Description

• Clinical and metabolic state resulting from decreased levels of free thyroid hormone or from resistance to hormone action
• Classified as primary, central, or peripheral based on pathology in the thyroid, the pituitary or hypothalamus, or peripheral tissue, respectively (1)
• Subclinical: serum TSH above the upper reference limit with a normal free thyroxine (T₄) and normal hypothalamic-pituitary-thyroid axis (2)
• Overt: elevated TSH, typically 4 to 5 mIU/L with a subnormal free T₄

Epidemiology

Incidence

• Women: 3.5/1,000 persons per year
• Men: 0.6/1,000 persons per year

Etiology and Pathophysiology

• Primary: abnormality at the thyroid gland (>95% of cases)
• Most common cause worldwide: environmental iodine deficiency (2)[A]
• Most common cause in the United States: Hashimoto thyroiditis (chronic autoimmune thyroiditis)
  • Hashimoto thyroiditis is characterized by loss of thyroid function secondary to autoimmune-mediated destruction from thyroid antibodies.
  • The typical course of the disease is gradual loss of thyroid function.
• Postablative/posttherapeutic: follows radioactive iodine therapy or total/subtotal thyroidectomy for hyperthyroidism; radiotherapy or surgery for thyroid cancer, benign nodular thyroid disease, or neck malignancies
• Transient hypothyroidism: de Quervain thyroiditis (viral), postpartum, silent thyroiditis (3)
• Drug use: propylthiouracil, methimazole, lithium, amiodarone, antiepileptic drugs, and newer chemotherapeutic agents such as tyrosine kinase inhibitors (sunitinib), interleukin-2, or interferon-α
• Central: hypothyroidism due to insufficient stimulation by TSH of an otherwise normal thyroid gland; can be secondary (level of the pituitary) or tertiary (level of the hypothalamus)
• Consumptive: T₃ and T₄ excessively degraded by ectopically produced type 3 iodothyronine deiodinase (rare)
• Other etiologies include genetic defects, tumors, vascular, empty sella syndrome, inflammatory, infiltrative, iatrogenic, posttrauma, or drug related.

Risk Factors

• Personal or family history of autoimmune diseases
• External head or neck irradiation; radioiodine therapy or thyroid surgery
• Abnormal thyroid examination, presence of goiter and/or TPOAb positivity
• Treatment with amiodarone, lithium, interferon-α, sunitinib, or sorafenib
• Down syndrome or Turner syndrome

Commonly Associated Conditions

• Pernicious anemia
• Celiac disease
• Primary adrenal failure (Addison disease)
• Rheumatoid arthritis, systemic lupus erythematosus
• Depression