FENCLOFENAC-SECONDARY EFFECTS UPON THE PITUITARY THYROID AXIS

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Abstract
To elucidate the mechanism of suppression of TSH responsiveness to TRH induced by the initiation of fenclofenac [a nonsteroidal antiinflammatory agent] therapy, the early period of drug administration was examined in detail and the effect of the drug during a TRH infusion was assessed [in humans]. The effect of fenclofenac upon the response of ACTH, cortisol, growth hormone and prolactin to insulin-induced hypoglycemia was examined. The effect of fenclofenac upon an equilibrium dialysis method for estimating free thyroid hormones was evaluated and was insignificant within the therapeutic concentration range of the drug. A sharp, short-lived rise in free thyroxine [T4] (21.7 .+-. 2.0 to 26.8 .+-. 1.9 pmol/l; P < 0.03) was observed 60 min after the 1st dose of fenclofenac. Repeated peaks of free T4 during chronic fenclofenac treatment, superimposed upon the previously described steady decline of free and total serum T4, are postulated to cause the observed suppression of TSH release which is present only until free and total serum Ty levels reach their nadir. The time course of the changes seen during TRH infusion suggested that the pituitary suppression was secondary to a rise in the free T4. The responses to hypoglycemia of those pituitary hormones examined were not affected by fenclofenac.