ALTERATIONS IN THE PITUITARY-THYROID AND PITUITARY-ADRENAL AXES - CONSEQUENCES OF LONG-TERM MIFEPRISTONE TREATMENT

The effects of short-term administration of the antiprogestin and anti glucocorticoid, mifepristone, have been well characterized. However, l ittle is known about the effects of prolonged administration of mifepr istone, We analyzed hormonal parameters in four female and three male patients with unresectable meningioma who were treated with mifepristo ne (200 mg/d) for 20 to 40 months. Serum samples were collected at mon thly intervals approximately 24 hours following mifepristone ingestion . Serum thyrotropin (TSH), thyroxine (T4), free T-4 (fT(4)), 3,5,3-tri iodothyronine (T-3), prolactin, and cortisol were analyzed by fluoroim munoassay, and androstenedione by radioimmunoassay (RIA), Levels of mi fepristone and its three most proximal metabolites were measured by hi gh-performance liquid chromatography, TSH values increased significant ly (P < .005, one-way ANOVA), with the most pronounced increase eviden t during the first 3 months of mifepristone treatment. Despite these c hanges, concentrations of TSH remained within the normal range through out the treatment period, There were no significant changes in serum T -4, fT(4), T-3 or prolactin; however, a transient decrease in serum T- 4 was noted at 2 to 3 months. Cortisol and androstenedione values incr eased significantly and in parallel (P < .05), suggesting an adrenal o rigin also for androstenedione. As during short-term administration, l evels of mifepristone and its metabolites remained stable in the micro molar range. Individual levels of mifepristone were significantly corr elated with those of TSH and cortisol. This suggests that the alterati ons in the pituitary-thyroid and -adrenal axes occurred in a concentra tion-dependent manner. It is concluded that long-term mifepristone tre atment results in resetting of the pituitary-thyroid balance, As in th e case with cortisol and androstenedione, it is likely that the altera tions in serum TSH are due to the antiglucocorticoid properties of mif epristone. The clinical significance of these biochemical alterations in thyroid homeostasis remains to be determined. However, monitoring t hyroid function during long-term mifepristone treatment appears to be warranted. Copyright (C) 1997 by W.B. Saunders Company.