endo 1.08 the thyroid gland gross anatomy and histology of the thyroid gland thyroid hormone...
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Endo 1.08 The thyroid gland
• Gross anatomy and histology of the thyroid gland
• Thyroid hormone synthesis
• Thyroid hormone secretion, peripheral conversion and metabolism
• Measurement of free T4 and TSH
• Actions of thyroid hormones, hyper-and hypothyroidism
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Blood supply
Superior and inferior thyroid arteries from external carotids and subclavian arteries respectively
Superior, middle and inferior thyroid veins
More blood per unit weight than kidney - goitre bruit
20 grams
4 cm
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Histology of the thyroid gland
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Thyroid hormones derived from two iodinated tyrosine molecules
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Synthesis of thyroid hormones
• Active uptake of iodide into follicular cell
• Iodide iodine - H2O 2 (catalysed by TPO)
• Active uptake of iodine at follicular/ colloid interface
• Incorporation of iodine onto tyrosine residues of thyroglobulin
• Coupling of iodinated tyrosines
• Storeage of T3 and T4
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Active transport of iodine (ATPase dependent) against electrical and chemical gradient - concentration of
iodine 30-50 times that of the circulation
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• Active uptake of iodine by a sodium iodide symporter
• Oxidation of iodide to iodine
• Iodination of tyrosine residues at apical/colloid interface to form MIT and DIT
• Uptake of thyroglobulin into the lumen of the follicle
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Incorporation of iodine onto tyrosine residues on the thyroglobulin molecule
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4) Release of T4 and T3 into circulation -
100g T4 & 10g T3/day
3) ~ 10% T4 undergoes mono-deiodination to T3 before secretion
2) Fusion of colloid droplets with lysosomes --> hydrolysis and release of thyroid hormones
1) Stimulated by TSH colloid droplets with the bound thyroid hormones are taken back into follicular cells by pinocytosis
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Daily production of thyroid hormone
secretion and serum
concentrations
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5’ 5
3’ 3
5’
5Thyroid hormone
metabolism
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Metabolism of thyroid hormones
Series of deiodinations by deiodinasesType 1 - liver, kidney, thyroid, pituitary gland,
CNS: 5’ and 5 positions
Type 2 - brain, brown fat, placenta, pituitary gland: 5’ position only: T4 T3 only: intracellular concentrations of T3
Type 3 - brain, placenta: 5 position only
T4 T3
Other metabolic pathways: sulphation, decarboxylation, conjugated with glucuronide
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Thyroxine (T4)
T3rT3
T3 S
TRIAC
T2T2
other pathways
T1 T1
thyronine
1 & 2 1 & 3
3,5,3’ 3,5’,3’
Type 1 - 5’ and 5
Type 2 - 5’ only
Type 3 - 5 only
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Control of thyroid hormone synthesis
and release and feedback control
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TSH Receptors
TSH
G protein linked receptor
cAMP IP3 + DAG
Protein Ca2+ Protein Kinase A CM Kinase
C(high concentrations)
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Actions of TSH
• Active uptake of iodine*
• Stimulates other reactions involved in thyroid hormone synthesis
• Stimulates the uptake of colloid
• Induces growth of the thyroid gland
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Thyroid hormone receptors
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Thyroid hormone receptors
• Type 2 receptors in nucleus - high affinity for T3
• Dimerize with another T3 receptor (homodimer) or retinoic acid receptor (heterodimer)
• Dimerized receptor + other transcription factors gene transcription
• Membrane receptors? Ion movements
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Isoforms of the thyroid hormone receptor
DBD
DBD
DBD
DBD
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T3
Dimerization of thyroid hormone receptors and gene activation/inactivation
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Functions of thyroid hormonesStimulate metabolic rate: increasing number and
size of mitochondria, increasing enzymes in the
metabolic chain, increasing Na+/K+ ATPase activity.
Resting metabolic rate may increase 100% with
excess thyroid hormones or decrease by 50% with a
deficiency
Positive inotropic and chronotropic effects on
the heartImportant in growth and development -
particularly skeleton and nervous system
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Feedback control of
thyroid hormone
synthesis and secretion
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Radioisotopic (technetium) scanning of the thyroid gland - regional function of the gland
No left lobe hyperthyroidism
hypothyroidism
Hot noduleCold nodule
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Measuring ‘free’ T4
1) Add serum sample or standard (T4 ) to latex beads coated with Abs
2) Add T4 labelled with alkaline phosphatase. This will bind to any unoccupied Ab binding sites
3) Add a substrate that will fluoresce when the alkaline phosphatase removes a phosphate group
4) Fluorescent intensity will be inversely proportional to the concentration of T4
Phosphate
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Assay of antibodies to the human TSH receptors
Patients serum Add Precipitate Count + TSH 125I-TSH
receptors (bovine) (porcine)
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Circulating concentrations of TSH and pituitary function test in normal and primary hyperthyroidism
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Saggital MR scans of a) normal and b) a patient with a craniopharyngioma causing bitemporal hemianopia and
hypopituitarism
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Primary hyperthyroidism Hypothyroidism
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Grave’s disease (10)
• Autoimmune - activating AB’s to TSH receptor
• High concentrations of circulating thyroid hormones, low TSH
• Weight loss, tachycardia, tiredness
• Diffuse goitre - TSH stimulating growth
• Opthalmompathy and dermopathy
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Symptoms and signs of hyperthyroidism
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Hashimoto’s (1o)
• Autoimmune - AB’s destruction of thyroid gland
• Low concentrations of thyroid hormones, high TSH
• Lethargy, intolerance to cold
• Lack of growth and development
• Diffuse goitre - lymphocytic infiltration of gland + TSH stimulated growth
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Symptoms and signs of hypothyroidism
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