Once the weight loss is established, the history, medication profile, physical examination, and conventional laboratory and radiologic investigations (eg, complete blood count, liver biochemical tests, kidney panel, serologic tests including HIV, thyroid-stimulating hormone [TSH] level, urinalysis, fecal occult blood test, chest radiography, and upper gastrointestinal series) usually reveal the cause. Whole-body CT imaging is increasingly used for diagnosis; one study found its diagnostic yield to be 33.5%. When these tests are normal, the second phase of evaluation should focus on more definitive gastrointestinal investigation (eg, tests for malabsorption, endoscopy) and cancer screening (eg, Papanicolaou smear, mammography, prostate-specific antigen [PSA]). However, one prospective case study in patients with unintentional weight loss showed that colonoscopy did not find colorectal cancer if weight loss was the sole indication for the test.
If the initial evaluation is unrevealing, follow-up is preferable to further diagnostic testing. Death at 2-year follow-up was not nearly as common in patients with unexplained involuntary weight loss (8%) as in those with weight loss due to malignant (79%) and established nonmalignant diseases (19%). Psychiatric consultation should be considered when there is evidence of depression, dementia, anorexia nervosa, or other emotional problems. Ultimately, in approximately 15–25% of cases, no cause for the weight loss can be found.