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THYROID PHYSIOLOGY AND IODINE

METABOLISM IN RELATION TO

GOITER AND CRETINISM

Prof. A. Querido

Profesor in Internal Medicine

Ryks University

Leiden

The thyroid gland is in higher vertebrates a highly structu-

red gland with endocrine function. The thyroid hormones

which are secreted, carry three or four Iodine atoms.

The thyroid hormones act on all body cells. In amphibia

they control the complex process of metamorphosis, which

includes the shedding of the tail of the tadpole and the

outgrowth of the legs. In mammalian vertebrates the thyroid

controls a large proportion of the oxygen consumption,

of linear growth, and of development also of the central

nervous system.

The basic units of the thyroid gland are the secretory

follicles, small spherical sacks. In the human it has a diameter

of about 1/10 - 1/2 mm. The Iodide enters the follicle cells

from the blood, and the hormones T

and T

leave the follicle

to the blood stream.

In the adult human, the thyroid

gland

weight about 20

grams, is situated before the

trachea, below the thyroid

cartilage. It has two lobes, at the right and left, connected

through the isthmus, which in most people is connected with

a third lobe, the pyramidal lobe.

The pathway of iodine metabolism in the thyroid

The specific properties of the thyroid gland are the ability:

1. to concentrate the in-organic Iodine ion (PII) when it

enters the cells of the thyroid. It shares this property with

Salivary glands, the gastric mucosa and the mammary

gland.

2. to produce a specific protein, thyroglobulin (mol. weight

650,000), which contains 115 tyrosine molecules: it is

stored in the lumen of the follicle.

3. to fix the lodide to the tyrosine molecules of thyroglo-

bulin, and to condense these iodinated tyrosines to thyro-

xine (T

) and triiodothyronine (T

) and finally

4. to split these hormones from thyroglobulin and to send

them into the blood stream.

The blood flow to the thyroid gland is rich. Through

a 20 gram normal thyroid gland flows 100 ml. blood per

minute, or 1% of the cardiac output. The thyroid gland is

only 0,03% of the body weight! The blood flow through

the thyroid gland may increase to 10 times the normal flow

in situations of thyrotoxicosis or endemic goiter!

Dibawakan pada Seminar Nasional I Gondok dan Kretin Endemik.

Semazang, 18 -- 20 Desember 1978.

Cermin Dunia Kedokteran No.

14,

1979.

The Iodine supply of the body is of paramount importance

for the normal function of the thyroid gland. More than 95%

of all Iodine in the body, about 10 mg, is present in the

thyroid gland. The molecular weight of thyroxine is about

770, of which 2/3 comes from the 4 large Iodine atoms!

If the body does not receive enough lodine with the food,

it cannot make sufficient thyroid hormones. As stated in

the beginning this has many consequences for the developing

fetus, for the child, and the adolescent. The central nervous

system connot develop adequately during pregnancy which

leads to mental retardation, the Corti-organ of the inner ear

does not differentiate, which causes loss of hearing, the

skeletal system does not differentiate or mature well, and

there is also retarded growth. All these signs and symptoms

are seen in the population of a severely Iodine deficient

region!

The normal daily Iodine intake should be between 100

and 200 ug per day (1 / 10 - 1/5 mg). The individual is with

such an intake in balance, that means the body will lose with

urine and feces an equal amount, and the body stores remain

the same. If the supply or intake of iodine is much less,

for instance 50 ug/day, the human body starts to use its

adaptation mechanisms. It increases the size, and herewith

the surface of the thyroid gland (goiter is the result) and it

increases the avidity, the concentration capacity of the

thyroid gland at its surface which interacts with plasma.

These 2 measures, the increase of surface and with it the

increase of blood flow, plus the increase of the capacity to

concentrate the Iodide from the plasma, is generally enough

to guarantee the gland sufficient lodide for a normal daily

hormone synthesis. We then speak of a compensated lodine

deficiency. This characterization may only be used, if under

all circumstances the body is supplied with enough thyroid

hormones and the plasma levels are normal. These circumstan-

ces are : during pregnancy, during lactation, during the gro-

wing period of the child, during adolescence and during

adult life.

It is quite clear that with a further decrease of Iodine

intake, a moment comes that the

thyroid

does

not

receive enough Iodide to make sufficient hormone under

all circumstances, regardless of its adaptation mechanisms.

In order to understand what then happens, and what is called

decompensated lodine defeciency, requires

more basic

knowledge of thyroid physiology and pathophysiology.

Until now we have not given attention to two aspects

of thyroid physiology. How is the thyroid function regulated,

and how proceeds Iodide metabolism in the body outside the

thyroid gland?

The thyroid does not function on its own, it is under con-

trol of thyrotrophic hormone, secreted by the anterior pituita-

ry. A thyroid in a organism without a pituitary does not

make thyroid hormones. The result is hypothyroidism, the

result of a lack of thyroid hormones. If the machinery of

the thyroid for thyroid hormone synthesis is defect (through

loss of tissue, through infection as an acute, sub-acute or

chronic thyroiditis, or defective enzymes) the thyroid connot

make

enough thyrotrophic hormone (TSH) release. The

TSH urges the thyroid to work harder, and sometimes

succeeds with it. In that case the level of thyroid hormones

in the blood is practically normal, but serum TSH is clearly

increased. However, this mechanism may not be successful,

in which case the serum thyroid hormone level will drop below

normal. This is what may happen in the severely Iodine

deficient individual.

Here the signal is also (with a normal

thyroid, which has no disease) the low serum level of thyroid

hormones, in this case because there is not enough Iodine

available to make the hormones. Serum TSH-level increases

but the thyroid cannot make more hormone, and we find

low serum T

and high serum TSH-levels.

Cermin Dunia Kedokteran No. 14, 1979

Also a few additional data about Iodine metabolism. The

thyroid has to produce about 60 80 ug T per day. It was

said before that if Iodine supply decreases, the thyroid adapts

by increase of size and surface, and by adding concentrating

capacity. If this adaptation is sufficient, we speak of compen-

sated Iodine deficiency. There is however also an other buffer

mechanism, not yet mentioned, which can support the defence

against lodine shortage over a short time of 3-6 months.

That is the lodine reserve within the gland, which amounts

to 10 mg present in thyroglobulin. This is roughly 200 times

the needed daily production! Furthermore the daily thyroxine

produced, is degrated during that day, and the lodide from

it is conserved and comes back to the plasma. The kidney

also

clears

plasma of Iodide, just as it clears urea, chloride

and many other substances. This Iodide is lost with the urine.

The lodide in the extracellular compartment therefore receives

lodide from two sides : from the food and from the break-

down of thyroxine. From this pool lodide goes to the thyroid

gland, and is Iodide lost through urine and faces. The loss

with the faces is however a very small fraction.

In the next figure the three situations of lodine metabolism

are indicated : the normale state the compensated state and

the decompensated state.

Histologically the goitrous gland initially keeps its structure

and becomes hyperplastic. The cells lining the follicles are

high, the colloid is decreased. After prolonged lodine defi-

ciency, with a continuous stimulus for growth to the gland,

encapsulated adenomas develop. They are often in the resting

state, and contain lots of colloid. Some may involute, other

may form hemorrhagic cysts. This is finally the histological

picture of the nodular goiter as we see it.

In the last scheme the findings in a population with diffe-

rent degree of Iodine deficiency are indicated.

Goiter is the first physical abnormality which is seen in lodine

deficiency. With refined methods, using radioactive Iodine,

it is possible to demonstrate the increase of the Iodide con-

centrating capacity before goiter is present. When the Iodine

deficiency is more severe, biochemical abnormalities in the

plasma will be present, and growth of children may be im-

paired. If the lodine deficiency is very severe (below 25 ug

I daily intake) the fetus is at risk, and may be born with

damage of the central nervous system (of which mental re-

tardation is only a part). The noncretinous part of the popu-

lation may suffer from hypothyroidism. It is on the basis

of urinary Iodine excretion that goiter endemias are classified

in 3 grades :

Grade I :

Goiter endemias with and average urinary lodine excretion of

more than 50 ug per g creatinine. At this level, thyroid hormo-

ne supply adequate for normal mental and physical develop-

ment can be anticipated.

Grade 11 :

Goiter endemias with an average urinary Iodine excretion of

between 25 and 50 ug per g creatinine. In these circumstances,

adequate thyroid hormone formation may be impaired.This

group is at risk for hypothyroidism but not for overt creti-

nisms.

Grade III

Goiter endemias with an average rinary

Iodine excretion 25

ug per g creatinine. Endemic cretinism is a serious risk in such a

population.

THE FUNCTIONAL CONSEQUENCES OF IODINE DEFICIENCY.

COMPENSATED

DECOMPENSATED

INTAKE I

BORDERLINE

DEFICIENT + DEFICIENT ++

CLINICAL

Goiter

Euthyroid

Adeq. Linear

growth

+ ?

Adeq. response

+ and

pregnancy

Cretinism

Suboptimal

mental develop-

ment

1. DJOKOMOELJANTO, R : Akibat defisiensi yodium berat.

Thesis,,

1974, Semarang. Indonesia.

2. STANBURY J.B, A.M. ERMANS, B.S. HETZEL, E.A. PRETELL

and A. QUERIDO. Endemic goiter and cretinism : Public health

signifecance and prevention,

WHO Choonicle, 1974, 28, 220 - 228.

3. QUERIDO A, N. BLEICHRODT and R. DJOKOMOELJANTO :

Thyroid hormones and human mental development. in : Matura

tion of the Nervous System. Progress in Brain Research, 1978. Ed.

M.A. Corner et al.

Cermin Dunia Kedokteran No. 14, 1979