بسم الله الرحمن الرحيم

1. بسم الله الرحمن الرحيم

2. Hyperthyroidism BY AmalKhalifa Ahmed Assistant professor of Internal Medicine

3. Introduction • What is Hyperthyroidism? • “Hyperthyroidism” refers to overactivity of the thyroid gland leading to excessive synthesis of thyroid hormones and accelerated metabolism in the peripheral tissues.

4. Introduction • Hyperthyroidism is common, affecting perhaps 2–5% of all females at some time and with a sex ratio of 5 : 1, most often between the ages of 20 and 40 years. • Nearly all cases (> 99%) are caused by intrinsic thyroid disease; a pituitary cause is extremely rare

5. Aetiology Primary (99%) Secondary (Rare) Thyroid Tissue Disease Over Secretion by Pituitary Pituitary Tumour Autoimmune (Graves Disease) Thyroid Stimulating Antibodies Increased TSH Production Increased Stimulation of TSH Receptors Increased Thyroxin Production

6. Hyperthyroidism • Common Causes (Primary) • Graves’ disease (autoimmune) • Toxic multinodular goitre • Solitary toxic nodule/adenoma

7. Hyperthyroidism • uncommon Causes (Primary) • Thyroiditis: viral (e.g. de Quervain’s), autoimmune, post-irradiation and postpartum • Gestational thyrotoxicosis (HCG stimulated) • Neonatal thyrotoxicosis (maternal thyroid antibodies) • Exogenous iodine: Drugs – amiodarone • Throtoxicosis factitia (secret T4 consumption)

8. Hyperthyroidism Rare Causes • TSH-secreting pituitary tumours • Metastatic differentiated thyroid carcinoma • HCG-producing tumours • Hyperfunctioning ovarian teratoma (strumaovarii

9. Graves’ disease • This is the most common cause of hyper-thyroidism and is due to an autoimmune process. • Serum IgG antibodies bind to TSH receptors in the thyroid, i.e. they behave like TSH. These antibodies are specific for Graves’ disease, can be measured in serum, are present in 85–90% of cases and decline with treatment. • Persistent high levels predict a relapse when drug treatment is stopped.

10. Graves’ disease • There is an association with HLA-B8, DR3 and DR2 and a 40% concordance rate amongst monozygotic twins with a 5% concordance rate in dizygotic twins.

11. Graves’ disease • Yersinia enterocolitica, Escherichia coli and other Gram negative organisms contain TSH binding sites. • This raises the possibility that the initiating event in the pathogenesis may be an infection with possible ‘molecular mimicry’ in a genetically susceptible individual, but the precise initiating mechanisms remain unproven in most cases.

12. Graves’ disease • Thyroid eye disease accompanies the hyperthyroidism in many cases but other components of Graves’ disease, e.g. Graves’ dermopathy, are very rare. • Rarely lymphadenopathy and splenomegaly may occur. • Graves’ disease is also associated with other autoimmune disorders such as pernicious anaemia, vitiligo and myasthenia gravis.

13. Graves’ disease • The natural history is one of fluctuation, many patients showing a pattern of alternating relapse and remission; • Only 40% of subjects have a single episode. • Many patients eventually become hypothyroid

14. Other causes of hyperthyroidism • Toxic solitary adenoma/nodule This is the cause of about 5% of cases of hyperthyroidism. It does not usually remit after a course of anti-thyroid drugs. • Toxic multinodular goitre This commonly occurs in older women. Again, anti - thyroid drugs are rarely successful in inducing a remission - although they can control the hyperthyroidism.

15. de Quervain 's thyroiditis • This is transient hyperthyroidism from an acute inflammatory process, probably viral in origin. • There is usually fever, malaise and pain in the neck with tachycardia and local thyroid tenderness. • Thyroid function tests show initial hyperthyroidism, the (ESR) and plasma viscosity are raised. • Hypothyroidism, usually transient. • Treatment of the acute phase is with aspirin, using short –term prednisolone in severely symptomatic cases.

16. Clinical features of hyperthyroidism

17. Clinical features of hyperthyroidism • The symptoms and signs of hyperthyroidism affect many systems • Symptomatology and signs vary with age and with the underlying aetiology.

18. Symptoms • Weight loss • Increased appetite • Irritability/behaviour change • Restlessness • Malaise • Muscle weakness • Tremors • Breathlessness • Palpitation • Heat intolerance • Itching

19. Symptoms • Thirst • Vomiting • Diarrhoea • Eye complaints (Only in Graves’ disease) • Goitre • Oligomenorrhoea • Loss of libido • Gynaecomastia • Tall stature (in children) • Sweating

20. Signs • Tremor • Proximal myopathy- Proximal muscle wasting • Hyperkinesis • Psychosis • Palmarerythema • Tachycardia or atrial fibrillation • Thyroid acropachy • Pretibialmyxoedema • Warm vasodilated peripheries • Systolic hypertension • Cardiac failure

21. Signs • Exophthalmos*(Only in Graves’ disease) • Lid lag and ‘stare’ • Conjunctival oedema • Ophthalmoplegia*(Only in Graves’ disease) • Periorbital oedema • Goitre, bruit • Weight loss

23. Graves' disease patient with exophthalmos and vitiligo.

24. note • The eye signs, pretibial myxoedema and thyroid acropachy occur only in Graves’ disease. • Pretibial myxoedema is an infiltration on the shin, essentially occurring only with eye disease. • Thyroid acropachy is very rare and consists of clubbing, swollen fingers and periosteal new bone formation

25. note • In the elderly, a frequent presentation is with atrial fibrillation, other tachycardias and/or heart failure, often with few other signs. • Thyroid function tests are mandatory in any patient with atrial fibrillation. • Children frequently present with excessive height or excessive growth rate, or with behavioural problems such as hyperactivity. They may also show weight gain rather than loss.

26. note • So-called ‘apathetic thyrotoxicosis’ in some elderly patients presents with a clinical picture more like hypothyroidism. • There may be very few signs and a high degree of clinical suspicion is essential.

27. HYPERTHYROIDISM DIAGNOSIS Serum T4 or fT4 Above Normal ? Primary Hyperthyroidism ? Secondary Hyperthyroidism

28. HYPERTHYROIDISM DIAGNOSIS (cont.) Serum TSH Above Normal Below Normal ? Secondary Hyperthyroidism ? Primary Hyperthyroidism

29. How To Diagnose Hyperthyroidism • TSH – is suppressed (< 0.05 mU/L), • Free T4 – expect to be high • Nuclear thyroid scintigraphy iodine 123 uptake and scan – expect iodine uptake to increased • Anti-thyroperoxidase antibody levels and thyroglobulin antibodies are present in most cases of Graves' disease.

30. Differential diagnosis • Hyperthyroidism is often clinically obvious but treatment should never be instituted without biochemical confirmation. • Differentiation of the mild case from anxiety states may be difficult; useful positive clinical markers are eye signs, a diffuse goitre, proximal myopathy and wasting. • Weight loss despite a normal or increased appetite is a very useful clinical symptom of hyperthyroidism. • The hyperdynamic circulation with warm peripheries seen with hyperthyroidism can be contrasted with the clammy hands of anxiety.

31. Treatments for Hyperthyroidism • Medical therapy • with antithyroid drugs such as propylthiouracil (100-200 mg/8 hourly)or carbimazole (20-40 mg/day) • Self-limited causes of hyperthyroidism, such as subacute thyroiditis, iodine-induced hyperthyroidism, and exogenous administration of T4, can be treated symptomatically. • For more significant cardiovascular symptoms, beta-adrenergic blockade with propranolol can be helpful.

32. Medical ttt (cont.) • Indications • Young women with Graves’ –Small goiter – Mild thyrotoxicosis - High titre of thyroid AB • Preoperative in severe cases • Advantages • Give remission rate 60% • Accepted by the patients • Avoid complications of surgery & I131 • Disadvantages of medical ttt • 40-% relapse rate • Duration of therapy 1.5-2 Ys • Agranulicytosis <0.05%, rashes <2% during Ist m of ttt

33. RelapseAbout 50% of patients will relapse after a course of carbimazole or propylthiouracil, mostly within the following 2 years but occasionally much later. Long-term anti-thyroid therapy is then used or surgery or radio therapy is considered

34. Surgical : Subtotal thyroidectomy • Indications • If there are pressure symptoms in retrosternal goiter • patient choice • persistent drug side-effects • poor compliance with drug therapy • recurrent hyperthyroidism after drugs. • Particular indications for surgery include: large goitre, which is unlikely to remit after anti thyroid medication. • Advantages of Surgery • Permanent relief of thyrotoxicosis in 95% of cases • Disadvantages • 10%becomes hypothyroidism • 1-2% becomes hypoparathyroidism - 6% damage of recurrent laryngeal • Ugly scare

35. Radioactive Iodine Ablation of the thyroid gland with radioactive iodine • Indications of Radioactive Iodine • Pts >45Ys • Relapse of thyrotoxicosis after thyroidectomy • Advantages • Accepted – Cheap. • Disadvantages • Assessment of the dose is difficult • High risk of long term hypothyoidism • Risk of carcinogenesis has been long debated, but it is now clear that overall cancer incidence and mortality are not increased after radioactive iodine

36. Follow-up Care • Patients who have been treated for hyperthyroidism need to be followed closely because they may develop Hypothyroidism or recurrent hyperthyroidism. Follow-up care includes the following: • Reducing medications after 4-6 weeks; the patient stop anti-thyroid medication in 12-18 months • Check thyroid function tests every 4-6 weeks • Monitor closely for remission.

37. Special situations in hyperthyroidism

38. Thyroid storm (Thyroid crisis) A life-threatening thyrotoxic crisis Initially the acute mortality rate was nearly 100%. In current practice, with aggressive therapy and early recognition of the syndrome, the mortality rate is 20%.

39. Thyroid Storm Causes • Surgery • Radioactive Iodine Therapy • Severe illness in unrecognized or inadequately treated thyrotoxicosis • Diagnosis • Clinical – tachycardia, hyperpyrexia, thyrotoxicosis hypertension, followed by hypotension and shock. • Labs (Low TSH, High T4, FT4) • Treatment • ttt is urgent. Propranolol in full doses is started immediately together with potassium iodide, antithyroid drugs, corticosteroids (which suppress many of the manifestations of hyperthyroidism) and full supportive measures. • Control of cardiac failure and tachycardia is also necessary

40. Hyperthyroidism in pregnancy andneonatal life • The high level of HCG found in pregnancy is a weak stimulator of the TSH receptor, commonly causing suppressed TSH with slightly elevated fT4/fT3 in the first trimester which may be associated with hyperemesis gravidarum. • True maternal hyperthyroidism during pregnancy is however uncommon and usually mild. • Diagnosis can be difficult because of the overlap with symptoms of normal pregnancy and misleading thyroid function tests, although TSH is largely reliable

41. Hyperthyroidism in pregnancy andneonatal life • The pathogenesis is almost always Graves’ disease. • Thyroid stimulating immunoglobulin (TSI) crosses the placenta to stimulate the fetal thyroid. • Carbimazole also crosses the placenta, but T4 does so poorly, so a ‘block-and-replace’ regimen is contraindicated. • The smallest dose of carbimazole necessary is used and the fetus must be monitored

42. Hyperthyroidism in pregnancy andneonatal life • The pediatrician should be informed and the infant checked immediately after birth – overtreatment with carbimazole can cause fetal goitre. • Breast-feeding while on usual doses of carbimazole or propylthiouracil appears to be safe. • If necessary (high doses needed, poor patient compliance or drug side-effects), surgery can be performed, preferably in the second trimester. • Radioactive iodine is absolutely contraindicated

43. The fetus and maternal Graves’ disease • Any mother with a history of Graves’ disease may have circulating TSI. • Even if she has been treated (e.g. by surgery),the immunoglobulin may still be present to stimulate the fetal thyroid, and the fetus can thus become hyperthyroid, while the mother remains euthyroid. • Any such patient should therefore be monitored during pregnancy

44. The fetus and maternal Graves’ disease • Fetal heart rate provides a direct biological assayof fetal thyroid status, and monitoring should be performed at least monthly. • Rates above 160 per minute are strongly suggestive of fetal hyperthyroidism, and maternal treatment with carbimazole and/or propranolol is used. • Untreated neonatal hyperthyroidism is probably associated with hyperactivity in later childhood

45. THYROID EYE DISEASE • The ophthalmopathy of Graves' disease is due to a specific immune response that causes retro-orbital inflammation. • Swelling and oedema of the extraocular muscles lead to limitation of movement and to proptosis which is usually bilateral but can sometimes be unilateral. • Ultimately increased pressure on the optic nerve may cause optic atrophy.

46. Clinic al features • Thyroid eye disease demonstrates a wide range of severity. • Prominence of the eyes and the 'stare' of lid retraction is relatively common. • More severe proptosis occurs in a minority of cases, and limitation and discomfort of eye movement. • Visual impairment due to optic nerve compression are relatively uncommon. • Proptosis and lid retraction maylimit the ability to close the eyes completely so that corneal damage may occur. • There is periorbital oedema and conjunctival oedema and inflammation.

47. Treatment • If the patient is thyrotoxic this should be treated. • hypothyroidism must be avoided. • Methylcellulose • Systemic steroids • Irradiation of the orbits • Lid surgery • Surgical decompression of the orbit • Corrective eye muscle surgery may improve diplopia

48. Thank you