Thyroid systems engineering : a primer in mathematical modeling of the hypothalamus-pituitary-thyroid axis / Simon Goede and Melvin Khee-Shing Leow.

Format:

Book

Author/Creator:

Goede, Simon Lucas, author.

Leow, Melvin Khee-Shing, author.

Series:

River Publishers series in biomedical engineering.

River Publishers Series in Biomedical Engineering

Language:

English

Subjects (All):

Physiology--Mathematical models.

Physiology.

Mathematical models.

Physical Description:

1 online resource (338 pages) : illustrations, tables.

Place of Publication:

Gistrup, Denmark : River Publishers, [2018]

Summary:

In recent years, a considerable amount of effort has been devoted, both in industry and academia, towards the behavioral modeling, evaluation and prediction of the hypothalamus pituitary thyroid system.Thyroid Systems Engineering targets an optimal treatment of people suffering from thyroid hormone disorders. The content is motivated by in-depth observations of such patients whose rich data supported the theoretical framework arising from formal mathematical reasoning, guided by the nature of thyroid physiology. Leveraging on the insights emerging from the unique combination of an electrical engineer working with a clinical thyroidologist, and both being scientists skilled in mathematics, the authors introduce this new discipline and field of scientific investigation aptly designated as Thyroid Systems Engineering.Readers will discover that mathematics can indeed model the behavior of the hypothalamus-pituitary-thyroid (HPT) axis. Focused on modeling, each of the eighteen chapters gives the reader a notion of the application of relevant mathematics to pertinent issues encountered in mainstream thyroidology. Many cellular processes resemble the flux of variables and states in a complex multi-parameter space through time analogous to current flow in electrical networks. It is then logical to apply the principles and physical laws of electrodynamics, electrical network theory, control systems theory and signal theory to many of the biological phenomena encountered in endocrinology. Such an approach is used liberally throughout the book and successfully yields elegant solutions to a number of models presented within.This book can serve as a reference to mathematical modeling in other aspects of endocrine physiology, and as the starting point for a fundamental course in medical modeling. It will appeal to postgraduates in electrical engineering, academic physicians and biomedical researchers. Further, readers equipped with advanced calculus, electrical network theory, control theory and signal theory should be able to follow the mathematical expositions that describe thyrotropic control. They represent a new discipline based on mathematical modeling in physiology applicable to medical diagnostics, measurement and treatment to cooperate in the clinical team and realize an optimized treatment for patients.

Contents:

Cover

Half Title

Series Page

Title Page

Copyright Page

Dedication

Table of Contents

Preface

Acknowledgements

List of Figures

List of Tables

List of Abbreviations

1: General Introduction

1.1 Introduction

2: Physiology of the HPT Axis

2.1 Synopsis of Thyroid Biochemistry and Molecular

2.2 Operation of the Hypothalamus-Pituitary (HP)

2.3 Thyroid Physiology

2.4 Physiological Feedback Representation of the HPT

References

3: Modeling Principles

3.1 Introduction

3.2 Modeling Examples

3.2.1 Modeling Example 1

3.3 Electrical Network Representation of the Leaking Water Container

3.4 Static Modeling

3.5 Modeling Examples from Solid-State Physics and Electronic Engineering

3.6 General Appearance and Decay Model with Electrical Network Elements

3.7 Appearance Time Constant

3.8 Determining the Value of The Appearance Time Constant

3.9 Discussion

3.10 Conclusion

4: Medical Statistics and Mathematical Modeling Make Strange Bedfellows

4.1 Introduction

4.2 Pitfalls in The Application of Inferential Statistical Methods

4.2.1 Explanation of the Observed Log-Linear Relationship Between [TSH] and [FT4]

4.3 Abuse of Mathematical Models

4.3.1 Critical Notes

4.4 Future Developments

4.5 Conclusion

5: Systems Theory Applied on the Modeling of the HPT Axis and First Principles of Feedback and Homeostasis

5.1 Introduction

5.2 Definition of System Components

5.3 System Dynamics

5.4 Frequency Response of the First-Order Low-Pass Section

5.5 Cascading System Blocks

5.6 Example of a Feedback System

5.6.1 Feed Forward Compensation

5.7 Discussion

6: The Mathematical Relationship Between [FT4] and [TSH]

6.1 Introduction

6.1.1 History.

6.2 Linear-Logarithmic Relationship Between [FT4] and [TSH]

6.3 Modeling the Curved [FT4]-[TSH] Characteristic

6.4 Properties of the Exponential Function

6.4.1 Effect of the Multiplier Model Parameter S

6.4.2 Effect of the Exponential Model Parameter

6.5 Dynamic Signal Transfer of the HP Characteristic

6.6 Generalized Expression of the HP Characteristic

6.7 Discussion

7: The Thyroid Gland and the Relationship Between [TSH] and [FT4]

7.1 Introduction

7.2 Model of the Thyroid Gland

7.3 Discussion

8: The Hypothalamus-Pituitary (HPT) Set Point Theory

8.1 Introduction

8.2 The Hypothalamus-Pituitary (HP) Control System

8.3 Derivation of the Point of Maximum Curvature from the HP Function

8.4 Theory Behind of the Physiology of the Homeostatic Control Process

8.5 Point of Maximum Curvature of the Thyroid Characteristic

8.6 Discussion

9: The Human Hypothalamus-Pituitary-Thyroid Control System

9.1 Introduction

9.2 Analysis of the HP Unit and Thyroid in the Closed-Loop Situation

9.3 Small-Signal Model of the Thyroid

9.4 Small-Signal Modeling of the Hypothalamus-Pituitary (HP) Unit

9.5 Loop Gain Analysis

9.6 Hypothalamus (TRH)-Pituitary (TSH) Transfer

9.7 The Detailed HPT Loop

9.8 Large-Signal Intercept Set Point

9.9 Discussion

10: Reference Ranges for TSH and FT4

10.1 Introduction

10.2 Reference Ranges for [FT4] and [TSH]

10.3 Set Point Determined Euthyroid Ranges for [TSH]

10.4 Different Reference Ranges in Different Laboratories

10.5 Discussion

10.6 Concluding Remarks

11: Extrapolation to the Set Point from a Single Available Measurement

11.1 Introduction

11.2 Calculation of [FT4] Assuming a Pre-Determined Set Point Value of [TSH].

11.3 Calculation of [TSH] Assuming a Set Point Value of [FT4] = 15 pmol/L

11.4 Extrapolation to a Set Point Using a "Phantom" [FT4]-[TSH] Point

11.5 Discussion

12: Measurement Methods, Error Sources, and Error Interpretation of FT4 and TSH Concentration Values

12.1 Introduction

12.2 Error Definitions and Error Sources

12.3 Measurement Theory

12.4 [FT4] and [TSH] Measurement or Thyroid Function Tests (TFTs)

12.5 Sensitivity of Model Parameter ' as a Function of [FT4] and [TSH]

12.6 Measurement Errors from [FT4] Rounding or Truncation Procedure

12.7 Absolute Deviation of [FT4] as a Function of Relative [TSH] Error

12.8 The Effect of Absolute Errors in [FT4] Resulting in Deviations of [TSH]

12.9 Errors from Physiological Memory Effects, or Hysteresis

12.10 Errors from Biochemical Assay Technology for [TSH] and [FT4]

12.11 Discussion

12.12 Conclusion

13: Model Identification, Validation, and Outlier Selection

13.1 Introduction

13.1.1 A Brief History of Celestial Modeling as a Prelude to Model Validation

13.2 Model Identification

13.3 Examples of [TSH], [FT4], and [FT3] Outlier Identification

13.4 Discussion

14: Half-Life and Plasma Appearance Dynamics of T3 and T4

14.1 Introduction

14.2 Half-Life (t1/2) of T4 and Calculation of the Decay Time Constant

14.2.1 Half-Life Modeling with Electrical Networks

14.3 Drug Input and Output Signals

14.3.1 Network Model

14.4 Decay Behavior after Finalization of Drug Appearance

14.5 Discussion

15: Pharmacokinetics of Liothyronine (L-T3) and Levothyroxine (L-T4)

15.1 Introduction

15.2 Thyroxine Kinetics

15.2.1 PK of L-T4 with T4 Level Dependent and Constant t1/2 When Administered as a Daily Dose

15.2.2 Derivation of the Steady-State Level.

15.3 Average Value of Time-Dependent Functions

15.4 RMS Value of Continuous Time-Dependent Functions

15.5 Weekly Administration of L-T4 at Seven Times the Normal Daily Dose

15.6 Triiodothyronine Kinetics

15.6.1 Accumulation of T3 Based on Various Dosages of Daily Liothyronine (L-T3)

15.6.2 Accumulation of T3 over a Period of 9 Days with a Daily Dose Dd of 12.5 g L-T3

15.7 Compensation Strategies When L-T4 Is Not Taken Regularly

15.7.1 Acceleration Toward Steady State for a 100 mg L-T4 Daily Dosing Scheme Within 1 Week

15.8 Calculation of a Reduced Dosing Scheme

15.9 Negative Long-Term Effects of Externally Administered T3

15.10 Discussion

Appendix

16: Circadian Feedback Dynamics and Set Point Stability Analysis of the Hypothalamus Pituitary Thyroid System

16.1 Introduction

16.2 Oscillators

16.3 Influence of [FT4] and [TSH] on Feedback Dynamics

16.4 [TSH] Oscillations

16.5 Data Analysis

16.6 Fourier Analysis

16.7 Convolution and Deconvolution

16.8 Thyroid Response

16.9 Set Point Stability

16.10 Discussion

16.11 Concluding Remarks

17: HPT Simulation with Trans-Linear Circuits

17.1 Introduction

17.2 Generalized Stimulated Gland Characteristics

17.3 Large-Signal Intercept Set Point

17.4 Differential Amplifiers

17.5 Trans-Linear Circuits

17.5.1 Introduction

17.5.2 Examples of Signal Processing with Trans-Linear Circuits

17.6 HPT Functions with Trans-Linear Circuits

17.7 The Electronic HP System Implementation

17.8 The Electronic Thyroid Implementation

17.9 Discussion

18: From Theory to Practice: Computer-Aided Set Point Application

18.1 Introduction

18.2 Thyroid-SPOT Software

18.3 Clinical Studies Using Thyroid-SPOT

18.4 Thyroid-SPOT (Set Point Optimization and Targeting).

18.5 Thyroid Function Tests

18.6 Interpretation of Test Results

Index

About the Authors.

Notes:

Includes index.

Includes bibliographical references at the end of each chapters and index.

Description based on print version record.

ISBN:

1-000-79278-1

1-00-333982-4

1-003-33982-4

1-000-79594-2

1-5231-3899-8

87-93609-58-2

9781003339823

OCLC:

1027171741