Dr Johannes Dietrich of our group has for some time beeen developing a computer programme to detect and analyse thyroid function changes and related influences on thyroid function. I append his summary of 2019's findings below:
You might find some things of interest eg selenium and Vit D effects
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].
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]
