Assessment of unintentional weight loss

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Last reviewed: 21 Oct 2024

Last updated: 25 Jun 2024

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 examination, the aetiology 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.

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 characterised 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 aged >65 years) is reportedly 15% to 20%; however, clinical and epidemiological 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 sub-group 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 gynecological 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-recognised in the primary care setting.[27]

Pathophysiology

The pathophysiology varies depending on the aetiology. 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., tumour 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 aetiologies are:[31]

Malignancy
Gastrointestinal conditions
Psychiatric causes

Other aetiologies 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

Differentials

Common

Stomach cancer
Colorectal cancer
Oesophageal cancer
Pancreatic cancer
Hepatoma
Small cell lung cancer
Non-small cell lung cancer
Non-Hodgkin's lymphoma
Hodgkin's lymphoma
Chronic leukaemia
Multiple myeloma
Oropharyngeal cancer
Laryngeal cancer
Ovarian cancer
Prostate cancer
Breast cancer
Coeliac disease
Exocrine pancreatic insufficiency
Crohn's disease
Ulcerative colitis
Mesenteric ischaemia
Depression
Bipolar disorder
Generalised anxiety disorder
Anorexia nervosa
Substance misuse
Parkinson's disease
Dementia
Hyperthyroidism
Tuberculosis
Adverse medication effects
Sarcopenia

Full details

Uncommon

Cholangiocarcinoma
Acute leukaemia
Zollinger-Ellison syndrome
VIPoma
Carcinoid syndrome
Peptic ulcer disease
Chronic hepatitis
Oesophageal webs, rings, and diverticula
Small intestinal bacterial overgrowth (SIBO)
Gastroparesis
Post-surgical complications
Stomatitis
Bulimia nervosa
Multiple sclerosis
Amyotrophic lateral sclerosis
Prion disease
Cardiac cachexia syndrome
Post-stroke complications
Pulmonary cachexia syndrome
Cystic fibrosis
Microscopic polyangiitis
Renal cachexia syndrome
Diabetes mellitus
Adrenal insufficiency
Hypopituitarism
Phaeochromocytoma
Rheumatoid arthritis
Systemic lupus erythematosus
Granulomatosis with polyangiitis
Polyarteritis nodosa
Systemic sclerosis (scleroderma)
Sarcoidosis
Mixed connective tissue disease (overlap syndromes)
Adult-onset Still disease
HIV infection
Mycobacterium avium complex (MAC)
Histoplasmosis
Amoebiasis
Giardiasis
Cryptosporidiosis
Cystoisosporiasis
Cyclosporiasis
Strongyloidiasis
Infective endocarditis
Whipple's disease
Bartonella infection
Inadequate nutrition
Elder abuse/neglect
Child abuse/neglect

Full details

Contributors

Authors

Christopher J. Wong, MD

Associate Professor

Division of General Internal Medicine

Department of Medicine

University of Washington

Seattle

Disclosures

CJW is an author of a reference cited in this topic. He also receives royalties from Springer for textbooks on perioperative medicine and primary care of solid organ transplant recipients.

Peer reviewers

Alan Shand, MD, FRCP (ed)

Clinical Director

Gastro-intestinal Unit

Western General Hospital

Edinburgh

Disclosures

AS declares that he has no competing interests.

Sherman M. Chamberlain, MD, FACP, AGAF, FACG

Professor of Medicine

Medical Director, Endoscopy

Section of Gastroenterology/Hepatology

Georgia Regents University-Medical College of Georgia

Augusta

Disclosures

SMC declares that he has no competing interests.

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Assessment of unintentional weight loss

Summary

Classification

Epidemiology

Pathophysiology

Differential diagnosis

Differentials

Common

Uncommon

Contributors

Authors

Christopher J. Wong, MD

Disclosures

Peer reviewers

Alan Shand, MD, FRCP (ed)

Disclosures

Sherman M. Chamberlain, MD, FACP, AGAF, FACG

Disclosures

Guidelines

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