As the ever-increasing numbers of people diagnosed with the various forms of thyroid gland dysfunction will tell you, correcting the problem is more than just swallowing your prescribed Thyroxin medication (1).
The incredible interactive complexity of hormones, nutrients and synthesis-conversion processes to ultimately enable thyroid receptor expression by active Triiodothyronine (T3) thyroid hormone is one of the marvels of our physiology, and medical researchers spend a happy lifetime studying it! (2)
It’s beyond the scope and intention of this article to detail the many intricate processes of thyroid function; here instead is a summarised overview:
Nutrients: minerals, trace elements and vitamins are all required in synergistic balance to synthesise (create) thyroid hormone, as well as drive it. Of these the ones generally regarded as most important are Vitamin D, Iodine, Zinc, Selenium and iron (3).
For the thyroid-adrenal axis to be optimal, the above nutrients should be at ideal ‘target’ levels, and the respective receptors should be in balance: –T3 (active thyroid hormone), Vitamin D (D3), Cortisol (CC) receptors – of these T3 is most important (Van Zanden: 2012).
T3, D3 and Cortisol exert their actions by binding to receptors on genes in the cell nucleus; D3 has a qualitative effect on T3 intra-nuclear receptors (i.e.: within the cell nucleus).
Cortisol has a quantitative effect by increasing intra-nuclear T3 receptor density, whilst there is also a constant ‘cross talk’ between D3 & T3 intra-nuclear nuclear receptors (Van Zanden: 2017).
Thyroid conversion ‘corruption’: occurs when physiological homeostasis is disrupted due to illness, significant injury or stress (4), elevated Copper or Cortisol levels, Vitamin D deficiency, heavy metal toxicity (HTM), or some patients taking prescribed T4 medication (1).
‘Inactive’ T4 thyroid hormone – which is naturally produced in our thyroid gland – is normally converted to T3 ‘active’ thyroid hormone, influencing every cell and functioning system in our body. When this conversion process is corrupted a de-activated, non-active form of T4 is produced – Reverse T3 (rT3).
Rising levels of Reverse T3 disrupts thyroid homeostasis by inhibiting the production and function of T3. rT3 binds to – but does not activate – T3 intra-cell receptors, thus effectively blocking T3 interface and activation.
In healthy, minimally stressed people, rT3 is rapidly purged from the body. When rT3 levels are allowed to become excessive, they exert a >100 times greater affinity to convert T4 to rT3 – thus producing further rT3 at the expense of T3.
Elevating levels of rT3 is a normal ‘biological hibernation signal’ in some hibernating animals such as bears and squirrels. In humans however rT3 acts to shut our bodies down to “await better times” (Van Zanden: 2012).
Elevated rT3 levels are commonly detected in coma-induced ICU patients, chronic fatigue, fibromyalgia and ongoing PTSD.
The consequences of an elevated rT3 is often UNDER-active thyroid-like symptoms despite seemingly ‘within range’ thyroid pathology results, tiredness, thinning scalp hair density, weight or mood disturbance.
rT3 influences normal scalp hair growth because it interferes with + blocks T3. T3 has the greatest hormonal influence on hair growth (or loss).
What influences thyroid conversion pathways?
The human body’s thyroid conversion process of inactive T4 to active T3, or T4 corruption to rT3 is mediated by peripheral selenium-based enzymes termed ‘deiodinases. There are three principal deiodinases which exert their influence on T4:
• D1: which (together with D2) influences conversion of T4 to T3.
• D2: primarily influences T3 cell availability.
• D3: interacts at a different location on the T4 hormone to cause rT3 conversion (ie: corruption) at the expense of T3. D3 activation is the body’s self-preservation response to protect cells from being exposed to a hyper-thyroid state (5) or essentially ‘hibernate’ the body in times of acute or chronic illness or severe stress.
Again – rT3 is a ‘mirror image’ of T3 which can bind to cell thyroid receptors but does not up-regulate (6) receptors.
Some common causes of an elevated rT3:
rT3 is a biomarker for dysregulation of homeostatic functioning; here are some common causes:
• Chronic illness and/or inflammatory disease in their many forms.
• Emotional or mood disturbances:
o Severe or protracted stressors from any area of life.
o Debilitating anxieties or panic attacks.
• Chronic insomnia or sleep disturbance due to sleep apnoea. Testing diurnal Cortisol (CC) levels via a salivary hormone profile will often reveal an ‘inverted’ CC signature in these patients.
• Elevated blood and/or body tissue levels of Mercury (Hg), Copper (Cu) or Arsenic are the more common toxic heavy metals which will elevate rT3. Testing is performed via hair mineral analysis (HMTA) and/or blood pathology.
Copyright Anthony Pearce 2017 (revised February 2026).
1. T4 (Thyroxin) medication is marketed under different brand names: Thyroxine, Oroxine, Eutrosig and others.
2. ‘Activation’ or ‘switching on’ of the thyroid receptor within the cell.
3. Further information on these nutrients please read article at my website: ‘Vitamins, Minerals and your Thyroid (what your Doctor may not know)
4. From any cause
5. Ie: excess T4, T3 cell saturation
6. Ie: ‘switch on’
I am ever indebted to my Mentor in this area (Dr. Philip Van Zanden) and again thank him for his ‘tutorial pearls’ over lunch!