Reference
Thyroid Research Glossary
Plain-language definitions of the deiodinase, reverse-T3, and T2 terms used across our research library. Each entry links to the full pillar where the mechanism is covered in depth.
Deiodinase
A family of three selenium-dependent enzymes (DIO1, DIO2, DIO3) that add or remove iodine atoms from thyroid hormone, converting it between active and inactive forms inside tissue. The deiodinases - not the thyroid gland alone - determine how much active T3 actually reaches the cells.
Deiodinase dysfunction guideDIO1 (Type 1 Deiodinase)
The peripheral workhorse enzyme, expressed mainly in liver and kidney. It supplies much of the T3 circulating in the bloodstream and is the primary enzyme that clears reverse T3. DIO1 is suppressed by inflammation and selenium deficiency.
Deiodinase dysfunction guideDIO2 (Type 2 Deiodinase)
The local activator. DIO2 makes T3 inside specific tissues (brain, pituitary, muscle, brown fat) for that tissue's own use. The pituitary's DIO2 sets TSH feedback, which is why TSH can read normal while peripheral tissues are T3-deficient.
Normal TSH, still hypothyroidDIO3 (Type 3 Deiodinase)
The off switch. DIO3 inactivates thyroid hormone by converting T4 into reverse T3 and T3 into 3,3'-T2. It is normally quiet in adults but reactivates under inflammation, hypoxia, and critical illness, driving the reverse-T3 pattern.
Reverse T3 complete guideReverse T3 (rT3)
An inactive form of thyroid hormone produced when DIO3 removes an inner-ring iodine from T4. Reverse T3 does not activate thyroid receptors; elevated levels indicate the deiodinase balance has shifted toward inactivation, as happens in chronic illness.
Reverse T3 complete guideFT3:rT3 Ratio
The ratio of free T3 to reverse T3, used as the single best serum proxy for whether thyroid hormone activation or inactivation is winning at the tissue level. A low ratio suggests deiodinase dysfunction even when TSH is normal.
FT3:rT3 ratio calculatorReverse T3 Dominance
A pattern in which DIO3 is overactive and DIO1 is suppressed, so reverse T3 accumulates faster than it is cleared while free T3 falls. The result is functional hypothyroidism at the tissue level despite a thyroid panel that can look normal.
Reverse T3 dominance guideNon-Thyroidal Illness Syndrome (NTIS)
Also called low-T3 syndrome. A state in which systemic illness or inflammation suppresses DIO1 and induces DIO3, producing low T3, elevated reverse T3, and a normal or low TSH. It is the textbook example of deiodinase dysfunction driven by cytokines and cortisol.
Deiodinase dysfunction guideSelenoprotein
A protein that carries the rare amino acid selenocysteine at its active site and requires selenium to function. All three deiodinases are selenoproteins, which is why selenium deficiency impairs thyroid hormone activation across the whole enzyme family at once.
Deiodinase dysfunction guideThr92Ala (DIO2 Polymorphism)
A common genetic variant in the DIO2 gene associated with reduced local T4-to-T3 activation. Affected individuals can have persistent hypothyroid symptoms despite a normal serum panel, because the impairment is at the tissue level and invisible to standard testing.
Deiodinase dysfunction guideWilson's Temperature Syndrome (WTS)
A research-community framework proposing that impaired T4-to-T3 conversion produces a low-body-temperature, low-metabolism state that standard TSH testing misses. It is not recognized as a formal diagnosis by mainstream endocrinology.
Wilson's Temperature Syndrome guideWT3 Protocol (Cyclic T3 Titration)
The Wilson's protocol of titrating sustained-release T3 upward to a temperature target, sustaining it for three weeks, then tapering. It is designed to override a reverse-T3-dominant state and let endogenous conversion reset at a corrected baseline.
WT3 protocol guideSustained-Release T3 (SR-T3)
Liothyronine (T3) formulated to release slowly over several hours rather than as the sharp peak of immediate-release Cytomel. The flatter serum curve reduces cardiovascular peak effects and is the formulation used in WT3-style research protocols.
Sustained-release T3 guide3,5-T2 (3,5-Diiodothyronine)
A downstream thyroid metabolite that acts on the mitochondria directly, binding cytochrome c oxidase (Complex IV) to raise cellular respiration without nuclear receptor activation. T3 cannot fully replicate this pathway, which is why T2 is studied alongside T3.
3,5-T2 complete guideT3-to-T2 Conversion
The deiodinase step that converts T3 into diiodothyronine (T2). Because it uses the same enzyme family as T4-to-T3 conversion, the same dysfunction that blocks the first step can block this one - the basis of the T3-protocol plateau hypothesis.
T3-to-T2 conversion problemCytochrome c Oxidase (Complex IV)
The terminal enzyme of the mitochondrial electron transport chain. 3,5-T2 binds its subunit Va to acutely increase aerobic respiration, the mechanism that distinguishes T2's rapid metabolic effect from T3's slower genomic action.
3,5-T2 complete guideDefinitions are provided for research-context education only. All compounds referenced are sold strictly for laboratory research and not for human consumption. See our research-use and safety framework and FAQ.