Involuntary Weight Loss

The hallmark of catabolic Involuntary Weight Loss (IWL) is the massive depletion of lean body tissue, which includes muscles, internal organ tissues, blood cells and intracellular and extracellular water. Cancer cachexia and AIDS wasting are but two examples of particularly devastating forms of IWL that compromise quality of life, decrease survival and increase complications and costs of healthcare. If patients with chronic obstructive pulmonary disease (COPD) with weight loss are included, greater than 5 million Americans will be defined as suffering from significant IWL in 2003. This number escalates significantly with the addition of those who experience the age-related weight loss condition known as geriatric sarcopenia.

The loss of lean muscle or tissue contributes to fatigue, impaired functionality in daily activities, deficient immunity and a broad spectrum of conditions that can compromise an individual’s ability to fight the underlying disease and tolerate its treatment. Significant weight loss and specifically, lost muscle, is one of the best predictors of survival in diseases such as cancer, HIV/AIDS, COPD, and in a number of conditions relating to the elderly.

Involuntary or unintentional weight loss may be obvious, as in advanced cancer or AIDS, or can be more subtle and insidious. Since two-thirds of US adults are estimated as being overweight or obese, IWL – which is predominantly the loss of muscle or lean body mass – can be ‘hidden’ until reaching an advanced stage. Clinicians are now beginning to understand the devastating effects that IWL can have on patients and have started to refer to this condition as the forgotten ‘vital’ sign.

References:

1.Iannuzzi-Sucich M, Prestwood KM, Kenny AM. “Prevalence of sarcopenia and predictors of skeletal muscle mass in healthy, older men and women.” J Gerontology A Biological Science Medical Science 2002; 57: M772-7 and, Roubenoff R. “Sarcopenia and its implications for the elderly”. European Journal of Clinical Nutrition, 2000 June; 54 Supplement 3:S40-7.

2.http://www.obesity.org/subs/fastfacts/obesity_US.shtml

The Forgotten "Vital" Sign

Standard ‘vital’ signs for a medical evaluation include temperature, pulse, blood pressure and respiration. They allow the clinician to assess the evident measures or ‘vitality’ of life. And while the ‘vitality’ of the patient may not be ‘measurable’ as such, the appearance of a person experiencing progressive weight loss is usually obvious to any observer – clinician, family or friend.

“Physicians tend to overlook involuntary weight loss while focusing on other more pressing aspects of disease, such as tumor size and metastases in patients with cancer, or viral load and the presence of other infections in AIDS patients. That is why it is appropriately called the “forgotten ‘vital’ sign,” said Dr. Jamie Von Roenn, MD, Professor of Medicine, Northwestern University, Division of Hematology/Oncology, and Department of Medicine Chicago, IL. “Some clinicians may take observable weight loss into account, but they don’t distinguish between the losses of fat versus muscle. The measurement of lean body mass loss and its significance to patient survival is critical to evaluating the whole patient and designing an appropriate treatment regimen,” she added.

The loss of lean muscle or tissue contributes to fatigue, impaired functionality in daily activities, deficient immunity and a broad spectrum of conditions that can compromise an individual’s ability to fight the underlying disease and tolerate its treatment. Significant weight loss and specifically, lost muscle, is one of the best predictors of survival and risk for complication in diseases such as cancer, HIV/AIDS, COPD, and in a number of conditions relating to the elderly.

Recognizing Involuntary Weight Loss

Weight loss and malnutrition can be a strong prognostic factor in a variety of diseases. Attention to weight loss early in the diagnoses of these diseases can help delay this devastating syndrome, and perhaps prevent it altogether. That’s why it’s so important for doctors to remember to pay close attention to this "vital" sign.

Beyond issues of complications and death, IWL impacts both the patient and family. People with IWL often complain that they don’t “feel like themselves.” When they look in a mirror, the frail, skeletal appearance - thin arms and legs, drawn faces and sunken cheeks and eyes - is a constant reminder that they are facing a potentially deadly disease. Depression, a loss of self-esteem and self-confidence are often the result in the change in body shape. People who are depressed and fatigued are less inclined to take steps to improve their health, such as preparing and eating regular nutritious meals and exercising.

Causes of Involuntary Weight Loss

The mechanism associated with IWL can vary from disease to disease and among individuals. In general, however, there are two main factors responsible for progressive IWL:

1. Inadequate intake of protein and calories to meet the requirements of the individual.
   This decrease in intake can be due to poor appetite (anorexia), or impediments to intake such as problems with swallowing, digestion or absorption. Decreased intake can result from a patient’s disease and/or treatment. For example, in patients with cancer, swallowing may be a problem due to tumors in the mouth, throat or other parts of the gastrointestinal tract. In other cases, powerful treatments, such as radiation and surgery, and side effects from chemotherapeutic or AIDS drugs, can result in nausea and vomiting and a diminished appetite. These conditions make it impossible to take in the nutrients the patient needs.


2. Metabolic changes in the patient.
   If intake was the whole picture in IWL related to cancer and AIDS, patients would recover if they somehow were given more calories, either through more appetizing meals or tube feeding. But increasing calories and protein alone seldom helps. Metabolic changes can occur in a number of medical conditions and by a variety of different mechanisms. Such changes can be mediated by hormones or by hormone-like proteins made by the body in response to specific conditions such as presence of infection, severe trauma or injury, cancer, or other catabolic conditions. These substances modulate a number of different types of cell functions and are often associated with decreases in muscle and other protein synthesis and/or increases in muscle or protein breakdown. One of the major effects of these metabolic changes is a disproportionate loss of muscle.

Risks of Involuntary Weight Loss

Weight loss itself can be deadly, especially lean body mass (LBM). Loss of about 40% of LBM can be fatal because LBM is the site of 99% of the body’s metabolic functions. Several reports have consistently found that as many as one in five patients with cancer will die from weight loss, malnutrition and its complications. Despite the appreciation of weight loss as a prognostic factor (of health) for more than seven decades, only recently is there a growing understanding of the science of involuntary weight loss and therapeutic options. In the 1930s, IWL of more than 10% was noted to increase complications and risk of death in surgical patients. In the 1970s, this was quantified with 10% loss as significant if it occurred within a period of six months with similar risks of 7.5% loss in three months, 5% in one month or 2% loss in one week. Work in AIDS has shown similar findings, with adverse outcomes with weight loss as little as 3%.

IWL in small amounts is significant for a number of reasons. The significant loss of lean body mass may complicate medical conditions which include decreased muscles required for breathing and coughing, decreased extremity muscle mass and function, decreased immunity and less functional organs with impaired tolerance of medications used to treat the underlying diseases.

Beyond issues of complications and death, IWL impacts both the patient and family. People with IWL often complain that they “don’t feel like themselves.” When they look in a mirror, the frail, skeletal appearance—thin arms and legs, drawn faces and sunken cheeks and eyes—is a constant reminder that they are facing a potentially deadly disease. Depression, a loss of self-esteem and self-confidence, is often the result in the change in body shape. People who are depressed and fatigued are less inclined to take steps to improve their health, such as preparing and eating regular nutritious meals and exercising.

Involuntary Weight Loss FAQ

1. What is involuntary weight loss?

Cancer cachexia and AIDS wasting are but two examples of particularly devastating forms of involuntary weight loss (IWL) that result in compromised quality of life, decreased survival, increased complications and increased costs of healthcare. This loss of functional tissue contributes to fatigue, impaired functionality in daily activities, deficient immunity and a broad spectrum of conditions that can compromise an individual’s ability to fight the underlying disease and tolerate its treatment.

Beyond issues of complications and death, IWL impacts both the patient and family in terms of ‘quality of life.’ People with IWL often complain that they “don’t feel like themselves”. When they look in a mirror, the frail, skeletal appearance—thin arms and legs, drawn faces and sunken cheeks and eyes—is a constant reminder that they are facing a potentially deadly disease. Depression, a loss of self-esteem and self-confidence are often the result of the change in body shape. People who are depressed and fatigued are less inclined to take steps to improve their health, such as preparing and eating regular nutritious meals and exercising.

2. How often do patients experience involuntary weight loss?

Given the numbers of individuals with just three conditions—cancer, chronic obstructive pulmonary disease (COPD) and AIDS—IWL is experienced by more than five million Americans in a given year. This does not include the numbers of individuals older than 65 years who experience moderate to severe geriatric sarcopenia (muscle deficiency) and those with major trauma.

For cancer, it is estimated that more than 1.3 million Americans will be newly diagnosed during 2003 and approximately 560,000 will die of their cancer or its complications. While estimates vary, 60-90% of patients with cancer will experience significant weight loss at some point during the course of their cancer.

It is estimated that there are approximately 16 million people with COPD while prevalence of significant IWL in this group is estimated to be approximately 25%. This translates to approximately 4 million people with significant IWL.

While the number of people in the U.S. who are HIV+ or who have AIDS is significantly smaller than those with cancer or COPD and while weight loss in this population is a less obvious problem in the US today than in the 1980s and early 1990s, in HIV/AIDS patients, IWL is still seen—even in the era of highly active antiretroviral therapy. It is estimated that approximately 18% of HIV/AIDS patients experience significant IWL. Furthermore, loss of lean body mass (LBM) is observed in people with HIV/AIDS, even if individuals have weight that is stable or increased.

3. Isn’t losing weight a good thing?

For most people it is. With obesity at epidemic levels, many people need to drop excess fat. But in conditions such as cancer, AIDS and COPD, the loss of weight is a sign of a metabolic malfunction in which lean body mass (LBM)—the muscles, organs, the immune system and blood cells—are lost as well. LBM depletion results in the gaunt and drawn, sickly appearance so common in cancer and AIDS wards, and if not treated, can be deadly.

4. Why does this happen?

The mechanism associated with IWL can vary from disease to disease and among individuals. In general, however, there are two main factors responsible for progressive IWL:

1. Inadequate intake of protein and calories to meet the requirements of the individual. This decrease in intake can be due to poor appetite (anorexia), or impediments to intake such as problems with swallowing, digestion or absorption. Decreased intake can result from a patient’s disease and/or treatment. For example, in patients with cancer, swallowing may be a problem due to tumors in the mouth, throat or other parts of the gastrointestinal tract. In other cases, powerful treatments, such as radiation and surgery, and side effects from chemotherapeutic or AIDS drugs, can result in nausea and vomiting and a diminished appetite. These conditions make it impossible to take in the nutrients the patient needs.

2. Metabolic changes in the patient. Metabolic changes can occur in a number of medical conditions and by a variety of different mechanisms. Such changes can be mediated by hormones or by hormone-like proteins made by the body in response to specific conditions such as presence of infection, severe trauma or injury, cancer or other catabolic conditions. These substances modulate a number of different types of cell functions and are often associated with decreases in muscle and other protein synthesis and/or increases in muscle or protein breakdown. One of the major effects of this metabolic change is a disproportionate loss of muscle.

5. How serious is IWL?

Weight loss itself can be deadly. The significant loss of LBM may cause medical conditions which include decreased muscles required for breathing and coughing, decreased extremity muscle mass and function, decreased immunity and less functional organs with impaired tolerance of medications used to treat the underlying disease.

Loss of about 40% of lean body mass can be fatal because it is the site of 99% of the body’s metabolic functions. Several reports have consistently found that as many as one in five patients with cancer will die from weight loss, malnutrition and its complications. Despite the appreciation of weight loss being used as a prognostic factor for more than seven decades, only recently is there a growing understanding of the science of IWL and therapeutic options available to treat the condition.

Beyond issues of complications and death, IWL impacts the quality of life both the patient and family. People with IWL often complain that they “don’t feel like themselves.” When they look in a mirror, the frail, skeletal appearance—thin arms and legs, drawn faces and sunken cheeks and eyes—is a constant reminder that they are facing a potentially deadly disease. Depression, a loss of self-esteem and self-confidence are often the result of the change in body shape. People who are depressed and fatigued are less inclined to take steps to improve their health, such as preparing and eating regular nutritious meals and exercising.

6. Why is it called "the forgotten 'vital' sign"?

Standard ‘vital’ signs for a medical evaluation include temperature, pulse and respiration. They allow the clinician to assess the evident measures or ‘vitality’ of life. Unfortunately, physicians tend to overlook IWL while focusing on other more pressing aspects of disease, such as tumor size and metastases in patients with cancer, or viral load and the presence of other infections in AIDS patients. Some clinicians may take observable weight loss into account, but they may not distinguish between the losses of fat versus muscle. The measurement of LBM and its significance to patient survival is critical to evaluating the whole patient and designing an appropriate treatment regimen. The active assessment and treatment of this as the “forgotten ‘vital’ sign” must be made a standard part of healthcare in the 21st century.

7. What are the common treatments used for IWL?

Methods to support weight gain and muscle anabolism include meeting the body’s protein and energy requirements, resistance exercise and various medications that can aid in protein retention and either increase protein synthesis and/or decrease protein breakdown. In the case of anorexia, which can lead to progressive weight loss, an obvious approach is to increase protein and calorie intake to meet the body’s requirements.

Medications that improve a patient’s food intake include corticosteroids, and US Food and Drug Administration (FDA) approved agents for appetite stimulation.

Two oral medications approved for appetite stimulation in AIDS-related weight loss include megestrol acetate and dronabinol. Both have been shown to improve appetite in people with weight loss associated with AIDS or cancer. However, use of dronabinol has not been shown to be associated with weight gain.

Megestrol acetate is an effective appetite stimulant and its use has been associated with increased weight and improved sense of well-being in patients with either AIDS or cancer. If weight gain and quality of life were the only issues, this would be a successful approach to IWL.

Recombinant human growth hormone is an injectable medication approved for AIDS wasting or cachexia. It has both anabolic and anticatabolic effects and its use is associated with increase in weight and increase in LBM. However, routine use of recombinant human growth hormone is limited by the fact that it must be injected on a daily basis, is significantly more expensive than appetite stimulants, and can be associated with such side effects as joint stiffness, fluid retention and various changes in blood chemistries such as blood glucose levels, liver function tests and blood lipids (i.e. cholesterol and triglycerides).

In the context of weight, the oral medication oxandrolone is indicated as an adjunctive therapy to promote weight gain after weight loss following extensive surgery, chronic infections, or severe trauma, and in some patients who, without definite pathophysiologic reasons, fail to gain or to maintain normal weight and to offset the protein catabolism associated with prolonged administration of corticosteroids.