Biology of Disease

Total T 4 and T 3 measurements were once used widely in pathology laboratories
but have the disadvantage that their values are dependent on plasma TBG
levels, which can give misleading results. When TBG levels increase, for
example in pregnancy or in females receiving estrogen-containing oral
contraceptives, then total T 4 and total T 3 are also increased even though the
individual is not hyperthyroid. Decreases in TBG concentrations occur in
malnutrition, protein loss, severe illness and malabsorption (Chapters 10 and
11 ) and causes a reduction in total T 4 and T 3. There has been some controversy
on the validity of free thyroid hormone measurements, but most laboratories
now determine free T 4 and T 3 , rather than the total concentration. Free T 4 and
particularly free T3,are usually increased in hyperthyroidism. Free T 4 is low in
hypothyroidism and is the preferred measurement for its detection because
free T 3 can be normal in hypothyroidism due to an increase in its peripheral
formation from T 4. In a few patients with hyperthyroidism, free T 4 is within the
reference range but free T 3 is increased and TSH is nearly always undetectable.
This form of hyperthyroidism is referred to as T 3 toxicosis.

In any systemic illness, such as myocardial infarction, fever or liver disease,
the normal metabolism of thyroid hormones is disturbed, reducing the
concentrations of T 4 and T 3 in the plasma because T 4 is converted to an
inactive isomer called reverse T 3 or rT 3 (Figure 7.20) and T 3 is not replenished
from T 4. Thyroid stimulating hormone levels may be normal or reduced and
concentrations of TBG, albumin and prealbumin may also decline. Patients
may have reduced T 4 , T 3 and TSH, although there is no thyroid dysfunction.
For this reason, thyroid function tests should not be performed on sick
patients until they recover. Table 7.3 outlines the results of tests used in
thyroid disorders. The TRH test is rarely used now in the diagnosis of thyroid
disease. It is almost exclusively used in the diagnosis of patients with pituitary
disease and to assess the capacity of the pituitary to secrete TSH. The patient
is given 200 Mg of TRH intravenously and the serum TSH is measured after
0, 20 and 60 min. A normal response involves a three- to fivefold increase in
TSH above the basal level. A slow rise in TSH (where the 60-min concentration
is greater than the one at 20 min) together with low basal levels of TSH and
thyroid hormones suggests hypothalamic disease, while a lack of response is
suggestive of pituitary hypothyroidism or hyperthyroidism (Figure 7.21).

THYROID HORMONE DISORDERS

CZhhVg6]bZY!BVjgZZc9Vlhdc!8]g^hHb^i]:YLddY &,*

Figure 7.20 Reverse T 3 (rT 3 ). Compare its

structure with those shown in Figure 7.17.

Test Hyperthyroidism Hypothyroidism Developing

hypothyroidism

T 3 toxicosis Nonthyroidal illness

TSH decreased increased increased increased decreased or normal

Free T 4 increased decreased normal normal decreased

Free T 3 considerable increase decreased or normal decreased or normal considerable increase decreased

Table 7.3Interpretation of results for thyroid function tests

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NH 2

CH COOH

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