Cushing's Syndrome in Pregnancy—treatment With Metyrapone

Abstract

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.

THERAPY OF ENDOCRINE DISEASE: Steroidogenesis enzyme inhibitors in Cushing's syndrome

“…Surgery is the preferred option, when it is safe during pregnancy or following delivery, while medical therapy is used to control hypercortisolism until surgery can be performed. Untreated maternal hypercortisolaemia has significant implications on maternal and foetal health and there is evidence that treatment improves the rate of live births (122,126). There are no approved medical treatments for use in pregnancy; however, there are several reports of the use of metyrapone or KTZ in this difficult clinical scenario.…”

“…There are concerns that metyrapone may affect the biosynthesis of steroids in the placenta; however, several case reports describe its use in the first (127,128,129), second (123,127,129,130,131,132) and third trimesters (123,126,129,130,133,134). Metyrapone is generally well tolerated and doses up to 3 g have been used to control hypercortisolaemia (123,130).…”

Cushing’s Syndrome in Pregnancy Secondary to Adrenal Adenoma

“…If the aetiology is adrenal adenoma, the therapeutic alternatives are unilateral adrenalectomy during pregnancy [10][11][12][13][14][15][16][17][18][19] Gormley et al [20] in 1982. Metyrapone, an inhibitor of 11ß-hydroxylase, leads to a reduction of cortisol levels.…”

“…Thirty-four patients with 37 pregnancies in the period between 1961 and 1996, including our case, were identified. Unilateral adrenalectomy was performed during pregnancy in 12 of these patients [10][11][12][13][14][15][16][17][18][19] (group I), non-surgical or conservative management was adopted in the remaining 25 pregnancies [15,20,[21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36] (group II) and all patients in group II received post partum adrenalectomy. Tables 1 and 2 compare the perinatal and maternal outcomes in group I and group II patients, respectively.…”

Pregnancy and pituitary disorders

“…Ketoconazole has been used in CS during pregnancy without untoward effects (28, 81,[96][97][98]. Although metyrapone may cause adrenal insufficiency in the neonate, it has been used during pregnancy but not always with symptom control (99)(100)(101)(102)(103)(104). Lindsay et al reported 20 women receiving medical therapy (11 patients metyrapone; 3, ketoconazole; 3, cyproheptadine; 1, aminoglutethimide; and 2, mitotane) for CS usually starting in the second or third trimester (28).…”