Cushing’s syndrome during pregnancy secondary to adrenal adenoma: Metyrapone treatment and laparoscopic adrenalectomy

Abstract

Cushing's syndrome during pregnancy is a rare and difficult to diagnose disorder. We describe the case of a 30-yr-old woman presenting with symptoms and signs of mild hypercortisolism, in which ACTH-independent Cushing's syndrome was diagnosed. Urinary cortisol excretion was elevated and circadian rhythm of cortisol was absent. ACTH levels were low. In addition, plasma cortisol failed to suppress after a high dexamethasone dose. An abdominal computed tomography scan confirmed a left adrenal mass. While diagnosis work-up was still in progress, the patient became pregnant and wanted to carry her pregnancy to full-term. Hypercortisolism was successfully controlled with metyrapone, which was started at 8 weeks of gestation. At 16 weeks of gestation, a laparoscopic left adrenalectomy was performed. Pathologic examination of the gland showed a benign adrenocortical adenoma. The patient developed secondary adrenal insufficiency and was discharged on 20 mg hydrocortisone daily dose. At 30 weeks of gestation, the patient had a pre-term rupture of membranes and underwent spontaneous vaginal delivery. The newborn was a normal virilized male who weighed 1280 g. No apparent metyrapone-induced teratogenic effects were observed and there was no clinical or biochemical suppression of adrenocortical function. In conclusion, in adrenal Cushing's syndrome during pregnancy, medical treatment with metyrapone as soon as the diagnosis is made, in combination with laparoscopic surgery during the second trimester, are useful in preventing complications secondary to hypercortisolism and safe both for the mother and infant.

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

“…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).…”

“…Metyrapone is generally well tolerated and doses up to 3 g have been used to control hypercortisolaemia (123,130). It is not thought to be teratogenic and there are reports of administration in the 1st trimester during foetal organogenesis with no reports of congenital anomalies (128,129). A block-and-replace approach is usually used although dose titration has also been used (130).…”

MANAGEMENT OF ENDOCRINE DISEASE: Management of pregnant patients with Cushing's syndrome

“…Of these, treatment with steroidogenesis inhibitors, particularly with metyrapone, was the option used most often (26) ( Table 1). This drug was used in 69% of cases and showed good control of hypercortisolism in most of them, with one report of adrenal insufficiency (17,27). The most worrisome side effects of metyrapone are an increase in precursors such as 11-deoxycorticosterone, worsened hypertension, and an increase in preeclampsia frequency.…”

Adrenal Disease and Pregnancy

“…Metyrapone has side effects including hypertension and preeclampsia. (Blanco et al, 2006). Ketoconazol therapy is associated with intrauterine growth retardation, but no malformation or neonatal adrenal insufficienc (Berwaerts et al, 1999).…”