1. Fundamentals

The structure parameters are calculated from serum concentrations of thyrotropin (TSH), free thyroxine (FT4), and free triiodothyronine (FT3)^[1]. The equations are derived from a platform for nonlinear modelling of endocrine feedback loops (MiMe-NoCoDI approach)^[2][3].

The calculations require simultaneous measurements of the hormones in steady-state conditions, i.e., if the patient receives treatment with thyroid hormones, the dosage should have been unchanged for at least four to six weeks. Calculating SPINA-GT is not meaningful under treatment with levothyroxine. Likewise, SPINA-GD is not informative under therapy with liothyronine.

SPINA-GT correlates positively with thyroid volume and the extent of perfusion in ultrasound investigations and negatively with the titres of autoantibodies directed to thyroid tissue. It has a higher retest reliability than determinations of TSH, FT4 or FT3^[1].

SPINA-GD correlates with the conversion rate of T4 to T3 in slow tissue pools and is associated with the supply of selenium, an essential trace element for the formation of deiodinases^[1].

Calculating SPINA-GT and SPINA-GD has helped to identify additional regulatory motifs of thyroid homeostasis^[4]. The methods have been used in multiple clinical studies with more than 10,000 included patients.

2. Calculation

The parameters are calculated as follows^[1]

[math]\displaystyle{SPINA\text{-}GT=\frac{\beta_T(D_T+[TSH])(1+K_{41}[TBG]+K_{42}[TTR])[FT4]}{\alpha_T[TSH]}}[/math]

[math]\displaystyle{SPINA\text{-}GD=\frac{\beta_{31}(K_{M1}+[FT4])(1+K_{30}[TBG])[FT3]}{\alpha_{31}[FT4]}}[/math]

[TSH]: Serum thyrotropin concentration (in mIU/L or μIU/mL)
[FT4]: Serum free T4 concentration (in pmol/L)
[FT3]: Serum free T3 concentration (in pmol/L)
α_T: Dilution factor for T4 (reciprocal of apparent volume of distribution, 0.1 L⁻¹)
β_T: Clearance exponent for T4 (1.1e-6 sec⁻¹), i.e., rate constant for degradation
α₃₁: Dilution factor for T3 (reciprocal of apparent volume of distribution, 0.026 L⁻¹)
β₃₁: Clearance exponent for T3 (8e-6 sec⁻¹) (i.e., rate constant for degradation)
K₄₁: Binding constant T4-TBG (2e10 L/mol)
K₄₂: Binding constant T4-TBPA (2e8 L/mol)
D_T: EC₅₀ for TSH (2.75 mU/L)
K_M1: Binding constant of type-1-deiodinase (5e-7 mol/L)
K₃₀: Binding constant T3-TBG (2e9 L/mol)

3. Interpretation

Reference ranges have been reported to be 1.41–8.47 for SPINA-GT and 20–40 for SPINA-GD^[1]. SPINA-GT is an ultrasensitive (and specific) biomarker for primary disorders of the thyroid gland^[5]. SPINA-GD provides an estimate for total deiodinase activity. The parameters have predictive value for the development of thyroid disorders even in the euthyroid range^[6] and for all-cause mortality in large populations^[3]. Their use is, therefore, a recommended supplementary tool for pediatric populations^[6], for the assessment in the occupational health system^[7] and the management of hypothyroidism^[5].