3. Follicles: the Functional Units of the Thyroid Gland Follicles Are the Sites Where Key Thyroid Elements Function: Thyroglobulin (Tg) Tyrosine Iodine Thyroxine (T 4 ) Triiodotyrosine (T 3 )

5. The follicular epithelial cells synthesise thyroid hormones by incorporating iodine into the amino acid tyrosine on the surface of thyroglobulin (Tg), a protein secreted into the colloid of the follicle

8. T3 and T4 circulate in plasma almost entirely (> 99%) bound to transport proteins, mainly thyroxine-binding globulin (TBG). It is the unbound or free hormones which diffuse into tissues and exert diverse metabolic actions. While it is possible to measure the concentration of total or free T3 and T4 in plasma.

10. Physiology The functions of thyroid hormone are 1- Faceletate growth and development. 2- Interfere with carbohydrate protein and fat metabolism. 3- Increase oxygen consumption by the tissue, basal metabolic rate, and heat production. 4- Increase oxygen release from HB. 5- Augmentation of adrenalin and noradrenalin function.

11. Thyrotoxicosis))Hyperthyroidism  “Hyperthyroidism” refers to overactivity of the thyroid gland leading to excessive synthesis of thyroid hormones and accelerated metabolism in the peripheral tissues. The secretion of thyroid hormone is no longer under the regulatory control of the hypothalamic-pituitary center.

12. 1- Graves' disease 2- Multinodular goitre 3- Toxic adenoma

16. Epidemiology Prevalence of hyperthyroidism in the general population is 1.2% Graves’ Disease – most common etiology 0.4% Graves’ Disease is more common in females (7:1 ratio)

17. GRAVES' DISEASE The most common manifestation is thyrotoxicosis 1-with or without a diffuse goitre. 2- ophthalmopathy 3- and rarely pretibial myxoedema These features usually occur in thyrotoxic patients,. Graves' disease can occur at any age but is unusual before puberty and most commonly affects women aged 30-50 years

18. GRAVES' DISEASE  The thyrotoxicosis results from the production of IgG antibodies directed against the TSH receptor on the thyroid follicular cell, which stimulate thyroid hormone production and, in the majority, goitre formation. These antibodies are termed thyroid-stimulating immunoglobulins or TSH receptor antibodies (TRAb)

19. The Classic Triad of Graves’ Disease 1-Hyperthyroidism (90%) 2-Ophthalmopathy (20-40%) proptosis, ophthalmoplegia, conjunctival irritation 3-Dermopathy (0.5-4.3%) localized myxedema, usually pretibial especially common with severe ophthalmopathy

20. Graves’ Ophthalmopathy Antibodies to the TSH receptor also target retroorbital tissues T-cell inflammatory infiltrate -> fibroblast exophthalmus Severe: keratopathy, diplopia,,com- pressive optic neuropathy

21. Eyes 1) Lid lag slowly moving point from above eye level to below and see if eyelid smoothly follows movement of eye - 2) Lid retraction Lid retraction due to exophalmos (protrusion)

22. Pretibial myxedema  Activation of fibroblasts leads to increased hyaluronic acid and chondroitin sulfate Asymmetric, raised, firm, pink-to-purple, brown plaques of nonpitting edema on the anterior leg

24. Features of Hyperthyroidism Weight loss, heat intolerance Thinning of hair, softening of nails Stare and eyelid lag Palpitations, symptoms of heart failure Dyspnea, decreased exercise tolerance Diarrhea Frequency, nocturia Psychosis, agitation, depression

25. Cardiac manifestations Palpitations Dyspnoea on exertion Angina Ankle swelling

26. Sinus tachycardia Atrial fibrillation Systolic hypertension/ increased pulse pressure Cardiac failure

27. Gastroenterology  Diarrhoea, steatorrhoea, hyperdefecation Vomiting

28. Neuromuscular Anxiety, irritability, emotional lability, psyachosis Tremor Muscle weakness Periodic paralysis

29. Hyper-reflexia sustained clonus Proximal myopathy Bulbar myopathy

30. Dermatological Sweating Pruritis Alopecia

31. Reproductive Amenorrhoea Infertility abortion Loss of libido impotence

32. Signs and Symptoms of Hyperthyroidism Bulging Eyes/Unblinking Stare Menstrual Irregularities or Light Period Excessive Vomiting in Pregnancy First-Trimester Miscarriage Family History of Thyroid Disease or Diabetes Nervousness Irritability Difficulty Sleeping Swelling (Goiter) Frequent Bowel Movements Warm, Moist Palms Hoarseness or Deepening of Voice Difficulty Swallowing Rapid or Irregular Heartbeat Infertility Weight Loss Heat Intolerance Increased Sweating Persistent Sore or Dry Throat

33. investications Thyroid function tests 1-Total T3 = 1.2 to 2.8 nmol\L 2-Total T4 = 150 nmol\L 3-TSH 0.5 to 5 mU\L.

34. measuring of: 1- freeT4=10-30nmol\L 2- freeT3=0.3-3.3nmol\L 3- TSH = 0.5 to 5 mU\L which is the most sensitive and specific test for the diagnosis of hyper- and hypothyroidism 4- Autoantibody assessment: include TPH (thyroid peroxidase), and anti thyroglobulin anti body.

35. Diagnostic Imaging Radioactive Iodine Uptake Shows distribution of uptake Technetium-99 Pertechnetate Uptake Distinguishes high-uptake from low-uptake Thyroid ultrasonography Identifies nodules Doppler can distinguish high from low-uptake

36. Thyroid scanning: iodine 123 (123I) and iodine 131 (131I) Technetium Tc 99m pertechnetate (99mTc).The images obtained by these studies provide the size and shape of the gland and the distribution of functional activity.

37. Guide in thyrotoxicosis treatment The choice of therapy depends on: 1-Age of the patient 2-Size of the thyroid 3-Type of thyroxicosis

38. Guide in thyrotoxicosis treatment 1-Graves below 45 year anti thyroid drug 2-No response or large goiter or recurrence surgery 3-Graves above 45 year RAI 4-Toxic multinoduler surgery 5-Toxic nodule surgery. if not fit RAI 6-Recurrent after surgery above 45 year RAI Pregnancy surgery in the first and second trimester Antithyroid (propylthiuracil) in the third trimester in low doses.

39. Antithyroid drugs carbimazole 40-60 mg daily prophylthiouracil 400-600 mg daily. There is subjective improvement within 10-14 days and the patient is usually clinically and biochemically euthyroid at 3-4 weeks, when the dose can be reduced. The maintenance dose is determined by measurement of T4 and TSH, attempting to keep both hormones within their respective reference ranges...

40. Adverse effects  Rash  Arthralgias  Urticaria  GI symptoms  Agranulocytosis

41.  β-adrenoceptor antagonist (β-blocker), such as propranolol (160 mg daily) or nadolol (40-80 mg daily), will alleviate but not abolish symptoms within 24-48 hours. Beta-blockers cannot be recommended for long-term treatment, but they are extremely useful in the short term, e.g. for patients awaiting hospital consultation or following 131I therapy.

42. Radioactive iodine  131I is administered orally as a single dose and is trapped and organified in the thyroid.Although it will decay within the thyroid in a few weeks, the effects of its radiation are long-lasting, with cumulative effects on follicular cell survival and replication.

43. Subtotal thyroidectomy  Patients must be rendered euthyroid with antithyroid drugs before operation. Potassium iodide, 60 mg 8- hourly orally, is often added for 2 weeks before surgery to inhibit thyroid hormone release and reduce the size and vascularity of the gland, making surgery technically easier. Complications of surgery are rare.

44. Treatment of Ophthalmopathy  Mild Symptoms  Eye shades, artificial tears  Progressive symptoms (injection, pain)  Oral steroids – typical dosage from 30-40mg/day for 4 weeks  Impending corneal ulceration, loss of vision  Oral versus IV steroids  Orbital Decompression surgery