Bouras EP, Lange SM, Scolapio JS.
Rational approach to patients with unintentional weight loss.
Mayo Clin Proc. 2001 Sep;76(9):923-9. doi: 10.4065/76.9.923.
Abstract/Text
Unintentional weight loss is a problem encountered frequently in clinical practice. Weight loss and low body weight have potentially serious clinical implications. Although a nonspecific observation, weight loss is often of concern to both patients and physicians. There are multiple potential etiologies and special factors to consider in selected groups, such as older adults. A rational approach to these patients is based on an understanding of the relevant biologic, psychological, and social factors identified during a thorough history and physical examination. The goal of this article is to discuss the clinical importance, review potential pathophysiology, and discuss specific etiologies of unintentional weight loss that will enable the clinician to formulate a practical stepwise approach to patient evaluation and management.
Huffman GB.
Evaluating and treating unintentional weight loss in the elderly.
Am Fam Physician. 2002 Feb 15;65(4):640-50.
Abstract/Text
Elderly patients with unintentional weight loss are at higher risk for infection, depression and death. The leading causes of involuntary weight loss are depression (especially in residents of long-term care facilities), cancer (lung and gastrointestinal malignancies), cardiac disorders and benign gastrointestinal diseases. Medications that may cause nausea and vomiting, dysphagia, dysgeusia and anorexia have been implicated. Polypharmacy can cause unintended weight loss, as can psychotropic medication reduction (i.e., by unmasking problems such as anxiety). A specific cause is not identified in approximately one quarter of elderly patients with unintentional weight loss. A reasonable work-up includes tests dictated by the history and physical examination, a fecal occult blood test, a complete blood count, a chemistry panel, an ultrasensitive thyroid-stimulating hormone test and a urinalysis. Upper gastrointestinal studies have a reasonably high yield in selected patients. Management is directed at treating underlying causes and providing nutritional support. Consideration should be given to the patient's environment and interest in and ability to eat food, the amelioration of symptoms and the provision of adequate nutrition. The U.S. Food and Drug Administration has labeled no appetite stimulants for the treatment of weight loss in the elderly.
Nicholson BD, Aveyard P, Price SJ, Hobbs FR, Koshiaris C, Hamilton W.
Prioritising primary care patients with unexpected weight loss for cancer investigation: diagnostic accuracy study.
BMJ. 2020 Aug 13;370:m2651. doi: 10.1136/bmj.m2651. Epub 2020 Aug 13.
Abstract/Text
OBJECTIVE: To quantify the predictive value of unexpected weight loss (WL) for cancer according to patient's age, sex, smoking status, and concurrent clinical features (symptoms, signs, and abnormal blood test results).
DESIGN: Diagnostic accuracy study.
SETTING: Clinical Practice Research Datalink electronic health records data linked to the National Cancer Registration and Analysis Service in primary care, England.
PARTICIPANTS: 63 973 adults (≥18 years) with a code for unexpected WL from 1 January 2000 to 31 December 2012.
MAIN OUTCOME MEASURES: Cancer diagnosis in the six months after the earliest weight loss code (index date). Codes for additional clinical features were identified in the three months before to one month after the index date. Diagnostic accuracy measures included positive and negative likelihood ratios, positive predictive values, and diagnostic odds ratios.
RESULTS: Of 63 973 adults with unexpected WL, 37 215 (58.2%) were women, 33 167 (51.8%) were aged 60 years or older, and 16 793 (26.3%) were ever smokers. 908 (1.4%) had a diagnosis of cancer within six months of the index date, of whom 882 (97.1%) were aged 50 years or older. The positive predictive value for cancer was above the 3% threshold recommended by the National Institute for Health and Care Excellence for urgent investigation in male ever smokers aged 50 years or older, but not in women at any age. 10 additional clinical features were associated with cancer in men with unexpected WL, and 11 in women. Positive likelihood ratios in men ranged from 1.86 (95% confidence interval 1.32 to 2.62) for non-cardiac chest pain to 6.10 (3.44 to 10.79) for abdominal mass, and in women from 1.62 (1.15 to 2.29) for back pain to 20.9 (10.7 to 40.9) for jaundice. Abnormal blood test results associated with cancer included low albumin levels (4.67, 4.14 to 5.27) and raised values for platelets (4.57, 3.88 to 5.38), calcium (4.28, 3.05 to 6.02), total white cell count (3.76, 3.30 to 4.28), and C reactive protein (3.59, 3.31 to 3.89). However, no normal blood test result in isolation ruled out cancer. Clinical features co-occurring with unexpected WL were associated with multiple cancer sites.
CONCLUSION: The risk of cancer in adults with unexpected WL presenting to primary care is 2% or less and does not merit investigation under current UK guidelines. However, in male ever smokers aged 50 years or older and in patients with concurrent clinical features, the risk of cancer warrants referral for invasive investigation. Clinical features typically associated with specific cancer sites are markers of several cancer types when they occur with unexpected WL.
© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
Withrow DR, Oke J, Friedemann Smith C, Hobbs R, Nicholson BD.
Serious disease risk among patients with unexpected weight loss: a matched cohort of over 70 000 primary care presentations.
J Cachexia Sarcopenia Muscle. 2022 Dec;13(6):2661-2668. doi: 10.1002/jcsm.13056. Epub 2022 Sep 3.
Abstract/Text
BACKGROUND: Unexpected weight loss (UWL) in patients consulting in primary care presents dilemmas for management because of the broad differential diagnoses associated with UWL. Research on the risks of serious disease among patients with UWL to date has largely taken place in secondary care, limiting generalizability to primary care patients. In this study, we use a large matched cohort study to estimate the risks of 12 serious diseases among patients presenting to primary care with UWL where this was recorded, stratified by age and sex, in order to inform a rational clinical approach to patients presenting with UWL.
METHODS: This was a retrospective matched cohort study using electronic health records (EHRs) from the UK Clinical Practice Research Datalink (CPRD). Each patient with UWL (ascertained from EHR coding) was matched to five patients without UWL and followed until the earliest of a diagnosis of the serious disease, date of death, exit from the CPRD database, or end of the study. Observed absolute risks of the 12 serious diseases were estimated as probabilities, and hazard ratios (HRs) were estimated with Cox proportional hazards models.
RESULTS: Between 2000 and 2012, 70 193 patients in CPRD had at least one record of UWL and were matched with 295 579 patients without UWL. Patients with UWL had significantly higher risk of nearly all serious diseases examined compared with patients without. HRs ranged from 1.43 for congestive heart failure [95% confidence interval (CI): 1.27-1.62] to 9.70 for malabsorption (95% CI: 6.81-13.82). The absolute risks of any given serious disease were relatively low (<6% after 1 year). The magnitude and rank order of absolute risks varied by age and sex. Depression was the most common diagnosis among women aged <80 with UWL (3.74% of women aged <60 and 2.46% of women aged 60-79), whereas diabetes was the most common in men <60 with UWL (2.96%) and cancer was the most common in men aged 60 and over with UWL (3.79% of men aged 60-70 and 5.28% of men aged ≥80).
CONCLUSIONS: This analysis provides new evidence to patients and clinicians about the risks of serious disease among patients presenting with UWL in primary care. Depending on age and sex, the results suggest that workup for UWL should include screening for diabetes, thyroid dysfunction, depression, and dementia. If performed in a timely manner, this workup could be used to triage patients eligible for cancer pathway referral.
© 2022 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.
Wang QL, Babic A, Rosenthal MH, Lee AA, Zhang Y, Zhang X, Song M, Rezende LFM, Lee DH, Biller L, Ng K, Giannakis M, Chan AT, Meyerhardt JA, Fuchs CS, Eliassen AH, Birmann BM, Stampfer MJ, Giovannucci EL, Kraft P, Nowak JA, Yuan C, Wolpin BM.
Cancer Diagnoses After Recent Weight Loss.
JAMA. 2024 Jan 23;331(4):318-328. doi: 10.1001/jama.2023.25869.
Abstract/Text
IMPORTANCE: Weight loss is common in primary care. Among individuals with recent weight loss, the rates of cancer during the subsequent 12 months are unclear compared with those without recent weight loss.
OBJECTIVE: To determine the rates of subsequent cancer diagnoses over 12 months among health professionals with weight loss during the prior 2 years compared with those without recent weight loss.
DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort analysis of females aged 40 years or older from the Nurses' Health Study who were followed up from June 1978 until June 30, 2016, and males aged 40 years or older from the Health Professionals Follow-Up Study who were followed up from January 1988 until January 31, 2016.
EXPOSURE: Recent weight change was calculated from the participant weights that were reported biennially. The intentionality of weight loss was categorized as high if both physical activity and diet quality increased, medium if only 1 increased, and low if neither increased.
MAIN OUTCOME AND MEASURES: Rates of cancer diagnosis during the 12 months after weight loss.
RESULTS: Among 157 474 participants (median age, 62 years [IQR, 54-70 years]; 111 912 were female [71.1%]; there were 2631 participants [1.7%] who self-identified as Asian, Native American, or Native Hawaiian; 2678 Black participants [1.7%]; and 149 903 White participants [95.2%]) and during 1.64 million person-years of follow-up, 15 809 incident cancer cases were identified (incident rate, 964 cases/100 000 person-years). During the 12 months after reported weight change, there were 1362 cancer cases/100 000 person-years among all participants with recent weight loss of greater than 10.0% of body weight compared with 869 cancer cases/100 000 person-years among those without recent weight loss (between-group difference, 493 cases/100 000 person-years [95% CI, 391-594 cases/100 000 person-years]; P < .001). Among participants categorized with low intentionality for weight loss, there were 2687 cancer cases/100 000 person-years for those with weight loss of greater than 10.0% of body weight compared with 1220 cancer cases/100 000 person-years for those without recent weight loss (between-group difference, 1467 cases/100 000 person-years [95% CI, 799-2135 cases/100 000 person-years]; P < .001). Cancer of the upper gastrointestinal tract (cancer of the esophagus, stomach, liver, biliary tract, or pancreas) was particularly common among participants with recent weight loss; there were 173 cancer cases/100 000 person-years for those with weight loss of greater than 10.0% of body weight compared with 36 cancer cases/100 000 person-years for those without recent weight loss (between-group difference, 137 cases/100 000 person-years [95% CI, 101-172 cases/100 000 person-years]; P < .001).
CONCLUSIONS AND RELEVANCE: Health professionals with weight loss within the prior 2 years had a significantly higher risk of cancer during the subsequent 12 months compared with those without recent weight loss. Cancer of the upper gastrointestinal tract was particularly common among participants with recent weight loss compared with those without recent weight loss.
Thompson MP, Morris LK.
Unexplained weight loss in the ambulatory elderly.
J Am Geriatr Soc. 1991 May;39(5):497-500. doi: 10.1111/j.1532-5415.1991.tb02496.x.
Abstract/Text
Significant unexplained and unintentional weight loss was found in 45 elderly patients who were identified by computer search of the diagnostic files of seven family practice centers. We performed a case series chart review study which revealed that 24% of the 45 cases had no definitive etiology for the weight loss after two years of extensive clinical investigation. Depression was found to be the most common diagnosis made (18%) followed by cancer (16%). Only four patients died during the study period and all had cancer. The most prevalent diagnosis in this group of ambulatory elderly patients did not prove to be cancer, as often though, but rather "unexplained weight loss." CT scans were not found to be helpful as screening tests in the evaluation of weight loss. Using the data from this study, the diagnostic evaluations of elderly patients with unexplained weight loss may be more efficiently directed.
Davis IJ, Marek SJ, Sridhar S, Wilkins T, Chamberlain SM.
Unintentional weight loss as the sole indication for colonoscopy is rarely associated with colorectal cancer.
J Am Board Fam Med. 2011 Mar-Apr;24(2):218-9. doi: 10.3122/jabfm.2011.02.100166.
Abstract/Text
INTRODUCTION: Weight loss is a commonly used indication for colonoscopy.
METHODS: This is a prospective case study of colonoscopies from 1998 to 2009. Descriptive statistics were used to evaluate age, sex, colonoscopy indications, and findings. Multiple logistic regression analysis was used to determine the odds of colorectal cancer (CRC) based on age, sex, and weight loss.
RESULTS: We reviewed 6425 colonoscopies. The mean age of patients was 57.4 years (SD, ±13.5 years), and 55% of patients were women. One hundred thirty-six (2.1%) of these had unintentional weight loss; for 32 patients (0.4%), unintentional weight loss was the only indication for the procedure. CRC was diagnosed in 116 patients (1.8%), but CRC was not detected in any patients for whom unintentional weight loss as the only indication for colonoscopy.
CONCLUSION: Based on our prospective case study, unintentional weight loss alone was not associated with CRC.
Lankisch P, Gerzmann M, Gerzmann JF, Lehnick D.
Unintentional weight loss: diagnosis and prognosis. The first prospective follow-up study from a secondary referral centre.
J Intern Med. 2001 Jan;249(1):41-6. doi: 10.1046/j.1365-2796.2001.00771.x.
Abstract/Text
OBJECTIVES: To establish the incidence and causes of unintentional weight loss and to compare prognoses.
DESIGN: Prospective.
SETTING: Secondary referral centre.
SUBJECTS: 158 patients (89 female, 56%; 69 male, 44%) referred by general physicians for unexplained weight loss or for other reasons. In the latter case, weight loss was established after admission to hospital. Follow-up lasted for up to 3 years.
MAIN OUTCOME MEASURE: Determining the course of weight loss in patients with diagnosed and undiagnosed causes.
RESULTS: The cause of weight loss was established in 132 (84%) patients and remained unclear in 26 (16%). Reasons were non-malignant (60% of patients) and malignant (24%) diseases. Psychological disorders represented 11% of the non-malignant group. A gastrointestinal disease caused weight loss in 50 (30%) patients. Of malignant disorders, 53% (20 of 38 patients) were gastrointestinal. Amongst the non-malignant group, 39% (30 of 77 patients) had somatic disorders. The prognosis for unknown causes of weight loss was the same as for non-malignant causes.
CONCLUSION: Contrary to common belief, weight loss is not usually due to a malignant disease. A gastrointestinal tract disorder accounts for weight loss in every third patient. If minimal diagnostic procedures cannot establish a diagnosis, then endoscopic investigation of the upper and lower gastrointestinal tract and function tests should be performed to exclude malabsorption.
Arroll B, Khin N, Kerse N.
Screening for depression in primary care with two verbally asked questions: cross sectional study.
BMJ. 2003 Nov 15;327(7424):1144-6. doi: 10.1136/bmj.327.7424.1144.
Abstract/Text
OBJECTIVE: To determine the diagnostic accuracy of two verbally asked questions for screening for depression.
DESIGN: Cross sectional criterion standard validation study.
SETTING: 15 general practices in New Zealand.
PARTICIPANTS: 421 consecutive patients not taking psychotropic drugs.
MAIN OUTCOME MEASURES: Sensitivity, specificity, and likelihood ratios of the two questions compared with the computerised composite international diagnostic interview.
RESULTS: The two screening questions showed a sensitivity and specificity of 97% (95% confidence interval, 83% to 99%) and 67% (62% to 72%), respectively. The likelihood ratio for a positive test was 2.9 (2.5 to 3.4) and the likelihood ratio for a negative test was 0.05 (0.01 to 0.35). Overall, 37% (157/421) of the patients screened positive for depression.
CONCLUSION: Two verbally asked questions for screening for depression would detect most cases of depression in general practice. The questions have the advantage of brevity. As treatment is more likely when doctors make the diagnosis, these questions may have even greater utility.
Arroll B, Goodyear-Smith F, Kerse N, Fishman T, Gunn J.
Effect of the addition of a "help" question to two screening questions on specificity for diagnosis of depression in general practice: diagnostic validity study.
BMJ. 2005 Oct 15;331(7521):884. doi: 10.1136/bmj.38607.464537.7C. Epub 2005 Sep 15.
Abstract/Text
OBJECTIVE: To determine the validity of two written screening questions for depression with the addition of a question inquiring if help is needed.
DESIGN: Cross sectional validation study.
SETTING: 19 general practitioners in six clinics in New Zealand.
PARTICIPANTS: 1025 consecutive patients receiving no psychotropic drugs.
MAIN OUTCOME MEASURES: Sensitivity, specificity, and likelihood ratios of the two screening questions, the help question, combinations of the screening and help questions, and diagnosis by general practitioners.
RESULTS: The help question alone had a sensitivity of 75% (95% confidence interval 60% to 85%) and a specificity of 94% (93% to 96%). The positive likelihood ratio for the help question was 13.0 (9.5 to 17.8) and the negative likelihood ratio was 0.27 (0.17 to 0.44). The likelihood ratio for patients wanting help today was 17.5 (11.8 to 31.9). The general practitioner diagnosis had a sensitivity of 79% (65% to 88%) and a specificity of 94% (92% to 95%).
CONCLUSION: Adding a question inquiring if help is needed to the two screening questions for depression improves the specificity of a general practitioner diagnosis of depression.
Saremi A, Hanson RL, Williams DE, Roumain J, Robin RW, Long JC, Goldman D, Knowler WC.
Validity of the CAGE questionnaire in an American Indian population.
J Stud Alcohol. 2001 May;62(3):294-300. doi: 10.15288/jsa.2001.62.294.
Abstract/Text
OBJECTIVE: This study evaluated the performance of the CAGE questionnaire (a set of four questions about alcoholism) in an American Indian population.
METHOD: We analyzed data from a cross-sectional study of 275 individuals (179 women) aged 21 years or older. Alcohol dependence was diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, Third Edition-Revised (DSM-III-R), based on a detailed psychiatric interview using the Schedule for Affective Disorders and Schizophrenia-Lifetime Version. Accuracy of the CAGE questionnaire was quantified as sensitivity, specificity, likelihood ratios and the area under receiver operating characteristics (ROC) curves, using the DSM-III-R diagnosis as the reference.
RESULTS: Of participants interviewed, 85% of men and 53% of women had a diagnosis of alcohol dependence by DSM-III-R. A CAGE score of > or = 2 had a sensitivity and specificity of 68% and 93%, respectively, in men and 62% and 79% in women, for the diagnosis of alcohol dependence. CAGE scores of 0, 1 and > or = 2 were associated with likelihood ratios of 0.3, 0.3 and 9.5, respectively, in men and 0.4, 0.7 and 1.5 in women. The area under the ROC curve was 81% for men and 75% for women.
CONCLUSIONS: These findings suggest that the CAGE questionnaire is a valid screening method, in this population, for identifying people likely to have alcohol dependence.
Robbins LJ.
Evaluation of weight loss in the elderly.
Geriatrics. 1989 Apr;44(4):31-4, 37.
Abstract/Text
Weight loss among elderly patients is a common clinical problem that may herald numerous medical and psychosocial disorders. Up to 50% of patients claiming weight loss will not have their complaint corroborated by medical records or family members. Since modest weight loss may occur as a physiologic change with advancing age, the practicing physician must have a working definition of pathologic weight loss that triggers an appropriate diagnostic evaluation. After a careful initial history, physical exam, and a limited laboratory test battery, physicians will identify most patients with physical causes for weight loss. Like many other geriatric syndromes, weight loss may require the identification and correction of multiple contributing factors.
