SAT-221 False-Positive Urinary Free Cortisol with Oral Contraceptive Use

Introduction It is well-established that estrogen-containing oral contraceptives can raise serum cortisol levels and yield false-positive results on dexamethasone suppression testing, however it is less known that they can raise urinary free cortisol levels by an unknown mechanism. Case presentation A 47-year old woman taking microgestin 1/20 oral contraceptive (OC) was found incidentally to have osteopenia on chest X-ray. Subsequent DEXA scan demonstrated osteoporosis. During the work-up to determine the underlying etiology of her osteoporosis, she underwent a 24-hour urinary free cortisol, which was 207 ug/24 hours (0-50 ug/24 hours). Serum cortisol was 40.1 (6.2-19.4 ug/dL) and overnight 1mg dexamethasone suppression test yielded a cortisol of 2.7. After one week off her OC, serum cortisol was 24.6. After five weeks off her OC, urinary free cortisol was 19 and 1mg dexamethasone suppression test yielded a cortisol of 0.8. On exam, the patient did not have any cushingoid features. MRI of the brain showed a small hypoenhancing lesion, which was determined by neurosurgery to be insignificant. Ultimately, the cause of her osteoporosis was thought to be likely secondary to vitamin D deficiency and calcium malabsorption due to celiac disease. Discussion The biochemical diagnosis of hypercortisolism during treatment with estrogen-containing OCs remains a challenge. Prior studies have demonstrated that serum cortisol levels are typically elevated during OC use and that 1mg dexamethasone suppression testing may yield false-positive results in more than 50% of cases. This is thought to be due to an increase in the major binding protein for cortisol, corticosteroid-binding globulin. Although it is commonly thought that OCs do not affect urinary free cortisol measurements, a recent study showed that more than one-third of women taking OCs had a mild elevation of urinary free cortisol. There are a few hypotheses for the mechanism by which OC use leads to elevated urinary free cortisol, including direct effect on steroidogenesis in the adrenal glands. Our patient had a significantly elevated 24-hour urinary free cortisol and an equivocal 1mg dexamethasone suppression test while on OCs that normalized with OC discontinuation. Further, serum cortisol decreased with OC discontinuation. Conclusion The 24-hour urinary free cortisol level may be altered by oral contraceptive use and is therefore not a valid tool to evaluate for hypercortisolism in women on OCs. References Nickelsen T, et al. (1989). The dexamethasone suppression test and long-term contraceptive treatment. Experimental and Clinical Endocrinology, 94, 275–280. Paschali M, et al. (2013). False positives on both dexamethasone testing and urinary free cortisol in women on oral contraception. Clin Endocrinol, 79, 443-445. Trainer PJ. (2002). Corticosteroids and pregnancy. Seminars in Reproductive Medicine, 20, 375–280.