Serum free thyroxine index

After treatment is initiated, patients should be examined and thyroid function tests (serum-free thyroxine index and total triiodothyronine concentrations) measured every 2 to 4 months. Once euthyroidism is established, follow-up every 4 to 6 months is reasonable. 

Answer The results of the laboratory tests confirm the hypothyroxinemia (i.e., low serum total T4 concentration). The calculated free thyroxine index... 

The etiology and pathogenesis of hypothyroidism are outlined in Table 38-5. Hypothyroidism can occur with or without thyroid enlargement (goiter). The laboratory diagnosis of hypothyroidism in the adult is easily made by the combination of a low free thyroxine (or low free thyroxine index) and elevated serum TSH (Table 38-2). 

Hypothyroid women frequently have anovulatory cycles and are therefore relatively infertile until restoration of the euthyroid state. This has led to the widespread use of thyroid hormone for infertility, although there is no evidence for its usefulness in infertile euthyroid patients. In a pregnant hypothyroid patient receiving thyroxine, it is extremely important that the daily dose of thyroxine be adequate because early development of the fetal brain depends on maternal thyroxine. In many hypothyroid patients, a modest increase in the thyroxine dose (about 20-30%) is required to normalize the serum TSH level during pregnancy. Because of the elevated maternal TBG, the free thyroxine index (FT4I) or free thyroxine (FT4) and TSH (Table 38-2) must be used to monitor maternal thyroxine dosages. 

Until recently it was not always possible to measure unbound thyroxine in serum directly because of the minute quantities involved. Therefore a free thyroxine index calculation was often made, since this value is proportional to the free thyroxine concentration. This index can be arrived at by multiplying a measure of thyroxine in the blood (usually the FBI) by a value derived from the measurement of thyroxine-unoccupied binding sites of thyroxine-binding proteins. This was possible since the uptake of thyroxine or triiodothyronine by red cells or resin is inversely proportional to the number of unoccupied binding sites. As thyroxine-binding sites become increasingly saturated, the free thyroxine levels increase. An example of this method of arriving at a free thyroxine index is the work of Clark and Horn (C5). Calculation of the free thyroxine index is valuable since the FBI determination and the resin uptake of Ts are determinations that are routinely made in many clinical laboratories. 

It is now well established that clinically euthyroid patients who have abnormalities in the serum Ti-binding proteins also have abnormalities in the serum total T4 level and in Tg resin uptake. Taking the example of the oral contraceptives, TBG is increased, but the abnormalities in total T4 and Tg uptake diverge in opposite directions—i.e., total T4 is elevated and Tg uptake is depressed. Clark and Horn (C17) took advantage of the inverse nature of these abnormalities and devised a free thyroxine index (FTI) from the mathematical product of FBI and Tg uptake, basing this on a similar index constructed from the measurement of the uptake of Tg by red blood cells (012). The theoretical considerations underlying the FTI are as follows (C17) ... 

H23. Howorth, P. J. N., and Maclagan, N. F., Clinical application of serum-total-thyroxine estimation, resin uptake and free thyroxine index. Lancet 1, 224-228 (1969). 

W13. Wellby, M. L., O Halloran, M, W., and Marshall, J., A comparison of effective thyroxine ratio, free thyroxine index and free thyroxine concentration in correcting for thyroxine-binding abnormalities in serum. CUn. Endocrinol. 3, 63-68... 

A means of expressing serum thyroxine values which takes into consideration any abnormalities in protein binding. It is thus analogous to the free thyroxine index. 

Although most circulating thyroxine is protein bound, it is the free fraction which is physiologically active. The free thyroxine index corrects the total serum thyroxine for any abnormalities there may be in protein binding (e.g. the low TBG levels found in hypoproteinaemic states or the high TBG levels found in... 

Measurement of the free (physiologically active) thyroxine in serum. This may be determined directly or can be derived (the free thyroxine index) if a T3 resin uptake or a thyroxine-binding globulin level is measured. 

Free thyroxine index. This can be calculated from the total serum thyroxine and either the T3 uptake value (q.v.) or the thyroxine-binding globulin level. 

If the total thyroxine in the patients serum has been determined at the same time, the free thyroxine index (FTI) can be determined. This gives an indication of the free (metabolically active) levels of the hormone in the serum. The FTI is given by the formulae ... 

The function of most albumin isoforms is normal, although some have abnormal binding affinities for thyroxine (T4). Binding may be increased, as in familial dysalbu-minemic hyperthyroxinemia, or decreased. Individuals with famihal dysalbuminemic hyperthyroxinemia are euthyroid but have elevated serum T4 and free T4 index the variant albumin comigrates with Alb A. Two glycosylated variants. Alb RedhiU and Alb Casebrook, have altered fatty acid binding properties. 

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