Recurrent ACTH-independent Cushing's syndrome in multiple pregnancies and its treatment with metyrapone

A 17-year-old primigravid woman presented with Cushing's syndrome. Typical clinical symptoms and signs developed at the beginning of pregnancy. By wee k 17 of gestation, plasma cortisol diurnal rhythm was absent and there was a paradoxical increase in plasma cortisol after a 1-mg dexamethasone overni ght suppression test. Basal urinary free cortisol was 10 times above the up per limit (in pregnancy) and ACTH levels were suppressed. The diagnosis of ACTH - independent Cushing's syndrome was established. MRI scans revealed n ormal adrenal and pituitary glands. To control hypercortisolism, the patien t was treated with metyrapone. At 34 weeks of gestation, the patient develo ped preeclampsia and underwent caesarean section. A female infant weighing 1070 g was delivered. No apparent metyrapone-induced teratogenic effects we re observed. Cushing's syndrome in the patient resolved within three weeks of delivery. No corticosteroid replacement therapy either for child or moth er was needed. Eight months after delivery the patient became pregnant agai n and rapidly developed Cushing's syndrome with typical clinical symptoms a nd signs and laboratory results (urinary free cortisol 6464 nmol/24 h). Thi s second pregnancy was unwanted and terminated by artificial abortion that was followed by rapid resolution of hypercortisolism. A third pregnancy, 12 months after delivery was also accompanied by the rapid development of hyp ercortisolism which recovered after artificial termination. The mechanisms by which pregnancy-induced Cushing's syndrome occurred in th is patient are unclear. Aberrant responsiveness or hyperresponsiveness of a drenocortical cells to a non-ACTH and non-CRH substance produced in excess in pregnancy should be considered. Metyrapone suppression of hypercortisolism currently represents the best tr eatment for these rare cases.