1. Endocrine disease Prepared by: Siti Norhaiza Binti Hadzir

2. Introduction Endocrinology- the study of hormones, which are secreted from specialized glands into the blood to influence the activity of cells at distance sites in the body.

3. Types of Hormones Peptides or proteins- hypothalamic factor (thyrotrophin releasing hormones), and pituitary gonadotropin. Amino acid derivatives- e.g thyroid hormones and adrenaline Steroid hormones- derivatives from cholesterol (e.g estrogen)

4. Measurement of Hormones Radioimmunoassay Monoclonal antibodies

5. Endocrine Disease Described as over or under secretion of hormones Failure of hormones responsiveness

6. Oversecretion Cushing’s disease where a pituitary adenoma secretes ACTH Underscretion Primary hypothyroidism where the thyroid gland is unable to make sufficient thyroid hormone despite continued stimulation by TSH Failure of hormone responsiveness Pseudohypoparathyroidism where pt become hypocalcemic despite elevated plasma PTH concentration because target organs lack a functioning receptor signaling mechanism Examples of Endocrine Disease

7. The Pituitary Gland The location Anterior pituitary-hormone secreted Posterior pituitary-hormone secreted Hypersecretion-tumours (prolactin secreting adenoma the most common) Hypopituitarism-is uncommon; the clinical presentation depends on the age, sex or the person.

11. Growth disorders Growth in children can be divided into 3 i) rapid growth-1 st 2 years –condition in utero and nutrition ii) Steady growth-around 9 years-mainly controlled by GH iii) puberty- sex hormones and GH -Other hormones involve in growth

12. Growth hormone insufficiency Is a rare cause of impaired physical growth. Test of GH insufficiency: - serum GH in response to exercise, nocturnal sample - Stimulant (clonidine) Treatment: genetically engineered GH for children

13. Excessive growth Extremely rapid linear growth (gigantism). The condition is rare often due to pituitary tumor. Other causes; congenital adrenal hyperplasia, hyperthyroidism, inherited disorders. ↑GH later in life-Acromegaly due to pituitary adenoma

14. Diagnosis of Acromegaly OGTT- a normal person will suppress GH in plasma in response to glucose load. Acromegaly-not suppress ↑ IGF 1 Treatment-surgery, radiotherapy, drugs (octreotide-somastostatin analogue) and bromocriptine

15. The Thyroid Gland The location Thyroid hormone- thyroxine (T 4 ) and tri- iodothyronine (T 3 ). Most cells capable of taking up T4 and deiodinating to the more biologically active T 3. It is T 3 which binds to receptors and triggers the end-organ effects of the thyroid hormones. T 4 can be metabolized to reverse T 3 (inactive)

17. Thyroid Hormone Action Essential for the normal maturation and metabolism of all the tissues in the body. Plasma concentration Total (nmol/L) free (pmol/L) Extent of protein binding Half life (days) T460-1449.0-26.099.986-7 T31.0-2.93.0-9.099.661-1.5 Thyroid hormones in blood

18. Regulation of thyroid hormones Hypothalamus Anterior pituitary Thyroid TRH TSH T4 + T3 + + _ _

19. Thyroid Function Test TSH (thyroid stimulating hormone) Total T4 (bound hormone + free) Free T4 TBG level Free T3 Total T3 (bound hormone + free) Titre of auto-antibodies to thyroid tissue antigens

20. TRH test Involves intravenous injection of TRH and the measurement of pituitary TSH secreted in response to the stimulation. Purposes: i) Investigation of pituitary disorders ii) Investigation of hyperthyroidism

21. TSH 2060 Time (minutes) TRH TSH 2060 Time (minutes) TRH Normal response Hyperthyroidism Normal response Secondary (pituitary) hypothyroid Primary hypothyroid Pituitary responses to TRH

22. Goitre A goitre is an enlarged thyroid gland. This may be associated with hypofunction, hyperfunction or indeed normal concentrations of thyroid hormones in blood.

23. Hypothyroidism 90% of cases of hypothyroidism occur as a consequence of: - autoimmune destruction of the thyroid gland (Hashimoto’s disease) - radioiodine or surgical treatment of hyperthyroidism

24. Diagnosis of Hypothyroidism Hypothyroidism is caused by a deficiency of thyroid hormones. Primary hypothyroidism – failure of the thyroid organ itself-elevated TSH concentration is diagnostic Secondary hypothyroidism-failure of pituitary to secrete TSH (less common). Treatment- thyroxine (tablet) therapy.

27. Non-thyroidal Illness In systemic illness the normal regulation of TSH, T4 and T3 secretion and subsequently metabolism of the thyroid hormones, is disturbed. ↑ T4 are converted to the reverse T3. Reduction in thyroid hormone activity does not result in an increased serum TSH concentration. TSH secretion is suppressed→ ↓ T4 and T3. TBG decrease

28. Neonatal Hypothyroidism The failure of the thyroid gland to develop properly during early embryonic growth. Children develop irreversible mental retardation and characteristic feature of cretinism. The screening test- ↑ blood TSH concentration.

29. Hyperthyroidism Hyperthyroidism can be result from: - Graves’ disease, diffuse toxic goitre - Toxic multinodular goitre - solitary toxic adenoma - thyroiditis - exogenously administered iodine and iodine- containing drugs, e.g amiodarone - excessive T4 and T3 ingestion

30. Graves’ disease An autoimmune disease in which antibodies to the TSH receptor on the surface of the thyroid cells appear to mimic the action of the pituitary hormones. The normal regulatory controls on T4 synthesis and secretion are lacking. Pituitary secretion of TSH is completely inhibited by the ↑ conc. of thyroid hormones in the blood-eyelid retraction

32. Diagnosis Suppressed TSH concentration,↑ T4 and T3- primary hyperthyriodism Occasionally, biochemical confirmation of suspected hyperthyroidism will prove more difficult e.g in pregnancy.

33. PtT4 nmol/L 55-144) T3 nmol/L (0.9-2.8) TSH mU/L (0.35-5.0) TBG mg/L (12-30) Free T4 pmol/L (9-24) Comment 11302.03.42518 Euthyroid 21753.61.13514 Euthyroid 31905.0<0.053630 Hprthyroid Thyroid hormone and binding protein results in pregnancy

34. Treatment Anti-thyroid drugs (such as carbimazole and propylthiouracil)- younger patient Radioiodine-therapy with sodium I 131 is commonly used in older pt. Most will require eventually require replacement thyroxine. Surgery-thyroidectomy

35. Thank you