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.

20 grams

4 cm

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

Histology of the thyroid gland .

Thyroid hormones derived from two iodinated tyrosine molecules √ .

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 . Synthesis of thyroid hormones • Active uptake of iodide into follicular cell • Iodide iodine .

concentration of iodine 30-50 times that of the circulation .Active transport of iodine (ATPase dependent) against electrical and chemical gradient .

• 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 .

Incorporation of iodine onto tyrosine residues on the thyroglobulin molecule .

4) Release of T4 and T3 into circulation - 100g T4 & 10 g 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 .

Daily production of thyroid hormone secretion and serum concentrations .

5’ Thyroid hormone 5 metabolism 5’ 5 3’ 3 .

placenta. pituitary gland. decarboxylation.liver. CNS: 5’ and 5 positions Type 2 . pituitary gland: 5’ position only: T4 T3 only: intracellular concentrations of T3 Type 3 . Metabolism of thyroid hormones Series of deiodinations by deiodinases Type 1 . thyroid.brain.brain. placenta: 5 position only T4 T3 Other metabolic pathways: sulphation. brown fat. kidney. conjugated with glucuronide .

5’ only T1 T1 Type 3 . Thyroxine (T4) other pathways 1&2 1&3 T3 S T3 3.5’.5 only thyronine .3’ rT3 3.5’ and 5 Type 2 .3’ T2 T2 Type 1 .5.

Control of thyroid hormone synthesis and release and feedback control .

TSH Receptors TSH G protein linked receptor cAMP IP3 + DAG Protein Ca2+ Protein Kinase A 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 .

Thyroid hormone receptors .

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 .

Isoforms of the thyroid hormone receptor DBD DBD DBD DBD .

Dimerization of thyroid hormone receptors and gene activation/inactivation T3 .

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increasing enzymes in the metabolic chain. Resting metabolic rate may increase 100% with excess thyroid hormones or decrease by 50% with a deficiency Positive inotropic and chronotropic effects on the heart Important in growth and development - particularly skeleton and nervous system . increasing Na+/K+ ATPase activity.Functions of thyroid hormones Stimulate metabolic rate: increasing number and size of mitochondria.

Feedback control of thyroid hormone synthesis and secretion .

Radioisotopic (technetium) scanning of the thyroid gland .regional function of the gland No left lobe hyperthyroidism hypothyroidism Hot nodule Cold nodule .

Measuring ‘free’ T4 Phosphate 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 .

Assay of antibodies to the human TSH receptors Patients serum Add Precipitate Count + TSH 125I-TSH receptors (bovine) (porcine) .

Circulating concentrations of TSH and pituitary function test in normal and primary hyperthyroidism .

Saggital MR scans of a) normal and b) a patient with a craniopharyngioma causing bitemporal hemianopia and hypopituitarism .

Primary hyperthyroidism Hypothyroidism .

tiredness • Diffuse goitre .TSH stimulating growth • Opthalmompathy and dermopathy . tachycardia. Grave’s disease (10) • Autoimmune .activating AB’s to TSH receptor • High concentrations of circulating thyroid hormones. low TSH • Weight loss.

Symptoms and signs of hyperthyroidism .

Hashimoto’s (1o) • Autoimmune . high TSH • Lethargy.AB’s destruction of thyroid gland • Low concentrations of thyroid hormones.lymphocytic infiltration of gland + TSH stimulated growth . intolerance to cold • Lack of growth and development • Diffuse goitre .

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Symptoms and signs of hypothyroidism .