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Thyroiditis
Robert A. Baldor, MD, FAAFP
image BASICS
DESCRIPTION
Inflammation of the thyroid gland that may be painful or painless
  • Thyroiditis with thyroid pain
    • Subacute granulomatous thyroiditis (nonsuppurative thyroiditis, de Quervain thyroiditis, or giant cell thyroiditis): self-limited; viral URI prodrome, symptoms and signs of thyroid dysfunction (variable)
    • Infectious/suppurative thyroiditis
      • Bacterial, fungal, mycobacterial, or parasitic infection of the thyroid
      • Most commonly associated with Streptococcus pyogenes, Staphylococcus aureus, and Streptococcus pneumoniae
    • Radiation-induced thyroiditis: from radioactive iodine therapy (1%) or external irradiation for lymphoma and head/neck cancers
  • Thyroiditis with no thyroid pain
    • Hashimoto (autoimmune) thyroiditis (chronic lymphocytic thyroiditis): most common etiology of chronic hypothyroidism; autoimmune disease; 90% of patients with high-serum antithyroid peroxidase (TPO) antibodies
    • Postpartum thyroiditis: episode of thyrotoxicosis, hypothyroidism, or thyrotoxicosis followed by hypothyroidism in the 1st year postpartum or after spontaneous/induced abortion in women who were without clinically evident thyroid disease before pregnancy
    • Painless (silent) thyroiditis (subacute lymphocytic thyroiditis): mild hyperthyroidism, small painless goiter, and no Graves ophthalmopathy/pretibial myxedema
    • Riedel (fibrous) thyroiditis: rare inflammatory process involving the thyroid and surrounding cervical tissues; associated with various forms of systemic fibrosis; presents as a firm mass in the thyroid commonly associated with compressive symptoms (dyspnea, dysphagia, hoarseness, and aphonia) caused by local infiltration of the advancing fibrotic process with hypocalcemia and hypothyroidism
    • Drug-induced thyroiditis: interferon-&agr;, interleukin-2, amiodarone, or lithium
EPIDEMIOLOGY
  • Subacute granulomatous thyroiditis: most common cause of thyroid pain; peaks during summer; incidence: 3/100,000/year; female > male (4:1); peak age: 40 to 50 years
  • Suppurative thyroiditis: commonly seen with preexisting thyroid disease/immunocompromise
  • Hashimoto thyroiditis: peak age of onset, 30 to 50 years; can occur in children; primarily a disease of women; female > male (7:1)
  • Postpartum thyroiditis: Female only; occurs within 12 months of pregnancy in 8-11% of pregnancies; occurs in 25% with type 1 diabetes mellitus; incidence is affected by genetic influences and iodine intake.
  • Painless (silent) thyroiditis: female > male (4:1) with peak age 30 to 40 years; common in areas of iodine sufficiency
  • Reidel thyroiditis: female > male (4:1); highest prevalence age 30 to 60 years
ETIOLOGY AND PATHOPHYSIOLOGY
  • Hashimoto disease: Antithyroid antibodies may be produced in response to an environmental antigen and cross-react with thyroid proteins (molecular mimicry). Precipitating factors include infection, stress, sex steroids, pregnancy, iodine intake, and radiation exposure.
  • Subacute granulomatous thyroiditis: probably viral
  • Postpartum thyroiditis: autoimmunity-induced discharge of preformed hormone from the thyroid
  • Painless (silent) thyroiditis: autoimmune
Genetics
Autoimmune thyroiditis is associated with the CT60 polymorphism of cytotoxic T-cell lymphocyte-associated antigen 4. Also associated with HLA-DR4, -DR5, and -DR6 in whites
RISK FACTORS
  • Hashimoto disease: family history of thyroid/autoimmune disease, personal history of autoimmune disease (type 1 diabetes, celiac disease), high iodine intake, cigarette smoking, selenium deficiency
  • Subacute granulomatous thyroiditis: recent viral respiratory infection
  • Suppurative thyroiditis: congenital abnormalities (persistent thyroglossal duct/piriform sinus fistula), greater age, immunosuppression
  • Radiation-induced thyroiditis: high-dose irradiation, younger age, female sex, preexisting hypothyroidism
  • Postpartum thyroiditis: smoking, history of spontaneous/induced abortion
  • Painless (silent) thyroiditis: iodine-deficient areas
GENERAL PREVENTION
Selenium may decrease inflammatory activity in pregnant women with autoimmune hypothyroidism and may reduce postpartum thyroiditis risk in those positive for TPO antibodies.
COMMONLY ASSOCIATED CONDITIONS
Postpartum thyroiditis: family history of autoimmune thyroid disease; HLA-DRB, -DR4, and -DR5
image DIAGNOSIS
PHYSICAL EXAM
  • Examine thyroid size, symmetry, and nodules.
    • Hashimoto disease: 90% have a symmetric, diffusely enlarged, painless gland, with a firm, pebbly texture; 10% have thyroid atrophy.
    • Postpartum thyroiditis: painless, small, nontender, firm goiter (2 to 6 months after delivery)
    • Reidel thyroiditis: rock-hard, wood-like, fixed, painless goiter, often accompanied by symptoms of esophageal/tracheal compression (stridor, dyspnea, a suffocating feeling, dysphagia, and hoarseness)
  • Signs of hypothyroid: delayed relaxation phase of deep tendon reflexes, nonpitting edema, dry skin, alopecia, bradycardia
  • Signs of hyperthyroid: moist palms, hyperreflexia, tachycardia/atrial fibrillation
DIFFERENTIAL DIAGNOSIS
Simple goiter; iodine-deficient/lithium-induced goiter; Graves disease; lymphoma; acute infectious thyroiditis; oropharynx and trachea infections; thyroid cancer; amiodarone; contrast dye; amyloid
DIAGNOSTIC TESTS & INTERPRETATION
  • Thyroid-stimulating hormone (TSH), anti-TPO antibodies
  • Hashimoto disease
    • High titers of anti-TPO antibodies
    • New subtype: IgG4 thyroiditis, which is histopathologically characterized by lymphoplasmacytic infiltration, fibrosis, increased numbers of IgG4-positive plasma cells, and high serum IgG4 levels; more closely associated with rapid progress, subclinical hypothyroidism, higher levels of circulating antibodies, and more diffuse low echogenicity (2)[C]
  • Subacute granulomatous thyroiditis
    • High T4, T3; low TSH during early stages and elevated later; TSH varies with phase (1)[C].
    • High thyroglobulin; normal levels of anti-TPO and antithyroglobulin antibodies (present in 25%, usually low titers)
    • Elevated erythrocyte sedimentation rate (ESR) (usually >50 mm/hr) and C-reactive protein; mild anemia and slight leukocytosis; LFTs are frequently abnormal during initial hyperthyroid phase and resolve over 1 to 2 months.
  • Suppurative thyroiditis
    • In the absence of preexisting thyroid disease, thyroid function is normal but hyper-/hypothyroidism may occur.
    • Elevated ESR and WBC with marked increase in left shift
    • Fine-needle aspiration (FNA) of the lesion with Gram stain and culture is the most useful diagnostic test.
  • Postpartum thyroiditis (3)[B]
    • Anti-TPO antibody positivity is the most useful marker for the prediction of postpartum thyroid dysfunction.
    • Women known to be anti-TPO-Ab + should have TSH measured at 6 to 12 weeks' gestation and at 6 months postpartum or as clinically indicated.
    • Thyrotoxic phase occurs 1 and 6 months postpartum (most commonly at 3 months) and usually lasts only 1 to 2 months.
    • Hypothyroidism occurs between 3 and 8 months (most commonly at 6 months).
    • Most patients (80%) have normal thyroid function at 1 year; 30-50% of patients develop permanent hypothyroidism within 9 years.
    • High thyroglobulin, normal ESR
  • P.1037

  • Painless (silent) thyroiditis
    • Hyperthyroid state in 5-20%: averages 3 to 4 months, and total duration of illness is <1 year, followed by hypothyroidism and then a return to normal state; some have primary/subclinical hypothyroidism.
    • ˜ 50% have anti-TPO antibodies (1)[C].
  • Reidel thyroiditis (4)[C]
    • Hypothyroidism due to extensive replacement of the gland by scar tissue. Anti-TPO antibodies are present in 2/3 of patients along with low radioactive iodine uptake (RAIU).
  • Drug-induced thyroiditis
    • Hyper-/hypothyroidism, low RAIU, and variable presence of anti-TPO antibodies
  • US: shows variable heterogeneous texture, hypoechogenic in subacute, painless (silent), and postpartum thyroiditis
  • Thyroid RAIU scan: decreased in all forms of thyroiditis but not helpful in establishing diagnosis of Hashimoto disease. High RAIU in hashitoxicosis, Graves disease
  • Random urine iodine measurement may be helpful to distinguish from other causes of low RAIU.
    • Urine iodine <500 &mgr;g/L (subacute granulomatous thyroiditis)
    • Urine iodine >1,000 &mgr;g/L (in patients with exposure to excess exogenous iodine/radiocontrast material)
Diagnostic Procedures/Other
  • Hashimoto with a dominant nodule should have FNA to rule out thyroid carcinoma.
  • Open biopsy is necessary for a definitive diagnosis of Reidel thyroiditis.
Test Interpretation
  • Hashimoto disease: lymphocytic infiltration with formation of Askanazy (Hürthle) cells, oxyphilic changes in follicular cells, fibrosis, thyroid atrophy
  • Subacute granulomatous thyroiditis: giant cells, mononuclear cell (granulomatous) infiltrate
  • Postpartum thyroiditis: lymphocytic infiltration, occasional germinal centers, disruption and collapse of thyroid follicles
  • Painless (silent) thyroiditis: lymphocytic infiltration, but without fibrosis, Askanazy cells, and extensive lymphoid follicle formation
image TREATMENT
GENERAL MEASURES
Analgesics for pain; corticosteroids for severe granulomatous thyroiditis
MEDICATION
  • Hashimoto disease (2)[C]
    • If hypothyroid/goitrous: levothyroxine (1.7 &mgr;g/kg/day for adults <50 years of age). If no cardiac complications and no adrenal insufficiency, 1/2 replacement dose and increase to full replacement in 10 days.
      • If >50 years of age or heart disease and/or adrenal insufficiency, begin with 25 &mgr;g/day and titrate to TSH of lower limit normal range.
  • If thyrotoxic and symptomatic: propylthiouracil and propranolol
  • An elevated TSH level in a woman who is pregnant or attempting to become pregnant is an indication for thyroid replacement.
  • Subacute granulomatous thyroiditis
    • Anti-inflammatory agents for 2 to 8 weeks (NSAIDs or aspirin)
    • Pain with no improvement in 2 to 3 days after NSAID use: Prednisone 40 mg/day; should result in pain relief in 1 to 2 days; if not, question diagnosis.
    • Severe pain: prednisone 40 to 60 mg/day discontinued over 4 to 6 weeks. If pain recurs, increase dose for several weeks and then taper.
    • Symptomatic hyperthyroidism: &bgr;-blockers while thyrotoxic (propranolol 40 to 120 mg/day)
    • Symptomatic hypothyroid phase: Levothyroxine, as mentioned earlier, target TSH in the normal range.
  • Suppurative thyroiditis
    • Parenteral empiric, broad-spectrum antibiotics, and surgical drainage
  • Painless (silent) thyroiditis
    • No treatment needed.
    • If symptomatic during hyperthyroid state, treat with &bgr;-blocker (propranolol 40 to 120 mg/day).
    • Prednisone shortens the period of hyperthyroidism. Monitor TSH every 4 to 8 weeks to confirm resolution.
    • Treat hypothyroid symptoms and asymptomatic patients with TSH >10 mU/L with levothyroxine (50 to 100 &mgr;g/day), to be discontinued after 3 to 6 months.
  • Postpartum thyroiditis (5)[C]
    • Treat symptomatic hyper-/hypothyroid state. Most do not need treatment.
    • Caution in breastfeeding mothers because &bgr;-blockers are secreted into breast milk.
    • For symptomatic hypothyroidism, treat with levothyroxine. Otherwise, remonitor in 4 to 8 weeks. Taper replacement hormone after 6 months if thyroid function has normalized.
  • Reidel thyroiditis (4)[C]
    • Corticosteroids in early stages but controversial thereafter. Prednisone 10 to 20 mg/day for 4 to 6 months, possibly continued thereafter if effective
    • Long-term anti-inflammatory medications to arrest progression and maintain a symptom-free course
    • Tamoxifen 10 to 20 mg twice daily as monotherapy or in conjunction with prednisone reduces mass size and clinical symptoms.
    • Methotrexate is used with some success.
    • Reduction of goiter seen with a combination of mycophenolate mofetil (1 g BID) and 100 mg/day prednisone
    • Debulking surgery is limited to isthmusectomy to relieve constrictive pressure when total thyroidectomy is not possible.
  • Drug-induced thyroiditis
    • Discontinue offending drug.
SURGERY/OTHER PROCEDURES
Enlarged painful thyroid or tracheal compression
image ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
Patient Monitoring
  • Hashimoto disease: Repeat thyroid function tests every 3 to 12 months.
  • Subacute granulomatous thyroiditis: Repeat thyroid function tests every 3 to 6 weeks until euthyroid, then every 6 to 12 months.
  • Postpartum thyroiditis: Check TSH annually.
  • Reidel thyroiditis: CT of cervical mediastinal region is recommended.
  • TSH every 6 months in patients on amiodarone
Pregnancy Considerations
  • Avoid radioisotope scanning if possible.
  • Keep TSH maximally suppressed.
  • If using RAIU scan, discard breast milk for 2 days because RAI is secreted in breast milk.
PROGNOSIS
  • Hashimoto disease: persistent goiter; eventual thyroid failure
  • Subacute granulomatous thyroiditis: 5-15% hypothyroid beyond a year: Some with eventual return to normal; remission may be slower in the elderly; recurrence rate: 1-4% after a year
  • Painless (silent) thyroiditis: 10-20% hypothyroid beyond a year; recurrence rate 5-10% (much higher in Japan)
  • Postpartum thyroiditis: 15-50% hypothyroid beyond a year; women may be euthyroid/continue to be hypothyroid at the end of 1st postpartum year. 70% recurrence rate in subsequent pregnancies; substantial risk exists for later development of hypothyroidism/goiter.
REFERENCES
1. Samuels MH. Subacute, silent, and postpartum thyroiditis. Med Clin North Am. 2012;96(2):223-233.
2. Li Y, Nishihara E, Kakudo K. Hashimoto's thyroiditis: old concepts and new insights. Curr Opin Rheumatol. 2011;23(1):102-107.
3. De Groot L, Abalovich M, Alexander EK, et al. Management of thyroid dysfunction during pregnancy and postpartum: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2012;97(8):2543-2565. doi:10.1210/jc.2011-2803
4. Hennessey JV. Clinical review: Riedel's thyroiditis: a clinical review. J Clin Endocrinol Metab. 2011;96(10):3031-3041.
5. Reid SM, Middleton P, Cossich MC, et al. Interventions for clinical and subclinical hypothyroidism in pregnancy. Cochrane Database Syst Rev. 2010;(7):CD007752.
Additional Reading
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Duntas LH. Selenium and the thyroid: a close-knit connection. J Clin Endocrinol Metab. 2010;95(12): 5180-5188.
See Also
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Hyperthyroidism; Hypothyroidism, Adult
Codes
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ICD10
  • E06.9 Thyroiditis, unspecified
  • E06.1 Subacute thyroiditis
  • E06.0 Acute thyroiditis
Clinical Pearls
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  • TSH elevation above the normal range indicates a hypothyroid state; suppressed TSH indicates hyperthyroid state. Follow up with free T3/T4 determination.
  • Follow patients on thyroid replacement with periodic TSH level.