Thyroid Hormone (TH)

Structures

Iodine

Synthesis

Secretion

Metabolism

Actions

Hypo- & hyper- thyroidism

Regulation

follicle

Reverse T3

Activity: T3 > T4 >> rT3

iodine

iodised salt

… no salt sale in the shops of Dushanbe

Blood

I–

T3T4

90% T4, 9% T3, 1% rT3

Thyroglobin

Regulation of Thyroid Hormone Concentrations

Hypothalamus

Cold

(neonates) +

+

Anterior Pituitary

+ (1)

Thyrotrophin Releasing hormone (TRH)

Thyroid Gland

Thyroid Stimulating Hormone (TSH) = Thyrotrophin

Thyroid stimulating immunoglobulins (TSI)

Thyroid hormone (TH)

1. TH synthesis

2. TH release

3. number & size of cells

Metabolism

T4

T3

rT3

di-iodothyronines I– split off

In: liver, kidney, pituitary

33%

45%

**

* Regulation:

T4 T3 inhibition by: propylthiouracil,

propanolol ( blocker)glucocorticoidsburns, trauma, renal failure, infarct food intake

In Blood

TH

(T4, T3)+

protein(thyroid binding

globulin & others)

Protein bound—T4

or T3)

mostfree

Free % small

< 0.5 %

gets into cells – biologically relevant

Thyroid Hormone Effects

4–5 times

T3 > T4 >> rT3

inert

Mechanism: steroid hormone-like

intracellular receptor

modulation of RNA synthesis

slow on-off effects

Thyroid Hormone Effects

1. Calorigenic actions

effect on intermediary metabolism

CHO / fat / protein

effect on growth & development

2. Sympathomimetic effects

facilitates actions of catecholamines

(adrenalin, noradrenalin)

Calorigenic actions

Heat producing

e.g. basal metabolic rate

heat production

energy use

O2 consumption

number & size mitochondria

MetabolismGlucose: rate absorption

uptake to cells

Fat: clearance lipoproteins

turnover

Protein: amino acid uptake

protein synthesis

• If T4 or T3 is too high, then protein catabolism

Vitamins: B12 absorption

carotene Vit. A

• If T4 or T3 is too high, then vitamin deficiencies

[ TH ]too little

too much

Protein Synthesis

net

Growth and development

in utero

& neonatesCNS

Sympathomimetic EffectsRelationship to catecholamines:• some similar effects• T4 / T3 adrenergic receptors

(number & affinity)• some effects of T4 / T3 can be treated with blockers

Excess T4 / T3

jumpy, anxioustremorpulse rate bounding pulse, systolic P

diastolic P peripheral vasodilation

Thyroid stimulating immunoglobulins = Thyroid stimulating

hormone

No negative feedback

Hypothyroidism:

• thyroid disease

• I– deficiency

Fetus:

impaired CNS development

Child: height, metal retardation

& cold intolerance, impaired mental function, coarse hair, dry skin, husky voice, reflexes

Goitre= size thyroid gland

• euthyroid

• hyperthyroid e.g. TSI

• hypothyroid e.g. I– deficiency,

autoimmune thyroiditis

I– deficiency T4 / T3

negative feedback pituitary

TSH secretion

number & size thyroid cells

Summary• T4, T3, (rT3)

• synthesis in colloid

• negative feedback regulation

pituitary & hypothalamus

• regulated metabolism

• free concentrations low but biologically relevant

• steroid hormone like – slow on-off

• actions: calorigenic on intermediary metabolism

potentiation of catecholamines actions