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- Clinical and metabolic state resulting from decreased levels of free thyroid hormone or from resistance to hormone action
- Primary (intrinsic thyroid disease) or central (secondary or tertiary resulting from hypothalamic-pituitary disease)
- Subclinical: serum TSH above the upper reference limit with a normal free T4 and normal hypothalamic-pituitary-thyroid axis (1)
- Overt: elevated TSH, usually >10 mIU/L with a subnormal free T4
- Women: 3.5 per 1,000 persons per year
- Men: 0.6 per 1,000 persons per year
- The National Health and Nutrition Examination Survey III (NHANES III), SHypo (subclinical hypothyroidism) 9.3%, overt 0.3–3.7% in an unselected U.S. population age >12 years, with upper limit TSH 4.5
- Framingham study, 5.9% of women and 2.3% of men age >60 years had a serum TSH >10 mIU/L.
Etiology and Pathophysiology
- Primary: abnormality at the thyroid gland (>95% of cases)
- Most common cause worldwide: environmental iodine deficiency (1)[A]
- Most common cause in the United States: Hashimoto thyroiditis (chronic autoimmune thyroiditis)
- Hashimoto is characterized pathologically by infiltration of the thyroid with sensitized T lymphocytes and serologically by circulating antithyroid antibodies.
- Autoimmunity to the thyroid gland is an inherited defect in immune surveillance, leading to abnormal regulation of immune responsiveness or alteration of presenting antigen in the thyroid (1).
- Postablative/posttherapeutic: follows radioactive iodine therapy or hemithyroidectomy for hyperthyroidism; radiotherapy or surgery for thyroid cancer, benign nodular thyroid disease or neck malignancies
- Transient hypothyroidism: De Quervain syndrome (viral), postpartum, silent thyroiditis (2)
- 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)
- Etiology involves genetic defects, tumors, vascular, empty sella syndrome, inflammatory, infiltrative, iatrogenic, posttrauma, or drug related.
- Women >60 years of age
- Personal or family history of autoimmune diseases
- Pregnant women or those with previous postpartum thyroiditis
- Previous head or neck irradiation
- Past history of thyroid dysfunction or thyroid surgery
- Abnormal thyroid examination, presence of goiter and/or TPOAb positivity
- Treatment with amiodarone, lithium, interferon-α, sunitinib, or sorafenib
- Those with Down syndrome or Turner syndrome
Commonly Associated Conditions
- Type 1 and 2 diabetes
- Pernicious anemia
- Primary adrenal failure (Addison disease)
- Myasthenia gravis
- Celiac disease
- Rheumatoid arthritis
- Systemic lupus erythematosus
- Genetic syndromes that have multiple autoimmune endocrinopathies (MAE) such as type 1 MAE and type 2 MAE.