今日の臨床サポート

やせ

著者: 中澤一弘1) 竜王ファミリークリニック

著者: 前野哲博2) 筑波大学医学医療系 地域医療教育学

監修: 前野哲博 筑波大学医学医療系 地域医療教育学

著者校正済:2022/03/02
現在監修レビュー中
患者向け説明資料

概要・推奨   

  1. 臨床的に問題となる体重減少を有する人は高齢者に多い。
  1. 臨床的に問題となる体重減少がみられる人の死亡率は高い。
  1. 意図せずに臨床的に問題となる体重減少が生じた人で原因が特定されるのは約80%であり、その原因として最も多いのは消化管由来の悪性腫瘍であった。
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薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、
著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適用の査定において保険適用及び保険適用外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適用の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
中澤一弘 : 特に申告事項無し[2022年]
前野哲博 : 特に申告事項無し[2022年]
監修:前野哲博 : 特に申告事項無し[2022年]

改訂のポイント:
  1. 悪液質、サルコペニアを含むやせの定義と概念を改訂した。

病態・疫学・診察

疫学情報・病態・注意事項  
  1. やせはエネルギーの摂取不足や消費量の亢進で生じる。
  1. やせでも例えば肥満者での緩やかな減量は問題とはなりにくいが、急激な体重減少は重大な疾患が隠れている可能性がある。原因疾患としては、悪性腫瘍、内分泌疾患、消化器疾患、感染症、心不全、腎不全、神経疾患、非感染性炎症疾患、精神科疾患、アルコール、麻薬、覚醒剤、薬剤性と多岐にわたる。
  1. 臨床的に問題となるやせは、6~12カ月で5%以上の体重減少と定義されている。
  1. 米国での疫学的調査によると、年間5%以上の体重減少者は5%であったとの報告がある。
  1. やせの危険因子は、年齢、喫煙、健康管理不足、肥満、無歯である。
  1. 悪液質とは、脂肪の減少の有無を問わずに筋肉の量が減少することで生じる体重減少である。複合的な代謝症候群であり、背景に何らかの疾患が存在している。
  1. サルコペニアとは、筋肉の量と強度および実行力の減少を特徴とした老年症候群である。背景疾患の有無は問わない。サルコペニアは機能障害、転倒、死亡率を上昇させる[1]。原因は多因子であり、テストステロンやエストロゲンの減少[2]、インスリン抵抗性[3]、運動不足[4]、タンパク質の摂取不足[5]などがある。
 
  1. 臨床的に問題となる体重減少を有する人は高齢者に多い(O)。
  1. 1989年に米国で45歳以上の9,144人を対象とした調査では、1年前の体重と比べて、減量を意図せずに5%以上体重が減少していた人が5%存在していた[6]
  1. 65歳以上の高齢者において、5~10年間で15~20%の人に体重減少がみられた[7]
 
  1. 臨床的に問題となる体重減少がみられる人の死亡率は高い(O)。
  1. イスラエルで公的サービスに従事する40~65歳の男性10,059人を対象とした調査では、5年間にわたって5kgより多く体重が減少していた人は、体重が増減1kg以内であった人と比べて、その後の18年間で死亡率が18%上昇していた[8]
  1. 米国で50~74.9歳の5,838人を12年以上追跡した調査では、6.9%に臨床的に問題となる体重減少がみられ、追跡期間中の死亡率は24%高かった[9]
  1. 施設入所者、進行性の肺疾患患者および心不全患者で体重減少がみられると死亡率が高くなる[10][11]
 
  1. 歯が一本もない状態で、義歯を装着しないでいると体重が減少するリスクが高い(O)。
  1. 英国で70歳以上の一般住民563人を対象に1年間追跡した研究において、歯がないままにしておくことは、1年後に10%の体重減少が生じる独立したリスク因子(オッズ比2.03)であった[12]
問診・診察のポイント  
 
  1. やせの申告が間違っている可能性もあるので、まずは本当に臨床的に問題となる、6カ月間で5%の体重減少かどうかを確認する。

これより先の閲覧には個人契約のトライアルまたはお申込みが必要です。

最新のエビデンスに基づいた二次文献データベース「今日の臨床サポート」。
常時アップデートされており、最新のエビデンスを各分野のエキスパートが豊富な図表や処方・検査例を交えて分かりやすく解説。日常臨床で遭遇するほぼ全ての症状・疾患から薬剤・検査情報まで瞬時に検索可能です。

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文献 

Ian Janssen
Influence of sarcopenia on the development of physical disability: the Cardiovascular Health Study.
J Am Geriatr Soc. 2006 Jan;54(1):56-62. doi: 10.1111/j.1532-5415.2005.00540.x.
Abstract/Text OBJECTIVES: To examine the temporal relationship between sarcopenia and disability in elderly men and women.
DESIGN: Cardiovascular Health Study, a longitudinal study of cardiovascular disease and its risk factors in older people.
SETTING: Four U.S. communities.
PARTICIPANTS: Five thousand thirty-six men and women aged 65 and older.
MEASUREMENTS: Whole-body skeletal muscle mass was measured at baseline, and subjects were classified as having normal muscle mass, moderate sarcopenia, or severe sarcopenia based on previously established thresholds. Disability was measured via questionnaire at baseline in up to eight annual follow-up examinations. The cross-sectional relationship between sarcopenia and prevalent disability at baseline was examined using logistic regression models. The longitudinal relation between sarcopenia and incident disability over 8 years of follow-up was examined using Cox proportional hazards models.
RESULTS: At baseline, the likelihood of disability was 79% greater in those with severe sarcopenia (P<.001) but was not significantly greater in those with moderate sarcopenia (P=.38) than in those with normal muscle mass. During the 8-year follow-up, the risk of developing disability was 27% greater in those with severe sarcopenia (P=.006) but was not statistically greater in those with moderate sarcopenia (P=.23) than in those with normal muscle mass.
CONCLUSION: Severe sarcopenia was a modest independent risk factor for the development of physical disability. The effect of sarcopenia on disability was considerably smaller in the longitudinal analysis than in the cross-sectional analysis.

PMID 16420198
Cherian Joseph, Anne M Kenny, Pamela Taxel, Joseph A Lorenzo, Gustavo Duque, George A Kuchel
Role of endocrine-immune dysregulation in osteoporosis, sarcopenia, frailty and fracture risk.
Mol Aspects Med. 2005 Jun;26(3):181-201. doi: 10.1016/j.mam.2005.01.004.
Abstract/Text Osteoporosis, a key predictor of hip fractures can be treated using a variety of safe and effective interventions. Nevertheless, optimally effective strategies for the prevention of hip fractures must also incorporate efforts to address a broad range of other potentially reversible factors. Hyperthyroidism, anticonvulsants, caffeine and smoking may decrease bone mass and increase fracture risk at any age. In older individuals it is important to also consider additional risk factors, including long-acting benzodiazepines, poor vision and sarcopenia. The presence of sarcopenia, an age-related decline in muscle bulk and quality enhances the risk of frailty and possibly also hip fracture, particularly if associated with diminished functional mobility, lower quadriceps strength and poor balance or body sway. In this review we examine evidence which indicates the presence of endocrine-immune dysregulation in both osteoporosis and sarcopenia. Post-menopausal declines in serum estrogen and androgen levels contribute to increases in local bone levels of cytoclastic cytokines, followed by increased osteoclastogenesis and bone loss. Similarly, the presence of decreased gonadal hormones and IGF-1, combined with unusually high peripheral levels of cytokines, inflammatory mediators and coagulation markers all enhance the risk of sarcopenia and frailty. We propose that a translational research approach which emphasizes common pathophysiologic mechanisms in osteoporosis and sarcopenia could accelerate the speed of discovery of effective strategies for both frailty and hip fracture prevention.

PMID 15811434
Blake B Rasmussen, Satoshi Fujita, Robert R Wolfe, Bettina Mittendorfer, Mona Roy, Vincent L Rowe, Elena Volpi
Insulin resistance of muscle protein metabolism in aging.
FASEB J. 2006 Apr;20(6):768-9. doi: 10.1096/fj.05-4607fje. Epub 2006 Feb 7.
Abstract/Text A reduced response of older skeletal muscle to anabolic stimuli may contribute to the development of sarcopenia. We hypothesized that muscle proteins are resistant to the anabolic action of insulin in the elderly. We examined the effects of hyperinsulinemia on muscle protein metabolism in young (25+/-2 year) and older (68+/-1 year) healthy subjects using stable isotope tracer techniques. Leg blood flow was higher in the young at baseline and increased during hyperinsulinemia, whereas it did not change in the elderly. Glucose concentrations and muscle uptake were not different between groups at baseline and during hyperinsulinemia. Leg phenylalanine net balance was not different at baseline and significantly increased in both groups with hyperinsulinemia (P<0.05) but to a greater extent in the young (P<0.05). Muscle protein synthesis increased only in the young during hyperinsulinemia. Muscle protein breakdown did not significantly change in either group, although it tended to decrease in the elderly. Changes in muscle protein synthesis were correlated with changes in leg amino acid delivery (R=0.89; P=0.0001) and blood flow (R=0.90; P<0.0001). In conclusion, skeletal muscle protein synthesis is resistant to the anabolic action of insulin in older subjects, which may be an important contributor to the development of sarcopenia.

PMID 16464955
T Rantanen, P Era, E Heikkinen
Physical activity and the changes in maximal isometric strength in men and women from the age of 75 to 80 years.
J Am Geriatr Soc. 1997 Dec;45(12):1439-45. doi: 10.1111/j.1532-5415.1997.tb03193.x.
Abstract/Text OBJECTIVE: To research the natural changes in maximal isometric strength, over a period of 5 years, in men and women aged 75 at baseline, and to study the effect of everyday physical activity on strength alterations.
DESIGN: A 5-year longitudinal study.
SETTING: Exercise laboratory.
PARTICIPANTS: The target group in 1989 was the total 75-year-old population of Jyväskylä. One hundred one men (81%) and 186 women (75%) participated in baseline strength tests, and after 5 years, 55 men and 111 women (70% and 72% of the survivors) took part in the follow-up measurements.
METHODS: Maximal isometric hand grip, arm flexion, knee extension, trunk flexion, and trunk extension forces were measured using dynamometers. Self-rated physical activity was recorded using a scale by Grimby (1986). Strength changes were compared between groups based on the amount of everyday physical activity: (1) remained active (AA, 24 men, 24 women); (2) remained sedentary (SS, 11 men, 43 women); (3) decreased activity (AS, 11 women); and (4) increased activity (SA, 32 women). AS and SA could be formed for women only because of the small number of men. All analyses were stratified by gender.
MAIN RESULTS: The average percentage change in strength over 5 years among survivors varied from a 4% increase in knee extension strength observed in men and women to a 16% decrease in grip strength in women. The grip strength decrease was greater in women than men. The AA men maintained their trunk extension strength at a higher level than the SS men. Time by group interactions in men were not significant. In women, the rate of decline in AS was 32% in grip and 27% in elbow flexion strength, which was greater than in the other activity groups. The AA women retained their knee extension strength at a higher level than the other groups. Those who died before follow-up tests exhibited poorer strength test results at baseline. Physical activity decreased over follow-up.
CONCLUSIONS: Strength alterations with age differed between muscle groups. Undertaking everyday physical activities such as household work, walking, and gardening, which are also the most common physically demanding activities of older people, may play an important role in maintaining strength at an adequate level for independent living.

PMID 9400552
Denise K Houston, Janet A Tooze, Katelyn Garcia, Marjolein Visser, Susan Rubin, Tamara B Harris, Anne B Newman, Stephen B Kritchevsky, Health ABC Study
Protein Intake and Mobility Limitation in Community-Dwelling Older Adults: the Health ABC Study.
J Am Geriatr Soc. 2017 Aug;65(8):1705-1711. doi: 10.1111/jgs.14856. Epub 2017 Mar 17.
Abstract/Text OBJECTIVES: The current Recommended Dietary Allowance (RDA) for protein is based on short-term nitrogen balance studies in young adults and may underestimate the amount needed to optimally preserve physical function in older adults. We examined the association between protein intake and the onset of mobility limitation over 6 years of follow-up in older adults in the Health ABC study.
DESIGN: Prospective cohort study.
SETTING: Memphis, Tennessee and Pittsburgh, Pennsylvania.
PARTICIPANTS: Community-dwelling, initially well-functioning adults aged 70-79 years (n = 1998).
MEASUREMENTS: Protein intake (g/kg body weight/d) was calculated using an interviewer-administered 108-item food frequency questionnaire at baseline. Mobility limitation was assessed semi-annually and defined as reporting any difficulty walking one-quarter of a mile or climbing 10 steps on 2 consecutive 6-month contacts. The association between protein intake and incident mobility limitation was examined using Cox proportional hazard regression models adjusting for demographics, behavioral characteristics, chronic conditions, total energy intake, and height.
RESULTS: Mean (SD) protein intake was 0.91 (0.38) g/kg body weight/d, with 43% reporting intakes less than the RDA (0.8 g/kg body weight/d). During 6 years of follow-up, 705 participants (35.3%) developed mobility limitations. Compared to participants in the upper tertile of protein intake (≥1.0 g/kg body weight/d), participants in the lower two tertiles of protein intake (<0.7 and 0.7 -<1.0 g/kg body weight/d) were at greater risk of developing mobility limitation over 6 years of follow-up (RR (95% CI): 1.86 (1.41-2.44) and 1.49 (1.20-1.84), respectively).
CONCLUSION: Lower protein intake was associated with increased risk of mobility limitation in community-dwelling, initially well-functioning older adults. These results suggest that protein intakes of ≥1.0 g/kg body weight/d may be optimal for maintaining physical function in older adults.

© 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society.
PMID 28306154
A A Meltzer, J E Everhart
Unintentional weight loss in the United States.
Am J Epidemiol. 1995 Nov 15;142(10):1039-46.
Abstract/Text Lower weight is usually considered advantageous to health, yet weight loss has been associated with increased mortality. An explanation for this paradox might be that the benefits of weight loss may depend on whether the loss is intentional or unintentional. The authors investigated whether intentional and unintentional weight loss differed in their associations with known risk factors for morbidity and mortality in a nationally representative sample of the US population. The sample consisted of 9,144 persons, aged 45 years and older, who answered questions regarding 1-year weight change in the diabetes risk factor Current Health Topic of the 1989 National Health Interview Survey (NHIS). Statistical analyses incorporated the sample weights and characteristics of the survey design. Relative to a common referent group, the factors associated with weight loss differed depending on whether the loss was defined as intentional loss, as unintentional loss, or regardless of intention. Restricting analysis to the 1,999 persons who lost weight, unintentional relative to intentional weight loss was significantly (p < 0.05) associated with older age, poorer health status, smoking, lower body mass index, and, in men only, widowhood and less education. Thus, unintentional weight loss may serve as a marker for factors that characterize persons at greater risk of mortality than persons undergoing intentional weight loss. Also, intention to lose weight may help clarify the relation between weight loss and mortality that, to this point, has shown counterintuitive results. Studies of the relation between weight loss and mortality should incorporate intention as a factor in the analysis.

PMID 7485049
Jenna McMinn, Claire Steel, Adam Bowman
Investigation and management of unintentional weight loss in older adults.
BMJ. 2011 Mar 29;342:d1732. doi: 10.1136/bmj.d1732. Epub 2011 Mar 29.
Abstract/Text
PMID 21447571
Abstract/Text Recent studies have suggested that weight loss in middle-aged persons antecedes increased mortality. Therefore, the authors sought to examine the association between changes in body weight and subsequent mortality, according to self-reported dieting status. The authors followed 9,228 men aged 40-65 years in 1963, for whom weight changes between 1963 and 1968 were recorded and extensive clinical, anthropometric, biochemical, and dietary assessments were made. Of these men, 2,471 reported being on a diet when first examined in 1963, and 636 were dieting primarily to lose weight. Mortality follow-up covered an 18-year period (1968-1986). Men who lost 5 kg or more between 1963 and 1968 ("extreme weight losers") exhibited the following age-pooled risks of mortality relative to the stable weight group: for total mortality, 1.36 (95% confidence interval (CI) 1.20-1.55); for all cardiovascular disease mortality, 1.40 (95% CI 1.16-1.69); for all non-cardiovascular disease mortality, 1.33 (95% CI 1.11-1.59); for coronary heart disease mortality, 1.55 (95% CI 1.25-1.93); and for cancer mortality, 0.90 (95% CI 0.65-1.24). After adjustment for differences in coronary heart disease risk factor levels and morbidity between these groups at the end of the weight change period (1968), the excess risks associated with extreme weight loss declined by approximately one third. They declined further if adjustment was made for 1963 (pre-weight-change period) morbidity and risk factor levels. Being on a slimming diet, as reported in 1963, was associated with an approximate doubling of excess mortality in men with extreme weight loss. Weight loss in 1963-1968 coincided with an increased incidence of coronary heart disease and diabetes mellitus and a declining level of serum total cholesterol. This and other studies indicate that both voluntary and involuntary weight loss might be associated with a small increase in the risk of all-cause mortality.

PMID 9753009
N R Sahyoun, M K Serdula, D A Galuska, X L Zhang, E R Pamuk
The epidemiology of recent involuntary weight loss in the United States population.
J Nutr Health Aging. 2004;8(6):510-7.
Abstract/Text BACKGROUND: Although recent involuntary weight loss (RIWL) has been associated with mortality, no national studies described the prevalence among the general population, characteristics and long-term outcomes of people with RIWL.
METHODS: The authors analyzed data from the NHANES II Mortality Study of 5838 individuals 50-74.9 years old who between 1976-1980 underwent a physical examination that included height and weight measurements, biochemical tests and responded to questions about involuntary weight loss within the past six months. Vital status was determined through 1992. Logistic regression was used to examine characteristics associated with RIWL and Cox proportional hazard modeling was used to measure associations between RIWL and mortality.
RESULTS: 13.3% of the population reported RIWL with 6.9% reporting > or = 5% RIWL. Obese individuals were at significantly higher risk of RIWL of > or = 5% compared to those with BMI 19-24.9 (OR=1.57. 95% CI: 1.13, 2.18). Other significant risk factors for RIWL included; poor self-reported health, cancer, high white blood cell count, low albumin and low hemoglobin levels, age and current smoking status. RIWL of > or = 5% was significantly associated with mortality (RR=1.24, 95% CI: 1.01, 1.53).
CONCLUSION: In summary, RIWL is fairly common among community-dwelling older adults, occurs disproportionately among obese individuals, is associated with characteristics of poor health and independently associated with mortality. These results indicate that RIWL needs to be considered an adverse health indicator even among obese individuals and despite the absence of several clinical indicators of disease.

PMID 15543425
R A Murden, N K Ainslie
Recent weight loss is related to short-term mortality in nursing homes.
J Gen Intern Med. 1994 Nov;9(11):648-50. doi: 10.1007/BF02600311.
Abstract/Text A two-year review of weight changes and mortality in nursing home residents was completed. Factors examined included age, gender, principal diagnosis, cause of death, and amount and duration of weight loss before death. A 10% loss of body weight over a six-month interval strongly predicted mortality in the ensuing six months, with sensitivity 0.60, specificity 0.91, positive predictive value 0.62 and negative predictive value 0.90. Diagnosis and cause of death did not appear to influence this relationship. Routine weight measurements may be useful as predictors of six-month survival in certain nursing home residents.

PMID 7853074
Eun Kyeung Song, Yongjik Lee, Debra K Moser, Rebecca L Dekker, Seok-Min Kang, Terry A Lennie
The link of unintentional weight loss to cardiac event-free survival in patients with heart failure.
J Cardiovasc Nurs. 2014 Sep-Oct;29(5):439-47. doi: 10.1097/JCN.0b013e3182a46ba8.
Abstract/Text BACKGROUND: Patients with heart failure (HF) commonly have unintentional weight loss, depressive symptoms, and elevated levels of high-sensitivity C-reactive protein (hsCRP). Each of these variables has been independently associated with shorter cardiac event-free survival. However, little data exist on the relationships of unintentional weight loss, hsCRP level, and depressive symptoms to cardiac event-free survival.
OBJECTIVE: The aims of this study were to determine (1) whether depressive symptoms and elevated hsCRP level predicted unintentional weight loss and (2) whether unintentional weight loss predicted shorter cardiac event-free survival.
METHODS: This was a prospective study of 243 consecutive HF patients (61% men, 61 ± 14 years old) enrolled during an index hospitalization for HF exacerbation. Patients provided blood samples to measure hsCRP level and completed the Beck Depression Inventory to assess depressive symptoms at discharge. Body weight was measured at discharge and 6 months later. Unintentional weight loss was defined as weight loss of greater than 6% of body weight since discharge. Cardiac event-free survival was followed for 1 year after the second measurement of body weight through monthly telephone interviews. Hierarchical logistic regression was used to determine whether depressive symptoms and elevated hsCRP level predicted unintentional weight loss. Cox hazard regression was used to determine whether unintentional weight loss predicted cardiac event-free survival.
RESULTS: Thirty-five patients (14.4%) experienced unintentional weight loss at 6 months after discharge. Hierarchical Cox hazard regression revealed that patients with unintentional weight loss had a 3.2 times higher risk for cardiac events, adjusting for other clinical factors (P < .001). In hierarchical logistic regression, elevated hsCRP level (odds ratio, 1.49; 95% confidence interval, 1.15-1.92) and depressive symptoms (odds ratio, 1.07, 95% confidence interval, 1.02-1.12) independently predicted unintentional weight loss.
CONCLUSIONS: Unintentional weight loss was an independent predictor of poor outcomes. Heart failure patients with depressive symptoms and elevated hsCRP levels are at a higher risk for unintentional weight loss.

PMID 24088622
C S Ritchie, K Joshipura, R A Silliman, B Miller, C W Douglas
Oral health problems and significant weight loss among community-dwelling older adults.
J Gerontol A Biol Sci Med Sci. 2000 Jul;55(7):M366-71.
Abstract/Text BACKGROUND: Studies of hospitalized and institutionalized older adults suggest a relationship between poor oral health and subsequent weight loss. Given the association between weight loss and subsequent mortality and morbidity, we evaluated how oral health problems contributed to significant weight loss over a 1-year period among a representative sample of community-dwelling older adults.
METHODS: The study population consisted of 563 adults aged 70 years and older living at home in rural and urban areas in six New England states. Baseline data included information regarding health status, functional status, physical activity, disease diagnoses, lifestyle behaviors, and cognitive and affective status. Dentists performed oral health assessments. One year later, participants were called and asked questions regarding their health and dietary practices and their current weight.
RESULTS: Over the 1-year period of follow-up, approximately one third of the sample had lost 4% or more of their previous total body weight; 6% of men and 11% of women lost 10% or more of their previous body weight. Of the subjects, 37% were edentulous; most of these individuals wore full dentures. With gender, income, advanced age, and baseline weight controlled for, edentulousness remained an independent risk factor for significant weight loss (odds ratio 1.63 for 4% weight loss and 2.03 for 10% weight loss). Individuals with increasing numbers of posterior teeth and functional units were at slightly lower risk for weight loss; however, these associations did not reach statistical significance.
CONCLUSIONS: Dentate status is an important risk factor for clinically significant weight loss among community-dwelling older adults.

PMID 10898252
Christoph Metalidis, Daniël C Knockaert, Herman Bobbaers, Steven Vanderschueren
Involuntary weight loss. Does a negative baseline evaluation provide adequate reassurance?
Eur J Intern Med. 2008 Jul;19(5):345-9. doi: 10.1016/j.ejim.2007.09.019. Epub 2007 Nov 26.
Abstract/Text BACKGROUND: Involuntary weight loss frequently poses a diagnostic challenge. Patient and physician alike want to exclude malignant and other major organic illness. The present study aimed to evaluate whether a negative baseline evaluation (consisting of clinical examination, standard laboratory examination, chest X-ray, and abdominal ultrasound) lowers the probability of evolving organic illness in patients with significant unexplained weight loss.
METHODS: Prospective observational study of 101 consecutive patients presenting to a general internal medicine department of a university hospital with an unexplained unintentional weight loss of at least 5% within 6-12 months. Laboratory tests of interest included C-reactive protein, albumin, haemoglobin, and liver function tests.
RESULTS: Weight loss of the 101 patients [age (mean, interquartile range): 64 (51-71) years, 46% male] averaged 10 (7-15) kg. Organic causes were found in 57 patients (56%), including malignancy in 22 (22%). In 44 patients without obvious organic cause for the weight loss (44%), a psychiatric disorder was implicated in 16 (16%) and no cause was established in 28 (28%), despite vigorous effort and follow-up of at least 6 months. Baseline evaluation was entirely normal in none of the 22 patients (0%) with malignancy, in 2 of the 35 (5.7%) with non-malignant organic disease, and in 23 of the 44 (52%) without physical diagnosis. Additional testing, oftentimes extensive, after a normal baseline evaluation led to one additional physical diagnosis (lactose intolerance).
CONCLUSION: In patients presenting with substantial unintentional weight loss, major organic and especially malignant diseases seem highly unlikely when a baseline evaluation is completely normal. In this setting, a watchful waiting approach may be preferable to undirected and invasive testing.

PMID 18549937
J L Hernández, P Matorras, J A Riancho, J González-Macías
Involuntary weight loss without specific symptoms: a clinical prediction score for malignant neoplasm.
QJM. 2003 Sep;96(9):649-55.
Abstract/Text BACKGROUND: Involuntary weight loss (IWL) is a non-specific symptom frequently found in the setting of a malignant neoplasm. There is no established diagnostic approach for patients presenting with isolated IWL, i.e. without data suggesting a particular organ involvement or system disorder.
AIM: To assess the clinical probability of cancer in patients with isolated IWL by means of a score based on simple clinical and laboratory parameters.
DESIGN: Retrospective analysis, followed by prospective model validation.
METHODS: We analysed data from 328 patients who were treated at our Internal Medicine Department because of isolated IWL from January 1991 to December 1997. A predictive model for cancer was developed and validated. For use in clinical practice, a prediction score was derived from the regression model.
RESULTS: There were 236 in-patients (72%) and 92 out-patients (28%). Malignancies were the most frequent cause of isolated IWL (35%), followed by psychiatric disorders (24%). Age, white blood count, and serum albumin, alkaline phosphatase, and lactate dehydrogenase levels were selected as the best predictors. The regression model discriminated relatively well between patients with or without a malignant neoplasm (area under the ROC curve 0.90, 95%CI 0.88-0.92). Model sensitivity was 69%, specificity 93% and positive likelihood ratio 9.9 (using a cut-off point of 0.5).
DISCUSSION: We believe this to be the first study to attempt a systematic approach to the diagnosis of isolated IWL. The approach, based on very simple clinical and laboratory data, should assist the physician in a rational approach to such patients.

PMID 12925720
Marc Decramer, Fernando De Benedetto, Adriana Del Ponte, Stefano Marinari
Systemic effects of COPD.
Respir Med. 2005 Dec;99 Suppl B:S3-10. doi: 10.1016/j.rmed.2005.09.010. Epub 2005 Oct 10.
Abstract/Text Chronic obstructive pulmonary disease (COPD) is characterised by a range of pathological changes of the respiratory system, including airflow limitation secondary to structural changes of the small airways and loss of alveolar attachments, inflammation, ciliary dysfunction, and increased mucous production. COPD also has significant systemic consequences. The relationships between these pulmonary and nonpulmonary morbidities are not fully understood, and this further complicates the assessment of disease severity and prognosis. Although improving lung function and disease symptoms have been the main focus of COPD management, these parameters alone do not reflect the full burden of disease. More recent endeavours have highlighted the potential role of addressing physical limitations imposed by systemic alterations. It is evident that systemic manifestations are common in COPD. Indeed, many patients demonstrate a gradual and significant weight loss that exacerbates the course and prognosis of disease. This weight loss is often accompanied by peripheral muscle dysfunction and weakness, which markedly contribute to exercise limitation and impaired quality of life. Weight loss has been postulated to be the result of a high metabolic rate that is not compensated for by increased dietary intake. The cause of this elevated metabolism is a matter of much debate, and several factors have been implicated. Similarly, the processes underlying depletion of muscle mass and function have not been fully delineated. The impact of the systemic manifestations of COPD is substantial, and although many attempts have been made to elucidate the mechanisms underlying these manifestations, there are important questions, which remain to be answered. An increase in our understanding in this field will doubtless highlight potential therapeutic targets, and assist in guiding future therapeutic development.

PMID 16219454
M Rabinovitz, S D Pitlik, M Leifer, M Garty, J B Rosenfeld
Unintentional weight loss. A retrospective analysis of 154 cases.
Arch Intern Med. 1986 Jan;146(1):186-7.
Abstract/Text Unintentional weight loss (UWL) was documented in 154 patients (2.8%) admitted to an internal medicine department during a two-year period. A retrospective analysis of the clinical charts showed that more than one third (36.3%) were found to have a neoplasm, involving preponderantly the gastrointestinal tract. Patients with neoplasia were older and more frequently had abnormal physical findings and significantly lower values of serum albumin as well as higher values of alkaline phosphatase than other patients. Despite extensive investigations, in 36 patients (23.3%) UWL remained unexplained even after prolonged follow-up periods. The remaining 62 patients had a variety of disorders, preponderantly gastrointestinal tract (26 patients) and psychiatric (16 patients) diseases. Endocrinologic disorders such as diabetes mellitus and hyperthyroidism were relatively uncommon (3.8%). Unintentional weight loss is a relatively common problem in clinical practice. Familiarity with the spectrum of disorders associated with UWL as well as selected clinical and laboratory values may help in the initial examination of these patients.

PMID 3942450
José L Hernández, José A Riancho, Pedro Matorras, Jesús González-Macías
Clinical evaluation for cancer in patients with involuntary weight loss without specific symptoms.
Am J Med. 2003 Jun 1;114(8):631-7.
Abstract/Text PURPOSE: There is no established diagnostic approach to rule out cancer in patients who present with involuntary weight loss in the absence of other symptoms (isolated involuntary weight loss). We sought to evaluate the efficiency of various diagnostic studies used in these patients.
METHODS: We studied 306 patients referred to an urban tertiary care teaching hospital for isolated involuntary weight loss, 276 of whom were followed for at least 1 year or until a final diagnosis was reached. We collected data about the diagnostic approach, the causes of unintentional weight loss, and survival.
RESULTS: Of the 276 patients, 104 (38%) had cancer, mainly of the digestive system (54%, n = 56). The first diagnostic clue usually came from routine blood tests (complete blood count, erythrocyte sedimentation rate, and a biochemical profile), which led to a more targeted diagnostic procedure, such as abdominal ultrasonography, computed tomography, and gastrointestinal endoscopy. Only 2 patients with cancer had normal results in all of these tests. Nine of the patients with cancer were not detected during the initial evaluation. Median survival was 2 months among patients with cancer, and only 9 survived longer than 1 year.
CONCLUSION: These results suggest that a clinical approach, including routine laboratory tests (complete blood count, erythrocyte sedimentation rate, and serum albumin, aminotransferases, gamma-glutamyl transpeptidase, alkaline phosphatase, and lactate dehydrogenase levels) and abdominal ultrasonography, seems to be appropriate for detecting the majority of cases of cancer among patients with isolated involuntary weight loss.

PMID 12798450
P Lankisch, M Gerzmann, J F Gerzmann, D Lehnick
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.
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.

PMID 11168783
Grace Brooke Huffman
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.

PMID 11871682

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