[SPINA] Reviewing 2019

Di Jan 14 21:40:19 CET 2020

Dear subscribers,

with respect to SPINA, 2019 was again a fascinating year. Multiple papers by several brilliant groups have used the methodology to get interesting new findings.

Numerous studies by a Polish group used SPINA Thyr to discover notable interactions between thyroid homeostasis, insulin-glucose metabolism and sex hormones. One of these studies demonstrated thyroid’s secretory capacity (SPINA-GT) to predict sexual function and depressive symptoms in young women with overt hyperthyroidism [1]. A second study found that supplementation with selenomethionine increases total peripheral step-up deiodinase activity (SPINA-GD) in euthyroid women with autoimmune thyroiditis [2]. This is not too surprising, since selenium is an essential trace element, which is necessary for synthesis and function of deiodinases. Interestingly, however, in the same study it was observed that supplementation with selenium (in interaction with vitamin D) is also able to increase SPINA-GT. This suggests selenium to be also necessary for the biology of the thyroid itself [1]. Although this finding was somewhat astonishing it was confirmed in a third study, which included men suffering from autoimmune thyroiditis [3]. The most convincing explanation is that selenium and vitamin D are able to modulate autoimmune surveillance, which consecutively has influence on thyroid function. This, of course, fits well old observations that both selenium and vitamin D play important roles in inflammatory thyroid diseases [4, 5].

Interestingly, sex hormones might come into play here, too. Two studies in men with comorbid hypogonadism and autoimmune thyroiditis revealed that both vitamin D and selenomethionine supplementation were able to increase SPINA-GT in this group, too, but that this effect is potentiated by substitution therapy with testosterone [6, 7]. Even supplementation with testosterone alone is able to increase SPINA-GT in parallel to reducing antibody titres [8]. Initiation of therapy with metformin had a similar increasing effect on SPINA-GT, but in men with hypogonadism only [9]. Unsurprisingly, spironolactone, which has also anti-androgenic effects, is able to decrease SPINA-GT [10]. In summary, the interaction between sex hormones and thyroid homeostasis seems to be an important, although previously under-recognised, fact.

This is also illustrated by a study in 136 women with and without polycystic ovary syndrome (PCOS). It described SPINA-GD to decrease after glucose load, but in subjects with PCOS only [11]. The change in SPINA-GD correlated to plasma triglyceride and insulin concentrations, but again in the PCOS group only. Conversely, a negative correlation was found between SPINA-GD and total cholesterol concentration. This might suggest that type 2 allostatic load, a well-known complication of metabolic syndrome, is superimposed by type 1 allostatic load, especially in the context of nutrient load. The authors also suggested that this mechanism might promote atherosclerosis in affected subjects.

Another study found both SPINA-GT and SPINA-GD to be increased in Graves’ disease, whereas Jostel’s TSH index as a marker for the function of the central component of the feedback loop was decreased [12]. These observations are interesting independent confirmations of the theories of TSH-T3 feedforward control (aka TSH-T3 shunt) and the ultrashort feedback loop of TSH in the pituitary [12].

A Chinese group observed that SPINA-GD correlates to both FEV1 and FEV1/FVC ratio in elderly adults with asthma [13]. This is another example for type 1 thyroid allostasis (non-thyroidal illness syndrome, euthyroid sick syndrome or TACITUS) in chronic illness. A similar observation was made by another Chinese group in a population with 240 subjects suffering from pyogenic liver abscess, where SPINA-GD correlated to markers of inflammation, malnutrition and liver failure [14].

In an own study we showed that hypodeiodination as a manifestation of TACITUS is common in patients suffering from polytrauma, too [15]. Here, SPINA-GD was a significant predictor for poor prognosis, even after adjusting for other important risk indicators including age, APACHE II score and plasma protein binding of thyroid hormones [15].

One study slightly beyond SPINA may be interesting, too: An international group from the US and Spain found that an increased set point of thyroid function, as assessed by a novel marker of thyroid hormone feedback at the pituitary site, which they call Thyroid Feedback Quantile-based Index (TFQI), is associated with diabetes and metabolic syndrome [16]. This observation underpins the important comorbidity pattern of type 2 thyroid allostasis with unfavourable metabolic phenotypes. We will include TFQI calculation in subsequent versions of the SPINA Thyr software.

In 2019 we could celebrate 20 years of the SPINA methodology. What began in May 1999 as a poster at the 2nd congress of the European Federation of Internal Medicine in Florence grew to an increasingly used procedure. The number of research projects using SPINA continues to increase every year [17]. The method may help to provide long-awaited personalised decision criteria for the treatment of patients suffering from thyroid disease [18, 19].

At the very end of 2019, we were able to release version 4.1.0 (Bonfire) of SPINA Thyr for macOS, Windows and Linux. This new version introduces a small number of new features and a larger number of bug fixes. On the same day, SPINA Thyr has been curated by the European projects zenodo and OpenAIRE. Therefore, it is now possible to cite the software with the DOI 10.5281/zenodo.3596049 [20].

Did you know that the SPINA team has a Twitter account? Current news are released via https://twitter.com/SPINATeam .

In 2020 we will publish important study results on SPINA Thyr with respect to cardiovascular end points, which could prove to be another important application of the methodology [21]. Stay tuned with our Twitter account or  this list to get this and other news timely.

All the best for 2020,
JWD

References:

1. Krysiak R, Kowalcze K, Okopień B. Sexual function and depressive symptoms in young women with overt hyperthyroidism. Eur J Obstet Gynecol Reprod Biol. 2019 Mar;234:43-48. doi: 10.1016/j.ejogrb.2018.12.035. PMID: 30654201. https://pubmed.ncbi.nlm.nih.gov/30654201 https://doi.org/10.1016/j.ejogrb.2018.12.035

2. Krysiak R, Kowalcze K, Okopień B. Selenomethionine potentiates the impact of vitamin D on thyroid autoimmunity in euthyroid women with Hashimoto's thyroiditis and low vitamin D status. Pharmacol Rep. 2019 Apr;71(2):367-373. doi: 10.1016/j.pharep.2018.12.006. PMID: 30844687. https://pubmed.ncbi.nlm.nih.gov/30844687 https://doi.org/10.1016/j.pharep.2018.12.006

3. Krysiak R, Szkróbka W, Okopień B. The effect of vitamin D and selenomethionine on thyroid antibody titers, hypothalamic-pituitary-thyroid axis activity and thyroid function tests in men with Hashimoto's thyroiditis: A pilot study. Pharmacol Rep. 2019 Apr;71(2):243-247. doi: 10.1016/j.pharep.2018.10.012. PMID: 30818086. https://pubmed.ncbi.nlm.nih.gov/30818086 https://doi.org/10.1016/j.pharep.2018.10.012

4. Gärtner R, Gasnier BC, Dietrich JW, Krebs B, Angstwurm MW. Selenium supplementation in patients with autoimmune thyroiditis decreases thyroid peroxidase antibodies concentrations. J Clin Endocrinol Metab. 2002;87(4):1687–1691. doi:10.1210/jcem.87.4.8421 https://pubmed.ncbi.nlm.nih.gov/11932302 https://doi.org/10.1210/jcem.87.4.8421

5. Kivity S, Agmon-Levin N, Zisappl M, Shapira Y, Nagy EV, Dankó K, Szekanecz Z, Langevitz P, Shoenfeld Y. Vitamin D and autoimmune thyroid diseases. Cell Mol Immunol. 2011 May;8(3):243-7. doi: 10.1038/cmi.2010.73. Epub 2011 Jan 31. PMID: 21278761; PMCID: PMC4012880. https://pubmed.ncbi.nlm.nih.gov/21278761 https://doi.org/10.1038/cmi.2010.73

6. Krysiak R, Kowalcze K, Okopień B. The effect of vitamin D on thyroid autoimmunity in euthyroid men with autoimmune thyroiditis and testosterone deficiency. Pharmacol Rep. 2019 Oct;71(5):798-803. doi: 10.1016/j.pharep.2019.04.010. PMID: 31377561. https://pubmed.ncbi.nlm.nih.gov/31377561 https://doi.org/10.1016/j.pharep.2019.04.010

7. Krysiak R, Kowalcze K, Okopień B. The Effect of Selenomethionine on Thyroid Autoimmunity in Euthyroid Men With Hashimoto Thyroiditis and Testosterone Deficiency. J Clin Pharmacol. 2019 Nov;59(11):1477-1484. doi: 10.1002/jcph.1447. PMID: 31106856. https://pubmed.ncbi.nlm.nih.gov/31106856 https://doi.org/10.1002/jcph.1447

8. Krysiak R, Kowalcze K, Okopień B. The effect of testosterone on thyroid autoimmunity in euthyroid men with Hashimoto's thyroiditis and low testosterone levels. J Clin Pharm Ther. 2019 Oct;44(5):742-749. doi: 10.1111/jcpt.12987. PMID: 31183891. https://pubmed.ncbi.nlm.nih.gov/31183891 https://doi.org/10.1111/jcpt.12987

9. Krysiak R, Szkróbka W, Okopień B. The Impact of Testosterone on Metformin Action on Hypothalamic-Pituitary-Thyroid Axis Activity in Men: A Pilot Study. J Clin Pharmacol. 2020 Feb;60(2):164-171. doi: 10.1002/jcph.1507. PMID: 31389032. https://pubmed.ncbi.nlm.nih.gov/31389032 https://doi.org/10.1002/jcph.1507

10. Krysiak R, Kowalcze K, Okopień B. The effect of spironolactone on thyroid autoimmunity in euthyroid men with Hashimoto's thyroiditis. J Clin Pharm Ther. 2020 Feb;45(1):152-159. doi: 10.1111/jcpt.13046. PMID: 31520539. https://pubmed.ncbi.nlm.nih.gov/31520539 https://doi.org/10.1111/jcpt.13046

11. Adamska A, Krentowska A, Łebkowska A, Hryniewicka J, Leśniewska M, Adamski M, Kowalska I. Decreased deiodinase activity after glucose load could lead to atherosclerosis in euthyroid women with polycystic ovary syndrome. Endocrine. 2019 Jul;65(1):184-191. doi: 10.1007/s12020-019-01913-0. PMID: 30945110; PMCID: PMC6606654. https://pubmed.ncbi.nlm.nih.gov/30945110 https://doi.org/10.1007/s12020-019-01913-0

12. Polak A, Grywalska E, Klatka J, Roliński J, Matyjaszek-Matuszek B, Klatka M. Toll-Like Receptors-2 and -4 in Graves' Disease-Key Players or Bystanders? Int J Mol Sci. 2019 Sep 24;20(19):4732. doi: 10.3390/ijms20194732. PMID: 31554206; PMCID: PMC6801632. https://pubmed.ncbi.nlm.nih.gov/31554206 https://doi.org/10.3390/ijms20194732

13. Bingyan Z, Dong W. Impact of thyroid hormones on asthma in older adults. J Int Med Res. 2019 Sep;47(9):4114-4125. doi: 10.1177/0300060519856465. PMID: 31280621; PMCID: PMC6753544. https://pubmed.ncbi.nlm.nih.gov/31280621https://doi.org/10.1177/0300060519856465

14. Xu J, Wang L. Low T3 Syndrome as a Predictor of Poor Prognosis in Patients With Pyogenic Liver Abscess. Front Endocrinol (Lausanne). 2019 Aug 6;10:541. doi: 10.3389/fendo.2019.00541. PMID: 31447784; PMCID: PMC6691090. https://pubmed.ncbi.nlm.nih.gov/31447784 https://doi.org/10.3389/fendo.2019.00541

15. Dietrich, J.W., Ackermann, A., Kasippillai, A. et al. Adaptive Veränderungen des Schilddrüsenstoffwechsels als Risikoindikatoren bei Traumata. Trauma Berufskrankh 21, 260–267 (2019) doi:10.1007/s10039-019-00438-z https://doi.org/10.1007/s10039-019-00438-z

16. Laclaustra M, Moreno-Franco B, Lou-Bonafonte JM, Mateo-Gallego R, Casasnovas JA, Guallar-Castillon P, Cenarro A, Civeira F. Impaired Sensitivity to Thyroid Hormones Is Associated With Diabetes and Metabolic Syndrome. Diabetes Care. 2019 Feb;42(2):303-310. doi: 10.2337/dc18-1410. PMID: 30552134. https://pubmed.ncbi.nlm.nih.gov/30552134 https://doi.org/10.2337/dc18-1410

17. 20 years of #SPINA_Thyr. https://twitter.com/SPINATeam/status/1176572655400640514

18. Hoermann R, Midgley JEM, Larisch R, Dietrich JW. Individualised requirements for optimum treatment of hypothyroidism: complex needs, limited options. Drugs Context. 2019 Aug 13;8:212597. doi: 10.7573/dic.212597. PMID: 31516533; PMCID: PMC6726361. https://pubmed.ncbi.nlm.nih.gov/31516533 https://doi.org/10.7573/dic.212597

19. Hoermann R, Midgley JEM, Larisch R, Dietrich JW. Functional and Symptomatic Individuality in the Response to Levothyroxine Treatment. Front Endocrinol (Lausanne). 2019 Sep 26;10:664. doi: 10.3389/fendo.2019.00664. PMID: 31616383; PMCID: PMC6775211. https://pubmed.ncbi.nlm.nih.gov/31616383 https://doi.org/10.3389/fendo.2019.00664

20. Dietrich, J W. SPINA Thyr (Version 4.1.0 (Bonfire)). RRID:SCR_014352. 2019. doi: 10.5281/zenodo.3596049 https://doi.org/10.5281/zenodo.3596049

21. Dietrich JW, Makimoto H, Müller P. Letter by Dietrich et al Regarding Article, "Thyroid Dysfunction in Heart Failure and Cardiovascular Outcomes". Circ Heart Fail. 2019 Apr;12(4):e005854. doi: 10.1161/CIRCHEARTFAILURE.118.005854. PMID: 30998389. https://pubmed.ncbi.nlm.nih.gov/30998389 https://doi.org/10.1161/circheartfailure.118.005854

-- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- --
-- PD Dr. med. Johannes W. Dietrich
-- Laboratory XU44, Endocrine Research
-- Medical Hospital I, Bergmannsheil University Hospitals
-- Ruhr University of Bochum
-- Buerkle-de-la-Camp-Platz 1, D-44789 Bochum, NRW, Germany
-- Phone: +49:234:302-6400, Fax: +49:234:302-6403
-- eMail: "johannes.dietrich at ruhr-uni-bochum.de"
-- http://www.thyreologie.com.de
-- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- --

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