Five Thyroid Patterns That Won’t Show Up on Standard Lab Tests

The five thyroid patterns

Thyroid physiology is complex and regulated by input from multiple endocrine glands, the immune system, the gut, and many cell-signaling molecules. Malfunctions in any one of these components can cause hypothyroid symptoms. However, these malfunctions are not revealed by a standard thyroid panel. Patients with hypothyroid symptoms but “normal” TSH and T4 according to the standard thyroid panel may be told that nothing is wrong with their thyroid glands and sent on their way. Some are handed prescriptions for thyroid hormone replacement. This one-size-fits-all approach to managing hypothyroidism ignores the multitude of factors that influence thyroid function and may even worsen symptoms in some patients. At best, it does our patients a disservice, and at worst it could be considered sheer negligence.

1.) Hypothyroidism caused by pituitary dysfunction

This pattern is caused by high cortisol. Cortisol, in turn, is elevated in response to active infection; (1) blood sugar dysregulation, hypoglycemia, insulin resistance, or chronic stress; (2) or pregnancy. These stressors fatigue the pituitary gland; as a result, it can’t release enough thyroid-stimulating hormone (TSH) to stimulate the thyroid gland to produce T4 and T3. In other words, there is nothing wrong with the thyroid gland itself; the problem lies with the pituitary gland. The key to correcting this pattern is to resolve the underlying causes of pituitary dysfunction by treating infection, balancing blood sugar, improving insulin sensitivity, and helping patients find ways to reduce their stress levels.

Patients with this pattern will present with hypothyroid symptoms, TSH below the functional range (1.8–3.0) but within the standard range (0.5–5.0), and T4 that is low in the functional range and possibly the standard range as well.

2.) Under-conversion of T4 to T3

T4 is the inactive form of thyroid hormone. It comprises 90 percent of thyroid hormone produced by the thyroid gland and must be converted to T3 before the body can utilize it. When T4 is not converted into T3 in adequate amounts, symptoms of hypothyroidism result. This pattern of thyroid dysfunction characterized by under-conversion of T4 to T3 has many potential causes, including inflammation, elevated cortisol, nutrient deficiencies, and intestinal dysbiosis. Patients with this pattern present with hypothyroid symptoms, normal TSH and T4, and low T3.

Twenty percent of thyroid hormone activation is initiated in the gastrointestinal tract by gut microbes, which produce deiodinase enzymes that convert T4 into T3. Disruption of the normal gut microbiota may reduce levels of beneficial bacteria that perform this crucial conversion, resulting in a decreased amount of T3 and symptoms of hypothyroidism. Lipopolysaccharides produced by pathogenic bacteria also impair T4 to T3 conversion by inhibiting thyroxine 5′-deiodinase, an enzyme that catalyzes the conversion.

T4 to T3 conversion occurs in cell membranes. Chronic inflammation involves the production of inflammatory cytokines, which damage cell membranes and impair thyroid hormone conversion. (7) Chronic fatigue syndrome and Crohn’s disease patients are two examples of patient subsets who may present with “low T3” syndrome due to chronic inflammation. (8, 9) High cortisol, which can become elevated due to chronic inflammation and stress, also suppresses the conversion of T4 to T3.

Nutrient status is essential in the pathogenesis of thyroid disorders. Nutrients such as iron and selenium serve as cofactors for enzymes involved in the conversion of T4 to T3. Deficiencies of iron and selenium may reduce T4-to-T3 conversion and promote symptoms of hypothyroidism. (11, 12)

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 tissues. High levels of TBG reduce levels of free thyroid hormone, causing hypothyroid symptoms. (13) Patients with this pattern have normal TSH and T4, low T3, high T3 uptake (a measure of the quantity of thyroxine-binding proteins such as prealbumin and albumin) and high TBG.

Elevated estrogen can raise TBG and cause hypothyroidism. (14) Estrogen may become elevated due to the use of birth control pills and estrogen hormone replacement therapy. The treatment for this pattern is to clear excess estrogen from the body.

4.) Hypothyroidism caused by decreased TBG

Low levels of TBG cause free thyroid hormone levels to rise because there are fewer proteins available to bind thyroid hormones. The high circulating levels of T4 and T3 induce cellular resistance to thyroid hormone, much like how cells develop insulin resistance upon continuous exposure to high levels of insulin. This problem means that even though there is plenty of thyroid hormone, cells can’t use it. As a result, symptoms of hypothyroidism develop. Patients with this pattern of thyroid dysfunction have normal TSH and T4, high T3, low T3 uptake, and low TBG.

Low TBG can be caused by a high testosterone level. (16) This thyroid pattern often occurs in women with PCOS and insulin resistance because these two conditions lead to elevated testosterone. Insulin sensitivity and blood sugar balance need to be restored to treat this pattern of thyroid dysfunction.

5.) Thyroid resistance

In this pattern of thyroid dysfunction, the thyroid and pituitary glands are functioning normally, but thyroid hormones are unable to get into cells where they are needed. TSH, T4, and T3 are all normal in this pattern. Unfortunately, we don’t have a method for testing the function of thyroid hormone receptors on cells, a tool that would be extremely helpful in this situation. However, testing for HPA axis dysfunction using methods such as the DUTCH test may be useful because chronic stress and high cortisol are two key contributors to this pattern. (17) Elevated homocysteine and genetic factors can also cause thyroid hormone resistance. (18, 19) Correcting imbalances in the HPA axis may help to resolve this pattern.

How to test for the five thyroid patterns

The standard thyroid panel is insufficient for detecting these five patterns of thyroid dysfunction. Additional tests are needed to determine which thyroid pattern is affecting your patient.

A comprehensive panel of thyroid markers. This panel should include TSH, T3, T4, free T3, and free T4.

DUTCH test for assessing HPA axis function. This test can help you determine whether chronic stress and high cortisol are causing pituitary dysfunction, under-conversion of T4 to T3, or thyroid hormone resistance.

Estrogen and testosterone. Measuring these hormones can help you determine whether elevated or decreased TBG, respectively, are the cause of your patient’s hypothyroidism.

Fasting blood sugar and hemoglobin A1c to assess blood sugar imbalances and insulin resistance, which contribute to hypothyroidism caused by pituitary dysfunction.

Ferritin and serum selenium, to identify deficiencies of iron and selenium.

Assess gut health: Stool testing, hydrogen breath testing for SIBO, and a urine organic acids profile can be used to identify potential gut infections and dysbiosis contributing to hypothyroidism.