HYPOTHYROIDISM

ETIOLOGY

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
Primary 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
Transient 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
Secondary 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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