thyrotoxicosis , causes, diagnosis and treatment

Definition, causes, pathogenesis, diagnosis and treatment

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

2. Causes

3. Causes of thyrotoxicosis

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

5. 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

6. 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)

7. pre tibial myxedema pre tibial myxedema Lid lag

8. 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

9. Diagnosis Typical clinical presentation Markedly suppressed TSH (<0.05 µIU/mL) Elevated FT 4 and FT 3 (Markedly in Graves) Thyroid antibodies – by Elisa – anti-TPO, TSI ECG to demonstrate cardiac manifestations Nuclear Scintigraphy to differentiate the causes

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

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

12. Anti Thyroid Drugs (ATD) 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 T 4 to T 3 No action Inhibits conversion Adverse reactions Rashes, Neutropenia Rashes, ↑Neutropenia Dosage 20 to 40 mg/ OD PO 100 to 150mg qid PO

13. 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

14. 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

15. 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.

16. 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

17. 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

18. 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

19. 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

20. 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

21. Than you