Hashimoto thyroiditis

Hashimoto thyroiditis is the most common type of autoimmune thyroiditis and the leading cause of hypothyroidism in the United States. Although it is thought to be due to chronic autoimmune-mediated lymphocytic inflammation and destruction of the thyroid tissue, the exact pathophysiology remains unclear. Patients may initially be asymptomatic or show signs of thyrotoxicosis, progressing to hypothyroidism as the organ parenchyma is destroyed. Diagnosis is based on a combination of clinical features, thyroid antibodies, and thyroid function tests. Additional studies (e.g., ultrasound, fine-needle aspiration) may be obtained to rule out alternative conditions and may support the diagnosis. Management consists of lifelong monitoring and, in most cases, hormone replacement therapy with levothyroxine.

• Prevalence
  • 5% in the US ^[1]
  • Hashimoto disease is the most common form of thyroiditis and the most frequent cause of hypothyroidism in the US.
  • Iodine deficiency is the most common cause of hypothyroidism worldwide. ^[2]
• Sex: ♀ > ♂ (7:1)
• Age of onset: occurs in all age groups; most prevalent in women aged 30–50 years

Epidemiological data refers to the US, unless otherwise specified.

• Unknown etiology: Genetic and environmental factors likely play a role.
• Immunological mechanisms
  • Associations with HLA-DR3, and DR5 have been proposed. ^[3]
  • Cellular (especially T cells) and humoral immune responses are activated; → active B lymphocytes produce thyroid peroxidase antibodies (TPOAbs) and thyroglobulin antibodies (TgAbs) → destruction of thyroid tissue

• Early-stage
  • Primarily asymptomatic
  • Goiter: nontender or painless, rubbery thyroid with moderate and symmetrical enlargement ^[2]
  • Hashitoxicosis may occur: transient thyrotoxicosis due to follicular rupture of hormone-containing thyroid tissue that manifests with signs of hyperthyroidism (e.g., irritability, heat intolerance, diarrhea)
• Late-stage
  • Thyroid may be normal-sized or small if extensive fibrosis has occurred.
  • Signs of hypothyroidism (e.g., cold intolerance, constipation, fatigue)

• Hashimoto encephalopathy ^[4][5]
  • Definition: a rare neurological syndrome associated with high TPOAb or TgAb titers
  • Clinical features: widely variable, including impairment of cognitive function and vigilance, ataxia, myoclonus, seizures, psychosis
  • Treatment: glucocorticoids

Consider Hashimoto thyroiditis in patients with signs of hypothyroidism, thyrotoxicosis (less common), and/or painless goiter.

Approach ^[6][7][8]

• Obtain for all patients:
  • Thyroid function tests
  • Thyroid antibodies to confirm the diagnosis
• In patients with goiter or suspected thyroid nodules: Obtain a thyroid ultrasound.
• Consider additional studies to rule out differential diagnoses.
  • See “Diagnostic workup for hypothyroidism.”
  • See “Diagnostic workup of hyperthyroidism.”
  • See “Diagnostics” in “Thyroid cancer.”

Diagnosis of Hashimoto thyroiditis is based on clinical features, thyroid function tests, and positive TPOAbs and/or TgAbs.

Laboratory studies ^[6][9]

• Thyroid function tests (TFTs)
  • Early-stage: Transient hashitoxicosis may appear (↓ TSH, ↑ FT3, and ↑ FT4).
  • Progression: subclinical hypothyroidism (mildly ↑ TSH; normal FT3 and FT4)
  • Late-stage: overt hypothyroidism (↑ TSH; ↓ FT4 and ↓ FT3)
• Thyroid antibodies ^[10]
  • Anti-TPOAbs (formerly anti-microsomal antibodies): positive in up to 95% of patients ^[6]
  • Anti-TgAbs: positive in 60–80% of patients ^[6]
• Other laboratory findings ^[11]
  • CBC: mild anemia
  • ↑ ESR
  • Additional findings depend on the phase of disease. (See “Hypothyroidism diagnostics” and “Hyperthyroidism diagnostics.”)

TPOAbs are positive in 70–80% of patients with Graves disease and in ∼15% of individuals without thyroid disease. ^[10]

Additional studies

The following studies are not required for diagnosis but may be performed during workups for thyroid disorders or goiter to rule out differential diagnoses (e.g., multinodular goiter or malignancy).

• Thyroid ultrasound ^[11]
  • Often shows diffuse hypoechogenicity
  • May show heterogeneous thyroid enlargement or atrophy ^[6]
  • In patients with thyroid nodules, it can show sonographic signs of thyroid malignancy.
• Fine-needle aspiration
  • Indications: patients with focal nodules to exclude malignancy (see “Workup of thyroid nodules”) ^[11][12]
  • Findings: diffuse lymphocytic infiltration (cytotoxic T lymphocytes) with germinal centers, oncocytic-metaplastic cells (Hurthle cells), and fibrotic tissue ^[13]
• Radioactive iodine uptake test (RIUT) ^[8]
  • Rarely used due to variable results
  • Iodine uptake may be decreased in patients with transient thyrotoxicosis.

• See “Differential diagnoses of hypothyroidism” and “Overview of common causes of primary hypothyroidism.”
• Subacute thyroiditis (de Quervain thyroiditis) ^[2]
• Diffuse toxic goiter/Graves disease
• Nontoxic/multinodular goiter
• Riedel thyroiditis (Riedel struma) ^[14]
  • Rare, special form of autoimmune thyroiditis ^[15]
  • Characterized by inflammatory infiltration and fibrosclerotic changes of thyroid tissue ^[2][15]
  • Part of the IgG4-related disease spectrum, which includes conditions sharing histopathological features of fibrosclerosis in different organs (e.g., sclerosing sialadenitis, retroperitoneal fibrosis, autoimmune pancreatitis, aortitis, etc.)
  • Goiter ^[2]
    • Painless, hard (stone-like), fixed
    • May compress surrounding tissues (e.g., trachea, esophagus), mimicking invasive growth of malignant tumor (e.g., feeling of anterior neck pressure, dysphagia, hoarseness , stridor, dyspnea)
  • Approx. 30% of affected individuals have hypothyroidism. ^[14]
  • Surgery may be necessary due to compression.
• Acute suppurative thyroiditis
  • Definition: extremely rare bacterial infection of the thyroid gland
  • Symptoms/clinical features: acute febrile course with tenderness
  • Diagnosis: ultrasound
  • Treatment: administration of broad-spectrum antibiotics (e.g., clindamycin or amoxicillin with clavulanate); in the case of abscess formation, opening of the abscess and culture of the abscess contents in addition to an antibiogram
  • Complications: mediastinitis

The differential diagnoses listed here are not exhaustive.

Treatment ^[6][12][16]

Lifelong oral levothyroxine replacement is required in most patients with Hashimoto thyroiditis.

• Overt hypothyroidism
  • Full-dose levothyroxine in young, healthy patients ^[16]
  • OR low-dose levothyroxine depending on age and comorbidities ^[12][16]
  • See “Levothyroxine replacement” in “Hypothyroidism” for details on dosage.
• Subclinical hypothyroidism: Consider low-dose levothyroxine. ^[9][16]
• Hashitoxicosis: symptomatic therapy for thyrotoxicosis with ß-blockers ^[12]
• Goiter: Thyroidectomy may be considered in patients with obstructive symptoms or for cosmetic reasons. ^[8]

Monitoring

• For all phases (including euthyroidism) ^[6]
  • Lifelong annual TSH measurements
  • Clinical assessment for lymphoma and associated autoimmune diseases
• After levothyroxine initiation or dosage change
  • TSH level after 4–6 weeks ^[6][16]
  • See “Levothyroxine replacement” in “Hypothyroidism” for details on monitoring and dose adjustments.

Patients with Hashimoto thyroiditis are at increased risk of having or developing other autoimmune diseases (e.g., type 1 diabetes, SLE, Graves disease, Addison disease) and non-Hodgkin lymphoma. ^[6]

• Myxedema coma
• Primary thyroid lymphoma ^[17]
  • Epidemiology: 40- to 80-fold increase in risk in patients with Hashimoto thyroiditis
  • Pathophysiology: usually originating from B cells

We list the most important complications. The selection is not exhaustive.