Hypothyroidism, Adult



  • 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



  • 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

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