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  1. Book ; Online: Homeostasis and Allostasis of Thyroid Function

    Hoermann, Rudolf / Midgley, John E. M. / Dietrich, Johannes W.

    2018  

    Abstract: 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 ... ...

    Abstract 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 defined exclusively by an abnormal TSH response in the presence of thyroid hormone concentrations within the reference range. Although this approach was able to deliver a conceptually straightforward disease definition problems surfaced in clinical practice as neither the diagnostic reference range nor the appropriate threshold for initiating substitution treatment are universally agreed upon for subclinical thyroid disorders.-

    The situation is further aggravated by the so-called syndrome T, which comprises a substantial but heterogeneous group of L-T4 treated patients with hypothyroidism with reduced quality of life despite "normal" TSH values.

    A limited understanding of the physiological relationships between TSH and thyroid hormones may be a main reason for clinical difficulties in dealing with the causes of syndrome T and tailoring substitution therapy for hypothyroid patients with subclinical thyroid disorders.

    Feedback regulation has recently been shown to be much more complex than previously assumed.-

    The concept of homeostatic control has also been extended to include the lesser known but equally important allostatic thyroid regulation.The latter aims at adaptive homeostasis or stability through changing setpoints and modulating structural parameters of feedback control, as may be appropriate to adapt to a vast array of conditions spanning from fetal life, aging, pregnancy, exercise, starvation, obesity, psychiatric disorders to the severe non-thyroidal illness syndrome.

    A better understanding of homeostatic and allostatic mechanisms, which govern the behaviour of pituitary-thyroid feedback control, is on the horizon. This promises to improve the diagnostic utility of laboratory methods, laying the foundation for personalised methods to optimise dosage and modality of substitution therapy.-
    Keywords Medicine (General) ; Diseases of the endocrine glands. Clinical endocrinology
    Size 1 electronic resource (107 p.)
    Publisher Frontiers Media SA
    Document type Book ; Online
    Note English ; Open Access
    HBZ-ID HT020101884
    ISBN 9782889455706 ; 288945570X
    Database ZB MED Catalogue: Medicine, Health, Nutrition, Environment, Agriculture

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  2. Book ; Thesis: Jenseits des TSH

    Dietrich, Johannes Wolfgang Christian

    In-silico- und in-vivo-Untersuchungen zum zentralen und peripheren Schilddrüsenhormonstoffwechsel

    2016  

    Institution Ruhr-Universität Bochum
    Author's details von Dr. med. Johannes Wolfgang Christian Dietrich aus Salzburg
    Language German
    Size Zahlreiche Zählungen, Illustrationen
    Publishing place Bochum
    Publishing country Germany
    Document type Book ; Thesis
    Thesis / German Habilitation thesis Habilitationsschrift, Ruhr-Universität Bochum, 2017
    HBZ-ID HT019485135
    Database Catalogue ZB MED Medicine, Health

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    In stock of ZB MED Cologne/Königswinter

    Shelf markLoan statusLocation
    2018 E 437 order for loan Magazin

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  3. Article ; Online: Understanding the restrictions in the prescription and use of potentially beneficial diabetes medications associated with low socio-economic status.

    Nauck, Michael A / Dietrich, Johannes W

    The Lancet regional health. Europe

    2022  Volume 14, Page(s) 100318

    Language English
    Publishing date 2022-02-02
    Publishing country England
    Document type Journal Article
    ISSN 2666-7762
    ISSN (online) 2666-7762
    DOI 10.1016/j.lanepe.2022.100318
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Effect of Radioiodine Treatment on Quality of Life in Patients with Subclinical Hyperthyroidism: A Prospective Controlled Study.

    Larisch, Rolf / Midgley, John E M / Dietrich, Johannes W / Hoermann, Rudolf

    Nuklearmedizin. Nuclear medicine

    2024  

    Abstract: 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 ... ...

    Title translation Einfluss einer Radiojodtherapie auf die Lebensqualität von Patienten mit latenter Hyperthyreose: Eine prospektive kontrollierte Studie.
    Abstract 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 hyperthyroidism mostly due to toxic nodular goitre undergoing RIT, compared to a control group of euthyroid subjects. Study design was monocentric, prospective, controlled. Fifty control subjects were enrolled and 51 RIT patients. Most subjects were examined at least twice at an interval of 6 months, with visits immediately before and 6 months after treatment in the RIT group. QoL was estimated with the ThyPRO questionnaire, using its composite scale as primary outcome. Treatment effect was the mean adjusted difference (MAD) between groups over time, using repeated? measures mixed? effects models.
    Results: TSH concentrations were lower in the RIT group prior to treatment and recovered thereafter slightly above the level of the control group. Correspondingly, QoL improved significantly after 6 months from a worse level in the RIT group, compared to controls (MAD -10.3 [95% CI -14.9, -5.7], p<0.001). QoL improvements were strong for general items, but less pronounced for the hyperthyroid domain. Compared to controls, thyroid volume, thyroid functional capacity (SPINA-GT) and deiodinase activity (SPINA-GD) were significantly reduced in the RIT group.
    Conclusion: Patients with subclinical hyperthyroidism improve both biochemically and in their QoL after RIT, compared to controls. QoL assessment should have a wider role in clinical practice to complement biochemical tests and help with treatment decisions.
    Language English
    Publishing date 2024-01-23
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 2030804-8
    ISSN 2567-6407 ; 0029-5566
    ISSN (online) 2567-6407
    ISSN 0029-5566
    DOI 10.1055/a-2240-8087
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Whole-exome sequencing in familial type 2 diabetes identifies an atypical missense variant in the RyR2 gene.

    Bansal, Vikas / Winkelmann, Bernhard R / Dietrich, Johannes W / Boehm, Bernhard O

    Frontiers in endocrinology

    2024  Volume 15, Page(s) 1258982

    Abstract: 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 ...

    Abstract 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-penetrance disease variants in coding regions of the genome. We performed whole-exome sequencing on four related individuals with T2DM - including one individual diagnosed at the age of 33 years. The individuals were negative for mutations in monogenic diabetes genes, had a strong family history of T2DM, and presented with several characteristics of metabolic syndrome. A missense variant (p.N2291D) in the type 2 ryanodine receptor (
    MeSH term(s) Adult ; Animals ; Humans ; Mice ; Diabetes Mellitus, Type 2/complications ; Diabetes Mellitus, Type 2/genetics ; Exome Sequencing ; Genome-Wide Association Study ; Glucose ; Glucose Intolerance ; Mutation, Missense ; Ryanodine Receptor Calcium Release Channel/genetics
    Chemical Substances Glucose (IY9XDZ35W2) ; Ryanodine Receptor Calcium Release Channel ; RyR2 protein, human ; ryanodine receptor 2. mouse
    Language English
    Publishing date 2024-02-20
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2592084-4
    ISSN 1664-2392
    ISSN 1664-2392
    DOI 10.3389/fendo.2024.1258982
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: The role of supporting and disruptive mechanisms of FT3 homeostasis in regulating the hypothalamic-pituitary-thyroid axis.

    Hoermann, Rudolf / Pekker, Mark J / Midgley, John E M / Dietrich, Johannes W

    Therapeutic advances in endocrinology and metabolism

    2023  Volume 14, Page(s) 20420188231158163

    Abstract: 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 ...

    Abstract 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 used mathematical modelling to further examine mechanisms that exist in the HPT axis regulation for protecting circulating FT3 levels.
    Methods: A mathematical model consisting of a system of four coupled first-order parameterized non-linear ordinary differential equations (ODEs) was developed, accounting for the interdependencies between the hormones in the HPT axis regulation. While TRH and TSH feed forward to the pituitary and thyroid, respectively, FT4 and FT3 feed backward to both the pituitary and hypothalamus. Stable equilibrium solutions of the ODE system express homeostasis for a particular variable, such as FT3, if this variable stays in a narrow range while certain other parameter(s) and system variable(s) may vary substantially.
    Results: The model predicts that (1) TSH-feedforward protects FT3 levels if the FT4 production rate declines and (2) combined negative feedback by FT4 and FT3 on both TSH and TRH production rates keeps FT3 levels insensitive to moderate changes in FT4 production rates and FT4 levels. The optimum FT4 and FT3 feedback and TRH and TSH-feedforward ranges that preserve FT3 homeostasis were found by numerical continuation analysis. Model predictions were in close agreement with clinical studies and individual patient examples of hypothyroidism and hyperthyroidism.
    Conclusions: These findings further extend the concept of HPT axis regulation beyond TSH and FT4 to integrate the more active sister hormone FT3 and mechanisms of FT3 homeostasis. Disruption of homeostatic mechanisms leads to disease. This provides a perspective for novel testable concepts in clinical studies to therapeutically target the disruptive mechanisms.
    Language English
    Publishing date 2023-03-14
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2554822-0
    ISSN 2042-0196 ; 2042-0188
    ISSN (online) 2042-0196
    ISSN 2042-0188
    DOI 10.1177/20420188231158163
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Characteristics predicting the efficacy of SGLT-2 inhibitors versus GLP-1 receptor agonists on major adverse cardiovascular events in type 2 diabetes mellitus: a meta-analysis study.

    Sohn, Minji / Dietrich, Johannes W / Nauck, Michael A / Lim, Soo

    Cardiovascular diabetology

    2023  Volume 22, Issue 1, Page(s) 153

    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 ...

    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 differential response to either SGLT-2i or GLP-1RA.
    Methods: PubMed, Cochrane CENTRAL, and EMBASE were searched from 2008 to 2022 for SGLT-2i or GLP-1RA randomized trials that reported 3-point major adverse cardiovascular events (3P-MACE). Baseline clinical and biochemical characteristics included age, sex, body mass index (BMI), HbA1c, estimated glomerular filtration rate (eGFR), albuminuria, preexisting cardiovascular disease (CVD), and heart failure (HF). Absolute and relative risk reductions (ARR and RRR) regarding incidence rates for 3P-MACE with a 95% confidence interval were calculated. The association of average baseline characteristics in each study with the ARR and RRR for 3P-MACE was investigated by meta-regression analyses (random-effects model, assuming inter-study heterogeneity). Meta-analysis was also conducted to investigate whether the efficacy of SGLT-2i or GLP-1RA on 3P-MACE reduction could differ according to the patient's characteristics (e.g., HbA1c above/below cutoff).
    Results: After a critical assessment of 1,172 articles, 13 cardiovascular outcome trials with a total of 111,565 participants were selected. In meta-regression analysis, the more patients with reduced eGFR in the studies, the greater ARR by SGLT-2i or GLP-1RA therapy. Similarly, in the meta-analysis, SGLT-2i therapy tended to be more effective in reducing 3P-MACE in people with eGFR < 60 ml/min/1.73 m
    Conclusions: Because decreased eGFR [significant] and albuminuria [trend] were found to predict a better efficacy for SGLT-2i in 3P-MACE reduction, this class of drug should be preferred in such patients. However, GLP-1RA may be considered for patients with normal eGFR because it showed better efficacy than SGLT-2i in this subgroup [trend].
    MeSH term(s) Humans ; Albuminuria ; Cardiovascular Diseases/diagnosis ; Cardiovascular Diseases/epidemiology ; Cardiovascular Diseases/prevention & control ; Diabetes Mellitus, Type 2/diagnosis ; Diabetes Mellitus, Type 2/drug therapy ; Diabetes Mellitus, Type 2/epidemiology ; Glucagon-Like Peptide-1 Receptor/agonists ; Glycated Hemoglobin ; Heart Failure ; Sodium-Glucose Transporter 2 Inhibitors/adverse effects
    Chemical Substances Glucagon-Like Peptide-1 Receptor ; Glycated Hemoglobin ; Sodium-Glucose Transporter 2 Inhibitors
    Language English
    Publishing date 2023-06-28
    Publishing country England
    Document type Meta-Analysis ; Journal Article
    ZDB-ID 2093769-6
    ISSN 1475-2840 ; 1475-2840
    ISSN (online) 1475-2840
    ISSN 1475-2840
    DOI 10.1186/s12933-023-01877-6
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: Minor perturbations of thyroid homeostasis and major cardiovascular endpoints-Physiological mechanisms and clinical evidence.

    Müller, Patrick / Leow, Melvin Khee-Shing / Dietrich, Johannes W

    Frontiers in cardiovascular medicine

    2022  Volume 9, Page(s) 942971

    Abstract: 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 ... ...

    Abstract 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 association of FT4 concentration with major adverse cardiovascular end points (MACE), but this association only partially extends to TSH. The risk for cardiovascular death is increased in both subclinical hypothyroidism and subclinical thyrotoxicosis. Several published studies found associations of TSH and FT4 concentrations, respectively, with major cardiovascular endpoints. Both reduced and elevated TSH concentrations predict the cardiovascular risk, and this association extends to TSH gradients within the reference range. Likewise, increased FT4 concentrations, but high-normal FT4 within its reference range as well, herald a poor outcome. These observations translate to a monotonic and sensitive effect of FT4 and a U-shaped relationship between TSH and cardiovascular risk. Up to now, the pathophysiological mechanism of this complex pattern of association is poorly understood. Integrating the available evidence suggests a dual etiology of elevated FT4 concentration, comprising both ensuing primary hypothyroidism and a raised set point of thyroid function, e. g. in the context of psychiatric disease, chronic stress and type 2 allostatic load. Addressing the association between thyroid homeostasis and cardiovascular diseases from a systems perspective could pave the way to new directions of research and a more personalized approach to the treatment of patients with cardiovascular risk.
    Language English
    Publishing date 2022-08-15
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2781496-8
    ISSN 2297-055X
    ISSN 2297-055X
    DOI 10.3389/fcvm.2022.942971
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article: Optimal Hormone Replacement Therapy in Hypothyroidism - A Model Predictive Control Approach.

    Wolff, Tobias M / Dietrich, Johannes W / Müller, Matthias A

    Frontiers in endocrinology

    2022  Volume 13, Page(s) 884018

    Abstract: 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 ... ...

    Abstract 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
    MeSH term(s) Hormone Replacement Therapy/methods ; Humans ; Hypothyroidism/drug therapy ; Thyroid Hormones/therapeutic use ; Thyroxine/therapeutic use ; Triiodothyronine/therapeutic use
    Chemical Substances Thyroid Hormones ; Triiodothyronine (06LU7C9H1V) ; Thyroxine (Q51BO43MG4)
    Language English
    Publishing date 2022-06-24
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2592084-4
    ISSN 1664-2392
    ISSN 1664-2392
    DOI 10.3389/fendo.2022.884018
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: Editorial: Thyroid hormones and cardiac arrhythmia.

    Dietrich, Johannes W / Müller, Patrick / Leow, Melvin Khee Shing

    Frontiers in endocrinology

    2022  Volume 13, Page(s) 1024476

    MeSH term(s) Arrhythmias, Cardiac ; Humans ; Thyroid Hormones
    Chemical Substances Thyroid Hormones
    Language English
    Publishing date 2022-09-06
    Publishing country Switzerland
    Document type Editorial
    ZDB-ID 2592084-4
    ISSN 1664-2392
    ISSN 1664-2392
    DOI 10.3389/fendo.2022.1024476
    Database MEDical Literature Analysis and Retrieval System OnLINE

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