Johannes W. Dietrich

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Johannes W. verified their affiliation via an institutional email.

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• PD Dr. med.
• Head of Department at Ruhr University Bochum

Although technical problems of thyroid testing have largely been resolved by modern assay technology, biological variation remains a challenge. This applies to subclinical thyroid disease, non-thyroidal illness syndrome, and those 10% of hypothyroid patients, who report impaired quality of life, despite normal thyrotropin (TSH) concentrations under...

The hypothalamus–pituitary–thyroid feedback control is a dynamic, adaptive system. In situations of illness and deprivation of energy representing type 1 allostasis, the stress response operates to alter both its set point and peripheral transfer parameters. In contrast, type 2 allostatic load, typically effective in psychosocial stress, pregnancy,...

It is well established that thyroid dysfunction is linked to an increased risk of cardiovascular morbidity and mortality. The pleiotropic action of thyroid hormones strongly impacts the cardiovascular system and affects both the generation of the normal heart rhythm and arrhythmia. A meta-analysis of published evidence suggests a positive associati...

Modelling insulin-glucose homeostasis may provide novel functional insights. In particular, simple models are clinically useful if they yield diagnostic methods. Examples include the homeostasis model assessment (HOMA) and the quantitative insulin sensitivity check index (QUICKI). However, limitations of these approaches have been criticised. Moreo...

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 condition...

In this work, we propose an approach to determine the dosages of antithyroid agents to treat hyperthyroid patients. Instead of relying on a trial-and-error approach as it is commonly done in clinical practice, we suggest to determine the dosages by means of a model predictive control (MPC) scheme. To this end, we first extend a mathematical model o...

Background: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease often associated with metabolic disorders such as diabetes mellitus. Recent research suggests a link between systemic inflammation and insulin–glucose dysregulation in HS. This study investigates the relationship between insulin–glucose homeostasis, diabetes mellitus a...

Testhandbuch des KKB (Version 2.9.0). Dynamische Funktionstests untersuchen die Antwort des Regelkreises auf eine definierte Stell- oder Störgröße, damit die funktionelle Reserve der Homöostase abgeschätzt werden kann. Dynamische Funktionstests liefern Informationen über das Übergangsverhalten des Regelkreises, insbesondere über Zeitkonstanten un...

Endocrine diseases convey far-reaching consequences for individual health, ranging from a reduced quality of life over an increased risk of serious secondary diseases to acutely life-threatening conditions. In recent decades, endocrinology has faced considerable progress, for example in molecular biological research, assay technology and therapeuti...

Testhandbuch des KKB. Dynamische Funktionstests untersuchen die Antwort des Regelkreises auf eine definierte Stell- oder Störgröße, damit die funktionelle Reserve der Homöostase abgeschätzt werden kann. Dynamische Funktionstests liefern Informationen über das Übergangsverhalten des Regelkreises, insbesondere über Zeitkonstanten und die kurzfristige...

Feedback loops and other types of information processing structures play a pivotal role in maintaining the internal milieu of living organisms. Although methods of biomedical cyber-netics and systems biology help to translate between the structure and function of processing structures, computer simulations are necessary for studying nonlinear syste...

Despite treatment with levothyroxine, hypothyroidism and autoimmune thyroiditis (AIT) may be associated with reduced quality of life (QoL), an enigmatic condition referred to as "syndrome T". Peripheral neuropathy, described in untreated thyroid disease, could be a contributing mechanism. We analysed autonomic and somatosensory function in 29 patie...

T2DM can be associated with fibrotic liver changes that can be quantified with MRE. In this study, we compared five common MRE sequences in patients with T2DM. We compared 70 MRE measurements in patients with T2DM who had received the following sequences respectively: gradient-echo (GRE), rapid GRE, fractional GRE, spin-echo echo-planar imaging (S...

Background Recently, abnormal thyroid function was shown to be common in patients with Takotsubo syndrome (TTS), being classified into “endocrine-type” and “stress-type” responses. The aim of this study was to investigate the association between thyroid homeostasis and TTS in a larger international registry. Methods In total 288 patients with TTS...

Genome-wide association studies have identified several hundred loci associated with type 2 diabetes mellitus (T2DM). Additionally, pathogenic variants in several genes are known to cause monogenic diabetes that overlaps clinically with T2DM. Whole-exome sequencing of related individuals with T2DM is a powerful approach to identify novel high-penet...

Radioiodine treatment (RIT) has a high success rate in both the treatment of hyperthyroidism and improving the quality of life (QoL) of symptomatic patients. In asymptomatic patients with subclinical hyperthyroidism thyroid related QoL outcomes are less well known. Methods Study aim was to evaluate thyroid-related QoL in patients with subclinical h...

Hidradenitis suppurativa (HS) is a chronic skin disease that can have an association with endocrine disorders. There is conflicting information in the literature regarding the role of the thyroid gland in HS. This study aimed to close this knowledge gap and investigate how thyroid disease is involved in patients with HS. We carried out a case-contr...

Background: Psychosocial stress has been associated with the development and progression of atherosclerotic cardiovascular disease (CVD). Previously, we reported subtle differences in global longitudinal strain in somatically healthy women with a psychiatric diagnosis of borderline personality disorder (BPD). This study aimed to investigate the imp...

Zusammenfassung Hintergrund Chronischer Schmerz ist nach Unfällen und Operationen eine Langzeitkomplikation, deren Relevanz für Patienten im BG-lichen Heilverfahren in Deutschland kaum untersucht ist. Fragestellung Erste Statuserhebung der Häufigkeit chronischer Schmerzen nach Arbeitsunfall. Methoden In 2017 wurden chirurgisch-stationäre BG-Patient...

Testhandbuch des KKB Dynamische Funktionstests untersuchen die Antwort des Regelkreises auf eine definierte Stell- oder Störgröße, damit die funktionelle Reserve der Homöostase abgeschätzt werden kann. Dynamische Funktionstests liefern Informationen über das Übergangsverhalten des Regelkreises, insbesondere über Zeitkonstanten und die kurzfristige...

Although hyperthyroidism is a common disease, the pharmaceutical therapy is based on a trial-and-error approach. We extend a mathematical model of the pituitary-thyroid feedback loop such that the intake of one antithyroid agent, namely methimazole (MMI), can be considered and use a model predictive control (MPC) scheme to determine suitable dosage...

Abstract Background Recent large clinical trials have demonstrated cardiovascular benefits of similar overall magnitude for sodium–glucose cotransporter-2 inhibitor (SGLT-2i) and glucagon-like peptide-1 receptor agonist (GLP-1RA) therapy in subjects with type 2 diabetes. We sought to identify subgroups based on baseline characteristics with a diffe...

CyberUnits is a cross-platform class library for rapid development of high-performance computer simulations in life sciences. It supports modelling for biomedical cybernetics and systems biology with Object Pascal. The Bricks collection is a set of Pascal units that provides a class library for rapid programming of high-performance computer simula...

Dynamische Funktionstests untersuchen die Antwort des Regelkreises auf eine definierte Stell- oder Störgröße, damit die funktionelle Reserve der Homöostase abgeschätzt werden kann. Dynamische Funktionstests liefern Informationen über das Übergangsverhalten des Regelkreises, insbesondere über Zeitkonstanten und die kurzfristige Reaktion auf Einfluss...

Diabetes mellitus ist ein Überbegriff für verschiedene Erkrankungen des Stoffwechsels, die aufgrund von Insulinmangel und/oder verminderter Insulinwirkung zu erhöhten Blutzuckerwerten führen. Die Insulin-Glukose-Homöostase ist von fundamentaler Bedeutung für ein gesundes und unabhängiges Leben. Störungen umfassen schwere und häufige Erkrankungen, i...

The insulin-glucose homeostasis is of paramount importance for a healthy life. Its disorders include some of the most significant and also some of the most prevalent diseases in modern societies, including all forms of diabetes mellitus and prediabetes, but also hypoglycaemic disorders. All of the associated diseases confer a substantial risk for m...

Hidradenitis suppurativa (HS) is a chronic skin disease that is often associated with metabolic disorders. Diabetes mellitus (DM) is a frequent comorbidity in HS. There is currently no established screening for DM in HS patients. The aim of our study was to identify high-risk groups of HS patients that develop DM and to assess the frequency of diff...

The synthesis of thyroid hormones in the hypothalamic-pituitary-thyroid (HPT) axis was studied. For this purpose, a reaction model for HPT axis with stoichiometric relations between the main reaction species was postulated. Using the law of mass action, this model has been transformed into a set of nonlinear ordinary differential equations. This ne...

Abstract The use of extracorporeal membrane oxygenation (ECMO) is discussed to improve patients’ outcome in severe COVID-19 with respiratory failure, but data on ECMO remains controversial. The aim of the study was to determine the characteristics of patients under invasive mechanical ventilation (IMV) with or without veno-venous ECMO support and t...

Background Thyroid hormones are controlled by the hypothalamic–pituitary–thyroid (HPT) axis through a complex network of regulatory loops, involving the hormones TRH, TSH, FT4, and FT3. The relationship between TSH and FT4 is widely used for diagnosing thyroid diseases. However, mechanisms of FT3 homeostasis are not well understood. Objective We u...

Schilddrüsenerkrankungen gehören zu den hochprävalenten Krankheitsbildern. In den meisten Fällen ist die Symptomatik mild, und das Risiko entfaltet sich eher in einer langfristigen Erhöhung z. B. des kardiovaskulären Risikos. Einige Erkrankungen der Schilddrüse gehen jedoch mit einer akut und massiv erhöhten Morbidität und Mortalität einher. Hierzu...

Testhandbuch der Sektion Diabetologie, Endokrinologie und Stoffwechsel am Katholischen Klinikum Bochum und am Universitätsklinikum der Ruhr-Universität Bochum. Dynamische Funktionstests untersuchen die Antwort des Regelkreises auf eine definierte Stell- oder Störgröße, damit die funktionelle Reserve der Homöostase abgeschätzt werden kann. Dynamisc...

In this work, we propose an approach to determine the dosages of antithyroid agents to treat hyperthyroid patients. Instead of relying on a trial-and-error approach as it is commonly done in clinical practice, we suggest to determine the dosages by means of a model predictive control (MPC) scheme. To this end, we extend a mathematical model of the...

The differentiation of species in the evolution of life is marked by gradually increasing independence of the organism from external physical and chemical boundary conditions. This form of liberty, being characteristic for living systems, requires means of “autopoiesis”, i. e. information processing, self-regulation and self-organisation. The disco...

Introduction A mathematical model of the pituitary-thyroid feedback loop is extended to deepen the understanding of the Allan-Herndon-Dudley syndrome (AHDS). The AHDS is characterized by unusual thyroid hormone concentrations and a mutation in the SLC16A2 gene encoding for the monocarboxylate transporter 8 (MCT8). This mutation leads to a loss of t...

Contemporary endocrinology is faced with five challenges: Reliable diagnosis and differential diagnosis of hormonal disorders, optimising therapy for minimum short-term metabolic risk, adjusted treatment for reduced long-term cardiovascular risk, improving quality of life of affected patients and, in neoplastic diseases, optimised therapy for reduc...

Hidradenitis suppurativa (HS) is a chronic inflammatory disease manifesting in inverse body regions. In a systematic review, the role of hormones in HS will be presented to better understand the pathomechanisms of HS. The review is based on the PRISMA criteria. Systematic research was carried out using keywords. Subsequently, the data were analyzed...

Nahezu alle Erkrankungen der Schilddrüse gehen mit einer reduzierten Lebensqualität einher. Fragebögen zu krankheitsspezifischen Symptomen tragen zu einer verbesserten Diagnostik bei. Etwa 10 % aller von einer Hypothyreose Betroffenen klagen über persistierende Beschwerden (Syndrom T). Die Ursache für diesen Symptomenkomplex ist noch nicht geklärt....

Preventive programs and the development of specific therapeutic measures have helped to significantly reduce the load of cardiovascular risk over the previous decades. This applies to both the epidemiology of cardiovascular disease on the population level and the prognosis of individual patients affected by chronic disease. However, a significant r...

Is data-driven analysis sufficient for understanding the COVID-19 pandemic and for justifying public health regulations? In this paper, we argue that such analysis is insufficient. Rather what is needed is the identification and implementation of over-arching hypothesis-related and/or theory-based rationales to conduct effective SARS-CoV2/COVID-19...

In this paper, we address the problem of optimal thyroid hormone replacement strategy development for hypothyroid patients. This is challenging for the following reasons. First, it is difficult to determine the correct dosage leading to normalized serum thyroid hormone concentrations of a patient. Second, it remains unclear whether a levothyroxine...

Endocrine regulation in the hypothalamic-pituitary-thyroid (HPT) axis is orchestrated by physiological circuits which integrate multiple internal and external influences. Essentially, it provides either of the two responses to overt biological challenges: to defend the homeostatic range of a target hormone or adapt it to changing environmental cond...

Objective A mathematical model of the pituitary-thyroid feedback loop is extended to deepen the understanding of the Allan-Herndon-Dudley syndrome (AHDS). Background The AHDS is characterized by unusual thyroid hormone concentrations and a mutation in the SLC16A2 gene encoding for the monocarboxylate transporter 8 (MCT8). This mutation leads to a...

Strukturelle Veränderungen, Entzündungen und Funktionsstörungen der Schilddrüse sind hochprävalente Erkrankungen, die vielfältige somatische und psychische Folgen nach sich ziehen können. Gutachterliche Bedeutung erlangen sie insbesondere, wenn sie durch Verletzungen, medizinische Maßnahmen oder endokrine Disruptoren ausgelöst wurden. Zumindest vor...

Feedback loops are among the primary network motifs in living organisms, ensuring survival via homeostatic control of key metabolites and physical properties. However, from a scientific perspective, their characterization is unsatisfactory since the usual modelling methodology is incompatible with the physiological and biochemical basis of metaboli...

Erkrankungen der Schilddrüse gehören zu den häufigsten Volkskrankheiten. Sie verlaufen meist langsam und gehen mit einer chronischen Erhöhung des gesundheitlichen Risikos einher. Gelegentlich kommt es zu krisenhaften Entwicklungen, die zu akut lebensbedrohlichen Situationen mit signifikant erhöhter Mortalität führen. Hierzu gehören die thyreotoxisc...

Background: The relationship between thyroid function and cardiac disease is complex. Both hypothyroidism and thyrotoxicosis can predispose to ventricular arrhythmia and other major adverse cardiovascular events (MACE), so that a U-shaped relationship between thyroid signaling and the incidence of MACE has been postulated. Moreover, recently publis...

SimulaBeta is a continuous simulation program for insulin-glucose feedback control. It is based on a nonlinear MiMe-NoCoDI model.

Feedback loops are among the primary network motifs in living organisms, ensuring survival via homeostatic control of key metabolites and physical properties. However, from a scientific perspective, their characterization is unsatisfactory since the usual modelling methodology is incompatible with the physiological and biochemical basis of metaboli...

We read with great interest the current debate on the controversial issues that have long surrounded the treatment of subclinical hypothyroidism (1). The fact that the two discussants disagreed so strongly in their approach to a prevalent problem, routinely faced by clinicians around the globe, may indicate severe shortcomings in the current approa...

Die einschlägigen Leitlinien der Fachgesellschaften schlagen für die Diagnostik von Schilddrüsenfunktionsstörungen eine sogenannte Stufen- oder Reflexdiagnostik vor, in der am Anfang des diagnostischen Pfades eine TSH-Bestimmung steht. Nur bei pathologischem Ergebnis wird die Untersuchung der peripheren Schilddrüsenhormone und ggf. weiterer Biomark...

Precision medicine and molecular systems medicine (MSM) are highly utilized and successful approaches to improve understanding, diagnosis, and treatment of many diseases from bench-to-bedside. Especially in the COVID-19 pandemic, molecular techniques and biotechnological innovation have proven to be of utmost importance for rapid developments in di...

Background. Several reports have described Takotsubo syndrome (TTS) secondary to thyrotoxicosis. A complex interaction of central and peripheral catecholamines with thyroid homeostasis has been suggested. In this study, we analysed sequential thyroid hormone profiles during the acute phase of TTS. Methods. Thyrotropin (TSH), free T4 (FT4) and free...

Elevated concentrations of free thyroid hormones are established cardiovascular risk factors, but the association of thyrotropin (TSH) levels to hard endpoints is less clear. This may, at least in part, ensue from the fact that TSH secretion depends not only on the supply with thyroid hormones but on multiple confounders including genetic traits, m...

A recent debate has evaluated the primary test schema for assessing thyroid function, direct measurement of thyroid hormones or the pituitary hormone TSH.

Background The homeostatic euthyroid set point of the hypothalamus–pituitary–thyroid axis of any given individual is unique and oscillates narrowly within substantially broader normal population ranges of circulating free thyroxine (FT4) and thyroid-stimulating hormone (TSH), otherwise termed ‘thyroid function test (TFT)’. We developed a mathematic...

Study protocol of Thyro-CPR study (names of investigators blackened)

We read with great interest the Methodology Editorial on ‘Choosing between parametric and non-parametric tests’ by le Cessie et al. in the Journal (1). The topic is of wide interest to readers given that this is a frequent issue clinical researchers face in their daily work. The authors argue that the use of a t-test is preferable over non-parametr...

Background: Subclinical hyperthyroidism/thyrotoxicosis originates from different causes and clinical conditions, sharing the laboratory constellation of a suppressed TSH in the presence of thyroid hormone concentrations within the reference range. Aim: Presentation of hyperthyroidism can manifest itself in several ways. We questioned whether there...

The aim of the present study was to determine whether free thyroxine (FT4) and calculated thyroid parameters predict the incidence of ventricular arrhythmias in euthyroid heart failure patients with implantable cardioverter-defibrillators (ICD). In this open-label prospective cohort study, 115 consecutive euthyroid patients (mean age 62.9±1.3 years...

Background: Reactive endocrine adaptive reactions are well-known risk indicators in critical illnesses; however, very little is known about their role after severe trauma. This applies especially to low T3 syndrome as a subacute allostatic response of thyroid function, which is also known as nonthyroidal illness syndrome (NTIS), euthyroid sick syn...

Background: Defined by thyroid-pituitary feedback control, clinical diagnosis of hypothyroidism and hyperthyroidism has become synonymous with TSH measurement. Study aim: We combined in silico analysis and in vivo data to explore the central influences on thyroidal T3 production. Materials & methods: A system of five coupled first order nonlin...

This observational study assessed the concentrations of thyroid-stimulating hormone (TSH) and peripheral thyroid hormones as well as structural parameters of thyroid homeostasis in patients suffering from severe trauma 24 h and 72 h after admission to the intensive care unit.

This observational study assessed the concentrations of thyroid-stimulating hormone (TSH) and peripheral thyroid hormones as well as structural parameters of thyroid homeostasis in patients suffering from severe trauma 24 h and 72 h after admission to the intensive care unit.

Introduction: Homeostasis and allostasis are preconditions of independent life. Therefore, the underlying motifs of feedback control systems are among the essential and most basic biological information processing structures. Traditionally, the relation between structure and behaviour of control loop systems used to be investigated through linear...

Background: For significant numbers of patients dissatisfied on standard levothyroxine (LT4) treatment for hypothyroidism, patient-specific responses to T4 could play a significant role. Aim: To assess response heterogeneity to LT4 treatment, identifying confounders and hidden clusters within a patient panel, we performed a secondary analysis using...

The aim of this study was to investigate in a longitudinal approach whether levothyroxine (LT4) substitution has a different impact on quality of life (QoL) and thyroid related QoL in younger (<40 years) and older subjects (>60 years) with elevated thyroid-stimulating hormone (TSH) concentrations. The study included male and female patients with ne...

Levothyroxine (LT4) therapy has a long history, a well-defined pharmacological profile and a favourable safety record in the alleviation of hypothyroidism. However, questions remain in defining the threshold for the requirement of treatment in patients with subclinical hypothyroidism, assessing the dose adequacy of the drug, and selecting the best...

Background Controversy exists about the pathophysiology of different hemodynamic subgroups of AS. In particular, the mechanism of the paradoxical low-flow, low-gradient (PLFLG) AS with preserved ejection fraction (EF) is unclear. Methods A total of 41 patients with severe, symptomatic AS were divided into the following 4 subgroups based on the ech...

Reaction model based on the stoichiometric network of reactions between the species is an excellent starting point for formation of mathematical model expressed in a form of differential equations. In particular this modelling procedure is appropriate for chemical, physicochemical and biochemical processes (reaction systems), but it could be applie...

The pituitary-thyroid feedback control involves two classes of hormones, the peptide hormones thyroliberin (thyrotropin-releasing hormone, TRH) and thyrotropin (thyroid-stimulating hormone, TSH) and two thyroid hormones (T4 or thyroxine and T3 or triiodothyronine) [1]. These four hormones are main constituents of hypothalamic-pituitary-thyroid axis...

Zehn Monate postpartum stellt sich eine 32-Jährige mit Herzrasen, Schweißausbrüchen, Gewichtsverlust und Schwindel vor. Klinisch fallen eine erhöhte Körpertemperatur sowie eine vergrößert palpable Schilddrüse auf. In der Blutabnahme zeigen sich supprimierte TSH- sowie stark erhöhte FT3- und FT4-Konzentrationen, im EKG eine Sinustachykardie.

Background In the treatment for hypothyroidism, a historically symptom-orientated approach has given way to reliance on a single biochemical parameter, thyroid stimulating hormone (TSH). Main body The historical developments and motivation leading to that decision and its potential implications are explored from pathophysiological, clinical and st...

Local osteopenia and altered bone metabolism are major complications of complex regional pain syndrome (CRPS), but quantitative assessment is difficult unless using X-ray or dual-energy X-ray absorptiometry. Ultrasound-based measurement of bone density (UBD) is a possible alternative, but has never been used to detect unilateral disease such as CRP...

Thyroid hormones are critical for development and function of vertebral organisms. Both their lack and surplus involve a risk of severe disease, making tight physiological feedback control necessary. Recent research demonstrated, however, thyroid homoeostasis (HPT axis) to be a dynamic system, since the concentrations of the controlling hormone thy...

Dataset for the article "We miss the opportunity: pretreatment of osteoporosis in a German trauma center."