THYROTOXICOSIS

1. THYROTOXICOSIS ] DIPIN.S 2002 BATCH

2. CAUSES OF THYROTOXICOSIS WITH INCREASED THYROID SECRETION • Graves disease • Toxic nodular goitre • Toxic thyroid adenoma • Jod basedows hyperthyroidism • Secondary hyperthroidism due to TSH • Thyroiditis WITHOUT INCREASED THYROID SECRETION • Factitious hyperthyyroidism • Struma ovarii • Molar pregnancy • Rare metastatic thyroid ca.

3. PRIMARY THYROTOXICOSIS The goitre is diffuse and vascular, large or small, firm or soft, Thrill and a bruit may be present. The onset is abrupt. Hyperthyroidism is usually more severethan in secondary thyrotoxicosis but cardiac failure is rare.. SECONDARY THYROTOXICOSIS the goitre is nodular. The onset is insidious may present with cardiac failure or atrial fibrillation. hyperthyroidism is not severe. Eye signs other than lid lag and lid spasm (due to hyperthyroidism) are very rare.

4. PRIMARY THYROTOXICOSIS

5. GRAVES DISEASE • The commonest form of thyrotoxicosis • More prevalent in young adults • 6 times more common in females

6. HISTORY Caleb Parry(Welsh phy.)- first described (1825) Named after Robert Graves(1835)

7. AETIOLOGY • Genetic factors • Association with other autoimmune diseases- • Association with HLA DR3, B8,BW35, BW46 • Emotional uphaevals • Consumption of iodine excess Use of thyroid hormone

8. PATHOLOGY & PATHOGENESIS • Autoimmune disorder • Thyroid stimulating Igs produced against antigen in thyroid • Appear to be directed against TSH receptors TRAbs

9. THEORIES • Defect in suppresssor Tcells-allows helper T cells to stimulate TSI from B cells • Another theory is that an immune response is launched to altered antigens on the follicular cell surface

10. PATHOLOGY MACROSCOPY • Diffuse and smoothly enlarged • Vascularity incresed

11. MICROSCOPY • Hyperplastic columnar epithelium, pappilary projections. • Nuclei exhibit mitosis • Aggregates of lymphoid tissue • Vascularity increased • Minimal colloid

12. CLINICAL FEATURES • Heat intolerance • Increased thirst • Sweating • Weight loss • Menustrual irregularities • Emotional liability • Shortness of breath • Fatigue • Prominent eyes • Diarrhoea • Goitre • Hair loss and pruritus

13. SIGNS • Tremor • Warm moist skin • Tachycardia, AF, widened pulse pressure • Heart failure • Myopathy(proximal) • Hyper active tendon reflexes

15. FEATURES SPECIFIC TO GRAVES DISEASE Thyrotoxicosis Exophthalmos Goitre Classical triad

16. Other features Onycholysis(thyroid acropathy) Hair loss Pretibial myxoedema Gynaecomastia Audible bruit

17. THYROID OPHTHALMOPATHY • Spasm of upper eyelid with retraction and lid lag • External ophthalmoplegia • Exophthalmos with proptosis • Supra orbital and infraorbital swelling • Congestion and oedema of conjunctiva

18. Pathogenesis • cross-reaction of the thyroid antigen and ocular muscle antibodies is apossible explanation

19. Histologically, • Diffuse lymphocytic infiltration of the retro-orbital tissues occurs, • Fibroblast activation with glycosaminoglycan (a mucopolysaccharide) production leading to edema and fibrosis.

20. OPHTHALMOPATHY Protrusion opthalmoplegia (elevators are involved) {severe} diplopia Optic n. damage blindness (decreasing visual acuity Impaired colour vision) MALIGNANT EXOPHTHALMOS

21. Exophthalmos….. • result of increased retro-orbital tissue • assessed with an exophthalmometer (Hertel), [which measures the distance from the lateral bony orbital margin to the anterior surface of the cornea.]

22. DIAGNOSIS A cost-effective work-up can include • extensive history • physical examination, Thyroid function tests. • elevated levels of T3 and T4 , • a decreased or undetectable level of TSH should be demonstrated.

23. DIAGNOSIS (CONTD.) • Thyroid antibodies are elevated • A I123 radionuclide scan demonstrate diffuse uptake throughout an enlarged gland. • An ultrasound or computed tomography (CT) scan of the neck may be used to evaluate clinical landmarks).

24. TREATMENT STRATEGIES • Reducing functional mass of thyroid tissue by removal of large part of the gland • Destruction of most of the gland by I131 • Anti thyroid drugs to decrease seretion • Drugs that block beta adrenergic receptors

25. ANTI THYROID DRUGS • PROPYL THIOURACIL • METHIMAZOLE , CARBIMAZOLE • MECH. OF ACTION • Inhibit organicbinding of thyroid iodine and also inhibit coupling • PTU also inhibit peripheral conversion of T4to T3 • PTU is said to decrease thyroid antibody level

26. SIDE EFFECT • Rash, fever ,peripheral neuritis,polyarteritis,granulocytopenia, agranulocytosis,arthritis liver dysfuction PREGNANCY • Drug cross plancetae and also secreted in breast milk – PTU is preferred drug

27. DOSE • PTU 100-300mg tds • Methimazole 10-30mg tds ;then OD

28. BETA BLOCKERS • Hyperdynamic adrenergic effect of thyrotoxicosis are alleviated . • Decrease peripheral conversion • Reduce heart rate ,control tremor ,agitation • Not effective as sole mean of therapy as hyper metabolism and weight loss continue • Usually preferred - propranalol • May ppt heart failure and asthma

29. RESULTS • Improved symptom by 2 wks • Euthyriod by 6 wks • Given 12 –18 months [relapse 50%] • Thyroxine can be added to prevent hypothyroidism

30. RADIOACTIVE IODINE SUITABLE PATIENT • Small or medium sized goitre • Relapse after medical or surgical therapy • Contraindication to antithyriod drug or surgery

31. ABSOUTE Pregnancy Breast feeding RELATIVE Thyroid opthalmopathy Isolated thyroid nodule Toxic nodular goitre Young age CONTRAINDICATION

32. ADMINISTRATION • Should be euthyroid before I131 • Stop all anti thyroid drugs 2-3 wks prior for uptake • A drink of I131 sodium iodide • Initial dose is about 10 mci of I131

33. ADMINISTRATION • After std. treatment- euthyroid within 2 months. Some become hypothyroid • Long term follow up –hypothyroidism and recc. Hyperthyroidism may aggravate ophthalmopathy

34. COMPLICATIONS • Exacerbation of thyrotoxicosis • Overt thyroid storm • Hypothyroidism • Risk of foetal damage in pregnancy • Worsening of eye signs • Hyperparathyroidism

35. ADVANTAGES Avoidance of surgery Overall treatment cost is less Treatment ease DIADVANTAGES Hypothyroidism Adverse effect on opthalmopathy Reccurent thyrotoxicosis is managed by radioiodine because reoperation carries higher morbidity

36. SURGERY INDICATIONS • Intolerance or non compliance with anti thyroid drugs • When radioiodine is contraindicated • Young patients • Graves optthalmopathy

37. Indications(contd.) • Pregnancy • suspicious nodule in graves glands • Large toxic nodular goitre with low I131 uptake • Very large goitre and severe thyrotoxicosis at initial presentation

38. RISKS • R.L.N. injury • Hypoparathyroidism • Permanent hypothyroidism

39. PREOPERATIVE PREPERATION • Thyrotoxicosis is controlled medically -better nutritional state - provides normal homeostatic mechanisms and responses to stress of operation • Wait for 2 months after euthyroid-other wise more chance for thyroid storm • Treated with lugols iodine for 10 days prior to operation to decrease the vascularity of the gland

40. Preferred surgery TOTAL THYROIDECTOMY • Low chance for relapse but more chance for nerve damage and hypoparathyroidism SUBTOTAL AND NEAR TOTAL THYROIDECTOMY • Higher chance for relapse lesser complications

41. COMPLICATION • Hoarseness of voice • Hypoparathyroidism • Infection • Air embolism • Thyroid storm

42. ADVANTAGES Immediate cure Decreased long term incidence of hypothyroidism Decreased op visits Potential removal of a carcinoma DISADVANTAGES All complications Haematoma Hypertrophic scar

43. TREATMENT OF EXOPTHALMOS • Severity is independent of thyrotoxicosis • Treatment is directed to prevent infection and reduce periorbital swelling • High dose systemic corticosteroid (prednisolone 60mg) • Retrobulbar injection of depot steroids

44. SURGICAL INTERVENTIONS • Lateral tarsoraphy • Orbital decompression • Cryosurgical rduction of pituitary OTHERS • Radiation therapy with steroids • Plasma exchange therapy • Immunosupppressants-cyclosporine, azathioprine

45. THYROID STORM • Rarely during thyroidal or other surgery PRECIPITATING FACTORS • Infection, labour, administaration of iodine, after treatment with I131

46. MANIFESTATIONS • Hyperthermia, tachycardia, intense irritability, profuse sweating, hypertension, extreme anxiety, prostration,hypotension and death • All are adrenergic phenomenon • Caused by adrenergic outburst in a sensitised patient by thyroid hormone induction

47. MANGEMENT • Best management –prophylaxis • Patients with toxicity should be made euthyroid before operation. TREATMENT • Fluid replacement • Lugols iodine • Hydrocortisone (cortisol beakdown is increased) • Cooling blanket avoid aspirin

48. Reserpine and guanethidine (sympatholytic treatment) • Oxygen • Glucose infusion

49. SUMMARY • Thyrotoxicosis can be primary or secondary • Graves disease is the most common type • It is an autoimmune disorder • Classical triad – goitre, thyrotoxicois,exophthalmos • Investigations-T3 ,T4, TSH,thyroid antibodies

50. Treatment options are –drugs, radioactive iodine, surgery • Over 45: radioiodine. Under 45: surgery for the large goitre, antithyroid drugs for the small goitre. • Thyroid storm is an adrenergic outburst in a sensitised patient which is better prevented than treated