Finding the Source of ACTH-Dependent Cushing’s Syndrome

Presentation Number: MON 410
Date of Presentation: April 3rd, 2017

John Schempf*1 and Nacide G Ercan-Fang2
1University of Minnesota, 2Minneapolis Veterans Affairs Health Care System


ACTH-dependent Cushing’s Syndrome (CS) is well established and causes include Cushing’s disease (CD) and the ectopic ACTH syndrome (EAS). CD is more common, accounting for 80-85% of cases. We present a case of ACTH-dependent CS where treatment and diagnosis was complicated by a patient deferring key testing.

Mr. R is a 52 year-old male who presented with decreased libido, depression, and lower back pain. His medical history at presentation included schizoaffective disorder, alcohol and tobacco use, hyperlipidemia, and vitamin D deficiency. Thoracic spine x-rays showed multi-stage compression fractures in the thoracic spine. DEXA scan revealed osteopenia with the T-scores of -2.1 at the lumbar spine, -1.2 at hip, and -1.8 at femoral neck.

At the initial endocrinology visit he exhibited classic features of CS. Initial testing was pertinent for: testosterone 67.4 ng/dL (241-827) and serum cortisol 22 mcg/dL (4.3-22.4). His low testosterone was attributed to opioid-induced hypogonadism and testosterone patches were started. Additional testing included: 24-hour urine free cortisol (UFC) [447.7 ug/day (≤60), 160.4, and 960]; ACTH of 41.8 pg/mL (0-52); no serum cortisol suppression with 1mg dexamethasone; one day, 8mg high dose dexamethasone suppression testing (HDDST) serum cortisol from 16.6 to 6.2 and 24.6 to 5.1. Bilateral inferior petrosal sinus sampling (BIPSS) was offered, but the patient deferred due to proximity of the surgery to his brain. Pituitary MRI, pan-CT scan, and octreotide scans were unrevealing. Given the severity of his Cushing’s, bilateral adrenalectomy was pursued. His operative course was complicated by splenic injury necessitating splenectomy and only his left adrenal gland was removed. Initial repeat UFC testing was 56, but over the next 10 months, his UFC increased to 144 and his symptoms persisted. Repeat testing included ACTH of 96, HDDST with serum cortisol from 15 to 1, and negative pituitary MRI. He again declined BIPSS. After discussing medications and surgical options, he opted for right adrenalectomy, which went well. His UFC normalized and his Cushing features resolved. Repeat ACTH levels have remained elevated and the source of his ACTH is still unknown.

This case highlights the importance of differentiating between CD and EAS. The HDDST is often the first step and >50% suppression or suppression <5 is often cited as the cutoff for CD. His degree of suppression pointed more towards CD, but the sensitivity and specificity of the test varies. The current gold standard test is BIPSS, however in our case, the patient did not want to undergo this testing, which may have ultimately altered his treatment. In the modern era of medicine, patients and their doctors make shared, informed decisions. From a doctor’s perspective, these decisions can be frustrating, but we must all work within the bounds that our patients give us.


Nothing to Disclose: JS, NGE