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.
The product of SPINA-GD times the urinary iodine excretion can be used to assess iodine-independent factors affecting deiodinase activity, e.g. selenium deficiency.
[4] 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.[3] SPINA-GD correlates to the T4-T3 conversion rate in slow tissue pools, as determined with isotope-based measurements in healthy volunteers.
[1] It was also shown that GD correlates with resting energy expenditure,[5] body mass index[3][6][7] and thyrotropin levels in humans,[8][9] and that it is reduced in nonthyroidal illness with hypodeiodination.
[6][10][11][12][13] Multiple studies demonstrated SPINA-GD to rise after initiation of substitution therapy with selenium, a trace element that is essential for the synthesis of deiodinases.
[14][15][16][17][18] Conversely, it was observed that SPINA-GD is reduced in persons positive for autoantibodies to selenoprotein P, which is assumed to be involved in transport and storage of selenium.
[22] Recent research revealed total deiodinase activity to be higher in untreated hypothyroid patients as long as thyroid tissue is still present.
[28] Generally, SPINA-GD seems to be upregulated in metabolic syndrome, as demonstrated by a significant correlation to the triglyceride-glucose index, a marker of insulin resistance.
[37] Six months after the primary infection, it correlates negatively to the FS-14 score for fatigue in patients affected by Long COVID (PASC).
[38] In Graves' disease, SPINA-GD is initially elevated but decreases with antithyroid treatment in parallel to declining TSH receptor autoantibody titres.
[40] In certain psychiatric diseases, including major depression, bipolar disorder and schizophrenia SPINA-GD is reduced compared to healthy controls.
[44] In the general population it is, however, positively associated with the bone mineral density of the femoral neck and with reduced risk of osteoporosis.
[46] Deiodination capacity proved to be an independent predictor of substitution dose in several trials that included persons on replacement therapy with levothyroxine.
[47][48] Probably as a consequence of non-thyroidal illness syndrome, SPINA-GD predicts mortality in trauma[22] and postoperative atrial fibrillation in patients undergoing cardiac surgery.
[12] The association to mortality is retained even after adjustment for other established risk factors, including age, APACHE II score and plasma protein binding of thyroid hormones.
[22] Correlations were also shown to age, total atrial conduction time, and concentrations of 3,5-diiodothyronine and B-type natriuretic peptide.
[32] A study on subjects with Parkinson's disease found SPINA-GD to be significantly decreased in tremor-dominant and mixed subtypes compared to the akinetic-rigid type.
[50] Euthyroid sick syndrome may be the reason for variations of SPINA-GD in subjects treated with immune checkpoint inhibitors for cancer as well.
[58] In a cohort of manganese-exposed workers, SPINA-GD responded to a tenfold increase in concentrations of titanium, nickel, selenium and strontium.