DIFFICULTIES IN LAB. DIAGNOSIS OF THYROID DISEASE

DIFFICULTIES IN LAB.DIFFICULTIES IN LAB.
DIAGNOSIS OFDIAGNOSIS OF
THYROID DISEASETHYROID DISEASE
ByBy
Prof. Moustafa RizkProf. Moustafa Rizk
Prof. of Clinical PathologyProf. of Clinical Pathology
Faculty of Medicine, University of AlexandriaFaculty of Medicine, University of Alexandria..

Common Thyroid
Problems
[1] Those concerning the production of
hormone (too much, or too little) .
[2] Those due to increased growth of the
thyroid causing compression of important
neck structures or simply appearing as a
mass in the neck.
[3] The formation of nodules or lumps
within the thyroid which are worrisome for
the presence of thyroid cancer.
[4] Those which are cancerous.

Common Tests to Examine
Thyroid Gland Function
 No one single
laboratory test is
100% accurate in
diagnosing all types of
thyroid disease;
however,a combination
of two or more tests
can usually detect
even the slightest
abnormality of thyroid
function

Total T4
For example, a low
T4 level could
mean a diseased
thyroid gland or a
non-functioning
pituitary gland
which is not
stimulating the
thyroid to produce
T4.

Total T4
Since the pituitary gland would normally
release TSH if the T4 is low, a high TSH
level would confirm that the thyroid gland
(not the pituitary gland) is responsible for
the hypothyroidism, a condition sometimes
called primary hypothyroidism.

Total T4
If the T4 level is low and TSH is
not elevated, the pituitary gland is
more likely to be the cause for the
hypothyroidism.

Total T4
 Elevation or decrease in serum T4
may be due to change in TBG level
and not reflect clinical
hyperthyroidism or hypothyroidism.

Total T4
T4 levels may be elevated with increased
concentrations of TBG:
 Administration of oral contraceptives
 Pregnancy
 Infectious and chronic active hepatitis
 Biliary cirrhosis
 Congenital increase in TBG levels.

Total T4
T4 may be reduced when TBG levels
are decreased:
 Nephrotic syndrome,
 Androgen therapy
 Glucocorticoid therapy
 Major systemic illness
 Congenital decrease of TBG

Total T4
Drugs which compete for protein binding
sites, such as phenylbutazone,
diphenylhydantoin or salicylates, can result
in a depressed T4 measurement.
Serum T4 levels in neonates and infants
are higher than values in the normal adult,
due to the increased concentration of TBG
in neonate serum.

Thyroid Binding Globulin
If a patient appears to have normal
thyroid function, but an unexplained
high or low T4, or T3, it may be due
to an increase or decrease of TBG.
Direct measurement of TBG can be
done and will explain the abnormal
value.

Free Thyroxine Index
T4 values should be normalized for
individual variations in thyroxine
binding protein (TBP) capacity. The
Free Thyroxine Index (FTI) is
conventionally used to achieve this
measurement

Free Thyroxine Index
The Free thyroxine index is a calculation
we used to do before the FT4 test came
out on the market. By measuring serum
total T4 and the T3 uptake we were able
to figure out how much of the free T4 was
bound and how much was free, so it was
sort of a “prediction" of how much FT4
was available.

Free Thyroid Hormone
Since only the free or non-TBG
bound T4 results in clinical changes in
the patient, it is best to measure the
Free-T4 rather than the total T4.

 Free T3 and Free T4 levels are the only accurate
measure of the actual active thyroid hormone
levels in the blood.
 It is relatively common to find the Free T4 and
Free T3 hormone levels below normal when TSH is
in its normal range, even in the low end of its
normal range.
 When patients with these lab values are treated,
tremendous improvement , and a reduction of the
classic hypothyroid symptoms

 FT3 is typically elevated to a greater degree
than free T4 (FT4) in Graves' disease and in toxic
adenomas. In contrast, levels of FT4 are elevated
to a greater degree than FT3 in toxic
multinodular goiter and excessive T4 therapy.
 FT3 is useful in distinguishing these forms of
hyperthyroidism.
 FT3 may also be important in monitoring patients
on antithyroid therapy, where treatment is
focused on reducing the T3 production and the T4
conversion to T3.

Old Laboratory Tests
Unreliable
Most all older thyroid function panels
include the following:
Total T4
T3 Uptake (a count of the proteins
that bind up both T4 and T3)
Free Thyroxine Index (FTI).
These tests should be
abandoned because they are
unreliable as gauges of thyroid
function .

Total T3
Thyroxine (T4) represents 80% of the
thyroid hormone produced by the normal
gland and generally represents the overall
function of the gland. The other 20% is
triiodothyronine measured as T3 by
immunoassay.
Sometimes the diseased thyroid gland will
start producing very high levels of T3 but
still produce normal levels of T4.

Total T3
Clinically, measurements of serum T3
concentration are especially valuable
in diagnosing hyperthyroidism and in
following the course of therapy for
this disorder .
Total T3 measurements may be valuable when
hyperthyroidism is suspected and the free T4
estimate is normal.

Total T3
 Dietary iodide deficiency results in inadequate
production of thyroid hormones despite the
presence of normal thyroid tissue.
 In these cases, the serum T4 concentration is
often low, while the TSH concentration is
elevated. However, in iodine deficiency, these
results, together with a normal or slightly
elevated serum T3, are indicative of euthyroid
status in most individuals.

TSH
When the thyroid gland becomes
inefficient such as in early hypothyroidism,
the TSH becomes elevated even though
the T4 and T3 may still be within the
"normal" range.
This rise in TSH represents the
pituitary gland's response to a drop in
circulating thyroid hormone; it is usually
the first indication of thyroid gland
failure.

How is it used?
 diagnose a thyroid disorder in a person with
symptoms,
 screen healthy adults for thyroid disorders as
recommended by the American Thyroid
Association,
 screen newborns for an underactive thyroid,
 monitor thyroid replacement therapy in people
with hypothyroidism
 diagnose and monitor female infertility problems.

TSH
 A high TSH result often means an underactive
thyroid gland caused by failure of the gland
(hypothyroidism).
 Rarely, a high TSH result can indicate a problem
with the pituitary gland, such as a tumor, in what
is known as secondary hyperthyroidism.
 A high TSH value can also occur in people with
underactive thyroid glands who have been
receiving too little thyroid hormone medication.

TSH
 A low TSH result can indicate an overactive
thyroid gland (hyperthyroidism).
 A low TSH result can also indicate damage to the
pituitary gland that prevents it from producing
TSH.
 A low TSH result can also occur in people with an
underactive thyroid gland who are receiving too
much thyroid hormone medication.

TSH
When the doctor adjusts the dose of
thyroid hormone , The patient must
wait at least one to two months
before he goes to lab to check his
TSH again, so that his new dose can
have its full effect.

TRH Test
A baseline TSH of 5 or less usually
goes up to 10-20 after giving an
injection of TRH.
Patients with too much thyroid
hormone (thyroxine or
triiodothyronine) will not show a rise
in TSH when given TRH.

TRH Test
Patients who show too much response to
TRH (TSH rises greater than 40) may be
hypothyroid.
This test is also used patients who are
taking thyroid replacement to see if they
are on sufficient medication.
It is sometimes used to measure if the
pituitary gland is functioning.

Is there is a need to stop
taking thyroid pills for
these tests?
Most thyroid pills have a half life of
7 days which means they must be
stopped for four weeks (five half
lives) before accurate thyroid
testing is possible.

Thyroid Antibodies
Some people are found to have antibodies
against their own thyroid tissue. A
condition known as Hashimoto's
Thyroiditis is associated with a high level
of these thyroid autoantibodies in the
blood. Whether the antibodies cause the
disease or whether the disease causes the
antibodies is not known

Common Thyroid
Diseases
 1- Hypothyroidism
 2- Hyperthyroidism
 3- Goiters
5-Solitary Thyroid Nodules,
4-Thyroiditis
6-cancer

1-Hypothyroidism
 Hypothyroidism is a
condition in which the
body lacks sufficient
thyroid hormone.
Hypothyroidism is
more common than you
would believe...and,
millions of people are
currently hypothyroid
and don't know it

There are two fairly
common causes of
hypothyroidism.
 The first is a result of previous (or currently
ongoing) inflammation of the thyroid gland
which leaves a large percentage of the cells of
the thyroid damaged (or dead) and incapable of
producing sufficient hormone. The most common
cause of thyroid gland failure is called
autoimmune thyroiditis (also called Hashimoto's
thyroiditis), a form of thyroid inflammation
caused by the patient's own immune system.

The second major cause is the broad
category of "medical treatments". The
treatment of many thyroid conditions
warrants surgical removal of a portion or
all of the thyroid gland. If the total mass
of thyroid producing cells left within the
body are not enough to meat the needs of
the body, the patient will develop
hypothyroidism.

Hypothyroidism Diagnosis
The idea is to measure blood levels
of T4 or FT4 and TSH. In the
typical person with an under-active
thyroid gland, the blood level of T4
and FT4 will be low, while the TSH
level will be high.

In the more rare case of
hypothyroidism due to pituitary
failure, the thyroid hormone T4 will
be low, but the TSH level will also be
low.
.The real question in this situation is what is wrong with the pituitary?

The next question is: When is low too low,
and when is high too high? Blood levels
have "normal" ranges, but other factors
need to be taken into account as well, such
as the presence or absence of symptoms.
 Levels should be discussed with the
patient’s doctor so interpretation can be
of help (or not?) .

Although the majority of individuals
with hypothyroidism will be easy to
diagnose with these simple blood
tests, many millions will have this
disease in mild to moderate forms
which are more difficult to diagnose.

In other words, some patients with
very "mild" deviations in their thyroid
laboratory test results will feel just
fine while others will be quite
symptomatic.

It is important to help the patient
to FEEL better, not just make his lab
results better

2- Hyperthyroidism
 Hyperthyroidism
is a condition
caused by the
effects of too
much thyroid
hormone on
tissues of the
body.

Hyperthyroidism Causes
The most common underlying cause of
hyperthyroidism is Graves' disease.
Graves' disease is classified as an
autoimmune disease.
The antibodies that the patient's immune
system makes attach to specific activating
sites on thyroid gland which in turn cause
the thyroid to make more hormone.

Hyperthyroidism can also be caused
by a single nodule within the
thyroid instead of the entire
thyroid.
 Thyroiditis, can lead to the release of
excess amounts of thyroid hormones that are
normally stored in the gland .

3-Thyroid Goiter
 The term nontoxic goiter refers to enlargement of the
thyroid which is not associated with overproduction of
thyroid hormone or malignancy.
 The thyroid can become very large so that it can easily be
seen as a mass in the neck.
 A diet deficient in iodine can cause a goiter but this is
rarely the cause because of the readily available iodine in
our diets.
 A more common cause of goiter is an increase in TSH in
response to a defect in normal hormone synthesis within the
thyroid gland causing the thyroid to enlarge. This
enlargement usually takes many years to become manifest.

4-Thyroiditis
Hashimoto's Thyroiditis (also called
autoimmune or chronic lymphocytic
thyroiditis) is the most common
type of thyroiditis
During the course of this
disease, the cells of the thyroid
becomes inefficient in converting
iodine into thyroid hormone and
"compensates" by enlarging.

Hashimoto's Thyroiditis
As the disease progresses, the TSH
increases since the pituitary is trying
to induce the thyroid to make more
hormone, the T4 falls since the
thyroid can't make it, and the
patient becomes hypothyroid.
Thyroid antibodies are present in 95% of patients with
Hashimoto's Thyroiditis and serve as a useful "marker" in
identifying the disease without thyroid biopsy or surgery

De Quervain's
Thyroiditis
The thyroid gland generally swells rapidly
and is very painful and tender. The gland
discharges thyroid hormone into the blood
and the patients become hyperthyroid;
however the gland quits taking up iodine
(radioactive iodine uptake is very low) and
the hyperthyroidism generally resolves
over the next several weeks.
Thyroid antibodies are not present in the blood,
but the sedimentation rate, which measures
inflammation, is very high.

5-Thyroid Nodules
Three questions that should be answered
about all thyroid nodules:
Is the nodule one of the few that are
cancerous ?
Is the nodule causing trouble by pressing
on other structures in the neck ?
Is the nodule making too much thyroid
hormone ?
presence of hyperthyroidism or
hypothyroidism favors a benign nodule
Thyroid fine needle aspiration (FNA)
biopsy is the only non-surgical method
which can differentiate malignant and
benign nodules.

Thyroid cancer
 Calcitonin
 Thyroglobulin
 Calcium and ionized calcium
 Parathormon

DIFFICULTIES IN LAB. DIAGNOSIS OF THYROID DISEASE

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