According to the American Thyroid Association, 12+ percent of the U.S. population will develop a thyroid condition. An estimated 20 million Americans have a thyroid disorder or disease. As many as 60 percent of those affected are unaware of their condition. Women are affected by thyroid disorders more often than men.[reference]

If you tell your doctor you are concerned about thyroid problems, he or she will probably order a lab test. But what if the test comes back negative, yet your symptoms persist? Let’s say you can’t lose weight, always feel tired, and just feel terrible in general. You and your doctor are probably baffled by your normal thyroid blood test results.

Some thyroid problems cause symptoms without showing up on the standard thyroid panel. For example, you may be symptomatic but can’t detect the issue because your thyroid labs are in the normal range? If so, you may suffer from a less common thyroid disorder or thyroid-related dysfunction.

Patterns of Thyroid Symptoms and Dysfunction

Thyroid dysfunction and disease follows several different patterns. If you suspect you may have thyroid problems, the signs and symptoms you experience are an essential clue to understanding your issues.

Textbook Thyroid Disorders

Doctors are trained to look for common forms of thyroid dysfunction. They do this by reviewing mainstream medical guidelines that describe symptoms. Then they order the matching bloodwork to confirm the diagnosis.

Hypothyroidism

Hypothyroidism is the condition of having too little thyroid hormone. Signs and symptoms include a swollen thyroid gland, fatigue, lethargy, feeling cold all the time, hair loss or hair dryness, dry skin, high cholesterol, irritability, slow heart rate, and weight gain.

If your doctor suspects you have hypothyroidism, he or she will probably order a test for TSH (thyroid stimulating hormone). TSH is an endocrine hormone secreted from your pituitary. It tells your thyroid gland, located in your neck, to release thyroid hormones called T4 and T3.

High TSH is how most doctors confirm you have hypothyroidism. If your TSH test is low or normal, your doctor will likely conclude you don’t have hypothyroidism.

Hyperthyroidism

Hyperthyroidism is the opposite of hypothyroidism: too much thyroid hormone. Signs and symptoms of hyperthyroidism include unexpected weight loss, rapid or irregular heartbeat, other heart problems, excessive sweating, poor sleep quality, irritability, and a swollen thyroid gland. Some people with hyperthyroidism don’t experience noticeable symptoms.

If your doctor thinks you may have hyperthyroidism, he or she will order blood tests for TSH, T4, and T3. If your TSH levels are low, and your T4 or T3 levels are high, you will receive a hyperthyroidism diagnosis.

Hashimoto’s and Thyroid Autoimmune Disorders

Hashimoto’s and thyroid autoimmune disorders involve the disruption of thyroid function due to the immune system attacking the thyroid gland. They typically result in hypothyroidism. If you have high TSH and symptoms of hypothyroidism, your doctor may order lab tests. The levels of your thyroid antibodies might indicate whether you have an autoimmune issue that’s causing hypothyroidism.

Tumors of the thyroid gland or cancers affecting the thyroid or endocrine system (hypothalamus and pituitary) can also cause thyroid disease. Depending on the issue, this type of thyroid disease can cause hypothyroidism, hyperthyroidism, or thyroid issues that come and go.

Other Thyroid Issues

These thyroid problems can cause symptoms of classical hypothyroidism, but with subtle differences that can confuse anyone but a specialist in thyroid dysfunction.

Secondary Hypothyroidism

Secondary hypothyroidism is a form of hypothyroidism caused by pituitary dysfunction. The pituitary is a pea-sized gland attached to the base of the brain that controls the release of other endocrine glands like the thyroid. Chronically high levels of cortisol, one of your body’s main stress hormones, may lead to secondary hypothyroidism.

Chronic high levels of stress can create conditions that lead to secondary hypothyroidism. Other causes include blood sugar issues like hypoglycemia, insulin resistance, and high blood sugar levels. Sometimes a concussion or traumatic brain injury can reduce the function of the hypothalamus and pituitary, leading to secondary hypothyroidism.

In secondary hypothyroidism, your pituitary gland is unable to release enough TSH to produce T4 and T3. That’s why it’s difficult to detect: most doctors are trained to assume that hypothyroidism results in high TSH, whereas secondary hypothyroidism is a result of low TSH.

T4 to T3 Under-Conversion

Your thyroid hormone produces two main forms of thyroid hormone: T4 (also called thyroxine) and T3 (also called triiodothyronine). 80-90% of the thyroid hormone released from your thyroid is in the form of T4, and the rest is T3.

T4 is less active in the body than T3. Most cells in your body cannot utilize T4, which is why T4 is converted in tissues throughout your body into the more active T3. In under-conversion, the conversion of T4 into T3 is impaired, resulting in low thyroid hormone activity throughout the body despite normal TSH and T4 levels.

Causes of under-conversion include high cortisol levels, nutritional imbalances, and inflammation. Patients with under-conversion experience hypothyroid symptoms with normal lab results on TSH and T4, but have lower blood levels of T3.

Elevated Thyroid-Binding Globulin

Along with controlling the release of TSH, another way your body modulates the function of thyroid hormones in your body is with a transport protein called thyroid-binding globulin (TBG). TBG binds or “sticks” to thyroid hormones and renders them inactive as they’re transported through your bloodstream. If you have too much TBG, your thyroid is producing enough thyroid hormones, but TBG is inactivating them.

Elevated thyroid-binding globulin can be caused by sex hormone imbalances, like excessive estrogen levels, or by use of oral contraceptives in women.[reference] Patients with elevated TBG will have normal TSH, normal T4, low T3, high T3 uptake, and high TBG test numbers.

Decreased Thyroid-Binding Globulin

High levels of thyroid-binding globulin are a problem, but low TBG can also cause thyroid issues. Under conditions of decreased TBG, thyroid hormones temporarily become overactive because they aren’t bound to the transport protein. Over time, this overactivity can cause resistance to the effects of thyroid hormone, resulting in hypothyroid symptoms. Although there is plenty of thyroid hormone available in your body, your cells are unable to utilize it.

High levels of testosterone can cause decreased TBG levels.[reference] Low TBG is more common in women with polycystic ovarian syndrome (PCOS) and insulin resistance, each of which can lead to increased testosterone.

Patients with decreased TBG levels will have normal TSH, normal T4, high T3 levels, low T3 uptake, and low thyroid-binding globulin show up on their blood test results. To manage decreased TBG, insulin sensitivity and blood sugar tests — like fasting blood glucose, fasting insulin levels, glucose tolerance test, and hbA1C — are also helpful.

Resistance to Thyroid Hormones

In thyroid hormone resistance, thyroid hormone levels (TSH, T4, and T3) are normal, but cellular resistance creates thyroid dysfunction. This thyroid disorder is difficult to pinpoint because it doesn’t show up on tests.

An inherited genetic disorder causes some cases of thyroid resistance syndrome.[reference] High body-mass index, acute illness, and chronic stress are also linked to thyroid hormone resistance.[reference][reference]

Reverse T3

Reverse T3, or rT3 for short, is a hormone that’s structurally similar to T3, but resembles a mirror image of the active T3 molecule. Many cells in your body have thyroid receptors, which are like a lock-and-key system that allows thyroid hormone to act on your cells. At the cellular level, T3 activates the thyroid receptor, while reverse T3 inhibits it.

Reverse T3 is one way your body regulates thyroid function to stay in homeostasis, a healthy state of balance. When you are ill, stressed, or starving, your body will begin to convert T4 into reverse T3 instead of active T3. Reverse T3 is your body’s way of putting the brakes on your metabolism to conserve energy and counteract the effects of stress.

Some people get “stuck” in a high rT3 state due to chronic illness, stress, or overzealous attempts to lose weight. If you have high rT3, your TSH and T4 levels will be normal, but you will have high rT3 values and may have low levels of T3.

The Thyroid Test Gap

If you have symptoms of thyroid problems, but your lab results come back normal, you may have fallen into a testing “gap” most doctors don’t know exists. That means your hypothyroidism is clinically different from the more common forms of thyroid disorder.

For patients with uncommon thyroid problems, the standard thyroid testing parameters are flawed, but you can order additional tests to get a better idea of what’s going on with your body.

Who Should Get Tested?

If you have symptoms of hyperthyroidism, especially if they come and go, you may benefit from requesting another test for TSH, T4, and T3 hormone levels.

Our standard thyroid panel results came back normal, but you have the following hypothyroidism symptoms and you should consider more extensive testing for other thyroid issues:

  • Goiter (swelling in the front of the neck)
  • Fatigue
  • Cold sensitivity
  • Constipation
  • Dry skin
  • Sudden or unexplained weight gain
  • Puffy face
  • Muscle weakness or cramps
  • High cholesterol levels
  • Achy, tender, stiff muscles
  • Painful, stiff, or swollen joints
  • Heavy, disrupted, or irregular menses
  • Thinning hair
  • Slow heart rate
  • Depression issues
  • Brain fog
  • Infertility or miscarriage
  • Low sodium
  • History of autoimmune disease
  • Macrocytic anemia

Chances are if you went to your doctor to discuss thyroid problems, he or she ordered a thyroid-stimulating hormone (TSH) test. He or she may have also ordered a thyroxine (T4) test. However, these tests do not necessarily rule out uncommon thyroid disorders. You may have fallen into the thyroid testing gap.

Which Thyroid Tests to Order?

Comprehensive thyroid testing means testing more than just TSH and T4. TSH and T4 don’t tell the whole thyroid story. If you are concerned about less than optimal thyroid function, you can request additional tests to gain clarity.

Depending on your symptoms and medical history, the following tests can help detect less common thyroid problems and their causes:

  • Thyroid Stimulating Hormone (TSH)
  • Free T4 (FT4)
  • Thyroxine (T4)
  • Free T4 Index (FTI)
  • Reverse T3 (rT3)
  • Free T3 (fT3)
  • Thyroid Antibody Tests
  • Thyroid-Binding Globulin (TBG)
  • DUTCH Test
  • Fasting Blood Glucose
  • Fasting Insulin
  • Hemoglobin A1C (hbA1C)
  • Estradiol
  • Total Testosterone
  • Iron
  • Selenium

Understanding Test Results

Did you get normal results for your TSH or T4? If so, you can use TSH, T4, T3, FT4, and FTI to take a more in-depth look at your thyroid function. Even though some levels may be normal, you still need to retest them each time you get other thyroid lab work done. This will allow you to get a full picture of your thyroid function.

Reverse T3 can cause hypothyroid symptoms like weight gain and fatigue, even when TSH is normal. By testing rT3, you can determine whether it’s a hidden culprit in your hypothyroid symptoms. If your rT3 to T3 ratio is high, your body will be unable to use T3 normally.

Additional Testing

Thyroid antibody tests are useful if you or your doctor suspect you may have an autoimmune thyroid disorder like Hashimoto’s.

High levels of thyroid-binding globulin inactivate circulating thyroid hormones, which can cause hypothyroid symptoms. A TBG test can allow you to detect the root cause of your hypothyroid symptoms, even when TSH comes back normal.

The DUTCH test is an assessment of cortisol and other stress markers, which can be helpful for you or your doctor to determine the cause of thyroid problems like secondary hypothyroidism or under-conversion of T4 to T3.

Fasting blood glucose, fasting insulin, and hbA1C are markers of blood sugar imbalance and insulin resistance. Problems with blood sugar and insulin can contribute to secondary hypothyroidism and decreased thyroid-binding globulin levels.

Estrogen and testosterone, your body’s sex hormones, can also affect your body’s TBG levels. Too much estrogen can cause high levels of thyroid-binding globulin, while too much testosterone can cause decreased levels of TBG.

Iron and selenium are cofactors for the conversion of T4 to T3 in your body, meaning your body requires these minerals for optimum thyroid function. Deficiencies of iron and selenium can result in under-conversion of T4 to T3.

Other Testing Concerns

Screening for thyroid problems can be a delicate and complicated process. Knowing which tests to request for a better overview of your body’s thyroid function is a good start, but you must also be aware of other issues related to thyroid testing.

“Normal” ranges of TSH, T4, and other thyroid hormone tests can vary from one lab to another. This issue confuses patients and doctors and impedes effective treatment. The reason lab reference ranges vary for thyroid markers is because laboratories determine normal values using the “bell curve” method.

When you get a blood test, your results include your value — shown as an absolute number, like 1 milliunit per liter TSH — and a “reference range,” which is the so-called normal value for TSH. But the bell curve method means that what’s considered normal for thyroid lab values is based on the average value of patients who order thyroid tests, not on average values of healthy people or other evidence for determining a healthy TSH level.

Until recently, the TSH reference range at most labs was much higher than it is now, resulting in underdiagnosis of thyroid problems. Because of the prevalence of thyroid disorders, the reference range for TSH is still high enough that some people have thyroid problems — called subclinical thyroid disorders — and fall within the “normal” TSH range.

One solution to the issue of unreliable reference ranges is to find a doctor who uses specialized ranges, like a functional medicine doctor, or a thyroid specialist.

How to Manage Thyroid Problems

The standard method for treating hypothyroid problems is to prescribe levothyroxine (synthetic T4), but not every patient needs thyroid medication, and some disorders respond poorly to T4 monotherapy.

If you decide to take thyroid medication, be sure to request follow up lab tests beyond TSH and T4. Adjusting medication based on symptoms as well as lab results is a wise strategy.

If T4 monotherapy doesn’t work for you, or if you have an issue like under-conversion of T4 to T3 or high rT3, consider adding in T3 in the form of liothyronine (brand name Cytomel). It is a great way to ensure active thyroid hormone is available for your body to use.

Diets, Minerals and Thyroid Function

In order to be on the safe side, those with thyroid issues should avoid fluoride. Check toothpaste ingredients and drinking water. Standard concentrations of fluoride levels in drinking water are proven to impact TSH, T4, and T3 levels negatively.[reference]

Additionally, crash dieting can cause elevated rT3 levels and also mimic hypothyroid problems in other ways. If you have trouble losing weight, extreme diets are not the answer to your problems, especially if you are having thyroid symptoms.

Leptin resistance can elevate reverse T3, mimic thyroid symptoms, and cause thyroid autoimmunity.[reference] Leptin is an energy regulation hormone, sometimes called the fat-burning hormone. Scientists have linked leptin resistance with excessive fat storage, reduced energy expenditure, low energy levels, and obesity.[reference]

High carbohydrate intake, particularly processed carbs, can temporarily increase T3 levels, resulting in iodine deficiency over time.[reference] If you are trying to balance your thyroid levels and function, be sure to eat a moderate or low-carb diet.

Thyroid problems are associated with both iodine deficiency and iodine excess.[reference] Therefore, if you don’t use iodized salt, be sure to get at least 150 micrograms of iodine in your diet from natural sources. Be careful not to consume excessive quantities of iodine.

Here at Complete Care we don’t only take into account the labs, we also look at the symptoms.