n all determinations, most clinicians prefer to assess two more or less independent measures of thyroid function. For this purpose, an assessment of FT4 and sensitive TSH are suitable. As an initial single test, a sensitive TSH assay may be most cost-effective and specific. TSH should be 0 – .1 µU/ml in significant thyrotoxicosis, although values of .1 – .3 are seen in patients with mild illness, especially with smoldering toxic multinodular goiter in older patients(1.1). TSH can be low in some elderly patients without evidence of thyroid disease. TSH can be normal — or elevated — only if there are spurious test results from antibodies, or the thyrotoxicosis is TSH-driven, as in a pituitary TSH-secreting adenoma or pituitary resistance to thyroid hormone.
Measurement of FT4 or FTI(Free thyroxine index)is also usually diagnostic.The degree of elevation of the FT4 above normal provides an estimate of the severity of the disease. During replacement therapy with thyroxine the range of both FTI and FT4 values tend to be about 20% above the normal range, possibly because only T4 , rather than T4 and T3 from the thyroid, is providing the initial supply of hormone. Thus many patients will have an FT4 or FTI above normal when appropriately replaced and while TSH is in the normal range. Except for this, elevations of FT4 not due to thyrotoxicosis are unusual, and causes are given in Table 3. Of course the Total T4 level may normally be as high as 16 or 20 µg/dl in pregnancy, and can be elevated without thyrotoxicosis in patients with familial hyperthyroxinemia due to abnormal albumin, the presence of hereditary excess TBG, the presence of antibodies binding T4 , the thyroid hormone resistance syndrome, and conditions listed in Table 3. The T4 level may be normal in thyrotoxic patients who have depressed serum levels of T4 -binding protein or because of severe illness, even though they are toxic. Thus, thyrotoxicosis may exist when the total T4 level is in the normal range.However measurement of FT4, FT3, or FTI usually obviates this source of error and is the best test.
In the presence of typical symptoms, one measurement of suppressed TSH or elevated FT4 is sufficient to make a definite diagnosis, although it does not identify a cause. If the FT4 is normal, repetition is in order to rule out error, along with a second test such as serum FT3. A variety of methods for FT4 determination have become available, including commercial kits. Although these methods are usually reliable, assays using different kits do not always agree among themselves or with the determination of free T4 by dialysis. Usually T4 and T3 levels are both elevated in thyrotoxicosis, as is the FTI (Free Thyroxin Index), or an index constructed using the serum T3 and rT3U levels, and the newer measures of FT3.
|Table 3. Conditions Associated with Transient Elevations of the FT4 or FTI|
|Estrogen withdrawal||Rapid decrease in TBG level|
|Amphetamine abuse||Possibly induced TSH secretion(2)|
|Hyperemesis gravidarum||hCG, can cause thyrotoxicosis|
|Iodide administration||Thyroid autonomy|
|Beginning of T4 administration||Delayed T4 metabolism(3)|
|Severe illness (rarely)||Decreased T4 to T3 conversion (4)|
|Amiodarone treatment||Decreased T4 to T3 conversion, iodine load|
|Gallbladder contrast agents||Decreased T4 to T3 conversion, iodine load|
|Propranolol (large doses)||Inhibition of T4 to T3 conversion|
|Prednisone (rarely)||Inhibition of T4 to T3 conversion|
|High altitude exposure||Possibly hypothalamic activation|
|Selenium deficiency||Decreased T4 to T3 conversion|
T3 and FT3 ASSAY–
The serumT3 level determined by RIA is almost always elevated in thyrotoxicosis and is a useful but not commonly needed secondary test. Usually the serum T3 test is interpreted directly without use of a correction for protein binding, since alterations of TBG affect T3 to a lesser extent than T4. Any confusion caused by alterations in binding proteins can be avoided by use of a FT3 assay or T3 index calculated as for the FTI. Generally the FT3 assay is as diagnostically effective a