Continuing Education Activity

Riedel thyroiditis (also known as Riedel struma, chronic invasive fibrous thyroiditis, or ligneous struma) is a rare fibrotic condition that involves the thyroid gland and often invades the surrounding structures. It most commonly presents with obstructive symptoms such as dyspnea, dysphagia, and hoarseness as the structures surrounding the thyroid are involved. It can also present with hypoparathyroidism, hypothyroidism, or Horner syndrome. This activity outlines the evaluation and treatment of Riedel thyroiditis and explains the part played by the interprofessional team in improving care for patients with this condition.

Objectives:

• Describe the pathophysiology of Reidel thyroiditis.
• Review the presentation of Reidel thyroiditis.
• Summarize the treatment options for Reidel thyroiditis.
• Outline the importance of collaboration and communication among the interprofessional team members to relieve obstructive symptoms and prevent the progression of the disease by using glucocorticoids which will improve outcomes for those with Riedel thyroiditis.

Introduction

Riedel fibrosing thyroiditis is a rare disease characterized by chronic inflammation and fibrosis of the thyroid gland. It is also known as Riedel struma, ligneous struma, or chronic invasive fibrous thyroiditis.[1] Classically, it presents as hypothyroidism with a "stone-like, hard-as-wood" non-tender thyroid gland.

Over time, the thyroid parenchyma and surrounding structures are replaced with dense fibrous tissue, leading to the destruction of the follicular cells of the thyroid gland. The fibrosis then extends to involve local structures, such as the airways. This causes obstructive symptoms such as dyspnea, dysphagia, and hoarseness due to airway compression[2].  It can also present with hypothyroidism, hypoparathyroidism, or Horner syndrome.

Diagnosis can be made clinically with a physical exam; however, a biopsy showing dense fibrous tissue with a characteristic eosinophilic infiltrate is needed for confirmation. Management includes both medical therapy and surgery for symptomatic relief. The mainstay of treatment is glucocorticoids which can cause a dramatic improvement in the symptoms. Alternatives include tamoxifen, mycophenolate, and radiation in situations where the patient is non-responsive to steroids.[1] Surgery is indicated when all other alternatives have failed or when the patient has symptoms of airway compression. 

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, the 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, and 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

Out of the disorders that cause thyroiditis, Riedel thyroiditis is extremely rare compared to Hashimoto thyroiditis or subacute granulomatous thyroiditis.  The estimated incidence is suggested to be 1.06 cases per 100,000 people.[6] Patients are more likely to be adult females from 30 to 50 years of age.[7]

Pathophysiology

The hallmark of Riedel thyroiditis is the replacement of thyroid tissue with dense fibrotic tissue. Fibrosis involves extra-thyroidal structures, including the trachea, parathyroid glands, neck musculature, laryngeal nerves, and blood vessels. This causes the thyroid to become immobile and fixed and is described as stone-hard or woody on palpation.[8][1]

Histopathology

Histologically, a dense hyalinized matrix with scanty colloid and a characteristic eosinophilic cell infiltrate can be seen. No malignant or giant cells are present. Fine-needle-aspiration has a limited value in the diagnosis of Riedel thyroiditis. However, the following characteristics may suggest the diagnosis of Riedel thyroiditis. The smear is significant for moderately cellular and revealed fragments of fibrous tissue and spindle cells dispersed and formed small clusters. The spindle cells vary from bland-appearing fibroblasts with a uniform pale nucleus to myofibroblasts-like cells. The plump myofibroblast-like cells are scattered in small groups of maximal three cells. The myofibroblast-like cells have abundant basophilic cytoplasm, plump oval nuclei, and visible nucleoli on Papanicolaou stain. Occasional large myofibroblast-like cells are unremarkable for mitoses or increased the nuclear to cytoplasmic ratio. Scattered inflammatory cells consisting of a mixed population of lymphocytes, plasma cells, and neutrophils are present. The background of the smears showed no necrosis or malignant diathesis. Neither germinal center cells nor Hurtle cells should be identified to support the diagnosis of a fibrosing variant of Hashimoto thyroiditis.[9]

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 the involvement of the retrobulbar tissues.

On examination, a hard mass is palpable in the anterior neck, which may be immobile when 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.[10][1][11]

Evaluation

Thyroid function tests may reveal hypothyroidism in about 74% of 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 with 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 areas of inflammation and 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.[12][13]

Diagnostic criteria for Riedel thyroiditis are [14]:

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 due to the rarity of the disease.

Surgery with subtotal or partial thyroidectomy 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 the relief of compressive symptoms.[1][10]

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 compared with early disease, where inflammation is prominent.[15][16][17]

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.[18]

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.[19]

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.

Anaplastic carcinoma is an undifferentiated malignant tumor usually seen in older individuals that can clinically mimic Reidel thyroiditis with dysphagia or tracheal compression symptoms. Key differences are those with anaplastic carcinoma are older than 70 to 80 years of age, while those with Reidel thyroiditis are younger women in their fifth decade of life, and biopsy or FNA show no malignant cells.  

Other differentials include a fibrosing variant of Hashimoto thyroiditis characterized by high titers of anti-thyroid antibodies, the presence of Hurthle cells, lack of extra-thyroidal extension, and phlebitis.[1][20][21][22]

Prognosis

This condition usually has a good prognosis. Mild disease can be stable for years but can also be aggressive and rapidly progressive after any insult.  

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 to 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.[10][1]

Complications

The complications from Riedel thyroiditis are secondary to the 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 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 in association with other fibrosing disorders.
• Clinically, it presents as a woody hard mass in the neck region.
• The 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 of 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. Due to its rarity, it can be slow to diagnose (Level 4, 5). Patient care can be enhanced by a team of physicians, nurses, pharmacists, and other health professionals.  Once diagnosed, the patient will need routine follow-up with either a primary care physician or an endocrinologist for routine laboratory studies, imaging, and physical exams to monitor for the progression of the disease.  If the patient develops symptoms of tracheal compression despite medical therapy, they will need to be referred to a surgeon for a partial or subtotal thyroidectomy.