Loss of appetite and loss of weight

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17 Loss of appetite and loss of weight


A 64-year-old man presents with a 3-month history of upper abdominal pain associated with weight loss and mild diarrhoea. He describes the pain as a dull ache and, on specific questioning, says it radiates straight through to the back. The pain is sometimes made worse by eating, and comes and goes. He has lost about 8 kilograms in the last 3 months. He has had, up to three times daily, loose stools which are more smelly than normal, but are not pale and flush away without difficulty. He has lost his appetite. He has not noticed dark urine or pale stools. There is no history of arterial or venous thrombosis or embolism. An upper endoscopy 1 month ago was normal based on the report brought by the patient. He is an ex-smoker, having ceased 10 years ago. He has otherwise been in good health. There is no family history of gastrointestinal disease.

Physical examination is unremarkable. In particular, there are no palpable masses in the abdomen, no lymphadenopathy in any region, no jaundice, no signs of deep venous thrombosis, and no obvious skin lesions (specifically no nodular fat necrosis).

Because of the alarm features (recent unexplained weight loss with anorexia, and new onset of abdominal pain), a computed tomography (CT) scan of the abdomen is ordered. A low-density solid mass in the head of the pancreas that is 3 cm in greatest dimension is identified, with dilatation of the pancreatic duct. The tumour does not appear to extend beyond the pancreas and does not involve the coeliac axis or superior mesenteric artery; no regional lymph nodes are identified. There is no evidence of distant metastases in the liver or elsewhere. A Ca-19-9 level is normal. Although the imaging is typical for pancreatic cancer, an IgG4 level is measured to test for autoimmune pancreatitis; this is not elevated. The patient is referred to a surgeon with special experience in pancreatic disease for consideration of resection. An endoscopic ultrasound is performed to ensure the patient is suitable for curative surgery and, following this test and full discussion of the risks and benefits, the patient undergoes a Whipple’s procedure. Although the patient makes an excellent postoperative recovery, he expires 9 months later from metastatic pancreatic adenocarcinoma.


Body weight is normally constant despite changes in energy expenditure. The energy value of food is a measure of its capacity to produce heat and is expressed in terms of kilocalories per gram (kcal/g). The energy values of carbohydrates (4.1 kcal/g), proteins (5.6 kcal/g), and fats (9.4 kcal/g) differ significantly. Body mass index (BMI, in kg/m2) is calculated by the weight (in kilograms) divided by the square of the height (in metres). Someone with a BMI below 18.5 is considered underweight.

Anorexia refers to a loss of appetite. Appetite is a desire or inclination to satisfy one’s natural need for food. This is different from hunger, which is an uneasy or painful sensation caused by lack of food. Hunger may persist despite a loss of appetite. Satiation or satiety is a sensation of satisfaction experienced after adequate intake of food.

Weight loss is defined as a state when the caloric output (from the basal metabolic rate and voluntary activities) exceeds the input. Weight loss that equals or exceeds 5% of body weight (or 4.5 kg) over a 6-month period is arbitrarily defined as clinically significant. Most individuals can sustain a loss of 5–10% of their body weight without any significant health consequences. In a hospital or institutional setting, patients who have lost weight have increased morbidity and mortality, particularly elderly patients and cancer patients. Those who have lost 5 kg or more in the preceding 6 months also have an increased postoperative morbidity and mortality.

Pathophysiology of Anorexia and Weight Loss


Food intake is regulated by complex central and peripheral mechanisms. The central mechanisms act via the hypothalamus. There are two hypothalamic centres:

Destruction of the brain’s feeding centre can result in failure of the person to eat, leading to starvation and death. Conversely, injury to the satiety centre can lead to hyperphagia (exaggerated appetite) and obesity.

Satiation signals that are multiple (and redundant) help lead to the cessation of food intake. During meals, signals arising from the gastrointestinal tract (from gastric distension and intestinal hormone release including cholecystokinin [CCK], glucagon-like peptide [GLP-1] and peptide YY) help lead to meal cessation by inducing satiation, probably acting via sensory nerves travelling to the hindbrain. Additional adiposity signals (from body fat itself such as leptin, and hormones released in response to a meal such as insulin) circulate to the brain and interact with these other signals to regulate meal size. On the other hand, there are few known signals that control the initiation of meals (orexigenic signals) although increased ghrelin (from the stomach and duodenum) precedes increased food intake, and probably acts via the vagus nerve and directly on the brain.

Anorexia alone is not a symptom of diagnostic value and can occur in many gut and systemic diseases (Box 17.1). Anorexia should be differentiated from ‘sitophobia’, which is a term used to describe a fear of food because of subsequent abdominal pain. Sitophobia can occur with chronic mesenteric vascular insufficiency (abdominal angina) or small intestinal Crohn’s disease with partial obstruction. Anorexia should also be distinguished from early satiation (a feeling of fullness after eating a small amount such that a normal meal cannot be finished), such as occurs after a partial gastrectomy and in patients whose gastric fundus fails to relax (e.g. after a vagotomy, and in some patients with functional dyspepsia).

Weight loss

Involuntary weight loss is a common manifestation of a variety of disease processes (Table 17.1). Although the precise pathophysiological mechanisms inducing weight loss are unclear, multiple factors have been implicated.

Table 17.1 Selected causes of weight loss

Cause Examples
Medical conditions
Malignancy Carcinoma of the pancreas, stomach, oesophagus, colon, liver, lung, breast, kidney
Gastrointestinal and liver disease Malabsorptive states, inflammatory bowel disease, secondary to dysphagia, pancreatitis, hepatitis
Cardiovascular disease End-stage heart failure
Respiratory disease End-stage respiratory failure
Renal disease Chronic kidney disease
Endocrine disease Hyperthyroidism (and hypothyroidism-induced anorexia in elderly patients), hyperparathyroidism, diabetes mellitus, panhypopituitarism, Addison’s disease, phaeochromocytoma
Connective tissue disease Scleroderma, rheumatoid arthritis
Infections HIV, tuberculosis, pyogenic abscess, infective endocarditis, atypical Mycobacterium, systemic fungal infections
Neurological disease Stroke, dementia, Parkinson’s disease
Drugs Amphetamines, cocaine, opiates, serotonin reuptake inhibitors
Psychiatric conditions
Anorexia nervosa  
Bulimia nervosa  
Miscellaneous conditions
Oral disorders Ill-fitting dentures, candidiasis, gingivitis
Hyperemesis gravidarum  

Cancer patients may be unable to eat or may not feel like eating (secondary to treatment or depression). Failure to down-regulate energy expenditure in the face of decreased caloric intake can lead to energy imbalance, which may be one of the main mechanisms of weight loss in some cancers. Increased caloric utilisation by tumour tissue may also be a factor, although increases in resting energy expenditure have not been shown to occur in all patients with tumours. In the acquired immune deficiency syndrome (AIDS), poor oral intake, malabsorption, tumour development and repeated infections coupled with a relatively high resting energy expenditure may all have a role. In elderly people, preferential oxidation of fatty acids and an increase in anaerobic glucose metabolism result in inefficient expenditure or wastage of adenosine triphosphate.

At a molecular level, various mediators may be important in promoting loss of weight. Tumour necrosis factor (TNF) is a cytokine produced from activated lymphocytes and macrophages in cancer patients or in patients with emphysema or severe heart failure; in animal studies it gives rise to anorexia and weight loss. Pentoxifylline, an inhibitor of TNF, can reverse the above effects in animal studies. Interleukin-1, IL-1-beta and IL-6 are potent anorexic cytokines, increasing resting energy expenditure and promoting skeletal wasting.

Although reductions occur from both adipose tissue and muscle (lean mass) in weight loss, the extent from each source can differ. Obese people lose less lean mass than those who are not obese. In uncomplicated starvation, fat tissue is selectively depleted to spare muscle proteins. However in patients with AIDS or cancer, weight loss occurs predominantly from the muscle compartment.

Clinical Approach to Anorexia and Weight Loss

The differential diagnosis is extensive (Box 17.1 and Table 17.1), but investigations should be directed by the history and physical examination.


Determine whether the problem is acute or chronic and when it began. Enquire about any loosening of the patient’s clothes or changes in belt size. Also ask whether weight loss is ongoing. Previous records or photographs may be helpful for comparison. There are rare situations in which patients claim to have lost weight without having done so.

Next, determine the patient’s appetite and eating habits. Ask about the number of meals per day and their composition, and usual daily physical activity.

About one-third of patients with involuntary weight loss plus anorexia have a cancer; up to a quarter have no cause uncovered by tests. Depression is a common cause of weight loss.

Weight loss does not always accompany anorexia. Patients may actually have weight loss with an increase in appetite in malabsorption, hyperthyroidism, uncontrolled diabetes mellitus, phaeochromocytoma or occasionally with lymphoma or leukaemia.

Ask about other gastrointestinal symptoms. For example, recurrent vomiting may indicate bowel obstruction, while dysphagia may suggest oesophageal cancer. The occurrence of diarrhoea immediately after eating can occur in patients with a high intestinal fistula or malabsorption.

Ask whether the patient is afraid to eat because eating precipitates pain or other gastrointestinal symptoms. Abdominal pain that usually occurs after eating suggests peptic ulcer disease, chronic pancreatitis or chronic mesenteric ischaemia (abdominal angina). Pain after eating may also occur in patients with the irritable bowel syndrome or functional dyspepsia (Chs 6 and 7).

In elderly patients, poor dentition is a common but often overlooked problem. Oral disease resulting from conditions such as vitamin deficiencies, candidiasis or gingivitis can affect mastication. Ask about alterations in taste (dysgeusia), which may make food seem unpalatable. Zinc deficiency may sometimes be responsible for dysgeusia (Ch 3).

A detailed current drug history is important. Various medications, including digoxin (especially in toxic doses), amphetamines, chemotherapeutic agents and narcotic analgesics, can cause anorexia and associated nausea and vomiting, which may lead to subsequent weight loss. It is important to look up the side effects of drugs being taken if you are unsure.

Ask about previous medical conditions (e.g. pulmonary tuberculosis, renal disease, previous cancer, cardiac disease) and past surgery. Postgastrectomy syndromes can cause malabsorption (Ch 6). Prior abdominal surgery causes adhesions that can lead to chronic incomplete intestinal obstruction.

Cigarette smoking and alcohol use may be important (e.g. due to the associations with lung and other cancers and cirrhosis, respectively). The patient’s involvement in high-risk behaviour may be relevant (e.g. acquisition of HIV infection).

Ask about social isolation and symptoms of depression (including depressed mood, apathy, insomnia, fatigue, feelings of worthlessness, diminished ability to think and suicidal ideation). Depression, not malignancy, is the most common cause of weight loss in elderly patients and institutionalised patients, and is often missed. It may not always present in its ‘typical’ form. Ask about body image and self-induced vomiting; anorexia nervosa and bulimia nervosa are important causes of weight loss in young people.

Physical examination

Weigh the patient and measure the patient’s height, then calculate the BMI. Milder degrees of weight loss can exist with little or no wasting. In severe weight loss, muscle wasting will usually be obvious—look particularly at the temporalis, deltoid and quadriceps muscles. Body fat loss is suggested by hollowness of the cheeks and buttocks, and by subcutaneous fat content on pinching a fold of skin.

Measure the waist circumference—locate the upper hip bone and the top of the right iliac crest. Place the tape in a horizontal plane around the abdomen at the level of the iliac crest; make sure it is snug (but not too tight), is parallel to the floor and the patient has expired normally before taking the reading. In overweight adults (BMI 25 to 34.9 kg/m2), a waist circumference greater than 102 cm for men (or 88 cm for women) is associated with a greater risk of heart disease and metabolic syndrome. Assess hydration status and look for fluid overload (oedema).

Examine for specific features of vitamin and mineral deficiencies (Table 17.2). Glossitis, cheilosis or perioral dermatitis can result from deficiency of vitamins such as riboflavin, pyridoxine or niacin, whereas peripheral neuropathy or ataxia can occur due to lack of thiamine or vitamin B12.


Figure 17.1 Mini nutritional assessment

Reproduced with permission from Guigoz, Y, Vellas, B, Garry, PJ. Assessing the nutritional status of the elderly: The Mini Nutritional Assessment as part of the geriatric evaluation. Nutr Rev 1996; 54(1 Pt 2):S59. Copyright © 1996 International Life Sciences Institute.

Next, conduct a careful gastrointestinal examination. For instance, in a patient with weight loss and jaundice (Ch 23), a pancreatic cancer with biliary obstruction may be the explanation. If stigmata of chronic liver disease are present and abdominal examination reveals a liver mass with or without a bruit, cirrhosis with development of a hepatoma should be considered. Large abdominal masses can occasionally compress the stomach or small bowel, inducing anorexia (Ch 19).

Look for other clues on the general examination. Although usually not pathognomonic, they can help direct investigations of a particular organ system. For instance, clubbing may suggest the presence of co-existing chronic lung infection or cancer, whereas lymphadenopathy could point towards a possible lymphoma, metastatic cancer or chronic infection. In a febrile patient, the presence of a newly detected murmur may suggest a diagnosis of infective endocarditis, whereas localised bony tenderness could occur in osteomyelitis or with bone metastases.


The diagnostic work-up needs to be directed towards defining the extent of malnutrition and detecting the underlying cause of weight loss.

Tests to estimate nutritional status

Nutritional assessment helps to identify patients who are more likely to develop complications from their malnutrition and, hence, likely to benefit from supportive nutritional therapy. Assessment can be either clinical or based on laboratory tests and measurements.

Calculate the BMI (Box 17.2). Other anthropometric measurements include triceps skin-fold thickness and mid-arm muscle circumference to assess the fat reserve and the muscle mass of the body, respectively. These quantitative measurements are useful for follow-up of nutritional status.

Box 17.2 Classification of nutritional status by body mass index (BMI)

< 16.0 Severely malnourished
16–16.9 Moderately malnourished
17–18.4 Mildly malnourished
18.5–24.9 Normal

The subjective global assessment is based on the history and clinical findings. The degree of recent weight loss, dietary alterations, symptoms, the level of physical activity and stress due to illness (metabolic demand) is gauged from the history. Examination subjectively assesses the amount of fat reserve, muscle mass and oedema or ascites. Patients are then classified into one of three groups:

Laboratory tests that detect decreases in serum albumin or lymphocyte count (under 1.5 × 109/L (under 1500/mm3)) are crude but helpful estimates of nutritional status. Estimation of proteins with a shorter half-life, such as transferrin or prealbumin, should be undertaken if enteral or parenteral nutrition is being considered. Vitamin levels (e.g. fat-soluble vitamins A, D and K) need to be checked in patients with suspected severe malabsorption (e.g. pancreatic insufficiency).

To determine adequate protein intake, nitrogen balance can be assessed by estimating the protein intake and urinary urea nitrogen excretion. To assess adequate caloric intake, energy expenditure can be calculated using the Harris-Benedict equation, if weight, height and age are known. To determine lean body mass and total body fat, body composition can be simply measured using bioelectrical impedance.

The prognostic nutritional index predicts the likelihood of developing postoperative complications in patients undergoing gastrointestinal surgery. It is based on a simple linear equation incorporating measurements of serum proteins (albumin and transferrin concentration), subcutaneous fat (triceps skin fold), and immunologic function (delayed skin hypersensitivity).

In the elderly, the mini-nutritional assessment is a valid tool that allows subdivision of patients into nourished, malnourished or at risk of malnutrition (Fig 17.1).

Table 17.2 Clinical findings associated with vitamin and mineral deficiencies

Findings on physical examination Associated vitamin deficiencies
Dermatitis/cheilosis/glossitis Riboflavin (B2), pyridoxine (B6), niacin
Bleeding/swollen gums Vitamin C
Petechiae/ecchymoses Vitamins C and K
Perifollicular haemorrhages/keratitis Vitamin C
Rash (face/body: pustular, bullous, vesicular, seborrhoeic, acneiform), skin ulcers, alopecia Zinc
Peripheral neuropathy Thiamine/vitamin B12, chromium, vitamin E
Dementia/confusion Thiamine/niacin, zinc, manganese
Night blindness Vitamin A
Ophthalmoplegia Thiamine
Pallor (anaemia) Vitamin B12/folic acid, iron, copper
Dysgeusia Zinc
Fractures Vitamin D
Loosening of teeth, periosteal haemorrhages Vitamin C
Cardiac failure/cardiomyopathy Thiamine, selenium
Hypothyroidism Iodine

Tests aimed at detecting the cause

Diagnostic tests can be arbitrarily classified into those of a screening nature and those that target specific abnormalities detected by the history, physical examination or initial screening test results (Table 17.3). The tests are most successful in finding the cause when they are directed by the history and examination findings.

Table 17.3 Investigations for weight loss and examples of diseases to consider

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Diagnostic test Examples of diseases screened
Bedside tests
Urine analysis Renal cell cancer
Laboratory tests
Full blood count and iron studies Iron deficiency anaemia from gastrointestinal blood loss
Folate/vitamin B12 Macrocytic anaemia in bacterial overgrowth
Electrolytes Chronic kidney disease, Addison’s disease
Liver function tests