Pregnancy-induced Cushing syndrome mediated by overexpressing LHCGR with bilateral micronodular adrenocortical...

Pregnancy-induced Cushing syndrome (PICS), in which the onset of cortisol excess occurs during pregnancy with spontaneous remission postpartum, is a rare entity with serious maternal and fetal consequences. We describe the case of a 31-year-old woman who presented with pre-eclampsia at 24 weeks gestational age and florid features of hypercortisolism. Investigations revealed gross elevation of serum cortisol with absent diurnal rhythm, elevated 24-hour urinary free cortisol and suppressed adrenocorticotropic hormone. She required an emergency cesarean section for intrauterine fetal demise, attributed to placental abruption. Postpartum, she had normalization of serum cortisol and 24-hour urinary free cortisol, and late-night salivary cortisol was normal. Computed tomography scan showed bilateral adrenal micronodules. Additional investigations showed nonsuppressed cortisol after 1 and 8 mg dexamethasone. Moreover, serum cortisol increased 129% after stimulation with human chorionic gonadotropin. She underwent left adrenalectomy, with pathology indicating micronodular adrenocortical disease. Reverse transcription-polymerase chain reaction analysis showed an increased expression of LHCGR and reduced expressions of MC2R, PGR, and ERβ in her adrenal tissues, findings of probable relevance to her PICS. The combination of functional and expression testing provides convincing evidence for the rare luteinizing hormone/human chorionic gonadotropin-driven pathophysiology of this syndrome.