triiodothyronine--reverse and fenclofenac

Administration of the anti-inflammatory drug fenclofenac (600 mg bd) for 28 days to four females with thyrotoxicosis resulted in a rapid decline in thyroid hormone levels. The mean total thyroxine (T4) level of 173 +/- 8.6 (SEM) nmol/l before therapy was normalized to 70 +/- 6.4 nmol/l after administration of the drug for 7 days. Free T4 levels also decreased significantly but not to within the reference range in all subjects. Mean total triiodothyronine (T3) and reverse T3 levels declined from 6.2 +/- 0.9 nmol/l and 0.63 +/- 0.2 nmol/l respectively before therapy to 3.8 +/- 0.5 nmol/l and 0.52 +/- 0.1 nmol/l after 7 days' treatment but remained consistently elevated in all subjects. Clinical thyroid status remained unchanged despite these marked reductions in circulating thyroid hormone levels, suggesting that fenclofenac was of no therapeutic benefit.

Topics: Adult; Anti-Inflammatory Agents; Clinical Trials as Topic; Female; Humans; Hyperthyroidism; Middle Aged; Phenylacetates; Thyroid Gland; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

The non-steroidal anti-inflammatory agent fenclofenac competitively inhibits the binding of thyroxine(T4) and triiodothyronine (T3) by thyroxine-binding globulin(TBG). Eight male volunteers completed a 4-week study during which they took fenclofenac 600 mg twice daily. The concentration of fenclofenac in serum reached a plateau after 1 week of therapy after which the mean concentration(+/SEM) of the drug in serum was 78.6 o.2 mg/1. During the steady state period on treatment there were reductions of the mean serum concentrations of total T4 to 35% (P less than 0.001), total T3 to 55% (P less than 0.001), free T4 to 69% (P less than 0.001) and free T3 to 90% (NS) of the respective pretreatment values. There were also significant changes in the concentrations of thyrotropin and reverse T3 in serum. After starting treatment with fenclofenac serum concentrations of thyrotrophin fell to a nadir after 2-4 days at which time the mean concentration was 34% (P less than 0.01) of the pretreatment value, whilst reverse T3 values increased to a maximum of 136% (P less than 0.001) of the pretreatment values over 1-2 days. There was subsequently an increase of the thyrotrophin and a reduction in reverse T3 concentrations to normal by 2 weeks of pretreatment. Transient pituitary suppression was also suggested by the response to to thryotrophin-releasing hormone (TRH): 7 days after starting fenclofenac the mean thyrotrophin response was 62% (P less than 9.001) of the pretreatment value. After 4 weeks of fenclofenac the response of TRH had returned to normal. After discontinuing fenclofenac there was a transient increase in the mean concentration of thyrotrophin in serum, to 129% of the pretreatment value (P less than 0.001), with a subsequent return to normal. Four weeks after discontinuing fenclofenac the serum concentrations of thyroid hormones and thyrotrophin were normal.

Topics: Adult; Humans; Male; Phenylacetates; Thyroid Gland; Thyrotropin; Thyrotropin-Releasing Hormone; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse