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.

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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 caused by bacterial (espe- Postpartum Autoimmune Subacute Hyper, hypo, or < 5 percent High titer, persistent 5 to 7 percent of cially Streptococcus pyrogenes, Streptococcus both, then normal postpartum women aureus, or Streptococcus pneumoniae), fungal, Subacute lymphocytic Autoimmune Subacute Hyper, hypo, or < 5 percent Present, persistent 10 to 15 cases per mycobacterial, or parasitic infection of the both, then normal 100,000 persons thyroid. The thyroid gland generally is resis- Drug-induced tant to infection because of its rich blood Amiodarone Inflammation Acute or subacute Hyper or hypo Low Absent 10 percent supply, lymphatic drainage, high iodine and (Cordarone) hydrogen peroxide content, and encapsula- Interferon-alfa Inflammation Acute or subacute Hyper or hypo Low 5 to 10 percent 10 to 15 percent tion.3,4 Predisposing factors for suppurative (Infergen; Intron A, positive thyroiditis include congenital abnormalities Roferon-A, Rebetron such as persistent thyroglossal duct or piri- combination therapy) form sinus fistula, greater age, and immuno­ Interleukin-2 Inflammation Acute or subacute Hyper or hypo Low < 10 percent positive Undetermined 3,4 Lithium Autoimmune Acute or subacute Hyper then normal, Low 33 percent positive 13 cases per 100,000 suppression. Infection usually spreads to or low persons the thyroid from the adjacent structures directly or through the blood or lymphatic Riedel’s Fibrosis Chronic Normal or low Normal or low Present Undetermined system, or from a distant focus. Approxi- mately one half of patients with suppurative RAIU = radioactive iodine uptake; TPO = thyroid peroxidase; hyper = hyperthyroidism; hypo = hypothyroidism. thyroiditis have preexisting thyroid disease. *—May be present if patient has underlying Graves’ disease. Patients with suppurative thyroiditis com- monly present with acute unilateral anterior

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neck pain and erythema of the skin overly- antibiotics should be given, and surgical ing an exquisitely tender thyroid. Fever, drainage may be required. dysphagia, and dysphonia also are present. In the absence of preexisting thyroid disease, radiation-induced thyroiditis thyroid function most often is normal, but Approximately 1 percent of patients who have hyperthyroidism and hypothyroidism may radioactive iodine therapy for hyperthyroid- be present. The erythrocyte sedimentation ism develop radiation thyroiditis between rate is elevated, and the white blood cell five and 10 days after the procedure. The count generally shows a marked increase rapid destruction of the thyroid parenchyma with a left shift. Fine-needle aspiration of results in pain, tenderness, and an exacerba- the lesion with Gram stain and culture is tion of hyperthyroidism from the release of the most useful diagnostic test. Parenteral stored T4 and T3. A brief course of NSAIDs

Algorithm for the Diagnosis of Suspected Thyroiditis

Patient presents with suspected thyroiditis

Is there thyroid pain or tenderness?

No Yes

Is the patient receiving amiodarone Is there a history of (Cordarone), interferon-alfa radiation or trauma? (Infergen; Intron A, Roferon-A, Rebetron combination therapy), interleukin-2, or lithium? No Yes

Is the onset acute? Radiation or No Yes traumatic thyroiditis Is the patient postpartum? Drug-induced No Yes

RAIU at 24 hours No Yes

Hashimoto’s disease or TSH subacute lymphocytic thyroiditis Low Normal

Normal or high Low Subacute granulomatous Possible thyroiditis suppurative thyroiditis Postpartum thyroiditis RAIU at 24 hours or TSI or Hashimoto’s disease

Low High

Painless postpartum Graves’ disease thyroiditis

Figure 1. Algorithm for the evaluation of patients with suspected thyroiditis. (RAIU = radioactive iodine uptake; TSH = thyroid-stimulating hormone; TSI = thyroid-stimulating immunoglobulins.)

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or, rarely, prednisone in dosages of 40 to are associated with increased risk of hypo- 60 mg per day may be used to alleviate pain; thyroidism, the latter possibly because of a beta blocker often is required to block the thiocyanates in cigarette smoke. peripheral effects of the thyroid hormone. Circulating levels of antithyroid peroxi- The gland eventually undergoes extensive dase antibodies, usually in high titers, are fibrosis in approximately six to 18 weeks.5 a hallmark of Hashimoto’s disease and are Thyroiditis also may develop from radia- present in 90 to 95 percent of individuals tion therapy for lymphoma or head and with this diagnosis. Antithyroglobulin anti- neck cancers. The major risk factors for bodies are not as sensitive for the diagnosis, developing thyroid damage after exter- being present in only 20 to 50 percent of nal irradiation are high-dose irradiation, patients.3 TSH-receptor–blocking antibod- younger age, female sex, and preexisting ies may be present and may cause transient hypothyroidism.6,7 hypothyroidism in infants born to mothers with Hashimoto’s disease. RAIU may be trauma-induced thyroiditis low, normal, or high, and is not necessary Transient thyroiditis with pain and tender- for diagnosis. ness has been noted on rare occasions fol- The indications for treatment of Hashi- lowing physical trauma to the thyroid. Low moto’s disease are goiter or clinical hypothy- RAIU with normal or elevated T4 levels and roidism. There is conflicting normal or suppressed TSH levels may be evidence regarding the treat- As subacute granuloma- 8 found ; however, these findings add little ment of patients who have mild tous thyroiditis progresses practical information to the clinical history subclinical hypothyroidism there may be a “march” and, because the effects of trauma are self- with TSH levels between 4.5 of tenderness across the limited, work-up is not necessary. and 10 mcU per mL (4.5 and 10 gland, with new parts mU per L). The American Thy- of the thyroid becoming Painless Thyroiditis roid Association11 recommends hashimoto’s disease treatment, whereas a later con- painful and tender as pre- Hashimoto’s disease (also known as chronic sensus panel found insufficient viously involved portions lymphocytic thyroiditis or chronic auto­ data to recommend treatment, become less so. immune thyroiditis) is an autoimmune con- although finding it reasonable dition characterized by the infiltration of the for patients with TSH levels greater than thyroid by lymphocytes and the formation 10 mcU per mL.12 An elevated TSH level in of Askanazy (Hürthle) cells. It is the most a woman who is pregnant or attempting to common inflammatory disorder of the thy- become pregnant is a clear indication for roid in the United States. About seven times thyroid hormone replacement.13 more women are affected than men, with the The appearance of a rapidly growing nod- peak incidence occurring between 40 and ule should raise the suspicion of a primary 60 years of age.9 Around 90 percent of patients thyroid lymphoma, because this is 60 to have a symmetrical, diffusely enlarged gland 80 times more likely in patients with Hashi- with a firm, pebbly texture, whereas around moto’s disease than in the general popula- 10 percent have thyroid atrophy. The goiter tion.14 Hashimoto’s disease also is associated, usually is painless, although there have been although less strongly, with papillary car- reports of patients with prolonged, painful cinoma.15 A fine-needle aspiration of the Hashimoto’s disease.10 nodule should be evaluated for histologic The course of the disease varies. Patients diagnosis. Hashimoto’s disease may coexist may have normal thyroid function, frank with Graves’ disease,9 and may be associated clinical primary hypothyroidism associated with other autoimmune conditions such as with low free T4 and high TSH concentra- Addison’s disease, pernicious anemia, diabe- tions, or subclinical hypothyroidism with tes, vitiligo, and premature ovarian failure. normal free T4 and elevated TSH levels. Patients must therefore be monitored for the High iodide intake and cigarette smoking development of these conditions.

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painless postpartum thyroiditis Treatment of hyperthyroidism involves Approximately 5 to 7 percent of women who symptom relief with beta blockers, although give birth develop postpartum thyroiditis, caution is necessary in breastfeeding moth- probably as a result of an autoimmune pro- ers because beta blockers are secreted into cess.16 Approximately one half of these patients breast milk. Thioamides are not useful have a family history of autoimmune thyroid because the cause of hyperthyroidism is the disease, and there is an association with release of preformed hormone secondary to human leukocyte antigens HLA-DRB, -DR4, destruction of the gland. For symptomatic and -DR5, as in Hashimoto’s disease.16 hypothyroidism, levothyroxine may be initi- Most patients present with a painless, ated; treatment may be tapered and stopped small, nontender, firm goiter within two to after six to nine months. six months after delivery. Hypothyroidism Women with euthyroidism who have occurs in 43 percent of patients before the antithyroid peroxidase antibodies have a recovery phase, hyperthyroidism in 32 per- 25 percent risk of developing postpartum cent, and hyperthyroidism followed by hypo- thyroiditis; therefore, susceptible pregnant thyroidism in 25 percent.16 About one third of women—those with type 1 diabetes, a history patients with the hyperthyroid variant have of postpartum depression, or a strong family asymptomatic hyperthyroidism. Hyperthy- history of autoimmune thyroid disease— roidism usually occurs two to 10 months after should be screened for antithyroid peroxi- delivery, most commonly at three months, dase antibodies.16,18 Patients with postpartum with recovery taking place over the next two thyroiditis who have antithyroid peroxidase to three months. Hypothyroidism occurs antibodies have a 70 percent risk of recur- between two and 12 months rence following a subsequent pregnancy.18 after delivery, most commonly In 10 to 15 percent of at six months. Most patients subacute lymphocytic thyroiditis patients with subacute (80 percent) have normal thy- Subacute lymphocytic thyroiditis (also known granulomatous thyroiditis, roid function at one year. How- as silent sporadic thyroiditis or painless spo- hypothyroidism persists, ever, 30 to 50 percent of patients radic thyroiditis) is clinically and pathologi- requiring long-term levo- develop permanent hypothy- cally similar to postpartum thyroiditis but thyroxine therapy. roidism within nine years.16,17 occurs in the absence of pregnancy. It appears Factors predictive of perma- to be autoimmune in origin; the thyroid nent hypothyroidism include contains a lymphocytic infiltrate partially hypothyroidism during the acute phase of resembling Hashimoto’s disease but without postpartum thyroid disease, high levels of the fibrosis, Askanazy cells, and extensive antithyroid peroxidase antibodies, and a lymphoid follicle formation.19,20 Four times hypoechogenic ultrasound pattern.17 more women are affected than men, and the Elevated levels of antithyroid peroxi- risk is increased in persons who live in areas dase antibodies are found in 80 percent of of iodine sufficiency.3,18 patients, but the erythrocyte sedimentation About one half of patients with subacute rate typically is normal. It is important to lymphocytic thyroiditis present with a small distinguish painless postpartum thyroiditis goiter.20 Between 5 and 20 percent of patients from Graves’ disease occurring in the post- exhibit hyperthyroidism from release of pre- partum period. The presence of an audible formed T4 and T3, which may be followed by bruit over the gland, exophthalmos, hyper- hypothyroidism and then a return to nor- vascularity with increased blood flow seen mal in the majority of patients. The hyper- on Doppler ultrasonography, thyroid-stim- thyroid stage averages three to four months, ulating immunoglobulins in the serum, and and total duration of illness is less than one a high RAIU are characteristic of Graves’ year. About one half of patients have anti- disease but not of postpartum thyroiditis.5,16 thyroid peroxidase antibodies. Thyroid uptake and scan should not be per- Subacute lymphocytic thyroiditis is dis- formed in women who are breastfeeding. tinguished from subacute thyroiditis by the

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absence of thyroid pain and tenderness. It with some success.3,27,28 Tamoxifen response is differentiated from Graves’ disease by the may be mediated through the induction of lack of a thyroid thrill or bruit, ophthal- transforming growth factor–beta, a potent mopathy, pretibial myxedema, and thyroid- inhibitor of fibroblast growth.28 stimulating immunoglobulins, and by a low or absent rather than elevated RAIU. The Authors Treatment is similar to that of postpartum ARCHANA BINDRA, M.D., currently is a clinical endo- thyroiditis. crinologist in private practice on staff at San Joaquin Community Hospital in Bakersfield, Calif. She received drug-induced thyroiditis her medical degree at the King Edward Memorial Hospital Amiodarone (Cordarone), interferon-alfa in Mumbai, India, and completed a residency in internal medicine at the University of Southern California, Los (Infergen; Intron A, Roferon-A, Rebetron Angeles. While writing this article, Dr. Bindra was com- combination therapy), interleukin-2, and pleting a fellowship in endocrinology at Cedars-Sinai lithium may cause a destructive thyroiditis Medical Center, Los Angeles, Calif. with hyperthyroidism or hypothyroidism, GLENN D. BRAUNSTEIN, M.D., is chairman of the low RAIU, and variable presence of anti– Department of Medicine at Cedars-Sinai Medical Center thyroid peroxidase antibodies.21-25 Treatment and professor of medicine at the David Geffen School of Medicine at the University of California, Los Angeles is similar to that of subacute granuloma- (UCLA). He also holds the James R. Klinenberg Chair tous or lymphocytic thyroiditis. The thyroid in Medicine at Cedars-Sinai. Dr. Braunstein graduated abnormalities usually resolve with discon- from the University of California, San Francisco, School tinuation of the drug responsible. of Medicine, and completed his residency in internal medicine and endocrinology fellowship at the Peter Bent Brigham Hospital in Boston (now the Brigham and riedel’s thyroiditis Women’s Hospital), the National Institutes of Health in Riedel’s thyroiditis (also known as fibrous Bethesda, and at Harbor General Hospital-UCLA. thyroiditis) is a rare condition characterized Address correspondence to Glenn D. Braunstein, M.D., by an extensive fibrotic process of unknown Cedars-Sinai Medical Center, Room 2119, 8700 Beverly etiology involving the thyroid and adjacent Blvd., Los Angeles, CA 90048 (e-mail: braunstein@cshs. org). Reprints are not available from the authors. structures. It may be associated with a dif- fuse fibrotic process affecting multiple tis- Author disclosure: Nothing to disclose. sues (idiopathic multifocal fibrosclerosis)26 and may be unilateral or diffuse. Four times REFERENCES more women are affected than men, with the 1. Fatourechi V, Aniszewski JP, Fatourechi GZ, Atkinson highest prevalence occurring in individuals EJ, Jacobsen SJ. Clinical features and outcome of subacute thyroiditis in an incidence cohort: Olmstead between 30 and 60 years of age. County, Minnesota, study. J Clin Endocrinol Metab Patients present with a rock-hard, wood- 2003;88:2100-5. like, fixed, painless goiter, often accompa- 2. Martino E, Buratti L, Bartalena L, Mariotti S, Cupini C, nied by symptoms of esophageal or tracheal Aghini-Lombardi F, et al. High prevalence of subacute thyroiditis during summer season in Italy. J Endocrinol 27 compression. Thus, common complaints Invest 1987;10:321-3. are stridor, dyspnea, a suffocating feeling, 3. Pearce EN, Farwell AP, Braverman LE. Thyroid- dysphagia, and hoarseness. Approximately itis [published correction appears in N Engl J Med one third of patients have hypothyroidism 2003;349:620]. N Engl J Med 2003;348:2646-55. 4. Fukata S, Miyauchi A, Kuma K, Sugawara M. Acute sup- because of extensive replacement of the gland purative thyroiditis caused by an infected piriform sinus by scar tissue. Antithyroid peroxidase anti- fistula with thyrotoxicosis. Thyroid 2002;12:175-8. bodies are present in two thirds of patients, 5. Ginsberg J. Diagnosis and management of Graves’ and RAIU typically is low. Open biopsy or disease. CMAJ 2003;168:575-85. 6. van Santen HM, Vulsma T, Dijkgraaf MG, Blumer RM, resection is necessary for a definitive diagno- Heinen R, Jaspers MW, et al. No damaging effect of sis because fine-needle aspiration may have chemotherapy in addition to radiotherapy on the thy- a poor yield. Surgery to relieve tracheal and roid axis in young adult survivors of childhood cancer. J esophageal compression is the mainstay of Clin Endocrinol Metab 2003;88:3657-63. 7. Jereczek-Fossa BA, Alterio D, Jassem J, Gibelli B, Tradati treatment. Steroids, methotrexate, and tamox- N, Orecchia R. Radiotherapy-induced thyroid disorders. ifen (Nolvadex) have been used as treatment, Cancer Treat Rev 2004;30:369-84.

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8. Dickey RA, Parker JL, Feld S. Discovery of unsuspected 18. Muller AF, Drexhage HA, Berghout A. Postpartum thy- thyroid pathologic conditions after trauma to the ante- roiditis and autoimmune thyroiditis in women of child- rior neck area attributable to a motor vehicle accident: bearing age: recent insights and consequences for ante- relationship to use of the shoulder harness. Endocr natal and postnatal care. Endocr Rev 2001;22:605-30. Pract 2003;9:5-11. 19. Volpe R. Is silent thyroiditis an autoimmune disease? 9. Dayan CM, Daniels GH. Chronic autoimmune thyroid- Arch Intern Med 1988;148:1907-8. itis. N Engl J Med 1996;335:99-107. 20. Woolf PD. Transient painless thyroiditis with hyperthy- 10. Kon YC, DeGroot LJ. Painful Hashimoto’s thyroiditis as roidism: a variant of lymphocytic thyroiditis? Endocr an indication for thyroidectomy: clinical characteristics Rev 1980;1:411-20. and outcome in seven patients. J Clin Endocrinol Metab 21. Martino E, Bartalena L, Bogazzi F, Braverman LE. The 2003;88:2667-72. effects of amiodarone on the thyroid. Endocr Rev 11. Gharib H, Tuttle RM, Baskin HJ, Fish LH, Singer PA, 2001;22:240-54. McDermott MT. Subclinical thyroid dysfunction: a 22. Carella C, Mazziotti G, Amato G, Braverman LE, Roti joint statement on management from the American E. Clinical review 169: interferon-alpha-related thyroid Association of Clinical Endocrinologists, the American disease: pathophysiological, epidemiological, and clini- Thyroid Association, and the Endocrine Society. J Clin cal aspects. J Clin Endocrinol Metab 2004;89:3656-61. Endocrinol Metab 2005;90:581-5. 23. Schuppert F, Rambusch E, Kirchner H, Atzpodien J, 12. Surks MI, Ortiz E, Daniels GH, Sawin CT, Col NF, Cobin Kohn LD, von zur Muhlen A. Patients treated with inter- RH, et al. Subclinical thyroid disease: scientific review feron-alpha, interferon-beta, and interleukin-2 have a and guidelines for diagnosis and management. JAMA different thyroid autoantibody pattern than patients 2004;291:228-38. suffering from endogenous autoimmune thyroid dis- 13. Casey BM, Dashe JS, Wells CE, McIntire DD, Byrd W, ease. Thyroid 1997;7:837-42. Leveno KJ, et al. Subclinical hypothyroidism and preg- 24. Miller KK, Daniels GH. Association between lithium nancy outcomes. Obstet Gynecol 2005;105:239-45. use and thyrotoxicosis caused by silent thyroiditis. Clin 14. Thieblemont C, Mayer A, Dumontet C, Barbier Y, Cal- Endocrinol 2001;55:501-8. let-Bauchu E, Felman P, et al. Primary thyroid lymphoma 25. Dang AH, Hershman JM. Lithium-associated thyroiditis. is a heterogenous disease. J Clin Endocrinol Metab Endocr Pract 2002;8:232-6. 2002;87:105-11. 26. Yasmeen T, Khan S, Patel SG, Reeves WA, Gonsch 15. Prasad ML, Huang Y, Pellegata NS, de la Chapelle A, FA, de Bustros A, et al. Clinical case seminar: Riedel’s Kloos RT. Hashimoto’s thyroiditis with papillary thyroid thyroiditis: report of a case complicated by spontane- carcinoma (PTC)-like nuclear alterations express molec- ous hypoparathyroidism, recurrent laryngeal nerve ular markers of PTC. Histopathology 2004;45:39-46. injury, and Horner’s syndrome. J Clin Endocrinol Metab 16. Stagnaro-Green A. Clincial review 152: postpartum 2002;87:3543-7. thyroiditis. J Clin Endocrinol Metab 2002;87:4042-7. 27. Vaidya B, Harris PE, Barrett P, Kendall-Taylor P. Cortico- 17. Premawardhana LD, Parkes AB, Ammari F, John R, Darke steroid therapy in Riedel’s thyroiditis. Postgrad Med J C, Adams H, et al. Postpartum thyroiditis and long-term 1997;73:817-9. thyroid status: prognostic influence of thyroid per- 28. Pritchyk K, Newkirk K, Garlich P, Deeb Z. Tamoxifen oxidase antibodies and ultrasound echogenicity. J Clin therapy for Riedel’s thyroiditis. Laryngoscope 2004; Endocrinol Metab 2000;85:71-5. 114:1758-60.

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