SAT-220 Oral Contraceptives and Their Effect on the Evaluation of Cushing's Syndrome: A Case Report

Background In the evaluation of Cushing’s syndrome (CS), oral contraceptives may lead to false-positive results by raising the serum levels of cortisol-binding globulin (CBG). Clinical Case An 18-year old Chinese lady presented with weight gain, irregular menses and hirsutism. History was unremarkable for hypothyroidism, hyperprolactinemia, eating disorders, and exogenous steroid use. On examination, she was overweight (body mass index (BMI) 26.9 kg/m(2)) with rounded facies, hirsutism and dorsal cervical fat pad. Initial biochemical tests showed high cortisol and ACTH levels: ACTH 66.6 pmol/L (RI 0-10.2 pmol/L) and random cortisol 958 nmol/L (RI: 240-618 nmol/L). She was referred to our department for evaluation of possible Cushing’s syndrome. Further history revealed that the patient was on a combined estrogen-progestin oral contraceptive pill (OCP). Confirmatory tests after cessation of the OCP for 6 weeks revealed normal 24-hr urinary cortisol levels (231 and 255 nmol/day, RI: 59-413 nmol/day) and a normal 1 mg dexamethasone suppression test (44 nmol/L after administration of 1 mg dexamethasone overnight, RI <50nmol/L). A progesterone challenge test induced withdrawal bleeding, consistent with an estrogen-sufficient anovulatory state such as that seen in Polycystic Ovarian Syndrome. Regular menstrual cycles returned after deliberate weight loss to a BMI of 26.0 kg/m(2)). Discussion and Conclusion OCPs increase total cortisol concentrations by increasing circulating CBG without affecting the unbound fraction (1). Women on OCPs may hence display elevated serum total cortisol concentrations without increased cortisol activity. These elevations are dependent on estrogen dose, and usually not seen with progestogen-only or low-dose estrogen (0.05 mg mestranol or less) preparations (2). Other drugs interfering with cortisol clearance, such as CYP3A4 inhibitors and inducers, may also influence test results (3). Current guidelines suggest that estrogen-containing drugs should be discontinued for at least 6 weeks so as to prevent false-positive results, which can potentially lead to unnecessary procedures or surgery. A thorough drug history is therefore crucial in the evaluation of CS. References (1) Qureshi AC, Bahri A, Breen LA, et al. The influence of the route of oestrogen administration on serum levels of cortisol-binding globulin and total cortisol. Clin Endocrinol (Oxf). 2007; 66: 632-5 (2) C. W. Burke. The effect of oral contraceptives on cortisol metabolism. J Clin Pathol Suppl (Assoc Clin Pathol). 1969; 3: 11-18. (3) M. Vastbinder, M. Kuindersma et al. The influence of oral contraceptives on overnight 1 mg dexamethasone suppression test. Neth J Med. 2016 May;74(4): 158-61.