ESR [018] Thyroid Axis lecture 2024 2025
Page 1
Introduction to NGU School of Medicine
Overview of the institution aimed at fostering unbounded thinking among students.
Page 2
Subject Overview
Institution Details
NGU School of Medicine
Course Reference: ESR[018]
Focus: The Normal Thyroid Axis
Academic Year: 2024-2025
Department: Medical Biochemistry
Page 3
The Normal Thyroid Axis
Central theme of the session focusing on the thyroid gland's functions and hormone production.
Page 4
Session Aim
Objective: Familiarize NGU students with:
Biosynthesis of thyroid hormones
Mechanism of action
Page 5
Learning Outcomes
By the end of this session, you will be able to:
Describe the gross morphology of the thyroid gland using diagrams.
Sketch the structure of thyroid follicles.
Relate the follicle to T3 and T4 biosynthesis.
List and describe circulating binding proteins.
Explain why T4 is considered a prohormone.
Discuss the nature of T3 receptors.
Identify and explain the physiological actions of T3.
Page 6
Thyroid Anatomy
Examining morphological and anatomical aspects of the thyroid gland.
Page 7
Anatomy of the Thyroid Gland
Shape & Location:
Butterfly-shaped gland with 2 lobes joined by an isthmus.
Weighs between 15–40g, located below the larynx and in front of the trachea.
Gross enlargement results in goitre.
Page 8
Parathyroid Glands
Four parathyroid glands attached to the posterior thyroid surface.
Function: Sensing calcium levels and secreting parathyroid hormone (PTH).
Page 9
Follicular Structure
Production site for thyroid hormone consists of multiple acini (follicles).
Each follicle: spherical, surrounded by a single layer of epithelial cells, filled with colloid (mainly thyroglobulin).
Page 10
Cellular Components of Follicles
Components include:
Follicular Epithelial Cells: Surround the follicle.
C-cells: Secrete calcitonin.
Sympathetic Nerve Endings and Lymphatic Vessels: Present in the structure.
Basement Membrane and Capillaries: Essential for nutrient supply and hormone release.
Page 11
Follicular Activity
Underactive follicles: Flattened epithelial cells with increased colloid.
Overactive follicles: Taller columnar epithelial cells with reduced colloid.
Page 12
Hormone Synthesis Overview
Introduction to the synthesis processes of thyroid hormones.
Page 13
Types of Thyroid Hormones
Two primary hormone types:
Thyroid Follicles: Produce T4 (Thyroxine) and T3 (Triiodothyronine).
T4 is the primary secretion; T3 has greater biological activity.
Peripheral tissues convert T4 to T3 via deiodination.
C-cells: Produce calcitonin which antagonizes PTH (slight effect on calcium metabolism).
Page 14
Hormone Synthesis Details
Overview of thyroid hormone synthesis.
Page 15
Iodine Transport
Significant iodine levels required for hormone synthesis.
Iodide (I-) is actively transported from the blood into the follicular lumen, leading to concentration in the thyroid gland.
Page 16
Thyroglobulin Synthesis
Thyroglobulin: A tyrosine-rich protein synthesized in follicular epithelial cells, secreted into the lumen for hormone formation.
Page 17
Thyroid Peroxidase (TPO)
A crucial enzyme in colloid that:
Oxidizes iodide to iodine (I2).
Organifies iodine by linking it to tyrosine residues in thyroglobulin, leading to MIT (Monoiodotyrosine) and DIT (Diiodotyrosine) formation.
Efficiently couples DIT to produce T4.
Page 18
Coupling and Residues
Coupling Process:
Peroxidase couples DIT residues primarily for T4 production.
Some residues remain uncoupled in thyroglobulin, retaining MIT and DIT.
Page 19
Iodine Incorporation Mechanics
Chemical reactions leading to MIT and DIT formation.
Page 20
Hormone Synthesis Overview
Reiteration of thyroid hormone synthesis processes.
Page 21
Chemical Structures
Chemical structures of Thyroxine (T4) and Triiodothyronine (T3) provided for reference.
Page 22
TSH Effects Overview
Evaluating intracellular effects of TSH (Thyroid Stimulating Hormone).
Page 23
Endocytosis and Thyroglobulin
Thyroglobulin is endocytosed by follicular cells in response to TSH, serving as a reservoir due to high concentrations.
Defects in hormone synthesis may take months to show symptoms.
Page 24
Release of Thyroid Hormones
Thyroglobulin breakdown occurs in lysosomes following endocytosis, releasing T4, T3, MIT, and DIT.
Iodine is salvaged and returned to the follicular lumen.
Page 25
Blood Flow in the Thyroid
The thyroid exhibits exceptionally high blood flow, crucial for iodide delivery and thyroid hormone export.
Blood flow measured at 4-6 ml/min/g, surpassing that of the kidney, resulting in an audible "bruit" in overactive conditions.
Page 26
Thyroid Hormones in Circulation
Overview of thyroid hormones circulating in the bloodstream.
Page 27
Regulation of Secretion
Secretion driven by TSH with a normal range of 0.5-5.0 mU/mL; T3 and T4 levels provide negative feedback to regulate TSH secretion.
Page 28
Normal Concentrations
Total normal concentrations are as follows:
Total T4: 64 – 155 nmol/L
Total T3: 1.1 – 3.0 nmol/L
Page 29
Binding Proteins
99.9% of T3 and T4 are bound to three main proteins:
Thyroxine Binding Protein (TBG): 75% of bindings.
Transthyretin (Thyroxine Binding Prealbumin): 20%.
Albumin: 5%.
Only 0.1% remains free in circulation with Free T4 (12-31 pmol/L) and Free T3 (3-6 pmol/L).
Page 30
Regulation of Thyroid Hormones
Continued exploration of regulation mechanisms for thyroid hormones.
Page 31
Further Regulation Breakdown
Detailed analysis of thyroid hormone regulation.
Page 32
Physiological Actions Overview
Summary of physiological effects of thyroid hormones.
Page 33
T3 and T4 Actions
Description of how thyroid hormones exert their effects on various tissues.
Page 34
Effects of T3 and T4
T3 is more bioactive than T4 and influences:
Basal metabolism.
Growth and development, particularly with GH.
Cardiovascular function: Increased heart rate and contractility.
CNS function: Alertness regulation and fetal brain development.
Page 35
Hormonal Modulation
Hormonal Actions:
Thyroid hormones adjust the effects of other hormones.
Page 36
Synergistic Effects
Adrenaline collaborates with thyroid hormones, leading to increased lipolysis and heart rate; TRH inhibits secretion and release.
Page 37
Prohormonal Relationship
T4 is deiodinated to T3 which acts on nuclear receptors; emphasizes T4's role as a prohormone for T3.
Page 38
Target Cell Dynamics
The target cell equalizes T3 needs, showing active decision-making rather than mere hormonal acceptance.
Page 39
Deiodination Processes
Explains the two types of deiodination:
D3: Inactivates the hormone.
D1/D2: Activate the hormone.
Page 40
TSH Effects Summary
TSH stimulates all aspects related to thyroid gland activity.
Page 41
Long-term TSH Effects
TSH enhances thyroid capacity to produce hormones, leading to hypertrophy and hyperplasia of follicular cells. Excessive stimulation can result in conditions like Graves' disease.
Page 42
TSH Stimulation Effects
Effects of TSH include increased iodination, microvilli length on epithelial cells, intracellular volume, endocytosis, hormone release, iodide influx, and protein synthesis within thyroid tissue.
Page 43
Cellular Actions Summary
Overview of cellular actions of thyroid hormones in relation to cellular processes.
Page 44
Nuclear Receptors
T3 binds to nuclear receptors which are members of the steroid-thyroid receptor superfamily.
Page 45
Binding Dynamics
TR receptors bind to target DNA, influencing transcription processes.
Page 46
Co-factors in Action
Describe interactions with RXR and modification of gene expression through various receptor formations.
Page 47
More Receptor Functions
Importance of TR in modulating gene expression.
Page 48
Variation in Thyroid Receptors
Overview of different TR genes and the effects of alternative splicing on receptor expression in various tissues.
Page 49
TR Diversity in Humans
Presence of multiple TR types and their implications on function depending on tissue specificity.
Page 50
Receptor Variability Continuation
Further elaboration on the diversity of thyroid receptors in human physiology.
Page 51
Cellular Responses to T3 and T4
Summary of T3 and T4 physiological responses, including energy regulation and growth.
Page 52
Transcription Regulation
Describes dual transcription control mechanism through repressive and enhancing effects on gene transcription.
Page 53
Mitochondrial Effects of T3
Thyroid hormones significantly modify mitochondrial protein and lipid compositions, contributing to oxidative metabolism.
Page 54
Indirect Regulatory Factors
Increase in nuclear expressions of critical regulators affecting mitochondrial function due to T3 influence.
Page 55
Direct Mitochondrial Regulation
T3 binds to mitochondrial proteins to influence energy metabolism and trigger mtDNA replication.
Page 56
Mitochondrial Effects Conclusion
Summary of T3 functions within the mitochondria regarding energy regulation.
Page 57
Visual Anatomy of Thyroid Follicles
Observations from microscopy of thyroid structures.
Page 58
Vascularization of Thyroid
The thyroid is highly vascularized with a network of capillaries surrounding the follicles.
Page 59
Vascular Cast Representation
Visualization of vascular patterns associated with thyroid activity.
Page 60
Normal Thyroid Lumen Sectioning
Examination of normal thyroid tissue sections highlighting specific features.
Page 61
Staining Techniques
Use of staining to visualize normal thyroid tissues and component structures.
Page 62
Autoantibody Staining
Immunofluorescent staining using antibodies from hypothyroid patients for diagnostic purposes.
Page 63
Scanning Electron Microscopy
EM imaging revealing detailed morphology of normal thyroid structure.
Page 64
Follicle Visualization
Scanning EM used to analyze single follicle structure and cellular organization.
Page 65
Autoradiography Techniques
Iodinated thyroglobulin visualization through autoradiography in thyroid studies.
Page 66
Follicular Cell Surface Analysis
Investigation of luminal surfaces and secretory processes in follicular cells using EM.
Page 67
Embryological Anomalies
Discussion on thyroid developmental abnormalities linked to genetic mutations.
Page 68
Summary of Key Concepts
The thyroid is a specialized organ producing two primary hormones:
Thyroid hormones (iodinated tyrosine derivatives)
Calcitonin (peptide hormone)
Reviews the synthesis, control, and physiological effects of thyroid hormones.
Page 69
Suggested Readings
Recommended literature for deeper understanding of endocrinology and thyroid function.
Page 70
Conclusion
Closing remarks and thanks from NGU School of Medicine.