Sum activity of peripheral deiodinases

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.

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

$\hat G_D = {{\beta _{31} (K_{M1} + [FT_4 ])(1 + K_{30} [TBG])[FT_3 ]} \over {\alpha _{31} [FT_4 ]}}$

or

$\hat G_D = {{\beta _{31} (K_{M1} + [FT_4 ])[TT_3 ]} \over {\alpha _{31} [FT_4 ]}}$

$\alpha _{31}$: Dilution factor for T3 (reciprocal of apparent volume of distribution, 0.026 l⁻¹)
$\beta _{31}$: Clearance exponent for T3 (8e-6 sec⁻¹)
K_M1: Dissociation constant of type-1-deiodinase (5e-7 mol/l)
K₃₀: Dissociation constant T3-TBG (2e9 l/mol)^[1]

Reference Range

Lower limit	Upper limit	Unit
20[1]	40[1]	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.^[1]

Clinical significance

GD correlates with body mass index^[1][2][3] and thyrotropin levels in humans,^[4][5] and it is reduced in nonthyroidal illness with hypodeiodination.^{[2][6][7][8][9]} Recent research revealed total deiodinase activity to be higher in hypothyroid patients,^[5] 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.^[10]

See also

• Thyroid function tests
• Thyroid's secretory capacity

External links

• SPINA Thyr: Open source software for calculating GT and GD

References

1. Dietrich, J. W. (2002). Der Hypophysen-Schilddrüsen-Regelkreis. Berlin, Germany: Logos-Verlag Berlin. ISBN 978-3-89722-850-4. OCLC 50451543. 3897228505
2. Liu S, Ren J, Zhao Y, Han G, Hong Z, Yan D, Chen J, Gu G, Wang G, Wang X, Fan C, Li J (2013). "Nonthyroidal Illness Syndrome: ist it Far Away From Crohn's Disease?". J Clin Gastroenterol. 47 (2): 153–9. doi:10.1097/MCG.0b013e318254ea8a. PMID 22874844.
3. Dietrich JW, Landgrafe, G, Fotiadou, EH. TSH and Thyrotropic Agonists: Key Actors in Thyroid Homeostasis Journal of Thyroid Research, vol. 2012, Article ID 351864, 29 pages, 2012. doi:10.1155/2012/351864. PMID 23365787.
4. Hoermann R, Midgley JE, Larisch R, Dietrich JW. Is pituitary TSH an adequate measure of thyroid hormone-controlled homoeostasis during thyroxine treatment? Eur J Endocrinol. 2013;168(2):271-80. doi:10.1530/EJE-12-0819. PMID 23184912.
5. Hoermann R, Midgley JE, Giacobino A, Eckl WA, Wahl HG, Dietrich JW, Larisch R (2014). "Homeostatic equilibria between free thyroid hormones and pituitary thyrotropin are modulated by various influences including age, body mass index and treatment". Clin Endocrinol (Oxf) 81 (6): 907–15. doi:10.1111/cen.12527. PMID 24953754.
6. Rosolowska-Huszcz D, Kozlowska L, Rydzewski A (August 2005). "Influence of low protein diet on nonthyroidal illness syndrome in chronic renal failure". Endocrine 27 (3): 283–8. doi:10.1385/ENDO:27:3:283. PMID 16230785.
7. Han G, Ren J, Liu S, Gu G, Ren H, Yan D, Chen J, Wang G, Zhou B, Wu X, Yuan Y, Li J. Nonthyroidal illness syndrome in enterocutaneous fistulas. Am J Surg. 2013 Sep;206(3):386-92 doi:10.1016/j.amjsurg.2012.12.011. PMID 23809674.
8. Dietrich, JW; Müller, P; Schiedat, F; Schlömicher, M; Strauch, J; Chatzitomaris, A; Klein, HH; Mügge, A; Köhrle, J; Rijntjes, E; Lehmphul, I (2015). "Nonthyroidal Illness Syndrome in Cardiac Illness Involves Elevated Concentrations of 3,5-Diiodothyronine and Correlates with Atrial Remodeling". European Thyroid Journal 4: 129–37. doi:10.1159/000381543. PMC 4521060. PMID 26279999.
9. Fan, S; Ni, X; Wang, J; Zhang, Y; Tao, S; Chen, M; Li, Y; Li, J (February 2016). "Low Triiodothyronine Syndrome in Patients With Radiation Enteritis: Risk Factors and Clinical Outcomes an Observational Study.". Medicine 95 (6): e2640. doi:10.1097/MD.0000000000002640. PMID 26871787.
10. Midgley JE, Larisch R, Dietrich JW, Hoermann R. (August 2015). "Variation in the Biochemical Response to L-Thyroxine Therapy and Relationship with Peripheral Thyroid Hormone Conversion". Endocr Connect. 4: pii: EC–15–0056. doi:10.1530/EC-15-0056. PMID 26335522.