Natural Medicine Practitioners have a healthy respect for the importance of thyroid function and are known to go above and beyond the conventional approach to thyroid screening. In truth, the thyroid gland is vulnerable to various contemporary stressors, such as circadian rhythm disruption,^1,2 unprecedented exposure to endocrine disrupting chemicals (EDCs),³ chronic stress⁴ and dysbiosis.⁵ However, there is question over whether it is necessary to perform in-depth testing of thyroid function to uncover subclinical hypothyroidism that may have slipped through the cracks of conventional screening. Likewise, there is debate over whether correcting thyroid biomarkers to a narrow putative optimal range has benefits over sitting in the conventional range. Finally, symptoms linked to hypothyroidism are nonspecific and frequently experienced by many patients. Thus, it is worth considering whether the contribution of suboptimal thyroid function in a patient’s presentation could be overstated, and if other drivers could be responsible for their illness.

These conundrums highlight the challenges in discerning the role of thyroid function in patients’ health and the following is an attempt to help wade through the complexities. To explore these contentions, let’s first review testing thyroid parameters.

The TSH debate

When it comes to thyroid stimulating hormone (TSH), there is a commonly held belief that as a standalone test, it is not an accurate indicator of thyroid function and the conventional ranges are too broad. There is concern that TSH by itself is crude and will not detect a large proportion of subclinical hypothyroidism cases, leading many patients to ‘fall through the cracks’ and continue to suffer from suboptimal thyroid function.

However, a review of recent research reveals TSH reflects thyroid hormone concentration and activity. In fact, TSH has demonstrated that it beautifully reflects circulating thyroid hormone levels with a log-linear relationship. What this means is, if circulating thyroid hormone levels alter slightly, there will be a marked change in TSH levels – thus TSH reflects subtle changes in thyroid function. For this reason, expert organisations concur that TSH is the most reliable indicator of thyroid status at the tissue level.^6,7

Do the TSH goal posts need to change?

If TSH is accepted as a valuable marker, there is still the contention around current ranges being too broad. Some researchers and clinicians have challenged the conventional TSH range and suggested the TSH upper limit should be reduced to 2.5 mIU/L.⁸ From this perspective, a TSH above this level would be considered subclinical hypothyroidism, and efforts should be employed to lower the patient’s TSH levels, ideally to around 1.0 mIU/L. It seems the data supporting a lower TSH may have been taken out of context in terms of recommending treatment. Studies show that most people with normal thyroid function, especially people under the age of 50, have a TSH below 2.5 mIU/L.^9,10 However, TSH levels can fluctuate significantly with time of testing (TSH is higher in the morning), sleep deprivation, strenuous exercise, or working during the night or evening shifts.¹¹ These factors may account for the findings that healthy people can record fluctuations of up to 1.6 mIU/L over a year of monthly testing, i.e. they can regularly fall in the 2.5 – 4.5 mIU/L zone.¹² Essentially, the TSH range of 2.5 – 4.5 mIU/L can be seen as a ‘buffer zone’ that allows for normal variation.

“While there may be some controversy about where the normal range for TSH should lie, current clinical guidelines are clear that a TSH in the upper normal range does not reflect hypothyroidism”

Sheehan MT et al¹³

Another way of exploring this topic is to examine the outcomes of hypothyroidism treatment, whereby the patients’ TSH levels returned to the conventional TSH range. For instance, in a controlled-trial, administering escalating doses of thyroxine therapy to hypothyroid patients found no differences in measures of wellbeing or quality of life in those who achieved a TSH target of 0.3, 1.0, or 2.8 mIU/L, respectively.¹⁴ These results suggest there is not an ‘optimal’ zone in the normal TSH range.

Based on the current evidence, there is little to no clinical benefit in becoming fixated on trying to reduce TSH to sit in the lower end of the normal range. If a patient’s TSH is within conventional parameters and still has health complaints, then it is unlikely to be attributed to thyroid dysfunction, and it would be prudent to consider other causes of their symptomology.

Does reverse T3 offer clinical utility?

The clinical relevance of reverse T3 (rT3) has also been questioned by researchers. There is a school of thought that hypothyroidism may be due to a diversion of T4 to rT3 instead of T3. In this model, there is an inhibition of the enzyme deiodinase 2 that converts T4 to T3 and an increase in deiodinase 3, which instead converts T4 to rT3. Typically factors such as stress and inflammation are proposed to mediate this enzymatic railroading of T4 to rT3.¹⁵

Whilst the intricate biochemistry of thyroid hormone metabolism in peripheral tissues via deiodinase enzymes appears attractive and plausible, when compared to clinical observations, it becomes clear that rT3 is yet to demonstrate clinical utility. Moreover, the data points to any changes in T3 to rT3 ratios as a beneficial homeostatic mechanism rather than a pathological driver of h ypothyroidism. Reason being, rT3 is a metabolically inactive form of thyroid hormone and researchers believe that T4 is diverted to rT3 to help fine tune metabolism to match the body’s needs. The increased diversion to rT3 becomes critical during times when metabolism is slowed to benefit the host, such as during severe caloric restriction or heart failure, as a process of energy conservation.¹⁶

Outside of these scenarios, which would rarely be seen in a Natural Medicine practice, measuring rT3 probably provides no clinical insight. With respect to hypothyroidism, research shows rT3 to be low, rather than high, as the body in this instance is trying to provide as much active T3 as possible to restore metabolism. Overall, after 40 years of investigation, current research suggests rT3 is not a particularly useful biomarker of thyroid function.¹⁷

“Measuring serum reverse T3 levels has not, in general, proven clinically useful for the diagnosis of hypothyroidism… Few clinical situations require measurement of reverse T3 levels.”

Gomes-Lima C et al¹⁸

Thyroid testing essentials

While research indicates TSH is the most suitable test for screening thyroid function in patients, there are two other tests to date that may have clinical utility. Firstly, free T4 is beneficial when TSH is elevated to determine subclinical versus overt hypothyroidism. Note however, there is some debate on the reliability conventional immunoassay testing, as such, where finances and availability permit, the use of the gold standard free T4 by equilibrium dialysis is preferred.¹⁹

The other test to be considered if TSH is elevated, is anti-thyroid peroxidase (TPO) antibodies. These antibodies are a hallmark of autoimmune thyroid disease, especially Hashimoto’s thyroiditis. That said, elevated anti-TPO antibodies alone are not diagnostic of thyroid disease, as a significant portion of healthy subjects can possess high levels. Elevated anti-TPO antibodies in conjunction with TSH outside normal range suggests thyroid disease.²⁰

Managing subclinical hypothyroidism

Perhaps the bulk of thyroid complaints seen in clinical practice would be what conventional endocrinology classifies as subclinical hypothyroidism - elevated TSH (>4.5 mIU/L [typically values between 4.5 – 10.0 mIU/L]) and normal free T4. In this instance, the data is mixed on the benefits of thyroid hormone replacement. For example, in subclinical hypothyroidism, administrating thyroxine has not demonstrated improvements in inflammation,²¹ cognition in the elderly,²² fatigue, mood and weight.^23,24 In contrast, there has been improvements seen in infertility,²⁵ high cholesterol,²⁶ CVD risk,²⁷ and cognition problems in children.²⁸

Considering the information thus far, subclinical hypothyroidism can be viewed as a condition that does not warrant excessive alarm or need for rapid, aggressive therapy. Certainly, it would be ideal to see TSH levels return to the normal range, and interestingly, up to 65% of cases of subclinical hypothyroidism have been found to resolve over time without intervention.²⁹ Albeit, there are instances whereby a targeted approach should be taken to normalise TSH, such as:

• Anti-TPO antibodies are elevated;

• There is a family history of thyroid or cardiovascular disease;

• Cognition issues in children;

• TSH >10 mIU/L;

• The patient has current cardiovascular disease or associated risk factors (e.g. dyslipidaemia, hypertension), goitre, ovulatory dysfunction, infertility, recurrent miscarriages or clinical symptoms of hypothyroidism.^30,31,32

Figure 1 illustrates an algorithm to guide decision-making in cases of subclinical hypothyroidism.

Figure 1: Subclinical hypothyroidism decision tree. Adapted from Vaidya B et al²⁴

Natural thyroid support

There are several ingredients that have been shown to help manage subclinical and overt hypothyroidism, including lowering TSH and increasing free T4. These ingredients, rather than replacing deficient thyroid hormone, act by mitigating stress that impedes the thyroid and provide the nutrients that help catalyse thyroid hormone synthesis.

Iodine deficiency is a common and concerning issue in Australia and New Zealand, and a condition which clearly impedes thyroid function.^34,35 Iodine is a unique mineral, as it is thought that its only biological function is for incorporation into thyroglobulin for thyroid hormone synthesis. This considered, iodine has a small therapeutic window and doses even moderately higher than recommended amounts may actually have suppressive effects on thyroid function, especially in Hashimoto’s thyroiditis.^36,37 The current Australian recommended daily intake (RDI) for iodine is 150 μg/day, with the upper level intake for adult men and women 1100 μg/day (Table 1).³⁸ When using iodine therapeutically in patients with thyroid dysfunction, evaluate total combined daily intake of iodine and monitor thyroid hormone levels if altered thyroid function is suspected.³⁹

The minerals zinc and selenium have been studied together and in isolation, with results demonstrating safe and effective thyroid support.⁴¹ Additionally, a review of 16 clinical trials on the use of 80-200 μg/day of selenium for the management of Hashimoto’s thyroiditis found it significantly lowered anti-TPO antibodies after three months.⁴²

Finally, in a placebo-controlled trial, the adaptogen Withania somnifera was shown to improve thyroid parameters in patients with subclinical hypothyroidism. After eight weeks of treatment, patients receiving withania recorded a significant reduction in TSH and elevationsin fT3 and fT4, whereas these parameters were unchanged in the placebo group.⁴³

Table 1: Recommended dietary intake (RDI) and upper limit of iodine.³⁵

Drivers and masquerades of hypothyroidism

If a patient is found to have subclinical or overt hypothyroidism, then the Functional Medicine approach is to acknowledge that some endogenous and/or exogenous stressor may be behind the pathology. Circadian rhythm disruption,^44,45 psychological stress,⁴⁶ EDCs,⁴⁷ mould biotoxins⁴⁸ and dysbiosis (particularly small intestinal bacterial overgrowth [SIBO])⁴⁹ have all been found to place strain on the thyroid, such as elevate TSH and in some cases lower T4. Ergo, in addition to providing herbal and nutritional support for the thyroid, equal attention should be placed on identifying and eradicating the thyroid stressor.

If a patient presents with symptoms of hypothyroidism yet TSH is in range, even the higher end of the normal range, it is very likely that the patient has normal thyroid function and there are other causes of their symptoms. In this scenario, a deeper dive into thyroid biomarkers will not identify a hidden hypothyroidism, and it would be more productive to screen other areas that may masquerade hypothyroidism.

Nutrient deficiencies, dysbiosis,⁵⁰ mast cell activation syndrome (MCAS)⁵¹ and chronic infection^52,53 may all produce symptoms akin to hypothyroidism, warranting a thorough screening to identify the real culprits.

In summary, the current data suggests the standard tools of assessment and conventional ranges are adequate for screening hypothyroidism. Subclinical hypothyroidism typically isn’t a significant red flag, therefore a slow and conservative approach to management may be preferable. Furthermore, it would be valuable to be cognisant of other causes or drivers if the patient presents symptomatic, but is biochemically euthyroid by standard measures.