Saturday, June 27, 2015

TSH - A Critical Re-Evaluation of Its Non-Significance: Why Your TSH May Tell You Nothing About Your Thyroid Health

Symptoms of hypo- and hypothyroidism (figure from 
In previous articles about overtraining I've already touched on the possibility that training too much and eating to little can put you into a state where your TSH levels are low, even if the same goes for your free T3 and free T4 values.

Normally, your hypothalamus should correct low levels of the two active thyroid hormone T3 and T4 by increasing TSH. This physiological up-and-down is what doctors use to diagnose hypo- and hyperthyroidism by measuring TSH and in many cases only TSH - text-book practice, but still questionable against the background of the latest science.
Learn more about your thyroid, T3, and T4 at the SuppVersity

Green tea messes w/ your thyroid hormones

Overfeeding affects thyroid hormones

Fructose prevents decline of T3 while dieting

T2 has thyroid-suppressing ef-fects as T3 & T4

Dieting makes you "hypothyroid" - temporarily

Levothyroxine may not be enough →T4+T3?
Yes, even though everybody knows that you cannot judge the speed of a car by measuring how far its driver pushed the gas pedal into the floor, TSH remains the most commonly used endocrine test in clinical practice, when it comes to testing thyroid function; and this is despite the fact that more and more scientists are questioning the use of TSH, in general, and the reference ranges in particular.

Figure 1: Prevalence of thyroid antibodies across TSH intervals in women (top) and men (Spencer. 2007).
Speaking of reference ranger, if your TSH level is within the 1-1.5 mU/L range, you're considered "normal" (Biondi. 2013; Fontes. 2014; Vadiveloo. 2013). If your TSH is above 4.2-4.5 mU/L doctors believe this would indicate that your free T3 and free T4 levels were low, i.e. that your thyroid is not producing enough thyroid hormones and you're diagnosed hypothyroid - and this is where the problems begin.

After all, there is also an argument that a highly significant number of patients (up to 30%) with TSH above 3.0 mU/L have an occult autoimmune thyroid disease that may remain undiagnosed (Spencer. 2007 | see Figure 1). The same goes for people with subclinical hypothyrodism, simply because textbooks still say that TSH was all you need to test the health of your patients' thyroid.
T4 alone may not be enough: In patients with actual thyroidism, the standard treatment with levothyroxine (T4) only may not fully resolve their problems. I've written about the benefits and often cited risks of a combination therapy with T3 + T4 before, which is why I am not going to go into detail here. If you think your thyroid treatment makes things worse, though, I suggest you read my 2013 article "(Mis-)Managing Hypothyroidism: 7% Reduction in Energy Expenditure & Fat Oxidation in Patients on Levothyroxin (T4) Mono Therapy. Plus: Alternative Dessicated Thyroid?"
Figure 2: High(er) rates of thyroid antibodies in non-frail vs. frail elderly women are suggestive of a protective effect of thyroid antibodies (Wang. 2010).
In contrast to young people, in whom thyroid diseases (esp. hypothyroidism and autoimmune diseases) will often remain undiagosed if doctors rely on TSH, only.

Elderly patients (i.e. 70 plus years), on the other hand, may be falsely diagnosed with hypothyroidism due to age-related increase in TSH ranging to up to 6.0 mU/L - and that despite the fact that that there are no or irrelevantly small changes in free T3 and free T4. This is particularly important, because ill health effects as they are seen in young individuals are rare or non-existent in elderly patients with autoimmune thyroid diseases nor hypothyroidism.

Rather than being detrimental, a 2010 study by Wang et al., which found that elderly subjects with raised titres of thyroid autoantibodies are less frail than age-matched peers (see Figure 2), suggests that having anti-thyroid antibodies in the blood can actually protect older women from the age-induced loss of muscle mass and function - surprising, isn't it? In view of the fact that the TSH levels of elderly patients usually have to rise above 6-7 mU/L before there is an actual decline in T4 below the normal range, the upper limit for TSH in the elderly should be increased (Hadlow. 2013).
Sometimes it doesn't even take meds to bring your thyroid hormones back up - assuming they are not rock bottom, that is. You don't believe that? Well, reread the SuppVersity Classic "Dietary Thyroid Treatment: Beef, Green Vegetables, Full-Fat Milk & Butter Normalize TSH in Subclinical Hypothyroidism" | read it!
To treat or not to treat? This is question that can hardly be answered based on TSH values, only. In young patients, the upper limit may be too low. This is particularly true for women with subclinical hypothyroidism or autoimmune disease and TSH levels of ~3 mU/L whose low thyroid hormone levels will significantly increase (+72%) their risk of cardiovascular disease (Rodondi. 2006) - irrespective of being considered "subclinical hypothyroid" by most doctors.

So what can you do if your TSH is "normal", but you have symptoms? Ask your doctor to test fT3 and fT4 as well and look for one of the following patterns: (1) TSH low, fT4 low(-ish), fT3 low(-ish) → overtraining and/or undereating, (2) TSH normal, fT4 low, fT3 low → subclinical hypothyriodism or autoimmune thyroid disease (test for antibodies, to differentiate) - If your fT3 and fT4 are perfect nothing and neither (1) nor (2) applies, but you still "feel hypo" you probably have read about how "low thyroid is rampant" and "always undiagnosed" at suffer from "imaginary hypothyroidism" | Comment on FB!
  • Biondi, Bernadette. "The normal TSH reference range: what has changed in the last decade?." The Journal of clinical endocrinology and metabolism 98.9 (2013): 3584.
  • Fontes, Rosita, et al. "Reference interval of thyroid stimulating hormone and free thyroxine in a reference population over 60 years old and in very old subjects (over 80 years): comparison to young subjects." Thyroid research 6.1 (2013): 1-8.
  • Hadlow, Narelle C., et al. "The relationship between TSH and free T4 in a large population is complex and nonlinear and differs by age and sex." The Journal of Clinical Endocrinology & Metabolism 98.7 (2013): 2936-2943.
  • Lewandowski, Krzysztof. "Reference ranges for TSH and thyroid hormones." Thyroid Research 8.Suppl 1 (2015): A17.
  • Rodondi, Nicolas, et al. "Subclinical hypothyroidism and the risk of coronary heart disease: a meta-analysis." The American journal of medicine 119.7 (2006): 541-551.
  • Spencer, C. A., et al. "National Health and Nutrition Examination Survey III thyroid-stimulating hormone (TSH)-thyroperoxidase antibody relationships demonstrate that TSH upper reference limits may be skewed by occult thyroid dysfunction." The Journal of Clinical Endocrinology & Metabolism 92.11 (2007): 4236-4240.
  • Vadiveloo, Thenmalar, et al. "Age-and gender-specific TSH reference intervals in people with no obvious thyroid disease in Tayside, Scotland: the Thyroid Epidemiology, Audit, and Research Study (TEARS)." The Journal of Clinical Endocrinology & Metabolism 98.3 (2013): 1147-1153.
  • Wang, George C., et al. "Thyroid autoantibodies are associated with a reduced prevalence of frailty in community-dwelling older women." The Journal of Clinical Endocrinology & Metabolism 95.3 (2010): 1161-1168.