Cushing's syndrome during pregnancy: personal experience and review of the literature.

Cushing's syndrome (CS) occurs rarely during pregnancy. We investigated and treated four patients with pituitary-dependent Cushing's syndrome during pregnancy over a 15-yr period at the National Institutes of Health. Except for preservation of menses before conception, our patients presented with typical clinical features, increased urinary free cortisol, and loss of diurnal variation of cortisol. The diagnosis was facilitated, without complications, by the use of CRH testing and inferior petrosal sinus sampling in three women. Transsphenoidal pituitary surgery achieved remission in three women, but there were two fetal/neonatal deaths. This experience and review of 136 previous reports suggest that: 1) urinary free cortisol in CS patients overlaps the normal pregnant range; 2) ACTH levels are not suppressed in adrenal causes of CS, which may be identified by the 8-mg dexamethasone test; 3) inferior petrosal sinus sampling and transsphenoidal pituitary surgery, the optimal diagnostic test and treatment for nonpregnant patients with pituitary-dependent Cushing's syndrome, can safely facilitate the management of pregnant patients; and 4) surgery may achieve remission during pregnancy, but the prognosis for the fetus remains guarded. It is likely that earlier recognition and treatment would improve outcome. There is a need for development of criteria for interpretation of diagnostic tests and increased consideration of CS in pregnancy.