Endocrine System: Thyroid Gland
(Gloria Marie M. Valerio, MD)
The thyroid gland is a butterfly-shaped gland located at the
anterior part of the neck that is in front and on either side of the trachea.
The gland is divided into two lobes right and left and the two lobes are
joined by a midline isthmus which is approximately at the level of the
cricoid cartilage. In the normal adult, the average weight of the gland is
15-25 g and normally the gland is NOT palpable because the consistency
of the thyroid gland is almost the same as that of the neck muscles.
For example, there is a mass or an enlargement at the anterior
part of the neck how would you examine it to determine if it is the thyroid
gland? The examiner could be standing behind the patient and place the
fingers on the anterior part of the neck or the examiner could stay in front
and place the fingers on the anterior part of the neck. Ask the patient to
swallow, if the mass will move up during swallowing that means it is the
thyroid gland. Why will the thyroid gland move up during swallowing?
Because it has an embryonic connection with the posterior part of the
tongue which is the thyroglossal duct and in adults sometimes the
thyroglossal duct persists.
Located behind the thyroid gland is the recurrent laryngeal
nerve so when the thyroid gland enlarges, it compresses the recurrent
laryngeal nerve and that will cause the patient to develop hoarseness or if
during thryroidectomy surgical procedure that involves removal of a
part or entire thyroid gland, if the recurrent laryngeal nerve is
accidentally cut, that will now cause the patient to lose his voice.
Partly embedded behind the thyroid gland are the four
parathyroid glands. The parathyroid glands secrete the parathyroid
hormone whose main function is to increase plasma calcium level. For
example you have a hyperthyroid patient who underwent thyroidectomy.
After a couple of days, he developed tetany or spasms on the muscles of
the face, extremities and trunk on laboratory exam there is hypocalcemia.
The conclusion could be that parathyroid glands were accidentally
removed together with the thyroid gland or if during thyroidectomy,
blood supply to the parathyroid glands is compromised, PTH secretion
will decrease and the patient will also develop hypocalcemia.
1 Shannen Kaye B. Apolinario, RMT
PHOTO: Microscopic appearance of the thyroid gland, showing secretion of
thyroglobulin into the follicles
The thyroid gland is made up of many thyroid follicles or
acini which is actually the functional unit of the thyroid gland. The
thyroid follicle is made up of one layer of epithelial cells or what we call
thyroid follicular cells and these cells are responsible for the synthesis
and release of the thyroid hormones T3 and T4. At the center or lumen of
the follicle is the colloid which contains a large glycoprotein molecule that
is thyroglobulin. The function of the colloid is to store newly
synthesized thyroid hormones.
If the thyroid gland is inactive, the follicle is larger, the colloid
is more abundant but the follicular cells are flat. On the other hand, if the
thyroid gland is active, the follicle becomes smaller, the colloid is less
abundant and the follicular cells are taller or columnar.
The thyroid gland is well vascularized. Blood supply comes
from the superior and inferior thyroid arteries and blood flow to the
gland is 5 mL/g/min. In hyperthyroidism or hyperactivity of the thyroid
gland, blood supply to the gland also increases so that when you place the
diaphragm of the stethoscope at the anterior part of the neck, you could
actually hear blood flow to the gland and that is what we call a bruit. The
thyroid gland also receives sympathetic innervation. However,
sympathetic innervation will regulate only blood flow to the gland; it does
not regulate the secretory function of the gland.
Biosynthesis and Release of Thyroid Hormone
PHOTO: Thyroid cellular mechanisms for iodine transport, thyroxine and
triiodothyronine formation, and thyroxine and triiodothyronine release into the blood.
MIT, monoiodotyrosine; DIT, diiodotyrosine; T3, triiodothyronine;
T4, thyroxine; TG, thyroglobulin.
The photo represents the inside of a follicular cell (cytoplasm)
and it is separated from the ECF by its basolateral membrane (left side).
The cytoplasm of the follicular cell is separated from its lumen by the
apical membrane (right side). And in the biosynthesis of thyroid
hormones, the direction is from the ECF across the basolateral membrane
to the cytoplasm across the apical membrane to the lumen.
1. Iodide uptake or trapping = Na-I symporter
An important pre-requisite in the biosynthesis of thyroid
hormone is iodide and the main source of iodides in the body is dietary
like seafood, iodized salt, iodinated water, iodinated bread etc. Iodides although most of the MIT and DIT will undergo coupling and will be
may also come from medications, x-ray contrast materials but then again converted to T3 and T4, not all will couple so that in the lumen there is
the main source is dietary. The minimum requirement for iodides for little amount of individual MIT and DIT. This reaction number four is
normal thyroid function is 150 g. However, in the USA, a balanced diet catalyzed by the enzyme peroxidase.
can provide an individual with about 400 ug of iodides per day. Ingested
iodides are almost completely reabsorbed from the intestine into the That means that peroxidase can catalyze 3 out of 4 steps in the
circulating blood. In the circulating blood, 80% of the iodides will be biosynthesis of thyroid hormones: oxidation, organification and coupling.
taken up the kidneys and excreted through the urine while the remaining
20% will be taken up by the thyroid gland.
Storage
Actually the thyroid gland can take up iodides at the same time
it can also release iodides into the circulating blood so that the first step in What will happen after synthesis? Thyroid hormones will then
the biosynthesis of thyroid hormones is called iodide uptake or iodide be stored temporarily in the colloid bound to the thyroglobulin molecule.
trapping. This will involve active transport of iodides from the ECF to the How much thyroid hormones can be stored in the colloid? The amount that
cytoplasm of the follicular cell across the basolateral membrane. This is can be stored will be able to supply the body with thyroid hormones for
actually secondary active transport that will utilize a carrier protein 2-3 months.
which is the sodium-iodide symporter. This carrier protein can
transport 2 Na ions downhill, 1 I ion uphill in the same direction going
into the follicular cell. The energy that will fuel this carrier protein will
come from the activity of the Na-K ATPase pump. Take note that this
carrier protein is present not only in the follicular cell of the thyroid
gland, it can also be present in other cells or glands so these other cells or
glands can also take up iodides. Salivary glands, gastric mucosa, mammary
glands, placenta, choroid plexus and cilliary body can also actively
transport iodides but these other cells or glands are not influenced by
TSH or thyrotropin so although they take up iodides, they do not
synthesize thyroid hormones

There are also several anions that can compete with iodides for
binding with this carrier protein, examples include nitrate, thiocyanite,
and perchlorate. These anions can block the first step in the biosynthesis
of thyroid hormones by competitive inhibition with iodide so that at
times, they can be utilized as anti-thyroid drugs.

When iodides have entered the cytoplasm, the next step is that
it will cross the apical membrane into the lumen again aided by a carrier
protein which is now pendrin. Pendrin is Na independent; it is actually a
chloride-iodide transporter. The direction of iodide is from ECF to
cytoplasm to lumen.

Parallel to the transport of iodides, the follicular cells produce

a glycoprotein molecule that is thyroglobulin. Thyroglobulin contains
many amino acids most of which are residues of tyrosine. And after
synthesis, this thyroglobulin molecule is packaged in secretory vesicles
together with an enzyme that is peroxidase. And across the apical PHOTO: Synthesis (blue arrows) and secretion (red arrows) of thyroid hormones by
membrane, these secretory vesicles will extrude the thyroglobulin the thyroid epithelial cell. White arrows denote pathways involved in the conservation
of iodine and amino acids.
molecule and peroxidase and the process is by exocytosis. Now, not only
iodides are in the lumen but also the thyroglobulin and peroxidase are
Release
also outside of the apical membrane.
1. Endocytosis of the colloid at the apical borer
2. Oxidation = Iodide iodine
2. Proteolysis of thyroglobulin
3. Deiodination of MIT and DIT I
The next step will be iodides undergoing oxidation being
4. Secretion of T3 and T4
converted to iodine. This reaction is catalysed by the enzyme peroxidase.
Upon stimulation, what now are the steps involve in the release
3. Organification = tyrosine + iodide iodotyrosine
of thyroid hormones? It is in the opposite direction: from the lumen to the
ECF or plasma. The first step will be for the follicular cells to engulf the
The third step is called organification or iodination wherein
colloid and the process is by endocytosis or more specifically, pinocytosis.
the tyrosine component of the thyroglobulin molecule binds with iodine
So all four thyroid hormones is still bound to the thyroglobulin molecule,
producing two types of thyroid hormones which we call iodotyrosine. So
it will go back to the cytoplasm of the follicular cell. In the cytoplasm of
we have MIT or monoiodotyrosine and the other one is DIT or
the follicular cell, there are several proteases present that will now cause
diiodotyrosine. And this reaction is catalysed by the enzyme iodinase
breakdown of the thyroglobulin molecule.
and peroxidase.
The next step is proteolysis or breakdown of the thyroglobulin
4. Coupling = iodotyrosine MIT + DIT = T3
molecule so that will now release MIT, DIT, T3 and T4. It is still in the
DIT + DIT = T4
cytoplasm but no longer bound to the thyroglobulin molecule.
The fourth step is called coupling wherein two other thyroid
Another enzyme that is present in the cytoplasm is tyrosine
hormones are produced and we now call them iodothyronines so that
deiodinase that will now cause deiodination of MIT and DIT releasing
when one molecule of MIT couples with one molecule of DIT, this will
iodine. The iodine that will be released can be recycled meaning to say it
produce T3 or triiodothyronine. When two molecules of DIT couple, this
can be used again to synthesize new thyroid hormones or it can be
will produce T4 or tetraiodothyronine or thyroxine. All in all, there are
released into the plasma that is why thyroid gland can take up iodides
four types of thyroid horomones: MIT, DIT, T3 and T4. Take note that
and it can also release iodides in the plasma. Take note that the enzyme

2 Shannen Kaye B. Apolinario, RMT

tyrosine deiodinase acts only on the iodotyrosines MIT and DIT, it does
not act on the iodothyronines so that means MIT and DIT are not released
into the plasma, they undergo deiodination while still in the follicular cell
so they are considered inactive hormones or prohormones. The only
active thyroid hormones released into the circulating blood are T3 and
T4.
95% T4 peripheral tissue T3 / rT3
5% T3 20% thyroid gland
80% peripheral conversion of T4
In the circulating blood, 95% of thyroid hormones is T4, only
5% is T3. Although there is more T4 that T3 in the circulating blood,
when T4 reaches the peripheral tissues particularly the liver, muscle and
kidneys, it undergoes deiodination removal of iodine, and will now be
converted to T3 and this reaction is catalysed by the enzyme deiodinase
type 1. There is another enzyme in the peripheral tissues deiodinase
type 3 which will now convert T4 to reverse T3 or rT3. But reverse T3
has none of the biologic activities of T3.
Of the total amount of the circulating T3 in the blood, only 20%
actually comes from the thyroid gland so most of the circulating T3 will
come from peripheral conversion of T4.
Hormone Transport
1. TBG T4 > T3
2. Thyoxine Binding Prealbumin (TBPA) T4
3. Albumin little of T3 and T4
In the circulating blood, more than 99% of the thyroid
hormones are bound to plasma proteins so that means less than 1% is
free. Remember that protein bound hormone is biologically inactive, it is
the free hormone that is biologically active. What now are the plasma
proteins that will bind the thyroid hormones? The protein with the lowest
concentration in the plasma but with the highest affinity for thyroid
hormones is TBG or thyroid hormone binding globulin and it binds
more of T4 than T3. Another protein is the thyroxine binding pre-
albumin or transthyretin and this protein binds only T4. Protein with
the highest concentration in the plasma but with the lowest affinity for
thyroid hormones is albumin and albumin binds little of T4 and T3. As
you can see from here, there is more T3 that is free and more T4 that is
protein bound. Since it is the free hormone that is biologically active, that
means in terms of potency or biologic activity, T3 is more potent and
more active than T4 and it is mainly an excess in free T3 that will have a
negative feedback effect on the hypothalamus and anterior pituitary
gland.
Regulation of Thyroid Hormone Secretion
PHOTO: Regulation of thyroid secretion
3 Shannen Kaye B. Apolinario, RMT
Cold
Stress H-TRH (-)
AP TSH (-)
Thyroid gland T3 or T4 - - -if increased,
The major mechanism that regulates thyroid hormone
secretion is the hypothalamic-hypophyseal thyroid gland axis. Some
of the stimuli that can cause the hypothalamus to secrete TRH are cold
and stress. The hypothalamus will secrete the thyrotropin releasing
hormone or TRH. This is a tripeptide that will bind with membrane
receptors or thyrotrophs of the anterior pituitary gland utilizing the
phospholipase C 2nd messenger system to stimulate the secretion of
thyrotropin or TSH or thyroid stimulating hormone. TSH on the other
hand is a glycoprotein which will bind with membrane receptors on the
follicular cells of the thyroid gland this time utilizing cAMP as a 2 nd
messenger to stimulate the secretion of the thyroid hormones T3 and T4.
If there is TRH, there is TSH, there is T3 and T4 but if there is no TRH,
there is no TSH, no T3 and T4. On the other hand, T3 and T4 can also
regulate the secretion of TRH and TSH by exerting a negative feedback
effect, that is any excess free T3 and T4 but mainly excess free T3 will
inhibit the hypothalamus from secreting TRH and it will also inhibit the
anterior pituitary gland from secreting TSH.
( - ) Na-I symporter Increased iodine
( - ) organification
Aside from hypothalamic-hypophyseal thyroid gland axis,
although this is the major mechanism, the thyroid gland also has an
autoregulatory mechanism so it can regulate its own activity depending
on the availability of iodides and we call this the Wolff-Chaikoff effect.
Iodides have a unique relationship with the thyroid gland. Remember
that you need iodides for thyroid hormone synthesis but any deficiency
or excess in iodides will decrease thyroid hormone synthesis, it has to be
normal. If it is deficient, it is understandable that there is no precursor for
thyroid hormone synthesis; if it is in excess, thyroid hormone synthesis is
also decreased. If iodide intake is too much, there should be thyroid
hormone synthesis resulting to hyperthyroidism, but that does not
happen because of autoregulatory mechanism. If there is an excess in
iodides, the Na-I symporter is inhibited and at the same time
organification step is also inhibited so thyroid hormones synthesis is
decreased and hyperthyroidism will not occur. This will now persist for
several days, after which there will be Wolff-Chaikoff escape loss of
inhibition, and that will bring back synthesis of thyroid hormones to
normal.
TSH + membrane receptors =
( + ) Growth
Follicular cell size and number follicle
formation
( + ) Hormone synthesis and release
What are the specific effects of TSH on the thyroid gland? By
binding with receptors on the membrane of the follicular cells of the
thyroid gland, TSH can stimulate growth of the thyroid gland by
increasing the number and size of the follicular cells. So TSH can
stimulate follicular formation, it can therefore increase the size of the
thyroid gland. But aside from stimulating growth of the thyroid gland, it
can also increase the function of the thyroid gland by stimulating almost
all the steps involved in the synthesis and release of thyroid hormones. So
iodide uptake, oxidation, organification, coupling, endocytosis,
proteolysis of the thyroglobulin molecule and eventually release of T3
and T4 into the circulating blood are all stimulated. But take note all of
these effects will take several days but the most immediate action of TSH
on the thyroid gland is to increase proteolysis of the thyroglobulin molecule.
OAT P
OAT P1 MCT8
T4 T3
 What kind of hormone is T3 and T4 according to chemical
composition? Any hormone that is synthesized from tyrosine including
epinephrine and norpinhephrine is a biogenic amine. If it is a biogenic
amine, the receptors are present on the nucleus of the target cell. But
before T3 and T4 can bind with nuclear receptors, they have to cross first
the cell membrane and they will cross the cell membrane again aided by a
carrier protein which is called organic anion transporting polypeptide
(OAT-P). OAT-P is the carrier protein that will transport T3 and T4
across the cell membrane of the target cell and there are several types.
One is OAT-P 1 which has a preference for thyroxine and the other one is
MCT 8 which has a preference for T3.
T3 / T4 + nuclear receptors
(+) specific DNAs
Increased mRNAs
Increased formation and activity of intracellular membrane enzymes
With the aid of this carrier proteins, T3 and T4 will now be able
to cross the cell membrane and bind with nuclear receptors to stimulate
specific DNAs leading to the formation of mRNAs. After formation, this
mRNAs will move back into the cytoplasm to stimulate the ribosomes to
increase the formation and activity of many intracellular metabolic
enzymes including Na-K ATPase.
Increased intracellular metabolism/activity
Increased O2 consumption
Increased CO2 production
Increased heat production .
Increased basal metabolic rate (BMR)
What will be the effect of that to the cell? So by increasing the
formation and activity of intracellular metabolic enzymes, T3 and T4 will
therefore increase intracellular metabolism or activity. By increasing
intracellular metabolism or activity, there will be increase oxygen
consumption by the cells; there will also be increase carbon dioxide
production by the cells and increase heat production by the cells. And
since these effects are true in almost all cells of the body because thyroid
hormones can act on almost all cells of the body, it means that thyroid
hormone can increase the bodys basal metabolic rate. It can act on
almost all cells so not all are included as the target cells of T3 and T4
and the exceptions are spleen, lens of the eye and gonads.
Physiologic Action of Thyroid Hormones
4 Shannen Kaye B. Apolinario, RMT
PHOTO: Thyroid hormone activation of target cells. Thyroxine (T4) and
triiodothyronine (T3) readily diffuse through the cell membrane.Much of the T4 is
deiodinatedto form T3, which interacts with the thyroid hormone receptor,bound as a
heterodimer with a retinoid X receptor, of the thyroid hormone response element of
the gene. This causeseither increases or decreases in transcription of genes that lead
to formation of proteins, thus producing the thyroid hormoneresponse of the cell. The
actionsof thyroid hormone on cellsof several different systemsare shown. mRNA,
messenger ribonucleic acid.
Growth
o (+) physical and mental growth
We go to the specific physiologic actions of thyroid hormones
and we begin in children. In children, thyroid hormones are needed to
stimulate both physical and mental growth. With regards to physical
growth, thyroid hormones have a greater effect on skeletal rather than
soft tissue growth and that is one difference between thyroid hormone
and growth hormone. Growth hormone has an equal effect on bones and
soft tissue while the thyroid hormone has a greater effect to bones rather
than soft tissue so that in congenital hypothyroidism, this will produce
what we call a non-proportional type of dwarfism (ugly dwarf) and that
condition is called cretinism. It is not proportional because only the
bones will fail to grow but the soft tissues will continue to grow resulting
to features of short stature, short limbs, pot belly, small skull but with
macroglossa or large tongue. Compare that with a pituitary dwarf
absence of growth hormone, both bones and soft tissue will not grow
simultaneously resulting to a proportional dwarf (beautiful dwarf). Can
this be corrected? Physical retardation can be corrected as long as the
condition is diagnosed and treated with thyroid hormone therapy before
the closure of epiphyseal plates of the long bones.
Thyroid hormones are also needed for the normal
development of the brain in children so that in congenital
hypothyroidism or cretinism, there is mental retardation which is
another difference between a hypothyroid dwarf and a pituitary dwarf. In
pituitary dwarf, usually there is no retardation. Mental retardation can be
corrected as long as the condition is diagnosed and treated before the 6th
month of development. Beyond 6th months, mental retardation will
become permanent.
CNS
o Increased cerebration, increased synaptic transmission,
increased nerve myelinization
In adults, thyroid hormones increase cerebration, increase
nerve myelinazation and synaptic transmission.
What are the clinical manifestations of hyperthyroidism in
relation to the CNS? A hyperthyroid patient has hyperkinesia or is
hyperkinetic - he will always move and all of his movements like talking,
walking are all fast; insomnia; increased anxiety or nervousness; and
when you ask the patient to put his arms forward and you place a piece of
paper on top of the fingers, you will be able to observe fine tremors of the
fingers. A hypothyroid patient is hypokinetic sluggishness of movement
and speech, solemnness or drowsiness any time of the day, poor memory,
poor mental ability, and low IQ.
CVS
o (+) SAN Increased HR
o (+) myocardial contractility increased SV
o Increased HR, increased SV increased CO increased
SP
o Increased heat production VD decreased TPR
decreased DP
The actions of thyroid hormones on the CVS are either direct or
indirect. Indirect is mediated by increase epinephrine secretion from the
adrenal medulla. Thyroid hormones can stimulate the SA node increasing
the heart rate. They can stimulate myocardial contractility increasing the
stroke volume and if you remember cardiodynamics, an increase in heart
rate and stroke volume will increase the cardiac output and an increase in
cardiac output increases systolic pressure. Along with that, you have
increase cellular metabolism, increase heat production by the cells and
that will cause relaxation of the vascular smooth muscle so there will be
vasodilatation, decreasing total peripheral resistance, decreasing
diastolic pressure. So that means in hyperthyroidism, you have
tachycardia, palpitations, systolic hypertension and a wide pulse pressure
whereas in hypothyroidism, there is bradycardia.
GIT
o Increased motility, secretion, absorption
Thyroid hormones can increase gastrointestinal motility,
secretion and absorption. So that in hyperthyroidism, there is persistent
diarrhea while in hypothyroidism, there is chronic constipation.
Hematopoetic System
o Increased IC activity increased O2 consumption
decreased PO2 (+) erythropoiesis
With increase cellular metabolism and increase oxygen
consumption by the cells, oxygen tension in the blood decreases resulting
to hypoxia which will now stimulate red blood cell production or
erythropoiesis.
Respiratory System
o Increased IC activity decreased PO2, increased pCO2
(+) respiratory center increased respiratory activity
With decreased intracellular activity, oxygen tension
decreases, carbon dioxide tension increases and through stimulation of
the chemoreceptors central and peripheral, the respiratory center will
also be stimulated so that will increase respiratory activity.
Endocrine System
o Increased metabolism and clearance of various hormones
Thyroid hormones can also increase the metabolism and
clearance of the other endocrine hormones.
Bones
o Increased bone formation and resorption
In the bone, thyroid hormones can stimulate both bone
formation and bone resorption but in hyperthyroidism, resorption
becomes greater than formation. In hypothyroidism, both will decrease.
Muscle
The effect of thyroid hormones to muscles has something to do
with protein synthesis. A normal or physiologic dose of thyroid hormones
will increase protein synthesis therefore increasing muscle strength
normal or physiologic dose. In hyperthyroidism, there is increase protein
catabolism while in hypothyroidism, there is decrease protein synthesis.
In both cases, there will be a decrease in muscle strength but the
mechanisms are different.
Skin
o Increased thyroid hormone heat intolerance
o Decreased thyroid hormone cold intolerance
In hyperthyroidism, there is increase sweating, heat tolerance.
In hypothyroidism, the skin is dry and there is cold intolerance.
Body Weight
o Increased thyroid hormone increased appetite;
decreased body weight
o Decreased thyroid hormone decreased appetite;
increased body weight
In hyperthyroidism, there is weight loss in spite of an increase
in appetite and that is typical in a hyperthyroid patient. In
hypothyroidism, there is weight gain in spite of a lack of appetite.
Carbohydrate Metabolism
o Increased glucose absorption; increased cellular
utilization of glucose
5 Shannen Kaye B. Apolinario, RMT
Thyroid hormones can increase intestinal absorption of
glucose as well as cellular utilization of glucose. But again, in
hyperthyroidism, ephinephrine induced glycogenolysis in the liver is
stimulated so blood glucose can increase.
Fat Metabolism
o Increased lipolysis > increased lipogenesis
Thyroid hormones can also influence all aspects of fat
metabolism increase lipolysis, increase lipogenesis but more of
lipolysis. Same thing with cholesterol synthesis and degradation, there is
more of cholesterol degradation so that in hypothyroidism, there is
hypercholesterolemia.
Protein Metabolism
o Normal dose anabolic
In protein metabolism, what you need is a normal or
physiologic dose for the effect to be anabolic. In hyperthyroidism, you
have increase protein catabolism, in hypothyroidism, decrease protein
synthesis.
Vitamins
o Thyroid hormone (+) carotene to vitamin A
With increased thyroid hormone secretion, the body will need
more nutrients and vitamins and actually, thyroid hormones are needed
to convert carotene to vitamin A in the liver. In hypothyroidism, there is
carotenemia because carotene cannot be converted to vitamin A.
Adrenal Medulla
o (+) increased secretion of EP and NEP
Thyroid hormones stimulate the adrenal medulla to increase
the secretion of epinephrine and norepinephrine potentiating
sympathetic adrenergic effects.
Almost all of the organ systems are affected by T3 and T4
except for the spleen, lens of the eye and gonads. And almost all of their
actions are stimulatory.
Thyroid Disorders
Thyroid disorders
Thyroid enlargement Functional disorders
(goiter) (Hyperthyroidism,
Hypothyroidism)
This may involve the size of the gland and that enlarged
thyroid gland is called goiter. There are two types: if there is generalized
enlargement of the gland, meaning the entire gland is enlarged we call
that diffuse goiter. But if there is lumpy enlargement of the gland, that is
nodular or multi-nodular goiter.
Another will be functional disorder so if you have a
hyperfunctioning gland with hypersecretion of thyroid hormones, that is
hyperthyroidism. A hypofunctioning gland with hyposecretion of
thyroid hormones is hypothyroidism.
Hyperthyroidism Toxic
Goiters Euthyroidism Non-toxic
Hypothyroiddism
An enlarged thyroid gland may be a hyperfunctioning gland, a
normally functioning gland (euthyroid) or a hypofunctioning gland. So
that does not mean that goiter is only present if there is hyperthyroidism.
Remember that in goiter, we are just talking about the size and not the
function. If the gland is enlarged and at the same time it is
hyperfunctioning, that is what we call toxic goiter. An enlarged gland
that is either normally functioning or hypofunctioning is what we call Clinical manifestations of hypothyroidism include dry, coarse
non-toxic goiter. hair including the eyebrows, puffy face, enlarged thyroid gland so you can
have goiter, bradycardia, arthritis, cold intolerance, dry skin, easy
fatiguability, irregular menstrual cycle, weight gain, constipation, brittle
nails. Up to this, the most important clinical manifestation is myxedema
and in hypothyroidism, myxedema is generalized but it is most
pronounced in the face specially around the eyes. Also included are low
husky voice, carotenemia, low IQ, myxedema madness,
hypercholesterolemia due to decreased cholesterol degradation and a
low basal metabolic rate.

If hypothyroidism will occur in children or congenital

hypothyroidism, that is cretinism. And this will produce non-
proportional type of dwarfism so usually there is mental retardation, pot
belly, large tongue and usually the patient is deaf and mute.

PHOTO: The thyroid gland is located in the anterior aspect of the neck, where it is
easily visualized and palpated when enlarged (goiter).

WHO Classification of Goiter

Stage O no goiter, gland not palpable, not visible

Stage 1a palpable but not visible even when neck is fully

extended
PHOTO: A patient with myxedema
Stage 1b palpable but visible only when the neck is fully
extended; includes gland with nodules This is how a typical hypothyroid patient looks like. The
patient has a very dry skin and the expression on the face is very dull also
Stage 2 visible even when neck is in a normal position when there is puffiness around the eyes.
patient is near the examiner; no need to do palpation
Causes of Hypothyroidism
Stage 3 visible even at a considerable distance; very large Iodine deficiency (endemic goiter)
gland Intake of goitrogens
Thyroiditis (late stage) and thyroid cancer
TSH deficiency (pituitary disorder)
Clinical Correlates Post-thyroidectomy (total)
Post-radiation therapy
Functional disorders of the thyroid gland are hypothyroidism
and hyperthyroidism. What are the causes of hypothyroidism? One is iodine
deficiency. Remember we can classify hypothyroidism as to primary,
Hypothyroidism secondary, tertiary. Primary if there is thyroid gland failure, secondary if
the problem is in the anterior pituitary gland, tertiary if the problem is in
Myxedema the hypothalamus. If there is iodine deficiency, there will be decreased
After birth thyroid hormone synthesis and the condition is classified as primary
Slow and husky voice hypothyroidism. Increased intake of goitrogens which are chemical
Carotenemia substances present in food like cabbage and turnips that can block
Low IQ thyroid hormone synthesis is classified as primary hypothyroidism
Myxedema madenss because the problem is that there is no synthesis of the hormone.
Elevated cholesterol Thyroiditis or Hashimotos thyroiditis is an autoimmune disease so the
BMR = -40 plasma cells produce antibodies that destroy the Na-I symporter as well
as inhibit the activity of peroxidase is also classified as primary
hypothyroidism. Thyroid cancer is also primary hypothyroidism.

Cretinism Another cause is a tumor in the brain that compresses the

pituitary gland so there will be decreased secretion of the pituitary
Birth or before
hormones including TSH. If there is no TSH, thyroid hormone secretion is
Dwarf
also decrease. This is secondary hypothyroidism.
Mentally retarded
Potbellies
Another cause is when you have a previously hyperthryroid
Macroglossia patient who underwent total thyroidectomy so there is an absence of
Deaf and mute thyroid hormone synthesis. Also, when a previously hyperthyroid patient
who received radiation therapy, radioactive iodine when give in excess
can destroy not only the hyperfunctioning cells but also the surrounding
normally functioning cells so that will again depress the function of the
thyroid gland. Another case is when a hyperthyroid patient receiving
anti-thyroid drugs when these anti-thyroid drugs are given in excess,
again, that will depress the function of the thyroid gland. Post-
thyroidectomy, post-radiation therapy and excess anti-thyroid drugs, in
6 Shannen Kaye B. Apolinario, RMT
all of these are you have previously hyperthyroid patient so that means in
a hyperthyroid patient, if the treatment given is excessive the usual
complication is hypothyroidism.
Primary: Decreased TH, Increased TSH, Increased TRH
Secondary: Decreased TH, Decreased TSH, Increased TRH
Tertiary: Decreased TH, Decreased TSH, Decreased TRH
Hormonal picture: if it is primary hypothyroidism, you have
thyroid gland failure so there will be decrease thyroid hormone secretion.
Negative feedback is removed: increased TSH, increased TRH, goiter is
possible because of excessive amounts of TSH.
If it is secondary, the problem is in the anterior pituitary gland
so the first one to decrease is TSH. If there is no TSH, there will be no
thyroid hormone secretion but TRH is high. Goiter is unlikely to happen
because of the absence of TSH.
If it is hypothalamic, the first one to decrease is TRH therefore
both TRH and thyroid hormone secretion are decreased. There will be no
goiter because there is no TSH. So enlarged thyroid gland is possible in
hypothyroidism if the condition is primary.
Differential Diagnosis of Hypothyroidism
Type Serum T4 Serum TSh TH after TRH
Thyroidal Low Elevated Increased TSH,
low T4
Pituitary Low Low No change
Hypothalamic Low Low Increased TSH
and T4
The usual request will be to determine serum free T3, T4, TSH
but there is another test that can be requested to differentiate between
primary, secondary and tertiary hypothyroidism and that is to do at TRH
challenge or TRH test. First, you determine the free serum T4, TSH level
of the patient and then administer intravenously the TRH. When TRH is
given, determine again the T4, TSH levels if there are changes. If the
condition is primary or thyroidal, T4 level is decreased and TSH is
increased. If TRH is given, the anterior pituitary gland is expected to
respond so TSH will increase further and T4 is still decreased because the
problem is in the thyroid gland.
If the condition is secondary or pituitary, TSH level is low and
T4 is also low. When TRH is given, the anterior pituitary gland is not
expected to respond so TSH and T4 levels will not change both low.
Hypothalamic or tertiary, there is no TRH so the TSH and T4
levels are both decreased. When TRH is given, the anterior pituitary gland
will respond so TSH and T4 will increase.
7 Shannen Kaye B. Apolinario, RMT
How would you know if a baby is cretin? The limbs are short,
there is pot belly and magcroglossia until the he becomes an adult.
Cretinism is caused by iodine deficiency on the part of the mother.
Another cause could be you have a hyperthyroid mother taking anti-
thyroid drugs unknowingly that she is already pregnant so this anti-
thyroid drugs will cross the placenta to depress the development of the
fetal thyroid but that is rare.
Hyperthyroidism or Thyrotoxicosis
Thyrotoxicosis
Hyperphagia
Increased pulse pressure
BMR = +10 - +100
Prone to high output failure
Pre-tibial myxedema
Causes of hyperthyroidism
(thyrotoxicosis)
Thyroidal
Graves disease (Exopthalmic goiter)
with TSH receptor antibodies (TSI)
Solitary toxic adenoma (Plummers
disease)
Hashimotos thyroiditis (early stage)
Thyrotoxicosis simply means that you have a hyperfunctioning
gland that will increase the secretion of thyroid hormones. The different
clinical manifestations include hair loss, bulging eyes (exophthalmos),
increased sweating, goiter, tachycardia, insomnia, heat intolerance,
infertility, irritability, muscle weakness because of increased protein
catabolism, increased anxiety or nervousness, weight loss, diarrhea,
warm most palms, fine tremors of the fingers. Actually there are two
clinical manifestations that if you see in a patient, hyperthyroidism can
already be concluded and those are fine tremors and tachycardia.
Increased pulse pressure because of increased systolic and decreased
diastolic pressure, increase BMR, high output failure because of
heightened stimulation of heart resulting to increased activity. There is
also myxedema but it is localized, confined only at the anterior surface of
lower extremities called pre-tibial myxedema.
PHOTO: Pre-tibial myxedema (left) and Onycholysis (right)or separation of the nail
from the nail beds which is also common in hyperthyroidism.
What are the most common causes of hyperthyroidism? First is
primary. You also have an autoimmune disease that is exemplified by
Graves disease. This time, the plasma cells produce antibodies that
function just like TSH. The effect of antibodies is increased size, increased
secretion of thyroid hormone just like TSH and these antibodies are
called thyroid stimulating immunoglobulin (TSI). Both TSH and TSI
can stimulate the growth and function of the gland but the difference
between the two is that TSH is a hormone and TSI is an antibody so TSH
is subject to negative feedback if T3 and T4 increase. TSI on the other
hand does not have a negative feedback even if secretion of thyroid
hormones continually increases; there is still production of TSI.
You can have a solitary toxic adenoma. Adenoma is a hormone
secreting tumor which is usually benign.
Hashimotos thyroiditis in the early stage can cause
hyperthyroidism but in the late stage there will be hypothyroidism
because antibodies will completely destroy the target cell.
Primary: Increased TH, Decreased TSH, Decreased TRH
Secondary: Increased TH, Increased TSH, Decreased TRH
Tertiary: Increased TH, Increased TSH, Increased TRH
Hormonal picture: In primary hyperthyroidism, thyroid
hormones are increased so negative feedback is activated which
decreases TSH and TRH. A patient can have goiter most likely in Graves
disease because of TSI.
If this will not be effective and the gland continues to grow, you
can give radioactive iodine except if the patient is pregnant or has a heart
condition. This will destroy all hyperfunctioning cells.
If the condition is malignant, you can do now surgery. Total if
malignant, subtotal is benign. If you do subtotal, you leave at least 5 g of
the gland.
You cannot do surgery if the thyroid gland is hyperfunctioning
because subjecting the patient to surgery means subjecting the patient to
stress and stress will stimulate further release of thyroid hormones so
that will aggravate the condition specially the effect of thyroid hormones
to cardiovascular system and that is called thyroid crisis or thyroid
storm. For that, you have to give anti-thyroid drugs and iodides. If there
is excess in iodides, the function of thyroid gland will decrease. At least to
minimize the actions of thyroid hormones on the cardiovascular system,
you give or blocker.

Extrathyroidal
TSH secreting pituitary tumor
Fastidious or iatrogenic (exogenous T3, T4)
Ectopic thyroidal tissue

Secondary or extrathyroidal, there could be a TSH secreting

pituitary tumor so there is increased TSH, thyroid hormones, decreased
TRH and definitely there is goiter. The other secondary means that it is
secondary to another condition, not in the pituitary because those who
want to lose weight takes in thyroid hormones and this is iatrogenic.
Secondary could also cause of an ectopic thyroid tissue which is rare.

If is tertiary, all are increased, definitely there is goiter.

Differential Diagnosis of Hypothyroidism

Ultrasound Cystic Aspiration biopsy

Solid RAIU

Laboratory diagnosis again you request for serum free T3, T4

and TSH. If there is a mass at the anterior part of the neck, do an
ultrasound to determine if the mass is cystic (contains fluid) or if it a solid
mass. If it is just cystic, this will be followed by aspiration biopsy and the
result is usually benign. But upon ultrasound and the result is a solid
mass, the next step is radioactive iodine uptake. Radioactive iodine could
be administered intravenously, after 6 and 24 hours a scan in the neck is
passed to visualize how much of the administered iodide the thyroid
gland has taken up. Normally, after 6 hours the gland should take up 15%
of the administered iodide. After 24 hours, 25% should be taken up by the
gland. After 24 hours, if the body is abnormally low it means that there is
decreased uptake so the mass is non-functional and it is called cold
nodule. Usually if it non-functional or cold nodule, it is malignant. On the
other hand, if after 24 hours, the uptake is abnormally high, it means that
the mass is hyperfunctional and that is called hot nodule. If it is
hyperfunctional or hot nodule, usually it is benign.

Treatment
Anti-thyroidal drugs
PTU (-) T4 T3 (-) peroxidase
Methimazole catalysed steps
RAI
Surgery

For treatment, you can start with anti-thyroid drugs specially if

the patient is young, the gland is small and the disease is mild. Anions that
will compete with iodide and block the first step in the biosynthesis of
thyroid hormones. More commonly used are propylthiouracyl (PTU) and
methimazole these drugs will inhibit all peroxidase catalysed step in the
biosynthesis of thyroid hormones oxidation, organification and
To God belong wisdom and power; counsel and understanding are
coupling. In addition, PTU can also inhibit peripheral conversion of T4 to
His.
T3.
-Job 12:13

GOD BLESS YOU

8 Shannen Kaye B. Apolinario, RMT