Thyroid gland & thyroid hormones

Components of the endocrine system

Endocrine tissue (control)

Biologically active chemical

(synthesis, storage, release)

Transport in blood

Target cells (receptors & response)

Inactivation of chemical

Thyroid hormones

Two hormones

• Tri-iodothyronine (T3)

• Tetra-iodothyronine (T4) = thyroxine

I I

HO O CH2-CH(NH2)-COOH

I

I

N.B. Reverse T3

Control of thyroid gland

hypothalamus

anterior pituitary

thyroid

-

-

+

+

releasing hormone

trophic hormone

T3 & T4

Hypothalamic releasing hormones affecting anterior pituitary

Hypothalamus

(releasing hormone)

Thyrotrophin releasing hormone

(TRH)

Polypeptide hormone (3aa)

Anterior Pituitary

(trophic hormone)

Thyrotrophin

Thyroid stimulating hormone

(TSH)

Glycoprotein hormone

Control of thyroid gland

-

TRH

+

-

TSH

+

T3 & T4

hypothalamus

anterior pituitary

thyroid

Actions of TSH on thyroid gland

Binding of TSH to receptors on the surface of the follicle cells:

Acute effects (min-hr):

Stimulates synthesis, storage & secretion of T3 & T4

Chronic effects (days):

Stimulates growth & division of follicle cells – gland enlarges producing a goitre.

N.B – enlarged thyroid can be normal, under-active or over-active.

Synthesis of T3 & T4

Synthesis requires:• iodination of tyrosine.• coupling 2 tyrosine molecules.

Tyrosine molecules are part of the polypeptide chain of thyroglobulin:

• synthesised in follicular cells.• stored extracellularly in colloid.

Transport of thyroid hormones

T3/T4

thyroid

Bound>99%

freeblood

target tissues

response inactivation

Mechanism of thyroid hormone action

.Mito.

Response

T3

nucleus

T3 DNAR

mRNA

plasma membrane

T3T4

T4

mito. ?

General effects of thyroid hormones

Increase Basal Metabolic Rate:

↑ number & size of mitochondria.

↑ O2 consumption & heat production.

↑ nutrient utilisation.

Stimulate most metabolic pathways:

Catabolic > anabolic (lipolysis, glycolysis, glycogenolysis, proteolysis).

Promote normal growth & development of tissues:

↑ synthesis of specific proteins.

Increase responsiveness of tissues to sympathetic nervous system (noradrenaline) & various hormones (metabolic & reproductive).

Tissue specific effects of thyroid hormones

Nervous system – development (birth – puberty) & functioning (adults):

↑ myelination of nerve fibres & development of neurons.

↑ speed of reflexes.

↑ mental activity (alertness, emotional tone, memory).

Cardiovascular system:

↑ cardiac output.

direct effect on heart muscle & potentiates effect of noradrenaline.

Skin & subcutaneous tissue:

↑ turnover of proteins & glycoproteins (mucopolysaccharides).

Failure of normal thyroid development.

Hypothyroidism produces cretinism in the new born:• severe mental retardation due to failure in CNS development.

• coarse features, protruding tongue.

• diminished linear growth.

• delayed sexual development.

Reversible if treated within a few weeks.

∴ screen all new born (assay for T4 or TSH)

Hyperthyroidism & hypothyroidism

Hyperthyroidism

Signs & symptoms relate to:∀ ↑ BMR & catabolic activity

∀ ↑ sympathetic & CNS activity

(GI tract, CNS)

• Direct effects on tissues:

(CVS)

Hypothyroidism

∀ ↓

∀ ↓

• Direct effects on tissues:

(CVS, subcutaneous)

Signs & symptoms of hyperthyroidism

Heat intolerance, ↑ perspiration, warm moist hands.

Weight loss (lipid & protein).

Tachycardia (noticeable heart beat) often irregular – increased cardiac output.

Increased bowel movements - increased appetite.

Nervousness, irritability & emotional lability.Hyper-reflexive - possible tremor of outstretched hands.

Eye signs - exophthalmos

Major cause of hyperthyroidism

Grave’s disease:

Affects ~1% of the population (A// = 10/1).

Autoimmune disease:

• production of antibody that stimulates the TSH receptor on follicle cells (LATS).

Treat with carbimazole – inhibits incorporation of iodine into thyroglobulin.

Signs and symptoms of hypothyroidism

Cold intolerance, decreased perspiration, cold dry hands.

Mild weight gain.

Bradycardia – decreased cardiac output.

Constipation.

Mood swings - feeling anxious & depressed.

Poor concentration, poor memory, lack of initiative.

Oedema (myxoedema = dry firm waxy swelling of skin & subcutaneous tissue).

Dry skin, brittle nails, some hair loss.

Major cause of hypothyroidism

Hashimoto’s disease

Affects ~1% of the population (A// = 10/1).

Autoimmune disease:

• destruction of thyroid follicles.• production of antibody that blocks the TSH receptor on follicle cells.

Treat with oral T4 (100 – 200 µg/day).

Inactivation of thyroid hormones

T4 and T3 degraded by removal of Iodine - occurs in liver & kidney.

Half-life in plasma: T4 = 7-9 days T3 = 1-2 days

Longer half life of T4 due to greater affinity for binding proteins.

T4 used to treat hypothyroidism – easier to maintain constant blood concentration.