# Internal Medicine/Unintentional Weight Loss
## Involuntary Weight Loss and its Significance

Involuntary or unintentional weight loss (UWL) often develops gradually and can signal underlying serious health issues. Clinically significant weight loss is defined as a loss of 10 pounds (4.5 kg) or more, equivalent to >5% of one's body weight over 6 to 12 months. UWL is observed in up to 8% of adult outpatients and a substantial 27% of frail individuals aged 65 or older. Surprisingly, no identifiable cause is found in approximately one-quarter of patients, despite extensive investigations. Conversely, up to half of people claiming weight loss have no documented evidence to support their claims. Prognosis tends to be better for those without known causes, especially when weight loss is associated with neoplastic sources. Weight loss in older individuals leads to various adverse effects, including falls, fractures, pressure ulcers, compromised immune function, and reduced functional abilities. Notably, significant weight loss is linked to increased mortality rates, ranging from 9% to as high as 38% within 1 to 2.5 years when not addressed clinically.

## Physiology of Weight Regulation with Aging

In healthy aging individuals, total body weight typically peaks in their sixth decade of life and remains stable until their ninth decade, after which it gradually declines. In contrast, lean body mass (fat-free mass) starts decreasing at a rate of 0.3 kg per year during the third decade, with an accelerated decline beginning at age 60 in men and age 65 in women. These changes in lean body mass are primarily a result of the age-related decline in growth hormone secretion, which consequently affects levels of insulin-like growth factor type I (IGF-I). Loss of sex steroids, which occurs at menopause in women and more gradually in men, also contributes to shifts in body composition. In healthy elderly individuals, an increase in fat tissue partially compensates for the loss of lean body mass until very old age when both fat and skeletal muscle are lost. Cellular changes, such as telomere shortening and a decline in body cell mass, occur steadily with aging.

## Factors Contributing to Age-Related Weight Loss

Between the ages of 20 and 80, the mean daily energy intake decreases by up to 1200 kcal in men and 800 kcal in women. Reduced hunger is a consequence of decreased physical activity and loss of lean body mass, leading to lower calorie and food consumption requirements. Various age-related physiological changes predispose elderly individuals to weight loss, including diminished chemosensory function (smell and taste), less efficient chewing, delayed gastric emptying, and alterations in the neuroendocrine axis, including changes in hormone and peptide levels like leptin, cholecystokinin, and neuropeptide Y. These changes result in early satiety and a diminished appetite. Collectively, they contribute to what's known as the "anorexia of aging." Additionally, these physiological changes may coincide with social isolation, poverty, and immobility, further contributing to undernutrition.

## Causes of Unintentional Weight Loss

Most cases of UWL fall into one of four categories: (1) malignant neoplasms, (2) chronic inflammatory or infectious diseases, (3) metabolic disorders (e.g., hyperthyroidism and diabetes), or (4) psychiatric disorders. It's not uncommon for multiple causes to contribute to UWL in a single patient. Depending on the patient population, malignancy accounts for a quarter of cases, organic diseases for a third, and the rest are attributed to psychiatric diseases, medications, or unknown causes. Risk factors for undiagnosed cancer include a history of smoking, localizing symptoms, and abnormal laboratory tests.
The most frequent malignant causes of UWL involve the gastrointestinal, hepatobiliary, hematologic, lung, breast, genitourinary, ovarian, and prostate systems. Gastrointestinal diseases, such as peptic ulcers, inflammatory bowel disease, and chronic pancreatitis, also play a significant role. Additionally, various infections and metabolic disorders, like hyperthyroidism and diabetes, can lead to UWL. Medications, oral and dental problems, and social factors, such as isolation and poverty, can also contribute to UWL.

## Assessment and Treatment

Assessment of UWL involves evaluating anorexia (loss of appetite), sarcopenia (loss of muscle mass), cachexia (a combination of weight loss, muscle and adipose tissue loss, anorexia, and weakness), and dehydration. The obesity epidemic can complicate assessment, as excess adipose tissue may mask the development of sarcopenia and cachexia. Assessment methods include a comprehensive history and physical examination, blood tests, chest x-rays, and abdominal ultrasounds. Additionally, age-, sex-, and risk factor-specific cancer screening should be considered, and elderly patients should be screened for dementia and depression.
Treatment of UWL primarily focuses on identifying and addressing underlying causes. Withdrawal or modification of medications causing anorexia or nausea is recommended. Oral nutritional supplements may help reverse weight loss, and specific medications like mirtazapine can be beneficial in some cases. Exercise programs can increase muscle mass, strength, and endurance. Social factors, such as isolation and poverty, should also be addressed to improve nutritional intake.