ACTH-Independent Cushing’s Syndrome Diagnosed during Pregnancy- Successful Medical Management with Metyrapone

Presentation Number: MON 417
Date of Presentation: April 3rd, 2017

Alescia Linda Azzola*1, Genevieve Eastabrook2, Amanda J Brahm2, Doreen Matsui2, Daryl Gray2 and Stan Van Uum3
1Western University, London, ON, Canada, 2Western University, London, ON, 3Division of Endocrinology and Metabolism, Department of Medicine, Western University, London, ON, Canada


Background: Cushing syndrome is rarely diagnosed in pregnancy and limited literature is available to guide therapy. However, if left untreated, it is associated with significant maternal and fetal complications including preterm labor.

Clinical Case: 24 year old female at 25 weeks gestation, was assessed for concerns of excess cortisol including weight gain (BMI 44), hirsutism, chronic hypertension and widespread violaceous striations. 6 years prior to presentation, her first pregnancy was complicated by hypertension and an eclamptic seizure requiring emergency C-section at 33 weeks gestation. Cushing features were noted but not addressed.

Elevated 24hour urine cortisol at 1141 nmol/day ( normal < 275) and loss of diurnal variation with salivary cortisol levels (8am and 8pm levels of 44.5 and 61.1 nmol/L, respectively) confirmed Cushing syndrome, which was ACTH-independent (ACTH< 0.3 pmol/L). Abdominal MRI revealed a 3.7 cm left adrenal adenoma.

Management was discussed with a multi-disciplinary team. Although the literature would favour early surgical adrenalectomy, this patient was considered a high risk candidate for surgery due to morbid obesity and gravid uterus, approaching third trimester. She was treated with metyrapone.

Her overall condition including gestational diabetes and hypertension improved during successful control of hypercortisolism (based on saliva cortisol) with metyrapone therapy. Elective Caesarean section was performed at 35 weeks, this timing chosen to balance the risk of iatrogenic prematurity with that of further delaying definitive management of the patient’s Cushing syndrome. A healthy baby boy was delivered, who is being followed by paediatric endocrinology.Post-partum, transition to ketoconazole therapy was well tolerated with laparoscopic left adrenalectomy planned for the near future.

Discussion: This case report illustrates the additional complexity of Cushing syndrome management when detected in late pregnancy. In a high risk surgical patient, literature on medical therapy is also sparse. Therefore, multiple key endocrine points required exploration including safety of medical treatment in pregnancy, availability and effectiveness of metyrapone in pregnancy as well as unknown fetal risk. We discuss the establishment of a monitoring and titration protocol for this medication to avoid potentially detrimental effect to mother and fetus, and considerations for planning a caesarean section.


Nothing to Disclose: ALA, GE, AJB, DM, DG, SV