Hashimoto thyroiditis

Hashimoto disease is the most common form of autoimmune thyroiditis and the leading cause of hypothyroidism in the United States. Although currently thought to be due to chronic autoimmune-mediated lymphocytic inflammation of the thyroid tissue, the exact pathophysiology remains unclear. Patients are initially asymptomatic or hyperthyroid, progressing to hypothyroidism as the organ parenchyma is destroyed. Diagnosis is based on a combination of specific antibodies, thyroid function tests, and sonography of the thyroid. Treatment involves lifelong hormone replacement therapy with levothyroxine (L-thyroxine).

• 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 antibodies towards thyroid peroxidase (TPO) and thyroglobulin (Tg) → destruction of thyroid tissue
• Associations: increased risk for non-Hodgkin lymphoma (usually originating from B cells) and autoimmune diseases (e.g., type 1 diabetes, SLE, Graves disease, Addison disease) ^[4]

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

• Hashimoto encephalopathy: Hashimoto encephalopathy is triggered by autoantibodies present in Hashimoto thyroiditis. It may lead to cognitive and vigilance impairment, as well as ataxia, myoclonus, and epileptic seizures.

• Thyroid metabolism ^[5]
  • Early-stage: transient hyperthyroidism possible (↓ thyroid stimulating hormone (TSH), ↑ free triiodothyronine (FT3), and ↑ free thyroxine (FT4))
  • Progression: subclinical hypothyroidism (↑ TSH; FT3 and FT4 normal)
  • Late-stage: overt hypothyroidism (↑ TSH; ↓ FT4 and ↓ FT3)
• Antibody detection
  • Anti-TPO antibody positive (↑ anti-microsomal antibodies)
  • Anti-Tg antibody positive
  • See “Thyroid antibodies.”
• Other laboratory tests
  • Lipid profile: ↑ LDL and ↓ HDL
  • CBC: ↓ Hb

• Ultrasound
  • Indications: to assess thyroid size, echotexture, and to exclude thyroid nodules
  • Results depend on the form of Hashimoto thyroiditis.
    • Atrophic phenotype: reduction in thyroid size (mainly observed)
    • Goitrous phenotype: heterogeneous enlargement
• Fine-needle aspiration: to exclude malignancy or lymphoma, especially in cases of rapid goiter growth ^[6]
• Radioactive iodine uptake test (RIUT): Radioactive iodine uptake is variable, often patchy and irregular with either an increase or decrease in 99mTc uptake. There is ↓ absorption of radioactive technetium (↓ 99mTc uptake) in the thyroid during transient hyperthyroidism

Anti-TPO antibodies are also elevated in 70% of patients with Graves disease.

• Diffuse lymphocytic infiltration (cytotoxic T lymphocytes) with germinal center, oncocytic-metaplastic cells (Hurthle cells) and fibrotic tissue

• 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) ^[7]
  • Rare, special form of autoimmune thyroiditis ^[8]
  • Characterized by inflammatory infiltration and fibrosclerotic changes of thyroid tissue ^[2][8]
  • 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. ^[7]
  • 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.

• Levothyroxine (T4) replacement therapy
  • Life-long oral administration of L-thyroxine (T4)
  • Commence at a lower and more slow-acting dose with increasing severity of hypothyroidism because of the risk of cardiac side effects.
• Life-long monitoring
  • Due to decline in T4 production with increasing age
  • Life-long monitoring of thyroid parameters (primarily TSH) is necessary to adjust treatment accordingly and avoid hyperthyroidism

• Permanent hypothyroidism ^[2]
• Myxedema coma
• Thyroid lymphoma (the risk is 60 times higher in patients with Hashimoto thyroiditis) ^[9]

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