Download Thyroid hormone

Thyroid hormone
สุวัฒณี คุปติวุฒิ
ตึกจุฑาธุช หอง 101
Aims
Functional anatomy of thyroid gland
Synthesis, secretion and metabolism of the
thyroid hormones
The mechanism of thyroid hormone action
Role of thyroid hormone in development ,
growth and metabolism
Thyroid hormone deficiency and excess in
adult
1
Anatomy Relation of Thyroid gland
Cross section of Thyroid gland
Thyroid follicle
C cell
Thyroglobulin
store in colloid
of follicle
Follicle cells
2
Thyroid gland contains numerous follicles
Colloid is composed of thyroglobulin
Thyroid follicle produce and secrete thyroxine
(T4) and triiodothyronine (T3)
C cell or parafollicular cell produce calcitonin
Synthesis of Thyroid Hormone
Uptake of Iodine by thyroid
Coupling of Iodine to Thyroglobulin
Formation of T3, T4 from MIT / DIT
Storage of MIT / DIT in follicular space
Re-absorption of MIT / DIT
Release of T3, T4 into serum
Breakdown of T3, T4 with release of Iodine
3
3
T Peroxidase
Coupling
COLLOID
Reabsorption
T Peroxidase
Iodination
2
4
T Peroxidase
6
Deiodinase
Thyroglobulin I
5
1
Iodine from diet
I-
Lysosome
Iodine trap
Na+/Isymporter
BLOOD VESSEL
Perchlorate / excess I2
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4
Uptake of Iodine by thyroid
stimulated by Thyroid stimulationg hormone(TSH)
Coupling of Iodine to Thyroglobulin
Monoiodotyrosine (Thyroglobulin + one I-)
Diiodotyrosine (Thyroglobulin + two I-)
Thyroid Hormones
T4 ( THYROXINE )
T3 ( TRIIODOTHYRONINE )
Formation of T3, T4 from MIT / DIT
MIT + DIT = T3 (Triiodothyronine)
DIT + DIT = T4 (Thyroxine)
Catalyzed by thyroid peroxidase
5
Majority of circulating hormone is T4
98.5% T4
1.5% T3
D = deiodinase
The affinity of the receptor for T3 > T4 ~ 10 times
Thyroid H. are poorly soluble in water
Thyroid binding protein: thyroid binding globulin
(TBG), transthyrtein and albumin
Increased TBG:
- High estrogen states (pregnancy,HRT)
- Liver disease (early)
total
Free
Decreased TBG
- Androgens or anabolic steroids
- Liver disease
total
TSH
Free
TSH
Decreased binding to TBG
- Phenytoin (dilantin)
- Salicylates
6
Regulation of
of Thyroid
Thyroid Hormone
Hormone Secretion
Secretion
Regulation
Iodine uptake
Colloid endocytosis
Growth of thyroid gl
Thyroid Hormone
Hormone Action
Action
Thyroid
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Thyroid Hormone
Hormone Action
Action
Thyroid
Increase basal metabolism
Stimulate cellular
cellular respiration
respiration
-- Stimulate
¾ Increase oxidative phosphorylation enzymes
in cells such as cytochromes, cytochrome
oxidase
uncoupling proteins (UCP 1-3)
¾ Increase activity of Na+/K+ pumps
¾ Increase RBC and 2,3 DPG enzyme
O2 consumption
body heat production
Intermediary metabolisms
Lipid metabolism
-
Lipolysis
-
Cholesterol clearance
Carbohydrate metabolism
-
Blood glucose
glucose absorption from GI tract
gluconeogenesis
glucogenolysis
8
Protein metabolism
protein synthesis (normal level)
Na+-K+ pump, myosin ATPase activity, amount of
calcium both in skeletal and heart muscle
Normal muscle function
High level of thyroid hormone
protein breakdown
Inhibit creatine kinase
Growth and development
Maturation and differentiation effects
Stimulating GH & IGF production
Bone growth and bone resorption
Promote growth and development of the fetal
And neonatal brain
- Regulate synpatogenesis, neural integration,
myelination and cell migration
Increase reflex response to stimuli
9
------- Level of symphysis
Normal
Normal
22 years
years
Hypothyroid
Hypothyroid
88 years
years
Dwarf-not
Dwarf-not
hypothyroid
hypothyroid
years
88 years
Normal
Normal
years
88years
Infantile body proportion (upper > lower portion)
Cretinism = dwarfism + mental retardatyion
Cretinism
A Color Atlas of Endocrinology p66
10
Other function
Increase number and affinity of β-adrenergic
receptor
Heart rate, contractility & cardiac output
Vasodilatation
Blood flow
Decrease mucopolysaccharide synthesis
hypothyroid
Myxedema
Maintain gonadal functions
Before Rx
After Rx
11
Thyroid Autoregulation
Stabilize plasma T3 , T4 and TSH
Organic I2
I- uptake
TSH
Response to TSH
T3, T4 not
I2
Organic I2
T3
T4
Organic I2
I- uptake
Response to TSH
T3, T4 not
Wolff-Chaikoff effect
Higher doses I- cause
cessation of hormone
formation
z
Decrease organification
cause hypothyroid
z
This block is temporary.
temporary
Inorganic I-
z
Autoregulation fail
Block
total organification
z
Increasing doses of Iincrease hormone
synthesis initially
percent of I- Uptake
z
Dosage of stable iodide
( μg/rat)
12
Jod-Basedow
z
Aberration of the Wolff-Chaikoff effect
z
Excessive iodine loads induce hyperthyroidism
Thyroid
Thyroid Dysfunction
Dysfunction
Hyperthyroidism
Hypothyroidism
Goitre
with Euthyroid
- Puberty
- Pregnancy
with Hyperthyroid
- Graves ’ disease
with Hypothyroid
- I2 deficiency
- Goitrogen
- Dyshormonogenesis
13
Hypothyroidism
„
Decreased metabolic rate
„
Weight gain, reduced appetite
„
Dry and cold skin
„
Weak, flabby skeletal muscles, sluggish
„
Myxedema
„
Apathetic, somnolent
„
Coarse hair, rough dry skin
„
Decreased iodide uptake
„
Possible goiter
Hyperthyroidism
„
Increased metabolic rate
„
Weight loss, increased appetite
„
Warm flushed skin
„
Weak muscles that exhibit tremors
„
Exophthalmos
„
Hyperactivity, insomnia
„
Soft smooth hair and skin
„
Increased iodide uptake
„
Almost always develops goiter
14
Thyroid Antibodies
Antibodies
Thyroid
Destructive Ab
Antithyroid peroxidase (anti TPO)
Antithyroglobolin (anti TG)
Hypothyroidism
(Hashimoto thyroiditis)
Stimulating Ab
Anti-TSH receptor (TSI)
Hyperthyroidism
(Graves’ disease)
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