Thyroid Metabolic Hormones pdf - Endocrinology and Reproduction

intestinal tract into the blood in about the same manner as chlorides. Normally,

to every 100,000 parts sodium chloride.

iodine deficiency, common table salt is iodized with about 1 part sodium iodide

. To prevent

1 mg/week

, or about

each year

To form normal quantities of thyroxine, about 50 milligrams of ingested iodine

Iodine Is Required for Formation of Thyroxine

any other area of the body, with the possible exception of the adrenal cortex.

the weight of the gland each minute, which is a blood supply as great as that of

it can function in the body. The thyroid gland has a blood flow about five times

hormones within its molecule. Once the secretion has entered the follicles, it

, which contains the thyroid

that secrete into the interior of the follicles. The major constituent

in Figure 76–1, of large numbers of closed

The thyroid gland is composed, as shown

thyroxine.

ronine is about four times as potent as thyroxine, but it is present in the blood

tively the same, but they differ in rapidity and intensity of action. Triiodothy-

are functionally important. The functions of these two hormones are qualita-

roxine is eventually converted to triiodothyronine in the tissues, so that both

. However, almost all the thy-

, and 7 per cent

thyroxine

Metabolic Hormones

Synthesis and Secretion of the Thyroid

thyroid hormones, their metabolic functions, and regulation of their secretion.

The purpose of this chapter is to discuss the formation and secretion of the

, an important hormone for calcium

The thyroid gland also secretes

metabolic rate to 60 to 100 per cent above normal. Thyroid secretion is con-

below normal, and extreme excesses of thyroid secretion can increase the basal

the metabolic rate of the body. Complete lack of

tively. Both of these hormones profoundly increase

, respec-

, commonly called T

thyroxine

thyroid secretes two major hormones,

normally weighing 15 to 20 grams in adults. The

is one of the largest of the endocrine glands,

The thyroid gland, located immediately below the

Thyroid Metabolic Hormones

931

larynx on each side of and anterior to the trachea,

and

triiodothyronine

and T

thyroid secretion usually causes the basal metabolic rate to fall 40 to 50 per cent

trolled primarily by thyroid-stimulating hormone (TSH) secreted by the ante-
rior pituitary gland.

calcitonin

metabolism that is considered in detail in Chapter 79.

About 93 per cent of the metabolically active hormones secreted by the thyroid
gland is

triiodothyronine

in much smaller quantities and persists for a much shorter time than does

Physiologic Anatomy of the Thyroid Gland.

follicles (100 to 300 micrometers in

diameter) filled with a secretory substance called colloid and lined with cuboidal
epithelial cells
of colloid is the large glycoprotein thyroglobulin

must be absorbed back through the follicular epithelium into the blood before

in the form of iodides are required

Fate of Ingested Iodides.

Iodides ingested orally are absorbed from the gastro-

mones falls to zero.

from the cells, the rate of formation of thyroid hor-

stored thyroid gland colloid. When the peroxidase

brane of the cell or attached to it, thus providing the

The peroxidase is either located in the apical mem-

provide a potent system capable of oxidizing iodides.

, which

hydrogen peroxide

peroxidase

bining directly with the amino acid tyrosine. This oxi-

, that is then capable of com-

, either

oxidized form of iodine

The first essential step in the

thyroglobulin molecule. That is, the thyroxine and

mones. Thus, the thyroid hormones form

tyrosine amino acids, and they are the major substrates

, with a molecular weight of about

lar cells, as shown in Figure 76–2. The endoplasmic

The thyroid cells are typical protein-secreting glandu-

Triiodothyronine Formation

of Thyroxine and

pump in thyroid cells.

concentration of TSH; TSH stimulates and hypophy-

by several factors, the most important being the

centration ratio can rise to as high as 250 times. The

the thyroid gland becomes maximally active, this con-

about 30 times its concentration in the blood. When

gland, the iodide pump concentrates the iodide to

. In a normal

the cell. This is called

blood into the thyroid glandular cells and follicles. The

shown in Figure 76–2, is transport of iodides from the

The first stage in the formation of thyroid hormones,

Iodide Pump (Iodide Trapping)

hormones.

kidneys, but only after about one fifth are selectively

932

Unit XIV

Endocrinology and Reproduction

most of the iodides are rapidly excreted by the

removed from the circulating blood by the cells of the
thyroid gland and used for synthesis of the thyroid

basal membrane of the thyroid cell has the specific
ability to pump the iodide actively to the interior of

iodide trapping

rate of iodide trapping by the thyroid is influenced

sectomy greatly diminishes the activity of the iodide

Thyroglobulin, and Chemistry

Formation and Secretion of Thyroglobulin by the Thyroid Cells.

reticulum and Golgi apparatus synthesize and secrete
into the follicles a large glycoprotein molecule called
thyroglobulin
335,000.

Each molecule of thyroglobulin contains about 70

that combine with iodine to form the thyroid hor-

within the

triiodothyronine hormones formed from the tyrosine
amino acids remain part of the thyroglobulin molecule
during synthesis of the thyroid hormones and even
afterward as stored hormones in the follicular colloid.

Oxidation of the Iodide Ion.

formation of the thyroid hormones is conversion of
the iodide ions to an
nascent iodine (I

) or I

dation of iodine is promoted by the enzyme
and its accompanying

oxidized iodine at exactly the point in the cell where
the thyroglobulin molecule issues forth from the Golgi
apparatus and through the cell membrane into the

system is blocked or when it is hereditarily absent

Follicle

Cuboidal epithelial cells

Colloid

Red blood cells

of thyroglobulin into the follicles.

Microscopic appearance of the thyroid gland, showing secretion

Figure 76–1

yrosine

Golgi

MIT, DIT

DIT

Iodination

and

coupling

Peroxidase

Pinocytosis

Secretion

MIT

Proteases

Colloid
droplet

Deiodination

Thyroglobulin

precursor (T

)

, thyroglobulin.

, thyroxine; T

iodothyronine; T

MIT, monoiodotyrosine; DIT, diiodotyrosine; T

roxine and triiodothyronine release into the blood.

thyroxine and triiodothyronine formation, and thy-

Thyroid cellular mechanisms for iodine transport,

Figure 76–2

, tri-

nine. Therefore, the hormone finally delivered to and

ensuing few days, about one half of the thyroxine is

7 per cent is triiodothyronine. However, during the

Daily Rate of Secretion of Thyroxine and Triiodothyronine.

cling process.

become iodine-deficient because of failure of this recy-

tal absence of this deiodinase enzyme, many persons

forming additional thyroid hormones. In the congeni-

available again for recycling within the gland for

blood. Instead, their iodine is cleaved from them by a

ulin molecules. However, they are not secreted into the

cause release of thyroxine and triiodothyronine, these

but remains monoiodotyrosine and diiodotyrosine.

thyroid cell into the surrounding capillaries. Thus, the

free form. These then diffuse through the base of the

somes mixed with the colloid. Multiple

in the cell cytoplasm

thyroid cell. Then

released. This process occurs as follows: The apical

roglobulin molecule, and then these free hormones are

blood in measurable amounts; instead, thyroxine and

Thyroglobulin itself is not released into the circulating

Triiodothyronine from the

months.

ologic effects of deficiency are not observed for several

when synthesis of thyroid hormone ceases, the physi-

of thyroid hormones for 2 to 3 months. Therefore,

triiodothyronine molecules. In this form, the thyroid

hormones has run its course, each thyroglobulin mol-

amounts of hormone. After synthesis of the thyroid

The thyroid gland is unusual

sents about one fifteenth of the final hormones.

triiodothyronine,

the thyroglobulin molecule. Or one molecule of

thyroxine

The major hormonal product of the coupling reac-

another.

next few minutes, hours, and even days, more and more

. Then, during the

iodothyronine. Tyrosine is first iodized to

important thyroid hormones, thyroxine and tri-

Figure 76–3 shows the successive stages of

thyroglobulin molecule.

cell membrane into the follicle, iodine binds with

within seconds or minutes. Therefore, almost as rapidly

enzyme (Figure 76–2) that causes the process to occur

the amino acid tyrosine. In the thyroid cells, however,

of the thyroglobulin. Oxidized iodine even in the

The binding of iodine

Iodination of Tyrosine and Formation of the Thyroid Hormones—

Chapter 76

Thyroid Metabolic Hormones

933

“Organification” of Thyroglobulin.

with the thyroglobulin molecule is called organifica-
tion
molecular form will bind directly but very slowly with

the oxidized iodine is associated with an iodinase

as the thyroglobulin molecule is released from the
Golgi apparatus or as it is secreted through the apical

about one sixth of the tyrosine amino acids within the

iodination of tyrosine and final formation of the two

monoiodoty-

rosine and then to diiodotyrosine

of the iodotyrosine residues become coupled with one

tion is the molecule

that remains part of

monoiodotyrosine couples with one molecule of
diiodotyrosine to form

which repre-

Storage of Thyroglobulin.

among the endocrine glands in its ability to store large

ecule contains up to 30 thyroxine molecules and a few

hormones are stored in the follicles in an amount suf-
ficient to supply the body with its normal requirements

Release of Thyroxine and

Thyroid Gland

triiodothyronine must first be cleaved from the thy-

surface of the thyroid cells sends out pseudopod exten-
sions that close around small portions of the colloid to
form pinocytic vesicles that enter the apex of the

lysosomes

immediately fuse with these vesicles to form digestive
vesicles containing digestive enzymes from the lyso-

proteases

among the enzymes digest the thyroglobulin mole-
cules and release thyroxine and triiodothyronine in

thyroid hormones are released into the blood.

About three quarters of the iodinated tyrosine in

the thyroglobulin never becomes thyroid hormones

During the digestion of the thyroglobulin molecule to

iodinated tyrosines also are freed from the thyroglob-

deiodinase enzyme that makes virtually all this iodine

About 93 per cent of the thyroid hormone released
from the thyroid gland is normally thyroxine and only

slowly deiodinated to form additional triiodothyro-

CHNH

COOH

Diiodotyrosine

Monoiodotyrosine

Diiodotyrosine

CHNH

COOH

CHNH

COOH

CHNH

COOH

CHNH

COOH

Iodinase

Tyrosine

Monoiodotyrosine

Diiodotyrosine

3,5,3'-Triiodothyronine

Thyroxine

Chemistry of thyroxine and triiodothyronine formation.

Figure 76–3

ties of almost all the tissues of the body. The basal

The thyroid hormones increase the metabolic activi-

proteins.

much as sixfold. It is believed that most, if not all, of

percentages—some only slightly, and others at least as

However, not all the proteins are increased by similar

somes to form hundreds of new intracellular proteins.

hours by RNA translation on the cytoplasmic ribo-

are formed, followed within another few minutes or

large numbers of different types of messenger RNA

activated and initiate the transcription process. Then

binding with thyroid hormone, the receptors become

elements on the DNA. On

The thyroid hormone receptor usually forms a het-

hormone receptors are either attached to the DNA

The thyroid

cules that bind with the receptors is triiodothyronine.

very high affinity for triiodothyronine. Consequently,

nine. Intracellular thyroid hormone receptors have a

almost all the thyroxine, thus forming triiodothyro-

genetic transcription, one iodide is removed from

Triiodothyronine.

functional activity throughout the body.

synthesized. The net result is generalized increase in

proteins, transport proteins, and other substances are

body, great numbers of protein enzymes, structural

(Figure 76–5). Therefore, in virtually all cells of the

The general effect of thyroid hormone is to activate

of Genes

Transcription of Large Numbers

Thyroid Hormones

themselves.

tissue cells, followed by their slow release. However,

Most of the latency and prolonged period of action

activity occurring within 2 to 3 days.

times as rapidly as those of thyroxine, with a latent

The actions of triiodothyronine occur about four

activity persists for as long as 6 weeks to 2 months.

decreases with a half-life of about 15 days. Some of the

to 12 days, as shown in Figure 76–4. Thereafter, it

roxine activity begins. Once activity does begin, it

rate can be discerned for 2 to 3 days, thereby demon-

human being, essentially no effect on the metabolic

used slowly over a period of days or weeks.

this time in the target cells themselves, and they are

iodothyronine. Therefore, they are again stored, but

iodothyronine again bind with intracellular proteins,

On entering the tissue cells, both thyroxine and tri-

released to the cells in about 1 day.

to the tissue cells about every 6 days, whereas half the

cells slowly. Half the thyroxine in the blood is released

in particular, thyroxine—are released to the tissue

proteins for the thyroid hormones, these substances—

Thyroxine and Triiodothyronine Are Released Slowly to Tissue

thyroxine-binding prealbumin

thyroxine-binding globulin

synthesized by the liver. They combine mainly with

with several of the plasma proteins, all of which are

On entering the blood, over 99 per cent of the thy-

Thyroxine and Triiodothyronine Are Bound to Plasma Proteins.

Triiodothyronine to Tissues

Transport of Thyroxine and

of about 35 micrograms of triiodothyronine per day.

used by the tissues is mainly triiodothyronine, a total

934

Unit XIV

Endocrinology and Reproduction

roxine and triiodothyronine combines immediately

and much less so with

and albumin.

Cells.

Because of high affinity of the plasma-binding

triiodothyronine—because of its lower affinity—is

the thyroxine binding more strongly than the tri-

Thyroid Hormones Have Slow Onset and Long Duration of Action.

After injection of a large quantity of thyroxine into a

strating that there is a long latent period before thy-

increases progressively and reaches a maximum in 10

period as short as 6 to 12 hours and maximal cellular

of these hormones are probably caused by their
binding with proteins both in the plasma and in the

we shall see in subsequent discussions that part of the
latent period also results from the manner in which
these hormones perform their functions in the cells

Physiologic Functions of the

Thyroid Hormones Increase the

nuclear transcription of large numbers of genes

Most of the Thyroxine Secreted by the Thyroid Is Converted to

Before acting on the genes to increase

more than 90 per cent of the thyroid hormone mole-

Thyroid Hormones Activate Nuclear Receptors.

genetic strands or located in proximity to them.

erodimer with retinoid X receptor (RXR) at specific
thyroid hormone response

the actions of thyroid hormone result from the subse-
quent enzymatic and other functions of these new

Thyroid Hormones Increase Cellular
Metabolic Activity

Basal metabolic rate

Days

Thyroxine injected

by administering a single large dose of thyroxine.

Approximate prolonged effect on the basal metabolic rate caused

Figure 76–4

most cells to become leaky to sodium ions, which

hormone increases the body’s metabolic rate. In fact,

produced in the body, it has been suggested that this

the cell membranes of some tissues. Because this

This in turn increases the rate of

ATPase

Thyroid Hormones Increase Active Transport of Ions Through

the cause of the increase.

gize cellular function. However, the increase in the

formation of adenosine triphosphate (ATP) to ener-

of mitochondria, which in turn increases the rate of

Therefore, one of the principal functions of thyroxine

Furthermore, the total membrane surface area of the

animal’s body increase in size as well as number.

to an animal, the mitochondria in most cells of the

When thyroxine or triiodothyronine is given

are excited, and the activities of most of the other

people is greatly accelerated. The mental processes

catabolism is also increased. The growth rate of young

thesis is increased, at the same time the rate of protein

greatly accelerated. Although the rate of protein syn-

secreted. The rate of utilization of foods for energy is

Chapter 76

Thyroid Metabolic Hormones

935

metabolic rate can increase to 60 to 100 per cent above
normal when large quantities of the hormones are

endocrine glands are increased.

Thyroid Hormones Increase the Number and Activity of Mito-
chondria.

mitochondria increases almost directly in proportion
to the increased metabolic rate of the whole animal.

might be simply to increase the number and activity

number and activity of mitochondria could be the
result of increased activity of the cells as well as

Cell Membranes.

One of the enzymes that increases its

activity in response to thyroid hormone is Na

-K

transport of both sodium and potassium ions through

process uses energy and increases the amount of heat

might be one of the mechanisms by which thyroid

thyroid hormone also causes the cell membranes of

further activates the sodium pump and further
increases heat production.

-ATPase

Tissue blood flow

Iodinase

Cell membrane

Cytoplasm

Nuclear
membrane

Nucleus

Thyroid
hormone
receptor

Thyroid

hormone

response

Thyroid

hormone

response

Gene

transcription

Gene

transcription

mRNA

Synthesis of

new proteins

Synthesis of

new proteins

Metabolism

Cardiac output

Heart rate
Heart strength
Respiration

Cardiac output

Heart rate
Heart strength
Respiration

Mitochondria
Na

-K

consumption

Glucose absorption
Gluconeogenesis
Glycogenolysis
Lipolysis
Protein synthesis
BMR

Mitochondria
Na

-K

consumption

Glucose absorption
Gluconeogenesis
Glycogenolysis
Lipolysis
Protein synthesis
BMR

Many other

systems

Many other

systems

Gene

Retinoid X

receptor

Cardiovascular

CNS

development

CNS

development

Growth

are shown. mRNA, messenger

of several different systems

of thyroid hormone on cells

response of the cell. The actions

producing the thyroid hormone

to formation of proteins, thus

either increases or decreases in

the thyroid hormone response

with a retinoid X receptor, of

ceptor, bound as a heterodimer

with the thyroid hormone re-

nated to form T

diffuse through the cell mem-

) readily

triiodothyronine (T

target cells. Thyroxine (T

Thyroid hormone activation of

Figure 76–5

) and

brane. Much of the T

is deiodi-

, which interacts

element of the gene. This causes

transcription of genes that lead

ribonucleic acid.

Decreased Body Weight.

cause very high basal metabolic rates.

of thyroid hormones and the basal metabolic rate.

rate falls almost to one-half normal. Figure 76–6 shows

thyroid hormone is produced, the basal metabolic

100 per cent above normal. Conversely, when no

the body, excessive quantities of the hormone can

quantities of vitamins are made available.

hormone is secreted, unless at the same time increased

tive vitamin deficiency can occur when excess thyroid

causes increased need for vitamins. Therefore, a rela-

some of the enzymes or coenzymes, thyroid hormone

of cholesterol in these lipoproteins by the liver cells.

low-density lipoprotein receptors on the liver cells,

in the bile and consequent loss in the feces. A possible

osclerosis, discussed in Chapter 68.

deposition of fat in the liver as well. The large increase

plasma concentrations of cholesterol, phospholipids,

the free fatty acids. Conversely,

phospholipids, and triglycerides in the plasma, even

ates the oxidation of free fatty acids by the cells.

other tissue element. This also increases the free fatty

rapidly from the fat tissue, which decreases the fat

of thyroid hormone. In particular, lipids are mobilized

thyroid hormone.

lism. All these effects probably result from the overall

tract, and even increased insulin secretion with its

cells, enhanced glycolysis, enhanced gluconeogenesis,

bolism, including rapid uptake of glucose by the

Thyroid hormone

Effects of Thyroid Hormone

more fully later in the chapter.

mentally deficient throughout life. This is discussed

birth, the child without a thyroid gland will remain

and the brain remains smaller than normal. Without

thyroid hormone, growth and maturation of the brain

fetal life and for the first few years of postnatal life.

at an early age, so that the duration of growth and

siderably taller at an earlier age. However, the bones

growth often occurs, causing the child to become con-

In those who are hyperthyroid, excessive skeletal

are hypothyroid, the rate of growth is greatly retarded.

is manifest mainly in growing children. In those who

In humans, the effect of thyroid hormone on growth

change of the tadpole into the frog.

on growth. For instance, it has long been known that

Thyroid hormone has both general and specific effects

Effect of Thyroid Hormone on Growth

936

Unit XIV

Endocrinology and Reproduction

thyroid hormone is essential for the metamorphic

also mature more rapidly and the epiphyses close

the eventual height of the adult may actually be
shortened.

An important effect of thyroid hormone is to

promote growth and development of the brain during

If the fetus does not secrete sufficient quantities of

both before birth and afterward are greatly retarded,

specific thyroid therapy within days or weeks after

on Specific Bodily Mechanisms

Stimulation of Carbohydrate Metabolism.

stimulates almost all aspects of carbohydrate meta-

increased rate of absorption from the gastrointestinal

resultant secondary effects on carbohydrate metabo-

increase in cellular metabolic enzymes caused by

Stimulation of Fat Metabolism.

Essentially all aspects of

fat metabolism are also enhanced under the influence

stores of the body to a greater extent than almost any

acid concentration in the plasma and greatly acceler-

Effect on Plasma and Liver Fats.

Increased thyroid

hormone decreases the concentrations of cholesterol,

though it increases
decreased thyroid secretion greatly increases the

and triglycerides and almost always causes excessive

in circulating plasma cholesterol in prolonged

hypothyroidism is often associated with severe ather-

One of the mechanisms by which thyroid hormone

decreases the plasma cholesterol concentration is to
increase significantly the rate of cholesterol secretion

mechanism for the increased cholesterol secretion is
that thyroid hormone induces increased numbers of

leading to rapid removal of low-density lipoproteins
from the plasma by the liver and subsequent secretion

Increased Requirement for Vitamins.

Because thyroid

hormone increases the quantities of many bodily
enzymes and because vitamins are essential parts of

Increased Basal Metabolic Rate.

Because thyroid

hormone increases metabolism in almost all cells of

occasionally increase the basal metabolic rate 60 to

the approximate relation between the daily supply

Extreme amounts of the hormones are required to

Greatly increased thyroid

hormone almost always decreases the body weight,

300

200

100

Basal metabolic rate

Thyroid hormones (

g/day)

Thyroid hormones (

g/day)

secretion to the basal metabolic rate.

Approximate relation of daily rate of thyroid hormone (T

Figure 76–6

and T

)

sexual function, thyroid secretion needs to be

For normal

tion by the adrenal glands.

and, therefore, increased rate of glucocorticoid secre-

liver. This leads to feedback increase in adrenocorti-

hormone. Thyroid hormone also increases the rate at

a consequence, increases the need for parathyroid

metabolic activities related to bone formation and, as

the pancreas. Also, thyroid hormone increases many

tissues for the hormones. For instance, increased thy-

endocrine glands, but it also increases the need of the

times lasting 12 to 14 hours a day.

is characteristic of hypothyroidism, with sleep some-

it is difficult to sleep. Conversely, extreme somnolence

excitable effects of thyroid hormone on the synapses,

has a feeling of constant tiredness, but because of the

central nervous system, the hyperthyroid subject often

spinal cord that control muscle tone. The tremor is an

This tremor is believed to be caused by increased reac-

fingers and noting the degree of vibration of the paper.

10 to 15 times per second. The tremor can be observed

shivering, because it occurs at the rapid frequency of

coarse tremor that occurs in Parkinson’s disease or in

hyperthyroidism is a fine muscle tremor. This is not the

Muscle Tremor.

hormone causes the muscles to become sluggish, and

excess protein catabolism. Conversely, lack of thyroid

excessive, the muscles become weakened because of

vigor, but when the quantity of hormone becomes

anxiety complexes, extreme worry, and paranoia.

ness and many psychoneurotic tendencies, such as

thyroid hormone decreases this function. The hyper-

but also often dissociates this; conversely, lack of

In general,

Excitatory Effects on the Central Nervous System.

diarrhea. Lack of thyroid hormone can cause consti-

gastrointestinal tract. Hyperthyroidism often results in

discussed, thyroid hormone increases both the rates of

increased appetite and food intake, which has been

Increased Gastrointestinal Motility.

carbon dioxide; these effects activate all the mecha-

The increased rate of metabolism

vated in hyperthyroidism 10 to 15 mm Hg and the

sure is often increased, with the systolic pressure ele-

through the tissues between heartbeats, the pulse pres-

thyroid hormone. Because of increased blood flow

The

Normal Arterial Pressure.

catabolism. Indeed, some severely thyrotoxic patients

markedly,

the heart muscle strength becomes

However, when thyroid hormone is increased

strength that occurs in mild fevers and during exercise.

secreted. This is analogous to the increase in heart

The increased enzymatic

which in turn increases the heart rate. This effect is of

cardiac output. Therefore, thyroid hormone seems to

The heart rate increases con-

output also increases, sometimes rising to 60 per cent

a consequence of the increased blood flow, cardiac

increased need for heat elimination from the body. As

tissues, thus increasing blood flow. The rate of blood

tissues. These effects cause vasodilation in most body

Increased Blood Flow and Cardiac Output.

Effect of Thyroid Hormones on the Cardiovascular System

the metabolic rate.

appetite, and this may counterbalance the change in

occur, because thyroid hormone also increases the

increases the body weight; these effects do not always

Chapter 76

Thyroid Metabolic Hormones

937

and greatly decreased hormone almost always

Increased

metabolism in the tissues causes more rapid utilization
of oxygen than normal and release of greater than
normal quantities of metabolic end products from the

flow in the skin especially increases because of the

or more above normal when excessive thyroid
hormone is present and falling to only 50 per cent of
normal in very severe hypothyroidism.

Increased Heart Rate.

siderably more under the influence of thyroid
hormone than would be expected from the increase in

have a direct effect on the excitability of the heart,

particular importance because the heart rate is one of
the sensitive physical signs that the clinician uses in
determining whether a patient has excessive or dimin-
ished thyroid hormone production.

Increased Heart Strength.

activity caused by increased thyroid hormone produc-
tion apparently increases the strength of the heart
when only a slight excess of thyroid hormone is

depressed because of long-term excessive protein

die of cardiac decompensation secondary to myocar-
dial failure and to increased cardiac load imposed by
the increase in cardiac output.

mean arterial pressure

usually remains about normal after administration of

diastolic pressure reduced a corresponding amount.

Increased Respiration.

increases the utilization of oxygen and formation of

nisms that increase the rate and depth of respiration.

In addition to

secretion of the digestive juices and the motility of the

pation.

thyroid hormone increases the rapidity of cerebration

thyroid individual is likely to have extreme nervous-

Effect on the Function of the Muscles.

Slight increase in

thyroid hormone usually makes the muscles react with

they relax slowly after a contraction.

One of the most characteristic signs of

easily by placing a sheet of paper on the extended

tivity of the neuronal synapses in the areas of the

important means for assessing the degree of thyroid
hormone effect on the central nervous system.

Effect on Sleep.

Because of the exhausting effect of

thyroid hormone on the musculature and on the

Effect on Other Endocrine Glands.

Increased thyroid

hormone increases the rates of secretion of most other

roxine secretion increases the rate of glucose metabo-
lism everywhere in the body and therefore causes a
corresponding need for increased insulin secretion by

which adrenal glucocorticoids are inactivated by the

cotropic hormone production by the anterior pituitary

Effect of Thyroid Hormone on Sexual Function.

ing the rate of TRH secretion by the hypothalamus,

Effects of Cold and Other Neurogenic Stimuli on TRH and TSH

tually leads to TSH release.

including calcium ions and diacyl glycerol, which even-

lowed by a cascade of other second messengers,

cells to produce large amounts of phospholipase C, fol-

pholipase second messenger system

pituitary cell membrane.This in turn

produce TSH is first to bind with TRH receptors in the

the TSH-secreting cells of the anterior pituitary to

The molecular mechanism by which TRH causes

greatly but is not reduced to zero.

secretion of TSH by the anterior pituitary decreases

anterior pituitary gland becomes blocked, the rate of

itary gland cells to increase their output of TSH. When

. TRH directly affects the anterior pitu-

pyroglutamyl-histidyl-

substance, a tripeptide amide—

TRH has been obtained in pure form. It is a simple

hypophysial portal blood, as explained in Chapter 74.

the median eminence, the TRH is then transported to

in the median eminence of the hypothalamus. From

, which is secreted by nerve endings

hormone (TRH)

by a hypothalamic hormone,

Anterior pituitary secretion of TSH is controlled

Hormone from the Hypothalamus

Regulated by Thyrotropin-Releasing

ger” in many other target tissues of the body, as

similar to the function of cAMP as a “second messen-

This method for control of thyroid cell activity is

thyroid glandular tissue itself.

The result is both an immediate increase in secretion

to activate protein kinase, which

mation of cAMP inside the cell. Finally, the cAMP acts

in the membrane, which increases the for-

surfaces of the thyroid cell. This then activates

with specific TSH receptors on the basal membrane

The first event in this activation is binding of TSH

from activation of the “second messenger”

is now clear that most, if not all, of these effects result

many and varied effects of TSH on the thyroid cell. It

In the past, it was difficult to explain the

Cyclic Adenosine Monophosphate Mediates the Stimulatory

develop fully.

nine into the blood within 30 minutes. The other

of TSH is to initiate proteolysis of the thyroglobulin,

The most important early effect after administration

activities of the thyroid glandular cells.

In summary, TSH increases all the known secretory

Increased size and increased secretory activity of

to form the

glandular cells, sometimes increasing the ratio of

increases the rate of “iodide trapping” in the

, which

has already been stored in the follicles, with

triiodothyronine by the thyroid gland. Its specific

in Chapter 74, increases the secretion of thyroxine and

weight of about 28,000. This hormone, also discussed

pituitary hormone, a glycoprotein with a molecular

, is an anterior

TSH, also known as

TSH (from the Anterior Pituitary Gland) Increases Thyroid Secre-

thyroid secretion. These mechanisms are as follows.

must be secreted at all times; to achieve this, specific

body, precisely the right amount of thyroid hormone

To maintain normal levels of metabolic activity in the

Hormone Secretion

Regulation of Thyroid

functions.

The action of thyroid hormone on the gonads

common, and occasionally amenorrhea results.

, which means greatly reduced bleeding, is

confusing, in the hyperthyroid woman,

greatly decreased libido. To make the picture still more

A hypothyroid woman, like a man, is likely to have

Yet, strangely enough, in other women thyroid lack

tively, excessive and frequent menstrual bleeding.

that is, respec-

In women, lack of thyroid hormone often causes

of the hormone, however, sometimes cause impotence.

hormone is likely to cause loss of libido; great excesses

approximately normal. In men, lack of thyroid

938

Unit XIV

Endocrinology and Reproduction

menorrhagia and polymenorrhea—

may cause irregular periods and occasionally even
amenorrhea.

oligomenor-

rhea

cannot be pinpointed to a specific function but prob-
ably results from a combination of direct metabolic
effects on the gonads as well as excitatory and
inhibitory feedback effects operating through the
anterior pituitary hormones that control the sexual

feedback mechanisms operate through the hypothala-
mus and anterior pituitary gland to control the rate of

tion.

thyrotropin

effects on the thyroid gland are as follows:
1. Increased proteolysis of the thyroglobulin that

resultant release of the thyroid hormones into
the circulating blood and diminishment of the
follicular substance itself

2. Increased activity of the iodide pump

intracellular to extracellular iodide concentration
in the glandular substance to as much as eight
times normal

3. Increased iodination of tyrosine

thyroid hormones

the thyroid cells

5. Increased number of thyroid cells plus a change

from cuboidal to columnar cells and much
infolding of the thyroid epithelium into the
follicles

which causes release of thyroxine and triiodothyro-

effects require hours or even days and weeks to

Effect of TSH.

cyclic

adenosine monophosphate (cAMP) system of the cell.

adeny-

lyl cyclase

as a second messenger
causes multiple phosphorylations throughout the cell.

of thyroid hormones and prolonged growth of the

discussed in Chapter 74.

Anterior Pituitary Secretion of TSH Is

thyrotropin-releasing

the anterior pituitary by way of the hypothalamic-

proline-amide

the blood portal system from the hypothalamus to the

activates the phos-

inside the pituitary

Secretion.

One of the best-known stimuli for increas-

phases of thyroid activity, they slightly decrease the size

of the thyroid hormones from the storage colloid, there

concentrations. Because this is the first step in release

normal endocytosis of colloid from the follicles by the

hormones is also decreased. Even more important, the

The effect is to reduce the rate of iodide trapping, so

but often they remain decreased for only a few weeks.

level), most activities of the thyroid gland are decreased,

When iodides are present in the blood

of the glandular tissue and forming a goiter.

by the anterior pituitary gland, thus promoting growth

tremendous feedback enhancement of TSH secretion

formation of thyroglobulin. The absence of thyroxine

Propylthiouracil, like thiocyanate, does not prevent

thyroxine or triiodothyronine.

thyroid hormone from iodides and tyrosine. The mech-

lthiouracil (and other, similar compounds, such as

goiter.

greatly enlarged thyroid gland, which is called a

fore, the use of thiocyanates and some other ions to

form adequate quantities of thyroid hormones. There-

the anterior pituitary gland, which causes overgrowth of

mones in turn leads to increased secretion of TSH by

thyroid hormones. This deficiency of the thyroid hor-

cells does not stop the formation of thyroglobulin; it

The decreased availability of iodide in the glandular

iodide transport into the cell— that is, inhibition of the

cyanate (or one of the other ions as well) in high enough

nitrate ions. Therefore, the administration of thio-

can also pump thiocyanate ions, perchlorate ions, and

The same active

Thiocyanate Ions Decrease Iodide Trapping.

others, and they can be explained as follows.

The mechanism by which each of

inorganic iodides.

, and high concentrations

propylthiouracil

roid substances. The best known of these substances are

mones in the circulating body fluids.

anism of the feedback, its effect is to maintain an

anterior pituitary gland itself. Regardless of the mech-

secretion of TSH mainly by a direct effect on the

Therefore, as shown in Figure 76–7, it is probable that

itary has been separated from the hypothalamus.

falls essentially to zero. Almost all this feedback

about 1.75 times normal, the rate of TSH secretion

When the rate of thyroid hormone secretion rises to

decreases secretion of TSH by the anterior pituitary.

to Decrease Anterior Pituitary

Feedback Effect of Thyroid Hormone

ated by way of the hypothalamus.

cut, demonstrating that both of these effects are medi-

fore exert an inverse effect on the heat control center.

in secretion of TSH, perhaps because these states

affect the secretion of thyroid hormones. Excitement

output of TRH and TSH and therefore indirectly

Various emotional reactions can also affect the

Indeed, persons moving to arctic regions have been

gland, is exposure of an animal to cold. This effect

and therefore TSH secretion by the anterior pituitary

Chapter 76

Thyroid Metabolic Hormones

939

almost certainly results from excitation of the hypo-
thalamic centers for body temperature control.
Exposure of rats for several weeks to severe cold
increases the output of thyroid hormones sometimes
to more than 100 per cent of normal and can increase
the basal metabolic rate as much as 50 per cent.

known to develop basal metabolic rates 15 to 20 per
cent above normal.

and anxiety—conditions that greatly stimulate the
sympathetic nervous system—cause an acute decrease

increase the metabolic rate and body heat and there-

Neither these emotional effects nor the effect of

cold is observed after the hypophysial stalk has been

Secretion of TSH

Increased thyroid hormone in the body fluids

depressant effect occurs even when the anterior pitu-

increased thyroid hormone inhibits anterior pituitary

almost constant concentration of free thyroid hor-

Antithyroid Substances

Drugs that suppress thyroid secretion are called antithy-

thiocyanate,
of
these blocks thyroid secretion is different from the

pump that transports iodide ions into the thyroid cells

concentration can cause competitive inhibition of

iodide-trapping mechanism.

merely prevents the thyroglobulin that is formed from
becoming iodinated and therefore from forming the

the thyroid gland even though the gland still does not

block thyroid secretion can lead to development of a

Propylthiouracil Decreases Thyroid Hormone Formation.

Propy-

methimazole and carbimazole) prevents formation of

anism of this is partly to block the peroxidase enzyme
that is required for iodination of tyrosine and partly to
block the coupling of two iodinated tyrosines to form

and triiodothyronine in the thyroglobulin can lead to

Iodides in High Concentrations Decrease Thyroid Activity and
Thyroid Gland Size.

in high concentration (100 times the normal plasma

that the rate of iodination of tyrosine to form thyroid

thyroid glandular cells is paralyzed by the high iodide

is almost immediate shutdown of thyroid hormone
secretion into the blood.

Because iodides in high concentrations decrease all

of the thyroid gland and especially decrease its blood

Hypothalamus
(? increased temperature)

(Thyrotropin-releasing hormone)

Anterior pituitary

Hypertrophy

Iodine

Thyroxine

Thyroid

Increased
secretion

Thyroid-

stimulating

hormone

Cells

Increased

metabolism

Inhibits

Regulation of thyroid secretion.

Figure 76–7

thyroidism itself, is an autoimmune process. The exoph-

is much reason to believe that exophthalmos, like hyper-

who have high concentrations of TSIs. Therefore, there

with the eye muscles. Furthermore, the concentration of

changes in the extraocular muscles. In most patients,

The cause of the protruding eyes is edematous

blinks or is asleep. As a result, the epithelial surfaces of

vision. Much more often, the eyes are damaged because

about one third of hyperthyroid patients, and the con-

thalmos.

shown in Figure 76–8. This condition is called

develop some degree of protrusion of the eyeballs, as

hands.

fatigue but inability to sleep, and (9) tremor of the

nervousness or other psychic disorders, (8) extreme

varying degrees of diarrhea, (6) muscle weakness, (7)

weight loss (sometimes as much as 100 pounds), (5)

to heat, (3) increased sweating, (4) mild to extreme

hormones: (1) a high state of excitability, (2) intolerance

The symptoms of hyperthyroidism are obvious from the

adenoma depresses the production of TSH by the pitu-

secrete large quantities of thyroid hormone, secretory

evidence of any autoimmune disease. An interesting

hyperthyroidism, in that it usually is not associated with

hormone. This is different from the more usual type of

thyroid gland itself.

cell antigens was released from the thyroid cells, and this

time in the history of the person, an excess of thyroid

developed against thyroid tissue. Presumably, at some

The antibodies that cause hyperthyroidism almost

mation of TSH.

caused by TSI in turn suppresses anterior pituitary for-

TSH. The high level of thyroid hormone secretion

long as 12 hours, in contrast to a little over 1 hour for

stimulating effect on the thyroid gland, lasting for as

and are designated TSI. They have a prolonged

with resultant development of hyperthyroidism. These

continual activation of the cAMP system of the cells,

same membrane receptors that bind TSH. They induce

the blood of almost all these patients. These substances

have actions similar to those of TSH are found in

are essentially zero. However, other substances that

plasma TSH concentrations are less than normal

are similar to those caused by excessive TSH. However,

The changes in the thyroid gland in most instances

increases its rate of secretion severalfold; radioactive

number of cells is increased greatly. Also, each cell

of the follicular cell lining into the follicles, so that the

normal size, with tremendous hyperplasia and infolding

In most patients with hyperthyroidism, the

Causes of Hyperthyroidism (Toxic Goiter, Thyrotoxicosis, Graves’

development, diagnosis, and treatment of hyperthy-

of thyroid hormone. However, some specific effects

Diseases of the Thyroid

especially to decrease the amount of bleeding.

gland to decrease the necessary amount of surgery,

reason, iodides are frequently administered to patients

caused by most of the other antithyroid agents. For this

supply, in contradistinction to the opposite effects

940

Unit XIV

Endocrinology and Reproduction

for 2 to 3 weeks before surgical removal of the thyroid

Hyperthyroidism

Most effects of hyperthyroidism are obvious from the
preceding discussion of the various physiologic effects

should be mentioned in connection especially with the

roidism.

Disease).

thyroid gland is increased to two to three times

iodine uptake studies indicate that some of these hyper-
plastic glands secrete thyroid hormone at rates 5 to 15
times normal.

rather than enhanced in almost all patients and often

are immunoglobulin antibodies that bind with the

antibodies are called thyroid-stimulating immunoglobu-
lin

certainly occur as the result of autoimmunity that has

has resulted in the formation of antibodies against the

Thyroid Adenoma.

Hyperthyroidism occasionally results

from a localized adenoma (a tumor) that develops in the
thyroid tissue and secretes large quantities of thyroid

effect of the adenoma is that as long as it continues to

function in the remainder of the thyroid gland is almost
totally inhibited because the thyroid hormone from the

itary gland.

Symptoms of Hyperthyroidism

preceding discussion of the physiology of the thyroid

Exophthalmos.

Most people with hyperthyroidism

exoph-

A major degree of exophthalmos occurs in

dition sometimes becomes so severe that the eyeball
protrusion stretches the optic nerve enough to damage

the eyelids do not close completely when the person

the eyes become dry and irritated and often infected,
resulting in ulceration of the cornea.

swelling of the retro-orbital tissues and degenerative

immunoglobulins can be found in the blood that react

these immunoglobulins is usually highest in patients

thalmos usually is greatly ameliorated with treatment of
the hyperthyroidism.

40. (Courtesy Dr. Leonard Posey.)

eyes and retraction of the superior eyelids. The basal metabolic

Patient with exophthalmic hyperthyroidism. Note protrusion of the

Figure 76–8

rate was

thyroid gland, the physiologic effects are the same. They

thyroid gland by irradiation, or surgical removal of the

goiter, idiopathic colloid goiter, destruction of the

hypothyroidism is due to thyroiditis, endemic colloid

Whether

especially in some varieties of turnips and cabbages.

thyroid gland. Such goitrogenic substances are found

thus also leading to TSH-stimulated enlargement of the

that have a propylthiouracil-type of antithyroid activity,

Finally, some foods contain

thus leading to iodine deficiency

, which

, so that the final thyroid

, in which the iodides

Deficient peroxidase system

, in which

Deficient iodide-trapping mechanism

formation of the thyroid hormones. Among the abnor-

In some persons with colloid goiter, the thyroid gland

being destroyed by thyroiditis.

why these glands usually are nodular, with some por-

noninflamed portions of the gland. This could explain

increased TSH secretion and progressive growth of the

causes slight hypothyroidism, which then leads to

therefore, it has been suggested that the thyroiditis

patients with idiopathic colloid goiter is not known, but

The exact cause of the enlarged thyroid gland in

hormone is depressed, as in endemic colloid goiter.

thyroid hormones, but more frequently, the secretion of

in people who do not have iodine deficiency. These

Idiopathic Nontoxic Colloid Goiter.

to 10 to 20 times normal size.

tremendous in size, and the thyroid gland may increase

duction by the anterior pituitary. The follicles become

fore does not cause the normal suppression of TSH pro-

of iodine, thyroxine and triiodothyronine production

the gland grows larger and larger. But because of lack

amounts of thyroglobulin colloid into the follicles, and

to secrete excessively large quantities of TSH. The TSH

TSH by the anterior pituitary; this causes the pituitary

result, no hormone is available to inhibit production of

duction of both thyroxine and triiodothyronine. As a

goiters is the following: Lack of iodine prevents pro-

The mechanism for development of large endemic

endemic goiters.

extremely large thyroid glands, called

tity. Therefore, in the days before iodized table salt,

the United States, insufficient iodine is present in the

Swiss Alps, the Andes, and the Great Lakes region of

hormone. In certain areas of the world, notably in the

each year

term “goiter” means a greatly enlarged thyroid gland.

The

Endemic Colloid Goiter Caused by Dietary Iodide Deficiency.

as follows.

opment of enlarged thyroid glands, called

hypothyroidism also occur, often associated with devel-

secretion of thyroid hormone. Several other types of

fibrosis of the gland, with resultant diminished or absent

mation.This causes progressive deterioration and finally

autoimmune “thyroiditis,” which means thyroid inflam-

it. The thyroid glands of most of these patients first have

tiated by autoimmunity against the thyroid gland, but

Hypothyroidism, like hyperthyroidism, probably is ini-

to those of hyperthyroidism, but there are a few

The effects of hypothyroidism, in general, are opposite

several weeks later. If the patient is still hyperthyroid,

is given to the patient, whose condition is reassessed

thyroid gland. Usually 5 millicuries of radioactive iodine

active, it can destroy most of the secretory cells of the

1 day after injection. If this injected iodine is radio-

absorbed by the hyperplastic, toxic thyroid gland within

Treatment of the Hyperplastic Thyroid Gland with

modern procedures, operative mortality was 1 in 25.

the better hospitals, whereas before development of

dures, the operative mortality is less than 1 in 1000 in

supply to diminish. By using these preoperative proce-

normal. Then, administration of high concentrations of

propylthiouracil, usually for several weeks, until the

before the operation. This is done by administering

most of the thyroid gland. In general, it is desirable to

The most direct

Physiology of Treatment in Hyperthyroidism.

radioimmunoassay. This is usually high in

3. The concentration of TSI is measured by

of TSH is so completely suppressed by the

type of thyrotoxicosis, anterior pituitary secretion

measured by radioimmunoassay. In the usual

2. The concentration of TSH in the plasma is

1. The basal metabolic rate is usually increased to

using appropriate radioimmunoassay procedures.

direct measurement of the concentration of “free” thy-

hyperthyroidism, the most accurate diagnostic test is

For the usual case of

Diagnostic Tests for Hyperthyroidism.

Chapter 76

Thyroid Metabolic Hormones

941

roxine (and sometimes triiodothyronine) in the plasma,

Other tests that are sometimes used are as follows:

+30

+60 in severe hyperthyroidism.

large amounts of circulating thyroxine and
triiodothyronine that there is almost no plasma
TSH.

thyrotoxicosis but low in thyroid adenoma.

treatment for hyperthyroidism is surgical removal of

prepare the patient for surgical removal of the gland

basal metabolic rate of the patient has returned to

iodides for 1 to 2 weeks immediately before operation
causes the gland itself to recede in size and its blood

Radioactive Iodine

Eighty to 90 per cent of an injected dose of iodide is

additional doses are administered until normal thyroid
status is reached.

Hypothyroidism

physiologic mechanisms peculiar to hypothyroidism.

immunity that destroys the gland rather than stimulates

thyroid goiter,

As pointed out in the discussion of iodine metabolism,
about 50 milligrams of iodine are required

for the formation of adequate quantities of thyroid

soil for the foodstuffs to contain even this minute quan-

many people who lived in these areas developed

then stimulates the thyroid cells to secrete tremendous

does not occur in the thyroglobulin molecule and there-

Enlarged thyroid glands

similar to those of endemic colloid goiter can also occur

goitrous glands may secrete normal quantities of

most of these patients show signs of mild thyroiditis;

tions of the gland growing while other portions are

has an abnormality of the enzyme system required for

malities often encountered are the following:
1.

iodine is not pumped adequately into the thyroid
cells

are not oxidized to the iodine state

3. Deficient coupling of iodinated tyrosines in the

thyroglobulin molecule
hormones cannot be formed

4. Deficiency of the deiodinase enzyme

prevents recovery of iodine from the iodinated
tyrosines that are not coupled to form the thyroid
hormones (this is about two thirds of the iodine),

goitrogenic substances

Physiologic Characteristics of Hypothyroidism.

breathing, inducing a characteristic guttural breathing

with cretinism an obese, stocky, and short appearance.

tissues are likely to enlarge excessively, giving the child

a result of this disproportionate rate of growth, the soft

teristically more inhibited than is soft tissue growth. As

mental powers.

retardation of the growth, branching, and myelination

growth remains permanently retarded. This results from

tinism is treated within a few weeks after birth, mental

normal return of physical growth, but unless the cre-

Treatment of the neonate with cretinism at any time

neonate’s movements become sluggish and both physi-

mother while in utero, but a few weeks after birth, the

have cretinoid tendencies.

in the diet, and whole populaces of an endemic geo-

tinism varies greatly, depending on the amount of iodine

). The severity of endemic cre-

genetic defect of the gland, or from iodine lack in the

), from failure of the

mental retardation. It results from congenital lack of a

fetal life, infancy, or childhood. This condition is char-

their 90s after treatment for more than 50 years.

thyroxine. Furthermore, proper treatment of the

more than 1 month. Consequently, it is easy to maintain

of thyroxine on the basal metabolic rate, demonstrating

Figure 76–4 shows the effect

Treatment of Hypothyroidism.

50. And the secretion of

ranges between

the blood is low. The basal metabolic rate in myxedema

site results in hypothyroidism. The free thyroxine in

The tests already

Diagnostic Tests in Hypothyroidism.

in turn results in peripheral vascular disease, deafness,

those with myxedema, develop atherosclerosis, which

Therefore, many hypothyroid patients, particularly

is usually associated with increased atherosclerosis.

cholesterol in the bile. The increase in blood cholesterol

As pointed out earlier,

the nonpitting type.

the excess fluid, it is mainly immobile, and the edema is

interstitial fluid to increase. Because of the gel nature of

interstitial spaces, and this causes the total quantity of

condition, for reasons not explained, greatly increased

under the eyes and swelling of the face. In this

76–9 shows such a patient, demonstrating bagginess

almost total lack of thyroid hormone function. Figure

Myxedema

cases, development of an edematous appearance

development of a froglike husky voice, and, in severe

weight, constipation, mental sluggishness, failure of

decreased blood volume, sometimes increased body

ness, slowed heart rate, decreased cardiac output,

up to 12 to 14 hours a day, extreme muscular sluggish-

942

Unit XIV

Endocrinology and Reproduction

include fatigue and extreme somnolence with sleeping

many trophic functions in the body evidenced by
depressed growth of hair and scaliness of the skin,

throughout the body called myxedema.

Myxedema.

develops in the patient with

quantities of hyaluronic acid and chondroitin sulfate
bound with protein form excessive tissue gel in the

Atherosclerosis in Hypothyroidism.

lack of thyroid hormone increases the quantity of blood
cholesterol because of altered fat and cholesterol
metabolism and diminished liver excretion of

and coronary artery disease with consequent early
death.

described for diagnosis of hyperthyroidism give oppo-

-30 and -

TSH by the anterior pituitary when a test dose of
TRH is administered is usually greatly increased
(except in those rare instances of hypothyroidism
caused by depressed response of the pituitary gland to
TRH).

that the hormone normally has a duration of action of

a steady level of thyroid hormone activity in the body
by daily oral ingestion of a tablet or more containing

hypothyroid patient results in such complete normality
that formerly myxedematous patients have lived into

Cretinism

Cretinism is caused by extreme hypothyroidism during

acterized especially by failure of body growth and by

thyroid gland (congenital cretinism
thyroid gland to produce thyroid hormone because of a

diet (endemic cretinism

graphic iodine-deficient soil area have been known to

A neonate without a thyroid gland may have normal

appearance and function because it was supplied with
some (but usually not enough) thyroid hormone by the

cal and mental growth begin to be greatly retarded.

with adequate iodine or thyroxine usually causes

of the neuronal cells of the central nervous system at
this critical time in the normal development of the

Skeletal growth in the child with cretinism is charac-

Occasionally the tongue becomes so large in relation to
the skeletal growth that it obstructs swallowing and

that sometimes chokes the child.

Patient with myxedema. (Courtesy Dr. Herbert Langford.)

Figure 76–9

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Yen PM: Physiological and molecular basis of thyroid

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Vasudevan N, Ogawa S, Pfaff D: Estrogen and thyroid

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Chapter 76

Thyroid Metabolic Hormones

943

References