Other Causes of Thyroiditis

Thyroiditis is an inflammatory condition of the thyroid and has a number of causes, which may be focal or diffuse, and are often associated with either over- or underactivity of the thyroid.  The major types of thyroiditis are listed below:

  • Hashimoto's thyroiditis (follow link to separate webpage)
  • Subacute (nonsuppurative or 'de Quervain's') thyroiditis
  • Postpartum thyroiditis
  • Reidel's thyroiditis
  • Suppurative thyroiditis
  • Silent thyroiditis
  • Radiation thyroiditis
  • Amiodarone-induced thyroiditis

Hashimoto's thyroiditis is by far the most common cause of thyroiditis, and is dealt with on another webpage (follow the link above). The other less frequent causes of thyroiditis are dealt with on this webpage.

Subacute (Nonsuppurative, Giant Cell, or 'de Quervain's') Thyroiditis

Fig.1: De Quervain's thyroiditis cytology showing degenerative follicular cells and giant cellsThis condition was first described in 1904. It is caused by a viral infection, and is characterised by an enlarged tender thyroid with fever, muscle aches and malaise. It occurs typically in the 2nd to 5th decades of life.

Although viral particles have never been identified within the thyroid, episodes often follow upper respiratory tract infections caused by various viruses, including influenza, adenovirus, mumps, and coxsackievirus. It is unclear, however, whether the destructive thyroiditis in De Quervain patients is caused by direct viral infection of the gland or by the patient's response to the viral infection.

De Quervain's thyroiditis is not associated with autoimmune (Hashimoto's) thyroiditis. The transient presence of thyroid autoantibodies (eg, peroxidase and antithyroglobulin antibodies) has been noted in the acute phase of the disease, but this has been attributed to a virally induced autoimmune response and has not been implicated in the pathological process. 

There is a phase of thyroid overactivity, followed by underactivity, and finally the thyroid function returns to normal (euthyroid). In contrast to autoimmune thyroid disease, the immune response in subacute de Quervain's thyroiditis is not self-perpetuating; therefore, the process is limited, before resolving completely.

The diagnosis is made by the clinical findings and some investigations. During the acute phase the serum T3 and T4 concentrations are elevated, which then become subnormal in those patients who enter a hypothyroid phase. There is an increase in the CRP and ESR, and no uptake on the thyroid nuclear scan. Antibodies tend to be normal or only slightly raised.

FNA cytology if performed will show follicular cells with degenerative changes, lymphocytes and polymorphs, epithelioid and granulomatous giant cells (Fig. 1). FNA may provide unclear results in the acute stage, when atypical follicular cells may appear in the aspirate, mimicking thyroid carcinoma.

Ultrasound of the thyroid most commonly shows poorly defined regions of decreased echogenicity with decreased vascularity in the affected areas. These can be bilateral or unilateral. The thyroid gland size is mostly normal but can occasionally be enlarged or smaller in size. These US findings can be misleading, often showing quite bizarre appearances, and with the addition of enlarged reactive lymph nodes in the neck, mimicking the appearance of carcinoma. Nuclear scan tends to have a characteristic low uptake.

Treatment is directed at controlling the pain, and aspirin or NSAIDs are effective; rarely a short course of steroids is needed. In some patients who have a significant hypothyroid phase treatment with thyroxine is necessary, but rarely needs to extend beyond 3 to 4 months. There is no indication for surgery unless fine needle aspiration raises doubts about the diagnosis.

Postpartum Thyroiditis

This condition is a form of transient thyrotoxicosis that occurs in 5-10% of women who have had previous thyrotoxicosis and normal thyroid function during pregnancy. It is more common in women who have had other autoimmune diseases such as SLE or type 1 diabetes.

It occurs up to 12 months after delivery, but usually from eight weeks to four months postpartum. It has a variable severity, but typically the symptoms are mild, there are no eye signs, and the disease is self-limiting. The thyroid swelling is usually insignificant.

There are three courses that postpartum thyroiditis can follow:

  • a hyperthyroid phase followed by a return to normal thyroid function (20%)
  • a hypothyroid phase alone (50%)
  • a hyperthyroid phase followed by a hypothyroid phase (30%)

The cause is not entirely understood, but it appears to be an autoimmune disease, characterised by the presence of peroxidase antibodies in the circulation. As many as 30% to 50% of the women who have antiperoxidase antibody in their blood during the first trimester of pregnancy will develop postpartum thyroiditis. A low uptake on the thyroid scan (compared with the high uptake of Graves' disease) confirms the diagnosis, but the radioactive scan should be used with care in breast-feeding mothers.

Standard anti-thyroid treatment for the thyrotoxic phase is not necessary as the disease is self-limiting. Any toxic symptoms, such as tremors, palpitations or a rapid heart rate, are best controlled by a short course of beta-blockers. Treatment during the hypothyroid phase depends upon the severity of symptoms and how low the hormone levels become, but some women will require several months of thyroid hormone supplementation.

The disease may well recur following subsequent pregnancies, so close monitoring of thyroid function will be required.

Reidel's Thyroiditis

This is an exceptionally rare condition, first described by Bernhard Reidel in the German literature in 1896. The patient has a woody hard thyroid (ligneous thyroiditis). The main histological differential diagnosis is the fibrous form of Hashimoto's thyroiditis, which unlike Reidel's thyroiditis (RT) is limited to the thyroid. Reidel himself mistook his first case for malignant disease, attempting to resect the thyroid mass, but had to abandon the operation due to the involvement of adjacent structures.

The aetiology is unknown, but it is felt that the condition is not primarily a thyroid disease but rather a manifestation of the systemic disorder multifocal fibrosclerosis, or IgG4-related systemic disease (IgG4-RSD). Approximately one third of RT cases are associated with clinical findings of multifocal fibrosclerosis at the time of diagnosis.

These disorders have in common a preponderance of excess IgG4. The disorders are characterized by lymphoplasmacytic infiltrates containing IgG4-positive plasma cells. These infiltrates ultimately lead to fibrosis and elevated serum levels of IgG4.

This uncommon syndrome is characterized by fibrosis involving multiple organ systems. The manifestations outside the neck can include retroperitoneal fibrosis, mediastinal fibrosis, orbital pseudotumor, pulmonary fibrosis, sclerosing cholangitis, lacrimal gland fibrosis, and fibrous parotitis. RT may just be one manifestation of this multifocal disease and the histological changes in RT closely resemble those observed in multifocal fibrosclerosis.

Unlike most thyroid diseases it is only slightly more common in women than men. It may occur in children but more commonly in the adult and elderly patient. The soft tissues of the neck are invaded by fibrous tissue, which strangulates the neck structures, causing swallowing and breathing difficulties. The disease may be asymptomatic or if the fibrous reaction has destroyed the thyroid there may be frank hypothyroidism.

Open biopsy of the thyroid is usually necessary, since fine needle biopsy (FNA) is usually inadequate due to the woody nature of the thyroid.

Treatment is difficult, but a number of options are available. Systemic steroids (prednisolone) and tamoxifen can inhibit fibrogenesis, while newer agents such as rituximab and follistatin can both be effective. If there is hypothyroidism then thyroxine is indicated.

The surgical approach is the same as suggested by Reidel and is limited to freeing the windpipe, splitting the thyroid isthmus to permit the two lobes to fall laterally. The cut surface does not bleed. Extensive surgery or an attempt at thyroid removal is not necessary and can be horrendously difficult. Despite the invasive nature of the disease, if the windpipe is freed recurrent obstruction is unusual. Once the diagnosis is made some localised forms have an excellent prognosis.

Suppurative Thyroiditis

This is a rare condition, but more common if there is a pre-existing goitre. It can be caused by bacterial, fungal, mycobacterial and parasitic infections, as a result of trauma, haematogenous seeding from another site in the body, or direct extension from a deep-seated neck abscess. It can occur after tonsillitis, parotitis, otitis, or mastoid infection.

Presentation is with fever, pain, pharyngitis and dysphagia (difficulty swallowing), but thyroid function is normal. Ultrasound or CT will diagnose the condition, along with aspiration of pus sample; treatment is with IV broad-spectrum antibiotics and drainage of any collection of pus. 

Radiation Thyroiditis

When radioactive iodine is used to destroy the thyroid in patients with thyroid cancer the thyroid may become tender. A short course of steroids usually settles the symptoms.

Silent Thyroiditis

This is a painless form of sub-acute thyroiditis, similar to post partum thyroiditis but occurring in men and non-pregnant women. Its cause is unclear but many factors have been cited. Two outbreaks of silent thyroiditis in the USA are now known to be due to contamination of minced beef with thyroid tissue. This entity is now known as "hamburger thyrotoxicosis". 

The thyroid gland is small, the thyroid overactivity is usually mild and transient and there is little uptake on the thyroid scan. Patients with silent thyroiditis are often treated incorrectly with antithyroid drugs because the condition is mistaken for Graves’ disease. The use of antithyroid drugs is inappropriate because increased hormone production is not the cause of thyrotoxicosis in painless thyroiditis, but rather release of pre-formed thyroid hormone from cells damaged by inflammation. Treatment at most is a short course of beta-blockers to control the symptoms of transient overactivity. Very rarely the symptoms are so severe that a short course of steroids is indicated.

One very interesting form of silent thyroiditis is "palpation thyroiditis". Rough handling of the thyroid on clinical examination can cause significant structural changes with no thyroid hormone abnormalities. Often in the post-operative period following a parathyroidectomy there may be changes in the thyroid function and even frank transient thyrotoxicosis due to trauma to the thyroid.

Drug-induced Thyroiditis

Fig.2: Histology of amiodarone-induced thyroiditis with presence of foamy macrophages. (Picture: Justin Du Plessis)

There are a number of drugs that can induce thyroiditis: 

  • Amiodarone
  • Interferon (used in Hepatitis C & myelodysplasia)
  • Iodine-containing contrast
  • Lithium
  • Interleukin-2

Amiodarone is the most common form of drug-related thyroiditis. Besides causing thyrotoxicosis in patients with pre-existing thyroid disease (Type 1 amiodarone-induced thyrotoxicosis) the drug itself can cause thyroiditis in 5%–10% of users, typically after about 2 years of therapy (see also Thyrotoxicosis).

This Type 2 amiodarone-induced hyperthyroidism is the most common form in Australia. It is characterised by the release of pre-formed thyroid hormone from damaged cells and is treated by a course of steroids. It can be very difficult to treat however and thyroidectomy may have to be performed to gain control.

The histology of amiodarone-induced thyroiditis is characterised by the presence of foamy macrophages in the colloid (Fig. 2).