SPINA

Introduction

Principles of the Method

Clinical Appraisal

Calculation (Online and SW-Download)

 

Clinical Appraisal


Overview
Sensitivity, Specificity, Likelihood Ratios, ROC-Curves

References
Selection

SPINA Thyr has been evaluated in clinical trials covering more than 10,000 subjects. The results of all trials suggest calculated structure parameters to mirror thyroid biology probably better than levels of TSH, FT4 or FT3.

SPINA-GT correlates with thyroid volume and iodine supply, and it has a higher retest reliability than TSH, free T4 or free T3. SPINA-GD mirrors hypodeiodination in cases of NTIS (TACITUS syndrome), where it is significantly reduced, and it correlates with age, BNP concentration, PA-TDI inverval and serum concentration of 3,5-T2. Additionally, it is an independent predictor of L-T4 substitution dose.

Trial
Year
Included subjects
Main results
SPINA I 2002
228
SPINA-GT and SPINA-GD have highest specificity for diagnosis of various thyroid disorders. SPINA-GT correlates with thyroid volume and substitution therapy with iodide, SPINA-GD correlates with BMI.
Rosolowska-Huszcz et al. 2005
17
SPINA-GT correlates with creatinine clearance.
SPINA II 2012
20
SPINA-GT has higher reliability compared to TSH, FT4, FT3 and SPINA-GD.
Liu et al. 2012
44
SPINA-GD is significantly reduced in NTIS (TACITUS syndrome), SPINA-GT is not significantly elevated.
Han et al. 2013
226
SPINA-GD significantly reduced in NTIS.
Hoermann et al. 2013
1994
SPINA-GD correlates in untreated patients with TSH levels and is significantly reduced in patients under substitution therapy.
Midgley et al. 2013
6641
LS depends from state of thyroid homeostasis and interacts with GT.
Hoermann et al. 2014
1796
TSH, FT4 and FT3 each have their individual, but also interlocking roles to play in thyroid homeostasis. GD correlates with TSH and is significantly reduced after initiation of L-T4 substitution therapy.
Dietrich et al. 2015
39
SPINA-GD ist reduced in patients with NTIS, predicts postoperative atrial fibrillation and correlates to age, 3,5-T2 concentrations, BNP levels and PA-TDI interval.
Midgley et al. 2015
353
SPINA-GD is an inpedendent predictor for levothyroxine dose in patients on substitution therapy.
Fan et al. 2016
39
SPINA-GD significantly reduced in NTIS.
Wang et al. 2016
219
SPINA-GT significantly reduced in obesity with mild thyroid secretory insufficiency.

Currently, the AQUA-FONTIS Study, the largest proxpective study on non-thyroidal illness syndrome, is investigating the utility of SPINA for diagnosing and predicting the outcome of non-thyroidal illness syndrome in crtically ill patients.

In 2016, two overview articles on clinical and research applications of calculated parameters of thyroid homeostasis have been published in the Research Topic Homeostasis and Allostasis of Thyroid Function of the journal Frontiers in Endocrinology.

 

References

Dietrich, J. W., U. Mitzdorf, R. Weitkunat und C. R. Pickardt (1997). "The pituitary-thyroid feedback control: stability and oscillations in a new nonlinear model." Journal of Endocrinological Investigation 20 (Suppl. to no. 5): 100.

Dietrich, J., M. Fischer, J. Jauch, E. Pantke, R. Gärtner und C. R. Pickardt (1999). "SPINA-THYR: A Novel Systems Theoretic Approach to Determine the Secretion Capacity of the Thyroid Gland." European Jounal of Internal Medicine 10, Suppl. 1 (5/1999): S34.

Dietrich, J. W., A. Tesche, C. R. Pickardt und U. Mitzdorf (2002). Fractal Properties of the Thyrotropic Feedback Control: Implications of a Nonlinear Model Compared with Empirical Data. In: Cybernetics and Systems 2002. R. Trappl (Hrsg). Vienna.

Dietrich JW, Tesche A, Pickardt CR, Mitzdorf U (2004). Thyrotropic Feedback Control: Evidence for an Additional Ultrashort Feedback Loop from Fractal Analysis. Cybernetics and Systems. 35(4):315-31.

Rosolowska-Huszcz D, Kozlowska L, Rydzewski A (2005). Influence of low protein diet on nonthyroidal illness syndrome in chronic renal failure. Endocrine. 27(3):283-8

Dietrich, J. W. und B. O. Boehm (2006). Equilibrium behaviour of feedback-coupled physiological saturation kinetics. In: Cybernetics and Systems 2006. R. Trappl (Hrsg). Vienna, Austrian Society for Cybernetic Studies. 1: 269-74.

Dietrich JW, Stachon A, Antic B, Klein HH, Hering S (2008). The AQUA-FONTIS Study: Protocol of a multidisciplinary, cross-sectional and prospective longitudinal study for developing standardized diagnostics and classification of non-thyroidal illness syndrome. BMC Endocr Disord. 13;8(1):13.

Liu S, Ren J, Zhao Y, Han G, Hong Z, Yan D, Chen J, Gu G, Wang G, Wang X, Fan C, Li J. Nonthyroidal Illness Syndrome: Is it Far Away From Crohn's Disease? J Clin Gastroenterol. 2012 Aug 7. [Epub ahead of print] PMID 22874844

Dietrich, J. W., G. Landgrafe, E. H. Fotiadou (2012). TSH and thyrotropic agonists: Key actors in thyroid homeostasis. Journal of Thyroid Research, vol. 2012, Article ID 351864, 29 pages, 2012. PMID 23365787, doi:10.1155/2012/351864.

Hoermann, R., J. E. M. Midgley, R. Larisch, J. W. Dietrich (2013). Is Pituitary Thyrotropin an Adequate Measure Of Thyroid Hormone-Controlled Homeostasis During Thyroxine Treatment?. European Journal of Endocrinology 168(2):271-80. PMID 23184912, doi:10.1530/EJE-12-0819.

Midgley, J. E. M., R. Hoermann, R. Larisch, J. W. Dietrich (2013). Physiological states and functional relation between thyrotropin and free thyroxine in thyroid health and disease: in vivo and in silico data suggest a hierarchical model. Journal of Clinical Pathology 66(4):335-42. PMID 23423518, doi:10.1136/jclinpath-2012-201213

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. Epub 2013 Jun 27. PMID 23809674.

Hoermann R, Midgley JE, Giacobino A, Eckl WA, Wahl HG, Dietrich JW, Larisch R. Homeostatic Equilibria Between Free Thyroid Hormones and Pituitary Thyrotropin Are Modulated By Various Influences Including Age, Body Mass Index and Treatment. Clin Endocrinol (Oxf). 2014 Dec;81(6):907-15. doi: 10.1111/cen.12527. Epub 2014 Jul 7. PMID 24953754.

Hoermann R, Midgley JE, Larisch R, Dietrich JW (2015). Integration of Peripheral and Glandular Regulation of Triiodothyronine Production by Thyrotropin in Untreated and Thyroxine-Treated Subjects. Hormone and Metabolic Research 2015; 47(9):674-80, PMID 25750078 doi: 10.1055/s-0034-1398616.

Dietrich JW, Müller P, Schiedat F, Schlömicher M, Strauch J, Chatzitomaris A, Klein HH, Mügge A, Köhrle J, Rijntjes E, Lehmphul I. Nonthyroidal Illness Syndrome in Cardiac Illness Involves Elevated Concentrations of 3,5-Diiodothyronine and Correlates with Atrial Remodeling. Eur Thyroid J. 2015 Jun;4(2):129-37. doi: 10.1159/000381543. Epub 2015 May 23. PMID 26279999, PMCID PMC4521060.

Midgley JE, Larisch R, Dietrich JW, Hoermann R. Variation in the Biochemical Response to L-Thyroxine Therapy and Relationship with Peripheral Thyroid Hormone Conversion. Endocr Connect. 2015 Aug 11. pii: EC-15-0056. [Epub ahead of print] PMID 26265111.

Fan S, Ni X, Wang J, Zhang Y, Tao S, Chen M, Li Y, Li J. Low Triiodothyronine Syndrome in Patients With Radiation Enteritis: Risk Factors and Clinical Outcomes an Observational Study. Medicine (Baltimore). 2016 Feb;95(6):e2640. doi: 10.1097/MD.0000000000002640. PubMed PMID 26871787.

Wang X, Liu H, Chen J, Huang Y, Li L, Rampersad S, Qu S. Metabolic Characteristics in Obese Patients Complicated by Mild Thyroid Hormone Deficiency. Horm Metab Res. 2016 May;48(5):331-7. doi: 10.1055/s-0042-105150. PMID 27101096.

Dietrich JW, Landgrafe-Mende G, Wiora E, Chatzitomaris A, Klein HH., Midgley JE, Hoermann R. Calculated parameters of thyroid homeostasis: Emerging tools for differential diagnosis and clinical research. Frontiers in Endocrinology. 2016; 7:00057. doi: 10.3389/fendo.2016.00057.


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