From the Guidelines
The most appropriate initial lab work for a patient with unspecified symptoms should be guided by a thorough history and physical examination, and should include a comprehensive metabolic panel (CMP), complete blood count (CBC), thyroid function tests (TSH, free T4), urinalysis, and inflammatory markers such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) as baseline assessments. These tests provide valuable information about organ function, electrolyte balance, and potential infections or anemias. According to the most recent guideline evidence 1, laboratory tests in the evaluation of cognitive or behavioral symptoms should be multi-tiered and individualized to the patient’s medical risks and profile, with routine Tier 1 laboratory studies obtained in all patients.
The diagnostic approach should prioritize a thorough history and physical examination to avoid unnecessary testing while ensuring potentially serious conditions aren't missed. Depending on the patient's age, sex, and risk factors, consider additional testing such as hemoglobin A1c for diabetes screening, lipid panel for cardiovascular risk assessment, and vitamin D and B12 levels to rule out common deficiencies that can cause vague symptoms. If the patient reports specific symptom patterns, targeted testing may be warranted - for example, ferritin for fatigue, troponin for chest pain, or liver function tests for abdominal complaints. As recommended by the Alzheimer's Association clinical practice guideline 1, when diagnostic uncertainty remains, the clinician can obtain additional laboratory tests guided by the patient’s individual medical, neuropsychiatric, and risk profile.
Previous studies have shown that routine laboratory testing is not always necessary and that selective testing based on clinical evaluation is often more appropriate 1. However, the most recent evidence suggests a more individualized approach, taking into account the patient's medical risks and profile. After initial testing, follow-up investigations can be determined based on preliminary results and the evolution of symptoms. Key considerations include:
- Comprehensive metabolic panel (CMP) and complete blood count (CBC) as baseline assessments
- Thyroid function tests (TSH, free T4) and urinalysis
- Inflammatory markers such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)
- Additional testing based on patient's age, sex, and risk factors, such as hemoglobin A1c, lipid panel, vitamin D, and B12 levels
- Targeted testing based on specific symptom patterns, such as ferritin, troponin, or liver function tests.
From the Research
Lab Work for Unspecified Symptoms
When a patient presents with unspecified symptoms, it can be challenging to determine the appropriate lab work to order. However, based on the available evidence, here are some considerations:
- Thyroid function tests, such as Thyroid-Stimulating Hormone (TSH), free thyroxine (FT4), and triiodothyronine (T3), may be useful in evaluating patients with symptoms such as anxiety, insomnia, palpitations, unintentional weight loss, diarrhea, and heat intolerance 2, 3, 4.
- TSH level is the preferred test for initial evaluation of suspected primary hypothyroidism, and if TSH is abnormal, a free thyroxine (T4) level will further narrow the diagnosis 4.
- If TSH is undetectable and free T4 is normal, a triiodothyronine (T3) level may be obtained 4.
- In patients with metabolic syndrome, thyroid function tests may reveal increased TSH levels with normal T3 and T4, suggesting thyroid receptor resistance 5.
- In patients with COVID-19, basal cortisol levels may be elevated, and this may be associated with disease severity, particularly in patients with diabetes mellitus 6.
Considerations for Lab Work
When ordering lab work for a patient with unspecified symptoms, consider the following:
- Clinical presentation and medical history
- Physical examination findings
- Potential underlying conditions, such as thyroid dysfunction or metabolic syndrome
- The need for additional testing, such as thyroid scintigraphy or adrenal function tests, depending on the initial lab results and clinical presentation 2, 3, 4, 6, 5