The syndrome of inappropriate ADH (SIADH) secretion is typically associated with ADH excess, which causes resorption of excessive amounts of free water, resulting in hyponatremia. Causes of SIADH include the secretion of ectopic ADH by malignant neoplasms (particularly small-cell carcinomas of the lung), non-neoplastic diseases of the lung, and local injury to the hypothalamus or neurohypophysis. The clinical manifestations of SIADH are dominated by hyponatremia, cerebral edema, and resultant neurologic dysfunction. Although total body water is increased, blood volume remains normal, and peripheral edema does not develop.
The thyroid gland consists of two bulky lateral lobes connected by a relatively thin isthmus, usually located below and anterior to the larynx. The thyroid gland develops embryologically from an evagination of the developing pharyngeal epithelium that descends from the foramen cecum at the base of the tongue to its normal position in the anterior neck. This pattern of descent explains the occasional presence of ectopic thyroid tissue, most commonly located at the base of the tongue (lingual thyroid) or at other sites abnormally high in the neck.
The thyroid is divided into lobules, each composed of about 20 to 40 evenly dispersed follicles. The follicles are lined by cuboidal to low columnar epithelium, which is filled with thyroglobulin, the iodinated precursor protein of active thyroid hormone. In response to trophic factors from the hypothalamus, TSH (also called thyrotropin) is released by thyrotrophs in the anterior pituitary into the circulation. The binding of TSH to its receptor on thyroid follicular epithelial cells results in activation and conformational change in the receptor, allowing it to associate with a stimulatory G-protein (
Fig. 20.6 ). As illustrated in
Fig. 20.3, activation of stimulatory G-protein results in an increase in intracellular cAMP levels, which stimulates thyroid hormone synthesis and release. Thyroid follicular epithelial cells convert thyroglobulin into thyroxine (T4) and lesser amounts of triiodothyronine (T3). T4 and T3 are released into the systemic circulation, where most of these peptides are bound to circulating plasma proteins, such as T4-binding globulin, for transport to peripheral tissues. The binding proteins maintain the serum unbound (free) T3 and T4 concentrations within narrow limits while ensuring that the hormones are readily available to the tissues.
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TRH Pituitary Thyroid T3, T4 T3, T4 Thyroid hormone receptor Target gene TSH TSH receptor G protein GTP GDP cAMP G Gene expression on