Diabetes
At the onset, weight loss is primarily caused by osmotic diuresis with polyuria/nocturia. Later glycosuria produces caloric loss, combined with the increased catabolic state of insulin deficiency and glucagon excess. In a patient with new diabetes and prominent weight loss, consider underlying pancreatic cancer.

Depression
It is recognized by sadness, anhedonia, anorexia, and sleep disturbance.

Inadequate intake
Common causes include painful oral lesions (phenytoin gum hypertrophy, vitamin deficiency glossitis, heavy metal intoxication, candidiasis, poor dentition), solitary living in the elderly, early dementia, food fads, abnormal taste (hepatitis, zinc deficiency, drugs), or abdominal pain associated with eating (intestinal ischemia). With protein-calorie malnutrition, the skin is dry and baggy. There is weakness, tremor, polyuria, edema, and ascites.

Drugs
Weight loss is associated with cholestyramine, digoxin, diuretics, oral hypoglycemics, cytotoxics, amphetamines, and sibutramine.

Hyperthyroidism
Despite an increased appetite, weight loss occurs. Tachycardia, fine tremor, silky skin, and eye signs (exophthalmos or lid lag) are useful clues. Apathetic hyperthyroidism can occur in elderly patients producing listlessness and tachycardia or atrial fibrillation.

Occult cancer
Pancreatic cancer is the prototype, with aversion to food, and weight loss (20 to 40 lbs.) that precedes visceral pain or jaundice, and is not proportional to size of the tumor. Weight loss is usually marked in gastric and pancreatic cancer, moderate in prostate, colon, and lung cancer, and mild in breast cancer.

Low cardiac output
Easy fatigability, dyspnea on exertion, bibasilar rales, peripheral edema, third and/or fourth heart sounds, and jugular venous distension are found.

Anorexia nervosa
The patient is preoccupied with body weight, yet is unconcerned about being obviously very thin. There is usually overactivity, often the form of vigorous exercise, despite cachexia. Secretiveness leads to the false appearance of involuntary weight loss. The SCOFF questionnaire is helpful in screening: 1) Do you make yourself Sick because you feel uncomfortably full? 2) Do you worry you have lost Control over how much you eat? 3) Have you recently lost more than One stone (14 lbs or 7.7 kg) in a three month period? 4) Do you believe yourself Fat when others say you are too thin? 5) Does Food dominate your life?

Malabsorption
Fat malabsorption produces sticky and greasy stools, borborygmi, abdominal distension, and vague abdominal pain. Malabsorption is also associated with loss of lipid-soluble vitamins, which sometimes produces peripheral neuropathy, anemia, dermatitis, or bleeding. Sprue causes a malabsorption syndrome, bone pain with compression deformities, and anxiety/depression.

Chronic infection
Fever is the key sign. Common occult causes include bacterial endocarditis, osteomyelitis, tuberculosis, and HIV.
Adrenal insufficiency
Fatigue, hypotension, and hyperpigmentation—especially when seen in the palmar creases or buccal mucosa—are important findings.

Emphysemia
Cachexia occurs in “pink puffers.” The patient will have a smoking history, a barrel chest with reduced breath sounds, and will be dyspneic on exertion.