Ganong's Review of Medical Physiology, 23rd Edition

CHAPTER 20The Thyroid Gland 311

be distinguished from jaundice because in the former condi-
tion the scleras are not yellow.
The skin normally contains a variety of proteins combined
with polysaccharides, hyaluronic acid, and chondroitin sulfu-

ric acid. In hypothyroidism, these complexes accumulate,

promoting water retention and the characteristic puffiness of

the skin (myxedema). When thyroid hormones are adminis-

tered, the proteins are metabolized, and diuresis continues

until the myxedema is cleared.

Milk secretion is decreased in hypothyroidism and stimu-

lated by thyroid hormones, a fact sometimes put to practical

use in the dairy industry. Thyroid hormones do not stimulate

TABLE 20–4 Causes of hyperthyroidism.

Thyroid overactivity

Solitary toxic adenoma

Toxic multinodular goiter

Hashimoto thyroiditis

TSH-secreting pituitary tumor

Mutations causing constitutive activation of TSH receptor

Other rare causes

Extrathyroidal

Administration of T 3 or T 4 (factitious or iatrogenic hyperthyroidism)

Ectopic thyroid tissue

TABLE 20–5 Physiologic effects
of thyroid hormones.

Target

Tissue Effect Mechanism

Heart Chronotropic

Inotropic

Increased number of β-adrenergic

receptors

Enhanced responses to circulating

catecholamines

Increased proportion of α-myosin

heavy chain (with higher ATPase

activity)

Adipose

tissue

Catabolic Stimulated lipolysis

Muscle Catabolic Increased protein breakdown

Bone Developmental Promote normal growth and skel-

etal development

Nervous

system

Developmental Promote normal brain develop-

ment

Gut Metabolic Increased rate of carbohydrate

absorption

Lipoprotein Metabolic Formation of LDL receptors

Other Calorigenic Stimulated oxygen consumption

by metabolically active tissues (ex-

ceptions: testes, uterus, lymph

nodes, spleen, anterior pituitary)

Increased metabolic rate

Modified and reproduced with permission from McPhee SJ, Lingarra VR, Ganong
WF (editors): Pathophysiology of Disease, 4th ed. McGraw-Hill, 2003.

CLINICAL BOX 20–3

Thyroid Hormone Resistance

Some mutations in the gene that codes for TRβ are associ-

ated with resistance to the effects of T 3 and T 4. Most com-

monly, there is resistance to thyroid hormones in the pe-

ripheral tissues and the anterior pituitary gland. Patients

with this abnormality are usually not clinically hypothyroid,

because they maintain plasma levels of T 3 and T 4 that are

high enough to overcome the resistance, and hTRα is unaf-

fected. However, plasma TSH is inappropriately high given

the high circulating T 3 and T 4 levels and is difficult to sup-

press with exogenous thyroid hormone. Some patients

have thyroid hormone resistance only in the pituitary. They

have hypermetabolism and elevated plasma T 3 and T 4 le-

vels with normal, nonsuppressible levels of TSH. A few pa-

tients apparently have peripheral resistance with normal

pituitary sensitivity. They have hypometabolism despite

normal plasma levels of T 3 , T 4 , and TSH, and they require

large doses of thyroid hormones to increase their meta-

bolic rate. An interesting finding is that attention deficit

hyperactivity disorder, a condition frequently diagnosed

in children who are overactive and impulsive, is much more

common in individuals with thyroid hormone resistance

than in the general population. This suggests that hTRβ

may play a special role in brain development.

FIGURE 20–13 Calorigenic responses of thyroidectomized

rats to subcutaneous injections of T 4 and T 3. (Redrawn and reproduced

with permission from Barker SB: Peripheral actions of thyroid hormones. Fed Proc

1962;21:635.)

80

60

40

20

20 40 60

Increased metabolism

(mL O

/100 g/h) 2

80 100

Dose (μg/kg/d)

T 3

T 4