Endocrine Abstracts

We report the clinical history of a 21-years old young female who, in February 2021, presented abdominal pain and biliary vomiting that lasted for two months. An esophagus-gastroduodenoscopy revealed a duodenal ulcerative lesion and proton pump inhibitory therapy was started with clinical benefit. One month later, the patient presented a facial acneiform rush with hirsutism for which she was referred to our attention. An abdominal MRI documented a well-circumscribed hyper-vascular round mass in the pancreatic head with a maximum diameter of 3.5 cm. The fine needle aspiration of the lesion revealed a well-differentiated neuroendocrine tumor, grade 2 (MIB1: 10%). Immunohistochemistry was positive for CK-CAM 5.2, chromogranin, sinaptofisin and a diffuse staining for ACTH in more than 50% of neoplastic elements was detected. Laboratory examination revealed high serum cortisol and ACTH concentrations, respectively 41,1 mcg/dl and 262 ng/l, associated with hyperglycemia and hypokalemia. Futhermore, the 68 Ga DOTA(0)-Phe(1)-Tyr(3)-octreotide (DOTATOC) positron emission tomography (PET) computed tomography demonstrated radiotracer activity within the pancreatic mass with high somatostatin receptor 2 and 5 (SSTR2-5) expression. The hormonal work up was conclusive for ectopic Cushing syndrome (EAS). Hence, the patient was discharged on Ketoconazole (KTZ) 200 mg PO twice a day with clinical and biochemical benefits. In June, the patient underwent duodenocefalopancreasectomy robot assisted surgery with resection of the pancreatic mass, peripancreatic lymph nodes and gallbladder. Histopathological exams confirmed the neuroendocrine origin of the tumor with a Ki67 of 15% and diffuse ACTH staining (pT3 N1 G2 R1). Three months after surgery, the CT scan revealed multiple hepatic metastases while the hormonal exams showed the hypercortisolism relapse. Hence, a double therapeutic approach was planned: oral therapy with osilodrostat (4 mg increased to 10 mg per day) and lanreotide (120 mg monthly). Urinary free cortisol (UFC) declined progressively and clinical signs of CS regressed during therapy. Unfortunately, the subsequent morphologic evaluation with CT, revealed a progression of the hepatic disease. According to the mild hepatic uptake of ^68-Ga and the extension of the hepatic disease, a radioreceptor therapy or a novel surgery approach were excluded. In December, capecitabine combined with temozolomide (CAPTEM) was started with no adverse events. The second cycle was stopped because of Sars-Cov2 infection of the young patient. In conclusion, EAS is a severe condition that requires rapid management of hypercortisolism; the choice of treatments must be performed in a multidisciplinary team, individualized for each patient, using a shared decision-making approach.