Effect of loop diuretics and nonsteroidal antiinflammatory drugs on thyrotropin release by rat anterior pituitary cells in vitro.

The close inverse-feedback relationship between serum free thyroxine (T4) and thyrotropin (TSH) is altered in some patients receiving therapeutic doses of drugs such as furosemide, fenclofenac, and diphenylhydantoin. We therefore examined the effect of nonsteroidal antiinflammatory drugs (NSAID), diuretics, and diphenylhydantoin on TSH release in rat anterior pituitary cells in primary culture. TSH content of the culture medium was measured at 22 hours at 37 degrees C either with or without thyrotropin-releasing hormone ([TRH] 10 nmol/L) in medium containing 0.5% bovine serum albumin. The mean basal TSH release by pituitary cells was 6.2 +/- 1.2 ng/mL (n = 10) and was not influenced by unlabeled triiodothyronine ([T3] 100 nmol/L) or any of the drugs tested at < or = 400 mumol/L, except ethyacrynic acid. TRH 10 nmol/L increased mean TSH release by 346% +/- 95% (n = 10). T3 1 and 100 nmol/L inhibited TRH-stimulated TSH release by 24% and 31%, respectively (P < .001), whereas TRH-stimulated TSH release was inhibited by 100 mumol/L meclofenamic acid (29%), fenclofenac (28%), furosemide (24%), and diphenylhydantoin (48%) (P < .001 v TRH alone). Meclofenamic acid and furosemide (100 mumol/L) did not significantly alter the inhibitory effect of T3 1 nmol/L on TRH-stimulated TSH release. These in vitro studies suggest that meclofenamic acid, fenclofenac, furosemide, and diphenylhydantoin could influence TSH release by attenuating the TSH response to TRH. This effect may influence T4-TSH relationships when these agents are used in vivo.