Subacute thyroiditis

Subacute thyroiditis refers to a transient patchy inflammation of the thyroid gland that is associated either with granuloma formation (subacute granulomatous thyroiditis) or lymphocytic infiltration (subacute lymphocytic thyroiditis). While subacute granulomatous thyroiditis usually occurs after a viral upper respiratory tract infection, subacute lymphocytic thyroiditis occurs either during the postpartum period, in association with other autoimmune diseases, or as a side effect of certain drugs. Both forms of subacute thyroiditis are more common among women and are characterized by a triphasic clinical course that classically transitions from hyperthyroidism to hypothyroidism, before returning to a euthyroid phase. During the thyrotoxic phase, patients usually complain of fever, malaise, and goiter, which is tender in subacute granulomatous thyroiditis and painless in subacute lymphocytic thyroiditis. Diagnosis is confirmed by a combination of raised ESR and decreased iodine uptake in a radioiodine uptake study. During the thyrotoxic phase, beta blockers may be used to control the symptoms of thyrotoxicosis, and NSAIDs may be used to control pain among patients with subacute granulomatous thyroiditis. Small doses of levothyroxine may be considered during the hypothyroid phase. As spontaneous remission is seen in about 80% of cases, symptomatic treatment is sufficient in most cases.

• Sex: ♀ > ♂ (3:1)
• Peak incidence: 30–50 years

References:^[1][2]

Epidemiological data refers to the US, unless otherwise specified.

Subacute thyroiditis is characterized by transient patchy inflammation of the thyroid gland (transient thyroiditis). Depending on the underlying cause, one of two types of histological changes is seen:

Subacute granulomatous thyroiditis (De Quervain thyroiditis)

Subacute granulomatous thyroiditis is characterized by damage to follicular cells, the appearance of large multinucleated giant cells, and the formation of granuloma and fibrosis.

• Also known as “giant cell thyroiditis” and “subacute thyroiditis”
• Viral infections: mumps virus, coxsackie virus, influenza virus, echovirus, adenovirus

Subacute lymphocytic thyroiditis

Subacute lymphocytic thyroiditis is characterized by damage to follicular cells with lymphocytic infiltration resembling Hashimoto thyroiditis, rather than granuloma formation.

• Drugs: α-interferon, lithium, amiodarone, interleukin-2, tyrosine kinase inhibitors
• Autoimmune disease
• Postpartum thyroiditis
  • Affects approx. 5% of women
  • Most prevalent in women with:
    • Type 1 diabetes mellitus
    • History of postpartum thyroiditis
    • Increased titers of thyroid peroxidase antibodies
  • Occurs within 1–12 months of delivery
  • Manifests with a period of transient thyrotoxicosis followed by hypothyroidism without thyroid enlargement or tenderness
  • Associated with increased titers of thyroid peroxidase antibodies.
  • Usually resolves spontaneously.

References:^[3]

Inflammation of the thyroid gland manifests with a triphasic response. The duration of each phase may vary:

1. Thyrotoxic phase
   • Lasts 2–8 weeks
   • Caused by damage to follicular cells and the release of pre-formed colloid (stored thyroid hormones)
2. Hypothyroid phase
   • Typically lasts 2–8 weeks; permanent in ∼ 15% of individuals with subacute granulomatous thyroiditis
   • Caused by depletion of pre-formed colloid and impaired synthesis of new thyroid hormones as a result of damage to follicular cells
3. Euthyroid phase: Thyroid function recovers and pathological changes are no longer visible in the thyroid gland.

The disease is self-limiting in most cases but a few patients may experience relapses, and permanent hypothyroidism occurs in ∼ 15% of cases!

Subacute granulomatous thyroiditis (De Quervain thyroiditis)

• Possible history of upper respiratory tract infections a few weeks prior to the onset of subacute thyroiditis
• Painful, diffuse, firm goiter, jaw pain
• Fever and/or malaise may be present.
• Features of hyperthyroidism followed by features of hypothyroidism

De Quervain causes pain.

Subacute lymphocytic thyroiditis

• Painless, diffuse, firm goiter (thyroid size may be normal)
• Features of hyperthyroidism followed by features of hypothyroidism

References:^[2]

• Thyroid function tests
  • Thyrotoxic phase: ↑ T₃ and T₄ , ↑ thyroglobulin, ↓ TSH
  • Hypothyroid phase: ↓ T₃ and T₄, ↑ TSH
• Confirmatory test
  • ↑ ESR
  • Radioiodine uptake study : ↓ iodine uptake (< 5%)
• Ultrasound: thyroid with poorly defined hypoechoic regions and decreased vascularity, giving rise to a cobblestone appearance
• Histology
  • Subacute granulomatous thyroiditis: granulomatous inflammation, multinucleated giant cells
  • Subacute lymphocytic thyroiditis: lymphocytic infiltration, sparse germinal centers

• Thyrotoxic phase
  • Consider beta-blockers to control symptoms of hyperthyroidism (i.e. palpitations and/or anxiety).
  • NSAIDs: pain control in the case of acute granulomatous thyroiditis
  • Occasionally corticosteroids (i.e. prednisolone)
  • Antithyroid drugs (e.g., methimazole) should not be administered.
  • See also “Symptomatic therapy for thyrotoxicosis.”
• Hypothyroid phase: : levothyroxine

Antithyroid drugs should not be administered in the thyrotoxic phase of subacute thyroiditis.