Disorders of the thyroid gland result primarily from autoimmune processes that stimulate the overproduction of thyroid hormones (thyrotoxicosis) or cause glandular destruction and underproduction of thyroid hormones (hypothyroidism). Neoplastic processes in the thyroid gland can lead to benign nodules or thyroid cancer.
Thyroidal production of the hormones thyroxine (T4) and triiodothyronine (T3) is controlled via a classic endocrine feedback loop (see Fig. 171-1). Some T3 is secreted by the thyroid, but most is produced by deiodination of T4 in peripheral tissues. Both T4 and T3 are bound to carrier proteins (thyroid-binding globulin [TBG], transthyretin [binds T4], and albumin) in the circulation. Increased levels of total T4 and T3 with normal free levels are seen in states of increased carrier proteins (pregnancy, estrogens, cirrhosis, hepatitis, and inherited disorders). Conversely, decreased total T4 and T3 levels with normal free levels are seen in severe systemic illness, chronic liver disease, and nephrosis.
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 173-1Causes of Hypothyroidism ||Download (.pdf) 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
Infiltrative disorders: amyloidosis, sarcoidosis, hemochromatosis, scleroderma, cystinosis, Riedel’s thyroiditis
Overexpression of type 3 deiodinase in infantile hemangioma
Silent thyroiditis, including postpartum 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