Riedel Thyroiditis

Article Author:
Shiva Kumar Gosi
Article Editor:
Vishnu Garla
Updated:
1/30/2019 8:42:25 AM
PubMed Link:
Riedel Thyroiditis

Introduction

Riedel thyroiditis is a pathology first described in 1896 by Riedel. It is a rare fibrotic condition which involves the thyroid gland and often invades the surrounding structures. It is also known as Riedel struma, ligneous struma, or chronic invasive fibrous thyroiditis.[1] Histologically, the thyroid parenchyma and surrounding structures get replaced with dense fibrous tissue. The etiology of Riedel thyroiditis is not known. Most commonly Riedel thyroiditis manifests with obstructive symptoms such as dyspnea, dysphagia, and hoarseness due to the involvement of the structures around the thyroid gland.[2] It can also present with hypothyroidism, hypoparathyroidism or Horner’s syndrome. Diagnosis confirmation is by performing a biopsy which shows dense fibrous tissue with a characteristic eosinophilic infiltrate. Management includes both surgical and medical treatment. The goal of surgery is done primarily to relieve obstructive symptoms. The mainstay of medical management is glucocorticoids which can cause dramatic improvement of the symptoms. Tamoxifen, mycophenolate, and radiation have also been therapeutic choices in non-responsive cases with variable success.[1]

Etiology

The etiology of Riedel thyroiditis is not definitively known. Various theories have suggested that it could be a variant of autoimmune thyroiditis or part of a systemic fibrosing disorder or an immunoglobulin G4 (IgG4) related disease. The presence of anti-thyroid antibodies, eosinophilic infiltrate, and response to glucocorticoid therapy are suggestive of autoimmune pathology.[3][4] However, lack of other antibodies, association with other autoimmune disorders, normal lymphocyte counts and complement levels suggest otherwise. Riedel thyroiditis has been known to be associated with orbital fibrosis, primary sclerosing cholangitis, mediastinal and retroperitoneal fibrosis, giving rise to the suspicion that it may be a part of a multifocal idiopathic fibrosclerosing disorder. However, the lack of a consistent association of Riedel thyroiditis with other fibrosing disorders does not support this cause.[5]

Epidemiology

Riedel's thyroiditis is a rare disease. Most patients are euthyroid, some may become hypothyroid and very few become hyperthyroid. It is more common in women.

Pathophysiology

The hallmark of Riedel thyroiditis is the replacement of thyroid tissue with dense fibrotic tissue. The fibrosis involves extra-thyroidal structures involving the trachea, parathyroid glands, neck musculature, laryngeal nerves, and blood vessels. Grossly, the tissue is gray in appearance and woody in its consistency. Histologically, its characteristics are a dense hyalinized matrix with scanty colloid, and a characteristic eosinophilic cell infiltrate. No malignant or giant cells are present. Occlusive phlebitis may also be present.[6][1]

History and Physical

The most common clinical presentation of Riedel thyroiditis is a hard and enlarged thyroid. Obstructive symptoms due to the involvement of neck structures are frequent. Dyspnea due to tracheal involvement, dysphagia due to esophageal involvement, stridor due to recurrent laryngeal nerve involvement, and venous sinus thrombosis due to the involvement of the vasculature can be present. Exophthalmos is secondary to involvement of the retrobulbar tissues. On examination, a hard mass is palpable in the anterior neck which may not move on swallowing as it is adherent to the surrounding neck structures. A positive Chvostek or Trousseau sign is indicative of hypoparathyroidism secondary to parathyroid gland involvement.[7][1][8]

Evaluation

Thyroid function tests may reveal hypothyroidism in about 74% patients. Hashimoto thyroiditis can occur concomitantly, and thyroid peroxidase (TPO) antibodies are positive in about 90% of patients with Riedel thyroiditis. In rare instances, it can accompany Graves disease or subacute thyroiditis.

Ultrasonography (USG) of the neck would show a hypoechoic hypovascular mass involving the extra-thyroidal tissues and occasionally encasing the carotid vessels. Elastography would reveal stiff inflammatory tissues consistent with fibrosis. On computed tomography (CT) scan the mass appears as hypodense and does not enhance on the administration of contrast. CT scan can assess the extra-thyroidal involvement more accurately than USG. Positron emission tomography (PET) scan shows intense uptake in the inflammatory areas of Riedel’ thyroiditis. PET scan is particularly useful in diagnosing remote areas of fibrosis which may occur in association with Riedel thyroiditis. Fine needle aspiration (FNA) of the mass is often inadequate but may show spindle cells, and fragments of fibrotic tissue. A definitive diagnosis can be made only by performing an open biopsy.[9][10]

Diagnostic criteria for Riedel thyroiditis are [11]:

  1. Extra-thyroidal extension of the inflammatory process.
  2. Presence of occlusive phlebitis
  3. Absence of granulomas, giant cells, lymphoid follicles or oncocytes.
  4. Absence of thyroid malignancy

Treatment / Management

There is no standardized treatment for Riedel thyroiditis due to the lack of outcome studies secondary to the rarity of the disease.

Surgery is indicated only to relieve compressive symptoms. Due to the lack of tissue planes between the fibrotic and normal thyroid tissue, surgical extirpation of the fibrotic tissue is rendered difficult. Unfortunately, complication rates as high as 39% have been reported even with limited surgical interventions. The consensus is to use minimal surgical intervention for relief of compressive symptoms.[1][7]

Glucocorticoids are the mainstay of medical treatment. The anti-inflammatory effects of glucocorticoids are most effective when used early in the disease process. There is no dosing guideline available however prednisone 15 mg to 100 mg daily has been shown to be effective in various reports. Response to the treatment is variable, with some cases showing dramatic improvement with a reversal of dysphonia and upper airway symptoms while others showed a complete lack of response. Nonresponse to glucocorticoids could be due to the increase in fibrosis seen in late disease as compared with early disease where inflammation is prominent.[12][13][14]

Tamoxifen is a selective estrogen receptor modulator (SERM) used in the treatment of Riedel thyroiditis and other systemic fibrosing disorders. It induces tumor growth factor beta (TGF-ß) which is a potent growth inhibitor. A dose of 10-20 mg, given alone or in combination with prednisone has been successful in decreasing the mass size.[15]

Mycophenolate mofetil is an immunosuppressive agent with anti-fibrotic properties which has therapeutic use in systemic fibrosis. It converts to mycophenolic acid which inhibits the antibody production from T and B lymphocytes. Levy et al. successfully used a combination of mycophenolate and prednisone, in a case of Riedel thyroiditis not responsive to tamoxifen and prednisone however further studies are needed to assess the role of mycophenolate in the treatment of Riedel thyroiditis.[16]

Differential Diagnosis

Riedel thyroiditis must be differentiated from other masses in the anterior neck which can infiltrate the surrounding extra-thyroidal tissues namely anaplastic thyroid carcinoma, thyroid lymphoma, and thyroid sarcoma. Other differentials include a fibrosing variant of Hashimoto thyroiditis which is characterized by high titers of anti-thyroid antibodies, the presence of Hurthle cells, lack of extra-thyroidal extension and phlebitis.[1][17][18][19]

Prognosis

The prognosis in Riedel thyroiditis is variable with mild cases being stable and aggressive cases being rapidly progressive. In general, there is a delay in diagnosis of up to 2 years due to the rarity and insidious nature of the disease. Mortality is for the most part due to tracheal compression. The disease-specific mortality rate has been reported to be around 6-10% in older studies. However, a recent study from Mayo clinic reported no increase in mortality over a follow-up period of 9.5 years and approximately 86% of patients had stable disease.[7][1]

Complications

The complications from Riedel thyroiditis are secondary to involvement of the extra-thyroidal tissues by the fibrotic process. Tracheal compression can result in dyspnea, stridor, and respiratory failure. Occlusion of the neck vessels can result in venous thrombosis. Involvement of the sympathetic trunk can result in Horner’s syndrome. About 14% have involvement of the parathyroid glands which results in hypoparathyroidism.

Riedel thyroiditis has also been observed to occur in association with other fibrotic disorders. Mediastinal fibrosis can present as superior vena caval (SVC) syndrome due to occlusion of the SVC. Retroperitoneal fibrosis can present with back or flank pain secondary to hydroureteronephrosis. Abdominal pain due to sclerosing cholangitis or pancreatic fibrosis may also be present. Exophthalmos due to the involvement of retro-orbital soft tissues can also be a presenting feature.

Pearls and Other Issues

  • Riedel thyroiditis is an extremely rare form of fibrosing thyroiditis. It can occur in isolation or association with other fibrosing disorders.
  • Clinically, it presents as a woody hard mass in the neck region.
  • Involvement of extrathyroidal structures in the neck is a characteristic feature and can result in dyspnea, dysphagia, stridor, and dysphonia.
  • Ultrasonography would show a hypoechoic hypovascular mass. CT and PET scans are useful for assessing extra-thyroidal extension and remote areas of fibrosis, respectively.
  • Establishing a diagnosis is by performing an open biopsy. Fibrous tissue with an eosinophilic infiltrate is characteristic of Riedel thyroiditis.
  • Surgery is challenging due to the lack of tissue planes between the fibrotic and normal tissue. Therefore, performing a limited extent surgery is for the relief of obstructive symptoms.
  • Medical treatment is with glucocorticoids and tamoxifen. There appears to be a potential role for mycophenolate mofetil which needs to be studied further.

Enhancing Healthcare Team Outcomes

Reidel thyroiditis is a rare disorder that often presents with vague signs and symptoms. The disorder is best managed by a multidisciplinary team because at present there are no universal guidelines on its management. The prognosis in Riedel thyroiditis is variable with mild cases being stable and aggressive cases being rapidly progressive. Mortality is for the most part due to tracheal compression. However, a recent study from Mayo clinic reported no increase in mortality over a follow-up period of 9.5 years and around 86% of patients had stable disease.[7][1]


References

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