The thyroid gland has profound effects on health and well-being. Yet most doctors don't look further than the one customary screening lab value, even if a person has symptoms.
The thyroid gland, located in the front of the neck just below the laryngeal prominence, or Adam’s apple, takes iodine from the diet and makes thyroid hormones through a series of steps. Think of your thyroid gland as the thermostat for the body; thyroid hormones affect a person in many ways including physical energy, temperature, skin and hair condition, bowel function, weight and mood.
Prevalence of Thyroid Disease
Thyroid diseases are generally categorized into two broad groups of disorders: abnormal function and abnormal growths in the gland. These problems are common in the general population, with some estimated 20 million Americans having some form of thyroid disease,1 especially among older people and women. Women are five to eight times more likely than men to have thyroid problems.1 Functional disorders are related to the gland producing either too little of thyroid hormones and are termed 'hypothyroidism' or too much of thyroid hormones and are referred to as 'hyperthyroidism'.
Abnormal growths can be either benign nodules or neoplasms, such as cancers. Benign nodules result from abnormal cell growth in the thyroid gland and are common, usually not causing serious health problems, though they can on occasion put pressure on the neck and cause trouble with swallowing or speaking. The thyroid usually functions normally even when nodules are present. Thyroid cancers are much less common than benign nodules. With treatment, the cure rate for thyroid cancer is more than 90 percent.2
Assessing Abnormal Thyroid Function
Thyroid function is determined through a complex negative feedback loops involving multiple endocrine organs, including the hypothalamus, pituitary and ultimately, the thyroid gland. Most of the possible thyroid-related laboratory tests to run are made by the thyroid gland itself, but not all.
Thyroid Stimulating Hormone (TSH): TSH is the 'go-to' test for clinicians. It is made by the pituitary and directs production of hormones by the thyroid gland. I describe it to my patients as a signal, or kick-in-the-rear, saying: 'Hey, thyroid, make your hormones!' A high TSH means the thyroid gland requires a lot of stimulation to get in gear, and this is what you see in hypothyroidism. The precision of this test has been largely praised by the medical community, and that has often been the basis for providers not ordering other tests beyond it. However, there has been less agreement about the most accurate reference range for this value. Indeed, even one proponent of near exclusive TSH testing noted "... though the normal range for TSH is generally listed at between 0.35 mIU/mL and 4.50 mIU/mL, it is likely that the 'most normal' range is between 0.5 mIU/mL and 2.50 mIU/mL".3
T4 (Thyroxine, tetraiodothyronine), Free (FT4): This is the amount of inactive, precursor hormone generated by the thyroid gland and circulating in the bloodstream. Beyond the TSH, assessment of free T4 is the most commonly ordered thyroid function test. Approximately 85% of the thyroid hormone generated is T4, and of that only about 1% is FT4, which is the only form of T4 readily able to bind to receptor sites.3. The reputation it has for not being reliable or accurate has left many clinicians disinclined to order it.
T4 (Thyroxine, tetraiodothyronine), Total (T4): Some T4 travels in the blood bound by protein, some travels freely and unbound. This value measures both types. It is considered of little efficacy because many factors unrelated to thyroid function can influence the proteins associated and amount of T4 showing up on the test. For example, one study found T4 total concentrations were "underrepresented when T4 was unbound, or thyroxine-binding globulin (TBG) bound (and) [t]otal T4 was overrepresented when T4 was albumin-bound, or transthyretin-bound. There were substantial disparities among assays applied to the same total T4 solutions".4
T3 (Triiodothyronine), Free (FT3): T3 is the active form of the thyroid hormones and FT3 measures serum T3 not bound to thyroid hormone-binding proteins such as thyroid hormone-binding globulin, transthyretin, or albumin. It is used, primarily in concert with TSH and FT4, for the diagnosis and management of hyperthyroidism when protein binding issues may be suspected. T3 binds to thyroid hormone receptors with an affinity about 20-30 times higher than that of T4 so it has much more substantial influence over physiological function.5.
T3 (Triiodothyronine), Total (T3): A total T3 test measures both forms of the active T3 hormone, whether it is bound or unbound. Its elevation is likely indicative of hyperthyroidism.
T3 Reverse (rT3): RT3 has less than 1% of the activity of T4. Psychosocial, chemical and physical stressors increase the production of rT3 through the activity of the enzyme deiodinase type 3, at the expense of lowering the physiologically active levels of T3. Think of this as potentially running interference with active thyroid hormone.
T3 Uptake (Thyroid Hormone-binding Ratio) / [THBR]: This is an indirect measure of binding protein saturation and it reflects available binding sites. This test was once used to help calculate an estimation of the FT4 concentration. These are rarely used now that there are direct methods available to measure FT4 and FT3. A high T3 uptake means binding proteins are more saturated than normal.
The Endocrine Society as well as the American Board of Internal Medicine both actively discourage physicians from readily ordering T3 or FT3 when managing patients with levothyroxine, a T4 medication.6 Their emphasis on the quality of the TSH test has many clinicians disinterested in ordering other thyroid hormone tests. Yet a high number of patients treated with the standard levothyroxine (T4) monotherapy continue to report symptoms suggestive of hypothyroidism; "... such patients may account for as many as 20% of hypothyroid patients. These patients usually have within range immunoassay values for TSH, total and free T3, and FT4, giving the suggestion of appropriate levothyroxine (T4) monotherapy".7 The vast majority of patients are not seeking additional testing unless they feel unwell. Twenty percent is a significant amount of people that don't feel quite right on their medications! Don't they deserve a more thorough investigation to possibly help discover why?
Sometimes the results can be surprising!
This patient had symptoms of low thyroid but had a TSH value well within normal limits. But a deeper look found that her body was low on BOTH forms of thyroid hormones! T4 as well as T3!
And even if we were to discount the findings since T4 and T3 are not as good of quality tests, let's consider in what way are they not as helpful? The answer here is also surprising. "Multiple studies show falsely normal values for T3, FT3, and FT4 by immunoassay that are below the reference interval when measured by (ultrafiltration) LC-MSMS, a reference method. ... This overestimation by immunoassay can be significant; ... [w]e hypothesize that many patients who still experience hypothyroid symptoms despite treatment with levothyroxine (T4) may actually have low levels of T3 that are incorrectly classified by the common immunoassay methods".7 With that said, then finding low levels of FT4, T4, FT3, or T3 should be even more noteworthy, especially if the person has symptoms, and their TSH is in the upper region of the not-universally-agreed-upon reference range.
While considerations do need to be made for what could be influencing binding proteins when interpreting thyroid hormone testing, the patient's level of discomfort should also be strongly considered when low levels of a hormone can have such over-arching affects on how a person feels, and some of the insight might be just a pen scratch on a lab requisition away.
References:
3. Sheehan, M. Biochemical Testing of the Thyroid: TSH is the Best and, Oftentimes, Only Test Needed - A Review for Primary Care. Clin Med Res. 2016 Jun; 14(2): 83–92.
5. Sandler B, et al. Thyroxine-thyroid hormone receptor interactions. J Biol Chem. 2004;279(53):55801–55808.
6. Sue, L. Reducing Inappropriate Serum T3 Laboratory Test Ordering in Patients With Treated Hypothyroidism. Endocr Pract. 2019 Dec;25(12):1312-1316.
7. Welsh, K. et al. How reliable are free thyroid and total T3 hormone assays? Eur J Endocrinol. 2016 Dec; 175(6): R255–R263.
The content and any recommendations in this article are for informational purposes only. They are not intended to replace the advice of the reader's own licensed healthcare professional or physician and are not intended to be taken as direct diagnostic or treatment directives. Any treatments described in this article may have known and unknown side effects and/or health hazards. Each reader is solely responsible for his or her own healthcare choices and decisions. The author advises the reader to discuss these ideas with a licensed naturopathic physician.