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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 involuntary weight loss? How would you frame the differential?

Significant involuntary weight loss (IWL) is defined as > 5% loss of usual body weight in the last 6–12 months. Significant IWL can be a harbinger of serious underlying disease. One study documented significantly increase mortality in men with IWL compared with men whose weight was stable or increased (36% vs ≈15%). There are a large number of diseases that can cause IWL, which are best organized by system (see below). The 4 most common causes of IWL are cancer (GI, lung, and lymphoma), ≈25%; nonmalignant GI diseases, 17%; depression and alcoholism, 14%; and unknown, 22%. Endocrine disorders account for 7% of IWL. Although cancer is the most common cause, it is not the cause in most patients.

Three pivotal points are worth remembering when evaluating the patient with IWL. First, the weight loss should be documented, because 25–50% of patients who complain of IWL, have not in fact lost weight. 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.

Second, inquire about symptoms of diarrhea or malabsorption. Symptoms of diarrhea, or large difficult to flush, malodorous stools suggests small bowel or pancreatic disease and directs the diagnostic search.

Third, obtain a truly comprehensive history (including a psychosocial 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 (Figure 27–1).

Figure 27-1

Diagnostic approach: involuntary weight loss.

Differential Diagnosis Ofinvoluntary Weight Loss

  1. Cardiovascular

    1. Heart failure (severe)

    1. Subacute bacterial endocarditis (SBE)

  2. Endocrine

    1. Adrenal insufficiency

    1. Diabetes mellitus

    1. Hyperthyroidism

  3. GI (organized from mouth to rectum)

    1. Poor dentition (50% of patients edentulous by age 65)

    1. Anosmia

    1. Esophageal disorders

      1. Esophageal stricture or web

      1. Dysmotility

      1. Esophageal cancer

    1. Gastric disorders

      1. Peptic ulcer disease (PUD)

      1. Gastric cancer

      1. Gastroparesis

      1. Gastric outlet obstruction

    1. Small bowel diseases

      1. Mesenteric ischemia

      1. Crohn disease

      1. Celiac sprue

      1. Bacterial overgrowth syndromes

      1. Lactose intolerance

    1. Pancreatic disease

      1. Acute pancreatitis

      1. Chronic pancreatitis

      1. Pancreatic insufficiency

      1. Pancreatic cancer

    1. Hepatic disease

      1. Hepatitis

      1. Cholelithiasis

      1. Cirrhosis

      1. Hepatocellular carcinoma

    1. Colonic diseases

      1. Chronic constipation

      1. Colon cancer

    1. Chronic GI infections

      1. Giardia lamblia

      1. Clostridium difficile

      1. Entamoeba histolytica

  4. Hematologic/oncologic

    1. Lung cancer

    1. Pancreatic cancer

    1. GI cancers

    1. Lymphoma

    1. Miscellaneous others

  5. Infectious: HIV infection or complications

  6. Neurologic

    1. Dementia

    1. Stroke


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