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  2. 2. GOALS OF TREATMENT: decrease hyperthyroid symptoms Establish euthyroid state Treatment is individualized !!!!! Because each patient has different manifestations. Main treatment modalities: (any one as initial therapy, then in combination) ANTITHYROID DRUGS RADIOTHERAPY SURGERY •WHICH TREATMENT T BEGIN WITH ???? TO +++ symptomatic therapy……… •Cardiac decompensation, Hospitalization • atrial fibrillation, /icu • thyroid storm Consideration is given to appropriate selection of patients for radioiodine therapy surgery or ATDs, as well as to the indications and contraindications for this therapy. Patient input into the treatment choice is important and must be discussed and considered.
  3. 3. SURGERY RADIOACTIVE IODINE ANTI THYROID DRUGS Large goiter >80 gm, with compessive symptoms. pts with comorbid conditions,with surgical risks. High likelyhood of remissions(mildmoderate disease High TRAb titer >40IU Young pts (,have >50%chances of relapse with ATDs) Low TRAb titers, moderate to severe Low uptake of IODINE 131 by the gland ,low/hypofunctioning nodule Goiter with good uptake of iodine old Pts with comorbidities :low life expectancy Coexistent hyperparathyroidism Noncompliant to ATD drugs Pts with risks of surgery, pregnancy/lactation,children ,with severe ophthalmopathy Suspected/documented thyroid malignancy Previously surgically treated pts. Previously operated pts or who need euthyroid state before surgery. PATIENT SELECTION PROS For prompt control of hyperthyroidism CONS Tx for GD ,avoidance of Sx ,cosmetic scar,betarays travel 2mm/nt damage surring tissue. ,can be performed in an outpatient Patients who cant follow safety rules of radiations,in nursing homes/outpt. Avoidance Sx,radiation, Possibility of remission setting Needs lifelong thyroxine replacement, Need prior methimisole before Sx Needs lifelong thyroxine replacement, Need prior methimisole before radiation Needs constant monitoring and dose adjustments, more risk of thyroid storm
  4. 4. ANTITYROID DRUGS : thioamides T3 ,fT4 HOW THEY WORK ! •They are actively transported into the thyroid gland where they inhibit both the orgaification of iodine to tyrosine residues in CARBAMIZOLE thyroglobulin and the coupling of iodotyrosines •Immunosuppressive within the thyroid gland, where the drugs are concentrated, decreases thyroid antigen expression and decreases prostaglandin and cytokine METHIMAZOLE release from thyroid cells. also inhibit the generation of oxygen radicals in T cells, B cells, decline in antigen presentation. PROPYLTHIOURACIL methimazole induces the expression of Fas ligand on the thyroid epithelial cell, thus inducing apoptosis infiltrating T cells TSH/THYROTROPIN BLOODSTREAM HYPERPLASTIC THYROID FOLLICLE WITH THYROGLOBULIN BINDING OF IODIDE •DECREASE HYPERTHYROID SYMPTOMS •MAINTAIN EUTHYROID STATE •AWAIT SPONTANEOUS REMISSION MONOIODOTYROSINE DIIODOTYROSINE ORGANIFICATION/ IODINATION COUPLING T4 DECREASED OUTPUT OF T3 T4 Tg T3 T3 AIMED AT: HYPERPLASTIC THYROID CELLS
  5. 5. CARBAMIZOLE METHIMAZOLE (MMI,tapazole) 10-20 mg 1t/day PO ADDED IODIDES Ten times more potent than PTU, and once-a-day dose is effective. Euthyroid state is achieved quickly Relapse may be observed 1-6 mo The serum half-life of MMI is four to six hours, Cross placental barrier, used from2nd trimester MONITOR T3 ,Ft4, EUTHYROID STATE ESTABLISHED IN 4-6 WEEKS DOSE REDUCED BY 50% 5-10 mg 1t/day PO CONTRAINDICATIONS •allergic reactions: antihistamine/RAIU/Sx •WBC,neutrophil<500/ mm3 •Liver transaminase >5 times upper normal limits MAINTENANCE Tx CONTINUED FOR 12-24 MO. TAPER, CONTROL T3 T4, NO SYMPTOMS STOP Rx. MONITOR EVERY 3 MO FOR NXT YEAR Major side effects • agranulocytosis •Hepatitis, •hepatic necrosis •vasculitis. MMI Tx :reduce dose steroids JAUNDICE, ACHOLIC STOOLS ,DARK URINE PRURITIC RASH PTU WHEN A PATIENT IS SAID TO BE IN REMISSION ?? Minor side effects: •Abdominal pains •Arthalgias •Bloating •Nausea •vomit PROPYLTHIOURACIL 50-150 mg 3t/day po Maintenance: 50 mg PO q8-12hr for up to 12-18 months; MONITOR T3 ,Ft4, then taper and Discontinue if euthyroidism restored (TSH) is normal Ptu preffered in pregnancy , 1st trimester, reduced dose pregnancy proceeds more protein bound Half life 75 minutes, Used whem MMI OR CARBAMIZOLE not optimal. •Utricarias •Hairloss •Headache,paresthesis •Fever,change in taste WHEN s TSH, Ft4 , T3 IS NORMAL FOR 1 YEAR AFTER DISCONTINUATION OF Rx
  6. 6. RADIOIODINE—(SINGLE SUFFICIENT RADIATION DOSE ) Discontinue ATDs 2 weeks prior to radiotherapy 5-10 mCi calculation based on wt and I131 uptake (FIXED DOSE 7 mCi/50-100GY) Can precipitate thyroid storm/aggravate graves ophthalmopathy DECREASED CLINICAL SYMPTOMS IN 4-6 WKS Tx: prednisolone 1 mg/kg x2-3mo FIRST FOLLOWUP IN 2MO THEN 4-6WK INTERVALS FOR NXT 6MO Taper few days before If MINIMUM RESPONSE radiotherapy By 3mo CONSIDER RETREATMENT When SIGNS OF HYPOTHYROIDISM Because of destruction of gland appears THYROID HORMONE REPLACEMENT STARTED LEVOTHYROXINE Lifelong ANNUAL FOLLOWUP. THYROID FUNCTION TESTS CONTRAINDICATIONS •Pregnancy,lactation •Planning pregnancy •Coexistent/susceptibi lity of thyroid cancer •Any metal device in body,
  7. 7. SURGERY : THYROIDECTOMY Surgery provides rapid treatment of Graves disease and permanent cure of hyperthyroidism in most patients, and it has "negligible mortality and acceptable morbidity" by experienced surgeons. PROPERATIVE PREPARATION : render the patient euthyroid is essential in order to prevent thyrotoxic crisis. CARBAMISOLE/METHIMAZOLE : 6 WEEKS PRIOR , 10-20 MG/D PO +/+ PROPRANOLOL : 10-40 MG 3T/D SSKI/LUGOL I2KI SOLUTION : 14 DAYS PRIOR , 50-250 MG(1-5 GTT OF 1G/ML) PO 3T/D continued postop also! •Reduce vascularity of gland,blood flow and intraoperative bleeding, •decrease activity of thyroid gland, action involves decreasing thyroidal iodide uptake, decreasing iodide oxidation and organification, and blocking release of thyroid hormones SUBTOTAL/NEAR TOTAL THYROIDECTOMY >>> TOTAL THYROIDECTOMY intention of leaving enough thyroid remnants behind to avoid hypothyroidism. MONITOR FOR PERMANENT HYPOTHYROIDISM ,(if>2mo) MONITOR SERUM TSH X6-8WKS fT4 T3 all patients require long-term follow-up.: LIFELONG HORMONE REPLACEMENT BY L-THYROXINE, 1.6-2.3MCG/KG/D
  8. 8. •HYPOCALCEMIA (Tx :) Oral calcium, calcitriol, iv Cagluconate if needed Prophylaxis : ca-carbonate 1250-2500mg 4t/d , taper to 500mg 1t/d the 1t/2d calcitriol 0.5 mcg/d …..x2wks Monitor serum calcium and make changes, Monitor for transient/permanent hypoparathyroidism. •DAMAGE TO RECURRENT LARYGEAL NERVE/VOCAL CORDS PARALYSIS,HYPOPARATHYROIDISM •INTRA N POSTOP BLEEDING, •COMPLICATIONS OF ANESTHESIA DUE TO SYMPTOMS LIKE HYPERTENSION,ARRYTHMIAS,ECT.
  9. 9. SYMPTOMATIC TREATMENT: usually symptoms receed with decrease of hyperthyroid state. BETABLOCKERS PROPRANOLOL MAX DOSES GLUCOCORTICOIDS 1)Myxedema/dermatopathy: topicaltriamcinolone/beclomethaso ne,topical dressing 2)OPHTHALMOPATHY a)mild-methycellulose eyedrops,tainted glasses b)moderate-severe- high dose pulsetherapy of prednisolone,methyprednisolone(12 0-140 mg 1t/wk x5wks iv) c)Orbit radiotherapy d)Orbital decompression (fibrate phase,euthyroid state) Cardiac arrthmias,palpitations,afib,heart failure ANTIDEPRRESANTS/SEDATIVES BENZODIAZEPINE, LITHIUM Anxiety Insomniai irritability, DIET LOW IN SALT, HIGH IN CALORIES TO MEET METABOLIC DEMANDS SUPPLEMENTS :CALCIUM,VIT D FOR BONE LOSS ANTIOXIDANTS,ORAL IRON IN SEVERE ANEMIA REDUCED PHYSICAL ACTIVITY. DIGOXIN EF<40% DIURETIC-furosemide+ spironolactone ACEinh-enelapril, ANTIARHYTHMICS-amiodarone, useful to normalise thyroid hormones. in PTUinduced hepatitis also