Johannes W. Dietrich

Ruhr-Universität Bochum | RUB · Diabetes, Endocrinology and Metabolism Section

Although hyperthyroidism predisposes to atrial fibrillation, previous trials have suggested decreased triiodothyronine (T3) concentrations to be associated with postoperative atrial fibrillation (POAF). Therapy with thyroid hormones (TH), however, did not reduce the risk of POAF. This study reevaluates the relation between thyroid hormone status, a...

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 L...

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...

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...

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...

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...

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...

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...

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...

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...

Controversial issues have long surrounded the treatment of subclinical hypothyroidism. The current debate should encourage further efforts to find a more clinically inclusive definition for subclinical thyroid disease, more deserving of this name.

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)

The question arises as to whether clinicians should be mainly interested in central tendency.

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."

Osteoporosis remains a major health concern due to high incidence of fragility fractures followed by higher mortality and morbidity. Implementation of guidelines for diagnosis and treatment of osteoporosis is critically discussed internationally. Aim of this study was to evaluate implementation of these guidelines regarding diagnosis and therapy of...

PUMA’s EDF+ engine is a collection of Object Pascal types, classes and procedures that support parsing, compiling and storing European Data Format (EDF) and EDF+ files.

The discovery of the negative feedback of thyroid hormones on pituitary thyroid- stimulating hormone (TSH) secretion, a classical endocrine feedback control system, has shaped diagnosis and treatment of thyroid disease for the last decades. Based on this concept, a unique diagnostic category of subclinical thyroid disorders was introduced, being de...

The homeostatic equilibrium point of the pituitary-thyroid axis is a dynamic attractor that is controlled by both central and peripheral factors. Rather than representing a fixed set point, the portal TRH concentration (purple) encodes an adaptive reference input that is governed by multiple nutritional, seasonal, inflammatory, environmental and em...

Randomised controlled trials are deemed to be the strongest class of evidence in evidence-based medicine. Failure of trials to prove superiority of T3/T4 combination therapy over standard LT4 monotherapy has greatly influenced guidelines, while not resolving the ongoing debate. Novel studies have recently produced more evidence from the examination...

Aim The present study examines the relationship between the sensitivity of TSH feedback and thyroid capacity in untreated patients with thyroid autoimmune disease (n= 86) and healthy controls (n= 271). Functional capacity was estimated at maximum TSH stimulation, and pituitary TSH response was FT4‐standardised with two established indices, the TSH...

Highlights • The extent of myocardial fibrosis and the degree of isoform-expression and phosphorylation changes in cardiomyocyte titin were unknown in different hemodynamic subgroups of AS, including “paradoxical” low-flow, low-gradient AS with preserved ejection fraction. • Hemodynamic subtypes of AS were found to exhibit increased cardiac fibrosi...

Despite significant progress in assay technology, diagnosis of functional thyroid disorders may still be a challenge, as illustrated by the vague upper limit of the reference range for serum thyrotropin (TSH). Diagnostical problems also apply to subjects affected by syndrome T, i.e., those 10% of hypothyroid patients who continue to suffer from poo...

Aim Patients on levothyroxine-treatment frequently have complaints although TSH is within the reference range. Moreover, FT3 is often low in these patients. The clinical significance of this disequilibrium is studied here. Patients, methods We conducted a retrospective longitudinal study including 319 patients with differentiated thyroid carcinoma...

In thyroid health, the pituitary hormone thyroid-stimulating hormone (TSH) raises glandular thyroid hormone production to a physiological level and enhances formation and conversion of T4 to the biologically more active T3. Overstimulation is limited by negative feedback control. In equilibrium defining the euthyroid state, the relationship between...

Origin and evolution of life are marked by increasing independence of the developing organisms from physical and chemical boundary conditions. Being characteristic of living systems this form of liberty demands processes of information processing, self-organisation and self-regulation. The discovery of these biological foundations hallmarked the tr...

Preface SPINA (structure parameter inference approach) is a cybernetic method for advanced interpretation of laboratory results. It allows for calculating constant structure parameters of endocrine feedback control systems in vivo from hormone levels that have been obtained from serum or plasma specimens. The method is based on mathematical and cyb...

Introduction The relationship between pituitary TSH and thyroid hormones is central to our understanding of thyroid physiology and thyroid function testing. Here, we generated distribution patterns by using validated tools of thyroid modelling. Methods We simulated patterns of individual set points under various conditions, based on a homeostati...

S2 Table. De-identified patient data in data interchange format.

S1 File. Supplementary code for the statistical platform R.