Screening and Case Finding About 2 to 7% of women over age 40 years may have slightly elevated serum TSH concentrations. The case for routine assessment of thyroid status is strongest in elderly
¾ Recent dose adjustment (TSH high, free T4 normal)
¾ Patient taking T3 (TSH low, free T4 normal)
¾ Patient noncompliant with hormone replacement
¾ Drugs affecting thyroid hormones: Glucocorticoids,
¾ Thyroid hormone resistance (TSH high, free T4 high,
¾ TSH-secreting tumor (TSH high, free T4 high, patient
¾ During antithyroid drug therapy, there can be patients
who have persistent serum T3 excess, despite normal
Effects of Drugs on Thyroid Function
¾ Altered hypothalamic or pituitary function
¾ Altered biosynthesis or release of thyroid hormones
¾ Displacement of T4 and T3 from binding proteins
¾ Reduced peripheral conversions of T4 to T3
¾ Inhibition of peripheral hormone activity.
Drugs that Affect Results of Thyroid Function Tests
Propylthiouracil Total T3 reduced both
Propranolol Total T3 reduced, T4
Glucocorticoids Total T3 reduced, T4
Relationship Between Serum Total T4 and Total T3
Concentrations in Various Disorders Serum T3 Concentration
FT3 and TSH Concentrations in Various Disorders Serum TSH Concentration
Free Thyroxine Measurements in Common
Conditions Affecting Thyroid-binding Proteins
Clinical conditions Free T4 Levels
Near Normal Concentration of Serum-Binding Proteins
Abnormal Concentration of Serum-Binding Proteins
Low total T4 non-thyroidal illness Normal or High
High total T4 non-thyroidal illness Normal or High
Free T4 and Free T3 in Various Disease Conditions
¾ Hyperthyroidism produces a primary increase in
free T4, whereas estrogens and idiopathic or genetic
conditions may produce a primary increase in TBP. In
both cases [T4 and TBP] increase, but in the former,
the patient is ill and requires treatment; in the latter,
the patient is euthyroid. Likewise, a low serum [T4 and
TBP] may be due to a primary decrease in [FT4] or to
a primary decrease in [TBP]. It is, therefore, clinically
important to differentiate between changes in [T4 and
TBP] that are due to primary changes in [FT4] (e.g.
hyper-or hypothyroidism) and those that are due to
¾ Serum TSH level is low in all forms of hyperthyroidism
except in rare cases in which hyperthyroidism is
mediated by TSH itself. When TSH level is low, free
T4 concentration should be measured and will be
elevated in most cases of hyperthyroidism. Finding a
low TSH level and an elevated free T4 level is usually
sufficient to establish the diagnosis of hyperthyroidism.
If TSH level is low but free T4 level is normal, a T3
measurement should be performed, since serum T3
concentration is often elevated earlier in the course
of hyperthyroidism and to a greater degree than is T4
concentration. Because only the free fraction of T3 is
active, the estimation of free T3 is helpful in adjusting
the total T3 for variations in binding proteins. It should
be remembered that numerous medications as well as
both acute and chronic illness may cause a transient
lowering of T3 concentration as well as a reduction in
¾ In Graves’ disease or toxic adenomas, serum total T3
and free T3 levels are typically elevated to a greater
degree than total T4 and free T4.
¾ T3 toxicosis—encountered in about 5% of hyperthyroid
population—total T3 and free T3 values increase.
¾ Serum total T4 and free T4 are disproportionately
elevated to a greater degree than total T3 and free T3
values in most patients with toxic multinodular goiter.
¾ Monitoring total T3 and free T3 values may also be of
importance in evaluating both the severity and the
response therapy in patients being treated for thyroid
storm or crisis in that the antithyroid drug therapies are
focused on reducing both thyroid gland T3 secretion
and peripheral tissue T3 production from T4.
¾ In nonthyroidal illness (NTI) and altered states of
nutrition there are two categories:
Low T3 state: Decrease in total T3 and free T3 while
maintaining normal total T4 and free T4. Observed in
mild or moderate NTIs or states of caloric deprivation
Low T3-T4 state: Total T4 also decreased, a case of
¾ Free T4 levels remain within or near the normal range
of values as serum total T4 levels decline.
¾ Decreased total T3 or normal free T4 or increased free
T4 results from acquired defect in serum T4-binding
¾ Also common are increases in the levels of the free
fraction of T4 and T3 which are caused by decrease
in serum concentrations of thyroid hormone-binding
proteins, changes in binding properties induced by
circulating inhibitors and drugs, or both. Low levels
of total T4 may be seen in nonthyroidal illnesses, but
total T4 concentrations in these patients are usually
normal or above normal as determined using reference
¾ Thus in nonthyroidal illnesses, abnormal thyroid test
results are not necessarily indicative of thyroid disease
but may demonstrate adaptations to the catabolic
state, many of these changes revert to normal when the
¾ Several test abnormalities may be seen in nonthyroidal
illnesses in euthyroid patients (the ‘euthyroid sick
syndrome’). The most common abnormalities are a
reduction in the serum total T3 concentration and an
elevation in the serum level of free T3. Also common are
increases in the levels of the free fraction of T4 and T3
which are caused by decrease in serum concentrations
of thyroid hormone-binding proteins, changes in
binding properties induced by circulating inhibitors
and drugs, or both. Low levels of total T4 may be seen
in nonthyroidal illnesses, but total T4 concentrations in
these patients are usually normal or above normal as
determined using reference methods.
¾ If total T4 (or free T4) level is normal, hypothyroidism is
most unlikely: however, a low T4 concentration is often
For definitive diagnosis, assessment of both serum TSH
and free T4 is required, but a more limited approach
can be used for initial case finding and follow-up. In the
interests of cost effectiveness, evaluation of thyroid status
may often begin with an assay for either serum TSH or free
T4, followed by further algorithm-based assessment if the
initial result is abnormal. As an initial test, serum total
T4 measurements give an unacceptable rate of abnormal
results, due to the frequency of abnormalities in serum
thyroid hormone-binding proteins.
Four distinct clinical situations in which evaluation
of thyroid function is done can be considered: testing of
unselected populations for case finding or screening,
testing of untreated patients who have clinical features
that suggest thyroid disease, assessment of the response
to treatment for thyroid dysfunction, and evaluation of
patients in whom associated illness or drug therapy are
likely to complicate clinical and laboratory assessment or
whose initial results are atypical or unclear.
About 2 to 7% of women over age 40 years may have
slightly elevated serum TSH concentrations. The case for
routine assessment of thyroid status is strongest in elderly
women who have any symptoms that could be consistent
with hypothyroidism. Among hospitalized patients, the
large majority of abnormal results are due to nonthyroidal
Most persons found to have either high or low
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