Reversible suppression of hypothalamo-pituitary-adrenal axis in Addison's disease due to ethinyl oestradiol-induced increase in total cortisol.

Abstract

Summary: An oral contraceptive pill (OCP)-induced increase in total cortisol lead to reversible suppression of the hypothalamic-pituitary-adrenal (HPA) axis and insulin resistance (IR) in a patient with Addison's disease. We suggest that this might influence the choice of an OCP in such patients. A 20-year-old female was diagnosed with Addison's disease (cortisol: 44 nmol/L, adrenocorticotropic hormone (ACTH): >500 pg/mL) and started on hydrocortisone (HC). Few months later, an OCP (30 μg ethinyl oestradiol (EE) and 3 mg drospirenone) was added. Total cortisol was above the upper assay detection limit (UADL), while ACTH was inappropriately 'normal': cortisol 8:00 (pre-dose) 83 nmol/L, post-dose 10:00 >1757 nmol/L, ACTH 8:00 (pre-dose) 24.1 pg/mL and post-dose 10:00 3.8 pg/mL. Even 5 mg of oral HC induced an increase in cortisol above UADL. The glucagon stimulation test (GST) showed brisk growth hormone secretion. The corticotropin-releasing hormone (CRH) test showed partial hypothalamic suppression of CRH release: minimal ACTH 42.4 pg/mL and maximal ACTH 87.3 pg/mL, i.e. relatively low levels for all cortisol concentrations <69 nmol/L. Withdrawal of the OCP resulted in the return of high ACTH concentrations typical for patients with Addison's disease on HC replacement. There was also a marked improvement in insulin resistance (a fall in homeostasis model assessment - insulin resistance (HOMA-IR) from 3.64 to 1.69 and a marked decline in mean insulin concentrations during GST). EE administration resulted in a massive increase in total cortisol with suppression of the HPA axis and IR suggestive of relative hypercortisolaemia. This raises the question of whether EE should be avoided as a contraceptive agent in women with adrenal failure.

Learning points: An OCP containing 30 μg EE induced relative and reversible hypercortisolaemia in a patient with Addison's disease with evidence of suppression of ACTH secretion on dynamic pituitary function tests.We suggest that, in some patients with adrenal failure, EE administration may lead to unrecognised relative hypercortisolaemia and IR.There is literature evidence that, in patients with Addison's disease, EE may decrease cortisol clearance.These alterations are reversible upon EE withdrawal and may have implications for the choice of a contraceptive agent in women with Addison's disease.