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PATIENT 
Mrs. M is an 85-year-old woman who comes to the office complaining of weight loss. She is quite concerned that she has something dreadful.
What is the differential diagnosis of unintentional weight loss? How would you frame the differential?
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CONSTRUCTING A DIFFERENTIAL DIAGNOSIS
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Significant unintentional weight loss is defined as > 5% loss of usual body weight in the last 6–12 months. Significant unintentional weight loss can be a harbinger of serious underlying disease. One study documented significantly increased mortality in men with unintentional weight loss compared with men whose weight was stable or increased (36% vs ≈15%).
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There are a large number of diseases that can cause unintentional weight loss, which are best organized by system (see below). The 4 most common causes of unintentional weight loss are cancer (most commonly gastrointestinal [GI] but also lung, lymphoma, and other malignancies), ≈29%; depression and alcoholism, 16%; nonmalignant GI diseases, 13%; and unknown, 22%. Endocrine disorders account for 7% of unintentional weight loss. Although cancer is the most common cause, it is not the cause in most patients. Dementia may also cause weight loss due to a combination of increased energy expenditure (due to agitation and pacing) and decreased caloric intake.
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Three pivotal points are worth remembering when evaluating patients with unintentional weight loss (Figure 32-1). First, the weight loss should be documented, because 25–50% of patients that complain of unintentional weight loss, have not in fact lost weight (and do not need to be evaluated). Elderly adults often lose muscle mass and simply look like they lost weight. Weight loss should be documented by comparing prior weights or, if these are unavailable, by finding a significant decrease in a patient’s clothing size.
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Clinicians should verify the weight loss or document significant changes in the patient’s clothing or belt size.
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Second, patients should be asked about diarrhea or other symptoms of malabsorption, including large, difficult to flush or malodorous stools. Such symptoms suggest small bowel or pancreatic disease and direct the diagnostic search.
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Third, obtain a truly comprehensive history (including a psychosocial history and medication history) and perform a detailed head to toe physical exam and a baseline laboratory evaluation to search for any subtle diagnostic clues that may help focus the evaluation. Basic labs should include a CBC with differential, urinalysis, renal panel, calcium, liver panel, fasting glucose, fecal occult blood test (FOBT), erythrocyte sedimentation rate (ESR), thyroid-stimulating hormone (TSH), HIV and chest radiograph. Additionally, health examinations should be brought up to date (eg, mammogram, Papanicolaou exam, colonoscopy, and low-dose chest CT scan for smokers with ≥ 30 pack year smoking history unless they quit > 15 years previously.)
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Abnormal findings discovered on ...