[SPINA] SPINA Thyr – Year in Review 2021

Sa Jan 1 23:57:02 CET 2022

Dear subscribers of the SPINA list:

It has become some sort of tradition to deliver in the beginning of a new year a retrospective view on the development of the SPINA methodology and the associated software. I don’t want to do without this now, too.

Mankind had to suffer from another Corona year. Certainly, most of us didn’t expect that the COVID-19 pandemic would wear on for such a long time.

Despite all difficulties, at least the SPINA methodology enjoyed continued attention. Again, multiple studies demonstrated the utility of the methodology for our pathophysiological understanding and for clinical applications.

Traditionally, the group of Robert Krysiak in Katowice uses to publish pharmacological trials using the SPINA technique. In a paper published in the journal Clinical and Experimental Pharmacology and Physiology they report a stimulatory effect of supplementation therapy with vitamin D on thyroid’s secretory capacity (SPINA-GT) in women [1]. This effect is potentiated by simultaneous therapy with dehydroepiandrosterone (DHEA). The group made a similar observation in men, where the effect was reduced in early-onset andro-genetic alopecia [2]. Both papers underscore the complex (and still not fully understood) interaction of sex hormones, vitamin D metabolism and thyroid homeostasis.

The already well-known effect of metformin treatment on SPINA-GT and thyroid function, in general, was confirmed by a new study that demonstrated thyroid’s secretory capacity to rise under metformin [3]. However, this effect was only observed in those women that also received hormone replacement therapy with oestradiol.

Already in the last retrospective, we reported on a Chinese study that showed the phenotype of Parkinsonian disease to be related to SPINA-GT and total deiodinase activity (SPINA-GD). This observation was now repeatedly delineated in a small Chinese review article [4].

Of course, it would be an act of omission to withhold negative results. A Chinese group didn’t find a relation between serum concentrations of the resolvin D1 (RVD1) and SPINA-GT or SPINA-GD (in a, however, very small population) [5]. They found, however, associations to the central set point of thyroid homeostasis, quantified with Jostel’s TSH index and TTSI.

A large population-based observational study from Germany including the SHIP and SHIP-2 cohorts found an age-dependent correlation of biomarkers of body composition with SPINA-GD and Jostel’s TSH index [6]. This may reflect effects of allostatic load. This paper was also reviewed and discussed in the blog of the German Society of Endocrinology (Deutsche Gesellschaft für Endokrinologie, DGE) [7].

Another population-based study, conducted in the Chinese province Fujian, found a significant negative correlation of markers for metabolic syndrome (e. g. BMI and WHR) and SPINA-GT [8]. Open remains the question if reduced thyroid’s secretory capacity reflects obesity-induced degeneration of the thyroid or a causative factor for metabolic syndrome.

A study including subjects undergoing coronary intervention could show reduced sum activity of peripheral step-up deiodinases (SPINA-GD) to be a significant predictor of major cardiovascular and cerebrovascular events (MACCE) [9]. This may reflect non-thyroid illness syndrome (NTIS) or thyroid allostasis in critical illness, tumours, uraemia and starvation (TACITUS).

Another Chinese study suggests SPINA-GT, SPINA-GD and a quite new marker for the central set point of the feedback loop (TFQI) to predict the development of impaired kidney function and renal failure [10]. TACITUS may play a role here as well.

The substantial role that endocrine disruptors play in the development of several chronic diseases is increasingly recognised. A study could now demonstrate a significant positive correlation between the urinary excretion of phthalates with SPINA-GT and SPINA-GD in subjects with type 2 diabetes [11].

For about 200 years it is known that thyroid hormones strongly influence the heart rhythm. The mechanism is, however, still poorly understood. In an own study, we could show that SPINA-GT significantly correlates to the Tp-e and JT intervals in ECG recordings [12]. These repolarisation markers are important predictors of severe arrhythmia and sudden cardiac death. Disturbed repolarisation may play a significant part in the increased cardiovascular risk in thyrotoxicosis.

At the end of the year, an interesting psychoendocrinological paper was published. In a cohort of subjects with schizophrenia, it could be demonstrated that SPINA-GT and markers of the central set point of the feedback loop significantly decrease under therapy with oxcarbazepine [13]. The paper that was published in the British Journal of Clinical Pharmacology delivers a possible explanation for the well-known, but still poorly understood influence of this dibenzazepine on thyroid function.

Together with markers for tissue effects of thyroid hormones structural parameters of the feedback loop including SPINA-GT and SPINA-GD might in future be helpful to solve the ongoing controversy of subclinical thyroid disorders [14].

Please keep again in mind that this list may be incomplete. Of course, I can only report on papers that are known to me. An automated PubMed query used by us is unable to find all publications as well. Any hints to overlooked papers are welcome.

On May 26th, 2021 we published SPINA Thyr 4.2. This version introduces some new functionality, including roaming support for managed Windows installations (as employed e. g. by large hospitals) and bug fixes. SPINA Thyr 4.2 is available for macOS, Windows and Linux.

Since its publication at SourceForge the software was downloaded there more than 10,000 times, from 116 countries in all continents except Antarctica (but including near-earth space). Please find current news on SPINA again via http://spina.sourceforge.net or our Twitter channel at https://twitter.com/SPINATeam.

Please allow me at the end a hint in my own account: On September 30th, 2021 I left after more than 16 years, nearly 10 of them as a consultant endocrinologist, the Bergmannsheil University Hospitals in order to become head of the newly founded Diabetes, Endocrinology and Metabolism section at the St. Josef Hospital in Bochum and of the Diabetes Centre Bochum/Hattingen in Blankenstein. After decades of a decline of endocrine departments in Germany, I am honoured to contribute to a turn of the tides and to help establish a new University-affiliated endocrine department that will be one of the largest in Western Germany. Therefore, please don’t use my eMail address at the Bergmannsheil hospitals any longer. The address at the Ruhr University continues to be valid.

With kind regards and best wishes for you in the new year 2022,
JWD

References

1. Krysiak R, Szkróbka W, Okopień B. Dehydroepiandrosterone potentiates the effect of vitamin D on thyroid autoimmunity in euthyroid women with autoimmune thyroiditis: A pilot study. Clin Exp Pharmacol Physiol. 2021 Feb;48(2):195-202. doi: 10.1111/1440-1681.13410. Epub 2020 Oct 16. PMID: 33007106. https://pubmed.ncbi.nlm.nih.gov/33007106/ https://doi.org/10.1111/1440-1681.13410

2. Krysiak R, Kowalcze K, Okopień B. The impact of exogenous vitamin D on thyroid autoimmunity in euthyroid men with autoimmune thyroiditis and early-onset androgenic alopecia. Pharmacol Rep. 2021 Oct;73(5):1439-1447. doi: 10.1007/s43440-021-00295-3. Epub 2021 Jun 9. PMID: 34106452; PMCID: PMC8460519. https://pubmed.ncbi.nlm.nih.gov/34106452/ https://doi.org/10.1007/s43440-021-00295-3 

3. Krysiak R, Kowalcze K, Okopień B. The impact of metformin on hypothalamic-pituitary-thyroid axis activity in postmenopausal women with untreated non-autoimmune subclinical hypothyroidism. Clin Exp Pharmacol Physiol. 2021 Nov;48(11):1469-1476. doi: 10.1111/1440-1681.13542. Epub 2021 Jun 29. PMID: 34145615. https://pubmed.ncbi.nlm.nih.gov/34145615/ https://doi.org/10.1111/1440-1681.13542 

4. 谭寅寅: 血清甲状腺激素和甲状腺稳态结构参数测定在帕金森病临床分型中的意义. https://cdmd.cnki.com.cn/Article/CDMD-10422-1020061647.htm

5. Song J, Sun R, Zhang Y, Fu Y, Zhao D. Role of the Specialized Pro-resolving Mediator Resolvin D1 in Hashimoto's Thyroiditis. Exp Clin Endocrinol Diabetes. 2021 Nov;129(11):791-797. doi: 10.1055/a-1345-0173. Epub 2021 Jan 19. PMID: 33465800. https://pubmed.ncbi.nlm.nih.gov/33465800/ https://doi.org/10.1055/a-1345-0173 

6. Ittermann T, Markus MRP, Bahls M, Felix SB, Steveling A, Nauck M, Völzke H, Dörr M. Low serum TSH levels are associated with low values of fat-free mass and body cell mass in the elderly. Sci Rep. 2021 May 18;11(1):10547. doi: 10.1038/s41598-021-90178-7. PMID: 34006958; PMCID: PMC8131378. https://pubmed.ncbi.nlm.nih.gov/34006958/ https://doi.org/10.1038/s41598-021-90178-7 

7. Dietrich JW. Erhöhte TSH-Konzentration bei Adipositas: Beginnende Hypothyreose oder Sollwert-Verstellung im Hypothalamus? Zum Weltschilddrüsentag am 25. Mai 2021. Blog der DGE. https://blog.endokrinologie.net/erhoehte-tsh-konzentration-bei-adipositas-4847/

8. Wu K, Zhou Y, Ke S, Huang J, Gao X, Li B, Lin X, Liu X, Liu X, Ma L, Wang L, Wu L, Wu L, Xie C, Xu J, Wang Y, Liu L. Lifestyle is associated with thyroid function in subclinical hypothyroidism: a cross-sectional study. BMC Endocr Disord. 2021 May 28;21(1):112. doi: 10.1186/s12902-021-00772-z. PMID: 34049544; PMCID: PMC8161919. https://pubmed.ncbi.nlm.nih.gov/34049544/ https://doi.org/10.1186/s12902-021-00772-z 

9. Yuan D, Jia S, Zhu P, Zhang C, Liu Y, Liu R, Xu J, Tang X, Zhao X, Gao R, Yang Y, Xu B, Gao Z, Yuan J. Usefulness of FT3 to FT4 Ratio to Predict Mortality in Euthyroid Patients With Prior Cardiovascular Events Undergoing PCI: Five-Year Findings From a Large Single-Center Cohort Study. Front Endocrinol (Lausanne). 2021 Jul 5;12:700349. doi: 10.3389/fendo.2021.700349. PMID: 34290672; PMCID: PMC8287966. https://pubmed.ncbi.nlm.nih.gov/34290672/ https://doi.org/10.3389/fendo.2021.700349 

10. Yang S, Lai S, Wang Z, Liu A, Wang W, Guan H. Thyroid Feedback Quantile-based Index correlates strongly to renal function in euthyroid individuals. Ann Med. 2021 Dec;53(1):1945-1955. doi: 10.1080/07853890.2021.1993324. PMID: 34726096; PMCID: PMC8567884. https://pubmed.ncbi.nlm.nih.gov/34726096/ https://doi.org/10.1080/07853890.2021.1993324 

11. Chen Y, Zhang W, Chen J, Wang N, Chen C, Wang Y, Wan H, Chen B, Lu Y. Association of Phthalate Exposure with Thyroid Function and Thyroid Homeostasis Parameters in Type 2 Diabetes. J Diabetes Res. 2021 Oct 27;2021:4027380. doi: 10.1155/2021/4027380. PMID: 34746318; PMCID: PMC8566079. https://pubmed.ncbi.nlm.nih.gov/34746318/ https://doi.org/10.1155/2021/4027380 

12. Aweimer A, Schiedat F, Schöne D, Landgrafe-Mende G, Bogossian H, Mügge A, Patsalis PC, Gotzmann M, Akin I, El-Battrawy I, Dietrich JW. Abnormal Cardiac Repolarization in Thyroid Diseases: Results of an Observational Study. Front Cardiovasc Med. 2021 Nov 23;8:738517. doi: 10.3389/fcvm.2021.738517. PMID: 34888359; PMCID: PMC8649843. https://pubmed.ncbi.nlm.nih.gov/34888359/ https://doi.org/10.3389/fcvm.2021.738517 

13. Zhai D, Chen J, Guo B, Retnakaran R, Gao S, Zhang X, Hao W, Zhang R, Zhao Y, Wen SW. Oxcarbazepine was associated with risks of newly developed hypothyroxinaemia and impaired central set point of thyroid homeostasis in schizophrenia patients. Br J Clin Pharmacol. 2021 Dec 1. doi: 10.1111/bcp.15163. Epub ahead of print. PMID: 34855997. https://pubmed.ncbi.nlm.nih.gov/34855997/ https://doi.org/10.1111/bcp.15163 

14. Hoermann R, Midgley JEM, Larisch R, Dietrich JW. Treatment options for subclinical hypothyroidism. Eur J Endocrinol. 2021 Aug 4;185(3):L5-L6. doi: 10.1530/EJE-20-1405. PMID: 34243143. https://pubmed.ncbi.nlm.nih.gov/34243143/ https://doi.org/10.1530/eje-20-1405

-- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- --
-- PD Dr. med. Johannes W. Dietrich
-- Diabetes, Endocrinology and Metabolism Section
-- Department of Medicine I, St. Josef Hospital
-- Ruhr University of Bochum
-- Gudrunstr. 56, D-44791 Bochum, NRW, Germany
-- Phone: +49:234:509-2311, Fax: +49:234:509-2309
-- eMail: "johannes.dietrich at ruhr-uni-bochum.de"
-- http://www.thyreologie.com.de
-- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- —

Call for papers: We have launched a Research Topic on Thyroid Hormones and Cardiac Arrhythmia in the journals Frontiers in Endocrinology and Frontiers in Cardiovascular Medicine.
To participate please visit https://www.frontiersin.org/research-topics/16898/thyroid-hormones-and-cardiac-arrhythmia.

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