Johannes W. Dietrich

, i.e. persistent symptoms and reduced despite normal concentration, affects 10% of patients on . Careful, multimodal and personalised treatment can result in significantly improved outcomes.

doi.org/10.1007/978-981-96-368

Therapeutic flow chart: Proposed algorithm for the treatment of syndrome T (SORSHOT). The approach includes optimising dosage and modality of treatment, considering treatment with L-T3, treating common and important comorbidities and correcting mineral and vitamin deficiencies.
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Johannes W. Dietrich

For the diagnosis and management of , measuring (thyrotropin) concentration is necessary, but it isn’t sufficient. Additional help to improve diagnostic power and to identify of dysregulation.

doi.org/10.1007/978-981-96-368

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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Johannes W. Dietrich boosted
SPINA Team

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/spina

doi.org/10.5281/zenodo.15249620

doi.org/10.5281/zenodo.15874589

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

The background of our observation is poorly understood, but others could confirm the findings, e. g. in this case report.

medcentral.com/pain/crps/compl

Figure with a line plot of several parameters over time: Parathyroid Hormone (PTCH), calcium, and Vitamin D results from 2009 to 2020. Gaps signify CRPS-inciting event in 2016 and parathyroid surgery in 2020, respectively, not a delay in monitoring.
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Johannes W. Dietrich

Complex regional pain syndrome (CRPS) goes along with secondary . Our group was the first to describe this. The mechanism leading to is unclear, but it may contribute to the loss of bone substance in .

pubmed.ncbi.nlm.nih.gov/307479

doi.org/10.1097/j.pain.0000000

Table: Parameters of calcium homeostasis in patients with complex regional pain syndrome (CRPS) showing that parathyroid hormone (PTH) is higher in CRPS and calcium is slightly lower compared to healthy persons. This suggests secondary hyperparathyroidism (sHPT).
Figure with bar plots showing the z-score of bone mineral density (mean ± SD) in affected and contralateral limbs of patients with CRPS, unilateral limb pain of other origin, osteoporosis, osteopenia and healthy volunteers.
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Johannes W. Dietrich

The interaction of three hormones, , and , lays the foundation for and its responses.

It is necessary to forgo a univariable sight and to consider the evolution of the multihormonal working point to understand health and disease.

doi.org/10.1007/978-981-96-368

Null isokline plot with FT4 on the abscissa and TSH on the ordinate. Together, the thyroid response to TSH (FT4 curve) and the feedback of thyroid hormones on pituitary TSH (TSH curve) define a working point, i.e. the finite equilibrium solution of interlocking TSH–FT4 pairs. Working points are unique to an individual, show little variation, unless disturbed by internal or external strain, and translocate along isoclines.
Null isokline plot with FT4 on the abscissa and TSH on the ordinate. Allostatic influences such as obesity, age, pregnancy, and non-thyroidal illness have dislocating effects on isoclines and working points. Open circles indicate expected variation (10% for FT4 and 30% for TSH) surrounding a working point characteristic for a person. The area included between the 2.5 and 97.5 percentiles represents the population reference range.
Three-dimensional plot with the sum activity of type 1 (GD1) and type 2 deiodinase (GD2) on the abscissa and ordinate, and FT3 on the applicate. A combination of peripheral and central mechanisms leads 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 boosted
SPINA Team

Release candidate 3 for the software SPINA Carb Cyclone is available for macOS, Windows and Linux.

sourceforge.net/projects/spina

doi.org/10.5281/zenodo.1524962

doi.org/10.5281/zenodo.1571022

#SPINA_Carb #SPINA_GBeta #SPINA_GR #SPINA_DI #HOMA

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Johannes W. Dietrich

Multiple feedforward motifs and feedback loops maintain and . The mechanism of relational stability maintains T3 in a balanced and safe range, even in conditions of declining thyroid function.

doi.org/10.1007/978-981-96-368

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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Johannes W. Dietrich boosted
SPINA Team

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/fendo.2025.159

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 to the presence of cancer.
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Johannes W. Dietrich

Signalling via 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/10.1007/978-981-96-368

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

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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Johannes W. Dietrich

Relational stability is a major motif of the intertwined feedback loops of . The integrated systemic roles and interdependent homeostatically regulated equilibrium of TSH, FT4 and ​s maintains appropriate FT3 concentrations.

doi.org/10.1007/978-981-96-368

Figure from chapter 2 of the book "Hypothyroidism – A Paradigm Shift". Relational stability between TSH, FT4 and FT3 and preservation of FT3 homeostasis (a), FT3 concentrations do not parallel the decline of FT4 concentrations but remain homeostatically controlled and stable over a wide range of TSH values (b).
Figure from chapter 2 of the book "Hypothyroidism – A Paradigm Shift". Absence of relational stability and loss of FT3 homeostasis in athyreotic LT4-treated patients 2.1 above, FT3 homeostasis is broken in the absence of a functioning thyroid gland. It is no longer preserved and protected by TSH and FT4 (a). Rather, FT3 levels are now correlated with both FT4 and TSH concentrations (b).
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Johannes W. Dietrich

Our eBook on 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 disorders.

The book is available in EPUB and PDF formats.

doi.org/10.1007/978-981-96-368

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..
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Johannes W. Dietrich

Eine ist eine gefürchtete Komplikation eines mellitus. Weniger bekannt ist, dass auch andere endokrine Erkrankungen zu einer Ketoazidose führen können. In unserem neuesten Paper stellen wir eine besondere Ursache vor.

pubmed.ncbi.nlm.nih.gov/403889
doi.org/10.1055/a-2540-9824

Handflächen der Patientin. Zu sehen ist eine bräunliche Verfärbung der Haut mit regionaler Hyperpigmentierung, u. a. an den Handlinien.
Steuerung der Lipolyse durch Hormone und Mediatoren über die hormonsensitive Lipase (HSL). ACTH: Adrenocorticotropes Hormon; AMP: Adenosinmonophosphat; AMPK: AMP-Kinase; ATP: Adenosintriphosphat; FA: Fettsäuren; HSL-P: phosphorylierte HSL; STH: somatotropes Hormon; TAG: Triacylglycerol; TSH: Thyreotropin. Die vertikalen Pfeile neben den Hormonen und Metaboliten geben die Richtung der Veränderung bei Hunger-Ketonämie und APS Typ 2 an. *bei der Patientin gemessen; **wahrscheinliche Veränderung.
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Johannes W. Dietrich boosted
SPINA Team

Release candidate 2 of #SPINA_Carb is available for testing.

sourceforge.net/projects/spina

doi.org/10.5281/zenodo.1545407

doi.org/10.5281/zenodo.1524962

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

hormones play a pivotal role in and the attunement to hot and cold ​s. Recent research found global patterns of variants in the UCP1 and UCP3 genes and -GD (step-up activity), suggesting integrated adaptation.

doi.org/10.3390/biology1405045

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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Johannes W. Dietrich boosted
SPINA Team

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/spina

doi.org/10.5281/zenodo.1524962

doi.org/10.5281/zenodo.1524962

Screenshot of SPINA Carb Release Candidate 1 for macOS
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Johannes W. Dietrich

The new model can not only explain why primary thyroid disorders act as cardiovascular risk factors but also why chronic stress and type 2 allostatic load increase the hazard for adverse outcomes.

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Johannes W. Dietrich

Interestingly, both subclinical and predict . The free thyroxine (FT4) concentration is more associated with the HR for cardiovascular events than thyrotropin (TSH) levels. Our observations yield an integrated model including psychosocial and somatic mechanisms.

An integrated model for the association between thyroid homeostasis and major cardiovascular events. In the dyshomeostatic type of thyrogenic arrhythmia elevated FT4 concentration, caused by primary thyrotoxicosis, increases the risk for severe arrhythmia as a major cause for cardiovascular mortality. The TSH concentration is reduced in this case, represented by the left, declining, branch of the U-shaped relation between TSH level and risk (A). In the allostatic type, mainly caused by type 2 allostatic load and genetic traits, the set point of thyroid homeostasis is raised, resulting in increased TSH and FT4 concentration and subsequently elevated risk for arrhythmia. This situation is mirrored in the right, rising, branch of the relation between TSH concentration and cardiovascular risk (B). In any case, elevated concentrations of T3, T4 and other T3-agonistic thyroid hormones increase the sensitivity to catecholamines and sympathetic signaling (via upregulated expression of beta1 and beta2 adrenoceptors), thereby contributing to reduced stress tolerance. SPINA-GT, “gain of thyroid,” i.e., thyroid’s secretory capacity.
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Johannes W. Dietrich boosted
SPINA Team

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/402304
doi.org/10.3389/fendo.2025.136

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).
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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