Cushing's disease in pregnancy is difficult to diagnose and manage. Pregnancy is a state of physiological hypercortisolism, making reference ranges for cortisol levels and screening tests difficult to establish. There are significant maternal, fetal and obstetric outcomes associated with Cushing's in pregnancy.
We present a case of a 31 year old female (CM) who develops relapsed Cushing's disease in early pregnancy. She had a history of Cushing's disease at age 20 with transphenoidal sinus surgery. Histopathology demonstrated ACTH staining pituitary adenoma.
CM developed clinical features of relapse at age 30 with weight gain and facial rounding and this was biochemically confirmed with elevated 24 hour urinary free cortisol (UFC) of 420mol/24hr (54-319) and raised midnight salivary cortisol of 17nmol/L (RR <4). Around the time of these results she fell pregnant. A non-contrast pituitary MRI demonstrated a 6x4mm microadenoma.
She developed gestational diabetes requiring insulin and hypertension at 6 weeks. Given the early onset of these conditions and the high risk of pre-eclampsia, stillbirth and premature delivery with Cushing's disease in pregnancy, surgical management was planned in second trimester. Petrosal sinus sampling demonstrated a central to peripheral gradient and she underwent transphenoidal sinus surgery at 17 weeks . Histopathology demonstrated adenoma with positive ACTH staining and Ki67 of 6%, with evidence of tumour invasion into bone. Her insulin and antihypertensive requirements stabilised though postoperative cortisol levels remained high. Fetal growth measured in the 15th centile. CM had premature rupture of membranes at 35 weeks, delivering a healthy infant with uncomplicated delivery. 24 hour UFC have normalised post partum though definitive cure is unlikely. Planning of further pregnancies will represent a challenge.
This case outlines challenges associated with management of Cushing's in pregnancy in regards to interpreting reference values, balancing maternal and fetal outcomes and selecting treatment options.