TSH: Too much, too little or just enough? - The Goldilocks hormone

Thyroid stimulating hormone (TSH) is perhaps the most well-known hormone when it comes to thyroid function and is often used in isolation as a screening tool for thyroid dysfunction. Interestingly however, debate has been raised as to just how sensitive TSH testing is for identifying thyroid dysfunction, in particular, in light of research suggesting the current reference ranges used by most labs are too wide.

Whilst there is much consensus on the lower end of the reference range (typically 0.2 - 0.4 mIU/L), experts continue to challenge the upper end of the reference range used by most labs. For example, as I mentioned in this post, many labs still use a reference range of 0.5-4.5 for TSH, despite the American Association of Clinical Endocrinologists (and a number of other influential bodies) recommending an upper limit of 3.0 mIU/L. This is based on research that within a healthy population, the average TSH is approximately 1.5 mIU/L, and that a TSH greater than 2.5 or 3 mIU/L may be suggestive of thyroid dysfunction (1) (2). For example, according to the National Academy of Clinical Biochemists, 95% of individuals without evidence of thyroid disease have TSH concentrations of less than 2.5 mIU/L, suggesting a review of the current reference ranges may be warranted (3). Further to this, analysis of the scientific literature reveals a positive correlation between TSH and thyroid peroxidase antibodies, meaning higher TSH levels are associated with increased likelihood of autoimmune thyroid disease. Research has also found that TSH levels are often slightly higher in women, and tend to rise with age, regardless of the presence of thyroid disease (4). Whilst labs are yet to establish separate reference ranges for men, women and individuals of different ages (except in some cases children), these factors are worth bearing in mind. Other factors that need to be accounted for when interpreting TSH results include pregnancy, use of certain medications, use of high dose biotin supplements, non-thyroidal illness and conditions associated with central hypothyroidism, such as anorexia nervosa (5).

TSH - The Problem with Having Too Much

Whilst debate exists on exactly how much TSH is suggestive of thyroid dysfunction, evidence is clear that higher levels of TSH are associated with deleterious health effects and therefore need to be investigated and addressed. TSH is released by the pituitary (a small gland in the brain) to stimulate thyroid tissue to produce thyroid hormone. It is also a known growth factor, affecting the growth and function of thyroid cells. This is why a raised TSH is both an indicator of hypothyroidism (see paragraph below), as well as a risk factor for the growth of thyroid tissue. As a growth factor, high levels of TSH are associated with increased risk of thyroid enlargement (goitre), thyroid nodules and thyroid cancer (6). Of particular concern is the fact that higher TSH levels are positively correlated with risk of advanced-stage thyroid cancer, even within normal ranges (7) (8). For these reasons, it is essential that any aberration in TSH level is appropriately investigated and monitored by a suitably-qualified healthcare practitioner.

In the case of autoimmune hypothyroidism (Hashimoto’s disease), damage to the thyroid gland compromises thyroid hormone production, typically leading to a drop in free T4 and free T3 levels. In response, the pituitary sends out more TSH, to stimulate the thyroid to produce more thyroid hormone. As a consequence, we see a rise in TSH and if the process is allowed to continue, the thyroid may enlarge to trap more iodine and produce more thyroid hormone. In such cases, patients are typically prescribed levo-thyroxine, which replaces the missing thyroid hormone and with appropriate dosing, enables normalisation of TSH.

TSH - The Problem with Having Too Little

Whilst high TSH readings are certainly more common than low ones, low TSH readings may be equally problematic, and certainly warrant investigation. In individuals not on thyroid hormone replacement medication, a low TSH typically indicates hyperthyroidism, meaning the thyroid is making too much thyroid hormone. The most common cause of this is an autoimmune condition called Graves’ Disease. As a result of excessive thyroid hormone production, the pituitary reduces or ceases production of TSH, to minimise stimulation of thyroid tissue. This is a compensatory mechanism, designed to help keep thyroid hormone levels within a healthy range. Another cause of low TSH is a condition called central hypothyroidism; this is where dysfunction of the pituitary or hypothalamus (parts of the brain) results in reduced TSH production, leading to a decline in thyroid activity and thyroid hormone production. Common causes include severe stress or illness, anorexia nervosa and use of certain medications.

The last cause of low TSH I’ll discuss in this article is over-replacement with thyroid hormone medications. In this case, if the amount of thyroid hormone administered exceeds the body’s requirements, TSH levels may drop to reduce endogenous thyroid hormone production. In some cases, this is the aim of treatment. For example, thyroid cancer patients are often prescribed relatively high doses of thyroid medication, to intentionally suppress TSH levels. This is because of the reasons I discussed above linking TSH level to growth of thyroid tissue - the aim of suppressing TSH in such cases is to minimise growth of thyroid tissue and thus the potential recurrence or spread of thyroid cancer.

In non-thyroid cancer cases, suppression of TSH may indicate over-replacement of thyroid hormone and that a revision of a patient’s medication dose is warranted. This may occur with recent prescription of thyroid hormone medications and/or in cases where dose requirements have lessened over time (possibly due to partial recovery of thyroid function, improved thyroid hormone absorption, changes in thyroid hormone requirements during pregnancy or post-partum, and/or increased patient compliance with thyroid hormone administration). In both cases however, a doctor or endocrinologist will typically advise adjusting the prescribed dose and rechecking within 4-8 weeks to ensure normalisation of TSH is achieved. Prescription of T3-only medications can also result in suppression of TSH, however this is something best discussed with the prescribing physician.

Interestingly, one of the concerns around TSH suppression is the potential for thyroid gland atrophy to occur due to lack of stimulation (9). As discussed above, TSH is a growth factor, and too much can cause excessive growth of the thyroid tissue. On the other hand, the thyroid requires adequate stimulation by TSH to maintain proper structure and function. For this reason, excessive suppression of TSH is known to cause thyroid atrophy, as in essence, the brain is no longer communicating with the thyroid. This is certainly not a problem for patients with a history of thyroid cancer (under the guidance of their oncologist and endocrinologist), however, it may be a problem for those with hypothyroidism who rely on medications such as Thyroxine. Essentially, over-replacement of their thyroid hormone may lead to TSH suppression, which long term, can result in atrophy of the remaining thyroid tissue, thus potentially increasing their medication requirements. Whilst this may not be a concern for some individuals (as on diagnosis, many are told they will have to gradually increase their dose over time anyway), it may be a concern for those wanting to preserve as much active thyroid tissue as possible and potentially limit the extent to which they need to increase their Thyroxine dose over time. Of course, the matter of TSH and what constitutes ‘too much’ or ‘too little’ is very much an individual one, affected by a wide array of factors. For this reason, I often refer to it as the ‘Goldilocks hormone’ as it needs to be ‘just right’ to maintain the long term health, structure and function of the thyroid gland.

The Take Hormone Message

Ultimately, our understanding of TSH is continually evolving and expanding as researchers add to the growing body of information on the matter. For this reason, it’s essential to work with healthcare professionals who are committed to staying abreast of this research and are experts in their chosen field. The body of literature is brimming with examples in which a TSH that is too high or too low may become problematic, so I recommend working closely with a healthcare professional to ensure a TSH (and ideally, T4 and T3) within not only the ‘normal’ range, but within an optimal range for your personal health and circumstances.

x Niki