Effect of acetaminophen, Diazepam and nordiol on free thyroxine index in human serum

Abstract

The major problem in vitro testings of thyroid function such as by total serum T4 is the effect of some drugs interfering with its concentration, which will be altered when the amount or the binding effectiveness of serum proteins is changed. To prevent the error in patients with abnormalities of thyrobinding proteins, a free thyroxine index (FTI) is introduced in this study as the test because it is simple and more diagnosis. FTI is derived from measurement of the total serum T4 concentration divided by the value of T3 -uptake or the vacant binding-sites for T4 .. Studies have suggested that FTI value is directly proportional to the concentration of free T4 , which is the component in serum that exerts biological action. Therefore, the initial part of this work is mostly devoted to development of RIA for total serum T4 by several important modifications, using polyethylene glycol (PEG) as precipitating agent, and also including of quality control and cross-reactivity testings. The great majority of investigation for the effects of some drugs on the concentration of thyroid hormone has been performed in experimental animals. Studies of the effects of acetaminophen (paracetamol – analgesic), diazepam (valium - tranquilizer) and nordiol (oral - contraceptive) on total serum T4 - T3-uptake and FTI in man are more realistic than those made in animals, because the results are directly applicable. Thus, short-term treatments of acetaminophen & diazepam were 5 day orally administration, but nordiol was given for a month to healthy women. Results of the control and the treatment groups were compared. It appeared that the values of all three parameters mentioned above were not changed by acetaminophen (p < 0.4-0.9). For diazepam treated subjects, only total serum T4 concentration were significantly decreased (p < 0.001), confirming that diazepam displaces T4 for TBG-binding sites, but no significant difference (p < 0.4-0.6) was found between the values of T3-uptake and FTI. In case of nordiol, an oral contraceptive drug, it significantly increases total serum T4 (p < 0.01) and T3-uptake (p < 0.05), but the values of FTI are not significantly changed (P <0.1), confirmimg that FTI is a very good index of thyroid function test because essay values for total T4 and T3-uptake will be altered, whereas FTI values will be not affected by these drugs.