Always tired: which blood tests provide useful answers

A reference interval contains the middle 95 percent of a reference population. It answers one question: does this result fall within the range found in most of the healthy people studied?

Two points follow. A value near the lower boundary may be statistically unremarkable and still matter clinically for one person. A value can also change substantially within the interval without ever being flagged. A result that falls from 90 in spring to 35 later in the year represents a change that remains invisible on a standard printout.

In short: a laboratory report begins the interpretation. Medical history, examination, and time complete it.

Germany has a useful guideline for unexplained fatigue. The DEGAM S3 guideline on fatigue recommends glucose, a full blood count, ESR or CRP, transaminases or γ-GT, and TSH as initial testing. Additional laboratory investigations should follow when previous findings or specific clinical information support them.

This foundation is our starting point. We extend it selectively when the medical history, physical examination, or course of symptoms provides a reason. A 60-minute first appointment creates the time needed to choose the relevant values.

Ferritin estimates iron stores. The WHO defines depleted stores in adults at a ferritin concentration below 15 µg/l. The range above that threshold deserves clinical attention too.

In a randomised BMJ study, 144 women aged 18 to 55 with unexplained fatigue and no anaemia received either iron or placebo for four weeks. Fatigue improved more in the iron group, with the subgroup effect observed at ferritin concentrations up to 50 µg/l. A later CMAJ study in menstruating women with low ferritin found a reduction in fatigue of almost half from baseline over twelve weeks, approximately 19 percent more than with placebo.

Two limitations matter. Ferritin is an acute-phase protein and rises during inflammation and infection, so it is interpreted alongside CRP. Iron also rarely explains the full picture: fatigue in the BMJ trial remained at 4.5 out of 10 after four weeks of treatment.

In short: ferritin, CRP, the blood count, and transferrin saturation form one picture. Results between 15 and 50 µg/l require an individual clinical assessment.

TSH belongs in initial testing because hypothyroidism can contribute to fatigue, sensitivity to cold, dry skin, and weight changes. Two details are important when reading it.

First, TSH follows a circadian rhythm and varies within the same person. A single borderline result should therefore be repeated before a diagnosis is made, ideally at a comparable time of day.

Second, variation within one person is narrower than variation across the population. A person’s usual range sits within the laboratory interval, which makes change over time clinically useful. If TSH remains elevated or symptoms persist, we may add free T4 and TPO antibodies.

For vitamin D, population data provides useful context. In the DEGS1 survey by the Robert Koch Institute, the average 25(OH)D concentration was around 46 nmol/l, and approximately 62 percent of adults did not reach the 50 nmol/l level used for bone health. Status varies considerably by season, so one February result partly describes a Berlin winter. Methodological standardisation of the measurements substantially reduced the proportion classified as deficient in the same survey, demonstrating how strongly the assay affects interpretation.

For vitamin B12, total B12 alone has limited sensitivity. Holotranscobalamin, or active B12, falls earlier, while functional markers such as methylmalonic acid and homocysteine indicate whether metabolism is already affected. A useful overview appears in the Deutsches Ärzteblatt. The diagnostic advantage of holotranscobalamin remains under discussion, so we interpret these values alongside diet, medication, and symptoms.

In short: season, assay method, diet, and medication belong in the interpretation of both values.

One result describes one day. Treatment needs a direction. We use four steps:

• Baseline. Medical history, examination, and a panel selected for the clinical question.
• Goals. Define in advance what should change, both in measured values and symptoms.
• Implementation. A prioritised plan with manageable actions.
• Review. Repeat relevant measurements after eight to twelve weeks, using the same laboratory and a comparable time of day.

The final step determines how useful the comparison will be. Results from different laboratories and different times of day are only partly comparable. Results collected under consistent conditions show a clearer direction.

Persistent fatigue deserves more than a quick glance at the words “within range.” A sound assessment begins with guideline-based testing, adds selected values when the history and examination support them, interprets results in context, and uses follow-up measurements to evaluate progress.

If you have been tired for months and previous results have provided no explanation, bring them to the appointment. The first consultation lasts 60 minutes, and we review them with you.