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Sum activity of peripheral deiodinases

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Reference range
  
20–40 nmol/s

LOINC
  
82367-4

The sum activity of peripheral deiodinases (GD, also referred to as deiodination capacity, total deiodinase activity or SPINA-GD) is the maximum amount of triiodothyronine produced per time-unit under conditions of substrate saturation. It is assumed to reflect the activity of deiodinases outside the central nervous system and other isolated compartments. GD is therefore expected to reflect predominantly the activity of type I deiodinase.

Contents

How to determine GD

GD can be determined experimentally by exposing a cell culture system to saturating concentrations of T4 and measuring the T3 production. Whole body deiodination activity can be assessed by measuring production of radioactive iodine after loading the organism with marked thyroxine.

However, both approaches are faced with draw-backs. Measuring deiodination in cell culture delivers little, if any, information on total deiodination activity. Using marked thyroxine exposes the body to thyrotoxicosis and radioactivity. Additionally, it is not possible to differentiate step-up reactions resulting in T3 production from the step-down reaction catalyzed by type 3 deiodination, which mediates production of reverse T3.

In vivo, it may therefore be beneficial to estimate GD from equilibrium levels of T4 and T3. It is obtained with

G ^ D = β 31 ( K M 1 + [ F T 4 ] ) ( 1 + K 30 [ T B G ] ) [ F T 3 ] α 31 [ F T 4 ]

or

G ^ D = β 31 ( K M 1 + [ F T 4 ] ) [ T T 3 ] α 31 [ F T 4 ]

α 31 : Dilution factor for T3 (reciprocal of apparent volume of distribution, 0.026 l−1)
β 31 : Clearance exponent for T3 (8e-6 sec−1)
KM1: Dissociation constant of type-1-deiodinase (5e-7 mol/l)
K30: Dissociation constant T3-TBG (2e9 l/mol)

Reference Range

The equations and their parameters are calibrated for adult humans with a body mass of 70 kg and a plasma volume of ca. 2.5 l.

Clinical significance

GD correlates with body mass index and thyrotropin levels in humans, and it is reduced in nonthyroidal illness with hypodeiodination. Recent research revealed total deiodinase activity to be higher in hypothyroid patients, which may ensue from the existence of an effective TSH-deiodinase axis or TSH-T3 shunt.

Deiodination capacity proved to be an inpedendent predictor of substitution dose in a trial with over 300 patients on replacement therapy with levothyroxine.

References

Sum activity of peripheral deiodinases Wikipedia