Hyperthyroidism.

1. Thyrotoxicosis Dr/Mohammed Bamashmos(MD) Professor of Internal Medicine and Endocrinology Sana'a University ,Yemen

4. Causes

5. Causes of thyrotoxicosis

12. Clinical Symptoms • Nervousness,Anxiety • Increased perspiration • Heat intolerance • Tremor • Hyperactivity • Palpitations • Weight loss despite increased appetite • Reduction in menstrual flow or oligo-menorrhea

13. Common Signs Hyperactivity, Hyper kinesis Sinus tachycardia or atrial arrhythmia, AF, CHF Systolic hypertension, wide pulse pressure Warm, moist, soft and smooth skin- warm handshake Excessive perspiration, palmar erythema, Onycholysis Lid lag and stare (sympathetic over activity) Fine tremor of out stretched hands – format's sign Large muscle weakness, Diarrhea, Gynecomastia

14. Specific to Graves Disease Diffuse painless and firm enlargement of thyroid Thyroid bruit is audible Ophthalmopathy – Eye manifestations – 50% of cases Gritty feeling in eyes, periorbital edema, conjunctival edema (chemosis), poor lid closure, extraocular muscle dysfunction, diplopia, pain on eye movements and proptosis. Dermoacropathy – Skin/limb manifestations – 20% of cases Deposition of glycosamino glycans in the dermis of the lower leg – non pitting edema, associated with erythema and thickening of the skin, without pain or pruritus - called（pre tibial myxedema)

15. pre tibial myxedema Lid lag pre tibial myxedema

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

17. Diagnosis • Typical clinical presentation • Markedly suppressed TSH (<0.05 µIU/mL) • Elevated FT4 and FT3 (Markedly in Graves) • Thyroid antibodies – by Elisa – anti-TPO, TSI • ECG to demonstrate cardiac manifestations • Nuclear Scintigraphy to differentiate the causes

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

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

24. Imp. considerations Methimazole Propylthiouracil Efficacy Very potent Potent Duration of action Long acting BID/OD Short acting QID/TID In pregnancy Contraindicated Safely can be given Mechanism of action Iodination, Coupling Iodination, Coupling Conversion of T4 to T3 No action Inhibits conversion Adverse reactions Rashes, Neutropenia Rashes, ↑Neutropenia Dosage 20 to 40 mg/ OD PO 100 to 150mg qid PO Anti Thyroid Drugs (ATD)

25. 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

28. Radioactive Iodine • for Grave’s disease and toxic nodular goiter • Inexpensive, Safe • Highly effective • Easy to administer • 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

29. 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.

30. Radioactive Iodine • Use of anti-thyroid drugs with iodine is not recommended in most cases • May improve safety for severe or complicated cases • Beta blockers used to control symptoms before radioactive iodine and can be combined throughout Tx • Iodine containing meds need to be stopped several weeks before therapy • Never given for children and pregnant/ lactating women • Not recommended with patients of severe Ophthalmopathy • Not advisable in chronic smokers

31. Surgery • Radioactive iodine has replaced surgery for Tx of hyperthyroidism • Subtotal thyroidectomy is most common • Surgical treatment is reserved for • Severe hyperthyroidism in children • Pregnant women who can’t tolerate ATD • Large goiters with severe Ophthalmopathy • Large MNGs with pressure symptoms • Who require quick normalization of thyroid function

38. Drug Treatment of Thyroid Storm(table 216-6) Decrease de novo synthesis: Porpylthiouracil 600-1000mg PO initially, followed by 200-250 mg q 4 hrs Methimazole 40 mg PO initial dose, then 25 mg PO q6h Prevent releases of hormone (after synthesis blockade intiated) Iodine Iaponoric acid (Telepaque) 1 gm IV q8h for the first 24 h, then500 mg bid or Potassium iodide (SSKI) 5 drops PO q6h or Lugol solution 8-10 drops PO q6h Lithuim 800-1200 mg PO every day

39. Prevent peripheral effects: • B-Blocker • Guanethidine 30-40 mg PO q 6 h • Other consideration: • Corticosteroids Hydrocortisone 100 mg IV q 8 h or dexamethosone 2 mg IV q 6 hr • Antipyretics Cooling blanket acteaminophen 650 mg PO q 4-6h

40. Endoscopic subtotal thyroidectomy • Embolization of thyroid arteries • Plasmaphoresis • Percutaneous ethanol injection into toxic nodule • L-Carnitine supplementation may improve symptoms and may prevent bone loss