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SPINA Team @spinateam.bsky.social · 20/09/2026

The R package for #SPINA has been upgraded to version 5.1. It includes both #SPINA_Thyr and #SPINA_Carb. More information is available at cran.r-project.org/web/packages... Packages for macOS and Linux are ready. For Windows, they will be available in a few days. @r-foundation.bsky.social #RStats

Screenshot of the statistical environment R showing the package manager with a suggested upgrade of the SPINA package to version 5.1.

Screenshot of the statistical environment R showing general information on the SPINA package in version 5.1.

Screenshot of the statistical environment R showing information on SPINA.GBeta, along with demo code.

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Johannes W. Dietrich @drjwdietrich.bsky.social · 13/08/2026

Given the possibility of #Syndrome_T, not all patients who undergo #hemithyroidectomy will benefit. Two new risk scores identify predictors for #hypothyroidism, warranting therapy with #levothyroxine. #thyroid #QoL doi.org/10.3390/diag... 🧪 🩺 #MedSky @medsky.social Endocrinology #Endosky

Table: Two simplified clinical risk scores for predicting postoperative hypothyroidism after hemithyroidectomy. Score 1 contains preoperative TSH, remnant thyroid volume and heterogeneity in ultrasound. Score 2 includes TSH and thyroid autoantibodies.

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SPINA Team @spinateam.bsky.social · 13/08/2026

After #hemithyroidectomy, some patients will develop #hypothyroidism, whilst in others the #thyroid continues to function. The best parameter to predict postoperative hypothyroidism is #SPINA-GT. #SPINA_Thyr doi.org/10.3390/diag...

Figure: Receiver operating characteristic (ROC) curves of preoperative TSH, TSHI, SPINA-GT, remnant thyroid volume, and remnant thyroid volume-to-BSA ratio for predicting postoperative hypothyroidism after hemithyroidectomy. SPINA-GT has the highest area under the curve.

Table: Univariable logistic regression analysis of predictors of postoperative hypothyroidism. SPINA-GT has the highest odds ratio and Nagelkerke R^2.

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Johannes W. Dietrich @drjwdietrich.bsky.social · 06/08/2026

#Thyroid dysfunction may cause sudden death. However, thyroid hormones respond to #stress as well. A recent autopsy study found #SPINA-GD or Jostel's TSH index increased in all cases, highlighting the importance of type 2 #allostatic_load. pubmed.ncbi.nlm.nih.gov/41997212/ doi.org/10.1055/a-28...

Table: Thyroid and cardiovascular pathology and interpretation in cases of sudden death with thyrotoxicosis

Supplementary table: Thyroid homeostasis indices (SPINA-GT, SPINA-GD and Jostel's TSH index) and thyroid hormone therapy in seven autopsy cases of sudden death in thyrotoxicosis

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SPINA Team @spinateam.bsky.social · 28/07/2026

#Thyroid #hormones play a critical role in the central nervous system. Recent research shows that #SPINA-GT is associated with progression-related motor heterogeneity in spinocerebellar ataxia type 3. pubmed.ncbi.nlm.nih.gov/42251968/ doi.org/10.1016/j.nb... www.livivo.de/doc/M42251968

Table: Clinical characteristics and thyroid-related measures of ATXN3 carriers and healthy controls. SPINA-GT is significantly higher in carriers of CAG repeat expansions in the ATXN3 gene than in healthy controls and especially in ataxic carriers.

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Johannes W. Dietrich @drjwdietrich.bsky.social · 15/07/2026

Our book on #Hypothyroidism is now available in 5 formats: Printed hardcover, printed softcover (both in full colour), MyCopy softcover (price reduced, monochrome, for members of universities) and 2 eBooks (PDF and EPUB), rendering it accessible to more readers. doi.org/10.1007/978-...

Printed versions of the book "Hypothyroidism" by Rudolf Hoermann and Johannes W. Dietrich, Springer Singapore 2025

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Johannes W. Dietrich @drjwdietrich.bsky.social · 16/06/2026

#MCT8 deficiency or #Allan-Herndon-Dudley syndrome is a rare disorder of #thyroid hormone transport, leading to severe neurodevelopmental delay. See our newest paper for monitoring recommendations. pubmed.ncbi.nlm.nih.gov/41926547/ doi.org/10.1159/0005... www.livivo.de/doc/M41926547

Title page of the paper "Clinical and Biochemical Monitoring of Monocarboxylate Transporter 8 Deficiency (Allan-Herndon-Dudley Syndrome) across the Lifespan: Practical Considerations for Multidisciplinary Care"

Graphical abstract summarising the multidisciplinary consensus process.

Table: Proposed panel of biomarkers for monitoring in MCT8 deficiency

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SPINA Team @spinateam.bsky.social · 13/06/2026

In women with latent (i. e., euthyroid) autoimmune #thyroiditis, both #SPINA-GT and #SPINA-GD rise in #pregnancy, provided the supply of #selenium and vitamin D is sufficient. This observation may reflect physiological type 2 #allostatic reactions or reduced autoimmunity. doi.org/10.3390/nu18...

Table from the paper: Thyroid antibodies, hormones, and calculated parameters of thyroid homeostasis in mothers of female infants included in the study (the intent-to-treat analysis). SPINA-GT and SPINA-GD rise in parallel to declining thyroid autoantibodies.

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SPINA Team @spinateam.bsky.social · 16/05/2026

The Mediterranean diet reduces the workload of pancreatic #beta-cells, as measured by their secretory capacity (#SPINA-GBeta). 🩺 #MedSky @medsky.social #Endocrinology #Endosky pubmed.ncbi.nlm.nih.gov/42124052/ doi.org/10.3390/nu18... www.livivo.de/doc/M42124052

Figure from the paper showing the evolution of SPINA-GBeta with different levels of adherence to Mediterranean diet and exercise. SPINA-GBeta is reduced in the group with high adherence to Mediterranean diet, probably due to diminished workload of pancreatic beta-cells.

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Johannes W. Dietrich @drjwdietrich.bsky.social · 15/05/2026

Wiley sent us a note that our paper defining the static disposition index #SPINA-DI is among the top-viewed articles of the Journal of Diabetes. pubmed.ncbi.nlm.nih.gov/38169110/ doi.org/10.1111/1753... www.livivo.de/doc/M38169110

Certificat stating that the article "A novel simple disposition index (SPINA-DI) from fasting insulin and glucose concentration as a robust measure of carbohydrate homeostasis" is among the top-viewed papers in the Journal of Diabetes.

Abstract

Aims: The widely used dynamic disposition index, derived from oral glucose tolerance testing, is an integrative measure of the homeostatic performance of the insulin-glucose feedback control. Its collection is, however, time consuming and expensive. We, therefore, pursued the question if such a measure can be calculated at baseline/fasting conditions using plasma concentrations of insulin and glucose.

Methods: A new fasting-based disposition index (structure parameter inference approach-disposition index [SPINA-DI]) was calculated as the product of the reconstructed insulin receptor gain (SPINA-GR) times the secretory capacity of pancreatic beta cells (SPINA-GBeta). The novel index was evaluated in computer simulations and in three independent, multiethnic cohorts. The objectives were distribution in various populations, diagnostic performance, reliability and correlation to established physiological biomarkers of carbohydrate metabolism.

Results: Mathematical and in-silico analysis demonstrated SPINA-DI to mirror the hyperbolic relationship between insulin sensitivity and beta-cell function and to represent an optimum of the homeostatic control. It significantly correlates to the oral glucose tolerance test based disposition index and other important physiological parameters. Furthermore, it revealed higher discriminatory power for the diagnosis of (pre)diabetes and superior retest reliability than other static and dynamic function tests of glucose homeostasis.

Conclusions: SPINA-DI is a novel simple reliable and inexpensive marker of insulin-glucose homeostasis suitable for screening purposes and a wider clinical application.

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SPINA Team @spinateam.bsky.social · 10/05/2026

Another study highlights advantages of SPINA-GBeta over the #HOMA method, here with correlation to the adherence of #mediterranean diet. #SPINA_Carb #SPINA-GBeta #SPINA-GR #SPINA-DI doi.org/10.3390/nu18...

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SPINA Team @spinateam.bsky.social · 10/04/2026

#SPINA-GT correlates to the grading of colour #Doppler #ultrasound investigations in #hyperthyroidism and #thyrotoxicosis. pubmed.ncbi.nlm.nih.gov/35942151/ www.livivo.de/doc/M35942151 doi.org/10.1155/2022...

Figure from the paper: Two levels of perfusion in colour Doppler ultrasound. Low perfusion corresponds to level 1, high perfusion to level 2.

Table from the paper: SPINA-GT is significantly higher in level 2 perfusion than in level 1 perfusion.

Table from the paper: SPINA-GT correlates to colour Doppler ultrasound grading.

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SPINA Team @spinateam.bsky.social · 07/04/2026

In an adjusted model, #SPINA-GD correlates significantly with type 2 allostatic load. It parallels the association to central markers of thyroid homeostasis, underscoring the TSH-T3 feedforward control. #thyroid #allostasis pubmed.ncbi.nlm.nih.gov/41941533/ doi.org/10.1080/1025...

Table of the paper: Unadjusted and adjusted correlation models for the association between allostatic load and calculated biomarkers of thyroid homeostasis. The allostatic load correlates with Jostel's TSH index (TSHI), TTSI, TFQI and SPINA-GD.

Table of the paper: In adjusted models, SPINA-GD is higher in quartiles 2 to 4 of allostatic load than in the baseline quartile 1.

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SimulAdrenTeam @simuladrenteam.bsky.social · 24/03/2026

#SimulAdren underwent a major upgrade. Version 2.0 introduces significant new features, e.g., support for different models, initial conditions, first-order delay kinetics (ASIA elements), and model continuation. simuladren.sourceforge.io doi.org/10.5281/zeno... doi.org/10.5281/zeno...

Screenshot of SimulAdren 2.0 (Rubycon) on macOS 13.7 (Ventura).

Screenshot of SimulAdren 2.0 (Rubycon) on Windows 11

Screenshot of SimulAdren 2.0 (Rubycon) on Fedora Linux 38

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Johannes W. Dietrich @drjwdietrich.bsky.social · 20/03/2026

Mathematical modelling, computer #simulation, and machine learning upgrade #endocrinology. Applying principles of #biocybernetics and #biophysics, they enjoy growing interest and deliver novel methods for research, diagnosis, and therapy. pubmed.ncbi.nlm.nih.gov/41852474/ doi.org/10.3389/fend...

Two bar plots from the paper:

Yearly numbers of publications in PubMed from 1965 to 2025 on mathematical modelling in endocrinology and diabetes with (left) and without (right) machine learning.

Search terms were “(“mathematical modelling” OR “computer simulation” OR “machine learning”) AND (endocrinology OR endocrine OR hormone OR hormonal OR diabetes)” for the left plot and “(“mathematical modelling” OR “computer simulation”) AND (endocrinology OR endocrine OR hormone OR hormonal OR diabetes)” for the right plot.

The left chart shows a dramatic increase, peaking sharply in the year 2025 at nearly 3000 publications. The right chart shows moderate growth with peaks around four hundred around the year 2025.

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Johannes W. Dietrich @drjwdietrich.bsky.social · 25/01/2026

#Takotsubo syndrome (TTS) is a poorly understood life-threatening #cardiomyopathy. With machine learning, we found 3 signatures of #thyroid #homeostasis heralding the prognosis of patients affected by TTS. pubmed.ncbi.nlm.nih.gov/38502972/ doi.org/10.1016/j.eb... www.livivo.de/doc/M38502972

Figure: Definition of clusters. Thyroid response and pituitary response curves denote the median of thyroid’s secretory capacity (SPINA-GT) and empirical thyrotropic pituitary response.

Figure: Association of clusters with total fatality (left) and time-course of survival (right).

Table: Characteristics of the three clusters. The figures in the first two lines refer to medoids of TSH and FT4 concentration as identified by the clustering algorithm.

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Johannes W. Dietrich @drjwdietrich.bsky.social · 24/12/2025

#Takotsubo syndrome is a dangerous stress-related #heart disease. Since #T3 upregulates β-receptors, we assumed a link to #thyroid homeostasis. With machine learning, we identified interesting allostatic patterns. www.livivo.de/doc/M33179374 pubmed.ncbi.nlm.nih.gov/33179374/ doi.org/10.1111/joim...

Figure: Bivariate null isokline plot of first measured FT4 and TSH serum concentrations per subject in relation to percentiles of subsystem responses of thyroid homeostasis. Shown are three different point clouds, representing three clusters: Normal controls (green dots in the center), critically-ill patients with acute coronary syndroms (black dots in the lower zone of TSH concentration) and patientes with Takotsubo syndrome (red dots in two cloucs with low and high TSH concentration).

Distribution (mean ± SEM) of measured and derived parameters in TTS during the first seven days of treatment. The shaded rectangles mark the reference ranges for the respective parameters. *P < 0.05, **P < 0.01, ***P < 0.001, *****P < 1e–5 compared to reference range with binomial test; P values are adjusted with the Benjamini–Hochberg method. SPINA-GT is elevated, and SPINA-GD is reduced during the first three days of Takotsubo syndrome. TTSI is elevated on day 3, representing a high set point of thyroid homeostasis as a consequence of type 2 allostatic load.

Abnormal thyroid function in Takotsubo syndrome is marked by two distinct phenotypes: an endocrine type representing primary hyperthyroidism and a stress type with an elevated set point of thyroid homeostasis. The results suggest a stress-dependent adaptive endocrine response or type 2 thyroid allostasis.

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SPINA Team @spinateam.bsky.social · 26/09/2025

Mathematical modelling of #insulin-#glucose #homeostasis delivers new and improved methods for metabolic endotyping. #prediabetes #diabetes #metabolic_syndrome #betacell pubmed.ncbi.nlm.nih.gov/36271244/ doi.org/10.1038/s415...

Information processing structure of the feedback model. [G](t): glucose concentration; S(t): insulin secretion rate; [I](t): insulin concentration; M(t): proximal insulin signalling; N(t) distal insulin signalling; P(t): constitutive glucose production rate; Q(t): regulated glucose production rate; W(t): intestinal glucose absorption rate; R(t): glucose arrival rate. G1 and G3 represent gains of ASIA elements. Units of measurement are displayed in the small, rounded boxes with red margins.

Circular Maps of the correlation networks of novel biomarkers for insulin-glucose homeostasis with anthropometric and experimental data in the NHANES cohort (A) and the clamp study (B). Shown are significant correlations (p < 0.05) only, and line thickness indicates the strength of negative (blue) or positive (red) correlation. A green segment in the inner ring indicates a reduction of the corresponding biomarker in subjects with diabetes.

Plot of SPINA-GBeta against SPINA-GR, suggesting a compensatory rise of beta cell function in the case of declining insulin sensitivity in subjects with normal glucose homeostasis (green dots). This ability of beta cell compensation is partly lost in subjects with prediabetes (orange dots) or diabetes (red dots).

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SPINA Team @spinateam.bsky.social · 20/09/2025

Gestational #diabetes mellitus (GDM) is linked to significant adverse outcomes for both mothers and their offspring. Since #SPINA-GBeta outperforms #HOMA-Beta, its use is advised as a preferred calculated #biomarker for the evolution and pathophysiology of #GDM. pubmed.ncbi.nlm.nih.gov/40943638/

Molecular Mechanisms in gestational diabetes mellitus (GDM). Pregnancy-induced insulin resistance is driven by placental hormones
(human placental lactogen (hPL), placental growth hormone, estrogen, progesterone, cortisol) and inflammatory cytokines (tumour necrosis factor α (TNF α), interleukin 6 (IL-6), interleukin 1β (IL-1β)). Inadequate β-cell adaptation due to mitochondrial dysfunction, and impaired incretin
signaling leads to hyperglycemia. Dysregulated adipokines (decreased adiponectin, increased leptin, resistin, visfatin), oxidative stress, and epigenetic modifications (deoxyribonucleic acid (DNA) methylation, non-coding ribonucleic acids (RNAs)) further exacerbate disease and contribute to adverse maternal and fetal outcomes.

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Johannes W. Dietrich @drjwdietrich.bsky.social · 07/09/2025

Are you researching #endocrine #feedback control systems? Our Research Topic "Mechanistic, Machine Learning and Hybrid Models of the 'Other' Endocrine Regulatory Systems in Health and Disease: Volume II" is still open for submission. www.frontiersin.org/research-top... #endocrinology #cybernetics

Screenshot of the web site of the Research Topic "Mechanistic, Machine Learning and Hybrid Models of the 'Other' Endocrine Regulatory Systems in Health and Disease: Volume II" in Frontiers in Systems Endocrinology

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Johannes W. Dietrich @drjwdietrich.bsky.social · 17/08/2025

Patients with #hypothyroidism, even when treated with levothyroxine (L-T4), face increased risk of #dementia and #fatality. Fortunately, the risk can be lowered again by a combination therapy with L-T4 and L-T3, as shown by a recent study. pubmed.ncbi.nlm.nih.gov/40579157/ doi.org/10.1210/clin...

Table showing increased risk of dementia, atrial fibrillation and fatality in patients with treated hypothyroidism in a follow-up of 20 years

Forest plot showing increased risk of dementia in patients with treated hypothyroidism

Table with the results of multivariable regression analysis, showing significantly increased risk for dementia and fatality in monotherapy with L-T4 compared to combination therapy of L-T4 and L-T3 or DTE

Table showing increased risk for dementia, atrial fibrillation and fatality in patients receiving monotherapy with L-T4 compared to combination therapy consisting of L-T4 and L-T3 or DTE.

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Johannes W. Dietrich @drjwdietrich.bsky.social · 19/07/2025

For the diagnosis and management of #hypothyroidism, measuring #TSH (thyrotropin) concentration is necessary, but it isn’t sufficient. Additional #biomarkers help to improve diagnostic power and to identify #endotypes of dysregulation. doi.org/10.1007/978-... 🧪 🩺 #MedSky

Sketch of pituitary-thyroid feedback control (HPT axis) maintaining thyroid homeostasis. This figure provides an overview of biomarkers for TR-alpha (Heart rate, ECG QT interval, JT interval, Tp-e interval and ostase concentration, painted in cyan) and TR-beta (concentrations of ceruloplasmin, copper, SHBG, CK, lipids, painted in orange) signalling and of functional biomarkers (SPINA-GT, SPINA-GD, Jostel’s TSH index, TTSI, TFQI, rounded boxes).

Positive and negative biomarkers for thyroid hormone action in tissues. Positive biomarkers for TR-alpha signalling include bone-specific alkaline phosphatase (ostase) and heart rate, negative biomarkers for TR-alpha signalling comprise QT interval, JT interval and TP-e interval in the ECG. Positive biomarkers for TR-beta signalling are 3-methylhistidine, coeruloplasmin, copper and sex-hormone binding globulin (SHBG), negative biomarkers for TR-beta signalling include lipids (total cholesterol, low-density lipoprotein [LDL], high-density lipoprotein [HDL], lipoprotein a [Lp(a)] and triglycerides) and creatine kinase (CK).

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SPINA Team @spinateam.bsky.social · 19/07/2025

#SPINA_Thyr and #SPINA_Carb, two implementations of the structure parameter inference approach (SPINA), provide evidence-based improved methods for diagnosis and endotyping of endocrine diseases. Now, thoroughly tested apps for Mac and Windows are available for free download. spina.sf.net

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SPINA Team @spinateam.bsky.social · 13/07/2025

SPINA Carb 5.1.0 Cyclone has been released in its final version. #SPINA-GBeta #SPINA-GR #SPINA-DI #SPINA_Carb #insulin #glucose #homeostasis #prediabetes #diabetes sourceforge.net/projects/spi... doi.org/10.5281/zeno... doi.org/10.5281/zeno...

Screenshot of SPINA Carb 5.1.0 Cycline on macOS 15.5 Sequoia, showing two Windows (entry and results).

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SPINA Team @spinateam.bsky.social · 21/06/2025

Release candidate 3 for the software SPINA Carb Cyclone is available for macOS, Windows and Linux. sourceforge.net/projects/spi... doi.org/10.5281/zeno... doi.org/10.5281/zeno... #SPINA_Carb #SPINA-GBeta #SPINA-GR #SPINA-DI #HOMA

Screenshot of release candidate 3 of SPINA Carb 5.1 Cyclone on mac OS 15.5 Sequoia

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Johannes W. Dietrich @drjwdietrich.bsky.social · 14/06/2025

Multiple feedforward motifs and feedback loops maintain #thyroid #homeostasis and #allostasis. The mechanism of relational stability maintains T3 in a balanced and safe range, even in conditions of declining thyroid function. doi.org/10.1007/978-... 🧪 🩺 #MedSky

Hypothalamic–pituitary–thyroid regulation is implemented by multiple feedforward motifs and feedback loops.

Demonstration of attainment of perfect FT3 homeostasis in hypothalamic–pituitary–thyroid axis regulation in a mathematical model. The interactive loops of the hypothalamic–pituitary–thyroid axis regulation enable the actions of TRH (not shown), TSH, and FT4 to cooperate in a way to produce an equilibrium solution of perfect homeostasis for FT3. This is an example of relational stability. The strengths of all limbs have been normalised.

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SPINA Team @spinateam.bsky.social · 08/06/2025

In patients undergoing #thyroid surgery due to nodules, #SPINA-GT is lower (and the set point of the homeostatic system higher) in cases of thyroid cancer compared to benign nodules. doi.org/10.3389/fend...

Table: Characteristics of euthyroid subjects with benign disease or differentiated thyroid cancer. Patients with cancer have lower SPINA-GT and a higher set point (TSHI and TT4RI) than patients with benign nodules.

Table: Association between thyroid parameters (per SD change) and differentiated thyroid cancer in total subjects. SPINA-GT is negatively associated with the presence of cancer.

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Johannes W. Dietrich @drjwdietrich.bsky.social · 07/06/2025

Signalling via #thyroid hormones is more than T3 and T4. It involves 27 molecules based on the thyronine skeleton, 10 transmembrane transporters, 3 deiodinases, 6 receptors, and 4 types of action, unfolding a complex firework of possibilities, explaining health and disease. doi.org/10.1007/978-...

Table from the book "Hypothyroidism – a Paradigm Shift" by Hoermann and Dietrich: Four receptor types (THRalpha1, THRbeta1, THRbeta2, THRbeta3, p43 and alphaVbeta3) convey thyroid signals in different tissues.

Table from the book "Hypothyroidism – a Paradigm Shift" by Hoermann and Dietrich: Eleven types of transporters with different hormone- and tissue-specificity carry thyroid hormones through cell membranes.

Figure from the book "Hypothyroidism – a Paradigm Shift" by Hoermann and Dietrich, showing an opened cell with the interaction of different thyroid hormones, transporters, deiodinases and signaling types.

Table from the book "Hypothyroidism – a Paradigm Shift" by Hoermann and Dietrich: Three types of deiodinases mediate step-up and step-down reactions interconverting thyroid hormones and leading to activation and inactivation.

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Johannes W. Dietrich @drjwdietrich.bsky.social · 04/06/2025

Our book is now available in printed form. Use the code SPRAUT to get a discount of 20% at Springer Nature. link.springer.com/book/9789819...

A stack with several printed books, "Hypothyroidism – A Paradigm Shift" by Rudolf Hoermann and Johannes W. Dietrich.

Flyer for the book "Hypothyroidism – A Paradigm Shift" by Rudolf Hoermann and Johannes W. Dietrich. Use the code SPRAUT to get a discount of 20% at Springer Nature.

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SimThyrTeam @simthyrteam.bsky.social · 31/05/2025

Computer simulations with #SimThyr enhance our understanding of the physiology of hypothalamic-pituitary-thyroid feedback control. This applies, for example, to the evolution of #TACITUS syndrome. #thyroid #hypothyroidism #NTIS #biocybernetics doi.org/10.1007/978-...

Figure from the book "Hypothyroidism: A Paradigm Shift" by Hoermann and Dietrich: Combination of peripheral and central mechanisms leading to the low-T3 syndrome. The activities of peripheral (GD1) and central (GD2) deiodinases diverge to cause the low-T3 phenotype. The graph shown has been produced by computer simulation with the free app SimThyr.

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Johannes W. Dietrich @drjwdietrich.bsky.social · 27/05/2025

Our eBook on #hypothyroidism has been published. The new cybernetic theory presented here summarises our scientific work of more than 20 years and lays the foundation for improved diagnosis and therapy of #thyroid disorders. The book is available in EPUB and PDF formats. doi.org/10.1007/978-...

Title page of the book "Hypothyroidism" by Hoermann and Dietrich.

This book revolutionizes our understanding of the regulation of the hypothalamic-pituitary-thyroid axis and the homeostasis of the thyroid system, offering a groundbreaking framework for diagnosing and treating hypothyroidism. By challenging conventional approaches, it addresses the pressing need for improved treatment quality, especially for patients experiencing persistent symptoms despite standard levothyroxine therapy. Delve into a comprehensive exploration of hypothyroidism, from its definition and pathophysiology to patient presentation and endocrine regulation. The chapters illuminate critical topics such as iodine metabolism, thyroid hormone signaling, and the intricacies of the hypothalamic-pituitary-thyroid axis. With contributions from leading experts, this book presents a paradigm shift in clinical care by integrating recent advances in thyroid regulation into practical treatment strategies. Readers will uncover why many patients fail to respond adequately to current treatments and discover innovative approaches to diagnosis and therapy. Ideal for medical professionals, researchers, clinicians, and specialists interested in thyroid disease, this book is also invaluable for general practitioners and informed patients seeking deeper insights into their condition. Aspiring endocrinologists will find it particularly educational, aligning with curriculum requirements while offering a fresh perspective on thyroid health. With its focus on cutting-edge research and practical applications, this volume is indispensable for anyone dedicated to improving patient care in the field of endocrinology.

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SPINA Team @spinateam.bsky.social · 18/05/2025

Release candidate 2 of #SPINA_Carb is available for testing. sourceforge.net/projects/spi... doi.org/10.5281/zeno... doi.org/10.5281/zeno...

Screenshot of SPINA Carb 5.1.0 (Cyclone) RC2 on macOS Ventura 13.7.5.

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Johannes W. Dietrich @drjwdietrich.bsky.social · 26/04/2025

#Thyroid hormones play a pivotal role in #thermoregulation and the attunement to hot and cold #climates. Recent research found global patterns of variants in the UCP1 and UCP3 genes and #SPINA-GD (step-up #deiodinase activity), suggesting integrated adaptation. 🧪 🩺 #MedSky doi.org/10.3390/biol...

Figure 1. Effect of the rs3811787 of UCP1 gene in human adaptation to cold: (a) The levels of FT3 as a function of rs3811787 genotypes of the UCP1 gene; (b) Association analysis of the TT rs3811787 genotype between SPINA-GD; (c) Association analysis of the TT rs3811787 genotype between BSA; (d) The geographical distribution of the frequencies of the T rs3811787 (UCP1) allele in global human populations to identify signals of natural selection for cold climate adaptation.

Figure 2. Effect of the rs1800849 of UCP3 gene on human adaptation to cold: (a) The levels of FT3 as a function of rs1800849 genotypes of the UCP3 gene; (b) Association analysis of TT rs1800849 genotype between SPINA-GD; (c) Association analysis of TT rs1800849 genotype between BSA; (d) The geographical distribution of frequencies of the T rs1800849 (UCP3) allele in global human populations to identify signals of natural selection for cold climate adaptation.

Figure 3. The mechanism of BAT-mediated regulation of thyroid hormones and basal metabolic rate from the allelic variants rs3811787 of the UCP1 gene. Note. In the carriers of the T allele, with the active form of the UCP1 protein, brown adipocytes mitochondria use higher concentrations of T3 for increased heat generation during adaptive thermogenesis, which increases T3 clearance and in response increases peripheral deiodination (SPINA-GD), which raises blood levels of FT3 and basal metabolic rate. In carriers of the C allele, with a less active form of the protein, brown adipocytes will use less T3, which will not significantly increase SPINA-GD and blood levels of FT3, hence the metabolic rate will not significantly improve.

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SPINA Team @spinateam.bsky.social · 21/04/2025

After intensive internal testing, the release candidate 1 of the #SPINA_Carb app is available. This is the "sister" app for #SPINA_Thyr, and it is provided for purposes of testing. sourceforge.net/projects/spi... doi.org/10.5281/zeno... doi.org/10.5281/zeno...

Screenshot of SPINA Carb Release Candidate 1 for macOS

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SPINA Team @spinateam.bsky.social · 20/04/2025

Calculating #SPINA-GT is useful in paediatrics, as recently shown in a research paper by the Medical School of Patras. SPINA-GT is significantly reduced in subclinical hypothyroidism and even in the upper 2 quartiles of normal TSH. pubmed.ncbi.nlm.nih.gov/40230485/ doi.org/10.3389/fend...

Box plots showing SPINA GT actual vs predicted values (a) in all euthyroid children divided in groups by quartiles of TSH values and (b) in children with normal TSH in the upper 2 quartiles and children with mild and severe SH (**P < 0.001, *P<0.01). The comparison with predicted results rules out that this association is due to spurious correlation.

Table: TSH concentrations (min and max) in euthyroid (by quartiles) and children with SH and their corresponding SPINA-GT value (median and mean) along with the frequency of thyroid antibody positivity.

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Johannes W. Dietrich @drjwdietrich.bsky.social · 20/04/2025

#Thyroid hormones profoundly impact the #cardiovascular system. They act at all levels, ranging from the tier of ion currents over cellular processes to the macroscopic levels of myocardial tissue and even the whole organism. 🧪 🩺 #MedSky doi.org/10.3389/fcvm... pubmed.ncbi.nlm.nih.gov/36046184/

Thyroid hormone signalling involves four different mechanisms. T4 is a prohormone with respect to genomic signaling, but a true fast-acting hormone regarding type 4 action (which is inhibited by the iodothyroacetate TETRAC). Genomic action (type 1, type 2 and mitochondrial signaling) occurs on a slow time scale, whereas non-genomic effects (type 3 and type 4 signaling) represent a fast response (A). Thyroid hormone receptors (THR) usually act as heterodimers. Without thyroid hormone bound they block the transcription together with corepressors. Iodothyronines displace the corepressors and stimulate gene expression together with coactivators (B). Tissue specific distributions of THRs further contribute to the diversity of signaling patterns in the organism (C). AF-1, activation function 1; AF-2, activation function 2; D2, type 2 deiodinase; DBD, DNA-binding domain; HAT, histone acetyl-transferase; HDAc, histone deacetylase; LBD, ligand-binding domain; RXR, retinoid X receptor; TRE, thyroid-hormone response element.

Thyroid hormones have a profound effect on the intracellular processes of rhythm generation. The figure shows mechanisms of rhythm generation in cardiomyocytes based on a model by Maltsev et al. Two loops, an external membrane loop and an internal calcium loop, independently ensure the generation of impulses. Therefore, they provide some redundancy, but they are also intertwined at the stage of slow L-type Ca2+ current (ICaL) activation. Thyroid hormone signalling can modulate both loops simultaneously via interfaces at several sites, and direct myocardial effects of TSH are largely opposing. gK, ionic conductance for K+; INCX, Na+/Ca2+ exchange current; ICaT, T-type Ca2+ current; If , hyperpolarisation-activated “funny” current; IK, voltage-gated K+ current; Ist , sustained non-selective current; Ito, transient outward potassium current; LCR, local Ca2+ release; SERCA, sarcoendoplasmic reticulum Ca2+-ATPase; SR, sarcoplasmic reticulum.

Selected mechanisms of arrhythmogenesis by thyroid hormones at the cellular level. T3 (and other active thyroid hormones) upregulate the gene expression of beta1 and beta2 adrenoceptors via classical genomic signaling, but downregulate protective beta3 adrenoceptor expression. The transcription of critical genes for the formation of gap junctions is downregulated as well. Potassium channels are regulated via classical type 1 signaling and via non-genomic effects (type 4 action) as well. Purple arrows indicate the effects of gene expression (transcription, translation and associated processing steps), green arrows visualize the impact of T3-agonistic thyroid hormones.

$On a macroscopic level, elevated concentrations of thyroid hormones promote arrhythmia by slowing down electrical conduction and reducing the effective refractory period. (A,B) Simplified model of the effects of thyroid hormone signalling facilitating disorders of impulse conduction. Iodothyronine action reduces both the effective refractory period (ERP) and the conduction velocity (θ). As a consequence, the wavelength of excitation λ = ERP x θ may get shorter than the dimensions of a potential re-entry circuit, thus giving rise to re-entrant tachycardia.$

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SPINA Team @spinateam.bsky.social · 13/04/2025

#Hidradenitis suppurativa (acne inversa) is linked to #diabetes mellitus. In the affected, #SPINA-GR is reduced and not compensated by #SPINA-GBeta, resulting in low #SPINA-DI. This phenomenon may be mediated by #inflammation, as shown by ties to #haptoglobin. pubmed.ncbi.nlm.nih.gov/40217596/

Table showing endotypes of insulin-glucose homeostasis in patients with hidradenitis suppurative (HS or acne inversa) and different expressions of haptoglobin concentration. In persons with HS and a high haptoglobin concentration, insulin sensitivity (SPINA-GR) and beta-cell function (SPINA-GBeta) are similar but combine to provide a reduced disposition index (SPINA-DI).

Plot of SPINA-GBeta versus SPINA-GR in patients with HS and controls: The majority of patients with HS and diabetes are faced with rather low insulin sensitivity and a lack of dynamic compensation via pancreatic beta-cell function, resulting in a reduced disposition index.

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Johannes W. Dietrich @drjwdietrich.bsky.social · 30/03/2025

Medical treatment of #hyperthyroidism, i.e. #thyrotoxicosis due to overproduction of #thyroid hormone, remains a challenge. We developed a new dosage methodology based on model predictive control (MPC), which is faster and more stable than the usual trial-and-error approach. doi.org/10.1016/j.if...

Fig. 1. Simplified block diagram of the pituitary-thyroid feedback loop. The thyroid produces the hormones T3 and T4. On the one hand, this process is stimulated by TSH, a hormone secreted from the pituitary. On the other hand, this process is inhibited by Methimazole (MMI), an antithyroid agent (i.e., a medication), which constitutes the control input in this work. The hormone T4 gets converted into T3 by the enzymes 5’-deiodinase type I (D1) and 5’-deiodinase type II (D2). Finally, TRH (which is a natural hormone, and not a medication) stimulates the production of TSH.

Fig. 2. Illustration of the guidelines given by the American Thyroid association (ATA) (Ross et al., 2016). The treating physician may encounter many difficulties to select one precise dosage using these (rather vague) recommendations.

Fig. 3. Simulation results of an exemplary treatment based on the guidelines introduced in Ross et al. (2016). We apply the mean medication dosage for each interval, e.g., if the concentration of FT4 (which is proportional to T4) is within 27−42 pmol/L, we apply 7.5 mg. As disturbances, we consider forgotten dosages and measurement noise as explained in Section 3.

Fig. 4. Course of the hormone concentrations and the corresponding MMI dosages that are taken orally once per day. The dosages are determined by the MPC scheme introduced in Subsection 2.2. As explained in Section 3, we consider forgotten dosages, a model-plant mismatch, and some measurement noise as disturbances.

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Johannes W. Dietrich @drjwdietrich.bsky.social · 21/03/2025

#Diabetes mellitus is common in hidradenitis suppurativa (acne inversa). Affected persons are faced with low insulin sensitivity ( #SPINA-GR ) and a lack of dynamic compensation via beta-cell function ( #SPINA-GBeta ), resulting in a reduced disposition index ( #SPINA-DI ). doi.org/10.3390/jcm1...

Measured and calculated biomarkers for insulin–glucose homeostasis in patients with hidradenitis suppurativa (acne inversa, HS) and controls. Reconstructed insulin receptor gain (SPINA-GR) is reduced in HS, and the secretory capacity of pancreatic beta cells (SPINA-GBeta) is compensatorily increased.

Parameters of insulin–glucose homeostasis in patients with HS and with and without diabetes mellitus. In persons affected by both HS and diabetes mellitus, reduced SPINA-GR is insufficiently compensated by SPINA-GBeta, resulting in reduced static disposition index (SPINA-DI) and diabetes.

In persons with HS and a high haptoglobin concentration, insulin sensitivity (SPINA-GR) and beta-cell function (SPINA-GBeta) are similar but combine to provide a reduced disposition index (SPINA-DI).

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SPINA Team @spinateam.bsky.social · 02/03/2025

Again, a study shows that #environmental #toxicants, i.e. endocrine #disruptors, strongly affect #thyroid #homeostasis. For calculated biomarkers, i.e. #SPINA-GT and #SPINA-GD, this effect is more pronounced than for #TSH. pubmed.ncbi.nlm.nih.gov/39826653/ doi.org/10.1016/j.en...

Association between urinary chemicals and thyroid hormones, GD, and GT in the total population (Groups 1 and 2 combined): results from Quantile Gcomputation modeling. Age, BMI, urinary creatinine, education level, and group were adjusted. ‘Total’ includes MnBP, MBzP, ΣDEHPm, BPA, MeP, EtP, and PrP. ‘Phthalate metabolites’ include MnBP, MBzP, and ΣDEHPm. ‘Parabens’ include MeP, EtP, and PrP. *p < 0.05; #p < 0.1.

Phthalate metabolites measured in both groups included mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-(2-ethyl-5-oxohexyl)phthalate (MEOHP), mono(5-carboxy-2-ethylpentyl) phthalate (MECPP), mono-n-butyl phthalate (MnBP), and MBzP. For parabens, methylparaben (MeP), EtP, and propylparaben (PrP) were measured.

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SPINA Team @spinateam.bsky.social · 08/02/2025

Growing evidence supports a role of sensorimotor and autonomic #neuropathy in #syndrome_T or #SORSHOT, i.e. reduced quality of life in treated #hypothyroidism. #SPINA_GT and #SPINA_GD predict nerve function and depression. pubmed.ncbi.nlm.nih.gov/38811750/ doi.org/10.1038/s415...

Scatterplots showing a significant correlation of functional parameters of thyroid homeostasis (SPINA-GT and SPINA-GD) with the mechanical pain sensitivity (MPS) of QST (A), respiratory arrhythmia in HRV analysis (B) and depression percentiles in HADS (C).

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SPINA Team @spinateam.bsky.social · 02/02/2025

Again, a study showed a strong influence of endocrine disruptors on #thyroid homeostasis. Exposure to butylparaben significantly reduces #SPINA-GD, whereas ethylparaben slightly increases #SPINA_GT in pregnancy. pubmed.ncbi.nlm.nih.gov/39889471/ doi.org/10.1016/j.ec...

Figure (Forest plot): Changes in the levels of thyroid hormone indicators in relation to a 1 ng/mL increase in paraben exposure across trimesters. Data are presented in terms of adjusted regression coefficient and 95% confidence interval values. Exposure to butylparaben significantly reduces #SPINA-GD, whereas ethylparaben slightly increases #SPINA_GT in pregnancy, depending on the trimenon.

Forest plot: Results of generalized estimating equation–based analyses of the associations between thyroid hormones and urinary parabens in pregnant women (N = 207). The effect on SPINA-GD is different from and stronger than that on T3/T4 ratio.

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SPINA Team @spinateam.bsky.social · 03/03/2024

#SPINA_GD is reduced in major #depression, #bipolar disorder and #schizophrenia, whereas #SPINA_GT is elevated in schizophrenia and bipolar disorder, marking a unique profile of #thyroid_allostasis. pubmed.ncbi.nlm.nih.gov/38277991/ doi.org/10.1016/j.ps...

Table: Comparison of demographic factors, thyroid function and structure parameters of thyroid homeostasis among psychiatric patients and controls

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SPINA Team @spinateam.bsky.social · 24/03/2024

#SPINA_GT, #SPINA_GD and Jostel's TSH index (#JTI or #TSHI) are predictors of survival in patients with #Takotsubo syndrome (#stress #cardiomyopathy), as recently demonstrated in the international GEIST registry. 🩺 pubmed.ncbi.nlm.nih.gov/38502972/ doi.org/10.1016/j.eb...

Table: Markers of thyroid function in the study population: FT3 and SPINA-GD are significantly decreased in non-survivors, whereas SPINA-GT is increased in fatal cases of Takotsubo syndrome.

Kaplan–Meier survival curves based on cutoff values derived from phi statistics. Low TSH, FT3, SPINA-GD and JTI as well as high FT4 and SPINA-GT predict shorter survival in Takotsubo syndrome.

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