Changes in thyroid function tests during short-term salsalate use

Although long-term administration of salsalate depresses blood levels of both total thyroxine (T-4) and total triiodothyronine (T-3) 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 T-4 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 T-3 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 T-4/T-3 ratio was 51.7 +/-: 7.7 at baseline and remained unchanged after 3 days. Levels of reverse T-3 (rT(3)) were reduced from 0.24 +/- 0.05 nmol/L to 0.18 +/- 0.02 nmol/L on day 3 (P < .05). While the free T-4 index (FTI) declined in parallel with total T-4, the free T-4 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 T-4, total T-3, and rT(3) to about 75% of baseline levels after 3 days without altering the T-4/T-3 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. Copyright (C) 1999 by W.B. Saunders Company.