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Thyroid function is reflected by free thyroid hormone concentrations which
constitute only a minute fraction of the total amount of thyroid hormones
in the circulation. Total thyroid hormone concentrations may therefore
fail to adequately reflect thyroid function and may vary depending on influences
on thyroid hormone binding proteins. The most common situations causing
alterations in binding protein concentrations are pregnancy, liver diseases,
and use of estrogens. These considerations make determination of free thyroid
hormone concentrations most desirable. The sole determination of total
T4 without a direct or indirect estimate of its protein binding has nowadays
to be considered inappropriate. The methods for direct determination of
free thyroid hormones have definitely been improved over the past years.
Methods may be separated into one step and two step procedures. The one
step procedures are based on the use of T4 or T3 analogues carrying a radioactive,
enzymatic, luminescent or fluorescent label. These analogues compete with
the free thyroid hormones for binding to specific antibodies, but fail
to interact itself with serum binding proteins. Alternatively to labelling
the hormone analogue, some new methods employ labelled antibodies instead
of labelled hormone analogues. Two step procedures first achieve extraction
of thyroid hormones with the use of a solid phase antibody and assess concentration
of extracted hormones in a second independent step. Two step assays and
modern one step procedures show less interference with unspecific factors
(Table 2) and appear to be more reliable in patients with severe nonthyroidal
illness.
Table 2:Criteria of quality assessment for routine TSH assays
As a rule, thyroid hormone measurements should always be interpreted in connection with serum TSH. Interpretation is straight forward in most cases except for severely ill patients with NTI syndrome and rarely for patients with TSH producing pituitary adenoma or thyroid hormone resistance (Table 3). Table 3: Conditions with low TSH in the absence of overt hyperthyroidism and with elevated TSH values in the absence of overt hypothyroidism Low TSH in absence of overt hyperthyroidism
Thyroid hormone resistance is characterized by a clinically euthyroid or hyperthyroid state, abnormally elevated free thyroid hormone concentrations, and normal or even increased TSH values. Hyperthyroidism in the presence of an increased or normal TSH is also found in secondary hyperthyroidism due to a TSH producing pituitary adenoma. Differential diagnosis can be done by TRH stimulation which can significantly increase TSH values only in thyroid hormone resistance and by determination of free alpha-subunit which is characteristically elevated in TSH-producing adenomas. Table 4 shows the results of in vitro thyroid testing in a patient with TSH producing pituitary adenoma and with thyroid hormone resistance syndrome. Thyroid Autoantibodies Table 4: Results of in vitro thyroid testing with TSH-producing pituitary adenoma (patient U. R.) and in a patient with thyroid hormone resistance syndrome (patient C. K.). Both patients show similar elevations of total T4 (reference range 58-154 nmol/l), FT4 (reference range 10-25 pmol/l), total T3 (reference range 1.23-3.08 nmol/l). Basal TSH levels were also elevated in both patients. Significant stimulation by TRH, however, couldonly be achieved in thyroid hormone resistance syndrome.
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