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"Normal TSH values may not rule out patients that are hypothyroid. It is possible that a large number of hypothyroid individuals are missed using TSH as a screening tool, which is a problem for the patient, who remains hypothyroid, and to the healthcare system as a whole.” (Ling et al., 2018)
From a patient’s point of view, thyroid testing leaves a lot to be desired. What is a patient to do when their labs are “normal,” but they’re living with signs and symptoms of low thyroid—some of them downright debilitating? This describes the not uncommon scenario of someone whose thyroid stimulating hormone (TSH) and thyroxine (T4) levels were the only thyroid-related tests performed, and both were normal. They may leave a practitioner’s office with no explanation for why they have low energy, why they have constipation, depression, high cholesterol, are losing hair, and why they’re gaining weight despite no changes to their diet and exercise. And no explanation means no treatment. No way forward. Is there a better way to serve these patients?
It’s no secret that thyroid testing and treatment are controversial topics. Some professionals are confident that testing TSH alone is sufficient to identify thyroid dysfunction. Others would prefer to see both TSH and T4, while still others would insist that a more comprehensive thyroid panel is worth performing in order to identify imbalances or deficiencies, particularly when TSH and T4 are normal but a patient presents with undeniable signs and symptoms of low thyroid. This is not an unusual situation, but if more in-depth tests are not ordered, then the patient is left thinking it’s “all in their head” and that there is no remedy except to “get over it” and learn to live with it.
Numerous people fit this scenario: normal TSH and normal T4, but total and/or free T3 that are overtly low or are toward the lower end of a broad range. The difficulty in treating thyroid patients is partly an artifact of the reference ranges used and whether or not these are appropriate in all cases. Reference ranges differ among different labs, but one study cited a case using the following ranges for free T3, total T3, and total T4:
|
FT3 |
1.8 – 4.2 pg/mL |
|
TT3 |
90 – 215 ng/dL |
|
T4 |
4.5 – 12.5 ug/dL |
The range from high to low for each of these represents more than a doubling of the hormone level. The upper end of the range for total T4 is close to triple the lower end. One patient’s free T3 could be nearly half that of another’s, and both would be considered “normal.” For this reason, it may be prudent to use lab values as a guide in conjunction with clinical judgment and experience to formulate and evaluate treatment based on symptoms.
The most common treatment for hypothyroidism in the US is monotherapy with levothyroxine, which provides only T4. However, treatment with T4 alone often does not resolve hypothyroid symptoms. This is because T3 is far more potent than T4 (T3, not T4, is considered the “bioactive” form of thyroid hormone), and in many people the peripheral conversion of T4 to T3 is insufficient. Even when the conversion appears to result in an adequate blood level of T3, as much as 20% of patients may still have bothersome hypothyroid signs & symptoms. Being “on thyroid medication” is no guarantee that a patient will actually feel better if it’s not the appropriate type or dose. (Combination T4/T3 therapy is more common outside the US.)
The waters become even murkier when reverse T3 (rT3) is taken into account. Reverse T3 is considered a metabolically inactive or inert form of T3 that is elevated during times of physiological trauma or stress, including caloric restriction. Some researchers believe that is it not inactive, but rather, may induce hypometabolic effects, but even if it has no overt effects of its own, it may act as a competitive inhibitor to T3, binding to T3 receptors and therefore blocking or reducing efficacy of active T3. Clinicians with experience in this area have determined that even when free T3 falls within the normal range, if rT3 is elevated, this skewed ratio may result in hypothyroid signs and symptoms—again, also within the presence of normal TSH and T4. Reverse T3 is not commonly measured, but it may be included in a comprehensive thyroid panel. Here again, though, the reference ranges are quite wide (10-24 ng/dL or 90-350 pg/mL), so “low” and “high” may be relative terms. Plus, T3 performs its actions intracellularly, so even if total and free T3 are measured and found to be “normal,” this isn’t necessarily an accurate reflection of what is occurring where the hormone actually induces its effects.
Numerous adaptations take place within the crosstalk between the thyroid, pituitary and hypothalamus, such that TSH and T4 may be normal when total and/or free T3 are low, and a patient is symptomatic. If only TSH and T4 are ordered, this will be missed, and not only will the patient continue to suffer reduced quality of life, but the healthcare system overall may be unduly burdened. If the patient is given medications to treat the individual signs and symptoms of low thyroid—for example, a statin for elevated cholesterol, an antidepressant for the depression, and an appetite suppressant to combat the weight gain—then individual symptoms are being treated piecemeal rather than addressing the underlying cause, the resolution of which would improve all the diverse symptoms.
Practitioners with experience in this area said it well: “Clinicians must use clinical skills and patient-centered concerns in the optimum evaluation and treatment of their patients and not succumb to blindly following an arbitrary system of defined normal lab values in making therapeutic decisions that greatly affect the well-being of their patients.”
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