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In medicine, an accurate diagnosis is critical to determine the most effective course of treatment. Often, when a patient gets back normal thyroid blood test results, but they still experience hypothyroid symptoms, they're left wondering what's wrong and what to do next.
Ahead, a look at each thyroid biomarker, how to interpret thyroid function patterns, and what to do if you still experience hypothyroid symptoms with normal labs.
It's first helpful to understand how the thyroid works to understand your thyroid blood test results.
The thyroid gland is part of the endocrine system, located at the base of the neck. The hypothalamus, pituitary gland, and the thyroid gland all work together to regulate thyroid hormone function. Thyrotropin-releasing hormone (TRH) from the hypothalamus signals the release of thyroid-stimulating hormone (TSH) from the pituitary gland. TSH then stimulates, as the name implies, the production of thyroid hormones from the thyroid gland.
The thyroid gland produces an inactive thyroid hormone called thyroxine (T4) and an active thyroid hormone called triiodothyronine (T3). The inactive thyroid hormone converts peripherally (meaning, in tissues other than the thyroid) to either activate thyroid hormone (T3) or an alternative inactive thyroid hormone (reverse T3).
As mentioned, the thyroid gland gets input from the hypothalamus via the pituitary gland. In return, free T3 and free T4 send feedback to the hypothalamus and pituitary glands to regulate normal function.
When the hypothalamus senses low thyroid hormone levels, it increases TRH, causing the pituitary gland to increase TSH. The elevated TSH levels then increase thyroid hormone production, returning the body to normal function.
Alternatively, if thyroid levels become too high, the hypothalamus stops sending TRH to the pituitary. Then, the pituitary stops sending TSH to the thyroid. The thyroid stops the production and release of thyroid hormone until proper thyroid function levels restore.
Small changes in free T3 or free T4 can result in significant changes in TSH. However, small changes in TSH may not reflect significant changes in free T3 or free T4.
Each person has a particular set point for their free t3 and free T4 levels—a physiological value around which the normal range fluctuates. So, changes in a patient's free T3 or free T4 levels within the normal range may result in an abnormal TSH value. This relationship indicates that TSH, in the absence of hypothalamic or pituitary disease, is a very sensitive marker and why it's historically been the primary test for thyroid function.
Thyroid-stimulating hormone (TSH)
Traditionally, many doctors only test for thyroid-stimulating hormone (TSH) to assess thyroid health. Still, it doesn't always give a complete picture of what's happening with the thyroid.
Experts continue to debate the upper and lower limits of normal TSH levels. We recommend that you work with a trustworthy doctor who takes a comprehensive approach to understand your TSH values as they relate to the other markers.
Free thyroxine (T4)
Thyroxine is the biologically inactive form of thyroid hormone in your blood. It is responsible for digestion, heart rate, muscle formation, brain development, and healthy bones. The thyroid gland produces T4, and it is transformed into T3 by organs, including the liver and kidneys.
Thyroxine exists in two forms in the body: free T4 and bound T4. Free (unbound) T4 does not bond to the protein in your blood, which allows it to enter the body tissues that need to use it. However, most of the T4 in the bloodstream is bonded to protein (known as bound T4), preventing it from entering these tissues.
Free triiodothyronine (T3)
Triiodothyronine is the biologically active form of thyroid hormone, with 20% produced from the thyroid gland and 80% converted from thyroxine (T4) that has been processed by the liver and kidneys. T3 plays a vital role in all metabolic functions in the same way that T4 does.
Like T4, nearly all of the triiodothyronine (T3) found in the blood bounds to protein. The rest is unbound (free).
Thyroid peroxidase (TPO) antibodies
Thyroid peroxidase (TPO) is one of the primary enzymes involved in the production of T3 and T4, catalyzing several steps in the process. However, suppose there are elevated levels of antibodies in the blood. In that case, it suggests that your immune system is attacking normal, healthy tissue. The presence of TPO antibodies outside the normal range likely indicates the presence of Hashimoto's thyroiditis.
On their own, the presence of thyroid antibodies does not necessarily mean hypothyroidism. Instead, Hashimoto's is the most common cause of hypothyroidism. So, the presence of thyroid antibodies may predict the risk of developing hypothyroidism. It's important to monitor thyroid function to take action before the disease progresses.
Patients may experience elevated levels of TPO antibodies for many years before noticing any hypothyroid symptoms. However, with progression, the thyroid becomes less and less capable. You may begin to experience signs and symptoms of an underactive thyroid.
Low TSH and high FT4 (and FT3)
This pattern may indicate primary hyperthyroidism.
High TSH and low FT4 (and FT3)
This pattern may indicate primary hypothyroidism.
Low TSH and normal FT4 and/or FT3
This pattern may indicate subclinical hyperthyroidism, characterized by "normal" thyroid hormone levels but low TSH.
High TSH and normal FT4 (and FT3)
This pattern of results may indicate subclinical hypothyroidism, characterized by "normal" thyroid hormone levels but high TSH. In this instance, a measure of TPO antibodies may guide decision-making because a positive reading of TPO antibodies predicts a higher risk of progression to overt hypothyroidism.
Low FT4 (and/or low FT3) with (inappropriately) normal or low TSH
This pattern of results may indicate non-thyroidal illness. However, suppose there isn't an apparent alternative diagnosis. In that case, your doctor might consider the possibility of central hypothyroidism (e.g., a disorder of the hypothalamus or pituitary glands).
High FT4 (and/or high FT3) with (inappropriately) normal or elevated TSH
This unusual pattern may indicate assay interference or confounding effects of medication.
It can feel frustrating to get your lab results back only to learn that everything is "normal," despite not feeling that way. It's certainly possible to still have low thyroid symptoms with normal labs.
Ahead, other factors that may be contributing to your symptoms. Of course, none of these is a medical diagnosis. We recommend that you work with a doctor who takes a proactive approach to uncover the root cause of your troubles.
Subclinical hypothyroidism is a mildly elevated TSH level in the presence of normal free T4. You may or may not experience mild symptoms of hypothyroidism. It is challenging to determine which symptoms, if any, are related to subclinical hypothyroidism as the symptoms are often nonspecific and could be related to any number of other things.
Clinical symptoms of hypothyroidism usually present when the disease is fully developed. Still, there may be a correlation between higher TSH levels and the severity of symptoms.
Symptoms of hypothyroidism may include:
- Weakness, lethargy, fatigue
- Dry skin
- Coarse hair
- Cold intolerance
- Weight gain
- Muscle cramps
- Voice hoarseness
- Irregular periods
If you or your doctor suspect subclinical hypothyroidism, it may be beneficial to first retest to confirm the finding before starting thyroid hormone replacement therapy.
Vitamin or mineral deficiencies
Micronutrients, which include vitamins and minerals, are essential to our body's function. (Not to be confused with macronutrients, which are the big nutrition categories like carbohydrates, fats, and proteins.) Our bodies need adequate micronutrients for a healthy metabolism, immune function, growth and development, bone health, and many more processes.
Common deficiencies include iron, vitamin D, folate, and vitamin B-12. These deficiencies may cause symptoms similar to those of hypothyroidism like fatigue, aches and pains, or skin and hair issues. Typically, a nutrient-deficient state is simple to confirm with lab testing and treat with the appropriate supplements.
Hypothalamic and/or pituitary disease
A properly-functioning hypothalamic-pituitary-thyroid axis is necessary for the reliable interpretation of thyroid function tests. Disruption of this hormonal axis is uncommon but could be the cause of hypothyroid symptoms.
Central hypothyroidism (not to be confused with primary hypothyroidism) is a disorder of the hypothalamus or pituitary glands. It is considered hypothyroidism due to insufficient stimulation by thyroid-stimulating hormone (TSH) of an otherwise normal thyroid gland. Central hypothyroidism can originate from secondary hypothyroidism (a problem with the pituitary) or tertiary hypothyroidism (a problem with the hypothalamus).
In adults, central hypothyroidism is usually due to small tumors on the pituitary gland (macroadenomas), pituitary surgeries, or radiation exposure. If you or your doctor suspect central hypothyroidism, your doctor can confirm this diagnosis with a thyrotropin-releasing hormone stimulation test.
Stress is anything that disrupts the body's natural balance (homeostasis). Sometimes hearing your doctor chalk up your symptoms to stress can feel unsatisfying. Immediately, we think of the usual stressors like a heavy workload, financial worries, significant life shifts, etc. But other factors that we think of less frequently as "stress" also burden the adrenal glands.
The adrenal glands are two small glands located above the kidneys. They secrete hormones like cortisol, epinephrine, and norepinephrine, which regulate the stress response.
Things like blood sugar imbalance, gut dysfunction, food intolerances, chronic infections, environmental toxins, and inflammation can cause the adrenal glands to produce more stress hormones. Like many hypothyroid symptoms, adrenal stress symptoms are often nonspecific and can affect virtually every system in the body.
Common symptoms of adrenal stress are:
- Decreased immunity
- Decrease sleep quality
- Mood swings
- Sugar and caffeine cravings
- Irritability or lightheadedness
- Eating to relieve fatigue
- Dizziness when standing
- Gastric ulcers
Weak adrenals may cause hypothyroid symptoms without any problem in the thyroid gland itself. You can take a saliva cortisol test or a urine cortisol test to assess adrenal hormones.
Poor thyroid hormone conversion
Your body needs to convert T4 into T3 to be able to use it. If the conversion of T4 to T3 is weak, you may experience some common hypothyroid symptoms.
Some causes of poor thyroid hormone conversion may include:
Leptin is a protein produced by fatty tissue that helps to regulate fat storage in the body. If the body shows resistance to leptin, where the leptin is unable to produce its usual effects to stimulate weight loss, the body senses it as starvation. Then, the body increases fat stores instead of burning excess fat.
Similarly, insulin resistance, diabetes, or metabolic syndrome may also impact the conversion of T4 to T3. Insulin is a hormone produced in the pancreas that regulates the amount of glucose in the blood. If the body shows resistance to insulin, your muscle tissues and liver don't easily take up glucose. Instead, the body will store the excess sugar in the fat cells.
—Acute or chronic dieting
Acute or chronic dieting can significantly decrease T3 levels, which substantially reduces metabolic function. The thyroid levels and metabolism aren't able to return to normal levels with chronic dieting. The body stays in starvation mode for years, making it challenging to lose or maintain lost weight. It's essential to fuel your body with enough calories, focusing on nutrient-rich foods like fruits, veggies, wild-caught fish, nuts, and seeds.
Numerous toxins can block tissue thyroid receptors and reduce the T4 to T3 conversion. Often human-made, these chemicals are in everyday products that we use and ingest, including plastic bottles, detergents, food, toys, cosmetics, and pesticides.
A note from Paloma Health
If your lab results come back normal, but you still experience symptoms that resemble hypothyroidism, we recommend finding a trustworthy primary care physician who takes a comprehensive approach to understand the root cause of your symptoms and optimize your treatment!