Approach to unintentional weight loss: Clinical sciences

Unintentional weight loss refers to a weight loss greater than 5 percent of body weight over 6 to 12 months in an individual who is not purposefully trying to lose weight. Unintentional weight loss can occur due to non-disease-related causes like medication side effects or socioeconomic factors. However, it could also occur due to disease-related causes, more specifically due to increased metabolic demands, impaired caloric intake, as well as gastrointestinal and neuropsychiatric conditions.

Now, if your patient presents with unintentional weight loss, first, obtain a focused history and physical exam. Your patient will report weight loss over 6 to 12 months, despite not trying to lose weight. Additionally, they might report fatigue. Next, the physical exam will typically reveal muscle wasting, loss of subcutaneous fat, and, in severe cases, cachexia. With these findings, diagnose unintentional weight loss.

Next, assess whether or not your patient is taking medications associated with adverse effects that might affect food intake! For example, anticholinergics are associated with dry mouth; chemotherapeutics and metformin can cause nausea; while antidepressants can suppress appetite. If your patient is taking any of the following medications, discontinue medication and check if the patient’s body weight is improving over time! If body weight improves, the underlying cause is the medication's adverse effects.

On the other hand, if your patient is not taking medications associated with weight loss, assess their socioeconomic factors. If your patient reports isolation, functional limitations, financial barriers, or poor access to transportation, diagnose unintentional weight loss due to socioeconomic factors!

However, if history reveals normal socioeconomic factors, assess for signs or symptoms suggesting an underlying medical condition. These include recurrent or chronic illness or infection and frequent vomiting or abnormal stooling. If any of these signs or symptoms are present, consider weight loss due to increased metabolic demands, impaired caloric intake, or gastrointestinal conditions!

First, let’s focus on increased metabolic demands, starting with advanced cardiopulmonary or renal disease. If your patient has a known history of congestive heart failure, COPD, or CKD and their physical exam reveals signs of decompensation, like labored breathing, adventitious breath sounds and peripheral edema, diagnose unintentional weight loss due to advanced cardiopulmonary or renal disease!

Here’s a clinical pearl to keep in mind! Tumor necrosis factor-alpha or TNF-α is a cytokine that causes weight loss in conditions such as heart failure, COPD, and malignancy. Moreover, TNF-α suppresses appetite and reduces gastrointestinal motility and gastric secretions.

Next, let’s discuss common endocrine conditions associated with weight loss, like diabetes mellitus and hyperthyroidism. In diabetes, history will reveal symptoms like fatigue, polyuria, polydipsia, and polyphagia, while in hyperthyroidism, your patient will typically report palpitations and heat intolerance. Next, individuals with diabetes will present with obesity and sometimes acanthosis nigricans. On the flip side, the physical exam in individuals with hyperthyroidism will reveal tachycardia, tremor, warm and moist skin, and sometimes goiter.

In these cases, you can be sure that you are dealing with endocrine conditions, so be sure to order additional labs, including hemoglobin A1C, fasting blood glucose, as well as TSH and free T4. If the hemoglobin A1c is equal to or greater than 6.5% OR fasting blood glucose is equal to or greater than 126 mg/dL, diagnose diabetes mellitus. However, regardless of TSH levels, if free T4 is high, diagnose hyperthyroidism!

Next up are infections! In this case, your patient might report close contact with a sick individual, recent travel, IV substance use, or high-risk sexual activity. They may report symptoms like fever, chills, muscle or joint pain, as well as additional symptoms based on the organ system involved, like cough or painful urination.

Next, the physical exam findings depend on the causative pathogen, but often it might reveal tachycardia, tachypnea, lymphadenopathy, abnormal breath sounds, rash, or genital lesions! At this point, consider infection as a cause of unintentional weight loss, so be sure to order labs, including CBC and consider cultures or serologies based on the suspected pathogen! If needed, don’t forget to order imaging, such as a chest X-ray or CT scan, which can help you identify the source of infection.

If lab testing or imaging identifies infection, or if you can make a clinical diagnosis based on your findings, diagnose infection as a cause of unintentional weight loss. Keep in mind that intestinal parasitic infections, such as Enterobius vermicularis, Giardia lamblia, and Entamoeba histolytica, commonly cause diarrhea and unintentional weight loss. If you suspect a parasitic infection, be sure to order stool ova and parasite studies.

Next up is malignancy! Your patient will typically report malaise, fever, and night sweats; and their exam might reveal lymphadenopathy, hepatosplenomegaly, or even a palpable mass. With these findings, consider malignancy as a cause of unintentional weight loss, so be sure to obtain additional diagnostic tests, which vary based on the suspected malignancy. These usually include imaging, like an MRI or CT scan to help locate the malignancy. If you suspect a hematologic malignancy, order a bone marrow biopsy but also additional diagnostic methods, such as flow cytometry and serum and urine protein electrophoresis. On the flip side, if you suspect solid cancer, obtain a tissue biopsy! If the biopsy reveals malignant cells, diagnose malignancy as the cause of unintentional weight loss!

Moving on to autoimmune conditions! In this case, symptoms vary based on the organ system that’s affected, but often your patient might report fever, fatigue, rash, and joint pain or swelling. Next, the physical exam often reveals lymphadenopathy, hepatosplenomegaly, muscle weakness, or joint deformities. With these findings, consider an autoimmune disease as a cause of unintentional weight loss.