Unintentional weight loss is often defined as weight loss of at least 5% of the patient's usual body weight that occurs within the preceding 6 to 12 months, and that is not the expected consequence of treatment of a known illness.[1] Unintentional weight loss is a diagnostic challenge because, while an underlying illness may be found after a thorough history and physical exam, the etiology may remain elusive and only be discovered through additional testing, the passage of time, or not at all. The most pressing concern is the assessment for the presence of cancer or other conditions for which early diagnosis may lead to better outcomes. There is a broad range of causes of unintentional weight loss including medical diseases, psychiatric illnesses, and social factors. These conditions may occur in isolation or in combination.
Summary
Classification
There is no formal consensus definition of unintentional weight loss; however, the weight loss must be considered unintentional by the patient and treating practitioner. The degree of unintentional weight loss has been defined in case series as being between 5% and 10% weight loss compared with usual body weight.[2] [3] [4] [5] [6] [7] [8] [9] Similarly, there is no strict definition of the time period in which the unintentional weight loss should occur; however, most case series used the criteria of weight loss developing within the preceding 3 to 12 months.
Related syndromes include cachexia and sarcopenia. Cachexia is a syndrome of weight loss characterized by decreased muscle mass in the presence of the metabolic effects of an underlying illness such as some types of cancer or advanced heart failure.[10] [11] [12] While all patients with cachexia have unintentional weight loss, not all patients with unintentional weight loss have cachexia. Sarcopenia is a geriatric syndrome of diminished muscle mass and function, which may or may not be accompanied by unintentional weight loss.[13]
A consensus definition of malnutrition includes unintentional weight loss (>5% in 3 months, or >10% of indefinite time) as a component of one set of diagnostic criteria.[14]
In the US, the Centers for Medicare and Medicaid Services require that long-term care facilities conduct an assessment when a resident has an unplanned weight loss problem (5% change in 30 days or 10% change in 180 days), together with another area of decline.[15]
Epidemiology
In population-based cohort studies, the prevalence of unintentional weight loss varies between 7% and 13%, with differences attributable to both demographics and duration of follow-up.[16] [17] [18] The prevalence in older adults (those ages >65 years) is reportedly 15% to 20%; however, clinical and epidemiologic studies have reported even higher prevalence in certain populations, with as many as 27% of community-dwelling elderly people and 50% to 60% of nursing home residents being affected.[19] [20] For patients with the most clinically applicable presentation (i.e., weight loss occurring within the preceding 6 months), the prevalence is approximately 7%.[18]
A significant association between mortality and unintentional weight loss in older people, and in overweight and obese subjects, has been demonstrated in subgroup analysis of one systematic review and meta-analysis.[21] In an earlier observational study, patients with recent unintentional weight loss (i.e., within 6 months), a weight loss of ≥5% was associated with an increase in subsequent mortality.[18]
Unintentional weight loss has been associated with increased perioperative complications in patients undergoing gynecologic surgery, colorectal surgery, and surgery for disseminated cancer.[22] [23] [24] Unintentional weight loss has been associated with high rates of hospital admission in an outpatient cohort and in patients with dementia in care home settings.[25] [26]
Unintentional weight loss represents a striking contrast to the epidemics of obesity in many countries and the commonplace experience of unsuccessful attempts at intentional weight reduction. Furthermore, unintentional weight loss may be under-recognized in the primary care setting.[27]
Pathophysiology
The pathophysiology varies depending on the etiology. Weight homeostasis is a complex process that includes the availability of food, physical activity, possible environmental exposures, and hormonal control with peptides such as leptin, cholecystokinin, and ghrelin.[28]
Unintentional weight loss owing to cachexia is associated with cytokines (e.g., tumor necrosis factor-alpha) that suppress appetite, promote muscle and fat breakdown, and increase energy expenditure.[29] [30] Normal homeostasis signaling is disrupted in cachexia syndromes, while these mechanisms are preserved in the setting of weight loss due purely to inadequate caloric intake.
Differential diagnosis
The differential diagnosis is extremely broad. In case series, the most common etiologies are:[31]
- Malignancy
- Gastrointestinal conditions
- Psychiatric causes
Other etiologies that should be considered include:
- Cachexia syndromes associated with organ failure (e.g., heart failure, chronic obstructive pulmonary disease, stage 5 chronic kidney disease)
- Endocrinopathies (e.g., hyperthyroidism, diabetes mellitus, adrenal insufficiency)
- Serious infections (e.g., tuberculosis, HIV)
- Medication adverse effects
- Substance misuse
- Social factors that prevent adequate access to food
Last updated
Citations
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McMinn J, Steel C, Bowman A. Investigation and management of unintentional weight loss in older adults. BMJ. 2011 Mar 29;342:d1732.[Abstract]
National Institute for Health and Care Excellence. Suspected cancer: recognition and referral. Oct 2023 [internet publication].[Full Text]
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