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PATIENT 
Mrs. M is an 85-year-old woman who comes to the office concerned about weight loss. She is worried that she has something serious.
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 and 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%). The evaluation of unintentional weight loss is complicated by its frequency among older adults; 15–20% of adults over 65 years of age may have unintentional weight loss, and the prevalence rises to 50–60% among nursing home residents. Body weight usually peaks about age 60 and then decreases gradually thereafter, especially after age 70, although the normal changes are small (< 1 lb/year).
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It should be noted that weight loss in the elderly is often part of an overall syndrome of functional decline called frailty, which includes weakness, slowness, low level of physical activity, self-reported exhaustion, and unintentional weight loss. When present, frailty has significant implications for morbidity and mortality in the elderly and frail patients have substantially higher morbidity and mortality that their age-matched peers.
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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 most common causes of unintentional weight loss in published studies are cancer (most commonly gastrointestinal [GI] but also lung, lymphoma, and other malignancies), ≈ 19–36%; 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. Mild cognitive impairment and 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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Four pivotal points are worth remembering when evaluating patients with unintentional weight loss (Figure 32-1). First, the weight loss should be documented if possible; 25–50% of patients that complain of unintentional weight loss have not in fact lost weight (and do not need to be evaluated for causes of weight loss). 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 and/or ...