Laboratory testing is a part of the primary care physician’s daily routine, but ordering more tests does not necessarily improve diagnostic accuracy. Instead, clinicians should order the right test for the right patient and interpret results within the broader clinical context, according to Benjamin Winter, MD, general practitioner and internist in private practice in Tribsees, Germany, and spokesperson for the German Society of General Practice and Family Medicine’s Section on General Practice.

Inflammatory Markers: Not a Substitute for Clinical Assessment

Inflammatory markers, such as C-reactive protein (CRP), are often measured in patients with a suspected infection. However, Winter cautioned against relying on CRP results in isolation.

Some patients with infections, including pneumonia, may have normal CRP levels, whereas elevated CRP levels do not reliably distinguish between bacterial and viral infections.

Speaking with Medscape’s German edition, Winter said, “There is no threshold at which you can say, ‘Above this level, it indicates a viral infection; below this level, a bacterial infection.’” “Despite decades of research, no clinically useful cutoff has been established.”

Instead, Winter advised that CRP is most valuable when interpreted alongside the patient’s history and physical examination.

For example, in rural practice, a markedly elevated CRP level in patients with suspected bowel inflammation may support immediate hospital referral rather than initial outpatient management.

Rheumatoid Arthritis: Laboratory Results Alone Are Not Enough

Appointments with rheumatologists are often difficult to obtain, so primary care physicians increasingly diagnose rheumatoid arthritis themselves, Winter noted. Although rheumatoid factor has long been considered the primary laboratory marker for diagnosis, anti-cyclic citrullinated peptide (anti-CCP) antibodies are now recognized as being more specific. However, both tests have limitations. Some patients with clinically typical rheumatoid arthritis test negative for both rheumatoid factor and anti-CCP antibodies.

“If the blood test is positive, the diagnosis is straightforward,” Winter said. However, negative rheumatoid factor and anti-CCP test results should not rule out rheumatoid arthritis when the clinical presentation is typical, and treatment should be initiated when clinically indicated.

Vitamin D: Routine Testing Rarely Changes Management

Few laboratory tests have generated as much public interest as vitamin D. Vitamin D testing is now widely available in pharmacies and drug stores. For Winter, this is “every family doctor’s nightmare.”

Over the years, vitamin D has been linked to a wide range of health conditions, from COVID prevention to cancer protection.

However, evidence from large, high-quality meta-analyses, including Cochrane reviews, does not support routine vitamin D testing or supplementation in asymptomatic individuals. Likewise, in patients with nonspecific symptoms, such as fatigue or weakness, vitamin D supplementation often does not improve clinical outcomes. “It just makes the blood look better,” Winter said.

Thyroid-Stimulating Hormone (TSH): Mild Elevations Do Not Always Require Treatment

Symptoms such as fatigue, weight gain, and reduced performance often prompt TSH measurements. “In fact, however, such symptoms are only very rarely caused by hypothyroidism,” Winter said.

The treatment thresholds for TSH levels have changed considerably in recent years. Although mildly elevated TSH levels were once considered an indication for treatment, therapy is now generally reserved for patients with TSH levels above established thresholds who also have compatible symptoms. However, many laboratories continue to report older reference ranges.

“Most laboratories report the upper limit of normal as 4.5 mU/L. However, national guidelines recommend considering treatment only when TSH levels exceed 10 mU/L,” Winter said.

D-Dimer: Use Only When Clinical Suspicion Is High

When interpreting D-dimer results, clinical history is essential. D-dimer levels can be elevated for many benign reasons, including minor injuries that cause bruising, nosebleeds, or other conditions associated with increased clotting activity, Winter said.

D-dimer testing is most useful when the pretest probability of venous thromboembolism is high. As an example, Winter described a woman who smoked, was using oral contraceptives, had recently completed a long bus journey, and presented with a swollen, erythematous leg. In this setting, D-dimer testing can help guide subsequent diagnostic evaluations.

In contrast, when the pretest probability is low, an elevated D-dimer result often leads to unnecessary additional testing rather than providing greater diagnostic certainty. According to Winter, rational laboratory testing begins not by drawing blood but by determining whether a laboratory test is likely to answer the clinical question.

This story was translated from Medscape’s German edition.