A. Autoimmune Thyroiditis

Several clinical entities are classified as autoimmune thyroiditis, including chronic lymphocytic thyroiditis, postpartum thyroiditis, and painless (silent) sporadic subacute thyroiditis. Dietary iodine supplementation (especially when excessive) and certain medications can cause autoimmune thyroiditis. The incidence of autoimmune thyroiditis varies by kindred, race, and sex. It is commonly familial. Elevated serum levels of antithyroid antibodies are detectable in the general population in 3% of men and 13% of women. Among United States adults, elevated levels of antithyroid antibodies are found in 14.3% of those who self-identify as White, 10.9% as Latino/a, and 5.3% as Black. Women over the age of 60 years have a 25% incidence of elevated serum levels of antithyroid antibodies, yet thyroid dysfunction develops in only a small subset of such individuals. However, 1% of the population has serum antithyroid antibody titers greater than 1:640, and they are at particular risk for thyroid dysfunction. Subclinical thyroiditis is extremely common; autopsy series have found focal thyroiditis in 40% of women and 20% of men. The humoral autoimmunity of autoimmune thyroiditis differs from that of Graves disease, where thyroid-stimulating immunoglobulins (TSI) bind to the TSH receptor in thyroid cell membranes and stimulate the gland to hyperfunction.

Childhood or occupational exposure to head-neck external beam radiation increases the lifetime risk of autoimmune thyroiditis. Women with gonadal dysgenesis (Turner syndrome) have a 15% incidence of thyroiditis by age 40 years.

B. Painful Subacute Thyroiditis

Also called de Quervain thyroiditis, granulomatous thyroiditis, and giant cell thyroiditis, painful subacute thyroiditis is relatively common. Multinucleated giant cells are found on histology in the characteristically tender thyroid gland. Like painless subacute thyroiditis, most affected patients have transient hyperthyroidism, followed by hypothyroidism. Painful subacute thyroiditis is typically associated with viral upper respiratory infection (including COVID-19) and may follow vaccinations, including SARS-CoV-2. Some patients also have antithyroid antibodies. Its incidence peaks in the summer to early autumn. It affects both sexes, but over 75% are middle-aged women. Subacute thyroiditis can also be a sequela of a drug-induced hypersensitivity syndrome.

C. Infectious (Suppurative) Thyroiditis

Infectious thyroiditis is rare among immunocompetent patients, since the thyroid is resistant to infection due to its vasculature, encapsulation, and high iodine content. Congenital pyriform sinus fistulas are a cause for recurrent infectious thyroiditis. It is usually bacterial but mycobacterial, fungal, and parasitic infections can occur, particularly in immunosuppressed individuals. In affected patients who are appropriately treated, when immunosuppression is reduced, the patient may experience an immune reconstitution inflammatory syndrome (IRIS) from residual antigens triggering the normal immune response.

D. Igg4-Related (Riedel) Thyroiditis

IgG₄-related thyroiditis, also called Riedel thyroiditis, invasive fibrous thyroiditis, Riedel struma, woody thyroiditis, ligneous thyroiditis, and invasive thyroiditis, is the rarest form of thyroiditis. It is found most frequently in middle-aged or older women and is usually part of a multifocal systemic fibrosis syndrome. It may occur as a thyroid manifestation of IgG₄-related systemic disease (see Part 22).

A. Symptoms and Signs

In autoimmune thyroiditis, the thyroid gland may be diffusely enlarged, firm, and finely nodular but is frequently not palpable. One thyroid lobe may be asymmetrically enlarged, raising concerns about neoplasm. Although patients may report neck tightness, pain and tenderness are not usually present. Other patients have no palpable goiter and no neck symptoms. The thyroid is fibrotic and atrophic in about 10% of cases, particularly in older women.

Symptoms and signs are mostly related to levels of thyroid hormone. Affected patients may have combinations of hyperthyroidism and hypothyroidism. For example, a patient with hypothyroidism might later develop hyperthyroidism that can wax and wane. Depression and chronic fatigue are more common, even after correction of hypothyroidism.

About one-third of patients have mild dry mouth (xerostomia) or dry eyes (keratoconjunctivitis sicca) related to Sjogren syndrome. Associated myasthenia gravis is usually of mild severity, mainly affecting the extraocular muscles and having a relatively low incidence of detectable AChR Ab or thymic disease. Associated celiac disease or gluten intolerance can produce fatigue or depression, sometimes in the absence of GI symptoms.

Postpartum thyroiditis is typically manifested by hyperthyroidism that begins 1-6 months after delivery and persists for only 1-2 months. Then, hypothyroidism tends to develop beginning 4-8 months after delivery.

In painless sporadic thyroiditis, thyrotoxic symptoms are usually mild; a small, nontender goiter may be palpated in about 50% of patients. The course is similar to postpartum thyroiditis.

Painful subacute thyroiditis presents with an acute, usually painful enlargement of the thyroid gland, often with dysphagia. About 38% of patients have one thyroid lobe involved, while 62% have both lobes involved. Those with bilateral involvement are likely to be more hyperthyroid. The majority of patients experience pain that may radiate to the ears, jaw, or upper chest. Patients usually have a low-grade fever and fatigue. The manifestations may persist for weeks or months. Thyrotoxicosis develops in 50% of affected patients and tends to last for several weeks. Subsequently, hypothyroidism develops that lasts 4-6 months. Normal thyroid function typically returns within 12 months, but persistent hypothyroidism develops in 5% of patients.

Infectious suppurative thyroiditis patients usually are febrile and have severe pain, tenderness, redness, and fluctuation in the region of the thyroid gland. In IgG₄-related thyroiditis, thyroid enlargement is often asymmetric; the gland is stony hard and adherent to the neck structures, causing signs of compression and invasion, including dysphagia, dyspnea, pain, and hoarseness. Related conditions include retroperitoneal fibrosis, fibrosing mediastinitis, sclerosing cervicitis, subretinal fibrosis, and sclerosing cholangitis.

B. Laboratory Findings

In autoimmune thyroiditis (including postpartum thyroiditis), there are usually increased circulating levels of the antithyroid antibodies TPO Ab (90%) or Tg Ab (40%). However, 5% of patients have no detectable antithyroid antibodies. Most patients with thyroiditis caused by immune checkpoint inhibitors have no detectable antithyroid antibodies. Antithyroid antibodies decline during pregnancy and are often undetectable in the third trimester. Once autoimmune thyroiditis has been diagnosed, monitoring of antibody levels is not helpful. If autoimmune thyroiditis leads to inadequate thyroid hormone release, the serum TSH level is elevated and thyroid hormone levels may be normal or decreased (hypothyroidism). Autoimmune thyroiditis may also lead to passive release of stored thyroid hormones, resulting in hyperthyroidism increased serum FT₄ levels that are proportionally higher than T₃ levels and suppressed TSH levels. Because T₄ is less active than T₃, the hyperthyroidism seen in autoimmune thyroiditis is usually less severe than with Graves disease.

Patients with autoimmune thyroiditis have a 15% incidence of having serum IgA tissue transglutaminase (tTG) antibody and at least 5% have clinically significant celiac disease.

In painful subacute thyroiditis, the ESR is markedly elevated while antithyroid antibody titers are low, distinguishing it from autoimmune thyroiditis. Subacute thyroiditis may result in passive release of stored thyroid hormones, resulting in hyperthyroidism. In infectious thyroiditis, both the leukocyte count and ESR are usually elevated.

C. Imaging

Ultrasound typically shows diffuse heterogeneous thyroid density and reduced echogenicity. It is useful to distinguish autoimmune thyroiditis from multinodular goiter, thyroid nodules that are suspicious for malignancy, and Graves disease. In thyroiditis, vascularity is reduced or normal, whereas in Graves disease, the thyroid gland is hypervascular.

Radioiodine (RAI) uptake and scan can help distinguish thyroiditis from Graves disease; painful subacute thyroiditis exhibits very low RAI uptake. RAI uptake may be normal or high with uneven uptake in chronic autoimmune thyroiditis (euthyroid or hypothyroid); CT or MRI is not useful in diagnosis.

[¹⁸ F] Fluorodeoxyglucose positron emission tomography (¹⁸ FDG-PET) scanning frequently shows diffuse thyroid uptake of isotope in cases of thyroiditis. In fact, of ¹⁸ FDG-PET scans done for any reason, about 3% show such uptake. However, discrete nodular areas of ¹⁸ FDG-PET uptake within the thyroid have a 50% chance of being malignant.

D. Fine-Needle Aspiration Cytology

Patients with autoimmune thyroiditis who have a thyroid nodule should have an ultrasound-guided FNA biopsy, since the risk of papillary thyroid cancer is about 8% in such nodules. When infectious (suppurative) thyroiditis is suspected, an FNA biopsy with Gram stain and culture is required. FNA biopsy is usually not required for painful subacute thyroiditis but shows characteristic giant multinucleated cells.

A. Autoimmune Thyroiditis

If hypothyroidism is present, levothyroxine should be given in usual replacement doses (0.05-0.2 mg orally daily) (see Hypothyroidism & Myxedema, below). If hyperthyroidism is present, see Hyperthyroidism (Thyrotoxicosis), below.

In patients with a large goiter and normal or elevated serum TSH, an attempt is made to shrink the goiter with levothyroxine in doses sufficient to drive the serum TSH below the reference range while maintaining clinical euthyroidism. Suppressive doses of T₄ tend to shrink the goiter an average of 30% over 6 months. If the goiter does not regress, lower replacement doses of levothyroxine may be given. If the thyroid gland is only minimally enlarged and the patient is euthyroid, regular observation is indicated, since hypothyroidism may develop, often years later.

Dietary supplementation with selenium 200 mcg/day reduces serum levels of TPO Ab. In pregnant women with autoimmune thyroiditis, selenium supplementation at 83 mcg orally daily reduced the usual rebound postpartum increase in antithyroid antibodies without side effects on mother or newborn, but the clinical impact is not known.

In one study involving 21 patients with autoimmune thyroiditis and subclinical hypothyroidism, simvastatin (20 mg orally daily) improved thyroid function over 8 weeks, possibly by stimulating apoptosis of certain types of lymphocytes. The long-term effectiveness of simvastatin therapy on the course of autoimmune thyroiditis is unknown.

B. Painful Subacute Thyroiditis

All treatment is empiric and must be continued for several weeks. Recurrence is common. The drug of choice is aspirin (325-650 mg orally every 4-6 hours, which relieves pain and inflammation) or NSAIDs. For patients with severe pain, prednisone, 20 mg orally daily for about 2 weeks, can be effective. Thyrotoxic symptoms are treated with propranolol, 10-40 mg orally every 6 hours, or propranolol ER, 60-160 mg orally daily. Iodinated contrast agents cause a prompt fall in serum T₃ levels and a dramatic improvement in thyrotoxic symptoms. Ipodate sodium (Bilivist, Oragrafin) or iopanoic acid (Telepaque) is given orally in doses of 500 mg orally daily until serum FT₄ levels return to normal. Transient hypothyroidism is treated with T₄ (0.05-0.1 mg orally daily) if symptomatic.

C. Infectious (Suppurative) Thyroiditis

Treatment is with antibiotics and with surgical drainage when fluctuation is marked. Immunocompromised individuals are particularly at risk, and coccidioidomycosis thyroiditis has been reported. Surgical thyroidectomy may be required.

D. Igg4-Related (Riedel) Thyroiditis

The treatment of choice is tamoxifen, 20 mg orally twice daily, which must be continued for years. Tamoxifen can induce partial to complete remissions in most patients within 3-6 months. Its mode of action appears to be unrelated to its antiestrogen activity. Short-term corticosteroid treatment may be added for partial alleviation of pain and compression symptoms. Surgical decompression usually fails to permanently alleviate compression symptoms; surgery is difficult due to dense fibrous adhesions, making surgical complications more likely. Rituximab may be useful for Riedel thyroiditis that is refractory to tamoxifen and corticosteroids.