Sum activity of peripheral deiodinases

Sum activity of peripheral deiodinases
Synonyms	SPINA-GD, GD, deiodination capacity, total deiodinase activity
Reference range	20–40 nmol/s
Test of	Maximum amount of T3 produced from T4 by peripheral deiodinases
LOINC	82367-4

The sum activity of peripheral deiodinases (G_D, also referred to as deiodination capacity, total deiodinase activity or, if calculated from levels of thyroid hormones, as 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

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

or

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

<math>\alpha _{31}</math>: Dilution factor for T3 (reciprocal of apparent volume of distribution, 0.026 l⁻¹)
<math>\beta _{31}</math>: 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)

Reference range

Lower limit	Upper limit	Unit
20	40	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.

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 . It was also shown that GD correlates with resting energy expenditure, body mass index and thyrotropin levels in humans, and that it is reduced in nonthyroidal illness with hypodeiodination.

Clinical utility

Compared to both healthy volunteers and subjects with hypothyroidism and thyrotoxicosis, SPINA-GD is reduced in subacute thyroiditis. In this condition, it has a higher specificity, positive and negative likelihood ratio than serum concentrations of thyrotropin, free T4 or free T3. These measures of diagnostic utility are also high in nodular goitre, where SPINA-GD is elevated. SPINA-GD is significantly reduced in euthyroid sick syndrome.

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. This effect may ensue from the existence of an effective TSH-deiodinase axis or TSH-T3 shunt. After total thyroidectomy or high-dose radioiodine therapy (e.g. in treated thyroid cancer) as well as after initiation of substitution therapy with levothyroxine the activity of step-up deiodinases decreases and the correlation of SPINA-GD to thyrotropin concentration is lost. SPINA-GD is also reduced in low-T3 syndrome and certain chronic diseases, e.g. chronic fatigue syndrome or geriatric asthma. In Graves's disease, initially elevated SPINA-GD decreaes with antithyroid treatment in parallel to declining TSH receptor autoantibody titres.

In hyperthyroid men both SPINA-GT and SPINA-GD negatively correlate to erectile function, intercourse satisfaction, orgasmic function and sexual desire. Substitution with selenomethionine results in increased SPINA-GD in subjects with autoimmune thyroiditis.

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

Probably as a consequence of non-thyroidal illness syndrome, SPINA-GD predicts mortality in trauma and postoperative atrial fibrillation in patients undergoing cardiac surgery. Correlations were also shown to age, total atrial conduction time and concentrations of 3,5-diiodothyronine and B-type natriuretic peptide. In a population suffering from pyogenic liver abscess SPINA-GD correlated to markers of malnutrition, inflammation and liver failure.

See also

• Thyroid function tests
• Thyroid's secretory capacity
• Jostel's TSH index
• Thyrotroph Thyroid Hormone Sensitivity Index
• SimThyr

External links

• SPINA Thyr: Open source software for calculating GT and GD
• Package "SPINA" for the statistical environment R