- 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 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.
- 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
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