Cushing's syndrome in pregnancy--treatment with metyrapone

A 23-year-old female presented with severe Cushing's syndrome in the 23rd week of pregnancy. Investigations showed plasma cortisol 770 nmol/l (08.00 h) and 850 nmol/l (23.00 h); plasma ACTH was 10 ng/l (08.00 h) and 27 ng/l (23.00 h); urinary free cortisol excretion was 2460 nmol/24 h. Dexamethasone 2 mg 6-hourly for 48 h suppressed the 08.00 h plasma cortisol only to 680 nmol/l. Abdominal C.T. scan showed a right adrenal adenoma. The patient was treated with metyrapone and a good clinical improvement ensued. Plasma cortisol was reduced to 300-500 nmol/l. Depsite ultrasonographic evidence of normal fetal growth, urinary oestriol excretion was markedly deficient. Prior to the spontaneous onset of labour, there was a marked rise in plasma cortisol despite continuous metyrapone treatment. A normal female infant was born at 37 weeks' gestation. The maternal adrenal adenoma was subsequently removed. The deficiency of oestriol synthesis during the pregnancy may be explained by metyrapone-induced inhibition of C19-hydroxylation.