Endocrine Physiology

1. Endocrine Physiology

2. The Thyroid Gland: • The thyroid gland produces the hormone thyroxine. • This gland is situated in the neck. It consists of two lateral lobes on either side of the trachea and larynx, and a connecting isthmus, which runs across the midline giving the gland a butterfly appearance.

4. Occasionally the gland extends into the thorax behind the sternum. • It has a rich blood supply from the thyroid arteries. • The thyroid gland weighs 25 g. in the healthy adult. • It has developed from a median diverticulumknown as the thyroglossal duct which arises from the floor of the embryonic mouth.

6. The gland itself is composed of cuboidal cells which line a very large number of closed spherical vesicles of up to 0·1 mm. in diameter. • These vesicles are filled with a semi-homogeneous material called colloid. This colloid contains the thyroid hormone in the storage form of a glycoprotein called thyroglobulin.

7. The thyroid gland is unique amongst the endocrine glands in that it stores its active principle in the cavity of these vesicles. • All the other endocrine glandsstore their hormones in the secreting cells. • The thyroid hormone thyroxine is split off from the thyroglobulin by a protein-splitting enzyme and circulates in the bloodcombined with the α–globulin fraction of the plasma proteins.

8. Formation of Thyroxine • Thyroxine is an iodine derivative of thyronine. • Thyroxine itself has four iodine atoms in the molecule. • Triiodothyronine (T3), the three-iodine compound, is even more active, and the circulating thyroxine may be converted to this compound by the cells. • Thyroxine is made by the body from the amino acid tyrosine.

9. For its synthesis inorganic iodide is concentrated in the cells of the thyroid. • The iodide is then organically bound and oxidized to iodine by the cytochrome enzyme system forming mono and diiodo compounds of tyrosine. • Oxidative couplingconvertsdiiodo-tyrosine to thyroxine.

11. Thyroxinestimulates metabolism in the tissues generally. • It raises the oxygen consumption and increases the heat produced. • It also promotes growth and development generally. Action of Thyroxine

12. The normal level of circulating thyroxinemaintains a basal metabolic rate (B.M.R.) of 40 Calories/m.2 body surface area/hour in a man, and 37 Calories/m.2 /hour in a woman. • Thyroxine and thyroid extracts are active when given by mouth.

13. They differ in this respect from the hormones which are proteins or polypeptides and which will be completely broken down to amino acids and destroyed by the protein-splitting enzymes of the digestive tract. • 1 mg. of thyroxine/day increases the metabolic requirements of a person from 2,500 to 3,500 Calories/day.

14. If only 2,500 Calories are eaten, the body reserves will be used up and there will be a loss of weight. • The secretion of thyroxine is regulated by the thyrotrophic hormone (TSH) from the anterior pituitary gland which, in turn, is regulated by the thyrotrophin-releasing factor (TRF or TSH­RF) from the hypothalamus.

15. The secretion starts in fetal life, reaches a maximum in childhood and declines later in life. • The level of thyroxine in the blood affects the release of TSH. • High levels of thyroxineinhibit the secretion of TSH which in turn reduces the activity of the thyroid gland. • The thyroid activity is thusself-regulated by a feedback system which is controlled by the level of thyroxinein the blood.

16. A swelling of the thyroid gland in the neck is called goitre. • It may be associated with eitherunder activity or over activity of the gland. • The goitre which occurs when there is a deficiency of iodine in the diet is associated with under activity of the gland. Goitre

17. To prevent such a deficiency in areas of the world where iodine is absent from the soil, iodide is added to the table salt. • Goitres due to over secretion of TSH, on the other hand, are associated with over activity of the thyroid gland.

18. Under-activity of the thyroid gland leads to: • Reduction in the metabolic processes in the body. • There is a fall in the basal metabolic rate to as much as 50% of normal. Under-activity of the Thyroid Gland (Hypothyroidism)

19. The body temperature is subnormal. • Both the heart rate and respiration are reduced. • There is a rise in the blood cholesterol level. • A deficiency of thyroid activity at birth leads to the child becoming a cretin. • The child is small. • Mentally retarded. • Usually has a large protruding tongue.

20. Such a child responds to thyroxine by mouth, but as the child may be as much as 6 months oldbefore the condition is diagnosed. • If the condition diagnosed after that age, it may be too late to restore completely the normal growth pattern.

21. A thyroid deficiency which occurs later in life leads to myxoedema. • There is a reduction in the metabolic rate and a lowering of the body temperature and heart rate. • Speech, thought and movement become very much slower. • There is an increase in weight due to the deposition of semi-fluid material which gives the name to this condition (G. myxa, mucus; oidema, swelling).

22. The face and eyelids become puffy. • The tongueswells and the skin becomes rough and coarse. • The hairthins on the scalp and eyebrows. • The menstrual cycle is disturbed in women. • Thyroxine by moutheffectively treats myxoedema.

24. Over-activity (Hyperthyroidism, Thyrotoxicosis) • This may be due to a primary over-activity of the thyroid gland itself or to an excess of TSH from the anterior pituitary which causes over-activity of the thyroid gland. • The metabolic processes of the body are speeded up.

25. There is an increase in heart rate (tachycardia). • An increase in pulmonary ventilation, oxygen consumption, carbon dioxide production and heat produced. • The tachycardia persists during sleep but this is difficult to determine since the subjects become very light sleepers and tend to wake up if their pulse is taken.

26. The BMR may be increased by as much as 50%. • As a result of the increased heat production the subject prefers the cold weather to the hot weather. • The subject becomes excessively nervous and irritable. • The hands show a tremor, particularly when held straight out.

27. Protrusion of the eyeballs (exophthalmos) gives an anxious staring expression. • This is seen particularly when the thyroid activity is due to an excess of TSH, although the cause is probably not due to the thyroxine or the TSH but to some unidentified exophthalmos substance from the anterior pituitary.

29. When the hyperthyroidism is such that, the subject becomes clinically ill the condition is termed thyrotoxicosis. • For example, the increased excitability of the cardiac muscle may lead to atrial fibrillationand heart failure. (Atrial fibrillation may occur following the ingestion of an excess of thyroxineas a treatment for obesity).

30. Thyrotoxicosis is treated by removal of most of the thyroid gland by surgery or by giving radio-active iodine. • Thiocarbamide compounds such as thiouracil, methimazole and carbimazoleprevent the incorporation of iodine in the tyrosine molecule.

31. Thiocyanate and perchloratecompounds interfere with the uptake of iodine by the thyroid gland. • Such compounds which reduce the formation of thyroxineare used to control thyrotoxicosis.

32. The ingestion of a large dose of iodine (or iodide) brings about a temporary remission (reduction) of thyrotoxicosis which lasts for a few weeks. • It is often given prior to a thyroidectomyoperation to decrease the vascularityof the gland and hence to reduce bleeding at the operation.

33. The mode of action of the iodine is not known. It does not bring about any long-termed improvement. • It has been known for over 50 years that an increase in thyroid activity reduces the level of cholesterol in the blood whereas a decrease in thyroid activity increases it.

34. The normal level of cholesterol is 200 mg/100 ml. plasma. • In myxoedema the concentration may be as high as600 mg/100 ml. (hypercholesterolaemia). • In thyrotoxicosisit may fall to 100 mg. per 100 ml.

35. The blood cholesterol level represents the balance between ingestion and formation on the one hand, and excretion and utilization on the other. • Although cholesterol is present in the diet (egg yolk, liver, meat fats), the greater part is synthesized in the liver and other tissues from acetyl co-A in a series of steps.

36. Cholesterol is also destroyed by the liver and excreted in the bile (as cholesterol itself and as cholic acid). • It is probably used as the precursor for the formation of steroid hormones. • However, cholesterol deposited in the walls of arteries may lead to athero-sc1erosis and arterial thrombosis.

37. The action of the thyroid gland on cholesterol metabolism is complex. • It stimulates the formation of cholesterol by the liver, but has a greater effect on increasing the excretion of cholesterol in the bile, and increasing the entry of cholesterol into cells. • The net result is that the blood level falls.