Sum activity of peripheral deiodinases

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Sum activity of peripheral deiodinases
SynonymsSPINA-GD, GD, deiodination capacity, total deiodinase activity
Reference range20–40 nmol/s
Test ofMaximum amount of T3 produced from T4 by peripheral deiodinases
MeSHD013960
LOINC82367-4

The sum activity of peripheral deiodinases (GD, also referred to as deiodination capacity, total deiodinase activity or, if calculated from levels of thyroid hormones, as SPINA-GD[a]) is the maximum amount of triiodothyronine produced per time-unit under conditions of substrate saturation.[1] 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.

How to determine GD

GD can be determined experimentally by exposing a

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.[2]

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

reverse T3. Distinguishing the contribution of distinct deiodinases is possible, however, by sequential approaches using deiodinase-specific blocking agents, but this approach is cumbersome and time-consuming.[2]

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

or

[FT4]: Serum free T4 concentration (in pmol/L)
[FT3]: Serum free T3 concentration (in pmol/L)
[TT3]: Serum total T3 concentration (in nmol/L)
: Dilution factor for T3 (reciprocal of apparent volume of distribution, 0.026 L−1)
:

Clearance exponent for T3 (8e-6 sec−1) (i. e., reaction rate constant
for degradation)
KM1: Binding constant of type-1-deiodinase (5e-7 mol/L)
K30: Binding constant T3-TBG (2e9 L/mol)[3]

The method is based on mathematical models of thyroid homeostasis.[1][3] Calculating deiodinase activity with one of these equations is an inverse problem. Therefore, certain conditions (e.g. stationarity) have to be fulfilled to deliver a reliable result.

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]

Reference range

Lower limit Upper limit Unit
20[3] 40[3] nmol/s

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]

Clinical significance

Validity

SPINA-GD correlates to the T4-T3 conversion rate in slow tissue pools, as determined with isotope-based measurements in healthy volunteers.

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.[4]

Clinical utility

Compared to both healthy volunteers and subjects with

toxic adenoma, toxic multinodular goitre or Graves' disease).[19] SPINA-GD may therefore be an effective biomarker for the differential diagnosis of thyrotoxicosis.[20][21]

Compared to healthy subjects, SPINA-GD is significantly reduced in euthyroid sick syndrome.[22]

Pathophysiological and therapeutic implications

Recent research revealed total deiodinase activity to be higher in untreated hypothyroid patients as long as thyroid tissue is still present.

radioiodine therapy as well.[26]

SPINA-GD is elevated in obesity. This applies to both the metabolically healthy obese (MHO) or metabolically unhealthy obese (MUO) phenotypes.

NHANES dataset[29] and in a Chinese study.[30] This positive association was age-dependent and with respect to BMI significant in young subjects only, but with respect to body cell mass stronger in elderly persons.[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.[31]

SPINA-GD is reduced in

non-thyroidal illness syndrome, so that the clinical phenotype represents overlapping type 1 and type 2 allostatic response. In a large register-based study, reduced SPINA-GD predicted a poor outcome of Takotsubo syndrome.[39]

In certain psychiatric diseases, including major depression, bipolar disorder and schizophrenia SPINA-GD is reduced compared to healthy controls.[40]

In hyperthyroid

erectile function, intercourse satisfaction, orgasmic function and sexual desire. Substitution with selenomethionine results in increased SPINA-GD in subjects with autoimmune thyroiditis.[14][15][16][17]

In subjects with

diabetes mellitus SPINA-GD is positively correlated to several bone resorption markers including the N-mid fragment of osteocalcin and procollagen type I N-terminal propeptide (P1NP), as well as, however in men only, the β-C-terminal cross-linked telopeptides of type I collagen (β-CTX).[42] In the general population it is, however, positively associated with the bone mineral density of the femoral neck and with reduced risk of osteoporosis.[43] In both diabetic and non-diabetic subsjects it correlates (negatively) with age and concentrations of c-reactive protein, troponin T and B-type natriuretic peptide, and (positively) with the concentrations of total cholesterol, low-density lipoprotein and triglycerides.[44]

Deiodination capacity proved to be an independent predictor of substitution dose in several trials that included persons on replacement therapy with levothyroxine.[45][46]

Probably as a consequence of

immune checkpoint inhibitors for cancer as well.[49]

phthalate metabolites[51][52][53] and negative correlation to paraben, mercury and bisphenol A concentration.[54][51][52] In a cohort of manganese-exposed workers, SPINA-GD responded to a tenfold increase in concentrations of titanium, nickel, selenium and strontium.[55]

See also

Notes

  1. ^ SPINA is an acronym for "structure parameter inference approach".

References

  1. ^
    S2CID 14210899
    .
  2. ^
    PMID 24001133
    .
  3. ^
    OL 24586469M
    .
  4. ^
    PMID 37423160
    .
  5. ^
    S2CID 44088904
    .
  6. ^
    S2CID 35344744
    .
  7. S2CID 15996441
    .
  8. PMID 23184912
    .
  9. ^
    S2CID 19341039
    .
  10. S2CID 25630198
    .
  11. PMID 23809674
    .
  12. ^
    S2CID 207639541
    .
  13. S2CID 14016461
    .
  14. ^
    S2CID 73481267
    .
  15. ^
    S2CID 73486105
    .
  16. ^
    S2CID 159040151
    .
  17. ^
    S2CID 220485158
    .
  18. PMID 37375719
    .
  19. PMID 32099819
    .
  20. ^ Dietrich JW. "SPINA in Science and Research: Year in Review: 2020". sourceforge.net. Retrieved 2 January 2021.
  21. PMC 11009531
    .
  22. ^
    S2CID 202673793
    .
  23. PMID 34888359
    .
  24. PMID 36401211
    .
  25. S2CID 6407766
    .
  26. S2CID 267198748
    .
  27. doi:10.3760/cma.j.cn311282-20221012-00579
    .
  28. ^
    PMID 34006958
    .
  29. PMID 28775711
    .
  30. PMID 37245234
    .
  31. PMID 37946276
    .
  32. ^
    S2CID 199435315
    .
  33. S2CID 4550317
    .
  34. PMID 32337292
    .
  35. PMID 34726096
    .
  36. S2CID 220698496
    .
  37. S2CID 195830014
    .
  38. PMID 33179374
    .
  39. PMID 38502972
    .
  40. PMID 38277991
    .
  41. PMID 30307028
    .
  42. PMID 35196256
    .
  43. S2CID 256899701
    .
  44. S2CID 256055662
    .
  45. PMID 26335522
    .
  46. PMID 36722311
    .
  47. PMID 38514790
    .
  48. S2CID 212752563
    .
  49. S2CID 248203797
    .
  50. S2CID 259916981
    .
  51. ^
    PMID 32464474
    .
  52. ^
    S2CID 229722026
    .
  53. PMID 34746318
    .
  54. S2CID 265514578
    .
  55. S2CID 262013667
    .

External links

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Sum activity of peripheral deiodinases
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