Deficient thyroid hormone production can be due to thyroid failure (primary hypothyroidism) or, less commonly, pituitary or hypothalamic disease (secondary hypothyroidism) (Table 173-1). Congenital hypothyroidism is present in 1 of 4000 newborns; the importance of its recognition and prompt treatment for child development has led to the adoption of neonatal screening programs. Transient hypothyroidism may occur in silent or subacute thyroiditis. Subclinical (or mild) hypothyroidism is a state of normal free thyroid hormone levels and mild elevation of thyroid-stimulating hormone (TSH). With higher TSH levels and low free T4 levels, symptoms become more readily apparent in clinical (or overt) hypothyroidism. In areas of iodine sufficiency, autoimmune disease and iatrogenic causes are the most common etiologies of hypothyroidism. The peak age of occurrence is around 60 years, and prevalence increases with age. Novel anticancer and immunomodulatory treatments, such as tyrosine kinase inhibitors and alemtuzumab, can also induce thyroid autoimmunity via their effects on T cell regulation.

TABLE 173-1: Causes of Hypothyroidism


Autoimmune hypothyroidism: Hashimoto’s thyroiditis, atrophic thyroiditis

Iatrogenic: 131I treatment, subtotal or total thyroidectomy, external irradiation of neck for lymphoma or cancer

Drugs: iodine excess (including iodine-containing contrast media and amiodarone), lithium, antithyroid drugs, p-aminosalicylic acid, interferon α and other cytokines, aminoglutethimide, sunitinib

Congenital hypothyroidism: absent or ectopic thyroid gland, dyshormonogenesis, TSH-R mutation

Iodine deficiency

Infiltrative disorders: amyloidosis, sarcoidosis, hemochromatosis, scleroderma, cystinosis, Riedel’s thyroiditis

Overexpression of type 3 deiodinase in infantile hemangioma


Silent thyroiditis, including postpartum thyroiditis

Subacute thyroiditis

Withdrawal of thyroxine treatment in individuals with an intact thyroid

After 131I treatment or subtotal thyroidectomy for Graves’ disease


Hypopituitarism: tumors, pituitary surgery or irradiation, infiltrative disorders, Sheehan’s syndrome, trauma, genetic forms of combined pituitary hormone deficiencies

Isolated TSH deficiency or inactivity

Bexarotene treatment

Hypothalamic disease: tumors, trauma, infiltrative disorders, idiopathic

Abbreviations: TSH, thyroid-stimulating hormone; TSH-R, TSH receptor.

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