TREATMENT

THYROTOXICOSIS

TEACHER: DR SVETLANA VLADIMIROVNASHAILEE PATEL,GROUP 39, 6th course,2013

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

SURGERY

RADIOTHERAPY

•WHICH TREATMENT TO BEGIN WITH ????T

+++ symptomatic therapy………•Cardiac decompensation,• atrial fibrillation,• thyroid storm

Hospitalization/icu

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.

SURGERY RADIOACTIVE IODINE ANTI THYROID DRUGS

Large goiter >80 gm, with compessive symptoms.

pts with comorbid conditions,with surgical risks.

High likelyhood of remissions(mild-moderate 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.

Patients who cant follow safety rules of radiations,in nursing homes/outpt.

PATIENT SELECTION

For prompt control of hyperthyroidism

Tx for GD ,avoidance of Sx ,cosmetic scar,betarays travel 2mm/nt damage surring tissue.

Avoidance Sx,radiation,

,can be performed in an outpatient setting

Possibility of remission

PROS

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

CONS

ANTITYROID DRUGS : thioamides

METHIMAZOLE

PROPYLTHIOURACIL COUPLING

Tg

T3

T4

BINDINGOF IODIDE

TSH/THYROTROPIN

HYPERPLASTIC THYROID FOLLICLE WITH THYROGLOBULIN

T3

MONOIODOTYROSINE

DIIODOTYROSINEORGANIFICATION/IODINATION

DECREASED OUTPUT OF T3 T4

HYPERPLASTIC THYROID CELLSBLOODSTREAM

•They are actively transported into the thyroid gland where they inhibit both the orgaification of iodine to tyrosine residues in 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 release from thyroid cells. also inhibit the generation of oxygen radicals in T cells, B cells, decline in antigen presentation. methimazole induces the expression of Fas ligand on the thyroid epithelial cell, thus inducing apoptosis infiltrating T cells

HOW THEY WORK !T3 ,fT4

AIMED AT: •DECREASE HYPERTHYROID SYMPTOMS•MAINTAIN EUTHYROID STATE•AWAIT SPONTANEOUS REMISSION

CARBAMIZOLE

METHIMAZOLE (MMI,tapazole)CARBAMIZOLE

10-20 mg 1t/day PO

MONITOR T3 ,Ft4,EUTHYROID STATE ESTABLISHED IN 4-6 WEEKS

DOSE REDUCED BY 50%5-10 mg 1t/day PO

MAINTENANCE Tx CONTINUED FOR12-24 MO.

TAPER, CONTROL T3 T4, NO SYMPTOMS STOP Rx.

MONITOR EVERY 3 MO FOR NXT YEAR

WHEN A PATIENT IS SAID TO BE IN REMISSION ?? WHEN s TSH, Ft4 , T3 IS NORMAL FOR 1 YEAR AFTER DISCONTINUATION OF Rx

Ten times more potent than PTU, and once-a-day dose is effective. Euthyroid state is achieved quicklyRelapse may be observed 1-6 mo The serum half-life of MMI is four to six hours, Cross placental barrier, used from2nd trimester

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 proceedsmore protein boundHalf life 75 minutes,Used whem MMI OR CARBAMIZOLE not optimal.

Major side effects• agranulocytosis•Hepatitis, •hepatic necrosis•vasculitis.

FEVER FATIGUE PHARYNGITIS

JAUNDICE, ACHOLIC STOOLS ,DARK URINE PRURITIC RASH

MMI

PTU

Minor side effects:•Abdominal pains•Arthalgias•Bloating•Nausea•vomit

•Utricarias•Hairloss•Headache,paresthesis•Fever,change in taste

CONTRAINDICATIONS•allergic reactions: antihistamine/RAIU/Sx•WBC,neutrophil<500/mm3•Liver transaminase >5 times upper normal limits

ADDED IODIDES

Tx :reduce dose steroids

RADIOIODINE—(SINGLE SUFFICIENT RADIATION DOSE )

5-10 mCi calculation based on wt and I131 uptake (FIXED DOSE 7 mCi/50-100GY)

Discontinue ATDs 2 weeks prior to radiotherapy

Can precipitate thyroid storm/aggravate graves ophthalmopathy

Tx: prednisolone 1 mg/kg x2-3mo

Taper few days before radiotherapy

DECREASED CLINICAL SYMPTOMS IN 4-6 WKS

FIRST FOLLOWUP IN 2MO

THEN 4-6WK INTERVALSFOR NXT 6MO

If MINIMUM RESPONSEBy 3mo CONSIDER RETREATMENT

When SIGNS OF HYPOTHYROIDISMBecause of destruction of gland appears

THYROID HORMONE REPLACEMENT STARTEDLEVOTHYROXINE

Lifelong ANNUAL FOLLOWUP.THYROID FUNCTION TESTS CONTRAINDICATIONS

•Pregnancy,lactation•Planning pregnancy•Coexistent/susceptibility of thyroid cancer•Any metal device in body,

SURGERY : THYROIDECTOMYSurgery 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.

all patients require long-term follow-up.: LIFELONG HORMONE REPLACEMENT BY L-THYROXINE, 1.6-2.3MCG/KG/D

MONITOR FOR PERMANENT HYPOTHYROIDISM ,(if>2mo)

MONITOR SERUM TSH X6-8WKS fT4 T3

•HYPOCALCEMIA (Tx :)

•DAMAGE TO RECURRENT LARYGEAL NERVE/VOCAL CORDS PARALYSIS,HYPOPARATHYROIDISM•INTRA N POSTOP BLEEDING, •COMPLICATIONS OF ANESTHESIA DUE TO SYMPTOMS LIKE HYPERTENSION,ARRYTHMIAS,ECT.

Oral calcium, calcitriol, iv Cagluconate if neededProphylaxis : ca-carbonate 1250-2500mg 4t/d , taper to 500mg 1t/d the 1t/2d calcitriol 0.5 mcg/d …..x2wksMonitor serum calcium and make changes,Monitor for transient/permanent hypoparathyroidism.

SYMPTOMATIC TREATMENT:usually symptoms receed with decrease of hyperthyroid state.

BETABLOCKERSPROPRANOLOL MAX DOSES

AnxietyInsomniaiirritability,

Cardiac arrthmias,palpitations,afib,heart failure

GLUCOCORTICOIDS1)Myxedema/dermatopathy: topicaltriamcinolone/beclomethasone,topical dressing

2)OPHTHALMOPATHYa)mild-methycellulose eyedrops,tainted glassesb)moderate-severe- high dose pulsetherapy of prednisolone,methyprednisolone(120-140 mg 1t/wk x5wks iv)c)Orbit radiotherapyd)Orbital decompression(fibrate phase,euthyroid state)

DIGOXINEF<40%

DIURETIC-furosemide+ spironolactoneACEinh-enelapril,

ANTIARHYTHMICS-amiodarone,useful to normalise thyroid hormones.in PTUinduced hepatitis also

ANTIDEPRRESANTS/SEDATIVESBENZODIAZEPINE,LITHIUM

DIET LOW IN SALT, HIGH IN CALORIES TO MEET METABOLIC DEMANDSSUPPLEMENTS :CALCIUM,VIT D FOR BONE LOSS ANTIOXIDANTS,ORAL IRON IN SEVERE ANEMIAREDUCED PHYSICAL ACTIVITY.

THYROID STORM