Mifepristone Prior to Surgery for the Management of ACTH Dependent Cushing's Syndrome of Unknown Etiology

Presentation Number: MON 409
Date of Presentation: April 3rd, 2017

Sapna Raghunathan*1, Afaf Albalawi1, Yiannis Apergis1 and Jonathan Fillmore2
1Griffin Hospital, Derby, CT, 2Endocrine Specialists, Trumbull, CT

Abstract

Introduction:

ACTH dependent Cushing’s Syndrome of unknown etiology, presents as a management challenge to the endocrinologist. Mifepristone, a glucocorticoid and progesterone antagonist, is now approved for the management of hyperglycemia in Cushing’s Syndrome recurrent post-surgery and in non-surgical candidates.

Case Description:

A 53 year old Caucasian woman presented with poorly controlled DM type 2 for 12 years and hirsutism for 1 year. Diabetes was previously managed with insulin and Albiglutide. She continued to require increasing doses of insulin for rising HbA1c. Physical examination initially revealed facial puffiness, increased facial hair and obesity. The patient stood 5' tall, weighed 218 pounds with a BMI of 42.58; BP was 160/80. Laboratory testing showed hypokalemia (2.9 mmol/L) and diabetes (HbA1c of 9.5). She complained of polyuria and polydipsia along with increasing fatigue, which were thought to be secondary to poorly controlled diabetes, initially. Considering these findings, tests to detect the presence of an ACTH-secreting tumor were initiated. 24-hour urinary cortisol (895 mcg/24 hr, N: 10-55 mcg/24 hr) and ACTH (72 pg/mL, N: 0.6-9 pg/mL) levels were elevated. FSH and LH levels were low-normal and prolactin was 24.2 ng/mL (N: 5-20 ng/mL). A high dose (8 mg) dexamethasone suppression test revealed highly elevated ACTH and cortisol levels. Following this, imaging was pursued to localize the source of ACTH secretion. Abdominal CT for adrenal hyperplasia, Chest CT for ectopic sources and Pituitary MRI for Cushing's disease and Octreotide scanning for ectopic ACTH production were within normal limits.The patient’s insulin requirement continued to rise during the course of the investigation. As the patient was resistant to further invasive investigations, the decision was made to start Mifepristone 300 mg QD. Further labs showed the presence of persistent hypokalemia and the patient was started on potassium supplementation. After 9 months of treatment with Mifepristone (dosage increased gradually from 300mg QD to 300 mg TID), the patient's condition improved significantly with a 33 pound weight loss, decrease in BMI to 37.37, HbA1C of 7.2, BP of 128/82, decreased facial puffiness and pedal edema.

Conclusion:

This case illustrates management in case of ACTH dependent Cushing’s Syndrome of unknown etiology. The current use of Mifepristone is limited to cases where cortisol levels continue to be elevated post surgical intervention and in patients who are non-surgical candidates. Investigations in our patient did not reveal a source of cortisol elevation, for surgical intervention. Therefore, medical management, such as Mifepristone can be initiated, prior to invasive procedures or surgery. This brings about both clinical and medical improvement in patients, as seen with this case.

 

Nothing to Disclose: SR, AA, YA, JF