Category: Adrenal Disorders
To review the clinical course and management of an interesting case of ectopic Cushing’s syndrome (ECS) in the setting of a metastatic pancreatic neuroendocrine tumor (pNET).
We reviewed clinical and laboratory data.
53 year old male with hypertension, obesity, type 2 diabetes mellitus and a large pNET with liver metastasis (diagnosed 5 months prior) was admitted due to weight gain, worsening edema, blood pressure (BP) and blood glucose (BG) control, as well as severe diarrhea with hypokalemia.
At the time of diagnosis, he was found to have elevated serotonin levels. FNA of pancreatic mass and liver lesion was consistent with well differentiated pNET. He was started on Octreotide LAR and Everolimus, however Everolimus was discontinued a week prior due to severe diarrhea and hypokalemia after it was initiated.
Further workup revealed elevated baseline ACTH and cortisol levels, and non-suppression of cortisol on 1 mg and 8 mg overnight dexamethasone suppression test. 24 hr urine free cortisol level was elevated 18 times the upper limit of normal. Gallium-68 Dotatate scan showed uptake in the pancreatic head mass, multiple intra-abdominal metastatic lymph nodes, liver metastases and a right femur metastatic lesion. Colonoscopy was performed after development of GI bleeding, which revealed a sigmoid colon mass, consistent with colon adenocarcinoma. Genetic evaluation is pending.
Spironolactone was started and titrated. He was not started on Ketoconazole due to elevated liver enzymes and liver metastases. Once potassium levels stabilized, he was started on Mifepristone with close monitoring of electrolytes and BG. Octreotide LAR was continued along with Mifepristone and Spironolactone. He improved significantly clinically with control of BG and BP. Later on, he started chemotherapy with Capecitabine and Temozolomide.
Based on the clinical presentation, ectopic ACTH secretion was suspected and confirmed. Addition of Mifepristone to Octreotide LAR led to symptom control. This combination of drugs has been reported to have synergistic activity attributed to glucocorticoid receptor antagonists, possibly causing upregulation of somatostatin receptors and thus leading to enhanced efficacy of somatostatin analogs.
Further treatment options may include peptide receptor radionuclide therapy with Lutetium-177 Dotatate.
Given the increased morbidity and mortality rate associated with untreated hypercortisolism, a high degree of suspicion should be maintained for possible ECS in the setting of metastatic pNET. This case also highlights the use of combination therapy with somatostatin analogs and glucocorticoid receptor antagonists with favorable results.
University of Florida
I am currently a second year fellow at University of Florida, Gainesville, FL in the division of Endocrinology, Diabetes and Metabolism. I completed my internal medicine residency at New York Methodist Hospital/Weill Cornell Medical College (New York Presbyterian Brooklyn Methodist Hospital) in Brooklyn, NY.
Assistant Professor of Medicine
University of Florida, Florida
Dr. Diana Barb received her medical degree from the University of Medicine and Pharmacy in Targu Mures Romania. She did a two year research fellowship, focusing on obesity, adiponectin and cancer at Beth Israel Deaconess Medical Center, Harvard Medical School in Boston, Massachusetts, followed by an Internship, Internal Medicine Residency and Endocrinology Fellowship at Emory University in Atlanta, Georgia. Subsequently, she joined the University of Florida as a Clinical Assistant Professor in the Division of Endocrinology, Diabetes & Metabolism.