Subacute thyroiditis

Subacute thyroiditis is a group of conditions characterized by transient inflammation of the thyroid that classically progresses through a triphasic course: thyrotoxicosis, followed by hypothyroidism, and eventually a return to a euthyroid state. The two main subtypes are subacute granulomatous thyroiditis (de Quervain thyroiditis), often preceded by a viral infection and manifests with a painful goiter, and subacute lymphocytic thyroiditis (silent or painless thyroiditis), which includes postpartum thyroiditis, and is caused by autoimmune disease and certain medications. Symptoms are generally milder than in other forms of thyrotoxicosis and hypothyroidism. Diagnostic studies reveal thyroid dysfunction and features of destructive thyroiditis on imaging (i.e., low or no iodine uptake on RAIU measurement, decreased vascularity on thyroid ultrasound with Doppler). In subacute granulomatous thyroiditis, inflammatory markers are elevated during the thyrotoxic phase, whereas they remain normal in subacute lymphocytic thyroiditis. Treatment is often unnecessary as thyroid dysfunction is typically mild. Beta blockers may be used to manage thyrotoxicosis symptoms, and NSAIDs or prednisone to manage the pain in subacute granulomatous thyroiditis. During the hypothyroid phase, levothyroxine replacement is indicated for symptomatic hypothyroidism and certain patients with postpartum thyroiditis. Most patients (over 80%) become euthyroid within a year, though recurrence is possible, and some may develop permanent hypothyroidism.

• 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. Depending on the underlying cause, one of two types of histological changes is seen.

Subacute thyroiditis classically has a triphasic clinical course. The duration of each phase may vary (see “Clinical features”).

1. Thyrotoxic phase: caused by damage to follicular cells and the release of preformed colloid (stored thyroid hormones)
2. Hypothyroid phase: caused by depletion of preformed colloid and impaired synthesis of new thyroid hormones as a result of damage to follicular cells
3. Euthyroid phase: thyroid function recovers; pathological changes are no longer visible in the thyroid gland.

The classic triphasic course occurs in approximately 30% of patients. Some may experience only the thyrotoxic phase, while others may go through only the hypothyroid phase.

Prodrome ^[3][6]

• Can occur in patients with subacute granulomatous thyroiditis
• Consists of nonspecific symptoms (malaise, fatigue, low-grade fever) often preceded by an upper respiratory tract infection

Goiter ^[3]

• Subacute granulomatous thyroiditis
  • Painful, diffuse, firm goiter
  • Pain may radiate to the jaw and ears
  • Pain is exacerbated with swallowing, coughing, and neck movement
• Subacute lymphocytic thyroiditis: painless goiter

De Quervain thyroiditis is a common cause of thyroid pain. ^[3]

Thyrotoxic phase ^[3]

• Manifests with clinical features of hyperthyroidism
• Subacute granulomatous thyroiditis
  • Occurs in ∼ 50% of patients
  • Lasts 3–6 weeks
• Subacute lymphocytic thyroiditis
  • Occurs in up to 20% of patients
  • Lasts 3–4 months

Hypothyroid phase ^[3]

• Manifests with clinical features of hypothyroidism
• Occurs in ∼ 30% of patients
• Typically lasts ≤ 6 months; permanent in ∼ 15% of individuals

Approach ^[3][4][6]

• Obtain a comprehensive clinical history and perform a thorough physical examination.
  • Evaluate for clinical signs of thyroid dysfunction.
  • Assess thyroid size, symmetry, nodularity, and tenderness to palpation.
  • Evaluate for an underlying cause, including performing a thorough medication review.
  • See “Overview of subacute thyroiditis” for expected findings.
• Obtain thyroid function tests (TFTs).
• In patients with thyrotoxicosis, obtain: ^[3][8]
  • Thyroid imaging
  • Inflammatory markers (in patients with a painful thyroid)
• Consider additional studies as needed to rule out differential diagnoses; see:
  • Diagnostic workup for hyperthyroidism
  • Diagnostic workup for hypothyroidism

Screen TFTs every 3–6 months in patients taking medications associated with drug-induced thyroiditis. ^[3]

TFTs ^[3][6]

• Thyrotoxic phase: : ↓ TSH, ↑ T₃ and T₄, ↑ thyroglobulin
• Hypothyroid phase: ↓ T₃ and T₄, ↑ TSH

Compared to thyrotoxicosis in other conditions (e.g., Graves disease), the thyroid dysfunction is mild and the T₃:T₄ ratio is lower in subacute thyroiditis. See “Overview of thyroid function tests.” ^[3]

Inflammatory markers ^[3][4]

• Indication: initial evaluation in individuals with a painful goiter
• Findings ^[3]
  • Subacute granulomatous thyroiditis: ↑ ESR (> 50 mm/hour), ↑ CRP, ↑ WBC during the thyrotoxic phase
  • Subacute lymphocytic thyroiditis: normal values

Thyroid imaging ^[3][4][8]

RAIU measurement

• Indication: evaluation of thyrotoxicosis of unknown cause in nonpregnant adults
• Findings: minimal or no uptake of radioactive iodine throughout the thyroid gland

Thyroid ultrasound with Doppler

• Indication: : evaluation of thyrotoxicosis of unknown cause in pregnant or lactating individuals
• Findings: thyroid with heterogeneous hypoechoic regions and decreased vascularity

Additional studies

Thyroid antibodies ^[3][9]

• Indications: not routinely indicated; consider to rule out differential diagnoses
• Findings
  • TRAbs: negative
  • Anti-TPO antibodies: positive in 50% of patients with subacute lymphocytic thyroiditis ^[3][9][10]
  • Anti-Tg antibodies: may be positive during the thyrotoxic phase ^[11][12]

Fine-needle aspiration biopsy

• Indications ^[4]
  • Diagnostic uncertainty
  • Suspected neoplasm
  • Suspected acute suppurative thyroiditis (e.g., high fever, leukocytosis, cervical lymphadenopathy)
• Findings ^[3]
  • Subacute granulomatous thyroiditis: granulomatous inflammation, multinucleated giant cells
  • Subacute lymphocytic thyroiditis: lymphocytic infiltration, sparse germinal centers

• Painful thyroid ^[4]
  • Acute suppurative thyroiditis
  • Radiation-induced thyroiditis
• Other causes of destructive thyroiditis
• See also “Differential diagnoses of hyperthyroidism” and “Overview of common causes of primary hypothyroidism.”

The differential diagnoses listed here are not exhaustive.

General principles ^[3][4][5]

• Subacute thyroiditis is a self-limited disease and thyroid dysfunction is typically mild.
• Management is symptomatic.
  • Thyrotoxic phase: beta blockers, NSAIDs, corticosteroids as needed
  • Symptomatic hypothyroidism: levothyroxine replacement until thyroid function recovers
• Regular follow-up and TFTs are necessary to monitor for changes in thyroid function.
• For management of postpartum thyroiditis, see “Special patient groups.”

Thyrotoxic phase

• Do not administer antithyroid drugs (e.g., methimazole). ^[3][4][6]
• Initiate symptomatic management as needed, e.g.:
  • Symptomatic treatment for thyrotoxicosis (e.g., beta blockers) ^[3][5]
  • Analgesia for patients with pain from subacute granulomatous thyroiditis ^[3]
    • Mild pain: NSAIDs, e.g., ibuprofen (see “Oral analgesics” for dosages)
    • Moderate, severe, or refractory pain : corticosteroids, e.g., prednisone ^[3][4]
• Drug-induced thyroiditis: Consider discontinuing medication in consultation with a specialist ^[3][4]
• Monitor thyroid function every 2–4 weeks. ^[13]

Antithyroid drugs are ineffective for subacute thyroiditis. ^[3]

Hypothyroid phase

• Treatment is usually unnecessary as symptoms are typically mild or absent. ^[3]
• Patients with overt hypothyroidism
  • Start levothyroxine replacement. ^[13]
  • Treatment duration is normally 3–6 months, but lifelong therapy may be required. ^[3]
  • Monitor TFTs 4–8 weeks after: ^[5][14]
    • Treatment initiation
    • Dosage changes
    • Cessation of therapy
  • See also “Management of hypothyroidism.”

In most cases, subacute thyroiditis is self-limited, but some patients experience recurrence, and permanent hypothyroidism occurs in ∼ 15% of patients. ^[3]

• Most cases self-resolve within 12 months. ^[4]
• Permanent hypothyroidism occurs in ∼ 15% of individuals. ^[3]
• Recurrence occurs in:
  • Up to 4% of patients with subacute granulomatous thyroiditis ^[3]
  • 5–10% of patients with subacute lymphocytic thyroiditis ^[3][4]

Postpartum thyroiditis ^[3][5]

• An autoimmune-mediated destructive thyroiditis that occurs within 12 months of the end of pregnancy
• Affects ∼ 5–10% of pregnant individuals ^[3][4]
• Most prevalent in individuals with: ^[4]
  • Personal or family history of autoimmune thyroid disease ^[3]
  • Type 1 diabetes
  • History of postpartum thyroiditis ^[4]

Clinical features ^[5]

• Similar to clinical features of subacute lymphocytic thyroiditis in nonpostpartum patients
• Features manifest within 1–12 months of delivery or spontaneous or induced abortion ^[3][5]
  • Hyperthyroidism usually occurs 1–6 months postpartum
  • Hypothyroidism develops 3–12 months postpartum. ^[5]
• May be associated with postpartum depression

Hypothyroidism symptoms are more common than hyperthyroidism symptoms, which are typically mild or absent in individuals with postpartum thyroiditis. ^[5]

Screen patients with depression, including postpartum depression, for thyroid dysfunction. ^[5]

Diagnostics ^[5]

The diagnostic workup is similar to diagnostics for subacute thyroiditis in nonpostpartum patients.

• In patients with thyrotoxicosis, the following tests are recommended to differentiate postpartum thyroiditis from Graves' disease. ^[3][4][5]
  • Total T3 and total T4
  • TRAb ^[4]
  • Consider thyroid imaging. ^[3][5]
• See “Postpartum thyroiditis vs. Graves disease” for findings.

RAIU measurement is contraindicated in pregnancy and lactation. If RAIU measurement is necessary during lactation, iodine-123 or technetium-99m should be used, and patients are advised to pump and discard breast milk for 3–5 days afterward. ^[3][5]

Differential diagnosis

Postpartum thyroiditis is the most common cause of hyperthyroidism in the postpartum period, but the incidence of Graves disease is 3–4 times higher postpartum than in the nonpostpartum period. ^[3][5]

Treatment ^[3][5]

Similar to treatment of subacute thyroiditis in nonpostpartum patients with the following modifications:

• Symptomatic thyrotoxicosis
  • Use propranolol or metoprolol at the lowest effective dose in lactating patients.
  • Monitor TSH every 4–8 weeks to screen for the onset of hypothyroidism.
• Hypothyroid phase
  • Consider levothyroxine replacement in patients who:
    • Have overt hypothyroidism
    • Are breastfeeding
    • Are trying to conceive
    • Have a TSH level > 10 mU/L ^[3]
  • Continue replacement for 12 months and then gradually taper dosing.
  • Monitor TSH every 6–8 weeks and adjust dosing accordingly.
• Long-term follow-up: Annual TSH testing is recommended for all patients to screen for permanent hypothyroidism. ^[5]

Advise patients with hypothyroidism who are not on levothyroxine therapy to use contraception until euthyroidism is achieved. ^[5]