HYPERTHYROIDISM

1. HYPERTHYROIDISM Prevalence Women 2% Men 0.2% 15% of cases occur in patients older than 60 years of age

2. Clinical Symptoms Depends on • Age of patient • Magnitude of hormonal excess • Presence of co-morbid condition

3. Mechanism of Clinical Symptoms 1. Catabolism 2. Enhancement of sensitivity to catecholamines

4. Clinical Symptoms • Clinical manifestations of hyperthyroidism are largely independent of its cause. • However, causing disorder may have other effects.

5. Clinical Symptoms • Older patient presents with lack of clinical signs and symptoms, which makes diagnosis more difficult • Thyroid storm is a rare presentation, occurs after stressful illness in under treated or untreated patient. Characteristics -Delirium -Dehydration -Severe tachycardia -Vomiting -Fever -Diarrhea

6. Clinical symptoms • Skin -Warm -May be erythematous (due to increased blood flow) -Smooth- due to decrease in keratin -Sweaty and heat intolerance -Onycholysis –softening of nails and loosening of nail beds

7. Clinical symptoms • Hyperpigmentation -Due the patient increase ACTH secretion • Pruritis -mainly in graves disease • Thinning of hair • Vitilago and alopecia areata -mainly due to autoimmune disease • Infilterative dermopathy -Graves disease, most common on shins

8. Clinical symptoms • Eyes Stare Lid lag *Due to sympathetic over activity *Only Grave’s disease has ophthalmopathy -Inflammation of extraocular muscles, orbital fat and connective tissue. -This results in exopthalmos -More common in smokers

9. Clinical symptoms Eyes • Impaired eye muscle function (Diplopia) • Periorbital and conjunctival edema • Gritty feeling or pain in the eyes • Corneal ulceration due to lid lag and proptosis • Optic neuritis and even blindness

10. Clinical symptoms Cardiovascular System • Increased cardiac output (due to increased oxygen demand and increased cardiac contractibility. • Tachycardia • Widened pulse pressure • High output – heart failure

11. Clinical symptoms • Cardiovascular System • Atrial fibrillation, 10-20% of patients. More common in elderly • Atrial ectopy • 60% of A-fib will convert to normal sinus rhythm with treatment (4-months of becoming euthyroid) • Mitral valve problems • LVH and cardiomyopathy

12. Serum Lipids • Low total cholesterol • Low HDL • Low total cholesterol/HDL ratio

13. Respiratory System • Dyspnea on rest and with exertion • Oxygen consumpation and CO2 production increases. • Hypoxemia and hypercapnea, which stimulates ventilation • Respiratory muscle weakness • Decreased exercise capacity • Tracheal obstruction • May exacerbate asthma • Increased pulmonary arterial pressure

14. Clinical symptoms GI System -Weight loss due to increased calorigenesis -Hyperdefecation -Malabsorption -Steatorrhea -Celiac Disease (in Grave’s Disease) -Hyperphagia (weight gain in younger patient) -Anorexia- weight loss in elderly -Dysphagia -Abnormal LFT especially phosphate

15. Clinical symptoms Hematological System • Normochromic normocytic anemia • Serum ferritin may be high • Grave’s disese • ITP • Pernicious anemia • Anti-neutrophiliac antibody

16. Clinical symptoms GU System • Urinary frequency and nocturia • Enuresis is common in children

17. Clinical symptoms GU System Women • Increased SHBG • High serum estradiol • Low free estradiol • High LH • Reduce mid-cycle LH surge • Oligomenorrhea and amenorrhea • Anovulatory infertility

18. Clinical symptoms GU System Men • High SHBG • High total testosterone • Low free testosterone • High serum LH • High serum estradiol • Gynecomastia • Decreased libido • Erectile dysfunction • Decreased or abnormal sperm

19. Clinical symptoms • Skeletal System • Bone resorption • Increased porosity of cortical bone • Reduced volume of trabecular bone • Serum alkaline phosphate is increased • Increased osteoblasts • Inhibit PTH secretions • Decreased calcium absorption and increased excretion • Osteoporosis, Fractures

20. Clinical symptoms Skeletal System Grave’s disease is associated with thyroid acropathy -Clubbing of nails -Periosteal bone formation in metacarpal bone or phalanges

21. Clinical symptoms Neuromuscular System • Tremors-outstretched hand and tongue • Hyperactive tendon reflexes

22. Clinical symptoms Psychiatric • Hyperactivity • Emotional lability • Anxiety • Decreased concentration • Insomnia

23. Clinical symptoms Muscle Weakness • Proximal muscle weakness in 50% pts. • Decreased muscle mass and strength • May take up to six months after euthyroid state to gain strength • Hypokelemic periodic paralysis especially in Asian men (cause is not known) • Myesthenia Gravis, especially in Grave’s disease.

24. Clinical symptoms Endocrine • Increased sensitivity of pancreatic beta cells to glucose • Increased insulin secretion • Antagonism to peripheral action of insulin • Latter effects usually predominate leading to intolerance.

25. Etiology 1 Grave’s disease • Autoimmune disease caused by antibodies to TSH receptors • Can be familial and associated with other autoimmune diseases 2 Toxic multi-nodular goiter • 5% of all cases • 10 times more common in iodine deficient area • Typically occurs in older than 40 with long standing goiter

26. Etiology 3 Toxic adenoma • More common in young patients • Autonomically functioning nodule

27. Etiology 4 Thyroiditis Subacute • Abrupt onset due to leakage of hormones • Follows viral infection • Resolves within eight months • Can re-occur Lymphatic and postpartum • Transient inflammation • Postpartum can occur in 5-10% cases in the first 3-6 months • Transient hypothyroidism occurs before resolution

28. Etiology 5 Treatment Induced Hyperthyroidism Iodine Induced • Excess iodine indirect • Exposure to radiographic contrast media • Medication Excess iodine increases synthesis and release of thyroid hormone in iodine deficient and older patients with pre-existing goiters

29. Etiology Amiodarone Induced Thyroiditis • Up to 12% of patients, especially in iodine deficient cases • Most common cause of iodine excess in US. • Two types: *Type I - due to excess iodine Amiodarone contains 37% iodine. *Type II –– occurs in normal thyroid

30. Etiology Thyroid Hormone Induced • Factitious hyperthyroidism in accidental or intentional ingestion to lose weight • Tumors -Metastatic thyroid cancer -Ovarian tumor that produces thyriod hormone (struma ovarii) -Trophoblastic tumor -TSH secreting tumor

31. TSH level Signs and symptoms of hyperthyroid Low TSH High TSH (rare) Measure T4 High Secondary hyperthyroidism Image pituitary gland

32. Low TSH Measure Free T4 Level Normal High Primary hyperthyroidism Thyroid uptake Measure Free T3 Level High Normal -Subclinical hyperthyroidism -Resolving Hyperthyroidism -Medication -Pregnancy -New thyroid illness T3 Toxicosis Low High Measure thyroglobulin DIffuse Nodular decreased Increased Graves Multiple areas One “hot” area disease Exogenous hormone Thyroiditis Toxic adenoma Toxic multinodular goiter Iodide exposure Exrtraglandular production

33. Etiology • Hyperthyroidism with high RIU - Grave’s disease - Toxic adenoma - Toxic multinodular goiter - TSH- producing pituitary adenoma - Hyperemesis gravidarum - Trophoblastic disease

34. Etiology • Hyperthyroidism with low RIU - Subacute thyroiditis - Exogenous harmone intake - Ectopic ovarii - Metastatic follicular thyroid CA - Radiation thyroiditis - palpation thyroiditis - Amiodarone induced

35. Treatment • Treatment depends upon -Cause and severity of disease -Patients age -Goiter size -Comorbid condition -Treatment desired

36. Treatment The goal of therapy is to correct hyper-metabaolic state with fewest side effects and lowest incidence of hypothyroidism.

37. Options • Anti-thyroid drugs • Radioactive iodine • Surgery • Beta-blocker and iodides are adjuncts to above treatment

38. Beta Blockers • Prompt relief of adrenergic symptoms • Propranolol widely used • Any beta blocker can be used, but non-selectives have more direct effect on hyper-metabolism • Start with 10-20 mg q6h • Increase progressively until symptoms are controlled • Most cases 80-320 mg qd is sufficient • CCB can be used if beta blocker not tolerated or contraindicated

39. Iodides Iodide blocks peripheral conversion of T4 to T3 and inhibits hormone release. These are used as adjunct therapy • Before emergency non-thyroid surgery • Beta blockers cannot curtail symptoms • Decrease vascularity before surgery for Grave’s disease

40. Iodides Iodides are not used for routine treatment because of paradoxical increase of hormone release with prolonged use Commonly used: • Radiograph contrast agents -Iopanoic acid -Ipodate sodium • Potassium iodide Dose 1 gram/ 12 weeks

41. Anti-thyroid Drugs They interfere with organification of iodine—suppress thyroid hormone levels Two agents: -Tapazole (methimazole) -PTU (propylthiauracil)

42. Anti-thyroid Drugs • Remission rate: 60% when therapy continued for two years • Relapse in 50% of cases. • Relapse more common in -smokers -elevated TS antibodies at end of therapy

43. Anti-thyroid Drugs Methimazole Drug of choice for non-pregnant patients because of : • Low cost • Long half life • Lower incidence of side effects • Can be given in conjunction with beta-blocker • Beta-blockers can be tapered off after 4-8 weeks of therapy Dose 15-30 mg/day

44. Anti-thyroid Drugs • Methimazole • Monthly Free T4 or T3 until euthyroid • Maintenance dose 5-10 mg/day • TSH levels may remain undetectable for months after euthyroid and not to be used to monitor the therapy

45. Anti-thyroid Drugs Methimazole • At one year if patient is clinically and biochemically euthyroid and TS antibodies are not detectable, therapy can be discontinued • Monitor every three months for first year then annually • Relapses are more common in the first year but can occur years later • If relapse occurs, iodide or surgery although anti-thyroid drugs can be restarted

46. Anti-thyroid Drugs PTU • Prefered for pregnant patients • Methimazole is associated with rare genetic abnormalities Dose 100 mg t.i.d Maintenance 100-200 mg/day Goal: Keep Free T4 at upper level of normal

47. Anti-thyroid Drugs Complications • Agranulocytosis up to 0.5% • High with PTU • Can occur suddenly • Mostly reversible with supportive Tx • Routine WBC monitoring controversial • Some people monitor WBC every two weeks for first month then monthly • Advised to stop drug if they develop sudden fever or sore throat

48. Radioactive Iodine • Treatment of choice for Grave’s disease and toxic nodular goiter • Inexpensive • Highly effective • Easy to administer • Safe • Dose depends on estimated weight of gland • Higher dose increases success rate but higher chance of hypothyroidism • Some studies have shown increase of hypothyroidism irrespective of dose

49. Radioactive Iodine • Higher dose is favored in older patient • Cardiac disease • Other group needs prompt control • Toxic nodular goiter or toxic adenoma

50. Radioactive Iodine Side effects • 50% of Grave’s ophthalmology can develop or worsen by use of radioactive iodine • Use 40-50 mg Prednisone for at least three months can prevent or improve severe eye disease in 2/3 of patients • Use lower dose in ophthalmology because post Tx hypothyroidism may be associated with exacerbation of eye disease • Smoking makes ophthalmopathy worse.