DEGRADATION OF T4 AND T3 Some 20 to 30% of the total thyroid hormones (T4 and T3) are conjugated in the liver usually with glucuronic acid,

me. the iodine trapping mechanism becomes less efficient, and organification of extra .amount ofiodine does not occur The whole phenomenon is called auto re gulation of the thyroid gland In this way, the availafability of iodine for thyroxine synthesis remains constant even in the face of wide fluctuation of food iodine content Mechanism of auto regulation may be as follows less iodine makes The thyroid gland more sensitive to the TSH (recall, the TSH helps in iodinetrappping) and vice versa Exposure to cold and thyroid secretion are int err elated, specially in the new born When exposed tothe cold external world, the freshly bom baby shows a rise of TH secretion. It appears that the stimulus of cold acts on the hypothalamus -- increased secretion of TRH rise of TSH rise of T4. Hypothalamus - piturtary - thyroid axis can now be underswood. These three structures (viz hypo-pit_thy) act in a concert and taken together they form an axis. A break down, anywhere in the axis causes a break down of thyroid regulation and causes signs and symptoms (disease). DEGRADATION OF T4 AND T3 Some 20 to 30% of the total thyroid hormones (T4 and T3) are conjugated in the liver usually with glucuronic acid, and is exreted with bile and undergoes enterohepatic circulation. Rest of the hormone (i. e . about 70%) is deaminated. The deaminated products are tetraiodothyro acetic acid and triiodothyroacetic acid, [abbreviated, tetrac and triac respectively] They undergo still further changes and then finally metabolically disposed. APPLIED PHYSIOLOGY Hyp of unction Two forms of hypofunction of the thyroid are known, viz. cretinism and adult hypathyroidism. The clinical Fig. 6.2.5. Summarised view of signs and symptoms of cretinism features are described here,the description of laboratory features has been given later Cretinism it hypothyroidism in the young Clinical features, in a full blown cast, are. retardation of growth of all forms, namely, physical, mental and sexual As a result the child is dwarf, pot bellied (because the muscles of abdomen are weak but abdominal visceral growth not severely restricted) and mentally idiot or imbecile There is also no maturation of the external genitalia and secondary sex characteristics do not develop [NB. According to some, cretins should not be called dwarf as there is shortage of intelligence] Treatment of cretinism must commence early and if not started within first year of life.. as explained earlier in this chapter, no matter how thorough is the later day treatment, the child remains idiot Adult hypothyroidism The Full blown picture is known as myxedema because in advanced stage or the disease, hyaluronic acid and protein accumulation occur which in Turn attracts water {see earlier part of this chapter) In less severe forms, the clinical features are there is mental slowing, fall of hairs, excessive feeling ofcold, menstrual abnormality (usually menorrhtgia) and bradycardia Weight gain also occurs The laboratory findings and the physiological basis of drug therapy have been discussed later in this chapter Cause Ultimate cause of hypothyroidism is deficiency of thyroxine (i) In the cretins, this may be due to the fact that the mother suffered from iodine deficiency during the gestation period, a common cause in the sub Himalayan regions of India, and clinically called 'endemic cretinism', severe food iodine deficiency remains a major cause of hypothyroidism in These areas (ii) Another important cause is 'iatrogenic (i. e . produced as a result of treatment) Surgical removal of a part of the thyroid (for treating hypertyroidism) can result in too much removal of thyroid and produce hypothyroidism. Treatment of hyperthyroidism by radioactive iodine can also do this (iii) Autoimmune disease of the thyroid, (Hashimoto's disease) in which specific immunoglobulins, which destroy the thyroid, appear in the body, is another notable cause (iv) Other important causes are hypofunctioning of the anteror pituitary (Simmond's disease) or of hypothalamus. Hyperthyroidism (Grave's disease, Basedow's disease, exophthalmic goiter, thyrotoxicosis) In this condition, there is excess thyroxine in the body. There are three groups of signs and symptoms as follows: Swelling of the gland of oversecretion of thyroxine. There is usually a variable degree of swelling of the gland (goiter) and some protrusion or bulging of the eyeballs (exophtalmos), hence the condition is also clinically called' exophthalmic goiter' The rnajor efftcts of hypersecretion of the thyroidhormones are (A) Cardiovascular system, tachycardia, palpitation, high systolic blood pressure. (B) Nervous system fine tremor, mental restlessness, anxiety and a feeling of excessive heat, (C) General loss of weight. From what has been started in the functions of thyroid hormones (earlirer in this chapter), the explan ations of these symptoms should be reasonably obvious. The laboratory investigational features and the rationality of drug therapy have been discussed later on Cause, In this disease, a specific antibody, called thyroid stimulating antibody (TSAb) or thyroid stimulating immunoglobulin (TSF) is produced by B lymphocytes of the patient. The TSAb biologically behaves like the TSH of the anterior pituitary (i. e , it causes increased secretion of thyroxine) But it ts not influenced by the serum T3 or T4 levels Or in other words, the TSAb combines with the receptors meant for the TSH in the thyroid cells, but unlike the TSH, is not inhibited by the rising concentration of the Thyroxine, However, high concentration of the T4 and T3 m these patients cause suppression of the