Abstract
Introduction: Mifepristone (MFP) aka RU-486/Korlym is a synthetic steroid analog originally developed in 1980 as an abortifacient that is now used in the management of Cushing’s syndrome (CS). It is both a progesterone (PG) and glucocorticoid (GC) receptor blocker. CS is often associated with reproductive functional anomalies including hypogonadism, menstrual irregularities and infertility. Due to its mode of action, measurement of serum PG and/or cortisol in patients on MFP are inaccurate indices of systemic PG and/or GC deficiency or excess. However, the potential impact of MFP use on other serum steroid assays has not been widely studied. We report the case of a 55 yr old man on treatment with MFP for adrenal CS found to have striking artefactual changes in serum androgen and estrogen levels. Case Summary: A 55 yr old African American man was referred with poorly controlled type 2 diabetes, hypertension, hyperlipidemia, obesity and untreated hypogonadism. He had a 3.2cm left adrenal incidentaloma associated with adrenal CS and he chose medical management rather than surgery. Upon starting MFP at 300mg QD serum total estrogen (by radio-immunoassay; RIA) and estradiol (by chemiluminescence immunoassay; CIA) were markedly elevated while serum total, free, bioavailable testosterone and dihydrotestosterone were all markedly reduced. His HBA1c, weight and energy levels improved on MFP despite these findings. The serum steroid levels normalized to pre-treatment levels after stopping MFP for ~ 4weeks but the changes recurred after restarting therapy. After MFP dose escalation to 300mg BID the serum steroid levels normalized after stopping MFP for ~ 6 weeks. The artefactual low testosterone levels also occured with measurement by equilibrium dialysis but “normal accurate” results were obtained when measured by liquid chromatography-Tandem mass spectrometry (LC-TMS). He remains on MFP 300mg BID without need for androgen repletion. Discussion: With increased use of MFP for CS, indices for tracking its clinical and biochemical effects assume great importance. There are few reports of the possible effects of MFP on estrogen and testosterone serum assays despite its touted low cross reactivity with sex steroids. Our case suggests that the significance, extent and prevalence of artefactual changes on serum sex steroid assays may be underestimated and under- appreciated. Conclusions: Our case of wide disparities in serum estrogen and androgen measures in a patient on MFP indicates that caution needs to be exercised in the interpretation of such results in patients on current MFP therapy. Our clinical observations suggest depending on the dose that a wash out period of 4–6 weeks is required to ensure accurate measures. Studies to ascertain the prevalence of this artefactual effect are needed and it appears testosterone measurement by LC-TMS obviates the testosterone assay artefact.