M.Prasad NaiduMSc Medical Biochemistry,

Ph.D.Research Scholar

1. Hyperthyroidism 2. Thyroid Adenoma 3. Grave’s disease

Causes: Due to the presence of TSH like substances –

proved by RIA studies The conc of TSH was found to be 0/less in plasma of

Hyperthyroidism patients The TSH like substances are Abs which bind with

same membrane receptors of TSH These substances activate c-AMP system ↑T4 These Abs act for long time (12hrs) (TSH-1hr) The ↑ of high T4 caused by Abs suppresses TSH

production Usually these Abs are developed b/cos

autoimmunity

Some times – localised tumor develops in Thyroid tissue called Thyroidadenoma

TA secretes large quantities of T4&T3 It is not associated with autoimmunity As far as this adenoma remains active, the

other parts of Thyroid gland will not secrete the hormone.

This is b/cos the hormone from Adenoma ↓ depresses the production of TSH

Autoimmune disease Normally TSH combines with surface

receptors of thyroid cells syn of T4 But in GD , the TSH autoAbs (B-TSAB)

produced by B-lymphocytes (Plasma cells) activate the TSH-receptors & ↑ secretion of T4

Intolerance to heat ( due to ↑ BMR) ↑ sweating ( due to vasodialation) ↓ body wt ( Fat metabolism) ↑ motility of GIT diarrhoea Muscular weakness ↑protein catabolism Nervousness, extreme fatigue, inability to sleep, mild

tremor in the hands, psychoneurotic symptoms such as extreme anxiety/worry (stimulation of CNS)

Enlargement of Thyroid gland i.e, Toxic goiter Exophthalmos: Autoimmune some degree of protrusion of eye balls – if severe blindness

develops due to i)protrusion of eye ball stretches the optic nerve Ii) eye lids cannot be closed dry infection

↓ secretion of Thyroid hormones Autoimmune disease which causes

destruction of Gland In most patients it starts as the glandular

inflammation called – Thyroiditis Thyroiditis fibrosis of the gland Hypothyroiditis Myxedema (adults)

Cretinism (Children)

Due to hypothyroidism in adults Causes: occurs in severe conditions –

complete lack of thyroid hormones Signs & symptoms: Swelling of the face Bagginess under the eyes Non-pitting type of edema:- when pressed

it does not make pits and the edema is hard (accumulation of Pro+cho.SO4 which form hard tissue with ↑ accumulation of fluid)

Atherosclerosis: ↑ cholesterol – blood ↑ bp

Other general symptoms: Fatigue & muscular sluggishness Extreme somnolence ( 14-16 hrs/day) Menorrhagia & polymenorrhea ↓ Cordiovascular functions such as ↓heart rate,

↓ force of contraction of heart ↓ crodiac out put , ↓ blood volume

↑Body wt Constipation Mental sluggishness ↓ hair growth Scaliness of the skin Frog like husky voice

Children Causes: congenital absence of thyroid gland

(genetic disorder or lack of I2 in diet) Features: The newborn baby may appear normal at birth

(due to supply of T4 from mother) But after few weeks – starts developing sluggish

movements croacking sound while crying mentally retarded

Skeletal growth is more affected than soft tissues Tongue becomes so big – affects swallowing &

breathing Stunted growth

CRETINISMCRETINISM DWARFISMDWARFISM

Mental retardationMental retardation Development of Development of Nervous system is Nervous system is normalnormal

Diff parts of the body Diff parts of the body are disaapropriateare disaapropriate

ProportionateProportionate

Reproduction system Reproduction system is affectedis affected

normalnormal

Enlargement of thyroid gland Occurs both in hypothyroidism &

Hyperthyroidism Goiter in Hyperthyroidism Toxic Goiter Due to tumor of the gland – Size ↑ - ↑

number of hormones secreting cells ↑ hormone level – Toxic Goiter

Goiter in hypothyroidism –non toxic Goiter Only enlargement of gland – hormone

secretion is ↓

Based on the cause, Non-toxic Goiter is of 2 types i) Endemic Colloid Goiter:- Due to lack of I2 – I2 intake <50µg/day Therefore no formation of hormones By feed back mechanism, hypothalamus and anterior

pituitary are stimulated This ↑ secretion of TRH and TSH secretion of TGb

Follicles As there are no hormones to be cleaved, ↑ accumulation in

the follicles Therefore ↑ size of the gland In Swiss, Alps, Andes, Great region of US and in India –

Kashmir Valley Soil does not I2↓ Therefore Food stuffs lack I2 – very common before the

introduction of iodized salts

Enlargement of Thyroid gland occurs even without I2 deficiency

Exact cause not known These patients are first affected by

Thyroiditis which reduce synthesis of Thyroid hormones

Therefore secretion of TSH ↑ ↑ Size of the gland In some persons the abnormal enzyme

system leads to Goiter(due to deficiency of enzymes like peroxidase, iodinase and deiodinase which are required synthesis of T3&T4)

Goitrogenic Substances: ( Goitrogens) Eg: Goitrin Contains antithyroid substances like

propylthiouracil Therefore TSH secretion ↑ enlargement of

Thyroid gland Goitrogens in turnips, cabbage,

soyabeans The goitrogens become active only during

low I2 intake

Treatment for Hyperthyroidism:- 1. Surgical removal: Thyroidectomy 2. Antithyroid substances: Thiocyanate,

thiourylenes, high conc of inorganic iodides Treatment of hypothyroidism: Only treatment is administration of Thyroid

extract/ ingestion of pure thyroxine ( tablet)

Drugs which supress the secretion of T3&T4 1. Thiocyanate: the same active pump

which transports I- into Thyroid cells, transports thiocyanate also

So thiocyanate competitively inhibits I2 transport

I2 transport is inhibited ↓ synthesis of Thyroxine

Thiourea related substances Eg: Propylthiouracil and methimazole prevent the

formation of T4 from iodides and Tyr This is achieved by blocking peroxidase activity

and partly by blocking coupling of MIT & DIT During the use of these two antithyroid agents

even though the synthesis of Thyroid hormone is inhibited , the formation of TGb is not stopped

The deficiency of the hor ↑ TSH secretion ↑ Size Thyroid gland with more secretion of TGb

TGb accumation in gland enlargement non-toxic G

All phases of Thy.activity ↓ ↓ release of Thyroxine ↓ Size ↓ blood supply Therefore iodides are frequently

administrated to hyperthyroid patients

The most accurate diagnostic test is Direct measurement of conc of Free thyroid hormones in the plasma (T3&T4)

Measurement of BMR:- In Hyperthyroidism, ↑ 30-60% In hypothyroidism, ↓ 20-40% The measurement of TRH and TSH:- In Hyperthyroidism total absence of TRH

& TSH (due to –ve feed back mechanism by the ↑level of Thyroid hormones)