Thyroiditis ARCHANA BINDRA, M.D., and GLENN D. BRAUNSTEIN, M.D. Cedars-Sinai Medical Center, Los Angeles, California Thyroiditis is an inflammation of the thyroid gland that may be painful and tender when caused by infection, radiation, or trauma, or painless when caused by autoimmune conditions, medications, or an idiopathic fibrotic process. The most common forms are Hashimoto’s disease, subacute gran- ulomatous thyroiditis, postpartum thyroiditis, subacute lymphocytic thyroiditis, and drug-induced thyroiditis (caused by amiodarone, interferon-alfa, interleukin-2, or lithium). Patients may have euthyroidism, hyperthyroidism, or hypothyroidism, or may evolve from one condition to another over time. Diagnosis is by clinical context and findings, including the presence or absence of pain, tenderness, and autoantibodies. In addition, the degree of radioactive iodine uptake by the gland is reduced in most patients with viral, radiation-induced, traumatic, autoimmune, or drug-induced inflammation of the thyroid. Treatment primarily is directed at symptomatic relief of thyroid pain and tenderness, if present, and restoration of euthyroidism. (Am Fam Physician 2006;73:1769-76. Copyright © 2006 American Academy of Family Physicians.) hyroiditis is an inflammation of the myalgias, pharyngitis, low-grade fever, and thyroid gland that has several eti- fatigue, followed by a tender, diffuse goiter ologies and can be associated with and neck pain that often radiates up to the normal, elevated, or depressed thy- ear. As the disease progresses there may be a T roid function, often with evolution from one “march” of tenderness across the gland, with condition to another. The differentiation is new parts of the thyroid becoming painful based primarily on the clinical setting, rapid- and tender as previously involved portions ity of symptom onset, family history, and become less so. presence or absence of prodromal symptoms Hyperthyroidism is seen in one half of and neck pain. Although there is consider- affected individuals; it occurs when acti- able overlap, the various forms of thyroiditis vated cytotoxic T lymphocytes damage can be divided into those associated with the thyroid follicular cells, resulting in the thyroid pain and tenderness, and those that unregulated release of large amounts of thy- are painless (Table 1). An algorithm summa- roxine (T4) and triiodothyronine (T3) into rizing the diagnosis of suspected thyroiditis is the circulation. This process usually is tran- provided in Figure 1. sient, lasting three to six weeks and ceasing when the thyroid stores are exhausted. A Thyroiditis with Pain and Tenderness triphasic sequence commonly is observed, SUBACUTE GRANULOMATOUS THYROIDITIS in which patients have an initial phase of Subacute granulomatous thyroiditis (also hyperthyroidism accompanied by elevated known as giant cell thyroiditis, subacute free T4 and suppressed thyroid-stimulating thyroiditis, or de Quervain’s thyroiditis) is hormone (TSH) levels, followed by a phase 1 the most common cause of thyroid pain. It of hypothyroidism with low free T4 and high affects four times more women than men, and TSH levels, which may last weeks or up to most often occurs at 40 to 50 years of age.1 six months. Patients usually return to euthy- Subacute granulomatous thyroiditis usually roidism within six to 12 months. However, in is attributed to a viral infection. The summer 10 to 15 percent of patients, hypothyroidism peak incidence of thyroiditis coincides with persists, requiring long-term levothyroxine the peak incidences of coxsackievirus groups therapy.1,3 During transition from hyper- A and B and echovirus infections.2 thyroidism to hypothyroidism, low TSH and Symptoms and signs of subacute granu- free T4 levels may be found, which may be lomatous thyroiditis include a prodrome of mistaken for central hypothyroidism. May 15, 2006 ◆ Volume 73, Number 10 www.aafp.org/afp American Family Physician 1769 Downloaded from the American Family Physician Web site at www.aafp.org/afp. Copyright© 2006 American Academy of Family Physicians. For the private, noncommercial use of one individual user of the Web site. All other rights reserved. Contact [email protected] for copyright questions and/or permission requests. Thyroiditis SORT: KEY RECOMMENDATIONS FOR PRACTICE Evidence Clinical recommendation rating References Prednisone (40 to 60 mg daily) is recommended for patients with C 1 subacute thyroiditis when nonsteroidal anti-inflammatory drugs fail to provide pain relief. Treatment for subclinical hypothyroidism may be initiated in patients B 11, 12 with a thyroid-stimulating hormone level greater than 10 mcU per mL (10 mU per L). Thyroid hormone replacement should be initiated in women with an B 13 elevated thyroid-stimulating hormone level who are pregnant or attempting to become pregnant. Screening for antithyroid peroxidase antibodies should be considered B 16, 18 in women who are at high risk and are pregnant. A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evi- dence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, see page 1687 or http://www.aafp.org/afpsort.xml. TABLE 1 Types of Thyroiditis Type Cause Time course Thyroid function RAIU at 24 hours Anti-TPO antibodies Prevalence or incidence Painful Subacute granulomatous Infection Subacute Hyper, hypo, or < 5 percent Low or absent titer Four to five cases per (viral) both, then normal 100,000 persons Suppurative Infection Acute (nonbacterial Normal Normal Absent Undetermined but (nonviral) may be subacute) very rare Radiation or trauma Destruction Acute Hyper, hypo, or < 5 percent Absent* 1 percent of those of thyroid normal receiving 131I for Graves’ parenchyma disease Painless Hashimoto’s disease Autoimmune Chronic Normal or hypo Normal or low High titer, persistent 5 to 10 percent Postpartum Autoimmune Subacute Hyper, hypo, or < 5 percent High titer, persistent 5 to 7 percent of both, then normal postpartum women Subacute lymphocytic Autoimmune Subacute Hyper, hypo, or < 5 percent Present, persistent 10 to 15 cases per both, then normal 100,000 persons Drug-induced Amiodarone Inflammation Acute or subacute Hyper or hypo Low Absent 10 percent (Cordarone) Interferon-alfa Inflammation Acute or subacute Hyper or hypo Low 5 to 10 percent 10 to 15 percent (Infergen; Intron A, positive Roferon-A, Rebetron combination therapy) Interleukin-2 Inflammation Acute or subacute Hyper or hypo Low < 10 percent positive Undetermined Lithium Autoimmune Acute or subacute Hyper then normal, Low 33 percent positive 13 cases per 100,000 or low persons Riedel’s Fibrosis Chronic Normal or low Normal or low Present Undetermined RAIU = radioactive iodine uptake; TPO = thyroid peroxidase; hyper = hyperthyroidism; hypo = hypothyroidism. *—May be present if patient has underlying Graves’ disease. 1770 American Family Physician www.aafp.org/afp Volume 73, Number 10 ◆ May 15, 2006 Thyroiditis Other findings of subacute granuloma- thrill or bruit from the hypervascularity; tous thyroiditis are an elevated erythro- this does not occur in persons with sub- cyte sedimentation rate (often greater than acute thyroiditis. These differences in vas- 50 mm per hour), elevated C-reactive protein cularity also may be shown by Doppler level, mild anemia, and slight leukocytosis. ultrasonography. In patients with subacute Levels of antithyroid peroxidase and antithy- thyroiditis, the radioactive iodine uptake roglobulin antibodies generally are normal. (RAIU) at 24 hours is low (i.e., less than Hyperthyroidism from subacute thy- 5 percent), whereas in those with Graves’ roiditis must be differentiated from that disease it is elevated. found with Graves’ disease. Exophthalmos Treatment for subacute granulomatous and pretibial myxedema are characteris- thyroiditis consists of relieving the thyroid tics of Graves’ disease but are not found pain and tenderness with nonsteroidal anti- with subacute thyroiditis. The thyroid in inflammatory drugs (NSAIDs). The median patients with Graves’ disease may have a time from start of therapy to complete alle- viation of pain is five weeks.1 If no improve- ment occurs within one week, prednisone TABLE 1 may be given in a dosage of 40 to 60 mg daily Types of Thyroiditis tapered to complete discontinuation over four to six weeks. Type Cause Time course Thyroid function RAIU at 24 hours Anti-TPO antibodies Prevalence or incidence Although steroids provide complete pain Painful relief at a median of 48 hours, they do not Subacute granulomatous Infection Subacute Hyper, hypo, or < 5 percent Low or absent titer Four to five cases per prevent early- or late-onset thyroid dysfunc- 1 (viral) both, then normal 100,000 persons tion. Symptoms of hyperthyroidism are treated with beta blockers such as proprano- Suppurative Infection Acute (nonbacterial Normal Normal Absent Undetermined but lol (Inderal) or atenolol (Tenormin) until (nonviral) may be subacute) very rare the free T4 concentration returns to normal. Radiation or trauma Destruction Acute Hyper, hypo, or < 5 percent Absent* 1 percent of those Painful subacute thyroiditis recurs in about of thyroid normal receiving 131I for Graves’ 2 percent of individuals.1 parenchyma disease SUPPURATIVE THYROIDITIS Painless Hashimoto’s disease Autoimmune Chronic Normal or hypo Normal or low High titer, persistent 5 to 10 percent Suppurative thyroiditis is an extremely rare form of thyroiditis