M.Prasad Naidu MSc Medical Biochemistry, Ph.D.

Research Scholar

1. Hyperthyroidism 2. Thyroid Adenoma 3. Graves 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

CRETINISM Mental retardation

DWARFISM Development of Nervous system is normal Proportionate normal

Diff parts of the body are disaapropriate Reproduction system is affected

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 <50g/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 nontoxic 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)