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Prof. Dr. med. PhD
Gabor Szinnai
Department of Clinical Research
Profiles & Affiliations
Pediatric Thyroid Diseases

My main research interests are pediatric thyroid diseases with special focus on pharmacotherapy.

Thyroid hormones are essential for normal brain development, and for normal cognitive functions. Treatment of thyroid diseases is difficult in newborns and children. Over- or underdosing is an important problem in clinical practice. To mitigate the risk of negative neurological and developmental outcome, it is essential to establish an optimal, personalized dosing that is continuously fine-tuned in neonates, infants and children with hyper- or hypothyroidism.

In the context of a collaborative research project with Pediatric Pharmacology at UKBB, and Department of Mathematics, University of Konstanz we developped mathematical population pharmacokinetic-pharmacodynamic (PKPD) models that are able to describe and predict individual thyroid disease progression during treatment with thyroid hormone replacement therapy or anti-thyroid drugs based on routine clinical and laboratory data. Currently, these PKPD models are being enhanced and validated in a prospective international multicenter study, the OptiThyDose study. The ultimate aim is to provide simple personalized dosing to children with thyroid diseases avoiding under- or overdosing.


Further projects are focussing on glucocorticoid induced adrenal insufficiency in individuals with leukemia (LeukemiaCort study) and on water regulating hormone kinetics, mainly arginine vasopressin and its surrogate marker copeptin, in health and disease in children.

Selected Publications
Steffens, Britta, Koch, Gilbert, Gächter, Pascal, Claude, Fabien, Gotta, Verena, Bachmann, Freya, Schropp, Johannes, Janner, Marco, l’Allemand, Dagmar, Konrad, Daniel, Welzel, Tatjana, Szinnai, Gabor, & Pfister, Marc. (2023). Clinically practical pharmacometrics computer model to evaluate and personalize pharmacotherapy in pediatric rare diseases: application to Graves’ disease. Frontiers in Medicine, 10. https://doi.org/10.3389/fmed.2023.1099470
URLs
URLs
Atila C, Gaisl O, Vogt DR, Werlen L, Szinnai G, & Christ-Crain M. (2022). Glucagon-stimulated copeptin measurements in the differential diagnosis of diabetes insipidus: a double-blind, randomized, placebo-controlled study. European Journal of Endocrinology, 187(1), 65–74. https://doi.org/10.1530/eje-22-0033
URLs
URLs
Bachmann F, Koch G, Pfister M, Szinnai G, & Schropp J. (2021). OptiDose: Computing the Individualized Optimal Drug Dosing Regimen Using Optimal Control. Journal of Optimization Theory and Applications, 189(1), 46–65. https://doi.org/10.1007/s10957-021-01819-w
URLs
URLs
Koch, Gilbert, Steffens, Britta, Leroux, Stephanie, Gotta, Verena, Schropp, Johannes, Gächter, Pascal, Bachmann, Freya, Welzel, Tatjana, Janner, Marco, L’Allemand, Dagmar, Konrad, Daniel, Szinnai, Gabor, & Pfister, Marc. (2021). Modeling of levothyroxine in newborns and infants with congenital hypothyroidism: challenges and opportunities of a rare disease multi-center study. Journal of Pharmacokinetics and Pharmacodynamics, 48, 711–723. https://doi.org/10.1007/s10928-021-09765-w
URLs
URLs
Burckhardt MA, Gotta V, Beglinger S, Renggli L, Bachmann S, Hess M, Rentsch K, Pfister M, Koch G, Davis EA, Zumsteg U, Jones TW, & Szinnai G. (2020). Copeptin Kinetics and Its Relationship to Osmolality During Rehydration for Diabetic Ketoacidosis in Children. The Journal of Clinical Endocrinology and Metabolism, 105(11). https://doi.org/10.1210/clinem/dgaa568
URLs
URLs
Selected Projects & Collaborations
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LeukemiaCort: A Swiss prospective multicenter longitudinal assessment of hypothalamic-pituitary-adrenal axis suppression after glucocorticoid therapy for leukemia and lymphoblastic lymphoma in children. An explorative study.
Research Project  | 4 Project Members

Glucocorticoid therapy is an important component of the treatment regimen for childhood acute lymphoblastic leukaemia and lymphoblastic lymphoma by inducing apoptosis of lymphoblastic cells. However, the use of supraphysiological doses of glucocorticoids can lead to hypothalamic-pituitary-adrenal axis suppression. This suppression can result in a reduced cortisol response, leading to impaired stress response and inadequate host defence against infections, which can ultimately result in morbidity and mortality. To date, there is insufficient high-quality research to inform evidence-based guidelines for glucocorticoid replacement therapy in this populatioon.

Hence, in this prospective multicenter study, we aim to analyze the patterns of suppression of the hypothalamic-pituitary-adrenal axis suppression in children receiving glucocorticoid therapy for acute lymphoblastic leukaemia and lymphoblastic lymphoma.

Project cover
OptiThyDose: Intelligent Digital Decision Support Tool to Personalise Dosing for Children with Thyroid Diseases
Research Project  | 8 Project Members

Thyroid hormones are critical for normal brain development, growth, and puberty. Hypo-/hyperthyroidism manifests at birth or during childhood. Thus, prompt, adequate medical treatment is crucial to protect cognitive and physiological development in affected children. Current guidelines recommend standard dosing regimens, despite a wide spectrum of disease variability in terms of severity, activity and receptivity. Over- and under-dosing is frequent, making a decision support tool for optimal and fine-tuned personalised dosing essential for adequate medical care.

The aim of this project is to provide personalised treatment plans for children with a thyroid disease. The consortium will build upon their existing work on an intelligent decision support tool that optimises and computes personalised treatment dosing. The researchers will use computer models that consider individual disease characteristics obtained from observational studies in combination with optimal dosing algorithms to develop an intelligent clinical decision support tool “OptiThyDose” to personalise and optimize dosing regimens. OptiThyDose iteratively computes individual dose regimens based on the patient's age, weight and disease severity to restore and maintain thyroid hormone balance.