Diseases of the Thyroid

Thyroid-stimulating hormone (TSH) from the anterior pituitary stimulates the thyroid to secrete thyroxine; however, it also exerts a trophic (growth-stimulating) effect on the thyroid. This trophic effect is evident in people who develop an iodine-deficiency (endemic) goiter, or abnormal growth of

Blood plasma

Thyroid follicle rr

Thyroid uptake of iodide

(Iodide in plasma)

Peroxidase I2 (Iodine)

H2O2

Thyroglobulin

Monoiodotyrosine (MIT) Diiodotyrosine (DIT)

Colloid

Triiodothyronine (T3)

Endocyi0s/s ,

DIT+ DIT

Tetraiodothyronine

Bound to thyroglobulin

Thyroid hormone secretion

Thyroid hormone secretion

■ Figure 11.23 The production and storage of thyroid hormones. Iodide is actively transported into the follicular cells. In the colloid, it is converted into iodine and attached to tyrosine amino acids within the thyroglobulin protein. MIT (monoiodotyrosine) and DIT (diiodotyrosine) are used to produce T3 and T4 within the colloid. Upon stimulation by TSH, the thyroid hormones, bound to thyroglobulin, are taken into the follicular cells by pinocytosis. Hydrolysis reactions within the follicular cells release the free T4 and T3, which are secreted.

Lack Iodine

■ Figure 11.24 Endemic goiter is caused by insufficient iodine in the diet. A lack of iodine causes hypothyroidism, and the resulting elevation in TSH secretion stimulates the excessive growth of the thyroid.

the thyroid gland (fig. 11.24). In the absence of sufficient dietary iodine, the thyroid cannot produce adequate amounts of T4 and T3. The resulting lack of negative feedback inhibition causes abnormally high levels of TSH secretion, which in turn stimulates the abnormal growth of the thyroid. These events are summarized in figure 11.25.

People who have inadequate secretion of thyroid hormones are said to be hypothyroid. As might be predicted from the effects of thyroxine, people who are hypothyroid have an abnormally low basal metabolic rate and experience weight gain and lethargy. A thyroxine deficiency also decreases the ability to adapt to cold stress. Hypothyroidism in adults causes myxedema—accumulation of mucoproteins and fluid in subcutaneous connective tissues. Symptoms of this disease include swelling of the hands, face, feet, and tissues around the eyes.

Clinical Investigation Clue

Remember that Rosemary's puffiness was determined not to be myxedema, and that her blood T4 and T3 levels were normal. What disorder is ruled out by these observations?

Hypothyroidism can result from a thyroid gland defect or secondarily from insufficient thyrotropin-releasing hormone (TRH) secretion from the hypothalamus, or insufficient TSH secretion from the anterior pituitary, or insufficient iodine in the diet. In the latter case, excessive TSH secretion stimulates abnormal thyroid growth and the development of an endemic goiter, as described previously. The hypothyroidism and goiter caused by iodine deficiency can be reversed by iodine supplements.

Hypothalamus

Normal thyroid

Anterior pituitary

Thyroid

If iodine inadequate

If iodine adequate

Negative feedback

T3 and T4

Low negative feedback

Ante pitui

;rior tary

Exces

s TSH

Thyroid

Hypertorphy— produces goiter

Hypertorphy— produces goiter

Growth (goiter)

■ Figure 11.25 How iodine deficiency causes a goiter. Lack of adequate iodine in the diet interferes with the negative feedback control of TSH secretion, resulting in the formation of an endemic goiter.

A goiter can also be produced by another mechanism. In Graves' disease, autoantibodies (chapter 15) exert TSH-like effects on the thyroid. Since the production of these antibodies is not inhibited by negative feedback, the high secretion of thyrox-ine that results cannot turn off the excessive stimulation of the thyroid. As a result, the person is hyperthyroid (has excessive thyroxine secretion) and develops a goiter. This condition is called toxic goiter, or thyrotoxicosis. This condition is often accompanied by exophthalmos, or bulging eyes, due to edema in the orbits (fig. 11.26). The hyperthyroid state produces a high BMR accompanied by weight loss, nervousness, irritability, and an intolerance to heat. There is also a significant increase in cardiac output and blood pressure (chapter 14). The symptoms of hypothyroidism and hyperthyroidism are compared in table 11.8.

Because of its stimulation of protein synthesis, children need thyroxine for body growth and, most importantly, for the proper development of the central nervous system. The need for thyroxine is particularly great when the brain is undergoing its

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Table 11.8 Comparison of Hypothyroidism and Hyperthyroidism

Feature

Hypothyroid

Hyperthyroid

Growth and development

Impaired growth

Accelerated growth

Activity and sleep

Lethargy; increased sleep

Increased activity; decreased sleep

Temperature tolerance

Intolerance to cold

Intolerance to heat

Skin characteristics

Coarse, dry skin

Normal skin

Perspiration

Absent

Excessive

Pulse

Slow

Rapid

Gastrointestinal symptoms

Constipation; decreased appetite; increased weight

Frequent bowel movements; increased appetite; decreased weight

Reflexes

Slow

Rapid

Psychological aspects

Depression and apathy

Nervous, "emotional" state

Plasma T4 levels

Decreased

Increased

Hyperthyroid Appetite

■ Figure 11.26 A symptom of hyperthyroidism. Hyperthyroidism is characterized by an increased metabolic rate, weight loss, muscular weakness, and nervousness. The eyes may also protrude (exophthalmos) due to edema in the orbits.

greatest rate of development—from the end of the first trimester of prenatal life to 6 months after birth. Hypothyroidism during this time may result in cretinism (fig. 11.27). Unlike people with dwarfism, who have inadequate secretion of growth hormone from the anterior pituitary, people with cretinism suffer severe mental retardation. Treatment with thyroxine soon after birth, particularly before 1 month of age, has been found to completely or almost completely restore development of intelligence as measured by IQ tests administered 5 years later.

Cretinism Disease

■ Figure 11.27 Cretinism. Cretinism is a disease of infancy caused by an underactive thyroid gland.

Parathyroid hormone (PTH) is the only hormone secreted by the parathyroid glands. PTH, however, is the single most important hormone in the control of the calcium levels of the blood. It promotes a rise in blood calcium levels by acting on the bones, kidneys, and intestine (fig. 11.29). Regulation of calcium balance is described in more detail in chapter 19.

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