Thyroid hormone is responsible for many bodily functions so it is imperative to have optimal circulating levels. Yet, an estimated 20 million Americans have some form of thyroid disease. Up to 60 percent of these people are unaware of their condition. One in eight women will develop a thyroid disorder during her lifetime. Levothyroxine, a synthetic form of thyroid hormone, is the 4th highest selling drug in the U.S. Thirteen of the top 50 selling drugs are either directly or indirectly related to hypothyroidism.
The number of people suffering from thyroid disorders continues to rise each year. Hypothyroidism is one of the most common thyroid disorders. It is characterized by mental slowing, depression, dementia, weight gain, constipation, dry skin, hair loss, cold intolerance, hoarse voice, irregular menstruation, infertility, muscle stiffness and pain.
According to the American Association of Clinical Endocrinologists, 27 million Americans suffer from thyroid dysfunction – half go undiagnosed. Subclinical hypothyroidism may affect an additional 24 million Americans. Taken together, more than 50 million Americans are affected by some form of thyroid disorder. As you will see, diagnosing hypothyroidism is not as straight forward as ordering a simple blood test. New research demonstrates that thyroid hormone enters receptors differently depending on what tissue is being stimulated. In other words, the way the circulating thyroid hormone enters your pituitary gland and the way the same hormone enters heart or brain tissue is different. It is possible to have normal circulating levels and have underperformance of the thyroid hormone depending on how the thyroid hormone is being transported to the tissue.
This concept has profound clinical significance. Unfortunately, many physicians are not aware of these new developments in thyroid hormone transport. This results in an over-reliance on the sole use of standard thyroid blood tests (e.g., thyroid-stimulating hormone (TSH) and T4 levels) to determine the presence or absence of hypothyroidism. This leads to the misdiagnosis of many hypothyroid patients. These patients are misdiagnosed with depression or some other disease associated with hypothyroidism. This over-reliance on standard thyroid blood tests and the overconfidence of the diagnostic accuracy of standard thyroid blood tests may be particularly troublesome in the presence of a wide range of common conditions present in a large percentage of the population.
Every cell in the body has receptors for thyroid hormone. These hormones are responsible for the most basic aspects of body function, impacting all major systems of the body. Thyroid hormone directly acts on the brain, the G.I. tract, the cardiovascular system, bone metabolism, red blood cell metabolism, gall bladder and liver function, steroid hormone production, glucose metabolism, lipid and cholesterol metabolism, protein metabolism and body temperature regulation.
Studies show that 90% of people with hypothyroidism are producing antibodies to thyroid tissue. This causes the immune system to attack and destroy the thyroid, which over time causes a decline in thyroid hormone levels. This autoimmune form of hypothyroidism is called Hashimoto’s disease. Hashimoto’s is the most common autoimmune disorder in the U.S., affecting between 7-8% of the population. Hashimoto’s often manifests as a “polyendocrine autoimmune pattern”. This means that in addition to having antibodies to thyroid tissue, it’s not uncommon for Hashimoto’s patients to have antibodies to other tissues or enzymes as well.
Hypothyroidism patients need to understand that they don’t have a problem with their thyroid, they have a problem with their immune system attacking the thyroid. Unfortunately, misdiagnosis is common in the management of hypothyroidism. So many times, if you have hypothyroid symptoms but your lab tests are normal, you’ll be told you’re “fine”. If you insist you’re not, you might be sent home with an antidepressant, but no further clue about the cause of your symptoms. The following are the five major thyroid patterns that don’t show up on standard tests.
1. HYPOTHYROIDISM CAUSED BY PITUITARY DYSFUNCTION. This pattern is caused by elevated cortisol, which is in turn caused by active infection, blood sugar imbalances, chronic stress, pregnancy, hypoglycemia or insulin resistance. These stressors fatigue the pituitary gland at the base of the brain so that it can no longer signal the thyroid to release enough thyroid hormone. There may be nothing wrong with the thyroid gland itself. The pituitary isn’t sending it the right messages. With this pattern, you’ll have hypothyroid symptoms and a TSH below the functional range (1.8 – 3.0) but within the standard range (0.5 – 5.0). You will also have higher than optimal fasting insulin levels.
2. UNDER-CONVERSION OF T4 TO T3. T4 is the inactive form of thyroid hormone. It must be converted to T3 before the body can use it. More than 90% of thyroid hormone produced is T4. This common pattern is caused by inflammation and elevated cortisol levels. T4 to T3 conversion happens in cell membranes. High cortisol also suppresses the conversion of T4 to T3. Elevated cortisol levels also cause increase production of Reverse T3 (RT3) which is a metabolite of T4. Reverse T3 competes with T3 at the cell receptor. With this pattern you’ll have hypothyroid symptoms, but your TSH and T4 will be normal. If you have your T3 tested, which it rarely is in conventional settings, it will be low.
3. HYPOTHYROIDISM CAUSED BY ELEVATED TBG. Thyroid binding globulin (TBG) is the protein that transports thyroid hormone through the blood. When thyroid hormone is bound to TBG, it is inactive and unavailable to the tissues. When TBG levels are high, levels of unbound (free) thyroid hormone will be low, leading to hypothyroid symptoms. Elevated TBG is caused by high estrogen (high not optimal) levels, which are often associated with birth control pills or estrogen replacement not properly monitored. You can have high estrogen levels from estrogen metabolism problems or obesity. With this pattern, TSH and T4 will be normal. If tested, T3 will be low, and T3 uptake and TBG will be high.
4. HYPOTHYROIDISM CAUSED BY DECREASED TBG. This is the mirror image of the pattern above. When TBG levels are low, levels of free thyroid hormone will be high. You might think this would cause hyperthyroid symptoms. But too much free thyroid hormone in the bloodstream causes the cells to develop resistance to it. So, even though there’s more than enough thyroid hormone, the cells can’t use it and you’ll have hypothyroid – not hyperthyroid – symptoms. Decreased TBG is caused by high testosterone levels. In women, it is commonly associated with PCOS and insulin resistance. Reversing insulin resistance and restoring blood sugar balance is the key to treating this pattern. With this pattern, TSH and T4 will be normal. If tested, T3 will be high, and T3 uptake and TBG will be low.
5. THYROID RESISTANCE. In this pattern, both the thyroid and pituitary glands are functioning normally, but the hormones aren’t getting into the cells where they’re needed. This causes hypothyroid symptoms. Thyroid resistance is usually caused by chronic stress and high cortisol levels. It can also be caused by high homocysteine and genetic factors. In this pattern all lab test markers will be normal because we don’t have a way to test the function of cellular receptors directly.
The five patterns above are only a partial list. There are other reasons to have hypothyroid symptoms that don’t show up on standard lab tests. If you have hypothyroid symptoms, but your lab tests are normal, you may have one of them.
Not only do these patterns fail to show up on standard lab work, they don’t respond well to conventional thyroid hormone replacement. If your body can’t convert T4 to T3, or you have too much thyroid binding protein, or your cells are resistant, it doesn’t matter how much T4 you take; you won’t be able to use it.
I have personally treated multiple people who have complained of symptoms consistent with hypothyroidism but have a normal TSH and no other thyroid labs taken. Several have been treated with a commercial T4 only drug. When checking the other thyroid labs I have seen free T3 in the low 2s and below. You need both T3 and T4. T4 crosses the blood brain barrier while T3 does not. T3 is the thyroid that is used at the cellular level.
There are multiple reasons a person can experience hypothyroid symptoms and have normal thyroid labs. If you are on a commercial thyroid medication and are still having symptoms, I would suggest checking some other thyroid labs. Even if the other labs are normal, that doesn’t mean there is no need for treatment. I don’t always make my decision based on labs alone. Nutrition, labs, symptoms, and the patient’s history must also be considered.
There are functional medicine providers, like me, that successfully treat Hashimoto’s disease with lifestyle changes, nutrition, diet and supplements. If you are having hypothyroid symptoms and not being treated because your labs are normal, it might be a good time to begin a discussion with your health care provider about the best way to obtain optimal circulating thyroid levels.
Remember normal is not optimal,