AUTHOR AND EDITOR INFORMATION

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INTRODUCTION

Section 2 of 11  

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Background

Riedel 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. This feature differentiates it from other inflammatory or fibrotic disorders of the thyroid. Because of the encroachment beyond the thyroid capsule, other problems can be associated with RT, including hypoparathyroidism, hoarseness due to recurrent laryngeal involvement, and stridor due to tracheal compression. Some experts feel it is not primarily a thyroid disorder but rather a manifestation of a systemic disorder, namely multifocal fibrosclerosis. Approximately one third of RT cases are associated with clinical findings of multifocal fibrosclerosis at the time of diagnosis.

In 1883, Professor Bernhard Riedel first recognized the disease. He published a description of 2 cases in 1896 and a third case in 1897. 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.

Pathophysiology

The etiology of RT is unknown. One theory of pathogenesis postulates that RT results from an autoimmune process. A second theory holds RT to be a primary fibrotic disorder.

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)



• The pathological 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. Additionally, elevated levels of antithyroid antibodies may merely reflect exposure to the immune system of sequestered antigens released by the destruction of thyroid parenchyma from a primary fibrotic disorder.

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 one manifestation of this multifocal disease.

The histopathologic changes of RT closely resemble those observed in multifocal fibrosclerosis. Additionally, one third of published RT cases demonstrated at least one 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.

Frequency

United States

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

Mortality/Morbidity

The morbidity of RT 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.

Death due to airway compromise is very rare in treated patients.

A third of RT patients ultimately develop at least one extracervical manifestation of multifocal fibrosclerosis (eg, retroperitoneal fibrosis, mediastinal fibrosis, sclerosing cholangitis). In such patients, morbidity and mortality are largely related to the extracervical fibrosclerosis.

Race

Although predominantly reported in whites, RT has been described in all races.

Sex

RT is most often seen in women. In one review of 178 patients with RT, 83% were women.

Age

The mean age at diagnosis was 47.8 years (range, 23-77 y) in the same series of 178 patients.

CLINICAL

Section 3 of 11  

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History

• 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.



• 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.



• Involvement may be unilateral or bilobar.



• Thyroid function depends on the extent to which the normal thyroid gland has been replaced with fibrosis. Most patients are euthyroid. Hypothyroidism is noted in approximately 30% of cases. Rarely, hyperthyroidism can occur, but this is probably secondary to a coexisting condition.



• Local compressive symptoms, such as neck tightness or pressure, dyspnea, dysphagia, hoarseness, choking, and cough, are frequent. 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.



• Occasionally, spontaneous remission has been reported. Patients can also relapse.

Physical

See History.

• Clinical features of RT closely resemble those of anaplastic carcinoma of the thyroid. The patients note a nonpainful rapidly growing thyroid mass. One distinguishing feature of RT is the absence of associated cervical adenopathy. However, accurate diagnosis requires open biopsy. RT and anaplastic carcinoma of the thyroid can be distinguished by immunohistochemistry.



• Approximately one third of patients with RT have an associated extracervical manifestation of multifocal fibrosclerosis (eg, retroperitoneal fibrosis, mediastinal fibrosis, orbital pseudotumor, pulmonary fibrosis, sclerosing cholangitis, lacrimal gland fibrosis, fibrosing parotitis).

Causes

The etiology of RT is unknown.

DIFFERENTIALS

Section 4 of 11  

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WORKUP

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Lab Studies

• The laboratory findings of Riedel thyroiditis (RT) are nonspecific.



• The erythrocyte sedimentation rate (ESR) is generally elevated.



• Most patients remain euthyroid. Approximately 30% of patients become hypothyroid. Rarely, patients are hyperthyroid.



• In one review, antithyroid antibody levels were found to be elevated in 67% of 178 cases. However, it is not certain whether such autoantibodies are pathogenic or merely reflect exposure to the immune system of sequestered antigens released by the fibrotic destruction of normal thyroid parenchyma.

Imaging Studies

• In cases of RT, imaging studies may suggest the diagnosis, but findings can be nonspecific.



• Enlargement of the affected thyroid gland and compression or invasion of adjacent structures, such as the strap muscles, trachea, esophagus, or carotids, may be observed on CT scan or MRI. However, these studies cannot reliably distinguish between RT and invasive thyroid malignancy.
• • CT scan shows affected areas of the thyroid to be hypodense. The area is usually isodense with the neck muscles. Use of iodinated contrast has occasionally been reported as causing increased enhancement, but usually it is decreased, especially if extensive fibrosis is present.
  
  
  
  • On MRI, the affected thyroid gland is typically hypointense on T1- and T2-weighted images. Usually decreased enhancement has been reported with gadolinium contrast use, but occasionally increased enhancement has been reported.
     
• Nuclear thyroid scans generally demonstrate a cold area of uptake at the site of the affected thyroid gland.



• Thyroid ultrasonography has been reported to be homogenously hypoechoic, with loss of clear demarcation of the gland when fibrotic invasion of adjacent anatomic structures exists.

Procedures

• The diagnosis of RT requires histologic confirmation through open surgical biopsy.
• Fine-needle biopsy in patients with RT demonstrates fibrotic changes of the thyroid gland; however, this cannot be reliably distinguished from the fibrotic changes often associated with anaplastic thyroid carcinoma. The fibrotic changes and paucity of thyroid follicular cells usually results in an inadequate fine-needle aspiration biopsy. For this reason, an open surgical biopsy is essential in order to establish the correct diagnosis. This is most often performed in the course of a wedge resection of the thyroid isthmus designed to simultaneously alleviate compressive symptoms.

Histologic Findings

The involved portion of the thyroid gland in patients with RT is typically described as stony or woody. Involvement is most often unilateral but may also be bilateral. The thyroid mass is generally well circumscribed but not encapsulated. Extension of the fibrotic process to adjacent structures of the neck results in fixation of the thyroid mass and loss of tissue planes. Fibrosis may invade the strap muscles, trachea, esophagus, carotids, parathyroid glands, and laryngeal nerves. When incised, the involved tissue is relatively avascular, "cuts like cartilage," and is often white of pale gray. RT cannot be distinguished from anaplastic carcinoma based on gross pathologic findings.

In 1957, Woolner et al established the microscopic criteria for the diagnosis of RT. These criteria, since modified, include the following: (1) a fibroinflammatory process that involves all or a portion of the thyroid gland, (2) the presence of gross or microscopic extension of the fibrosis beyond the thyroid capsule into adjacent anatomic structures, and (3) complete or near-complete destruction of the involved portion of the thyroid gland with an absence of the giant cell reaction observed in granulomatous thyroiditis.

Collagen-laden fibrous bands infiltrate the involved portion of the thyroid gland. Ultimately, the thyroid acini are reduced or obliterated. A cellular infiltrate of lymphocytes, plasma cells, and eosinophils accompanies the fibrosis. Inflammatory cells within the walls of small arteries and veins may produce a local vasculitis. Invasion of the fibroinflammatory process beyond the thyroid capsule erases normal anatomic planes.

TREATMENT

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Medical Care

The rarity of Riedel thyroiditis (RT) makes controlled studies of therapy impractical. Recommendations for medical treatment have been largely based on empirical experience.

• Currently, corticosteroid therapy is the medical treatment of choice for patients with RT.
  • Most studies note reduction of goiter size and relief of local compressive symptoms, although some patients show no benefit.
  
  
  • Some investigators believe that a favorable response is more likely early in the course of the disease. Improvement is less likely to occur in patients with advanced RT when the affected portions of the thyroid gland have been completely replaced by fibrosis.
    
  
  
  • Corticosteroids are believed to act both by reducing inflammation and by inhibiting the actions of fibrinogenic cytokines.
    
  
  
  • No consensus has been reached on the dosing regimen of corticosteroids. All studies advocate an initially high dose to alleviate compressive symptoms, followed by gradual tapering over months to a lower maintenance dose.
    
  
  
  • Effectiveness of therapy can be judged by symptomatic improvement and by following reduction of the ESR and thyroid autoantibody levels. Many patients can be weaned from therapy, but others require more prolonged treatment.


• In many recent patients, tamoxifen has been started as primary therapy, obviating the negative consequences of steroid therapy. The usual dose found to be effective is 20 mg PO bid. Patients who respond can be tapered to 20 mg once each day or 10 mg bid. Because of the relatively infrequent occurrence of RT, comparison studies with tamoxifen and steroid therapy have not been undertaken. Few et al initially advocated tamoxifen in a study of 4 patients with progressive RT who were not responsive to corticosteroids or surgical decompression. Each of the 4 patients had a 50% or more decrease in the size of their thyroid mass, and one had total resolution.
  • An oral dose of 20 mg twice a day provided each patient with symptomatic improvement and a reduction in size of the involved tissue as measured on CT scan.
    
  
  
  • Estrogen receptors have not been demonstrated in RT tissue. Therefore, the mechanism of action was not proposed to be tamoxifen's antiestrogen activity but rather its induction of transforming growth factor-beta, a potent inhibitor of fibroblast proliferation.


• Correct hypothyroidism associated with RT with levothyroxine therapy. Many authorities advocate not only thyroid replacement but also suppression of thyroid-stimulating hormone (TSH) in all patients with RT, regardless of thyroid function. However, the degree to which TSH stimulates the fibroinflammatory processes of RT, if at all, is unknown. As such, recommendations for TSH suppression must be regarded as empirical.

Surgical Care

Surgery for patients with RT serves the dual purposes of establishing the diagnosis and relieving tracheal compression. A wedge resection of the thyroid isthmus remains the preferred method for accomplishing these ends.

• Open surgical biopsy is essential to definitively establish the diagnosis of RT and to exclude carcinoma.



• A wedge resection of the isthmus relieves tracheal compression. Grossly, the affected tissue is stony, hard, and white or pale gray in appearance. It has a similar feel to cartilage when incised.



• More extensive thyroid surgery is generally discouraged because extrathyroid fibrosclerosis alters the anatomy and obliterates surgical planes. The trachea, esophagus, carotids, recurrent laryngeal nerves, or parathyroid glands may be encased in fibrosis and are at increased risk for iatrogenic surgical damage.

Consultations

An endocrinologist should be consulted in the management of RT. Surgical consultation is necessary for a diagnostic open biopsy.

MEDICATION

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Drug Category: Corticosteroids

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

Drug Category: Antineoplastic agents

For progressive RT not responsive to corticosteroids or surgical decompression, or for those patients with contraindications to corticosteroid therapy. Provide symptomatic improvement and size reduction of the involved tissue as measured on CT scan.

Drug Category: Thyroid hormones

Used to correct hypothyroidism associated with RT.

FOLLOW-UP

Section 8 of 11  

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Further Inpatient Care

• The patient should be followed for progression of the RT and development of multifocal fibrosclerosis. Repeat imaging of the neck by CT scan or MRI should be performed at intervals defined by the rate of progression.
• TSH level should be routinely checked and maintained in the reference range with administration of levothyroxine as necessary.

Complications

• Airway obstruction
• Dysphonia
• Hoarseness
• Hypothyroidism
• Hypoparathyroidism
• Dysphagia

Prognosis

• RT is generally a self-limited disease with a favorable prognosis. Death due to airway compromise is very rare.
• One third of patients with RT ultimately develop at least one extracervical manifestation of multifocal fibrosclerosis. These include retroperitoneal fibrosis, mediastinal fibrosis, and sclerosing cholangitis. In such patients, the prognosis essentially becomes that of extracervical fibrosclerosis. When RT is diagnosed, it is therefore essential to perform abdominal and chest imaging studies to exclude these concomitant entities.

MISCELLANEOUS

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Medical/Legal Pitfalls

• Failure to correctly distinguish RT from anaplastic thyroid carcinoma or sclerosing variant of papillary carcinoma: Fine-needle biopsy cannot be relied upon to distinguish these entities because each may demonstrate fibrotic changes. An open surgical biopsy is essential to establish the correct diagnosis and to relieve tracheal compression, if present.



• Failure to distinguish between fibrotic Hashimoto thyroiditis and RT: Fibrosclerosis of the surrounding tissue by RT can lead to serious morbidity and death.

MULTIMEDIA

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Media file 1:  Riedel (fibrosing) thyroiditis. The atrophic thyroid follicles are surrounded by a dense inflammatory infiltrate composed of lymphocytes, plasma cells, and eosinophils and accompanied by dense fibrosis. The wide bands of keloid-type collagen located between the individual follicles and surrounding clusters are a common feature of this condition.
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Media file 2:  Riedel (fibrosing) thyroiditis. This vein shows infiltration of its wall by a heavy inflammatory infiltrate.
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Media type:  Image

Media file 3:  Riedel (fibrosing) thyroiditis. The inflammatory infiltrate and dense pink bands of fibrosis can obliterate thyroid follicles. Image courtesy of S.L. Lee.
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Media type:  Image

Media file 4:  Gross pathology of Riedel (fibrosing) thyroiditis. The cut edge is avascular with a characteristic white color. Image courtesy of S.L. Lee.
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Media type:  Photo

REFERENCES

Section 11 of 11

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• Beahrs OH, McConahey WM, Woolner LB. Invasive fibrous thyroiditis (Riedel's struma). J Clin Endocrinol Metab. Feb 1957;17(2):201-20. [Medline].
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• De M, Jaap A, Dempster J. Tamoxifen therapy in steroid resistant Reidel's thyroiditis. Scott Med J. Apr 2001;46(2):56-7. [Medline].
• Few J, Thompson NW, Angelos P, Simeone D, Giordano T, Reeve T. Riedel's thyroiditis: treatment with tamoxifen. Surgery. Dec 1996;120(6):993-8; discussion 998-9. [Medline].
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• Geissler B, Wagner T, Dorn R, Lindemann F. Extensive sterile abscess in an invasive fibrous thyroiditis (Riedel's thyroiditis) caused by an occlusive vasculitis. J Endocrinol Invest. Feb 2001;24(2):111-5. [Medline].
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• Malotte MJ, Chonkich GD, Zuppan CW. Riedel's thyroiditis. Arch Otolaryngol Head Neck Surg. Feb 1991;117(2):214-7. [Medline].
• Oguz KK, Kiratli H, Oguz O, Cila A, Oto A, Gokoz A. Multifocal fibrosclerosis: a new case report and review of the literature. Eur Radiol. May 2002;12(5):1134-8. [Medline].
• Ozgen A, Cila A. Riedel's thyroiditis in multifocal fibrosclerosis: CT and MR imaging findings. AJNR Am J Neuroradiol. Feb 2000;21(2):320-1. [Medline].
• Pritchyk K, Newkirk K, Garlich P, Deeb Z. Tamoxifen therapy for Riedel's thyroiditis. Laryngoscope. Oct 2004;114(10):1758-60. [Medline].
• Riedel BM. Die chronische, zur Bildung eisenharter Tumoren fuhrende Entzundung der Schilddruse. Verh. Dtsch. Ges. Chir. 1896;25:101-5.
• Schwaegerle SM, Bauer TW, Esselstyn CB Jr. Riedel's thyroiditis. Am J Clin Pathol. Dec 1988;90(6):715-22. [Medline].
• Tutuncu NB, Erbas T, Bayraktar M, Gedik O. Multifocal idiopathic fibrosclerosis manifesting with Riedel's thyroiditis. Endocr Pract. Nov-Dec 2000;6(6):447-9. [Medline].
• Vaidya B, Harris PE, Barrett P, Kendall-Taylor P. Corticosteroid therapy in Riedel's thyroiditis. Postgrad Med J. Dec 1997;73(866):817-9. [Medline].
• Wan SK, Chan JK, Tang SK. Paucicellular variant of anaplastic thyroid carcinoma. A mimic of Reidel's thyroiditis. Am J Clin Pathol. Apr 1996;105(4):388-93. [Medline].
• Zelmanovitz F, Zelmanovitz T, Beck M, Cerski CT, Schmid H, Czepielewski MA. Riedel's thyroiditis associated with high titers of antimicrosomal and antithyroglobulin antibodies and hypothyroidism. J Endocrinol Invest. Oct 1994;17(9):733-7. [Medline].

Article Last Updated: Jul 20, 2006