Changes in thyroid function tests during short-term salsalate use

Abstract

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.