Ganong's Review of Medical Physiology, 23rd Edition

CHAPTER 20The Thyroid Gland 307

levels and a reciprocal rise in RT 3. Selenium deficiency has the
same effect. A wide variety of nonthyroidal illnesses also sup-
press deiodinases. These include burns, trauma, advanced
cancer, cirrhosis, renal failure, myocardial infarction, and feb-
rile states. The low-T 3 state produced by these conditions dis-
appears with recovery. It is difficult to decide whether
individuals with the low-T 3 state produced by drugs and ill-
ness have mild hypothyroidism.
Diet also has a clear-cut effect on conversion of T 4 to T 3. In
fasted individuals, plasma T 3 is reduced by 10–20% within 24
h and by about 50% in 3 to 7 d, with a corresponding rise in
RT 3 (Figure 20–9). Free and bound T 4 levels remain essen-
tially normal. During more prolonged starvation, RT 3 returns
to normal but T 3 remains depressed. At the same time, the
basal metabolic rate (BMR) falls and urinary nitrogen excre-
tion, an index of protein breakdown, is decreased. Thus, the
decline in T 3 conserves calories and protein. Conversely,
overfeeding increases T 3 and reduces RT 3.

REGULATION OF

THYROID SECRETION

Thyroid function is regulated primarily by variations in the
circulating level of pituitary TSH (Figure 20–8). TSH secretion
is increased by the hypothalamic hormone thyrotropin-releas-
ing hormone (TRH; see Chapter 18) and inhibited in a nega-
tive feedback fashion by circulating free T 4 and T 3. The effect
of T 4 is enhanced by production of T 3 in the cytoplasm of the
pituitary cells by the 5'-D 2 they contain. TSH secretion is also

inhibited by stress, and in experimental animals it is increased

by cold and decreased by warmth.

CHEMISTRY & METABOLISM OF TSH

Human TSH is a glycoprotein that contains 211 amino acid res-

idues. It is made up of two subunits, designated α and β. The α

subunit is encoded by a gene on chromosome 6 and the β sub-

unit by a gene on chromosome 1. The α and β subunits become

noncovalently linked in the pituitary thyrotropes. TSH-α is

identical to the α subunit of LH, FSH, and hCG-α (see Chapters

24 and 25). The functional specificity of TSH is conferred by the

β subunit. The structure of TSH varies from species to species,

but other mammalian TSHs are biologically active in humans.

The biologic half-life of human TSH is about 60 min. TSH is

degraded for the most part in the kidneys and to a lesser extent

in the liver. Secretion is pulsatile, and mean output starts to rise

at about 9:00 PM, peaks at midnight, and then declines during

the day. The normal secretion rate is about 110 μg/d. The aver-

age plasma level is about 2 μg/mL (Figure 20–10).

Because the α subunit in hCG is the same as that in TSH,

large amounts of hCG can activate thyroid receptors nonspe-

cifically. In some patients with benign or malignant tumors of

placental origin, plasma hCG levels can rise so high that they

produce mild hyperthyroidism.

EFFECTS OF TSH ON THE THYROID

When the pituitary is removed, thyroid function is depressed

and the gland atrophies; when TSH is administered, thyroid

FIGURE 20–9 Effect of starvation on plasma levels of T 4 , T 3 ,
and RT 3 in humans. Similar changes occur in wasting diseases. The
scale for T 3 and RT 3 is on the left and the scale for T 4 is on the right.
(Reproduced with permission from Burger AG: New aspects of the peripheral action
of thyroid hormones. Triangle, Sandoz J Med Sci 1983;22:175. Copyright © 1983
Sandoz Ltd., Basel, Switzerland.)

Starvation

Days

240

200

160

120

80

40

0

− 4 − 2 0 2 4 6 8 10 +2 +4

12

10

8

6

4

2

0

T 4

T 3

RT 3

ng/dL μg/dL

FIGURE 20–10 Relation between plasma TSH, measured by

a highly sensitive radioimmunoassay, and plasma free T 4 ,

measured by dialysis (FT 4 ). Note that the TSH scale is a log scale.

Levothyroxine suppressed

(euthyroid) (n = 20)

Hypothyroid (primary) (n = 49)

Hyperthyroid (nonpituitary) (n = 56)

Euthyroid (n = 194)

1000

100

10

1

0.1

0.01

012345630

TSH (

μU/mL)

FT 4 (ng/dL)