A 17-year-old primigravid woman presented with
Cushing's syndrome. Typical clinical symptoms and signs developed at the beginning of pregnancy. By week 17 of gestation, plasma
cortisol diurnal rhythm was absent and there was a paradoxical increase in plasma
cortisol after a 1-mg
dexamethasone overnight suppression test. Basal urinary free
cortisol was 10 times above the upper limit (in pregnancy) and
ACTH levels were suppressed. The diagnosis of
ACTH--independent
Cushing's syndrome was established. MRI scans revealed normal adrenal and pituitary glands. To control
hypercortisolism, the patient was treated with
metyrapone. At 34 weeks of gestation, the patient developed
preeclampsia and underwent
caesarean section. A female infant weighing 1070 g was delivered. No apparent
metyrapone-induced teratogenic effects were observed.
Cushing's syndrome in the patient resolved within three weeks of delivery. No
corticosteroid replacement
therapy either for child or mother was needed. Eight months after delivery the patient became pregnant again and rapidly developed
Cushing's syndrome with typical clinical symptoms and signs and laboratory results (urinary free
cortisol 6464 nmol/24 h). This 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
hypercortisolism which recovered after artificial termination. The mechanisms by which pregnancy-induced
Cushing's syndrome occurred in this patient are unclear. Aberrant responsiveness or hyperresponsiveness of adrenocortical 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 treatment for these rare cases.