A 64-year-old man comes to the office for evaluation of low mood and anxiety that began 2 months ago. The patient says, "I'm sad and anxious but I can't explain why. I just have this feeling that something bad is going to happen to me." He says that his coworkers have noticed he seems more reserved than usual. The patient has been skipping lunch due to a decreased appetite and has lost 9 kg (20 lb) in the last few months. He continues to enjoy reading mystery novels and has no difficulty falling or remaining asleep. The patient formerly smoked tobacco, with a 20-pack-year history, but he does not use alcohol or illicit drugs. Medical history includes recently diagnosed diabetes mellitus. Vital signs are within normal limits. BMI is 19 kg/m2. Physical examination is unremarkable. The patient is thin and appears anxious. He reports no suicidal ideation, hallucinations, or delusions. TSH level is 4.0 µU/mL. Which of the following is the best next step in management?
This patient has some features of major depression (eg, low mood, isolation, weight loss) and anxiety. However, given his age, smoking history, marked weight loss, and recent diagnosis of diabetes mellitus (despite a lack of obesity), this presentation is concerning for pancreatic cancer.
Depression and associated anxiety may be prodromal features in more than one-third of patients with pancreatic cancer. Patients may describe nonspecific anxiety, a premonitory sensation ("something bad is going to happen"), and feeling "low" for no reason. The association between these psychiatric manifestations and pancreatic cancer is well documented. The mechanism is not clear, but hypotheses include an increase in inflammatory cytokines (eg, interleukin-6), a paraneoplastic syndrome, or alterations in pancreatic function (eg, hormone secretion).
New-onset diabetes mellitus may precede diagnosis in up to 25% of patients with pancreatic cancer and, in the appropriate clinical setting (eg, thin, older patient with a smoking history and marked weight loss), should raise suspicion for the diagnosis. In these patients, the pathophysiology of diabetes is possibly due to cancer-induced beta cell dysfunction or secretion of adrenomedullin (an insulin-regulating peptide hormone).
Therefore, the next step in the workup of this patient's suspected pancreatic cancer should include a CT of the abdomen, which is the preferred initial imaging test in nonjaundiced patients presenting with severe weight loss and other suspicious symptoms.
(Choice A) In the absence of localizing neurological symptoms and findings on physical examination, a brain MRI would not be indicated.
(Choice C) Electroconvulsive therapy is typically reserved for patients with severe depression who are unresponsive to other therapies or in need of emergency treatment. Ruling out a malignant etiology for this patient's depression takes priority.
(Choices D and E) Mirtazapine and paroxetine are antidepressant medications that may be used to treat depression but would not be indicated prior to completing an appropriate workup in a patient with a large number of medical red flags.
Educational objective:
Depression, weight loss, and new-onset diabetes mellitus may occur as early manifestations of pancreatic cancer. CT of the abdomen is indicated as part of the initial diagnostic evaluation.