Why Am I Always Tired? Lab Tests That Explain Fatigue

You’ve probably tried everything to figure out why you’re tired and you finally bring it up to your health care provider. Tiredness or fatigue is a symptom caused by anything from sadness to chronic inflammation to serious physical conditions. There are some common underlying conditions that could be the cause no matter what you do to get your energy back.

Your health care provider might have ordered some broad testing to start with such as a CBC, thyroid tests, iron studies, and maybe a few others based on your issues. What are these tests, how can you prepare for them, and how will these test results help with your fatigue?

What are the CBC, iron studies, and thyroid tests?

CBC stands for complete blood count. This is a panel of tests that screens important cells in the blood such as white blood cells, red blood cells, and platelets, and then evaluates their quality. It is important to have the right amount of these cells and to have enough hemoglobin in your red blood cells. Hemoglobin is a protein found inside the red blood cell. The hemoglobin protein found inside the red blood cell has iron. The iron carries oxygen from the lungs to the tissues of the body. It returns carbon dioxide to the lungs. If you don’t have enough hemoglobin, you can’t deliver enough oxygen to your cells and this will cause fatigue.

Iron is the most common deficiency in the world and can cause fatigue as one symptom. Iron studies performed at the same time as the CBC will allow your health care provider to compare the two sets of results. Iron studies usually include blood iron levels, ferritin, transferrin levels, and the saturation of transferrin. Ferritin is a protein that holds iron for storage. Transferrin is a protein that transports iron. Think of transferrin as a passenger train for iron. Transferrin is normally 20-50% saturated or think of it as 20-50% of the train seats are full. Iron gets transported to the bone marrow where hemoglobin is made.

The best test for thyroid health is the TSH or thyroid stimulating hormone. This hormone stimulates the thyroid gland which is important for metabolism and energy. The TSH will assess if your thyroid is managing your metabolic rate adequately.

Why are these tests ordered?

Anemia is a possible cause of fatigue and is commonly caused by a low hemoglobin. The CBC will have a hemoglobin result. If you have low iron levels, this can cause anemia and fatigue. If your iron is low, the iron studies will show why. The TSH is ordered because a slow metabolism can cause fatigue. These tests are ordered because the reasons for fatigue require different treatments and maybe further testing.

How should you prepare for the test?

The tests require a blood sample. No preparation is needed for the CBC, but it is best to collect all future CBC tests at the same time of the day as these numbers will vary during the day. A fasting, morning specimen is best for the iron studies because iron levels can change throughout the day. The specimen for TSH can be collected at the same time as the other tests. If you are taking thyroid medications, wait until at least two hours after you take the medication for the specimen collection.

What do the results mean?

The CBC can be thought of as a general screening test so there are quite a number of possible interpretations. The red blood cell count tells you if there are enough cells to carry the hemoglobin. The hemoglobin test can help to determine if you have anemia or some other problem with red cells while the other red blood cells help to determine the cause. The white blood cell count helps to determine if there is some type of inflammation or on-going stress. The differential helps to determine what the cause might be.

Anemia

Anemia is determined by the hemoglobin level and this varies by sex and age. See the table below to find which category fits you and determine if you may be anemic. There are several reasons for anemia and low iron is just one of them.

Your CBC will have a result for MCV which stands for mean corpuscular volume. A low MCV means the red blood cells are small and a high MCV means the red blood cells are large. A low MCV is common in iron deficiency anemias and a high MCV is often from vitamin B12 and/or folate deficiency. You may hear your health care provider refer to a low MCV as microcytic anemia. This means the red blood cells are smaller than normal. If your health care provider indicates you have a macrocytic anemia, this means the red blood cells are larger than normal. The CBC also has an MCHC result which stands for mean corpuscular hemoglobin concentration. This shows how much hemoglobin is inside your red blood cells. This is often decreased in iron deficiency anemia.

Iron Deficiency

You may be iron deficient and your hemoglobin in your red blood cells hasn’t been affected yet. Low iron will eventually cause a decreased hemoglobin, MCV, and MCHC if it hasn’t already. There are several reasons for iron deficiency and iron studies can help determine the cause. Iron deficiency can be caused by decreased iron intake, decreased iron absorption, or even hemorrhage from menstruation.

Here are some common patterns in conditions for iron deficiency:

Decreased iron intake: low blood iron, low ferritin, high transferrin, low transferrin percent saturation. Think of the passenger train. There will be a lot of transferrin available to transport the much-needed iron to the bone marrow, but there isn’t much iron to transport.

Decreased iron absorption in the intestines: Iron is not made in the body and must be obtained through diet. From foods, iron is then absorbed into the body through the small intestine if there is an issue within the intestine such as inflammation, this may cause a decrease in iron absorption. One example is Crohn's disease. As these may be a chronic (long term) issue, iron studies typically show a low iron level yet a high ferritin level.

Decreased bone marrow iron absorption: if the bone marrow can’t absorb the iron transported by transferrin, transferrin will be increased and saturated. This is like many passenger cars that are full of passengers.

Hemorrhage: Iron is always lost in a hemorrhage. You can become anemic if iron isn’t replenished fast enough because your body must make new red blood cells from hemorrhage. Your transferrin would be increased, but you may or may not have a normal saturation of iron depending on iron replenishment.

Thyroid Tests

A healthy thyroid gland is essential for a normal metabolism to be able to supply energy for daily activities. The thyroid gland is controlled by a small gland in your brain called the pituitary gland. The pituitary gland produces a hormone called Thyroid Stimulating Hormone (TSH). The thyroid produces the hormone Thyroxine (T4) to stimulate many metabolic functions in the body for energy. If you need more energy, the pituitary gland makes more TSH. The thyroid gland “sees” more TSH and then produces more T4. Your Doctor may use the term T4 when they are thinking of checking your thyroxine level.

If your thyroid gland produces less T4 hormone, then your thyroid gland is considered underactive. If your thyroid is underactive, a symptom you will have fatigue. An underactive thyroid gland, also known as hypothyroidism, requires a lot of stimulation from the thyroid stimulating hormone (TSH). If you have a high TSH result and a low T4, this indicates hypothyroidism.

When a doctor orders a thyroid function blood test, they are requesting to check TSH and T4 levels. In the clinical laboratory, TSH will be checked first. If the TSH is in the reference interval no further testing is needed. If the TSH is outside the reference interval, then T4 will be checked. There are 2 types of T4 tests. One is called Free T4 (FT4) the other is Total T4 (TT4). The most commonly ordered is Free T4.

Questions to ask your provider:

Should my CRP be tested to detect inflammation? Inflammation can impair iron absorption. Inflammation can also affect my results by increasing ferritin and decreasing transferrin. Inflammation can make it difficult to interpret my iron studies.

Should a reticulocyte be ordered if my hemoglobin is low? A reticulocyte test measures the number of young (immature) red blood cells. Is my bone marrow able to normally produce red blood cells?

If my MCV is high, should my B12 and folate be tested?

Do I have healthy kidneys and liver? The kidneys tell the bone marrow to produce red blood cells and the liver makes the proteins such as transferrin. Unhealthy kidneys can lose valuable proteins in the urine such as transferrin and decrease my transferrin result.

Does my ferritin level need to be tested to assess iron storage? Should a CRP be ordered with the ferritin since ferritin can be falsely elevated from inflammation? Is my RDW (red cell distribution width) within normal limits? Did my anemia happen recently or slowly over time?

If my TSH is high, should a thyroxine level be tested, (also known as Free T4) to confirm hypothyroidism?

I’m fatigued and my results are normal. Are there any other tests that can be performed to rule out other conditions?

Final takeaway

There are several causes of fatigue. If laboratory tests are performed it is important to correctly interpret them to get the correct treatment for fatigue. The following are some important influencers on laboratory results:

1. Oral contraceptives can increase ferritin and transferrin results.

2. Inflammation can increase ferritin, but decrease transferrin results.

3. Diminished liver and kidney function can affect laboratory results.

Author: Dr. Elizabeth Fisher DCLS, MHA, CC(NRCC), MLS(ASCP)CM, PBTCM is a qualified High Complexity Laboratory Director (HCLD), Clinical Consultant, and Medical Laboratory Scientist (MLS) generalist.

Brihi, J., Normal and Abnormal Complete Blood Count with Differential. StatPearls. Updated June 8, 2024. Accessed from: Normal and Abnormal Complete Blood Count With Differential Article

Guideline on Haemoglobin Cutoffs to define Anaemia in Individuals and Populations. World Health Organization. March 5, 2024. Accessed from: Guideline on haemoglobin cutoffs to define anaemia in individuals and populations

Ems, T., Lucia, K., Biochemistry, Iron Absorption. StatPearls. Updated April 17, 2023. Accessed from: Biochemistry, Iron Absorption Article