1. THYROTOXICOSIS AND HYPERTHYROIDISM An overview DR PRAVEEN SHETTY DEPARTMENT OF INTERNAL MEDICINE

2. Thyrotoxicosis Defined as the clinical,physiologic,and biochemical findings that result when the tissues are exposed to,and respond to,excess thyroid hormone. Rather than being a specific disease,thyrotoxicosis can originate in a variety of ways. RAIU is subnormal

3. Hyperthyroidism Denotes only those conditions in which sustained hyperfunction of the thyroid gland leads to thyrotoxicosis. Increased RAIU is the hallmark.

4. Varieties of Thyrotoxicosis Associated with thyroid hyperfunction: Excess production of TSH(rare) Abnormal thyroid stimulator-Eg:Graves’ disease Intrinsic thyroid autonomy- Eg:Hyperfunctioning adenoma, Toxic multinodular goitre Not associated with thyroid hyperfunction: Disorders of hormone storage-Eg:Subacute thyroiditis, chronic thyroiditis Extrathyroid source of hormone- Thyrotoxicosis factitia,ectopic thyroid tissue- struma ovarii, functioning follicular Ca.

5. Hyperthyroidism Graves’ disease Also known as Parry’s or Basedow’s disease. Graves’ disease is a disorder with three major manifestations: 1)Hyperthyroidism with diffuse goitre 2)Ophthalmopathy and 3)Dermopathy. These three manifestations may not appear together.

6. Incidence and prevalence Relatively common disease that can occur at any age More common in the 3 rd and 4 th decade Disease is more frequent in women(7:1) Genetic factors play a important role An overlap exsists with other autoimmune diseases suggesting Graves is also a autoimmune thyroid disease

7. Etiology and Pathogenesis Cause of Graves’ is unknown No single factor is responsible for the entire syndrome With respect to hyperthyroidism,the central disorder is a disruption of homeostatic mechanisms that normally control hormone secretion.This disruption results from the presence in the plasma of thyroid stimulating immunoglobulins(TSI’s) of IgG class and inhibition of the binding of TSH to its receptors(TBII’s).These factors represent TRAb’s.

8. Pathology Thyroid gland is diffusely enlarged,soft and vascular. There is parenchymatous hyperplasia and hypertrophy with lymphocytic infilteration. The ophthalmopathy is characterized by an inflammatory infilterate of the orbital contents,with lymphocytes,mast cells and plasma cells The dermopathy of Graves’ disease is characterized by thickening of the dermis,which is infilterated by lymphocytes and mucopolysaccharides

9. Clinical features The clinical manifestations include those that reflect the associated thyrotoxicosis and those specifically related to Graves’ disease

10. Clinical features of thyrotoxicosis Neuromuscular: Nervousness,irritability,emotional liability,psychosis Tremor Hyperreflexia,ill sustained clonus Muscle weakness,proximal myopathy,bulbar myopathy Reproductive:Amenorrhoea,Oligomenorrhoea Infertility,impotence

11. Thryotoxicosis.. Gastrointestinal: Weight loss despite increased appetite Hyperdefecation Diarrhoea and steatorrhoea Vomiting Cardiorespiratory: Palpitations,Sinus tachycardia,Atrial fibrillation Increased pulse pressure Dyspnea on exertion Angina,cardiomyopathy and heart failure

12. Thyrotoxicosis.. Others: Heat intolerance Increased sweating Fatigue Gynaecomastia Palmar erythema, Onycholysis

13. Manifestations of Graves’ disease The distinctive manifestations-diffuse hyperfunctioning goiter,ophthalmopathy,and dermopathy- appear in varying combinations,and in varying frequencies,goiter being the most common. Premature greying of hair and patchy vitiligo are non specific features of Graves’s

14. Goiter Is diffuse and toxic and maybe asymetric and lobular. There may be presence of bruit over the goiter

18. Ophthalmopathy Signs of Graves’s ophthalmopathy are divided into two components: 1) Spastic: Stare, lid lag and lid retraction which account for the “frightened” facies. 2) Mechanical: Proptosis of varying degrees,ophthalmoplegia,and congestive occulopathy characterized by chemosis,conjunctivitis,periorbital swelling and the potential complications of corneal ulceration,optic neiritis and optic atrophy.

22. Dermopathy Usually occurs over the dorsum of the legs or feet and is termed localized or pretibial myxedema. It is usually a late phenomenon The affected area is usually demarcated from the normal skin by being raised andthickened and having a peau d’ orange appearance;it may be pruritic and hyperpigmented. The most common presentation is non pitting oedema,but lesions maybe plaque like,nodular or polypoid. Clubbing of the fingers and toes accompanies and is termed thyroid acropachy

27. Differential diagnosis Anxiety Pheochromocytoma Hydatidiform mole Ectopic thyroid tissue(struma ovarii) Factitious thyrotoxicosis

28. Investigations Thyroid function test: TSH- Undetectable T 4 - Raised T 3 - Raised RAIU- Raised TSH-receptor antibodies(TRAb)-elevated in Graves’s disease Isotope scanning- Increased uptake

29. Other non specific findings Hepatic dysfunction- Raised AST,ALT Mild hypercalcemia Glycosuria- Associated diabetes mellitus

30. Treatment of Hyperthyroidism

31. Anti thyroid drugs Chemically block hormone synthesis Enhance evolution to remission Best indicated for children,adolescents,young adults and pregnant women. Propylthiouracil-100-150mg every 6or 8 hrs Carbimazole- 40-60mg daily initially for 3 weeks,then reduce to 20-40mg for another 8 weeks and maintain at 5-20mg daily for 18-24 months. Methimazole-active metabolite of Carbimazole

32. Duration of treatment 18-24 months Side effects- Rash Leukopenia Agranulocytosis

33. Control of adrenergic symptoms Adrenergic antagonists: Propranolol-40-120mg/day

34. Ablative therapy(Surgery & Iodine) Indications: Relapse or recurrance following drug therapy A large goiter Failure to follow medical regimen. Radioactive iodine is simple,effective and economical

35. Complications of ablative therapy Immediate complications of surgery: Bleeding,injury to recurrant laryngeal nerve and thyroid crises. Other complications Hypothyroidism Radiation thyroiditis

36. Complications of thyrotoxicosis 1)Cardiac- Heart failure Atrial fibrillation 2)Thyrotoxic crises: or ‘storm’: Fulminating increase in signs and symptoms of thyrotoxicosis. Occurs in medically untreated or inadequately treated patients.May be precipitated by surgery or sepsis The syndrome is characterized by extreme irritability,delirium or coma,fever 41°C or more,tachycardia,restlessness,hypotension,vomitin g and diarrhea.

37. Treatment of thyroid crisis Provide supportive care; Treat dehydration Administer glucose and saline Vitamin B complex and glucocorticoids Digitalization is required in those with atrial fibrillation Immediate and large doses of anti thyroid agents(Eg-propylthiouracil 100mg every 2h) Iodine intravenously or by mouth Propranolol 40-80mg every 6h Dexamethasone(2mg every 6h) and to be tapered later.

38. Treatment of ophthalmopathy and Dermopathy Methylcellulose eye drops Tinted glasses Persistant diplopia can be corrected by surgery Papilloedema,loss of visual field or acuity requires urgent treatment with prednisolone 60 mg daily. Majority of patients require no treatment other than reassurance. Dermopathy of Graves rarely requires treatment

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