As Goldilocks said of her porridge — this one’s too cold, this one’s too hot, and this one’s just right. If your body isn’t making the right amount of the thyroid hormones thyroxine (T4) and triiodothyronine (T3), you’re likely to find yourself on either side of “just right.”
Frank vs. Functional Hypothyroidism
Most people who suffer from thyroid issues fall into the “too cold” category and just don’t make enough thyroid hormones T4 and T3 — referred to as hypothyroidism. T3 action in the mitochondria increases metabolism and is responsible for heat production. So when T3 is low, your body temperature will be lower than normal.
More often than not, thyroid hormone testing shows adequate amounts of thyroid hormone despite clinical symptoms pointing directly at a thyroid-related issue. Functional hypothyroidism describes a patient who has normal or low-normal levels of T4 and T3, and somewhat normal TSH, but nevertheless suffers from many of the hallmark symptoms of a “thyroid problem”:
- Feeling cold all the time no matter what the room temperature
- Being depressed or having a low mood; apathy; and low libido
- Sluggish mental capacity — can’t focus or just can’t get those words out
- Low stamina and energy, mostly towards the end of the day
- A slow heart rate
- Constipation
- Brittle or dry hair and nails
This article focuses on some of the possible causes of functional hypothyroidism, with special reference to the essential element selenium that plays a key role in thyroid hormone synthesis and conversion of T4 to its bioactive counterpart T3 — and how heavy metals such as mercury and arsenic can interfere with this process.
Thyroid Hormone Synthesis: The Nuts and Bolts
Thyroid hormone synthesis relies on uptake and concentration of iodine in the thyroid gland by the sodium-iodine symporter. Thyroid-Stimulating Hormone (TSH), produced by the anterior pituitary gland, plays a key role in regulating most aspects of thyroid hormone synthesis — stimulating synthesis of the iodine symporter, thyroid peroxidase (TPO) and thyroglobulin, the protein precursor from which T4 and T3 are manufactured.
Once the thyroid gland has concentrated enough molecular iodine, TPO — an iron-dependent enzyme unique to the thyroid gland — begins the process of ionising iodine to the highly reactive iodide molecule. The iodine bonds to the tyrosine residues of thyroglobulin, and when most of the tyrosine residues have been iodinated, two iodinated tyrosine molecules coalesce to form the precursors of T4 and T3 in about an 80/20 ratio.
T4 and T3 are stored in the thyroid gland until they are released into the bloodstream where they are tightly bound to thyroid binding globulin (TBG). Only about 0.02% of the total T3 and T4 circulating in the bloodstream are released into the cells of tissues and are therefore considered bioavailable.
Selenium Is Essential to Thyroid Hormone Action
T4 to T3 or rT3 conversion is catalysed by 3 different selenium-dependent thyroid deiodinases referred to as D1, D2 and D3. D1 converts T4 to T3 in specific tissues such as the liver and kidneys. Most other tissues, including the brain and muscles, convert T4 to active T3 by D2 deiodinase. If conditions are not favourable for thyroid hormone activity — such as extreme stressors like starvation and sepsis — T4 is converted instead to reverse T3 (rT3) by D3, which reduces T4 to T3 conversion.
It is estimated that D2 deiodinase accounts for 50–80% of the T3 utilised by all cells. Vitamin D and cortisol also play an important role in the actions of T3 on thyroid receptors — this is why T3-bound thyroid receptors are optimally activated and balanced with physiological levels of vitamin D and cortisol.
How Heavy Metals Disrupt Thyroid Function
Selenium-Dependent Antioxidants Protect the Thyroid Gland
Thyroid hormone synthesis creates an enormous amount of hydrogen peroxide (H₂O₂) that is necessary to activate iodine and bind it to thyroglobulin. H₂O₂ is a Reactive Oxygen Species (ROS) essential to thyroid hormone synthesis, but excess levels need to be rapidly neutralised by antioxidants — otherwise they would oxidise and destroy the thyroid gland itself, leading to Hashimoto’s thyroiditis, Graves’ disease and thyroid cancer.
The principal antioxidant enzymes in play are glutathione peroxidase and thioredoxin reductase — both selenium-dependent enzymes that utilise glutathione to destroy H₂O₂ and convert it to water. Some of the highest tissue levels of these selenium-dependent antioxidants are found in the thyroid gland.
Mercury, Arsenic and Selenium Sequestration
Insufficient selenium intake, or sequestration of selenium through tight ionic bonding to heavy metals such as mercury, arsenic, cadmium and lead, can result in lower bioavailability of selenium for synthesis of protective antioxidant enzymes. Direct binding of heavy metals — particularly mercury and arsenic — to seleno-cysteine in the active catalytic site of glutathione peroxidase and thioredoxin-reductase will reduce synthesis of these enzymes and inactivate them.
Low selenium is closely linked to Hashimoto’s thyroiditis, where the thyroid gland begins to self-destruct from within, releasing excessive amounts of TPO and iodide-laden thyroglobulin into the bloodstream. The immune system recognises these as foreign molecules and mounts an autoimmune reaction — resulting in high levels of TPO antibodies (TPOab), which is characteristic of and diagnostic for Hashimoto’s thyroiditis.
If you suspect Hashimoto’s or autoimmune thyroid disease, our TPOab Test (Thyroid Peroxidase Antibody) measures TPO antibody levels from a simple at-home blood spot collection — the key diagnostic marker for Hashimoto’s thyroiditis.
Comprehensive Testing to Assess Thyroid Deficiency
Simply measuring T3, T4 and TSH in blood may not explain why patients can often present with “apparently normal” thyroid hormones but suffer from hallmark symptoms of thyroid deficiency.
If thyroid tests are within normal ranges but symptoms are problematic — even with thyroid therapy — consider also evaluating the status of essential elements iodine and selenium in combination with heavy metals. Our Thyroid, Heavy Metals & Essential Elements Test combines a full thyroid panel (TSH, Free T4, Free T3, TPO antibodies) with ICP-MS analysis of toxic and essential elements including iodine, selenium, mercury, arsenic and cadmium — providing the deepest available insight into the causes and treatment opportunities for functional thyroid dysfunction.
For those who want to start with iodine and thyroid function specifically, our Thyroid & Iodine Test Kit measures TSH, Free T4, Free T3, TPO antibodies and urinary iodine — identifying the iodine deficiency that is so often the missing piece in thyroid dysfunction.
Originally ZRT Laboratory. Reproduced with permission. Last reviewed: May 2026.