Fatigue and Low Energy Workup: Labs and Differential

What it does

The Fatigue / Low Energy Workup is a tiered checklist for the non-psychiatric causes of low energy. As you tick findings, the results panel builds a suggested laboratory workup and a differential diagnosis, and it flags red-flag findings that warrant urgent evaluation. It starts by asking what the patient means by "tired": sleepy or dozing (prioritize sleep disorders such as obstructive sleep apnea, insufficient sleep, and narcolepsy), low energy or worn out (pursue the systemic differential), or weak or short of breath (prioritize neuromuscular, cardiac, and pulmonary causes).

The three tiers

• Tier 1, red flags (screen first): unintentional weight loss, fever or night sweats, lymphadenopathy or hepatosplenomegaly, unexplained bleeding or pallor, cardiac symptoms, and focal neurologic signs. Any red flag triggers an alert to expedite evaluation before attributing fatigue to a benign or psychiatric cause.
• Tier 2, common pointers (ask in every case): sleep, thyroid, glucose, anemia, heart failure, lung disease, sedating medications, substances, nutrition and GI, and mood.
• Tier 3, targeted or rare (on specific clues): adrenal insufficiency, hemochromatosis, hypercalcemia, autoimmune disease, hypogonadism, chronic infection, tick exposure, environmental toxins, kidney or liver disease, neuromuscular disease, post-exertional malaise, and possible pregnancy.

Suggested labs

Six first-line tests are listed for most patients with unexplained, persistent fatigue: CBC with differential, TSH (with or without free T4), a comprehensive metabolic panel, HbA1c or fasting glucose, ferritin and iron studies, and CRP and/or ESR. Each checked finding adds its own targeted or second-line tests (for example polysomnography for suspected sleep apnea, or BNP and echocardiogram for heart failure) and its differential, with duplicates removed.

Report and limitations

The EMR-ready summary lists the date, the complaint type, any red flags, the Tier 2 and Tier 3 findings, first-line and targeted labs, and the differential. The tool is decision support only. Untargeted testing is low-yield, and the suggestions do not replace history, examination, clinical judgment, or age-appropriate cancer screening. The companion chapter, Low Energy: The Non-Psychiatric Workup, covers the topic in full.