What basic evaluation is recommended for an adult patient with unexplained weight loss?

Recommended Basic Evaluation for Unexplained Weight Loss

All adults with unexplained weight loss require a comprehensive metabolic panel, complete blood count, thyroid function tests (TSH), HbA1c, and chest X-ray as the foundational diagnostic workup. 1, 2

Quantifying Clinical Significance

Before initiating any workup, calculate the percentage of body weight lost:

• Weight loss >5% over 3 months or >10% over 6 months is clinically significant and mandates full evaluation 1, 2
• Document current BMI, as BMI <18.5 kg/m² (or <20 kg/m² if age >70 years) indicates severe undernutrition requiring urgent intervention 1, 2

Core Laboratory Panel

The initial laboratory evaluation should include:

Essential Tests

• Complete blood count (CBC) to screen for anemia, infection, and hematologic malignancy 1
• Comprehensive metabolic panel including electrolytes, renal function, glucose, calcium, liver enzymes, and serum albumin 1, 2
• Thyroid-stimulating hormone (TSH) to evaluate for hyperthyroidism or hypothyroidism 1, 2, 3
• Hemoglobin A1c or fasting glucose to screen for diabetes mellitus, as severe hyperglycemia with catabolic features commonly causes weight loss 1, 2
• Fasting lipid profile as part of comprehensive metabolic evaluation 2

Important Caveat About Albumin

Do not interpret low serum albumin as confirming malnutrition—it reflects systemic inflammation or acute illness severity rather than nutritional status 2. Albumin lacks specificity for diagnosing malnutrition and is highly sensitive to inflammation 2.

Mandatory Imaging

• Chest X-ray should be ordered for all patients given the high prevalence of lung malignancy (22-38% of significant weight loss cases are due to malignancy) 1
• Contrast-enhanced CT of chest, abdomen, and pelvis is recommended when initial evaluation does not reveal a clear cause, as occult neoplasms are common 1

Symptom-Directed History

Elicit specific symptoms to guide further evaluation:

Gastrointestinal Assessment

• Ask about dysphagia, abdominal pain, changes in bowel habits, bleeding, and early satiety, as gastrointestinal disorders account for approximately 30% of cases 1, 2

Constitutional Symptoms

• Assess for fever, night sweats, and pain characteristics to identify infectious, inflammatory, or malignant processes 1

Neurologic Red Flags

• If headaches accompany weight loss, urgent brain MRI with contrast is mandatory to exclude intracranial pathology 1
• Ophthalmologic examination should be performed urgently to assess for papilledema indicating increased intracranial pressure 1

Critical Medication Review

Review all current medications, as certain drugs cause weight loss:

• Antidepressants (particularly SSRIs) 4, 1
• Metformin and other antihyperglycemics 4, 1
• Consider alternatives if current medications are contributing 1

Psychiatric and Nutritional Screening

• Screen for depression, anxiety, eating disorders, and substance abuse, as psychiatric disorders account for 16% of cases when organic causes are excluded 1, 2
• Use validated nutritional screening tools such as MUST (Malnutrition Universal Screening Tool), NRS-2002, or Subjective Global Assessment 1, 2

Physical Examination Priorities

Beyond vital signs, specifically assess:

• Palpate thyroid and assess for tremor, tachycardia, or bradycardia 1
• Examine for lymphadenopathy, hepatosplenomegaly, and abdominal masses to detect occult infection, hematologic disease, or malignancy 1
• Inspect skin for acanthosis nigricans, hirsutism, and external signs of malignancy (skin lesions, oral lesions, breast masses) 1
• Assess for muscle wasting and subcutaneous fat loss 4

Age and Sex-Specific Considerations

For Women

• Mammography should be performed in all female patients as part of initial workup 1
• Measure CA 15-3 and CA 125 if gynecologic malignancy is suspected 1
• Consider pregnancy testing in women of childbearing age 5

For Men

• Obtain prostate-specific antigen (PSA) if prostate cancer is possible 1
• Order α-fetoprotein (AFP) and β-hCG if germ-cell tumors are suspected 1

When to Pursue Endoscopy

• Gastroscopy and colonoscopy are recommended whenever gastrointestinal symptoms suggest a primary tumor or when age-appropriate cancer screening is due 1
• Colonoscopy remains the standard screening tool for colorectal cancer in this population 1

Common Pitfalls to Avoid

• Watchful waiting is only appropriate if baseline evaluation is completely normal, patient remains clinically stable, and close monitoring can be ensured 1
• Do not delay evaluation in patients with >5% weight loss, as the likelihood of finding serious pathology is high 1, 2
• Never rely on BMI alone—it does not measure adipose tissue distribution or function, nor does it factor in weight-related health consequences 4

Follow-Up Strategy

• For patients with comorbid conditions like heart failure or unexplained weight changes, monitor weight more frequently than annually 1
• Consider inpatient evaluation if deterioration of medical status occurs 1