(CSEMP018) PREGNANCY INDUCED CUSHING'S SYNDROME

Abstract:

Background:
Pregnancy-induced Cushing’s syndrome (CS) represents a rare but emerging entity. The onset of cortisol excess occurs during pregnancy often followed by spontaneous remission postpartum. We describe a patient with pregnancy-induced CS.

Clinical

Case:
A 31-year-old nulliparous woman required admission at 24 weeks gestational age for early-onset pre-eclampsia. She displayed clinical features of CS (acne, hirsutism, dorsocervical adiposity, large striae, face roundness, hypertension, and bruising). Investigations showed elevated 24-hour urine free cortisol (UFC) and serum cortisol, with low adrenocorticotropic hormone (ACTH). Additionally, serum testosterone was increased (Table 1). Pelvic ultrasound revealed bilateral ovarian enlargement with prominent follicles consistent with ovarian hyperstimulation. Unfortunately, she required emergency C-section for intrauterine fetal demise, attributed to placental abruption. Postpartum, she had rapid improvement in biochemistry: serum cortisol, 24-hour UFC, late night salivary cortisol (LNSC), and testosterone normalized within 1 month (Table 1); however 1 mg and 8 mg dexamethasone suppression tests were abnormal with absent diurnal variation in cortisol. Pelvic imaging showed resolution in ovarian enlargement after 3.5 months. Although initial postpartum CT abdomen reported normal adrenals, re-interpretation suggested bilateral adrenal micronodules.

Over the next 15 months, she had cyclic symptoms of feeling hot, worsening acne-like lesions, striae, and edema associated with intermittent elevation of LNSC. During these episodes, ACTH and DHEAS were low. Moreover, there was incomplete cortisol suppression after 2 days of low-dose and high-dose dexamethasone. Adjunctive clues for possible cortisol excess demonstrated normal 24-hour UFC with absence of hypertension, hyperglycemia, and hypokalemia. Dynamic testing did not reveal paradoxical increase in 24-hour UFC with prolonged dexamethasone (Liddle’s test) on two occasions and genetic testing for endocrine neoplasia was negative. ACTH 250 mcg stimulation completed one year postpartum revealed 160% and 64% maximal increase in serum cortisol and testosterone, respectively. Stimulation with human chorionic gonadotropin (hCG) 6,500 units showed cortisol and testosterone elevations of 129% (24 hours) and 155% (96 hours), respectively, post administration (Table 2). Interestingly, response to GnRH 100 mcg stimulation was negative.

Currently, the patient plans to pursue pregnancy. She is scheduled for a unilateral adrenalectomy for diagnostic purposes and will receive metyrapone intrapartum.

Discussion:
Hypotheses of pregnancy-induced CS implicate aberrant receptor expression on the adrenal cortex. Such receptors include luteinizing hormone (LH)/hCG, melanocortin-2, or estradiol. In our case, dynamic testing suggests β-hCG mediated stimulation of LH/hCG-receptors. Although rare, pregnancy-induced CS requires awareness given adverse fetal outcomes. Targeted dynamic testing postpartum may help elucidate further mechanisms and identify therapeutic targets.