Control of thyroid function via thyroid-pituitary feedback is also discussed in Chapter 37. Hypothalamic cells secrete thyrotropin-releasing hormone (TRH) (Figure 38–3). TRH is secreted into capillaries of the pituitary portal venous system, and in the pituitary gland, TRH stimulates the synthesis and release of thyrotropin (thyroid-stimulating hormone, TSH). TSH in turn stimulates an adenylyl cyclase–mediated mechanism in the thyroid cell to increase the synthesis and release of T4 and T3. T3, the more active of the two hormones, acts in a negative feedback fashion in the pituitary to block the action of TSH and in the hypothalamus to
TABLE 38–1 Summary of thyroid hormone kinetics.
inhibit the synthesis and secretion of TRH. Other hormones or drugs may also affect the release of TRH or TSH.
B. Autoregulation of the Thyroid Gland
The thyroid gland also regulates its uptake of iodide and thyroid hormone synthesis by intrathyroidal mechanisms that are independent of TSH. These mechanisms are primarily related to the level of iodine in the blood. Large doses of iodine inhibit iodide organification (Wolff-Chaikoff block; see Figure 38–1). In certain disease states (eg, Hashimoto’s thyroiditis), this can inhibit thyroid hormone synthesis and result in hypothyroidism. Hyperthyroidism can result from the loss of the Wolff-Chaikoff block in susceptible individuals (eg, multinodular goiter).
C. Abnormal Thyroid Stimulators
In Graves’ disease (see below), lymphocytes secrete a TSH receptor–stimulating antibody (TSH-R Ab [stim]), also known as thyroid-stimulating immunoglobulin (TSI). This immunoglobulin binds to the TSH receptor and stimulates the gland in the same fashion as TSH itself. The duration of its effect, however, is much longer than that of TSH. TSH receptors are also found in orbital fibrocytes, which may be stimulated by high levels of TSH-R Ab [stim] and can cause ophthalmopathy.
The structural formulas of thyroxine and triiodothyronine as well as reverse triiodothyronine (rT3) are shown in Figure 38–2. All of these naturally occurring molecules are levo (l) isomers.
TABLE 38–2 Typical adult values for thyroid function tests.
1Results may vary with different laboratories. 2Exception is central hypothyroidism.
The synthetic dextro (d) isomer of thyroxine, dextrothyroxine, has approximately 4% of the biologic activity of the l-isomer as evidenced by its lesser ability to suppress TSH secretion and correct hypothyroidism.
Thyroxine is absorbed best in the duodenum and ileum; absorption is modified by intraluminal factors such as food, drugs, gastric acidity, and intestinal flora. Oral bioavailability of current preparations of l-thyroxine averages 70 to 80% (Table 38–1). In contrast, T3 is almost completely absorbed (95%). T4 and T3 absorption appears not to be affected by mild hypothyroidism but may be impaired in severe myxedema with ileus. These factors are important in switching from oral to parenteral therapy. For parenteral use, the intravenous route is preferred for both hormones.