Involuntary weight loss (IWL) is frequently insidious and can have important implications, often serving as a harbinger of serious underlying disease. Clinically important weight loss is defined as the loss of 10 pounds (4.5 kg) or >5% of one's body weight over a period of 6–12 months. IWL is encountered in up to 8% of all adult outpatients and 27% of frail persons age 65 years and older. There is no identifiable cause in up to one-quarter of patients despite extensive investigation. Conversely, up to half of people who claim to have lost weight have no documented evidence of weight loss. People with no known cause of weight loss generally have a better prognosis than do those with known causes, particularly when the source is neoplastic. Weight loss in older persons is associated with a variety of deleterious effects, including hip fracture, pressure ulcers, impaired immune function, decreased functional status, and death. Not surprisingly, significant weight loss is associated with increased mortality, which can range from 9% to as high as 38% within 1 to 2.5 years in the absence of clinical awareness and attention.
Physiology of Weight Regulation with Aging
(See also Chaps. 71 and 77) Among healthy aging people, total body weight peaks in the sixth decade of life and generally remains stable until the ninth decade, after which it gradually falls. In contrast, lean body mass (fat-free mass) begins to decline at a rate of 0.3 kg per year in the third decade, and the rate of decline increases further beginning at age 60 in men and age 65 in women. These changes in lean body mass largely reflect the age-dependent decline in growth hormone secretion and, consequently, circulating levels of insulin-like growth factor type I (IGF-I) that occur with normal aging. In the healthy elderly, an increase in fat tissue balances the loss in lean body mass until very old age, when loss of both fat and skeletal muscle occurs. Age-dependent changes also occur at the cellular level. Telomeres shorten, and body cell mass—the fat-free portion of cells—declines steadily with aging.
Between ages 20 and 80, mean energy intake is reduced by up to 1200 kcal/d in men and 800 kcal/d in women. Decreased hunger is a reflection of reduced physical activity and loss of lean body mass, producing lower demand for calories and food intake. Several important age-associated physiologic changes also predispose elderly persons to weight loss, such as declining chemosensory function (smell and taste), reduced efficiency of chewing, slowed gastric emptying, and alterations in the neuroendocrine axis, including changes in levels of leptin, cholecystokinin, neuropeptide Y, and other hormones and peptides. These changes are associated with early satiety and a decline in both appetite and the hedonistic appreciation of food. Collectively, they contribute to the "anorexia of aging."
Causes of Involuntary Weight Loss
Most causes of IWL belong to one of four categories: (1) malignantneoplasms, (2) chronic inflammatory or infectious diseases, (3) metabolic disorders (e.g., hyperthyroidism and diabetes), or (4) psychiatric disorders (Table 80-1). Not infrequently, more than one of these causes can be responsible for IWL. In most series, IWL is caused by malignant disease in a quarter of patients and by organic disease in one-third, with the remainder due to psychiatric disease, medications, or uncertain causes.
Table 80-1 Causes of Involuntary Weight Loss |Favorite Table|Download (.pdf)
Table 80-1 Causes of Involuntary Weight Loss
|Inflammatory bowel disease|
|Endocrine and metabolic|
|Chronic congestive heart failure|
|Chronic obstructive pulmonary disease|
|Renal insufficiency |
|Subacute bacterial endocarditis|
|Nonsteroidal anti-inflammatory drugs|
|Serotonin reuptake inhibitors|
|Angiotensin-converting enzyme inhibitors|
|Disorders of the mouth and teeth|
|Decreased taste and smell|
|Stroke Parkinson's disease|
|Psychiatric and behavioral|
|Increased activity or exercise|
The most common malignant causes of IWL are gastrointestinal, hepatobiliary, hematologic, lung, breast, genitourinary, ovarian, and prostate. Half of all patients with cancer lose some body weight; one-third lose more than 5% of their original body weight, and up to 20% of all cancer deaths are caused directly by cachexia (through immobility and/or cardiac/respiratory failure). The greatest incidence of weight loss is seen among patients with solid tumors. Malignancy that reveals itself through significant weight loss usually has a very poor prognosis.
In addition to malignancies, gastrointestinal causes are among the most prominent causes of IWL. Peptic ulcer disease, inflammatory bowel disease, dysmotility syndromes, chronic pancreatitis, celiac disease, constipation, and atrophic gastritis are some of the more common entities. Oral and dental problems are easily overlooked and may manifest with halitosis, poor oral hygiene, xerostomia, inability to chew, reduced masticatory force, nonocclusion, temporomandibular joint syndrome, edentulousness, and pain due to caries or abscesses.
Tuberculosis, fungal diseases, parasites, subacute bacterial endocarditis, and HIV are well-documented causes of IWL. Cardiovascular and pulmonary diseases cause unintentional weight loss through increased metabolic demand and decreased appetite and caloric intake. Uremia produces nausea, anorexia, and vomiting. Connective tissue diseases may increase metabolic demand and disrupt nutritional balance. As the incidence of diabetes mellitus increases with aging, the associated glucosuria can contribute to weight loss. Hyperthyroidism in the elderly may have less prominent sympathomimetic features and may present as "apathetic hyperthyroidism" or T3 toxicosis (Chap. 341).
Neurologic injuries such as stroke, quadriplegia, and multiple sclerosis may lead to visceral and autonomic dysfunction that can impair caloric intake. Dysphagia from these neurologic insults is a common mechanism. Functional disability that compromises activities of daily living (ADLs) is a common cause of undernutrition in the elderly. Visual impairment from ophthalmic or central nervous system disorders such as a tremor can limit the ability of people to prepare and eat meals. IWL may be one of the earliest manifestations of Alzheimer's dementia.
Isolation and depression are significant causes of IWL that may manifest as an inability to care for oneself, including nutritional needs. A cytokine-mediated inflammatory metabolic cascade can be both a cause of and a manifestation of depression. Bereavement can be a cause of IWL and, when present, is more pronounced in men. More intense forms of mental illness such as paranoid disorders may lead to delusions about food and cause weight loss. Alcoholism can be a significant source of weight loss and malnutrition.
Elderly persons living in poverty may have to choose between purchasing food and purchasing medications. Institutionalization is an independent risk factor, as up to 30–50% of nursing home patients have inadequate food intake.
Medications can cause anorexia, nausea, vomiting, gastrointestinal distress, diarrhea, dry mouth, and changes in taste. This is particularly an issue in the elderly, many of whom take five or more medications.
The four major manifestations of IWL are (1) anorexia (loss of appetite), (2) sarcopenia (loss of muscle mass), (3) cachexia (a syndrome that combines weight loss, loss of muscle and adipose tissue, anorexia, and weakness), and (4) dehydration. The current obesity epidemic adds complexity, as excess adipose tissue can mask the development of sarcopenia and delay awareness of the development of cachexia. If it is not possible to measure weight directly, a change in clothing size, corroboration of weight loss by a relative or friend, and a numeric estimate of weight loss provided by the patient are suggestive of true weight loss.
Initial assessment includes a comprehensive history and physical, a complete blood count, tests of liver enzyme levels, a C-reactive protein, erythrocyte sedimentation rate, renal function studies, thyroid function tests, chest radiography, and an abdominal ultrasound (Table 80-2). Age, sex, and risk factor–specific cancer screening tests, such as mammography and colonoscopy, should be performed (Chap. 82). Patients at risk should have HIV testing. All elderly patients with weight loss should undergo screening for dementia and depression by using instruments such as the Mini-Mental Status Examination and the Geriatric Depression Scale, respectively (Chap. 72). The Mini Nutritional Assessment (www.mna-elderly.com) and the Nutrition Screening Initiative (www.aafp.org/afp/980301ap/edits.html) are also available for the nutritional assessment of elderly patients. Almost all patients with a malignancy and >90% of those with other organic diseases have at least one laboratory abnormality. In patients presenting with substantial IWL, major organic and malignant diseases are unlikely when a baseline evaluation is completely normal. Careful follow-up rather than undirected testing is advised since the prognosis of weight loss of undetermined cause is generally favorable.
Table 80-2 Assessment and Testing for Involuntary Weight Loss |Favorite Table|Download (.pdf)
Table 80-2 Assessment and Testing for Involuntary Weight Loss
|5% weight loss in 30 d|
|10% weight loss in 180 d |
|Body mass index <21 |
|25% of food left uneaten after 7 d|
|Change in fit of clothing|
|Change in appetite, smell, or taste|
|Abdominal pain, nausea, vomiting, diarrhea, constipation, dysphagia|
|Complete physical exam, including dental evaluation|
|Recommended cancer screening|
|Mini-Mental State Examination*|
|Nutrition Screening Initiative*|
|Simplified Nutritional Assessment Questionnaire*|
|Observation of eating*|
|Activities of daily living*|
|Instrumental activities of daily living*|
|Complete blood count|
|Comprehensive electrolyte and metabolic panel, including liver and renal function tests |
|Thyroid function tests|
|Erythrocyte sedimentation rate|
|HIV testing, if indicated|
|Chest x-ray |
Treatment: Unintentional Weight Loss
The first priority in managing weight loss is to identify and treat the underlying causes systematically. Treatment of underlying metabolic, psychiatric, infectious, or other systemic disorders may be sufficient to restore weight and functional status gradually. Medications that cause nausea or anorexia should be withdrawn or changed, if possible. For those with unexplained IWL, oral nutritional supplements such as high-energy drinks sometimes reverse weight loss. Advising patients to consume supplements between meals rather than with a meal may help minimize appetite suppression and facilitate increased overall intake. Orexigenic, anabolic, and anticytokine agents are under investigation. In selected patients, the antidepressant mirtazapine results in a significant increase in body weight, body fat mass, and leptin concentration. Patients with wasting conditions who can comply with an appropriate exercise program gain muscle protein mass, strength, and endurance and may be more capable of performing ADL.