triiodothyronine--reverse and salicylsalicylic-acid

Although long-term administration of salsalate depresses blood levels of both total thyroxine (T4) and total triiodothyronine (T3) and at least transiently decreases serum thyrotropin (TSH), changes in thyroid function tests have not been fully characterized during its short-term use. It is also unclear if the observed changes are solely the result of decreased hormone binding to carrier proteins or if reduced hepatic 5'-monodeiodinase activity is important. Blood was sampled at baseline (day 0) and after 24 hours (day 1) and 72 hours (day 3) in eight subjects taking a therapeutic dose of salsalate 1,500 mg twice daily. Total T4 decreased from 90.1+/-7.7 nmol/L (mean+/-SD) on day 0 to 82.9+/-8.6 nmol/L on day 1 (P=.1 v baseline) and 68.6+/-8.7 nmol/L on day 3 (P=.0001). Total T3 decreased from 1.76+/-0.20 nmol/L to 1.61+/-0.16 nmol/L on day 1 (P<.05) and 1.31+/-0.27 nmol/L on day 3 (P=.002). The T4/T3 ratio was 51.7+/-7.7 at baseline and remained unchanged after 3 days. Levels of reverse T3 (rT3) were reduced from 0.24+/-0.05 nmol/L to 0.18+/-0.02 nmol/L on day 3 (P<.05). While the free T4 index (FTI) declined in parallel with total T4, the free T4 level by direct equilibrium dialysis (FTD) was unchanged after 3 days. Serum TSH decreased from 1.47+/-0.47 mU/L to 0.91+/-0.27 mU/L after 1 day (P<.05) and remained suppressed after 3 days (0.95+/-0.49 mU/L, P<.05). In conclusion, (1) therapeutic doses of salsalate significantly decrease serum concentrations of total T4, total T3, and rT3 to about 75% of baseline levels after 3 days without altering the T4/T3 ratio; (2) although the FTD does not change, serum TSH concentrations remain suppressed; and (3) the proportionate decrease in total thyroid hormone levels suggests that inhibition of hormone binding to serum proteins is more important in producing these changes than reduced hepatic 5'-monodeiodinase activity.

Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Blood Proteins; Female; Humans; Iodide Peroxidase; Liver; Male; Middle Aged; Salicylates; Thyroid Function Tests; Thyroid Gland; Thyrotropin; Thyroxine; Triiodothyronine, Reverse

This study examined salsalate ingestion as a model of the sequelae of acute inhibition of thyroid hormone binding to serum protein. One dose of salsalate (60-65 mg/kg) was administered to healthy volunteers. Serum salsalate concentrations peaked at 2 h (82 micrograms/mL), then declined at 8 h to 1.2 micrograms/mL. Serum total T4 (TT4) and total T3 (TT3) concentrations declined for 4 h, then recovered by 96 h, while T4 binding protein concentrations remained unchanged. TT3 was reduced to a greater extent than TT4 between 2 h and 72 h, and serum total reverse(r)T3 (TrT3) was transiently increased at 8 h. TSH concentrations fell while TT4 and TT3 fell, then recovered while TT4, TT3, and free T3, but not free T4, were still reduced. Subsequently, TSH overshot basal levels and continued to rise after 96 h while TT4, TT3, free T4, free T3, and TrT3 were all at basal levels. We postulate that an acute release of T4 and T3 from circulating transport proteins, induced by an inhibitor of binding, can result in large and rapid redistribution of T4 and T3 into tissue compartments associated with transiently reduced peripheral tissue 5'-monodeiodination and deranged TSH regulation.

Topics: Adult; Blood Proteins; Euthyroid Sick Syndromes; Female; Humans; Kinetics; Male; Models, Biological; Protein Binding; Salicylates; Thyrotropin; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

There are only three prior reports of abnormal thyroid function tests in patients who have received salsalate, the salicylate ester of salicylic acid. The authors report an elderly clinically euthyroid man who had thyroid function tests suggestive of central hypothyroidism while taking salsalate but whose thyroid tests returned to normal after the drug was discontinued. They also studied thyroid function tests, including free thyroxine (FT4) and reverse (T3), in two normal volunteers who took salsalate 750 mg twice daily for 1 week. In the normal subjects, total T4 and FT4 began to fall within 24 hours after the first dose of salsalate, and remained suppressed for at least 24 hours after the drug was discontinued. This rapidity of effect by salsalate is previously undescribed. There was also a fall in FT4, probably due to the use of diluted serum in the equilibrium dialysis FT4 assay. Because FT4 measurement using diluted serum or equilibrium dialysis may cause falsely low FT4 measurements, the authors believe ultrafiltration may be the only reliable method of measuring FT4 in these patients.

Topics: Aged; Aged, 80 and over; Humans; Male; Salicylates; Thyroid Function Tests; Thyroid Gland; Thyroxine; Triiodothyronine, Reverse