Recurrent ACTH-independent cushing's syndrome in multiple pregnancies

A 27-year-old woman presented with Cushing's syndrome. Typical clinical symptoms and signs developed at the beginning of each pregnancy. The latest three pregnancies all ended with natural abortion at about three months. It was the fourth time that she was pregnant. By week 18 of gestation, plasma cortisol diurnal rhythm was absent, basal urinary free cortisol was 1650 mu g/24 h and ACTH levels were suppressed. The diagnosis of ACTH-independent Cushing's syndrome was established. Cushing's syndrome in the patient resolved within four weeks of abortion. But signs and symptoms of hypercortisolism recurred in the fifth pregnancy and resolved soon after abortion during the follow-up. 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.