchez Sanchez C, et al. Fine-needle aspiration of subacute granulomatous thyroiditis (De Quervain's thyroiditis): a clinico-cytologic review of 36 cases. Diagn Cytopathol. Mar 1997;16(3):214-20. [Medline].
16. Ofner C, Hittmair A, Kroll I, Bangerl I, Zechmann W, Totsch M, et al. Fine needle aspiration cytodiagnosis of subacute (de Quervain's) thyroiditis in an endemic goitre area. Cytopathology. Feb 1994;5(1):33-40. [Medline].
17. Shabb NS, Salti I. Subacute thyroiditis: fine-needle aspiration cytology of 14 cases presenting with thyroid nodules. Diagn Cytopathol. Jan 2006;34(1):18-23. [Medline].
18. Weihl AC, Daniels GH, Ridgway EC, Maloof F. Thyroid function tests during the early phase of subacute thyroiditis. J Clin Endocrinol Metab. Jun 1977;44(6):1107-14. [Medline].
19. Aiello A, Cristofaro M, Carrozza F, Verdone F, Carile L. [Lymphocyte subpopulations and the soluble interleukin-2 receptor in Hashimoto's thyroiditis and subacute thyroiditis]. Clin Ter. Jun 30 1990;133(6):401-4. [Medline].
20. Bartalena L, Brogioni S, Grasso L, Martino E. Increased serum interleukin-6 concentration in patients with subacute thyroiditis: relationship with concomitant changes in serum T4-binding globulin concentration. J Endocrinol Invest. Mar 1993;16(3):213-8. [Medline].
21. Bartels PC, Boer RO. Subacute thyroiditis (de Quervain) presenting as a painless "cold" nodule. J Nucl Med. Sep 1987;28(9):1488-90. [Medline].
22. Benker G, Olbricht T, Windeck R, Wagner R, Albers H, Lederbogen S, et al. The sonographical and functional sequelae of de Quervain's subacute thyroiditis: long-term follow-up. Acta Endocrinol (Copenh). Apr 1988;117(4):435-41. [Medline].
23. Bianda T, Schmid C. De Quervain's subacute thyroiditis presenting as a painless solitary thyroid nodule. Postgrad Med J. Oct 1998;74(876):602-3. [Medline].
24. Burgi U, Mueller B. [ABC of thyroid diseases and their treatment]. Ther Umsch. Jul 1999;56(7):353-5. [Medline].
25. Cordray JP, Nys P, Merceron RE, Augusti A. [Frequency of hypothyroidism after De Quervain thyroiditis and contribution of ultrasonographic thyroid volume measurement]. Ann Med Interne (Paris). Mar 2001;152(2):84-8. [Medline].
26. Cortázar A, Ruiz de Gordejuela J, Zabalza I, Acinas O, Beitia JJ. [Painful lymphocytic subacute thyroiditis]. Med Clin (Barc). Jan 25 1992;98(3):98-100. [Medline].
27. Coup A, Howat AJ. De Quervain's thyroiditis. Cytopathology. Jun 1997;8(3):218-9. [Medline].
28. Dumitriu L, Gudovan E, Ursu H. Radioiodine treatment in recurrences of subacute thyroiditis. Endocrinologie. Jan-Mar 1990;28(1):21-3. [Medline].
29. Epishin AV, Svider IO, Rapita OD. [Effect of glucocorticoids on immunological indices in patients with subacute thyroiditis]. Vrach Delo. Apr 1989;(4):29-31. [Medline].
30. Espino Montoro A, Medina Perez M, Gonzalez Martín MC, Asencio Marchante R, Lopez Chozas JM, et al. [Subacute thyroiditis associated with positive antibodies to the Epstein-Barr virus]. An Med Interna. Oct 2000;17(10):546-8. [Medline].
31. Fredenrich A, Hieronimus S, Carré Y, Fenichel P, Harter M. [Late recurrence of subacute De Quervain-Crile thyroiditis]. Ann Endocrinol (Paris). Jul 1998;59(2):121-3. [Medline].
32. Fukata S, Matsuzuka F, Kobayashi A, Hirai K, Kuma K, Sugawara M. Development of Graves' disease after subacute thyroiditis: two unusual cases. Acta Endocrinol (Copenh). Jun 1992;126(6):495-6. [Medline].
33. Fukazawa H, Sakurada T, Tamura K, Yamamoto M, Yoshida K, Kaise K, et al. The influence of immunosuppressive acidic protein on the activity of peripheral K-lymphocytes in subacute thyroiditis. J Clin Endocrinol Metab. Jul 1990;71(1):193-8. [Medline].
34. Geva T, Theodor R. Atypical presentation of subacute thyroiditis. Arch Dis Child. Jul 1988;63(7):845-6. [Medline].
35. Grunenberger F, Chenard MP, Weber JC, Jaeck D, Schlienger JL. Relapse of Graves' disease after subacute thyroiditis. Thyroid. Aug 1998;8(8):683-5. [Medline].
36. Hamburger JI. The various presentations of thyroiditis. Diagnostic considerations. Ann Intern Med. Feb 1986;104(2):219-24. [Medline].
37. Hardoff R, Baron E, Sheinfeld M, Luboshitsky R. Localized manifestations of subacute thyroiditis presenting as solitary transient cold thyroid nodules. A report of 11 patients. Clin Nucl Med. Nov 1995;20(11):981-4. [Medline].
38. Hay ID. Thyroiditis: a clinical update. Mayo Clin Proc. Dec 1985;60(12):836-43. [Medline].
39. Hiromatsu Y, Ishibashi M, Nishida H, Kawamura S, Kaku H, Baba K, et al. Technetium-99 m sestamibi imaging in patients with subacute thyroiditis. Endocr J. Jun 2003;50(3):239-44. [Medline].
40. Hisaoka T, Momotani N, Yoshimura H, Ishikawa N, Ito K, Iino S. [A case of subacute thyroiditis with highly positive thyrotropin receptor antibodies and normal radioiodine uptake]. Nippon Naibunpi Gakkai Zasshi. Oct 20 1993;69(9):997-1002. [Medline].
41. Houghton DJ, Gray HW, MacKenzie K. The tender neck: thyroiditis or thyroid abscess?. Clin Endocrinol (Oxf). Apr 1998;48(4):521-4. [Medline].
42. Hwang SC, Jap TS, Ho LT, Ching KN. Subacute thyroiditis--61 cases review. Chung Hua I Hsueh Tsa Chih (Taipei). Feb 1989;43(2):113-8. [Medline].
43. Iitaka M, Momotani N, Hisaoka T, Noh JY, Ishikawa N, Ishii J, et al. TSH receptor antibody-associated thyroid dysfunction following subacute thyroiditis. Clin Endocrinol (Oxf). Apr 1998;48(4):445-53. [Medline].
44. Iitaka M, Momotani N, Ishii J, Ito K. Incidence of subacute thyroiditis recurrences after a prolonged latency: 24-year survey. J Clin Endocrinol Metab. Feb 1996;81(2):466-9. [Medline].
45. Intenzo CM, Park CH, Kim SM, Capuzzi DM, Cohen SN, Green P. Clinical, laboratory, and scintigraphic manifestations of subacute and chronic thyroiditis. Clin Nucl Med. Apr 1993;18(4):302-6. [Medline].
46. Ishizuki Y, Hirooka Y, Murata Y, Togashi K. [The functional outcome of patients with subacute thyroiditis]. Nippon Naibunpi Gakkai Zasshi. Mar 20 1992;68(3):154-65. [Medline].
47. Iwatani Y, Amino N, Hidaka Y, Kaneda T, Ichihara K, Tamaki H, et al. Decreases in alpha beta T cell receptor negative T cells and CD8 cells, and an increase in CD4+ CD8+ cells in active Hashimoto's disease and subacute thyroiditis. Clin Exp Immunol. Mar 1992;87(3):444-9. [Medline].
48. Karlsson FA, Totterman TH, Jansson R. Subacute thyroiditis: activated HLA-DR and interferon-gamma expressing T cytotoxic/suppressor cells in thyroid tissue and peripheral blood. Clin Endocrinol (Oxf). Nov 1986;25(5):487-93. [Medline].
49. Kimura M, Amino N, Takada K, Miyai K. Subacute thyroiditis associated with systemic multi-organ disorders. Endocrinol Jpn. Dec 1989;36(6):859-64. [Medline].
50. Kitchener MI, Chapman IM. Subacute thyroiditis: a review of 105 cases. Clin Nucl Med. Jun 1989;14(6):439-42. [Medline].
51. Koga M, Hiromatsu Y, Jimi A, Toda S, Koike N, Nonaka K. Immunohistochemical analysis of Bcl-2, Bax, and Bak expression in thyroid glands from patients with subacute thyroiditis. J Clin Endocrinol Metab. Jun 1999;84(6):2221-5. [Medline].
52. Kojima M, Nakamura S, Oyama T, Sugihara S, Sakata N, Masawa N. Cellular composition of subacute thyroiditis. an immunohistochemical study of six cases. Pathol Res Pract. 2002;198(12):833-7. [Medline].
53. Kramer AB, Roozendaal C, Dullaart RP. Familial occurrence of subacute thyroiditis associated with human leukocyte antigen-B35. Thyroid. Jul 2004;14(7):544-7. [Medline].
54. Lazarus, JH. Silent thyroiditis and subacute thyroiditis. In: Braverman LE, Utiger R, eds. Werner and Ingbar's The Thyroid: A Fundamental and Clinical Text. 7^th ed. New York, NY: JB Lippincott; 1996:577.
55. Leovey A. [Definition and clinical importance of thyroiditis]. Orv Hetil. May 2 1993;134(18):955-61. [Medline].
56. Levine SN. Current concepts of thyroiditis. Arch Intern Med. Oct 1983;143(10):1952-6. [Medline].
57. Lips P, Teule GJ, van der Linden JC, Gans RO. [A painful inflammation of the thyroid]. Ned Tijdschr Geneeskd. Jul 4 1998;142(27):1537-42. [Medline].
58. Luotola K, Hyoty H, Salmi J, Miettinen A, Helin H, Pasternack A. Evaluation of infectious etiology in subacute thyroiditis--lack of association with coxsackievirus infection. APMIS. Apr 1998;106(4):500-4. [Medline].
59. Madrońero-Vuelta AB, Sanahuja-Montesinos J, Bergua-Llop M, Araguás-Arasanz C. [Cerebral venous thrombosis associated to subacute De Quervain's thyroiditis in a carrier for the G20210A mutation of the prothrombin gene]. Rev Neurol. Sep 16-30 2004;39(6):533-5. [Medline].
60. Mak-Karaba I, Jerant-Patic V, Todorovic-Dilas L. [Subacute thyroiditis. A case report of an unusual etiology]. Med Pregl. 1995;48(3-4):117-9. [Medline].
61. Martino E, Buratti L, Bartalena L, Mariotti S, Cupini C, Aghini-Lombardi F, et al. High prevalence of subacute thyroiditis during summer season in Italy. J Endocrinol Invest. Jun 1987;10(3):321-3. [Medline].
62. McDonnell TJ, Korsmeyer SJ. Progression from lymphoid hyperplasia to high-grade malignant lymphoma in mice transgenic for the t(14; 18). Nature. Jan 17 1991;349(6306):254-6. [Medline].
63. Meier DA. Transient cold nodule of the thyroid due to localized subacute thyroiditis. Clin Nucl Med. Feb 1991;16(2):139. [Medline].
64. Milioniz HJ, Elisaf MS, Drosos AA, Tsatsoulis AA. Concurrence of giant cell arteritis in a patient with de quervain's thyroiditis. Clin Endocrinol (Oxf). Dec 1997;47(6):760-1. [Medline].
65. Mitani Y, Shigemasa C, Kouchi T, et al. Detection of thyroid-stimulating antibody in patients with inflammatory thyrotoxicosis. Horm Res. 1992;37(4-5):196-201. [Medline].
66. Mizokami T, Okamura K, Hirata T, Yamasaki K, Sato K, Ikenoue H, et al. Acute spontaneous hemorrhagic degeneration of the thyroid nodule with subacute thyroiditis-like symptoms and laboratory findings. Endocr J. Oct 1995;42(5):683-9. [Medline].
67. Mori K, Yoshida K, Funato T, Ishii T, Nomura T, Fukuzawa H, et al. Failure in detection of Epstein-Barr virus and cytomegalovirus in specimen obtained by fine needle aspiration biopsy of thyroid in patients with subacute thyroiditis. Tohoku J Exp Med. Sep 1998;186(1):13-7. [Medline].
68. Nakamura S, Hattori J, Ishiyama-Takuno M, Shima H, Matsui I, Sakata S. Non-suppressed thyroidal radioactive iodine uptake (RAIU) in thyrotoxic phase in a case of subacute thyroiditis with thyroid-stimulating antibodies (TSAb). Endocrinol Jpn. Oct 1992;39(5):469-76. [Medline].
69. Niklaus-Müller E, Müllhaupt B, Perschak H. [Steroid therapy and course of blood sedimentation rate in de Quervain's thyroiditis]. Schweiz Rundsch Med Prax. Jan 25 1994;83(4):95-100. [Medline].
70. Nikolai TF, Coombs GJ, McKenzie AK. Lymphocytic thyroiditis with spontaneously resolving hyperthyroidism and subacute thyroiditis. Long-term follow-up. Arch Intern Med. Oct 1981;141(11):1455-8. [Medline].
71. Ohsako N, Tamai H, Sudo T, Mukuta T, Tanaka H, Kuma K, et al. Clinical characteristics of subacute thyroiditis classified according to human leukocyte antigen typing. J Clin Endocrinol Metab. Dec 1995;80(12):3653-6. [Medline].
72. Oner A, Demircin G, Tinaztepe K, Akinci A, Tezic T. Henoch-Schonlein nephritis associated with subacute thyroiditis. Turk J Pediatr. Jan-Mar 1996;38(1):131-5. [Medline].
73. Ozata M, Bolu E, Sengul A, Altinsoy HI, Turan M, Corakci A, et al. Soluble intercellular adhesion molecule-1 concentrations in patients with subacute thyroiditis and in patients with Graves' disease with or without ophthalmopathy. Endocr J. Oct 1996;43(5):517-25. [Medline].
74. Piazza I, Girardi A. Painless giant cell thyroiditis. Postgrad Med J. Aug 1989;65(766):580-1. [Medline].
75. Prakash R, Jayaram G, Singh RP. Follicular thyroid carcinoma masquerading as subacute thyroiditis. Diagnosis using ultrasonography and radionuclide thyroid angiography. Australas Radiol. May 1991;35(2):174-7. [Medline].
76. Rajkovaca Z, Biukovic M, Mikac G, Skrobic M. [Correlation of ultrasound and radioisotope studies in subacute de Quervain thyroiditis]. Med Pregl. Mar-May 1999;52(3-5):141-5. [Medline].
77. Rhodes-Feuillette A, Lasneret J, Paulien S, Ogunkolade W, Peries J, Canivet M. Effects of human recombinant alpha and gamma and of highly purified natural beta interferons on simian Spumavirinae prototype (simian foamy virus 1) multiplication in human cells. Res Virol. Jan-Feb 1990;141(1):31-43. [Medline].
78. Rosenstein ED, Kramer N. Occult subacute thyroiditis mimicking classic giant cell arteritis. Arthritis Rheum. Nov 1994;37(11):1618-20. [Medline].
79. Rubin RA, Guay AT. Susceptibility to subacute thyroiditis is genetically influenced: familial occurrence in identical twins. Thyroid. 1991;1(2):157-61. [Medline].
80. Sakane S, Murakami Y, Sasaki M, Yamano Y, Takamatsu J, Kuma K, et al. Serum concentrations of granulocyte colony-stimulating factor (G-CSF) determined by a highly-sensitive chemiluminescent immunoassay during the clinical course of subacute thyroiditis. Endocr J. Jun 1995;42(3):391-6. [Medline].
81. Schnyder B, Hedinger C. [Occurrence of fibrosis in subacute de Quervain thyroiditis]. Schweiz Med Wochenschr. Aug 16 1986;116(33):1093-7. [Medline].
82. Schofield PM, Keal EE. Subacute thyroiditis associated with Chlamydia psittaci infection. Postgrad Med J. Jan 1986;62(723):33-4. [Medline].
83. Schubert MF, Kountz DS. Thyroiditis. A disease with many faces. Postgrad Med. Aug 1995;98(2):101-3, 107-8, 112. [Medline].
84. Shigemasa C, Abe K, Taniguchi S, Mitani Y, Ueta Y, Urabe K, et al. Serum free thyroxine and thyroxine-binding globulin concentrations in early phase of subacute thyroiditis. Endocrinol Jpn. Dec 1987;34(6):821-9. [Medline].
85. Singer PA. Thyroiditis. Acute, subacute, and chronic. Med Clin North Am. Jan 1991;75(1):61-77. [Medline].
86. Slijepcevic D, Trbojevic B, Vujovic S. [Thyroiditis]. Glas Srp Akad Nauka [Med]. 1991;(41):151-60. [Medline].
87. Tajiri J, Noguchi S, Morita M, Tamaru M, Murakami T, Murakami N. Serum sialic acid levels in the diagnosis and follow-up of subacute granulomatous thyroiditis. Endocr J. Feb 1993;40(1):83-7. [Medline].
88. Tajtakova M, Hancinova D, Gonsorcíkova V, Machanova Y, Jandosekova X. [Ultrasonography in subacute thyroiditis]. Vnitr Lek. May 1992;38(5):479-84. [Medline].
89. Tamai H, Nozaki T, Mukuta T, Morita T, Matsubayashi S, Kuma K, et al. The incidence of thyroid stimulating blocking antibodies during the hypothyroid phase in patients with subacute thyroiditis. J Clin Endocrinol Metab. Aug 1991;73(2):245-50. [Medline].
90. Tauveron I, Thieblot P, Marcheix JC. [Recurrence after 12 years of De Quervain-Crile subacute thyroiditis]. Rev Med Interne. Sep-Oct 1991;12(5):396. [Medline].
91. Toda S, Nishimura T, Yamada S, Koike N, Yonemitsu N, Watanabe K, et al. Immunohistochemical expression of growth factors in subacute thyroiditis and their effects on thyroid folliculogenesis and angiogenesis in collagen gel matrix culture. J Pathol. Aug 1999;188(4):415-22. [Medline].
92. Tokuda Y, Kasagi K, Iida Y, Yamamoto K, Hatabu H, Hidaka A, et al. Sonography of subacute thyroiditis: changes in the findings during the course of the disease. J Clin Ultrasound. Jan 1990;18(1):21-6. [Medline].
93. Topuzovic N, Smoje J, Karner I. The therapeutic approach in subacute (de Quervain's) thyroiditis. J Nucl Med. Oct 1997;38(10):1665. [Medline].
94. Vejlgaard TB, Nielsen OB. [Subacute thyroiditis in Parvovirus B19 infection]. Ugeskr Laeger. Oct 10 1994;156(41):6039-40. [Medline].
95. Vierhapper H, Bieglmayer C, Nowotny P, Waldhausl W. Normal serum concentrations of sex hormone binding-globulin in patients with hyperthyroidism due to subacute thyroiditis. Thyroid. Dec 1998;8(12):1107-11. [Medline].
96. Volpe R. The management of subacute (DeQuervain's) thyroiditis. Thyroid. 1993;3(3):253-5. [Medline].
97. Volpe R, Row VV, Ezrin C. Circulating viral and thyroid antibodies in subacute thyroiditis. J Clin Endocrinol Metab. Sep 1967;27(9):1275-84. [Medline].
98. Volta C, Carano N, Street ME, Bernasconi S. Atypical subacute thyroiditis caused by Epstein-Barr virus infection in a three-year-old girl. Thyroid. Oct 2005;15(10):1189-91. [Medline].
99. Vulpoi C, Zbranca E, Preda C, Ungureanu MC. [Contribution of ultrasonography in the evaluation of subacute thyroiditis]. Rev Med Chir Soc Med Nat Iasi. Oct-Dec 2001;105(4):749-55. [Medline].
100. Watts NB, Sewell CW. Carcinomatous involvement of the thyroid presenting as subacute thyroiditis. Am J Med Sci. Aug 1988;296(2):126-8. [Medline].
101. Weetman AP, Smallridge RC, Nutman TB, Burman KD. Persistent thyroid autoimmunity after subacute thyroiditis. J Clin Lab Immunol. May 1987;23(1):1-6. [Medline].
102. Weiss BM, Hepburn MJ, Mong DP. Subacute thyroiditis manifesting as fever of unknown origin. South Med J. Sep 2000;93(9):926-9. [Medline].
103. Werner J, Gelderblom H. Isolation of foamy virus from patients with de Quervain thyroiditis. Lancet. Aug 4 1979;2(8136):258-9. [Medline].
104. Yamamoto M, Saito S, Sakurada T, Tamura M, Kudo Y, Yoshida K, et al. Recurrence of subacute thyroiditis over 10 years after the first attack in three cases. Endocrinol Jpn. Dec 1988;35(6):833-9. [Medline].
105. Yamamoto M, Saito S, Sakurada T, Tamura M, Kudo Y, Yoshida K, et al. Recurrence of subacute thyroiditis over 10 years after the first attack in three cases. Endocrinol Jpn. Dec 1988;35(6):833-9. [Medline].
106. Yamashita T, Okamoto T, Kawada J, Iihara M, Tanaka R, Kanaji Y, et al. [Characteristics and clinical course of patients with subacute thyroiditis without typical signs and symptoms]. Nippon Naibunpi Gakkai Zasshi. Nov 20 1993;69(10):1057-61. [Medline].
107. Yang YS, Wu MZ, Cheng AL, Chang TC. Primary thyroid lymphoma mimicking subacute thyroiditis. Acta Cytol. Nov-Dec 2006;50(6):710-2. [Medline].
108. 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 Ultrasound. Sep 2002;30(7):442-4. [Medline].

Article Last Updated: Dec 7, 2007