relations may be either concordant or discordant. Laboratarians often face the problem of physicians complaining that the reports do not match with the clinical

 

Different Markers of Thyroid Function are Tested in

Combination for Assessment of Thyroid Status

¾ Total tri-iodothyronine (T3)

¾ Total thyroxine (T4)

¾ Thyrotropin (TSH) (by ultra-sensitive method)

¾ Free tri-iodothyronine (FT3)

¾ Free thyroxine (FT4)

¾ Anti-thyroglobulin (Anti-Tg) antibody

¾ Anti-thyroid peroxidase (Anti-TPO) or anti-microsomal

antibody

¾ T-uptake.

The Endocrine System 745

Information to be Taken before Sample Collection

The answers to the following questions will aid in the

accurate diagnosis of the patient:

¾ Whether male or female?

¾ Age?

¾ Symptoms?

¾ Is the patient on treatment—Replacement therapy

(thyroxine, cytomel), antithyroid drug?

¾ Does the patient suffer from any other illness—HIV,

hepatitis, tumor, and nephrotic syndrome?

¾ Has the patient had any major surgery, trauma, stress?

¾ Is the patient hospitalized?

¾ Is the patient on any other drugs—oral contraceptives,

estrogens, androgens, anabolic steroids, glucocorticoids,

propranolol, dopamine, and metaclopromide?

¾ Family history—Does anyone in the patient’s family

suffer from autoimmune disorders?

¾ Does the patient suffer from autoimmune or connective

tissue disorder.

¾ Has the patient had any neck/whole body irradiation?

¾ If the patient is a female—Does she have a regular

menstrual cycle? Pregnant or postmenopausal?

¾ Geographical location—Does the patient come from an

iodine deficient/excess region?

Tests for FT3/FT4 are gaining more importance in the

diagnosis of thyroid disorders. All limitations of total T3,

total T4 due to bound proteins is overcome by free T3 and

free T4. FT3 and FT4 are considered to be the “physiologically active hormones”.

FT3, FT4—Recommendations for Testing

Generally recommended in

¾ Monitoring treatment—thyroid replacement or

suppression.

¾ Hospitalized patients, where patients may show

symptoms of non-thyroidal illness.

¾ Pregnant women suffering from thyroid disorders.

¾ Patients known to take certain drugs which will interfere

with total T3 and total T4 test results.

¾ Elderly patients.

¾ Particularly if a patient’s thyroid function test does not

correlate with clinical history.

Free Thyroxine Index (FTI)

An estimate (index) related to free T4 levels in serum

can be calculated as the product of a T4 result and a T3

uptake ratio (T3UR) test. The reasoning is based on the

premise that the T3UR result is inversely proportional to

unsaturated thyroxine-binding globulin (UTBG) in serum,

and that free T4 varies directly with total T4 and inversely

with UTBG levels.

Thus, FT4 Index = T4 (total)× T3UR

Results may be expressed in any arbitrary terms and may

even be related to actual FT4 levels by calculation, using

actual values for FT4, T4, and T3UR on a number of normal

specimens. It has been observed that the FT4 index is

not as discriminatory as the actual estimation of FT4 by

equilibrium dialysis. In particular, aberrant results may

occur in patients whose TBG is abnormal and in patients

whose concentration of TBG is markedly increased or

decreased.

T3 Uptake Ratio (T3UR)

(An Index of the Unsaturated Thyroxine-binding

Globulin Fraction of Serum)

The test has nothing to do with the actual T3 serum level

in spite of its name which, unfortunately, is sometimes

abbreviated to “T3 test”. It must be emphasized that the

T3 uptake ratio and the true T3 (T3 by EIA) are entirely

different tests.

Clinical Significance

The T3 uptake ratio, in conjunction with the T3

measurement in serum, is used as a screening test of

thyroid function.

Pregnancy

Elevated T3 values are to be expected in euthyroid

patients. TBG and unsaturated TBG are both increased

in normal pregnancy. This appears towards the end of

the first trimester and is caused by increased estrogen

secretion. In such patients low-T3UR test values are to

be expected because of the increase in unsaturated TBG.

This is important because the normally expected lowT3UR values are not found in certain cases of habitual

threatened abortions as well as in pregnancy complicated

by hyperthyroidism.

High or Low-T4 in a Euthyroid Individual

In rare cases this is caused by a hereditary abnormality

in the level of TBG. Thus, in a eumetabolic person with

hereditary absence of TBG, a low-T3 will be found and the

T3UR test value will be high; the converse applies to the

person with a hereditary excess of TBG.

A Normal T3 in a Hypothyroid Patient

This can occur when the unsaturated TBG is elevated.

Thyroid Function Tests

Introduction

When a patient is referred by a clinician for thyroid

function tests, he may be symptomatic or asymptomatic.

746 Concise Book of Medical Laboratory Technology: Methods and Interpretations Symptomatic patients present vague symptoms and

complain that they just do not feel like themselves—may

be they are a little tired, are experiencing hot or cold spells,

or feel that their heartbeat is too fast or too slow. These

symptoms could mean that the patient is suffering from

thyroid disease or these could be symptoms related to

nonthyroidal diseases.

At the same time, the asymptomatic patient may be

suffering from thyroid illness and may be in need of

immediate diagnosis and therapy. In such conditions, it is

very crucial for the physician to accurately diagnose and

treat the patient or monitor treatment.

It is here that the clinical laboratory plays an

important role. The physician is totally dependent on

the interpretation of the pathologist. It is based on

the pathologist’s interpretation that the physician can

successfully diagnose and treat the patient.

Thyroid assays in general are extremely sensitive assays

as they involve measurement of hormones in microgram

and nanogram quantities. Also, the thyroid function and

thyroid hormones interact as part of a multiple gland

feedback loop, and hence are often interpreted together to

detect disease and understand its etiology.

In the past decade, important changes have taken place

in the strategy of thyroid function testing. Previously,

thyroid tests were dominated by T3 (total T3), T4 (total T4)

and TSH tests. People believed that if total T3 and total T4

are low, then TSH has to be high and vice versa. Here, they

are considered only the feedback mechanism between

the pituitary hormone TSH and thyroid gland hormones

total T3 and total T4. What they failed to consider here is

that there are other factors which affect total T3 and total

T4 levels. Moreover, total T3 and total T4 being in bound

form (bound to TBG) and are not the physiologically

active hormones participating in metabolic functions;

but it is the free hormones, free T3 and free T4, which are

physiologically active.

Throughout the world, there is a trend for TSH and free

T4 tests to replace the conventional total T3, total T4, TSH

tests for screening thyroid functions with conventional

thyroid screening strategy, total T3, total T4 and TSH. When

laboratory results are correlated with clinical findings, the

relations may be either concordant or discordant.

Laboratarians often face the problem of physicians

complaining that the reports do not match with the clinical

history of the patient, for example ‘abnormal’ total T4 in

absence of thyroid disease. Here the laboratarian only

correlates total T3, total T4 and TSH values; and as a result,

in such situations, clinicians are in a dilemma and often

doubt the methodology used.

If the laboratory results are discordant, a distinction

needs to be made between a previously unsuspected

diagnosis, subclinical disease, anomalous assay results,