A man with abdominal pain: enough evidence for surgery?

A 53-year-old man experienced periodic abdominal discomfort and a decreased capacity to work. His primary physician ordered a broad range of laboratory tests as part of the initial workup. The results revealed a greatly increased adrenocorticotropic hormone (ACTH) concentration of 1250 pg/mL ( 278 pmol/L) [reference interval 46 pg/mL ( 10.2 pmol/L)]. Cortisol was within the reference interval. Repeat measurements 4 weeks later confirmed the increased ACTH. Investigators rapidly excluded 2 well-known conditions associated with increased ACTH concentrations: Cushing disease (ACTH-producing pituitary tumor) and Addison disease (adrenal insufficiency) (1, 2 ). An investigation for an ectopic source of ACTH was begun (3 ). Over the next 18 months, the patient underwent a plethora of imaging studies. A series of conventional studies failed to provide an explanation for the increased ACTH, and ultimately a positron emission tomography/computed tomography (PET/CT) scan using a relatively new radiotracer, Ga-labeled 1,4,7, 10-tetraazacyclododecane-N,N ,N ,N -tetraacetic acid-D-Phe-Tyr-octreotide (Ga-DOTATOC), was performed (4 ). A 3.3-cm area in the head of the pancreas with an increased uptake of radiotracer was observed (Fig. 1). In light of the persistently increased ACTH concentration, this finding raised the suspicion of a pancreatic ACTH-secreting neuroendocrine tumor, a rare ectopic source of ACTH (3 ). Although MRI and conventional CT evaluations did not confirm the presence of a tumor, the patient was offered immediate surgical treatment. The patient declined the offer and subsequently sought second and third opinions at medical facilities in 2 different countries. In both facilities, a neuroendocrine tumor was deemed the likely cause of his problems, and surgery was again suggested. Wishing minimally invasive treatment, the patient contacted the Interventional Centre at our hospital, which offers laparoscopic resection of the pancreas. Preoperative investigations with MRI, optimized multiphase CT, and In-labeled diethylenetriamine pentaacetic acid octreotide (In-DTPA-octreotide) single-photon emission computed tomography/CT (SPECT/CT), a well-established protocol for visualizing neuroendocrine tumors (4 ), failed to identify the supposed tumor. The data from the previously positive Ga-DOTATOC PET/CT evaluation were requested for reinvestigation, and surgery was postponed. Laboratory results at our hospital were comparable with the earlier results. ACTH, measured in a morning sample on the Immulite 2000 platform (Siemens Healthcare Diagnostics), was highly increased at 923 pg/mL (203 pmol/L). Cortisol, measured concurrently on the Modular E platform (Roche Diagnostics), was normal at 16.9 g/dL (467 nmol/L) [reference interval for morning samples, 8–25 g/dL (220–690 nmol/L)]. Results for other hormones, electrolytes, and tumor markers (neuronspecific enolase, chromogranin A, serotonin metabolites) were unremarkable. An endocrinologist could not find convincing clinical evidence of pathology in the pituitary– adrenal axis (specifically, no hyperpigmentation of the skin) to support the laboratory findings. He suggested 1 Department of Medical Biochemistry, Oslo University Hospital – Radiumhospitalet, Oslo, Norway; 2 Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; 3 Interventional Centre and Department of Surgery, Oslo University Hospital – Rikshospitalet, Oslo, Norway; 4 Department of Surgery, Vestre Viken Hospital Trust, Drammen, Norway; 5 Department of Nuclear Medicine, Oslo University Hospital – Rikshospitalet, Oslo, Norway; 6 Department of Medical Biochemistry, Oslo University Hospital – Rikshospitalet, Oslo, Norway. * Address correspondence to this author at: Department of Medical Biochemistry, Oslo University Hospital, Radiumhospitalet, 0310 Oslo, Norway. Fax 4722730725; e-mail [email protected]. Received April 15, 2011; accepted July 13, 2011. Previously published online at DOI: 10.1373/clinchem.2011.167015 7 Nonstandard abbreviations: ACTH, adrenocorticotropic hormone; PET, positron emission tomography; CT, computed tomography; Ga-DOTATOC, Galabeled 1,4,7,10-tetraazacyclododecane-N,N ,N ,N -tetraacetic acid-D-PheTyr-octreotide; SPECT, single-photon emission computed tomography; InDTPA-octreotide, In-labeled diethylenetriamine pentaacetic acid octreotide. QUESTIONS TO CONSIDER