Approach to unintentional weight loss: Clinical sciences

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Introduction0:00–0:39

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.

Focused H&P0:39–1:13

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!

Medication adverse effects1:13–1:53

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.

Socioeconomic factors1:53–2:47

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.

Advanced cardiopulmonary/renal disease2:47–3:48

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.

Endocrine disease3:48–5:20

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!

Infection5:20–7:09

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.

Malignancy7:09–8:15

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!

Autoimmune disease8:15–9:39

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.
Next, based on your suspicion, check for autoantibodies, like antinuclear antibodies or rheumatoid factor; and based on the patient’s clinical picture, consider ordering imaging studies, or even a biopsy of affected tissues.
The lab results might reveal positive autoantibodies; while imaging could show disease-related abnormalities, such as joint space narrowing or erosions on joint X-ray.
Additionally, a tissue biopsy might reveal signs of an inflammatory process, such as immune complex deposition or infiltration of immune cells.
If this is the case, diagnose an autoimmune condition as the cause of unintentional weight loss.Alright, switching gears and moving on to conditions characterized by impaired caloric intake.

Oropharyngeal disease9:39–10:09

If your patient reports oral pain, poorly fitting dentures, chewing difficulties, or difficulty swallowing, assess the patient’s dentition and swallowing function.
If the evaluation reveals abnormal dentition or abnormal swallowing function, diagnose your patient with unintentional weight loss due to an oropharyngeal condition.
Now, switching gears and moving on to gastrointestinal conditions. If your patient reports abdominal discomfort, bloating, and diarrhea, consider malabsorption.

GI malabsorption10:09–11:15

Next, order CMP, B12, and iron levels, and don’t forget stool studies, such as fecal fat, as well as celiac disease antibodies.
You could also consider an upper endoscopy with biopsy. Labs will typically show electrolyte abnormalities, low albumin, and low B12 and iron levels.
You might also observe elevated fecal fat levels, which is a sign of fat malabsorption, while, in some cases, your patient might have positive celiac disease antibodies.
Finally, upper endoscopy might reveal mucosal abnormalities. These findings are suggestive of malabsorption, which is common in conditions like chronic pancreatitis and Celiac disease.Okay, next up are upper gastrointestinal conditions!

Upper GI Disorder11:15–12:26

In this case, your patient will report nausea, vomiting, early satiety, and sometimes dysphagia. These findings are suggestive of upper gastrointestinal disorder, so consider an upper endoscopy with biopsy.
Endoscopy might be normal, however, it could also reveal mucosal abnormalities and luminal irregularities like strictures or webs.
With these findings, diagnose an upper gastrointestinal condition, such as GERD, esophagitis, or peptic ulcer disease as the cause of unintentional weight loss.
Now, here’s a clinical pearl to keep in mind! Any condition or abnormality that occurs along the GI tract can cause unintentional weight loss, including lower GI disorders such as irritable bowel syndrome, inflammatory bowel disease, diverticulitis, and mesenteric ischemia!Alright, now let’s go all the way back and take a look at individuals with no underlying medical condition.

Underlying medical condition absent12:26–12:41

In this case, you should consider neuropsychiatric conditions, such as depression and dementia!Let’s start with depression.

Depression12:41–14:17

These patients may present with a depressed mood, fatigue, as well as anhedonia, which is a reduced ability to experience pleasure.
If the physical exam is normal, consider depression, so your next step is to use a screening tool, such as Patient Health Questionnaire 9 to test for depression and assess its severity.
This questionnaire asks patients to rate how often they experience symptoms of depression. A score of 5 or higher indicates that your patient has depression, and the higher the score, the higher the severity.Now, here’s a high-yield fact to keep in mind!
You can use the mnemonic SIG E CAPS to summarize the most important manifestations of depression! S stands for Sleep disturbances, while I stands for Interest loss in everyday activities that used to be pleasurable, like hobbies.
Additionally, patients may experience Guilt or sadness, as well as lack of Energy or extreme fatigue. Next, C stands for Concentration difficulty, and slowing down of the patient’s thoughts or emotional reactions.
Next, A refers to changes in Appetite; while P refers to Psychomotor agitation. Finally, patients might have recurrent Suicidal thoughts or preoccupation with death.Finally, let’s focus on dementia, which is usually seen in older patients who typically report episodes of confusion, memory loss, and mood changes.

Dementia14:17–15:30

More commonly, a family member or caregiver will bring these issues to your attention. Physical exam might reveal aphasia, which is the inability to express or understand speech, as well as apraxia, or the inability to perform movements or tasks when asked.
At this point, consider dementia and use a screening tool like the Mini-Mental Status Exam. If your patient scores a 23 or below, diagnose dementia!Here’s a clinical pearl to keep in mind!
Other neuropsychiatric conditions that can cause unintentional weight loss include anxiety, schizophrenia, and obsessive-compulsive disorder.
Moreover, conditions such as anorexia nervosa and bulimia nervosa can cause weight loss but it’s unclear whether it is intentional or not as there is likely a component of body dysmorphia and distorted weight perception.
Alright, as a quick recap… If your patient presents with unintentional weight loss, first assess for medication adverse effects.

Review15:30–16:15

If you rule out medications as a cause, assess the patient's socioeconomic factors, such as isolation, functional limitations, transportation, and financial barriers!
Next, assess for an underlying medical condition, and if present, evaluate for conditions associated with increased metabolic demands, impaired caloric intake, and gastrointestinal conditions.
On the flip side, if you rule out underlying conditions, evaluate the patient for neuropsychiatric conditions,