SPINA Thyr is a set of cybernetic methods for endotyping the hypothalamus-pituitary-thyroid feedback control system (HPT axis). The equations deliver calculated biomarkers (structure parameters) for the thyroid’s secretory capacity (SPINA-GT) and the sum activity of peripheral deiodinases (SPINA-GD).
- thyroid
- homeostasis
- hypothyroidism
- hyperthyroidism
- thyrotoxicosis
- deiodinase
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.
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)
αT: Dilution factor for T4 (reciprocal of apparent volume of distribution, 0.1 L−1)
βT: 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)
DT: EC50 for TSH (2.75 mU/L)
KM1: Binding constant of type-1-deiodinase (5e-7 mol/L)
K30: Binding constant T3-TBG (2e9 L/mol)
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. SPINA-GD provides an estimate for total deiodinase activity.
See also
References
- Johannes W. Dietrich; Gabi Landgrafe-Mende; Evelin Wiora; Apostolos Chatzitomaris; Harald H. Klein; John E. M. Midgley; Rudolf Hoermann; Calculated Parameters of Thyroid Homeostasis: Emerging Tools for Differential Diagnosis and Clinical Research. Front. Endocrinol. 2016, 7, 57, .
- Johannes W. Dietrich; Nina Siegmar; Jonas R. Hojjati; Oliver Gardt; Bernhard O. Boehm; CyberUnits Bricks: An Implementation Study of a Class Library for Simulating Nonlinear Biological Feedback Loops. ADCAIJ: Adv. Distrib. Comput. Artif. Intell. J. 2024, 13, e31762-e31762, .
- Dietrich, J.W.; P4-Endokrinologie – Kybernetische Perspektiven eines neuen Ansatzes. Leibniz Online 2024, 54, 1-23, .
- Rudolf Hoermann; John E.M. Midgley; Rolf Larisch; Johannes W. Dietrich; Relational Stability of Thyroid Hormones in Euthyroid Subjects and Patients with Autoimmune Thyroid Disease. Eur. Thyroid. J. 2016, 5, 171-179, .